FIRST EDITION

ANATOMY, PHYSIOLOGY & PATHOLOGY NOTES OF THE

ENDOCRINE
SYSTEM
 ENDOCRINE SYSTEM

TABLE OF CONTENTS
What’s included: Ready-to-study anatomy, physiology and pathology notes of the endocrine system
presented in succinct, intuitive and richly illustrated downloadable PDF documents. Once downloaded,
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Anatomy & Physiology Notes: Phaeochromocytoma

Diabetes
Overview of the Endocrine System
Calcium & Phosphate Balance Disorders
The Hypothalamus & Pituitary Gland
Parathyroid Disorders
The Pineal Gland
Gonadal Dysfunction
The Thyroid Gland
Multiple Endocrine Neoplasia Syndrome
Parathyroid Glands
The Adrenal Glands
The ‘Endocrine’ Pancreas
Calcium & Phosphate Homeostasis
Fluid & Electrolyte Homeostasis
Endocrine Regulation of Growth
Physiological Response to Stress
Reproductive Endocrinology

Pathology Notes
General Overview of Endocrine Disorders
Thyroid Dysfunction
Hypothyroidism (Incl. Hashimoto’s Disease)
Hyperthyroidism (Incl. Grave’s Disease)
Diagnosing Thyroid Dysfunction
Non-Toxic Goiters
Thyroid Neoplasms
Growth Dysfunction
Growth Hormone Deficiency (AKA. Pituitary
Dwarfism)
Gigantism/Acromegaly
ADH Disorders
Diabetes Insipidus
SIADH
Adrenal Cortex Dysfunction
Addison’s Disease
Waterhouse-Friderichsen Syndrome
Congenital Adrenal Hyperplasia
Conn’s Syndrome
Cushing Disease/Syndrome
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OVERVIEW OF
EMERGENCY
MEDICINE
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OVERVIEW OF
THE ENDOCRINE
SYSTEM

Endocrinology:
Endocrinology: The scientific study of Hormones (Chemical Messengers) and the endocrine organs.
Endocrine system is critical for maintaining Homeostasis

What is a Hormone
Chemical signaling molecules secreted by endocrine glands into the extracellular fluids to exert an
effect elsewhere in the body
Hormones travel in blood or lymph throughout the body
BIOLOGICAL SPECIFICITY: Hormones Interact with specific receptors of specific cells of specific organs.

Hormones Are Either Steroidal or Non-Steroidal:

Steroids Hormones:
Sex Hormones – Eg: Testosterone (Androgens), Oestrogens, Progestogens.
Adrenal Hormones – Eg: Glucocorticoids, Mineralocorticoids
(Derived from Cholesterol)

Non-Steroid Hormones:
Amino Acid Derivatives: Fatty-Acid Derivatives:
Catecholamines (Eg: Adrenaline, Nor- Eg: Prostaglandins
Adrenaline & Dopamine) (Derived from Tyrosine) Eg: Thromboxanes
Histamine (Derived from Histidine) Purines:
All Thyroid Hormones (Derived from Tyrosine) Eg: Adenosine
Proteins: Dissolved Gases:
All Pituitary Hormones Eg: Nitric Oxide
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Synthesis of Chemical Messengers:

Steroidogenesis:
All steroid hormones are derived from Cholesterol
There are 5 Families of Steroids, each with their main physiological member:
Progestogens (Progesterone)
Androgens (Testosterone)
Mineralocorticoids (Aldosterone)
Glucocorticoids (Cortisol)
Oestrogens (Oestrogen)

Protein/Peptide Synthesis & Processing:

Synthesis of polypeptide hormones can be more complex than Transcription & Translation.
Some Protein Hormones are initially synthesised as longer Pre-Prohormones
These Pre-Prohormones are then cleaved, leaving Prohormones
These Prohormones are then cleaved again, leaving active Hormones
Eg: Insulin:

‘Reactive’ Properties of Chemical Messengers:

Biological Specificity: Certain Chemical Messengers will only fit into certain receptors
Affinity: The degree to which a chemical is attracted towards a receptor
Efficacy: The degree of effectiveness of the binding of the messenger to the receptor
‘Agonists’: Chemical Messengers with High Affinity & High Efficacy
‘Antagonists’: Chemical Messengers with High Affinity but Low Efficacy
Note: There are no Endogenous Receptor-Antagonists, Only Exogenous (Drugs)
Hormone Binding Proteins: Proteins that inactivate hormones by binding to them, limiting
Bioactivity
Epitope: An Immunologically active binding site on a protein to which an antibody can attach
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Endocrine Glands:

Endocrine Glands are Ductless and secrete by Exocytosis into the Extracellular Fluid →
Diffuses into Blood

Classical Endocrine Glands:

Hypothalamus Thymus
Pituitary gland Adrenal glands
Pineal gland Pancreas (has exocrine parts for digestion)
Thyroid gland (endocrine part secretes insulin)
Parathyroid glands (dorsal aspect of Gonads: Testes/Ovaries (also exocrine)
thyroid gland)

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Long or Short-Range Signalling?

Endocrine: Some signals are “broadcasted” throughout the entire body via bloodstream. →
Hormones (produced by endocrine cells) [TV]
Autocrine: Signals that affect only cells of the same cell type as the emitting cell. [doctor
conference]
Paracrine: Signals (aka local mediators) that act on cells in the vicinity of the emitting cell but on
different cell types than the emitting cell. [Lecture]

CNX OpenStax, CC BY 4.0 <[Link] via Wikimedia Commons

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2 Main Receptor Types: (Intracellular

& Membrane-bound Receptors)

Intracellular Receptors:

Lipid-soluble hormones (steroid/thyroid hormones) & even gasses (nitric oxide-blood vessel
dilation)
Steroid hormones bind to receptor proteins in the cytosol or the nucleus that regulate gene
expression

OpenStax College, CC BY 3.0 , via Wikimedia Commons

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Plasma-Membrane-Bound-Receptors:

Most signal molecules can’t cross the plasma membrane of the target cell.
Most intracellular signalling proteins act as molecular switches activated by either
phosphorylation OR GTP-Binding (swapping a GDP for a GTP)
3 Types:
Ion-Channel-Linked Receptors
Resulting signal is a flow of ions across the membrane – produces an electric current.
Enzyme-Linked Receptors
When activated – act as enzymes or are associated with enzymes inside the cell.
G-Protein-Linked Receptors (more common)
Binds to a class of membrane-bound GTP-Binding-protein (G-Protein) → becomes
activated and released to migrate across the membrane, initiating a cascade of other
effects.
Some G-Proteins directly regulate ion channels in the plasma membrane.
Other G-Proteins activate membrane-bound enzymes. Eg: adenylyl-cyclase → increases
the [second messenger (cyclic-AMP)] → activates an intracellular signalling protein (eg:
A protein kinase) OR turns on genes via activated Protein Kinase ‘A’ (PKA).

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Tissue Responsiveness:
Receptor Downregulation:
Where a decreased receptor density in the membrane decreases the responsiveness of that cell to
that receptor’s stimuli.
This is achieved by Internalising the receptor-ligand complex, dissociating the ligand, and recycling
the receptor back to the surface.

Receptor Desensitisation:
Where a change in receptor structure decreases the responsiveness of that cell to that receptor’s
stimuli.
Why? To prevent multiple, rapid stimulations.
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Regulation of Hormone Release:

3 Mechanisms:

1- Humoral:
Where the concentration of a solute in the blood (Eg: High Glucose/Low Calcium) is
detected by a specific gland, stimulating hormone release (Eg: Insulin/Parathyroid
Hormone)

2- Neural:
Where the Nervous System Directly stimulates hormone release.
Eg: Sympathetic NS Activated→Stimulates Adrenal Medulla →
Secretes Catecholamines.

3- Hormonal:
Where one hormone stimulates the release of another hormone from a different cell.
Eg: The Hypothalamus secretes hormones → Stimulate Ant. Pituitary Secretes→
Hormones.
→
Eg: The Ant. Pituitary secretes Hormones Stimulate other organs to secrete hormones.

Feedback:
Negative:
Most common
Where the Biological Response
causes a Decreased Hormone
Release.
Maintains levels around a
stable intrinsic/pre-set level.
Involved in homeostatic control.

Positive:
Uncommon (Lactation &
Parturition)
Where the Biological Response
causes an Increased Hormone
Release
Are therefore Unstable
mechanisms
Terminate upon removal of
initial stimulus.
OpenStax College, CC BY 3.0 <[Link]
org/licenses/by/3.0>, via Wikimedia Commons
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Levels of Feedback Loops:

Feedback may occur at many different levels within an endocrine axis.

Ultra-Short Loop:
The secreted hormone feeds back to the same tissue that secreted it.
Eg: A Hypothalamic Hormone feeds back to the Hypothalamus.

Short Loop:
The secreted hormone feeds back to the tissue that stimulated its secretion.
Eg: The Hormone secreted by the Target Organ feeds back to the Pituitary.
Or. The Hormone secreted by the Pituitary feeds back to the Hypothalamus.

Long Loop:
The hormone secreted by the target organ feeds directly back to the Hypothalamus.
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Major Hormones & Their Functions:

Associated
Endocrine gland Chemical class Effect
hormones

Pituitary (anterior) Growth hormone (GH) Protein Promotes growth of

body tissues

Pituitary (anterior) Prolactin (PRL) Peptide Promotes milk

production

Pituitary (anterior) Thyroid-stimulating Glycoprotein Stimulates thyroid

hormone (TSH) hormone release

Pituitary (anterior) Adrenocorticotropic Peptide Stimulates hormone

hormone (ACTH) release by adrenal
cortex

Pituitary (anterior) Follicle-stimulating Glycoprotein Stimulates gamete

hormone (FSH) production

Pituitary (anterior) Luteinizing hormone Glycoprotein Stimulates androgen

(LH) production by gonads

Pituitary (posterior) Antidiuretic hormone Peptide Stimulates water

(ADH) reabsorption by
kidneys

Pituitary (posterior) Oxytocin Peptide Stimulates uterine

contractions during
childbirth

Thyroid Thyroxine (T₄), Amine Stimulate basal

triiodothyronine (T₃) metabolic rate

Thyroid Calcitonin Peptide Reduces blood Ca²⁺

levels

Parathyroid Parathyroid hormone Peptide Increases blood Ca²⁺

(PTH) levels
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Adrenal (cortex) Aldosterone Steroid Increases blood Na+

levels

Adrenal (cortex) Cortisol, corticosterone, Steroid Increase blood glucose

cortisone levels

Adrenal (medulla) Epinephrine, Amine Stimulate fight-or-flight

norepinephrine response

Pineal Melatonin Amine Regulates sleep cycles

Pancreas Insulin Protein Reduces blood glucose

levels

Pancreas Glucagon Protein Increases blood

glucose levels

Testes Testosterone Steroid Stimulates

development of male
secondary sex
characteristics and
sperm production

Ovaries Oestrogens and Steroid Stimulate development

progesterone of female secondary
sex characteristics and
prepare the body for
childbirth
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THE
HYPOTHALAMUS &
PITUITARY GLAND
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THE
HYPOTHALAMUS &
PITUITARY GLAND

The Hypothalamus:
Location:
In the diencephalon @ base of the brain, just below the thalamus.
‘Hypo’-Thalamus = Below the Thalamus

OpenStax College, CC BY 3.0 <[Link] via Wikimedia Commons

Functions:
The Hypothalamus receives information from multiple higher brain centres, integrates it, decides
on a response, and orders the pituitary to secrete specific hormones to elicit the response.
Ie: Links the nervous system to the endocrine system via the pituitary gland.
Controls body temperature, hunger, thirst, fatigue, anger, and cycles. Synthesizes & secretes
neurohormones (hypothalamic-releasing hormones) which stimulate or inhibit the secretion of
pituitary hormones
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Inputs:
RAS (Reticular Activating System/Substance) – Regulates drowsiness by releasing Serotonin.
Thalamus – Plays a role in Pain Perception
Neocortex & Limbic System – Emotional Centre
Optical System – Vision

Outputs:
Anterior Pituitary
Posterior Pituitary
Brain-Stem (Autonomic NS)
Hypothalamic Regulatory Hormones:
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[Link]

The Pituitary Gland:

Location:
Just Anterior to Pons of the Brainstem
Just Posterior to the Optic Chiasma
Just Inferior to the Hypothalamus
Connects superiorly to the hypothalamus (above it) via the Infundibulum
Function:
Secretes at least 9 hormones.
Function is controlled by hypothalamus (which secretes releasing/inhibiting hormones)
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Embryology of the Pituitary Gland:

Q: Why is the Anterior Pituitary Endocrine, but the Posterior Pituitary Neuronal?
A: Because they have different embryonic origins.
Anterior Pituitary:
Arises from an upward out-pouching of the Oral-Ectoderm from the roof of the oral cavity
called Rathke’s Pouch. This pouch pinches off from the oral cavity and is later separated by the
sphenoid bone.
Consists of Epithelial/Glandular Tissue, & therefore Manufactures & Secretes Hormones.
Posterior Pituitary:
Originates from a downward out-pouching of Neuro-Ectoderm from the brain in the floor of the
3rd ventricle.
Consists of Neural Tissue, & therefore Secretes Neurohormones.
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Anterior Pituitary: (Adenohypophysis)

Glandular Tissue (adeno = gland)

Responsible for Producing:

TSH (Thyroid Stimulating Hormone)
FSH/LH (Follicle Stimulating Hormone; Luteinizing Hormone)
PRL (Prolactin)
ACTH (Adreno CorticoTropic Hormone)
GH (Growth Hormone)

Different Cell Types in the Anterior Pituitary Secrete Specific Hormones:

Gonadotrophs: FSH & LH
Corticotrophs: ACTH (Adreno-Cortico-Tropic Hormone)
Thyrotrohps: TSH
Mammotrophs: Prolactin
Somatotrophs: Growth Hormone & Somatotropin

Histology – Glandular structure:

Clusters of acini surrounded by blood vessels
Acini - mosaics of different cells:
(acidophils –red, basophils – dark blue, chromophobes - colourless)
Note: Pituitary Tumours may be from any of the 3 cells
PLENTY of blood vessels (neither arteries or veins; but ‘Portal Vessels’ – Ie: Blood comes
only from the hypothalamus → carries the hypothalamic hormones.)

Mikael Häggström, M.D, CC0, via Wikimedia Commons

Blood Supply:
Arterial blood enters via Hypophyseal Branches of the Internal Carotid Arteries.

Venous Drainage:
Venous blood leaves via venules which drain into the Dural Sinuses.
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Posterior Pituitary: (Neurohypophysis)

Made of Nervous Tissue

Is essentially an Extension of the Hypothalamus

Supraoptic & Paraventricular Nuclei in the hypothalamus synthesize Oxytocin & ADH
→ Transport them to their axon terminals in the Posterior Pituitary.
Hormones released as needed via exocytosis in Post-Pituitary
ADH
Oxytocin

Histology – Just like normal brain tissue. (Neural

Origin)
Note: NO neurones, but plenty of axons.
Many supporting cells (Astrocytes, oligodendrocytes)
Plus Blood Vessels (neither arteries or veins; but
‘Portal Vessels’ – Ie: Blood comes only from the
hypothalamus → carries the hypothalamic hormones.)

Jensflorian, CC BY-SA 3.0 , via Wikimedia Commons

OpenStax College, CC BY 3.0 , via Wikimedia Commons

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Pituitary Hormones:

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OpenStax College, CC BY 3.0 , via Wikimedia Commons

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ACTH – Adrenocorticotropic Hormone:

Secreted By:
Corticotrophs in the Anterior Pituitary

Primary Action:
Stimulates adrenocortical cells in the Zona Fasciculata of the Adrenal Cortex to secrete
Glucocorticoids.
To reduce inflammation
To increase blood glucose levels
To increase lipolysis & proteolysis

Release is Stimulated By:

Corticotrophin Releasing Hormone (CRH)
CRH is secreted by the Hypothalamus in response to:
Stress
Low blood glucose
Low glucocorticoid levels
Increased Sympathetic Activity
Normal Diurnal Rhythm

Release is Regulated By:

Negative feedback loop between Hypothalamus-Pituitary-Adrenal glands

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GH - Growth Hormone:
Secreted By:
Somatotrophs in the Anterior Pituitary

Primary Action:
↑ Proportion of LEAN BODY MASS:
↑ Muscle Mass
↓ Adipose Tissue
Stimulates cell metabolism, growth and division throughout the body
Stimulates Protein Synthesis
Decreases Protein Breakdown
Stimulates Bone Osteoblast activity
Also has anti-insulin-like effects:
Stimulates Gluconeogenesis (Liver)
Stimulates Glycogenolysis (Liver)
Increases tissue insulin resistance
Stimulates Lipolysis (Adipose tissue)
Indirect Actions (Via Somatomedins/IGF’s):
↑
Linear Bone Growth ( Collagen & Protein Synthesis)
↑
Tissue Growth ( Protein Synthesis & Gene Replication/Transcription)

Release is Stimulated By:

Growth Hormone Releasing Hormone (GHRH)
GHRH is secreted by the Hypothalamus in a diurnal manner & in response to low GH levels
Also stimulated by Ghrelin from the stomach

Release is Regulated By:

Negative feedback loop between Hypothalamus & Pituitary gland

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TSH - Thyroid Stimulating Hormone:

Secreted By:
Thyrotrophs of the Anterior Pituitary

Primary Action:
Stimulates Thyroid Gland Growth
Stimulates Thyroid Hormone Synthesis
Stimulates Thyroid Hormone Release

Release is Stimulated By:

Thyrotropin-Releasing Hormone (TRH)
TRH is secreted by the Hypothalamus in response to:
Low T3/T4 Blood Levels
Decreased metabolism
Cold stress
High-energy-use situations

Release is Regulated By:

Negative feedback loop between Hypothalamus-Pituitary-Thyroid glands:

OpenStax College, CC BY 3.0 , via Wikimedia Commons

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FSH/LH – Follicle Stimulating Hormone &

Luteinizing Hormone:
Secreted By:
Gonadotrophs of the Anterior Pituitary

Primary Action:
Important in Puberty → Development of Sexual Characteristics:
Primary Sex Characteristics (Genital Development)
Secondary Sex Characteristics (Eg: Pubic hair, voice changes, breast development)
Important for Gamete Production
Males: LH → Leydig Cells →Produces Testosterone
Males: FSH → Sertoli Cells →Produce Sperm
Females: LH → Ovarian Follicles & Progesterone/Oestrogen Synthesis
Females: FSH → Recruits Ovarian Follicles early in menstrual cycle

Release is Stimulated By:

Gonadotropin-Releasing Hormone (GnRH)

Release is Regulated By:

Negative feedback loop between Hypothalamus, Anterior Pituitary & Gonads:

OpenStax College, CC BY 3.0 , via Wikimedia Commons

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PRL – Prolactin:
Secreted By:
Lactotrophs in the Anterior Pituitary

Primary Action:
Targets Breast Tissue:
→ Stimulates growth of glandular breast tissue during pregnancy
→ Stimulates Breast Milk Production after birth

Release is Stimulated By:

Prolactin-Releasing Hormone (PRH)

Release is Regulated By:

Complex feedback loop involving dopamine, suckling stimuli, and other sex hormones

[Link]
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ADH – Anti-Diuretic Hormone (AKA: “Vasopressin”):

Secreted By:
Posterior Pituitary

Primary Action:
Regulates Blood Pressure & Blood Volume
V1 Receptors →Arteriole Constriction →
Increased Systemic Vascular Resistance
V2 Receptors →Increases water reabsorption in the Renal Collecting Ducts

Release is Stimulated By:

Low blood volume
Increase of serum osmolality
Angiotensin-II

Release is Regulated By:

Feedback mechanism between Plasma osmolality & Osmoreceptors in Hypothalamus, Total
body water, and the Renin-Angiotensin System

[Link]
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Oxytocin:
Secreted By:
Posterior Pituitary

Primary Action:
Progression of Labour
Let-Down Reflex in Breastfeeding

Release is Stimulated By:

Baby Suckling (Breastfeeding)
Fetal head pushing against cervix (During Labour)

Release is Regulated By:

Positive Feedback Mechanisms:
Birth:
Breastfeeding

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THE
PINEAL GLAND
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THE
PINEAL GLAND

The Pineal Gland

Location:
In the ‘Epithalamus’ - Behind the Hypothalamus & Pituitary gland
Functions:
Synthetises Melatonin
Releases Melatonin at night due to Decreasing Light Levels
Regulates body’s Circadian Rhythm (Sleep/wake cycles)
Melatonin:
A hormone derived from serotonin
Modulates sleep patterns (both circadian and seasonal)
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THE
THYROID GLAND
 ENDOCRINE SYSTEM

THE
THYROID GLAND

The Thyroid Gland

General Info:
There are Thyroid-Hormone Receptors everywhere in the body.
75-100µg of Thyroid Hormone is secreted per day

Anatomy of Thyroid Gland:

A Bilobar Gland (2 Lobes – L&R) connected in the middle by the “Isthmus” of the Thyroid
Location:
Immediately below the Larynx on each side of, and anterior to, the Trachea.
Rich Blood Supply:
Required for Building Blocks of Hormones.
Required for Quick Release of Hormones.
Flow - Regulated by the Sympathetic NS.

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Composed of Millions of “Follicles”:

Each contains a pool of Thyroid “Colloid” of stored Thyroid Hormones bound to
Thyroglobulin.
Allows for a 2-3mth reserve of thyroid hormones.
Each pool is lined by a layer of “Principal/Follicle Cells” that secrete Thyroid Hormones (T3 &
T4).
There are also patches of “Parafollicular Cells” that secrete Calcitonin.

OpenStax College, CC BY 3.0 , via Wikimedia Commons

Thyroid Embryology:
Forms from Pharyngeal Pouches (@4-5wks)
Forms from the Endoderm germ layer.
Once formed, it migrates downwards & becomes Bi-lobed.
Note: Sometimes things go wrong during this migration, leaving a person’s thyroid gland
between the back of the tongue & where it normally sits (See dotted red line on pic below)
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Major Thyroid Hormones Produced

(And Proportions):

T₃ – Triiodothyronine (7%) (Iodinated Derivative of Tyrosine – 3x Iodines) (Most Biologically Active)

T₄ – Thyroxine (93%) (Iodinated Derivative of Tyrosine – 4x Iodines) (Less Biologically Active)

(Since these hormones are stored in the ‘Colloid’, there is ≈2-3mths of ‘backup’ Reserve

Calcitonin (Polypeptide)
Secreted By – The Parafollicular Cells of the Thyroid Gland
↓ ↓ ↑
Function: Plasma-Ca+ levels (By Osteoclast Activity & Osteoblast Activity)
↑
Stimulated By: Extracellular [Ca+ ] (Note: Opposite of PTH)

Iodine Balance:
Iodine is an essential component of the 2 major Thyroid Hormones & Is a Dietary
Requirement.

Of the Iodine ingested;

20% is Selectively Removed from blood by Thyroid Gland & used in Thyroid Hormone Synthesis.
80% is Excreted by the Kidneys

Iodine is Actively taken up by Thyroid Gland via “Iodine Trapping”.

The Rate of Iodine Uptake (Trapping) depends on TSH Concentration.

↑ TSH →↑ Thyroid Iodine Uptake
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How TSH Stimulates Thyroid Hormone

Synthesis/Secretion:
Binding of TSH to Follicle Cell →Activates AdenylylCyclase →↑ cAMP → Activates pKa
(Protein Kinase A) → Phosphorylates Various Enzymes in Follicle Cell → Changes Activity of:
↑ ↑
1. Cleavage of Thyroglobulin in Lysosomes (Ie: Release of T₃ & T₄)
↑
2. Activity of Iodine Pump (The Rate Limiting Step) →↑Iodine Available for Synthesis
↑
3. Iodination of Tyrosine →↑ Synthesis of DIT’s & MIT’s →↑Thyroid Hormone Synthesis
↑
4. Size & Secretory Activity of Follicle Cells
↑
5. # of Follicle Cells

Effects of TSH on the Thyroid:

Thyroid Follicle Hyperplasia
↑ Iodine Uptake from the Blood (Iodine Trapping)
↑ Thyroid Hormone Synthesis
↑ Release of T₃ & T₄

Synthesis of Thyroid Hormone: (Stimulated by TSH)

1. Active Uptake of Iodide by the Principal/Follicle Cells (Iodide “Trapping”):
Active Iodide uptake against massive Electrochemical Gradient.
Note: This is the Rate-Limiting Step of TH Synthesis.

2. Iodide Oxidation (by Peroxidase):

→
Oxidation of Iodide Ions (I- ) Iodine Molecules (I₂).

3. Secretion of Active Iodine into Lumen of Colloid:

4. Synthesis of Thyroglobulin by Rough-ER+Golgi & Secretion into Lumen of Colloid:

Tyrosines – the basis of Thyroglobulin (A large poly-peptide of ≈70 Tyrosines)

5. Iodines stick to the Tyrosines on the Thyroglobulin in Colloid → DIT or MIT (Di/Mono-Iodo
Tyrosine)
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Hormone Release Mechanism:

6. Some of the Thyroglobulin Colloid is Endocytosed + Combined with Lysosome:
Lysosomal Enzymes cleave the T₃ & T₄ from the Thyroglobulin.
Note: In the process, many of the unpaired DIT’s/MIT’s are also released. These are De-Iodinised
by Deiodinase. Both the freed Iodines & Tyrosines are recycled.

7. Vesicle of Cleaved T₃ & T₄ Breaks Down, Releasing Hormones into Cytosol

8. Hormones in Cytosol Diffuse through Basement Membrane →

Combine with Binding
Proteins in the Blood Stream (Thyroxine-Binding Protein/Albumin)

Häggström , Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). Public
Domain. CC0, via Wikimedia Commons
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Regulation of Thyroid Hormone Production/Release:

1. Hypothalamus Secretes “Thyrotropin-Releasing Hormone” (TRH) into portal circulation of
Pituitary.

2. TRH Stimulates Anterior Pituitary to Secrete “Thyroid Stimulating Hormone” (TSH).

3. TSH Stimulates Thyroid Gland to Secrete:

*Primarily Thyroxine (T₄ ) (The relatively inactive Thyroid Hormone →
converted to T₃ )
And Some Triiodothyronine (T₃ ) (The most active Thyroid Hormone)

4. T₃ & T₄ Circulate in the Bloodstream Eliciting their effects + Provide Neg:Feedback to Ant.
Pituitary

OpenStax College, CC BY 3.0 , via Wikimedia Commons

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Transport of Thyroid Hormones (Binding Proteins):

Note: 75-100µg of Thyroid Hormone is secreted per day

Thyroid hormone must be bound to carrier proteins when in bloodstream to avoid filtration by
kidneys.

3. TSH Stimulates Thyroid Gland to Secrete:

*Primarily Thyroxine (T₄ ) (The relatively inactive Thyroid Hormone→converted to T₃ )
And Some Triiodothyronine (T₃ ) (The most active Thyroid Hormone)

Common Thyroid-Hormone Carrier Proteins:

70% - “Thyroxine-Binding Globulin” (TBG)
30% - Albumin
Note: The minute %age of unbound Thyroid Hormones are those eliciting their effects
Ie: TH must be unbound to be able to enter cells & bind to Intracellular Receptors.

Mechanism of Action of Thyroid Hormone:

1. Thyroxine (T₄) reaches target cell

2. Binding Protein releases Thyroxine (T₄)
→
3. Thyroxine (T₄) diffuses into cytosol Converts to T₃
4. T₃ (The most active form) enters Nucleus→ Binds to Nuclear Receptor on DNA→ Alters Gene
Transcription.
5. Activating Different Genes→ →
leads to Change in Cell’s Protein/Enzyme profile Change in
Activity.

Cellular Changes:
↑ Carbohydrate/Fat Metabolism
↑ Glucose Uptake
↑ Protein Synthesis + Catabolism
↑ Mitochondrial Activity & Number
↑ Na/K-ATPase Activity

Bodily Changes:
↑
CVS: O₂ Consumption →↑ Cardiac Output, HR & Respiration
GIT:
↑ ↑
Food Intake ( Glucose Absorption from GIT)
↑Secretion of Digestive Juices
↑GIT Motility
 ENDOCRINE SYSTEM

Metabolism:
↑Metabolism (Basal Metabolic Rate)
↑Insulin Secretion
↑Lipolysis → Higher [FFA] in Plasma
↑Body Temp →Sweating
↑ ↑
Vitamin Requirements due to Quantities of Enzymes (Of which vitamins are a vital
component)

↑ ↑
Bone: Bone Turnover & Resorption
↑ ↑
Muscle: Speed of Muscle Contraction & Speed of Relaxation
↑
Sympathetic NS: Catecholamine Sensitivity of Heart, Muscle, Fat & Lymphocytes

Note: Because Thyroid Hormones act by Gene Activation, they are said to have a Long ‘Latent
Period’, during which they seem to have no discernible effect.
Thyroxine: 2-3 Days
Triiodothyronine: 6-12 Hours
 ENDOCRINE SYSTEM

PARATHYROID
GLANDS
 ENDOCRINE SYSTEM

PARATHYROID
GLANDS

Parathyroid Anatomy:
Macro Structures:
4x small Endocrine Glands on the Posterior Surface of the Thyroid Gland
2x on Left; 2x on Right
Size of a grain of rice.
Micro Structures:
Densely packed cells (As opposed to follicle structure of Thyroid Gland)
2 Cell Types:
Parathyroid Chief Cells:
Secrete Parathyroid Hormone (PTH)
Oxyphil Cells:
Unknown function.

OpenStax College, CC BY 3.0 , via Wikimedia Commons

 ENDOCRINE SYSTEM

Parathyroid Physiology:

Secretes Parathyroid Hormone → Important role in Calcium Homeostasis in Blood & Bones
(Important for Excitable Tissues)
(Important for Bone Integrity)

(Also has effects on Phosphate)

Note: Parathyroid Gland is NOT under Hypothalamic Control!!! – Functions Autonomously

Parathyroid Hormone (PTH):

Secreted by – The Chief Cells of the Parathyroid Glands

Release Stimulated By:

↓ Extracellular [Ca+ ] – Very Sensitive

Release Inhibited By:

↑ Extracellular [Ca+ ] – Very Sensitive

Aims to:
↑ Plasma-Ca+ levels (By Increasing Bone Ca+ /PResorption & ↓
Renal Ca+ Excretion)
↓ ↑
Plasma-Plevels (By Renal PExcretion so that it exceeds Bone PResorption )

Primary Effects:
Stimulates Osteoclasts → Mobilises Ca from Bone Matrix→↑ Calcium in Blood
Activates Vit-D in Kidneys →↑GI Absorption of Ca+→↑ Calcium in Blood
↑ Renal Calcium Reabsorption →↓ →↑
Renal Excretion Calcium in Blood
(Increases Renal Excretion of Phosphate →↓ Phosphate in Blood)
 ENDOCRINE SYSTEM

OpenStax College, CC BY 3.0 <[Link] via Wikimedia Commons

 ENDOCRINE SYSTEM

THE ADRENAL
GLANDS
 ENDOCRINE SYSTEM

THE ADRENAL
GLANDS

Anatomy of the Adrenal Glands:

Endocrine Glands that sit on top of the Kidneys
Retroperitoneal
Two Layers:
1- Cortex (3 Zones) (Remember GFR)
1- Zona Glomerulosa (Outer) → Mineralocorticoids (Aldosterone)
2- Zona Fasciculata → Glucocorticoids (Cortisol)
→
3- Zona Reticularis (Inner) Adrenal Androgens (DHEA)
2- Medulla (Middle)
Chromaffin Cells→ Catecholamines (Adrenaline, Noradrenaline)

OpenStax College, CC BY 3.0 , via Wikimedia Commons

 ENDOCRINE SYSTEM

Regulation of the Adrenal Glands:

Adrenal Cortex Secretions are controlled by ACTH (Adreno-Corticotropic Hormone) by Anterior

Pituitary
Anterior Pituitary releases ACTH in response to CRH (Corticotrophin Releasing Factor/Hormone)
Negative feedback loop:

Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014; 383 (9935): p.2152
-2167. doi: 10.1016/s0140-6736(13)61684-0 . | Open in Read by QxMD
 ENDOCRINE SYSTEM

Adrenocortical Hormones:
All Adrenocortical Hormones are Steroidal (Derived from cholesterol)
Adrenal cortex cells convert Cholesterol into →
‘Prognenolone’
Prognenolone → Zona Glomerulosa →
Aldosterone
Prognenolone → Zona Fasciculata →
Cortisol
Prognenolone → Zona Reticularis →
Testosterone & Oestrogen

Lefèvre, Lucile et al. “Adrenocortical growth and cancer.” Comprehensive Physiology 5 1 (2015): 293-326 .

Stress Hormones:
Corticosteroids (Cortisol) →↑
Blood Glucose, Immunosuppression, Bone Formation. ↓
Catecholamines (Adrenalines) →↑ ↑ ↓
Blood Glucose, HR & BP, Parasympathetics.
Electrolyte Balance:
Aldosterone (A Mineralocorticoid) →↑ ↑
Na+ Retention, K+ Excretion, BP ↑
 ENDOCRINE SYSTEM

Cortisol:
Secreted By:
Cells of the Zona Fasciculata of the Adrenal Cortex o Derived from Cholesterol

Metabolic Actions:
Increases Blood [Glucose] ; Stimulates Gluconeogenesis (Liver) →
Glucose Output by Liver
↑
Proteolysis (Muscle) Availability of Gluconeogenic Substrates in Blood (Glycerol + AA’s)
Lipolysis (Adipose) ↑
Availability of Gluconeogenic Substrates in Blood (Glycerol + AA’s)
→
Stimulates the Urea Cycle (Required to handle Wastes from Amino-Acid metabolism Glucose)
Glucose-Sparing Effect – (Inhibits Glucose Uptake (Muscle & Adipose)

Immune Actions:
Reduces intensity of immune/inflammatory responses.
By reducing the production of Inflammatory mediators
Eg: Prostaglandins, Thromboxanes, Leukotrienes
Eg: Interleukins, Interferon, TNF
By reducing T-Cell Proliferation
By reducing Neutrophil Phagocytosis

Other Actions:
Assists in maintaining blood pressure
Reduces bone formation
Increases renal filtration
Increases EPO (Erythropoietin) release

Release is Stimulated By Hypothalamus in Response to:

Stress (Infection, Trauma, Sympathetic overdrive, Psychological stressors)
Physical Activity
Low Blood Glucose
 ENDOCRINE SYSTEM

Release is Regulated By:

Hypothalamus Secretes Corticotrophin-Releasing Hormone (CRH) →
ACTH by Anterior Pituitary
Negative Feedback Mechanism between Hypothalamus, Pituitary & Adrenal gland

Yau JLW and Seckl JR, CC BY 3.0 <[Link] via Wikimedia Commons

[Link]
 ENDOCRINE SYSTEM

Aldosterone:
Secreted By:
Zona Glomerulosa Cells of the Adrenal Glands

Primary Actions:
Sodium Homeostasis →
Causes Na Reabsorption in the Renal Distal Tubules & Collecting Ducts
Regulates extracellular fluid volume (Via increasing blood Na concentration & renal
absorption)
Potassium Homeostasis →
Increases K Secretion in the Renal Distal Tubules & Collecting Ducts

Works by:
ACTIVATING the Na/K-ATPases in the
Principal Cells of Distal & Collecting
Ducts:
Increases Na+ & ClReabsorption
Increases K+ Secretion
Promotes Na+ -Channel (ENaC) Synthesis
& Insertion into Luminal Membrane:
Facilitates the Na+ Reabsorption
mentioned above.

[Link]

Release is Stimulated By Hypothalamus in Response to:

*Angiotensin-II, Part of the Renin-Angiotensin System (Due to Renin Release by Kidneys)
*Hyponatraemia (Low Na+ in Blood)
*Hyperkalaemia (High K+ in Blood)
Stress

Release is Regulated By:

OpenStax College, CC BY 3.0 , via Wikimedia Commons

 ENDOCRINE SYSTEM

THE ‘ENDOCRINE’
PANCREAS
 ENDOCRINE SYSTEM

THE ‘ENDOCRINE’
PANCREAS

Anatomy of the Pancreas:

Elongated, Horizontal, Retroperitoneal Organ
Head –Cupped by the Duodenum
Tail – abuts the spleen
Exocrine Component (99% of Cells) – Acinar Epithelial Cells + Duct Network
Produces pancreatic juice (incl. digestive enzymes)
Endocrine Component (1% of Cells) – Islets of Langerhans + 4 Cell Types. Of these:
↑
25% are Alpha (α) Cells – Secrete Glucagon ( BSL)
↓
60% are Beta (β) Cells – Secrete Insulin ( BSL)
10% are Delta (δ) Cells – Secrete Somatostatin
5% are PP Cells – Secrete Pancreatic Polypeptide (Plays a role in Satiety)

OpenStax College, CC BY 3.0 , via Wikimedia Commons

 ENDOCRINE SYSTEM

OpenStax College, CC BY 3.0 <[Link] via Wikimedia Commons

 ENDOCRINE SYSTEM

Pancreatic Hormones

Insulin:
Secreted By:
Beta (β) Cells of the Pancreas

Mechanism of Insulin Release from β-Cells of Pancreas:

↑
1. Blood Glucose →↑ Insulin-Independent Uptake of Glucose into Pancreas (Via GLUT-2)
2. →↑ ATP Production in β-Cell.
↑
3. ATP Closes the ATP-Gated-K+ Channels in β-Cell Membrane →
Depolarises the β-Cell
4. Depolarisation →
opens Voltage-Gated Ca+ Channels →
Influx of Ca+
5. Influx of Ca+ →Ca+ Mediated Exocytosis of Insulin Vesicles (Similar to ACh Release in
Muscles)

Prisonblues at the English-language Wikipedia, CC BY-SA 3.0 , via Wikimedia Commons

Insulin only affects Insulin-Sensitive Tissues (Ie: Those that expresses GLUT-4 Transporters):
Liver
Muscle
Adipose Tissue
 ENDOCRINE SYSTEM

Insulin doesn’t affect Insulin-Independent Tissues:

Blood Vessels (Endothelium)
Myocardium of Heart
Nervous System
Red Blood Cells
Kidneys
Eyes

Primary Actions:
Insulin →↑
Expression of GLUT-4 Transporters in cell membrane → ↑Glucose Uptake in
tissues

Current Trends in Pharmacological Treatment of Type II Diabetes Mellitus - Scientific Figure on ResearchGate.
Available from: [Link]

Fasted State:
There will be some GLUT-4 Transporters expressed in the Plasma Membrane.
However, most will be found in the membranes of Cytoplasmic Vesicles within the cell.
Fed State:
Binding of Insulin to Receptors →
Initiates a Signalling Cascade →
Movement of GLUT-4
Laden Vesicles to the Cell Surface
Upon reaching the Plasma Membrane, the vesicles fuse with it →↑
Plasma Membrane-
[GLUT-4].
↑
Plasma Membrane-[GLUT-4] →↑
Glucose Uptake
Signalling Cascade also Causes →
Glucose Metabolism
Protein Synthesis
Glycogen Synthesis
Inhibition of Gluconeogenesis
Lipid Synthesis.
 ENDOCRINE SYSTEM

Insulin Release is Stimulated By:

Parasympathetic NS (Rest & Digest)
↑ Blood [Amino Acids]
↑ Blood [Glucose]
Gastrointestinal Peptide (GIP)
Glucagon – (Weak Stimulator)

Insulin Release is Regulated By:

↑
Sympathetic NS (Acts to Blood [Glucose] for Fight/Flight Response)
Somatostatin
 ENDOCRINE SYSTEM

Glucagon:
Secreted By:
Pancreatic Alpha Cells

Primary Actions:
Acts to Increase Blood Glucose; by:
Stimulating Hepatic Glycogenolysis Stimulates Ketogenesis
Stimulating Hepatic Inhibits Hepatic Glycolysis
Gluconeogenesis Inhibits Fatty Acid Synthesis in Liver
Stimulates Lipolysis Inhibits Fat Deposition in Adipose
Stimulates Ketogenesis Tissue

[Link]

Release is Stimulated By: Increased Sympathetic Drive (Alpha

Low Glucose Levels (Eg: Between meals or while adrenergic receptors)
sleeping) Cholecystokinin (CCK)
Low Insulin levels Exercise`

Release is Regulated By:

Elevated Blood Glucose levels
Elevated Insulin Levels
Increased Parasympathetic
Drive (M3 muscarininc
receptors)
Amino Acids Alanine & Arginine
(Elevated following high protein
meal)
Somatostatin
 ENDOCRINE SYSTEM

The “Fed State” – Directly After a Meal:

↑INSULIN:
Stimulates: Inhibits:
Nutrient Uptake from the Blood: Gluconeogenesis (Liver)
Glucose (Liver, Muscle & Adipose) Ketogenesis (Liver)
↑
Via GLUT-4 Receptors (Muscle & Macromolecular Breakdown:
Adipose) Lipolysis (Liver & Adipose)
↑
Via Glucose Utilisation (Liver) Glycogenolysis (Liver & Muscle)
Amino Acids (Liver, Muscle & Adipose) Proteolysis (Liver, Muscle & Adipose)
Fatty Acids (Liver & Adipose)
↑
Via Lipoprotein Lipase (LPL) Activity
in Adipose Tissue.
Macromolecular Synthesis (& Storage):
Glycogenesis (Liver & Muscle) – (Note:
Glucose → Triglycerides in Adipose)
Proteingenesis (Liver, Muscle & Adipose)
Lipogenesis (Liver & Adipose)
Glycolysis – In all body cells

+ the “Incretin Effect”:

Incretins (Released by GIT after a meal)

Further Stimulates Insulin Release from
Pancreas.
Hence → The Insulin Response to Oral
Glucose is much Greater & Quicker than IV
Glucose.
:. New Avenue for Diabetes
Management:
Incretins:
Intestinal glucose intake→
Intestines release Incretins
(glucagon-like peptide-1 [GLP-1]
and Glucose-dependent
Insulinotropic Polypeptide [GIP])
→ ↑
Stimulate β Cells to Insulin
Release and Suppress α-Cells and
↓ Glucagon.
Note: Incretins are Destroyed by
Dipeptidyl Peptidase-4 (DPP-4)
:. By Inhibiting DPP, you can
Prolong the Action of Incretins
 ENDOCRINE SYSTEM

OpenStax College, CC BY 3.0 <[Link] via Wikimedia Commons

 ENDOCRINE SYSTEM

The “Fasted State” - ≈3hrs After a Meal:

↑GLUCAGON
→↑
*Activates Glycogenolysis (Liver) Blood [Glucose] (Note: Glucagon = Powerful Glycogenolytic)
→↑
Activates Gluconeogenesis (Liver) Blood [Glucose]
→↑
Stimulates Amino Acid Uptake (Liver) Gluconeogenesis →↑ Blood Glucose
→↑
Activates Lipolysis (Adipose) Blood [FA’s] (Note: Glucagon = Powerful Lipolytic)
Stimulates Ketogenesis (Liver)

↓INSULIN→ “Glucose-Sparing” Effect:

Increased Availability of Gluconeogenic Substrates:...due to:
↓ ↑
Inhibition of Gluconeogenesis – ( Level of Gluconeogenesis)
↓ ↑
Inhibition of Lipolysis – ( Level of Lipolysis)
↓ ↑
Inhibition of Proteolysis – ( Level of Proteolysis)
↓ Glucose Uptake by:
Muscle
Liver
Adipose
Glucose-Sparing → More Glucose for Brain & Nerves (Glucose = 1ᵒ Fuel)

Note: Insulin is Low, but is still high enough to prevent:

Massive Lipolysis (As Glucagon is a powerful lipolytic)
↑
Massive Ketogenesis (Normally, Insulin Inhibits Ketogenesis) – Therefore Low Insulin allows
some Ketogenesis but Prevents Ketoacidosis.)
Massive Proteolysis
 ENDOCRINE SYSTEM

OpenStax College, CC BY 3.0 , via Wikimedia Commons

 ENDOCRINE SYSTEM

CALCIUM &
PHOSPHATE
HOMEOSTASIS
 ENDOCRINE SYSTEM

CALCIUM &
PHOSPHATE
HOMEOSTASIS

Functions of Calcium & Phosphate:

Calcium:
Structural Purposes:
Development & Maintenance of Skeleton
Biochemical Purposes:
Mediates exchange between Intracellular & Extracellular Compartments (eg: ACh Release)
Responsible for many Endocrine & Exocrine Secretions.
Can act as a secondary messenger (Like cAMP).
Role in Muscle Contraction & Nerve Impulses
Role in Blood Clotting
Phosphate:
Structural Purposes:
Development & Maintenance of Skeleton
Phospholipids are a major structural component of Plasma Membrane
Biochemical Purposes:
Phosphate Release from Nucleotides (eg: ATP → ADP) is the Major Source of Cellular
Energy.
The Phosphodiester-Bond Provides the backbone for RNA & DNA.
Phosphorylation provides a basis for Receptor Activation & Signal Transduction.
(Magnesium - Also important):
Structural Purposes:
Important in Integrity of Bone
Note: 50% of body-Mg is stored in bone.
Biochemical Purposes:
Sufficient Mg+ is required to have Normal Ca+
Mg+ Regulation:
Mg+ Levels controlled by modulating Mg+ Reabsorption in the Distal Tubules of the Kidney:
Mg+ Reabsorption stimulated by:
↓ Extracellular Fluid Volume
↓ Plasma Mg+
Hypocalcaemia
Mechanism is unknown.
 ENDOCRINE SYSTEM

Bone Chemistry:
Bone Consists of 2 Things:

30% (By Weight) = Organic Bone Matrix:

90% of which is Collagen Fibres
10% of which is Ground Substance
70% (By Weight) = Bone Salts:
The major salt = Hydroxyapatite ( Ca₁₀(PO₄)₆(OH)₂ )
Consists of mainly Calcium & Phosphate.
Also contains other amorphous calcium salts used for rapid exchange (See below)

Ca+ Exchange Between Plasma & Bone:

Experiment: An Intravenous Ca+ injection dissipates within an hour. Likewise, large-scale removal
of Ca is just as quickly compensated for.
How? – The bone acts as a Calcium Exchanger, quickly mobilizing/depositing calcium salts to buffer
the Extracellular-Fluid Ca+ Concentration.

Serum Concentrations:
Bone Consists of 2 Things:

Calcium:
Levels depend on 3 Processes: Note: Only ≈1% of the Body’s Ca+ is
↑
Intestinal Absorption (Ie: To Serum Ca+) Extracellular. The Rest is Stored in
↓
Renal Excretion (Ie: To Serum Ca+) Bones.
Resorption/Deposition of Bone (Ie: To ↑ Hence, the Bones = Ca+ Reservoir.
Serum Ca+) Extracellular Ca+ exists in 3 Forms:
The Above Processes are Regulated by 3 50% Ionized = Ca+ NOT Bound to
Hormones: Anything (Diffusable)
PTH - Parathyroid Hormone (Note: This is the functionally
Calcitonin important form.)
Vitamin D (The Active Form) 10% In Covalent Compounds
Calcium levels are tightly regulated - @ ≈ (Diffusable)
9.4mg/dl OR 2.4mmol/L. 40% Bound to Plasma Proteins (Eg:
Albumin) (Non-Diffusable)
 ENDOCRINE SYSTEM

Phosphorus:
Levels depend on:
Age
Gender
Dietary Intake.
Calcium-Controlling Hormones.
Note: Only ≈1% of the Body’s Phosphate is Extracellular. The Rest is Stored in Bones.
Phosphorus levels are loosely regulated - @ ≈ 2.4 - 4.1 mg/dl.

Regulation of Plasma Ca+ & Phos. Levels:

Intestinal Absorption:

Calcium:
Normally, Ca+ is poorly absorbed by the Intestines.
Vitamin D Increases Ca+ Absorption by the Intestines (POTENT)
↑
PTH indirectly promotes Intestinal Ca+ Absorption by Vit-D Activation by the Kidneys.
Phosphate:
Absorption occurs very easily
(Ie: Almost all dietary Phosphate is absorbed into the blood, and later excreted in urine)

Intestinal Absorption:

Calcium:
Normally, 99% of Filtered Ca+ is Reabsorbed...
90% happens in PCT, Loop of Henle & early DCT.
10% happens in the late DCT – and is Very Selective (Depending on Blood-Ca+ )
If Blood-Ca+ is Above Normal – All remaining Ca+ is expelled in urine.
Note: Calcitonin weakly ↑ Calcium Excretion
If Blood-Ca+ is Below Normal – All remaining Ca+ is reabsorbed
Note: PTH Greatly ↓ ↑
Calcium Excretion in the Kidneys (Ie: Reabsorption)
Phosphate:
Renal Phosphate excretion is via an ‘Overflow Mechanism’:
If Blood-Phosphate is Below 1mmol/L – All filtered Phosphate is Reabsorbed
If Blood-Phosphate is Above 1mmol/L – Phosphate is excreted @ a rate relative to its conc.
Note: PTH Greatly ↑ Phosphate Excretion in the Kidneys.

Resorption/Deposition of Mineralized Bone:

PTH promotes Osteoclast Activity (Bone Resorption)

Vitamin D promotes Bone Calcification (Deposition) (Mechanism Unknown)
Calcitonin promotes Bone Calcification (Deposition) (By Inhibiting Osteoclast Activity)
 ENDOCRINE SYSTEM

The 3 Major Hormones:

1- Parathyroid Hormone (PTH):

Secreted by – The Chief Cells of the

Parathyroid Glands
Aims to:
↑ Plasma-Ca+ levels (By Increasing
Bone Ca+ /PResorption & ↓ Renal
Ca+ Excretion)
↓ ↑
Plasma-Plevels (By Renal
PExcretion so that it exceeds Bone
PResorption)

Primary Effects:
Mobilises Ca & Phos from bone Matrix (Bone Resorption) (By Stimulating Osteoclast Activity)
Stimulates Osteoblast & Osteoclast Proliferation → Promotes bone turnover.
Decreases Renal Excretion of Calcium (By Increasing Calcium Reabsorption in DCT)
Note: PTH is essential here to prevent excess loss of Calcium & therefore prevent calcium
depletion in ECF & Bone.
Increases Renal Excretion of Phosphate (By Preventing Phosphate Reabsorption in PCT)
→
Increases Activation of Vit-D in Kidneys Indirectly increases intestinal absorption of Ca+ /P- .
Stimulated By:
↓ Extracellular [Ca+ ] – Very Sensitive
Inhibited By:
↑ Extracellular [Ca+ ] – Very Sensitive
Regulators
 ENDOCRINE SYSTEM

2- Vitamin D:

Aims to:
↑ Plasma-Ca+ /Plevels (by Increasing intestinal Ca+ /Pabsorption)
Primary Effects:
↑ Intestinal Calcium Absorption
↑ Intestinal Phosphate Absorption (Even better than usual)
Aids PTH in mobilizing Ca & Phos from bone Matrix.
↑
(In Small Quantities, it can Bone Mineralization (Mechanism Unknown))
Vit-D Activation:
Vit-D itself is not the active form that causes the above effects. It must first be Activated.
Vit-D is converted through a series of reactions in the Skin, Liver & the Kidneys to produce
the final active product = 1,25-dihydroxycholecalciferol aka. 1,25(OH)2D3-
See Below for Steps:
Note: The conversion in the Liver has Neg:Feedback for 2 Important Reasons:
1- Prevents excessive 25-Hydroxycholecalciferol in the plasma, which in turn prevents
→
excessive activation by kidneys maintains Ca+ ion concentration.
2- Conserves the Vit-D3 stored in the Liver for future use. (Because the converted forms
only last a few weeks, whereas Vit-D3 lasts for months)
Note: The conversion in the Kidneys is controlled by PTH:
Without PTH, none of the 1,25(OH)2D3 is formed.
Therefore, PTH has a huge influence on the levels of body’s functional Vit-D.
Furthermore, since Plasma-Ca+ levels determine PTH levels, PlasmaCa+ has an
Indirect, but STRONG Negative Feedback Effect as well. (Even a slight increase in
[Ca+ ] above 10mg/dL, sharply suppresses PTH secretion →↓ 25-
Hydroxycholecalciferol – See Diagram)
 ENDOCRINE SYSTEM

3- Calcitonin:

Secreted By – The Parafollicular Cells of

the Thyroid Gland
Aims to:
↓ ↓
Plasma-Ca+ levels (By Osteoclast
Activity so that Bone Deposition is
Favoured)
This effect is much greater in
children due to rapid remodelling.
Primary Effects:
Decreases the Activity & Proliferation
of Osteoclasts→ Favours Bone-Salt
Deposition.
Stimulated By:
↑ Extracellular [Ca+ ] (Note: Opposite
of PTH)(See Below Diagrams)

Summary:

[Link]
 ENDOCRINE SYSTEM

FLUID &
ELECTROLYTE
HOMEOSTASIS
 ENDOCRINE SYSTEM

FLUID &
ELECTROLYTE
HOMEOSTASIS

Why Maintain Fluid & Electrolyte Balance?:

Critical for Normal Cell Function
Critical for Chemical Stability (Homeostasis) of Surrounding Fluids
*Electrolyte Balance (Particularly Na+ & K+ )
Critical for function of Excitable Tissues - Critical for Blood Pressure Homeostasis

FLUID BALANCE

Normal Adult Fluid Volume ≈ 40 Liters:

Extracellular = 15 Litres
3 Litres = Plasma
12 Litres = Interstitial Fluid
Intracellular = 25 Litres

Water Intake & Output:

Intake:
Produced in Metabolism
Contained in Foods
Consumed Fluids
Output:
Faeces (Obligatory)
Sweat (Obligatory)
Lungs (Obligatory)
Urine

[Link]
handle/2066/191611/[Link]
 ENDOCRINE SYSTEM

Regulation of Water Intake (Thirst) –

Hypothalamic Triggers:
Thirst Triggered by 2 Things:
1- A 10%+ Decrease in Plasma Volume....OR
2- A 1-2% Increase in Plasma Osmolality

1- Decreased Plasma Volume →

Reduced Blood Flow to Salivary Glands →
Cellular Dehydration of
Salivary Gland Cells→“Dry Mouth” →
Triggers Thirst Centre in Hypothalamus.

2- Increased Plasma Osmolality →

Directly Causes Cellular Dehydration of Osmoreceptors in the
Hypothalamus → Stimulates the Thirst Centre.

Note: Extracellular Dehydration →

Hypovolaemia → Baroreceptors stimulate Thirst Centre
causes Renin Release from Kidneys.

Regulation of Water Output:

Water loss is unavoidable (Obligatory Water Loss – From Lungs, Skin, Faeces, Minimum Urine
Output 500mL)

Aside from Obligatory Loss, the rest (lost through Urine) is Regulated by Anti-Diuretic Hormone
(ADH).

Anti-Diuretic Hormone (ADH) →

↓Water Output:
Acts to increase Blood Volume.
Released from the Posterior
Pituitary Gland
Released in response to:
↑ ↑
Plasma Osmolality ( [Na+
→
]) Stimulation of
Osmoreceptors in
Hypothalamus
↓ Plasma Volume.

[Link]
m/the-endocrine-system-7
 ENDOCRINE SYSTEM

Works by INCREASING H₂O Permeability of Distal & Collecting Ducts:

Distal Tubules & Collecting Ducts are Normally Impermeable to H₂O
However, the Presence of ADH →↑# of Aquaporins In Membrane →↑
Permeability to H₂O
↑ →
This Permeability to H₂O + High [Solute] in Medulla H₂O Reabsorption (From Collecting
→ →
Duct Interstitium Blood)

[Link]

Atrial Natriuretic Peptide (ANP) →↑

Water Output:
Acts to:
↓ blood volume
↓ Blood [Na]
Secreted by Atrial Myocytes of the
Heart
Released in response to:
High Blood Pressure (Atrial Stretch)
Works by:
Dilating Afferent Glomerular
Arteriole
Constricting Efferent Glomerular
Arteriole
↑ →↑
Filtration Pressure
→↑
Filtration H2O & Na
Excretion.
Inhibits Renin Secretion → Inhibits
Renin-Angiotensin System
Inhibits Aldosterone Secretion
from Adrenal Cortex.
Inhibits ADH Release from Post. [Link]
Pituitary [Link]
 ENDOCRINE SYSTEM

ELECTROLYTE BALANCE:

Significant Electrolytes:
Na+ = Major Extracellular Cation
Cl⁻ = Major Extracellular Anion ]
Account for 80% of Osmolality of Interstitial Fluid & Plasma
K+ = Major Intracellular Cation -Accounts for 50% of Osmolality of Intracellular Fluid

Why Maintain Electrolytes

Na+ = Important for Heart & Nerve Function/Cellular Transport
K+ = Important for Heart Function/Cellular Transport
(Note: too high Extracellular K+ interferes with Cardiac Function = Fatal)
Ca+ = Important for Muscle, Heart & Nerve Function/Bone Formation
Mg+ = Important for AcetylCholine Release → Important for Neural & Cardiac Function
HPO₄ ²⁻ = Important for Bone Formation (Bone salts – primarily calcium & phosphates)

Regulation of Na+ - (The Main Extracellular

Electrolyte):
Primary role in Fluid & Electrolyte Balance (Because
Water Follows Na+ Movement)
Extracellular [Na+ ] is normally stable & is Regulated
by levels of Aldosterone:
Aldosterone →↑ Na Resorption:
Aldosterone = Steroid Hormone Released from
The Adrenal Cortex.
Released in response to:
*Angiotensin-II, Part of the Renin-Angiotensin
System (Due to Renin Release by Kidneys)
*Hyponatraemia (Low Na+ in Blood)
*Hyperkalaemia (High K+ in Blood)
Stress
 ENDOCRINE SYSTEM

Effects:
Increases Na+ Reabsorption of the Principal Cells of the Distal & Collecting Ducts of the
Nephron.
If Aldosterone is High – All Na in Filtrate is reabsorbed
If Aldosterone is Low – No Na in Filtrate is reabsorbed
Works by:
ACTIVATING the Na/K-ATPases in the Principal Cells of Distal & Collecting Ducts:
Increases Na+ & ClReabsorption
Increases K+ Secretion
Promotes Na+ -Channel Synthesis & Insertion into Luminal Membrane:
Facilitates the Na+ Reabsorption mentioned above.

Case study notes, Acid base balance study; [Link]

 ENDOCRINE SYSTEM

Regulation of K+ : The Primary Intracellular

Electrolyte:
Primary Roles in Normal Neuromuscular Function, Membrane Potentials & Membrane Transport.
Deficient Intracellular K+:
Cell membrane will be more Negative than normal (Ie: Hyperpolarised)
Therefore, it’ll be harder to initialize an action potential as it takes more to reach threshold.
Excess Intracellular K+:
Cell membrane will be more Positive than normal (Ie: Depolarised)
Therefore, it’ll be easier to initialize an action potential as it takes less to reach threshold.
Effect on the Heart:
The heart is particularly sensitive to K+ Levels.
Both Too High & Too Low K+ Levels will Disrupt Electrical Conduction of the Heart → Can be
Fatal.
Regulating K+ Levels:
Relies solely on K+ Secretion by the “Principal Cells” in the Collecting Ducts of the Kidneys.
Principal Cells Detect [K+ ] in the Blood:
High Blood [K+ ] → K+ Secretion is Increased
High Blood [K+ ] → K+ Secretion is Decreased
Adrenal Glands Detect [K+ ] in the Blood:
High Blood [K+ ] DIRECTLY Stimulates Aldosterone Release from Adrenal Cortex.
Aldosterone → Activates Na+ /K+ -ATPase’s in the Distal Tubules & Collecting Ducts:
→
This Increases Reabsorption of Na+ , Cl- & H2O from Distal Tubule Interstitium
But ALSO causes Secretion of K+ into the Filtrate.

[Link]
 ENDOCRINE SYSTEM

ENDOCRINE
REGULATION
OF GROWTH
 ENDOCRINE SYSTEM

ENDOCRINE
REGULATION
OF GROWTH

Influences on Growth:
Genetics
Nutrition
Endocrine Factors
(Growth Hormone)
(IGF’s – Insulin-like Growth Factors)

Phases of Growth:
Note: These Differ in their Rates of Growth and Regulators/Contributors:

Major Regulators/Contributors

Phase of Growth
Nutrition Hormonal Genetics

Yes - #1 Insulin (Acts as a growth factor in this No

Foetal (In Utero) phase) IGF-I

Infantile (Birth → Yes - #1 GH & IGF is present, but in low amounts Yes – (Only after a few months after birth)
2yrs) – NOT Imperative.

-Ve influence only if - IGF Levels Increase Yes - #1

malnourished -GF Receptors Increase
Pre-Pubertal
(Childhood)
Note: Growth Velocity progressively declines during this phase (Transition from Infant → Child)
Note: Body Proportions start to change.

Ve influence only if Sex Hormones:

malnourished → GH Release
Pubertal (Early → Epiphyseal Closure
Teens) GH → Causes IGF Release
GH + IGF → Bone Elongation

Post-Pubertal Note: Growth Velocity peaks & then stays same for ≈6yrs.
(Late Teens) (The last 3 years mainly concern the Trunk)
 ENDOCRINE SYSTEM

Major Hormones involved with Growth:

Growth Hormone, AKA: Somatotropin
Insulin-like Growth Factors (Somatomedins) (IGF-I & IGF-II)
Somatostatin (Inhibits secretion of GH from Ant. Pit.) -
Thyroid Hormone
Cortisol – (Not Direct – has a ‘permissive’ role. Ie: Other growth hormones are more effective if it’s
present)
Sex Hormones (Oestrogen/Testosterone)

Note: Somatostatin = The Primary Inhibitor

of Growth:
Produced By Numerous Organs, Including:

]
Hypothalamus, Ie: In organs that Release other Hormones (Ie:
Placenta, Somatostatin = A safeguard to Mass-Release of
& Pancreas Mass-Release of Hormone) Hormone) – (Paracrine)

Primary Actions Include (but not limited to):

(Mostly an ‘Inhibitory Hormone’ - Can be
Endocrine/Paracrine/Autocrine/Luminal/Neurohormone)
In Pancreas: Inhibits Insulin Release; Also Inhibits Glucagon Release; Also inhibits Exocrine
Pancreas
In Anterior Pituitary: Inhibits GH release, TSH release, Prolactin release, & ACTH release
In GI Tract: Slows gastric emptying, Slows peristalsis, Suppresses pancreatic hormones
Release is Stimulated By:
Peptide ‘Urocortin3’ (Ucn3) released by Beta Cell to inhibit insulin release
Cholecystokinin (CCK) released by Antral D-Cells
Many other locally-relevant stimulants; (research ongoing)
Release is Regulated By:
Locally-relevant factors; (research ongoing)

Hypothalamic Hormone of Growth:

GHRH (Growth-Hormone Releasing Hormone):
Produced Mainly in: Hypothalamus (But also in GIT, Pancreas & Placenta)
GRF Release Stimulated By:
Dopamine
GABA
α-Adrenergic Agonists
Exerts Effects on: Somatotropes (Anterior Pituitary) →↑
Growth Hormone Release.
 ENDOCRINE SYSTEM

Anterior Pituitary Hormone of Growth:

Growth Hormone:

Produced by: Anterior Pituitary (After ≈2mths Organs Stimulated by Growth Hormone:
old) Liver - Hepatocyte Growth Factor
Blood Transport: ≈45% bound to Carrier Protein Chondrocyte - Fibroblast Growth Factor
– (Prolongs ½ Life) Kidney - Epidermal Growth Factor
Regulation of Release: Pancreas - Nerve Growth Factor Receptor
Stimulation: GRH - (Growth-Hormone Production
Releasing Hormone) Thymus - IL-1 (Interleukin 1) →
Bone Marrow
Inhibition: Somatostatin Proliferation
Actions: Uterus - Oestrogen Receptor Production
Growth-Promoter from Early Childhood → Breast - Oestrogen Receptor Production
Onwards
Longitudinal Bone Growth & Remodelling
Skeletal Muscle Growth
Liver Growth
Stimulates IGF-Binding Protein Synthesis
(Important carrier for IGF)
Stimulates IGF Synthesis
Metabolic Effects:
Stimulates:
Lipolysis
Ketogenesis
Gluconeogenesis
Protein Synthesis
Lactation
Inhibits Insulin Action.
Boosts Immune Function.

Liver & Other Tissues:

Insulin-Like Growth Factors (IGF’s):

Both IGF-I & IGF-II are Structurally Similar to Proinsulin (The Insulin Precursor)
IGF-I - Chromosome 12
IGF-II - Chromosome 11
Circulates bound to IGFBP (Insulin-like Growth Factor Binding Protein)
Bind to Specific Receptors
Stimulate Cell Division together with other Growth Factors.
Foetal Life:
Act in Paracrine Fashion
IGF made by all foetal tissues (However, mainly by liver after birth)
Absence of IGF-I in Foetal Life→ Intra Uterine Growth Retardation
 ENDOCRINE SYSTEM

The Growth Hormone Axis:

[Link]
 ENDOCRINE SYSTEM

PHYSIOLOGICAL
RESPONSE TO
STRESS
 ENDOCRINE SYSTEM

PHYSIOLOGICAL
RESPONSE TO
STRESS

Stress & The Hypothalamo-Pituitary Axis:

1- Stressors (Internal or External) trigger Receptors.
2- Receptors inform the Hypothalamus
3- Hypothalamus - Activates Sympathetic Pathways
Secretes Corticotrophin-Releasing Hormone →
Ant. Pituitary releases ACTH. -
4- Both Sympathetic Activation & ACTH Release →
Stimulate the Adrenal Glands to produce
Glucocorticoids.
5- Adrenal Glands - Secrete Catecholamines (Incl. Adrenaline)
Secrete Cortical Steroids (Incl. Cortisol)

Circadian rhythm of adrenal glucocorticoid Figure onResearchGate; [Link]

regulation-of-adrenal-GC-and-its-physiological-roles-GC-is-primarily_fig3_49835615
 ENDOCRINE SYSTEM

Schematic of the Body’s Response to Stress:

Metabolic Actions of Adrenaline/Epinephrine

(Fight/Flight Response Hormone):
↑Glycogenolysis (Liver) → ↑Blood-
↑Lipolysis (Adipose) → ↑Free Fatty-Acids. ] ↑Energy Precursor Levels in Blood
Glucose.

↑Glycogenolysis (Muscle)
→ Fuels Muscle Cells
→ Provides Lactate → Liver converts
back to Glucose (Gluconeogenesis) →
↑Blood-Glucose
 ENDOCRINE SYSTEM

The General Adaptation Syndrome (GAS) Theory:

Dr Hans Selye proposed the “General Adaptation Syndrome” as the Body’s Responses to Stress
He also noticed 3 Universal Symptoms of Chronic Stress:
Adrenal Cortex Enlargement
Atrophy of Lymphoid Tissues
Bleeding Ulcers in Stomach & GI Tract.
Overview:
Stress → Causes Physiological Changes →Causes Symptoms
There are 3 stages. Note: If the stress is overcome during one of the stages, the ‘GAS’ will
terminate in that stage
3 Stages of the General Adaptation Syndrome:
Stage 1: ALARM REACTION:
When we are surprised or threatened →
Immediate Physical Reaction.
Fight or Flight Response
Prepares the body for life-threatening situations, channelling resources away from things like
the Digestive & Immune Systems, to more immediate muscular needs.
↑ Sympathetic Nervous System
↑ Catecholamines from Adrenal Medulla
Stage 2: STAGE OF RESISTANCE:
If stressors continue, the body enters the Resistance Phase, where we feel like we’ve adapted
to the stressors, but the body is working at abnormally high levels to keep up with the ↑
demands.
↑ Cortisol Secretion
Sustained Catecholamine Actions
Stage 3: STAGE OF EXHAUSTION:
Eventually, the body gives up on maintaining a high level of stress. Parts of the body literally
start to break down → Sickness → Possible Death.
↓ Adaptive Endocrine & Neuroendocrine Functions

[Link]
 ENDOCRINE SYSTEM

Effects of Stress on The Immune System:

Similar to GAS theory, Acute Stress ENHANCES the Immune System, but Chronic Stress
SUPPRESSES it
The Effect of Stress on the Immune System is ‘BIPHASIC’:
↑
1- During Acute Stress – There is a shift towards Innate Immune Responses.
↑ ↑
( Granulocyte/Macrophage/NK-Cell Activity + Complement & Acute-Phase Proteins)

2- If Stress Continues – There is a shift from Cellular Immunity to Humoral Immunity.

↓ →
Type-1 Helper T-Cell Activity ( Become Macrophages)
↑ →
Type-2 Helper T-Cell Activity ( Become Plasma Cells → Secrete Antibodies)
3- If Chronic Stress – There is a Decrease in almost all functional Immune Responses
Hence: Increase in Stressor Duration → Shifts from Adaptive to Detrimenta
 ENDOCRINE SYSTEM

REPRODUCTIVE
ENDOCRINOLOGY
 ENDOCRINE SYSTEM

REPRODUCTIVE
ENDOCRINOLOGY

The Hypothalamic Sex Hormone:

Gonadotropin-Releasing Hormone (GnRH):
Peptide Hormone
Pulsatile Release (≈90mins)

The Pituitary Sex Hormones:

Gonadotropins - FSH & LH:
Are Glycoproteins
Released by the Anterior Pituitary in response to Pulsatile release (90mins) of GnRH.

Available from: [Link]

hypothalamic-pituitarygonadal-HPG-axes_fig5_268791949
 ENDOCRINE SYSTEM

Inhibin:
Produced by the
Sustentacular/Sertoli Cells
(Male) & Granulosa Cells
(Female).
Released in response to high
FSH.
Inhibits FSH release via
Hypothalamic Inhibition.

Note: Sex Hormone Binding Globulin is an Important Transporter:

Secreted by the Liver
↑
Increased by Oestrogen
↑
Decreased by Androgen
Constant in Males
↑↑
Cyclical in Females – (but During Pregnancy, →↑
Oestrogen SHBG)

The Important Androgens:

#1 – Testosterone - Affects
Mainly the Testes
40% - Bound to SHBG (Sex-
Hormone Binding Globulin)
60% - Bound to Albumin
2% - Free (Active) –
(Receptors are intracellular :.
Must be able to enter the
cell)
Dehydroepiandrosterone
(Sulphate) – DHEA(S) - Affects
Mainly the Periphery
Androstenedione - Affects
Mainly the Periphery
 ENDOCRINE SYSTEM

Actions of Androgens:
Primary Sex Characteristics:
Growth & Maturation of Reproductive Tract @ Puberty
Maintenance of Reproductive Tract in Adulthood
Libido
Enhance Spermatogenesis
Secondary Sex Characteristics:
Body Hair
Deep Voice
Thick, rough skin
Bone Growth
Androgen Binding Protein Synthesis (in Sertoli/Sustentacular Cells)
↑ Musculature
Measuring Androgen Levels – “The Free Androgen Index”:
Gives a measure of the “free” active fraction of Androgens.

The Important Female Reproductive Hormones:

What are they?

Oestrogen/Estrogen (3 types: Estradiol, Estrone, Estriol)
Progesterone
Secreted By:
Produced mainly by Ovaries (Corpus Luteum)
Some Estrogen is also produced in…
Adrenal Cortex
Adipose Tissue
Placenta (During Pregnancy)
Synthesis:
All Are Steroid Hormones…
Therefore, are produced from Cholesterol
1- Theca Cells (of ovarian follicle) convert Cholesterol to Pregnenolone
2- Some Pregnenolone converted directly to → Progesterone
3- Rest of Pregnenolone converted to → Dehydroepiandrosterone (DHEA) →
Androstenedione
4- Androstenedione diffuses to nearby Granulosa Cells which converts to →Testosterone
5- Testosterone converted to → Estrodiol
6- Estrodiol → Released into blood (bound to SHBG – Sex Hormone Binding Globulin)
 ENDOCRINE SYSTEM

Primary Actions of Estrogen/Oestrogen:

Puberty:
Maturation of Female Reproductive Organs (uterus, fallopian tubes, vagina)
Secondary sexual characteristics (e.g. breast growth, fat distribution)
Menstruation:
↑ Estrogen (pre-ovulation) → prepares uterine epithelium for implantation (endometrial
proliferation); endometrial secretion in collaboration with progesterone
Dominant hormone during the follicular phase of ovarian cycle; follicle maturation; initiates
ovulation via FSH, LH surge
Pregnancy:
Placenta secretes Estrogen to stimulate Myometrium development
Promotes cervical ‘ripening’ prior to labour.
Increases uterine responsiveness to oxytocin leading up to labour
Supports mammary duct growth
Systemic:
Anabolic effect on bones
Promotes skin elasticity, blood vessel flexibility
Promotes fat deposition
 ENDOCRINE SYSTEM

Primary Actions of Progesterone:

Menstruation:
Dominant hormone during Luteal/Secretory Phase of ovarian cycle
Maintains Pregnancy:
Reduces Myometrium irritability (Prevents pre-term labour)
Thickens Cervical Mucous Plug
Promotes breast gland development & milk production
Increases respiratory centre’s sensitivity to CO2 →Raises basal respiratory rate.
Systemic:
Augments Estrogen’s anabolic effect on bones →
Increased bone density
Promotes skin elasticity

Estrogen/Progesterone Release is Stimulated By:

Pulsatile releases of GnRH from Hypothalamus → FSH/LH Surges from Anterior Pituitary
FSH/LH → Stimulates maturation of Ovarian Follicles → Secrete Estrogen & Progesterone
Release is Regulated By:
Hypothalamo-Pituitary-Gonadal Feedback Axis (See over the page)
 ENDOCRINE SYSTEM

Hormonal Regulation of the Ovarian Cycle:

1) Day 1 – Hypothalamus increases levels of GnRH (Gonadotropin-Releasing Hormone) and
stimulates the Anterior Pituitary to produce FSH (Follicle-Stimulating Hormone)& LH (Luteinising
Hormone).
2) FSH & LH stimulate follicle growth, maturation & oestrogen secretion.
FSH targets follicle cells
LH targets the thecal cells – makes thecal cells produce androgen.
Androgen diffuses through basement membrane, where the granulosa cells convert it to
oestrogens.
3) Medium oestrogen levels exert negative feedback to the Ant. Pituitary, inhibiting FSH & LH
release.
Inhibin released by granulosa cells also exerts negative feedback on FSH release.
4) At a critically high oestrogen level, positive feedback is exerted on the brain & Ant. Pituitary.
5) Midcycle – This positive feedback causes the Ant. Pituitary to release a sudden burst of LH (and
also some FSH – role midcycle is currently unknown).
6) LH surge stimulates the primary oocyte of the dominant follicle to complete MEIOSIS I, forming a
secondary oocyte + first polar body.
LH surge also triggers ovulation.
After ovulation, oestrogen levels decline due to the damaged dominant oestrogen secretor.
7) LH Surge also transforms ruptured follicle into corpus luteum – stimulates it to produce
progesterone & oestrogen.
8) Corpus luteum secretes inhibin along with progesterone & oestrogen, exerting a strong negative
feedback signal to the Ant. Pituitary – Stops the release of LH & FSH.

→
End of cycle – LH levels fall corpus luteum degenerates →
no oestrogen or progesterone
production by Corpus Luteum → no negative feedback to the hypothalamus →
hypothalamus
increases FSH & LH levels →
Back to square #1-
 ENDOCRINE SYSTEM

Hormonal Regulation of Spermatogenesis:

1) Hypothalamus releases GnRH (gonadotropin-releasing hormone) which
2) stimulates the release of gonadotropins: FSH (Follicle stimulating hormone) & LH (Luteinizing
hormone).
3) FSH: stimulates sustentacular cells to release Androgen-binding protein (ABP) Makes →
spermatagonium, spermatocytes, and spermatozoa receptive to the androgen: Testosterone.
4) LH: stimulates the interstitial (Leydig) cells [Basally external to Seminiferous tubules] to
produce testosterone which triggers & maintains spermatogenesis.
5) Testosterone produced by Leydig (interstitial) cells inhibits GnRH production; as does Inhibin,
produced by the sustentacular (sertoli) cells.

When testosterone is at its peak → sperm count is high (20Mil+ ) →

inhibin levels rise GnRH →
→
decreases FSH & LH levels decrease →
Testosterone & ABP levels decrease →
spermatogenesis
slows.
When sperm count is low (20Mil - ) →
inhibin & testosterone levels are low →
no negative feedback
to hypothalamus →hypothalamus releases GnRH →
Ant. Pituitary releases LH & FSH FSH →
stimulates sustentacular (sertoli) cells to produce ABP; LH stimulates the interstitial (Leydig) cells to
→
produce testosterone Testosterone + ABP stimulates spermatogenic cells →
Spermatogenesis
increases.

OpenStax College, CC BY 3.0 <[Link] via Wikimedia Commons

 ENDOCRINE SYSTEM

Functional Micro-Anatomy of the Testes:

Leydig Cells (In Interstitium of the Testes):
#1 Function = Produce Testosterone (Stimulates Spermatogonia to enter Spermatogenesis)
Stimulated by LH (Luteinising Hormone)
Seminiferous Tubules (In Lobules of Testes):
Spermatogonia (Germ/Stem-Cells):
In Basal Lamina of Seminiferous Tubules
#1 Function = Are the precursors for Spermatogenesis
Stimulated by Testosterone.
Sertoli/Sustentacular Cells:
Make up the Walls of the Seminiferous Tubules
Main Functions =
Endocrine – Production of Androgen Binding Protein (ABP)
– (Makes Spermatogenic Cells receptive to Testosterone)
Endocrine – Production of Inhibin
– (Provides negative feedback to the Hypothalamus)
Blood-Testes Barrier (because spermatids are genetically unique & require protection
from autoimmunity)
Nourish Sperm
Phagocytosis – (mop up any dead/underdeveloped spermatids)
Produce Tubular Fluid – (Help transport the sperm)
Produce Plasminogen Activating Factor – (Help free the sperm from tubule wall)
 ENDOCRINE SYSTEM

GENERAL
OVERVIEW OF
ENDOCRINE
DISORDERS
 ENDOCRINE SYSTEM

GENERAL
OVERVIEW OF
ENDOCRINE
DISORDERS

Level-Of-Function Disorders:
Hypofunction Disorders: Hyperfunction Disorders:
Where the gland produces less than it Where the gland produces more than it
should. should.
Common Causes: Common Causes:
Loss of reserve Hyper-secretion
Hypo-secretion Loss of suppression
‘Agenesis’ – failure to develop ↑
Hyperplasia ( Proliferation)
embryonicaly Neoplastic Change (Tumour)
Atrophy – Wasting away due to Hyperstimulation
injury/disease/lack of use. Ectopic Sites of Secretion (Some far-off
Active Destruction tumours secreting hormone)
Tumour

Hierarchical Classification of Hypothalamo-

Pituitary Axis Disorders:
Note: Endocrine disorders of the Hypothalamo-Pituitary Axis are often classified in a Hierarchical
Fashion depending on the origin of the disorder:
Primary:
Disorder of the Target Gland
(eg: Primary Hypothyroidism – the Thyroid Gland itself is under-responsive to TSH stimulation)
Secondary:
Disorder of the Pituitary Gland
(eg: Secondary Hypothyroidism – the Pituitary Gland is under-producing TSH)
Tertiary:
Disorder of the Hypothalamus
(eg: Tertiary Hypothyroidism – the Hypothalamus is under-producing TRH)
 ENDOCRINE SYSTEM

Testing for an Endocrine Disorder:

Basal Hormone Testing:
A single ‘snapshot’ measurement of the concentrations of specific hormones.
Eg: High [Thyroid-Stimulating Hormone] → Therefore Primary Hypothyroidism.
Problem – Some secretions are Pulsatile, meaning random measurements don’t accurately
diagnose a disorder of that gland. The Solution: Dynamic Hormone Testing.
Dynamic Hormone Testing:
Using exogenous chemicals/hormones to Stimulate/Suppress activity of a target gland. This tests
the responsiveness of a target gland to feedback stimuli.
Suppression Tests:
When Hyperfunction is suspected, an inhibitor is administered and then the hormone
concentration is re-measured to see if it has decreased. If not, Hyperfunction is
confirmed.
Stimulation Tests:
When Hypofunction is suspected, a stimulator is administered and then the hormone
concentration is re-measured to see if it has increased. If not, Hypofunction is confirmed.

Overview of Common Endocrine Symptoms:

Diabetes (1 & 2): PolyCystic Ovarian Syndrome:
Weight Change Weight Gain
Polyuria, Nocturia & Thirst Hirsutism
Visual Disturbances Infertility
Infections & Immunosuppression
Cushings Syndrome:
Constant Hunger
Caused by Excess Corticosteroids
Nausea + Vomiting
Moon Facies (Fat, white, round faces)
Fatigue
Muscle Wasting + Weakness
DKA (Diabetic Ketoacidosis) =
Weight Gain (Truncal Obesity)
Emergency Presentation
Stretch Marks due to Weight Gain
Hyperthyroidism: Pituitary Adenoma:
Weight Loss Peripheral Vision Loss
Fatigue Compression symptoms or Secretory
Suppressed TSH Symptoms
Elevated T4 Secretory

Hypothyroidism:
→ eg: Prolactin → Galactorrhoea +
Gynecomastia
Weight gain
Pretibial Myxoedema
→ eg: GH→ Gigantism (Pre-Puberty) →
Acromegaly (Post Puberty)
Periorbital Oedema
Bradycardia
→ eg: ACTH: → Cushing’s Syndrome

Bradypnoea
 ENDOCRINE SYSTEM

Acromegaly: Anorexia:
Soft-Tissue Swelling Weight Loss
Arthritis Fatigue
Hyperhidrosis ↓ BMI
Headache + Visual Field Defect ↑ FSH + LH (Due to no ovulation)

Addison’s:
↑ GH
Hypokalaemia (often due to vomiting)
Autoimmune
Weight Loss
→ Arrhythmias

Fatigue
Hypotension
Hyponatraemia
Hyperkalaemia
Hyperpigmentation
 ENDOCRINE SYSTEM

THYROID
DYSFUNCTION
 ENDOCRINE SYSTEM

THYROID
DYSFUNCTION

HYPOTHYROIDISM (Most Common):

“Under-Secretion of Thyroid Hormone”
Pathophysiologies:
**Dietary: - Insufficient Iodine intake – (Worldwide greatest cause due to poverty)
**Autoimmune: ‘HASHIMOTO’S THYROIDITIS’
– Anti-Thyroid Peroxidase Antibodies (Anti-TPO-Abs) →↓ T3/T4 Production
- or Anti-Thyroglobulin Antibodies → Destroy T3/T4.
Classically Women >60yrs
Hypothalamic-Pituitary Disorder
Either a failure of Hypothalamus to produce enough TRH
Or a failure of the Pituitary to produce enough TSH
Effects of Hypothyroidism:
↓ Metabolic Rate
↓ Body Temperature & Cold Intolerance
↓ Sympathetic Sensitivity
If Extreme→ “Cretinism” – Severely stunted physical growth & mental development.
Clinical Features – Affects virtually ALL Systems:
General:
Fatigue
Cold Intolerance
Apathetic Face
Droopy Eyes
Hoarseness
Menstrual Irregularities
Muscle Weakness
CVS:
Bradycardia
Pericardial Effusion
↓ Cardiac Output
GI:
Weight Gain Despite Poor Appetite
Constipation
 ENDOCRINE SYSTEM

Neuro: Hair:
Paraesthesia Dry, Coarse, Loss of Lateral 1/3
Slow Speech Eyebrow
Mental Sluggishness MSK:
Skin: Muscle Cramps
↓
Pale, Cool, Dry (Due to Blood Flow) “Hung Reflexes” – Delayed Relaxation
NON-Pitting Oedema (Due to in deep tendon reflexes.
Accumulation of Hyaluronic Acid & Haem:
Glycosaminoglycans) Macrocytic Anaemia
Face & Periorbital Oedema

Diagnosis (See ‘Diagnosing Thyroid Dysfunction’ section for more details):

TSH Levels – To see if Secondary Hypothyroidism
T4/T3 Levels – To combine with TSH to confirm exact cause
If Hashimotos:
+ Anti-Thyroid Peroxidase Antibodies (Anti-TPO-Abs)
+ Anti-Thyroglobulin Antibodies

[Link]
 ENDOCRINE SYSTEM

Treatment of Hypothyroidism:
Thyroid Hormone Replacement:
L-Thyroxine (Thyroid Hormone Replacement)
*Thyroxine/levothyroxine (T4)
Note: Thyroxine is the preferred agent as it is the least biologically active – (Longer Half-life), and
can be Deiodinated by the body to T3 (Thyronine) when needed.

Complications of Hypothyroidism:
“CRETINISM”:

Terminology:
= “Hypothyroidism that develops in Infancy
or Early Childhood → Severely stunted
physical growth & mental development”
Aetiology:
Maternal Hypothyroidism (Typically Iodine
Deficiency)
Clinical Features:
Short Stature
Severe Mental Retardation
Coarse Facial Features
Protruding Tongue
Umbilical Hernia
(Note: Severity of Disease depends on When
Maternal Hypothyroidism occurred during
Pregnancy) Sir B. Bramwell, Sporadic [Link] BY 4.0 , via
Wikimedia Commons

*MYXOEDEMA COMA!:

Most Severe Complication

Aetiology:
Longstanding Undiagnosed Hypothyroidism + Precipitant (Infection/Surgery/MI/CHF
Clinical Features:
Hypothermia
Hypoventilation
Bradycardia
Hypertension
Hypoglycaemia
Stupor
 ENDOCRINE SYSTEM

Dermatology: MSK:
Acropachy (Digital Clubbing & Swelling; Fingers Bone Resorption →
Osteoporosis
& Toes) Haem:
Hair: Fine, Allopecia Lymphadenopathy (esp. Graves’
Skin: Soft, Warm, Flushed, Sweaty. Disease)
Vitiligo (Pigmentation) Others:
Soft Nails with Onycholysis (Plummer’s Nails) Menorrhagia
Pretibial Myxoedema

[Link]

Treatment of Hyperthyroidism:
Surgery (Thyroidectomy):
Total Vs Partial
Radioactive Iodine - Destroy Thyroid Follicular Tissue:
Radioactive Iodine (I125)
→
Note: Can kill too much thyroid tissue Hypothyroidism.
Anti-Thyroid Agents:
*Carbimazole
 ENDOCRINE SYSTEM

Complications of Hyperthyroidism:
THYROTOXIC STORM:

Aetiology: Differentials:
Precipitated by Infection/Trauma/Surgery/etc. In a Sepsis
Hyperthyroid Patient. Phaeochromocytoma
Malignant Hyperthermia

Pathogenesis: Lab Findings:

Pre-existing Hyperthyroidism →↑ Sympathetic Sensitivity ↑↑↑ T3/T4
+ Precipitant →↑ Catecholamine Levels → ↓↓↓ TSH
Sympathetic Symptoms. (Leukocytosis,
Hypercalcaemia, ↑LFTs)
→SEVERE Clinical Features – 50% MORTALITY: Treatment:
Extreme Fever § Tachycardia/Arrhythmias Treat Precipitating Factor,
Vascular Collapse (Hypotension) Plus:
Congestive Heart Failure/Pulmonary Oedema
Vomiting/Diarrhoea
Confusion/Delirium/Coma
 ENDOCRINE SYSTEM

DIAGNOSING THYROID DYSFUNCTION

Step 1 – Think…What Level is the Problem?

↓↑
Primary / -Thyroidism – (Glandular Level)
Eg: Primary Hyperthyroidism = Graves’ Disease
Eg: Primary Hypothyroidism = Hashimoto’s Disease -
↓↑
Secondary / -Thyroidism:
Problem with the Pituitary Gland or Hypothalamus (Ie: ↓TRH / TSH)
Step 1 – Think…What Level is the Problem?

Thyroid Function Tests:

→
Test Plasma T₃, T₄ & TSH levels To determine the ‘level’ of the dysfunction
(Primary/Secondary)
↑
If Primary Hypothyroidism: TSH Levels, ↓ T₃ & T₄ Levels
↓
If Primary Hyperthyroidism: TSH Levels,↑ T₃ & T₄ Levels
↓
If Secondary Hypothyroidism: TSH Levels, ↓ T₃ & T₄ Levels
↑
If Secondary Hyperthyroidism: TSH Levels,↑ T₃ & T₄ Levels

Thyroid Autoantibody Assays:

Grave’s – Presence of TsAb’s
(Thyroid-Stimulating Antibodies)
Hashimoto’s – Presence of Anti-
Thyroid Peroxidase Antibodies
(Anti-TPO-Abs)
or Anti-Thyroglobulin
Antibodies Note: Thyroid Peroxidase is contained within the Follicle Cells
themselves, whereas Thyroglobulin resides within the Colloid –
Hence the staining.
 ENDOCRINE SYSTEM

TRH Stimulation Test (Dynamic Testing)

Investigates Pituitary-TSH Deficiency

Imaging:
Ultrasound – for sizing.
RadioIsotope Methods (Nuclear Medicine) – (Radioactive Iodide) to measure activity of the
gland.
Can distinguish Inactive (Cold) & Overactive (Hot) Nodules.

Histopathology:
Ie: Biopsy.
 ENDOCRINE SYSTEM

NON-TOXIC GOITRES
(Diffuse & Multinodular Goitres):

Terminology:

Goitre = “Enlargement of the Thyroid”

Non-Toxic Goitre = “Enlargement of the Thyroid Gland in a EUTHYROID Individual that is NOT DUE
TO Inflammatory, or Neoplastic Changes”

(Simple) DIFFUSE GOITRE (Early):

Aetiologies:
Normal Physiological Conditions
(Adolescence, Pregnancy, Lactation)
– Ie: Conditions requiring
↑Metabolism
Iodine Deficiency – Most Common

Pathogenesis:
Note: Hyperplasia; NOT Neoplastic –
↑
(Due to TSH Stimulation)

Morphology:
Goitre is Mild, Diffuse & Symmetrical

Clinical Features:
Most Pts are Euthyroid

Ix:
↑↑TSH
Normal T3/T4 (Unless Severe - ↓T3/T4) [Link]

Complications:
Mechanical (Dysphagia, Airway
Obstruction)
Endocrine (Toxic Nodule →
Hyperthyroidism)
 ENDOCRINE SYSTEM

NON-TOXIC MULTINODULAR GOITRE (Late):

Aetiology:
Prolonged Hyperplasia of a Diffuse Goitre due to Iodine Deficiency

Pathogenesis:
1- Simple Diffuse Goitre due to Iodine Deficiency
2- Prolonged Hyperplasia of a Diffuse Goitre →→
Multinodular Goitre.

Morphology:
Asymmetrical, Multinodular, Multilobulated, Goitres
Can be MASSIVE
Nodules are Un-Encapsulated, & Contain Variable amounts of Colloid (Brown, Gelatinous)

Clinical Features:
Massive Goitre
Most Pts are Euthyroid

Complications:
Toxic Adenoma/Toxic Nodule.

(Credit: “Almazi”/Wikimedia Commons)

 ENDOCRINE SYSTEM

THYROID NEOPLASMS
(Adenomas & Carcinomas):

Terminology:

Hot Nodules - Those secreting Thyroid Hormones regardless of TSH Levels.

Cold Nodules – Those that are Hypofunctioning regardless of TSH Levels

Clinical Features:

Mostly Asymptomatic
Palpable (sometimes visible) lump in throat
Goitre (later sign)
Red Flags:
Rapid Growth
Firm/Hard
Immobile
Voice Hoarseness
Dyspnoea
Dysphagia
Lymphadenopathy
Green Flags:
Mobile, Painful & Inflammation – Non-Neoplastic.

Universal Investigations of Thyroid Neoplasms (Despite Patterns):

1- Imaging
2- TFTs
3- FNA + Biopsy
4- Surgical Resection & Histology.
 ENDOCRINE SYSTEM

THYROID ADENOMA: “FOLLICULAR ADENOMA”

(Benign Neoplasms) – 90%:

Cold or Hot Adenomas

Morphology:
Solitary, Spherical Mass
Well-Defined, Intact Fibrous Capsule
≈3cm Diameter
Colour:
↓
Cold Adenoma = Grey-White colour (Due to Colloid)
↑
Hot (Toxic) Adenoma = Red-Brown colour (Due to Colloid Content)
Areas of Haemorrhage, Fibrosis & Calcification (Similar to MNG)

Clinical Features:
Unilateral Painless Mass
Cold Adenomas = Euthyroid
Hot (Toxic) Adenomas = Hyperthyroid

Investigations:
As above

Complications:
Excellent Prognosis (post-surgery) – No Recurrence or Metastasis.

[Link]
 ENDOCRINE SYSTEM

THYROID CARCINOMAS
(Malignant Neoplasms) – 10%:

PAPILLARY CARCINOMA of the

Thyroid – MOST COMMON:
Clinical Features:
Asymptomatic, Mobile Thyroid Nodule (Indistinguishable from Benign Nodule)
Note: Presenting Symptom is often Cervical Lymphadenopathy.
Symptoms of Severe Disease: Dysphagia, Hoarseness, Cough

Investigations:
As above

Treatment:
Surgical Excision

Prognosis:
Malignant, but Clinically Benign – Ie: High survival rate (98% @ 10yrs).
Rarely extends outside the thyroid capsule or to other structures

[Link]
 ENDOCRINE SYSTEM

FOLLICULAR CARCINOMA of the Thyroid:

Morphology:
Single Nodules
May be Well-Demarcated (Similar to Follicular Adenoma) or Infiltrative
Grey-Tan Colour
Central Fibrosis & Calcification

Clinical Features:
Slow-Growing, Painless Nodules
Follicular Carcinoma prefers Haematogenous Metastasis rather than Lymphatic
:. No Lymphadenopathy
Aggressive - Spreads Early to Bone (May present as a pathological fracture)

Treatment:
Total Thyroidectomy
+ Radioactive Iodine Ablation for ?Metastases.
+ Supportive Thyroid Hormone Replacement

Follicular Neoplasms in the 4th Edition WHO Classification of Endocrine Organs;

[Link]
carcinoma-Multiple-invasions-by-tumor-nests-into_fig4_348663497
 ENDOCRINE SYSTEM

ANAPLASTIC CARCINOMA of the Thyroid:

Pathogenesis:
Typically arise due to De-Differentiation of a Papillary or Follicular Carcinoma

Morphology:
Invasion out of the Thyroid Capsule & Into Adjacent Structures (Eg: Trachea &
Jugular Vein)

Clinical Features:
Typically Elderly
Rapid-Growing Nodule
Compressive Symptoms: Dysphagia, Dyspnoea, Hoarseness, Cough

Treatment/Prognosis:
Highly Aggressive – Local Invasion & Metastasis @ Presentation
No Treatments
100% Mortality @ 1yr.

MEDULLARY CARCINOMA of the Thyroid:

Aetiology:
70% Sporadic Proto-oncogene Mutation.
30% Occur in Multiple Endocrine Neoplasia Syndrome Type 2 (MEN-2a & 2b)

Morphology:
Solitary if Sporadic; Multiple/Bilateral if MEN-2a/b.
Firm, Pale Grey-Tan, Areas of Haemorrhage & Necrosis
Invasion outside the Thyroid Capsule

Clinical Features:
Sporadic:
Thyroid Nodule + Dysphagia or Hoarseness
↑
Note: NO Hypocalcaemia, despite Calcitonin.
MEN-2 Also Involves:
(Thyroid Gland – Medullary Carcinoma of the Thyroid )
Adrenal Medulla – Phaeochromocytoma
Parathyroid Gland – Parathyroid Hyperplasia
 ENDOCRINE SYSTEM

Familial thyroid cancer: A review - Scientific Figure on ResearchGate. Available from:

[Link]
thyroid-carcinoma_fig13_50997813

Summary:
 ENDOCRINE SYSTEM

GROWTH
DYSFUNCTION
 ENDOCRINE SYSTEM

GROWTH
DYSFUNCTION

Defects in Endocrine Control of Growth:

Hyper: Hypo:
Too Much Growth Defective Growth Hormone Axis:
Hormone &/or Growth GH-Deficiency:
Factors (Rare): Primary GH Deficiency:
Eg: Childhood Hypothalamic Defect
Gigantism And/Or Pituitary Defect
Eg: Adults - Secondary Pituitary Deficiency:
Acromegaly Eg: Tumour & other Destructive Diseases.
Non-GH Causes: Eg: Psychosocial Deprivation (Ie: Kids in
Eg: Precocious abusive/non-supportive environments →
Puberty GH-Deficiency → exhibit slowed growth)
Bio-Inactive GH:
GH is produced by has little/no impact with
receptors.
Growth Hormone Insensitivity:
Primary GH Insensitivity:
GH Receptor Defect
IGF Synthesis Defect
IGF Receptor Defect
Signal Transduction Defect (GH/IGF) (Ie:
Secondary Messenger Defect)
Secondary GH Insensitivity:
GH-Inhibiting Antibodies
Malnutrition
Diabetes
Uraemia
Deficient in Other Hormones essential for
growth – Eg: Thyroid Hormone (Hypothyroidism)
 ENDOCRINE SYSTEM

General Treatment Principles of Short Stature:

Treatment Depends on Common Who Should Receive GH?

Origin of the Problem: Treatments: GH Deficiency
Is it Endocrine? Exogenous (Child/Adult)
What is the Defect? Growth Hormone Genetic Syndromes (Eg:
GH Deficiency Exogenous IGF-I Turners)
Receptor Defects Chronic Kidney Failure
IGF Deficiency (In Kids awaiting
Other? Transplant)
AIDS Wasting
Severe Burns
 ENDOCRINE SYSTEM

GROWTH HORMONE DEFICIENCY

(AKA. PITUITARY DWARFISM):
Aetiology: Pathogenesis:
Insufficient production of Growth Hormone Insufficient Growth Hormone
from the Pituitary → Abnormally short stature,
Can be Congenital (Present at birth) – Eg: but with NORMAL body
Genetic defects. proportions
Can be Acquired (develop later) – Eg: Severe
brain injury

Clinical Features: Diagnosis:

Slow or absent growth Clinical suspicion based on
Short stature (Below 5th percentile compared anthropomorphics (patient’s
to children of same age/sex) height, weight, arms/leg
Absent/delayed sexual development during lengths)
puberty Blood tests – Low levels of
May have symptoms of other co-existent Growth Hormone in the blood
Pituitary hormone deficiencies: Imaging – Xrays + MRI-Brain
Eg: Polyuria
Eg: Excessive thirst
Eg: Facial abnormalities

Treatment:
Synthetic Parenteral Growth Hormone Injections (Somatropin)
Replace any other pituitary hormone deficiencies
 ENDOCRINE SYSTEM

GIGANTISM/ACROMEGALY:
Aetiology: Pathogenesis:
Pituitary Adenoma Pituitary Adenoma → Secretes
Excess GH

Clinical Features: Diagnosis:

Insidious Onset IGF1 & GH Levels
Mostly Middle-Aged Adults Brain MRI
Symptoms:
Severe Disfigurement
Soft-Tissue Swelling (Hands, Feet,
Nose, Lips, Ears, Skin, Carpal
Tunnel)
Prominent Jaw & Supra-Orbital
Ridges
Hypertension
Compressive Pituitary Adenoma
→ Headache + Visual Field Defect

Treatment: Complications:
Surgical Removal of Pituitary Adenoma Hypertrophic Cardiomyopathy &
Somatostatin Analogues Heart Failure
Hypertension & Kidney Failure
Hyperglycaemia & Diabetes Mellitus
Accelerated Osteoarthrosis
Possible Malignancy

Elgee, CC BY 3.0 <[Link] via Wikimedia

Commons CSvBibra and Pat von Bibra, CC0, via Wikimedia Commons
 ENDOCRINE SYSTEM

ADH
DISORDERS
 ENDOCRINE SYSTEM

ADH
DISORDERS

Disorders of Fluid/Electrolyte-
Regulating Hormones:
Disorders of ADH:

DIABETES INSIPIDUS ( ADH): ↓

Condition characterised by Excessive Thirst & the inability to Concentrate Urine
2 Types:
Neurogenic (Neuro) - ADH Insufficiency
Nephrogenic (Renal) – Insensitivity of the kidneys to ADH
Signs/Symptoms:
Extreme Thirst
Excessive Urination
Risk of Hypokalaemia
Diagnosis Criteria:
Normal Blood Glucose
Normal Blood Bicarb To Rule out other causes of Excess Urination.
Normal Blood Calcium
Urinalysis – Low Osmolality, Electrolytes & Specific Gravity
Fluid Deprivation Test - No change in urine osmolality
Desmopressin Stimulation – Distinguishes between Neurogenic & Nephrogenic.
Treatment:
↑
Patients compensate by H2O Intake.
If Neurogenic – Desmopressin (Synthetic ADH) →↓ Urine Production.
If Nephrogenic – Hydrochlorothiazide Diuretic →↓ Urine Output in patients with DI
 ENDOCRINE SYSTEM

SIADH (Syndrome of Inappropriate ADH secretion) ( ADH): ↑

Caused by:
↓
Insensitivity of Hypothalamic Osmoreceptors to Plasma Osmolality
↓
Therefore, ADH release isn’t inhibited by Plasma Osmolality
(Other causes: Malignancy, Drugs, Primary Brain Injury, Infection, Hypothyroidism)
Condition characterised by Excessive ADH Release from Post. Pituitary Or Ectopic Source.
5 Cardinal Signs/Symptoms:
1- Fluid Overload (Without oedema or hypertension)
→
2- Hyponatraemia (Dilutional)
Headache
Nausea
Vomiting
Confusion
Convulsions (If Severe)
Coma (If Severe)
3- Natriuresis (Excretion of Sodium in Urine – usually excessive)
4- High Urine Osmolality relative to Plasma Osmolality.
5- Normal Renal & Adrenal Function
Treatment:
Fluid Intake Restriction
Drugs – (ADH Inhibitors):
Demeclocycline – Induces Nephrogenic Diabetes Insipidus as a Side Effect.
Hence desensitises ADH receptors in the Nephron.
Conivaptan – Inhibits 2 of the 3 ADH Receptors.
Tolvaptan – Competitive inhibition of ADH Receptors
 ENDOCRINE SYSTEM

[Link]
pathogenesis-and-clinical-findings/siadh/
 ENDOCRINE SYSTEM

ADRENAL CORTEX
DYSFUNCTION
 ENDOCRINE SYSTEM

ADRENAL
CORTEX
DYSFUNCTION

Adrenocortical Insufficiency
(Hyporadrenal) Syndromes:
ADDISON’S DISEASE (Primary Chronic
Adrenocortical Insufficiency):

Aetiologies (Multiple Possible):

Most Common = Autoimmune Adrenalitis (70%)

Pathogenesis (Autoimmune Adrenalitis):

↓↓ Aldosterone →
Hyponatraemia & Hyperkalaemia
↓↓ Cortisol

Clinical Features:
Initially: Progressive Weakness, Fatigue, Lethargy, Depression
Later:
GI - Anorexia, Weight Loss, Vomiting, Diarrhoea
Skin – Hyperpigmentation (Esp. Sun-Exposed & Pressure Point Areas)
↓
Electrolytes ( Aldosterone) – Hyponatraemia & Hyperkalaemia

Diagnosis:
Synacthen (Synthetic ACTH) Test →
(Measure Cortisol and Aldosterone 30mins after)
Adrenal-Autoantibodies
↑ ↓ ↑ ↑
UECs – ( K, Na, Urea Creatinine)
 ENDOCRINE SYSTEM

Treatment:
Cortisol Replacement (Hydrocortisone)
Correct Electrolytes

Complication - Addisonian Crisis:

Why: Stress/Acute disease → Adrenal Glands Cannot Respond → Crisis
Clinical Features:
Fever
Intractable Vomiting
Abdominal Pain
Hypotension
Coma
Shock (Vascular Collapse)
 ENDOCRINE SYSTEM

WATERHOUSE-FRIDERICHSEN SYNDROME
(Acute Adrenocortical Insufficiency):
Aetiology: Pathogenesis:
Overwhelming Sepsis Acute Haemorrhagic Infarction →
Adrenal Necrosis →
Acute Adrenal
Hypofunction:
→↓Aldosterone →
Salt & Water
Loss →Hypovolaemic Shock

Morphology Diagnosis:
Macro: Abrupt & Severe Clinical Course (Death
Haemorrhagic Mass (Blood Clot) in Hours-Days unless Treated)
Completely Obscures the Typically Meningococcal Septicaemia
Adrenal Gland :. Neck stiffness
Micro: :. DIC
Acute Haemorrhagic Necrosis Hypovolaemic Shock (Due to
(Starts in Medulla →
Spreads to ↓ Aldosterone)
Cortex)
Islands of Recognizable Cortical
Cells

Treatment:
Prompt Antibiotic Treatment
Fluids

Amadalvarez, CC BY-SA 4.0 , via Wikimedia Commons

 ENDOCRINE SYSTEM

CONGENITAL ADRENAL HYPERPLASIA (CAH) -

(Adrenogenital Syndromes/Virility Syndromes):
Aetiology: Pathogenesis:
Autosomal Recessive 21- 21-Hydroxylase Deficiency
Hydroxylase Deficiency →↓ Cortisol/Aldosterone Synthesis →
↑Androgen Synthesis

Clinical Features:
Androgen Excess:
Masculinisation of Females (Clitoral Hypertrophy/Hirsutism/Oligomenorrhoea)
Masculinisation of Males (Penile Enlargement/Precocious Puberty/Oligospermia)
Neonate with Ambiguous Genitalia
Mineralocorticoid (Aldosterone) Deficiency:
Hypotension & Salt Wasting.

[Link]
 ENDOCRINE SYSTEM

Adrenocortical Hyperfunction
(Hyperadrenal) Syndromes:

CONN’S SYNDROME
(& other Primary Hyper-Aldosteronisms):
Note: Aldosterone = Mineralocorticoid = Produced by the Zona Glomerulosa of the Adrenal Cortex.

Aetiology: Pathogenesis:
#1- Idiopathic Hyperplasia of Adrenal →Chronic Excess ↑↑ Aldosterone
Glands Secretion → ↓ →
Na+ Retention (& K+ )
#2- Aldosterone-Producing Adenoma Fluid Retention
(Conn’s Syndrome) → Hypertension
#3-(Rare) Aldosterone-Producing → Hypernatraemia
Carcinoma → Hypokalaemia

Clinical Features: Diagnosis:

**Universal Sign = Hypertension Very HIGH Aldosterone
Hypernatraemia (due to Renal Na Very Low Renin-Aldosterone Ratio (Ie:
Retention) ↓ ↑
Renin & Aldosterone)
Hypokalaemia (due to Renal K Wasting):

Treatment:
Idiopathic Hyperplasia: Spironolactone (Aldosterone Antagonist)
Adenomas (Conn’s): Surgical Resection

[Link]
 ENDOCRINE SYSTEM

CUSHING’S DISEASE/SYNDROME (Hypercortisolism):

Aetiology: Pathogenesis:
Cushing’s Syndrome: (Any cause of ACTH-Secreting Pituitary Adenoma →
Excess Glucocorticoid Levels) ↑ACTH Levels →↑
Cortisol
Cushing’s Disease: (Central – ACTH-
Secreting Pituitary Adenoma)

Clinical Features: Diagnosis:

Slow onset Dexamethasone Suppression Test
Early Features – (Hypertension & Weight (Central Vs. Primary)
Gain) ACTH Levels
Cortisol Levels
CT/MRI Brain (Pituitary Adenoma)

Treatment – Depends on Aetiology:

If Exogenous Cortisol – Wean Pt. off Cortisol.
If Pituitary Tumour (Cushing’s Disease) – Surgical Removal + Temp Cortisol Replacement.
If Adrenal Tumour – Surgical Removal + Temporary Cortisol Replacement.

Mikael Häggström, CC0, via Wikimedia Commons

Ozlem Celik, Mutlu Niyazoglu, Hikmet Soylu and Pinar Kadioglu, CC BY 2.5
<[Link] via Wikimedia Commons
 ENDOCRINE SYSTEM

PHAEOCHROMOCYTOMA
 ENDOCRINE SYSTEM

PHAEOCHROMOCYTOMA

PHAEOCHROMOCYTOMA

Aetiologies (Multiple Possible): Diagnosis:

Idiopathic Increased Urinary
May be familial (in MEN2 Syndrome) Catecholamines & VMA
(Vanillylmandelic Acid – A
Metabolite of Adrenaline & NA)
Pathogenesis
Tumour of the Medullary Chromaffin
Cells (Which produce
Catecholamines)
→ Increased Catecholamines
↑
( Adrenaline & Noradrenaline) Treatment:
→ Secondary Hypertension → Preoperative Sympatholytic Drugs
Hypertensive Crises (To prevent hypertensive crisis)
Surgical Resection

Clinical Features:
Young Age
10% Are Malignant
Symptoms:
#1- Paroxysmal Hypertension Complications:
Palpitations/Tachycardia - of Hypertension:
Headache Congestive Heart Failure
Sweating/Hot Flushes Pulmonary Oedema
Tremor Myocardial Infarction
Anxiety Ventricular Fibrillations
Nausea/Vomiting CVAs
(Note: Phaeos are a cause of
Surgically-Correctable Hypertension)
(Note: Phaeos May be associated
with MEN2 Syndromes)
 ENDOCRINE SYSTEM

Michael Feldman, MD, PhDUniversity of Pennsylvania School of Medicine, CC BY

2.0 <[Link] via Wikimedia Commons
 ENDOCRINE SYSTEM

DIABETES
 ENDOCRINE SYSTEM

DIABETES

Review of Insulin & Glucagon:

Insulin: Glucagon:
Released Due to: Released Due to:
↑ Blood Glucose ↓
Blood Glucose
↑ Blood Amino Acids ↓
Blood Amino Acids (Ie: Fasting)
Stimulates: Stimulates:
Glucose Uptake (Fat & Muscle) Glycogenolysis
Lipid Synthesis & Storage (Fat) Gluconeogenesis
Protein Deposition (Muscle) Lipolysis
Inhibits: Ketogenesis
Ketogenesis Inhibits:
Macromolecular Breakdown Macromolecular
Synthesis/Storage

Pancreatic regulation of glucose homeostasis - [Link]

glucose-levels-by-glucagon-and-insulin-When-blood-glucose-levels_fig3_297896821
 ENDOCRINE SYSTEM

Diabetes: General Information:

Diagnostic Criteria (The “7-11 Rule”):

Fasting BSL ≥ 7.0 mmol/L (Note: For Non-Pregnant)
Random BSL of >11 (Note: If Fasting BSL = 5.5-7.0 mmol/L → Perform OGTT)
OGTT – Oral Glucose Tolerance Test (Fasting) >11 @ 2hrs
Autoantibodies (If Type 1 Diabetes):
+ Anti-Islet-Cell Antibodies (Anti-ICAs)
+ Anti-Glutamic Acid Decarboxylase Antibodies (Anti-GADs)
(Note: HbA1c for monitoring only)
Note: People who have Impaired Glucose Tolerance and/or Impaired Fasting Glucose have
slightly raised fasting & Post Prandial BSL’s, but not high enough for diagnosis of diabetes.

Initial Presentation:
PPP – Polyuria, Polydipsia, Polyphagia
Unexplained Weight Loss/Fatigue/Lethargy
Recurrent/Persistent Infections, Delayed Healing & Immunosuppression (Eg: Genital Thrush)

Emergency Presentations:
HYPERs:
DKA - Diabetic Ketoacidosis
HONC - Hyperosmolar Non-Ketotic Coma
HYPOs:
Eg: Insulin Overdose/Over exercise/Missed Meal

Treatment:
Lifestyle (Diet + Exercise + Weight Loss)
Medications:
Insulins – (Broad range of Rapid to Long-Acting)
Oral Hypoglycaemic Agents:
“Insulin Secretagogues” – (*Sulfonylureas):
Biguanides - (*Metformin)
Incretin Mimetics:
Incretin Analogues – (*Exenatide):
DPP-4 Inhibitors – (*Sitagliptin)
 ENDOCRINE SYSTEM

Snapshot Overview of Types of Diabetes:

Type 1 Diabetes – Insulin Deficiency, Juvenile, Rapid Onset:

Aetiology – (Autoimmune Destruction of the β-Cells of the Pancreatic Islets)
Clinical Features – (Juvenile Disease, Rapid Onset)
Diagnosis – (+ Anti-GADs, Anti-Islet-Cell Antibodies (Anti-ICAs) & Insulin Auto Antibodies
(IAAs))
Treatment: - (Exogenous Insulin)
Complications – (Diabetic Ketoacidosis)

LADA – Latent Autoimmune Diabetes of Adults:

Aetiology – (Delayed Autoimmune Type I in Adults)
Clinical Features – (Slim Adults with Diabetes Symptoms)
Complications – (HONC, DKA)
Diagnosis – (Hyperglycaemia, + Anti-GADs, Anti-ICAs & Insulin Auto Antibodies)
Treatment – (Insulin)

Type 2 Diabetes – Insulin Resistance, Adults, Insidious Onset:

Aetiology – (Insulin Resistance And/Or Relative Insulin Deficiency)
Clinical Features – (Adults, Slow Onset +/- ‘Pre-Diabetic State’)
Diagnosis – (Random BSL >11, OGTT >11 @2hrs)
Treatment – (1- Diet & Lifestyle, 2- Orals [Metformin/Sulfonylureas/Incretins], 3- Insulin)

MODY – Maturity Onset Diabetes of Youth:

Aetiology – (Autosomal Dominant)
Pathogenesis – (Essentially a Type II DM in a Child)
Clinical Features – (Young, Non-Obese, Autosomal Dominant :. FamHx)
Treatment – (1- Orals [Metformin/Sulfonylureas/Incretins], 2- Insulin)
Complications – (Like Type II Diabetes (Ie: HONC rather than DKA))
 ENDOCRINE SYSTEM

Different Types of Diabetes:

Type 1 Diabetes – Insulin Deficient:

Autoimmune attack on the β-Cells of the Pancreatic Islets.
Results in a Physical Lack of Insulin Production
Aetiology can be Genetic & Environmental
Rapid Onset → Therefore Fewer Complications @ Diagnosis.
Presentation:
Hyperglycaemia
→
Ketonuria (Ketoacidosis)
Hyperventilation
Nausea
Vomiting
Abdo Pain
Rapid Significant Weight Loss
Excessive Hunger (Polyphagia)
Mental Fatigue
Treated with Exogenous Insulin
 ENDOCRINE SYSTEM

Type 2 Diabetes – Insulin Resistance:

Results from Insulin Resistance sometimes combined with Relative Insulin Deficiency.
Note: Obesity is the #1 Predisposer of Insulin Resistance:
Due to Change in Adipose-Release of ‘Adipokines’ – Hormones that Mediate Insulin
Resistance.
Incl: Resistin/Leptin/Adipopectin.
Peak onset @ ≈50yrs
Gradual Onset → Therefore ≈1/4 have Complications @ Diagnosis (Eg: Vascular)
Note: Many people spend years in a ‘Pre-Diabetic State’ – where BSL is higher than normal
but not high enough for a diagnosis of Type 2 Diabetes
Presentation:
Same as Type 1, Except:
No Ketonuria
Usually Overweight (Central Obesity)
Metabolic Syndrome (Due to Insulin Resistance):
↑ Circulating FFA’s
↑ Insulin
↑ Glucose
↓ HDL’s
↑ BP
Treated with Diet / Tablets / Exogenous Insulin
→
Note: Over time Insulin Resistance Increases & β-Cell Function Decreases
↑
Therefore the later stages require Amount of Treatment.
 ENDOCRINE SYSTEM

Complications of Diabetes:

Acute Complications:

Diabetic Keto-Acidosis (DKA):

Acute life threatening Caused By – (Type I Diabetes - Lack of

Insulin (Eg: Forgotten to take insulin))

Diagnosis:
Hyperglycaemia: High Glucose (>15 mmol/L)
Ketoacidosis: Low pH, Low Bicarbonate (< 15 mmol/L), Sweet Breath, Ketonuria

Symptoms:
– of Underlying Diabetes – (Polyuria, Polydipsia, Weight loss)
– of Hyperglycaemia – (Glycosuria/Osmotic dieresis, Severe Dehydration)
– of Hyperketonaemia →
KetoAcidosis – (Vomiting, Acetone Breath, Hyperventilation)
↓ ↓
- of Electrolyte Disturbances [ Na & K] – (Cardiac Arrhythmia / Bradycardia)

Treatment: Complications:
1- IV access → Correct Dehydration 40% mortality – medical emergency
2- Insulin Infusion →
Correct Severe Dehydration
Hyperglycaemia
3- Monitor/Correct Electrolytes – Particularly
Potassium
 ENDOCRINE SYSTEM

Complications of Diabetes:

Source: Sultan Chaudhry; [Link]

HONC – Hyperosmolar Non-ketotic Coma:

Caused By – (Type II Diabetes - Relatively Low Insulin/Insulin Insensitivity + Precipitant)

Diagnosis: Symptoms
Hyperglycaemia Confusion/Coma
NO KetoAcidosis Marked Dehydration
Osmolality > 330 mOsm/Kg Polyuria (Osmotic Diuresis)
Neurology – (Sensory/Motor Impairment,
Focal Seizures, Hyporeflexia, Tremors

Treatment: Complications:
IV Fluids Fatal if Untreated
Insulin + Potassium (Since Insulin
causes K+ Shift Into Cells)
Electrolyte Replacement (Esp.
Potassium)
 ENDOCRINE SYSTEM

Complications of Diabetes:

Hypoglycaemia (BSL < 6.0mmol/L):

Aetiology – (**Diabetes + Insulin Overdose / Alcohol / Sepsis)

Mild (BSL 3.5 - 6.0 mmol/L): Severe (BSL < 3.5 mmol/L):
↓ Insulin Secretion Neurogenic Symptoms:
↑ Counter Regulatory Hormones Adrenergic:
(Glucagon/Catecholamines/Cortisol/ Palpitations
GH) Anxiety
Tremor
Cholinergic:
Hunger
Sweating
Paraesthesia
Neuroglycopaenic Symptoms: •
Behaviour Change
Cognitive Seizures
Coma
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Complications Treatment:
Symptoms (Summary): of Diabetes:
Autonomic – (Sweating, Anxiety, #1 – Oral/IV Glucose
Hunger, Tremor, Palpitations, (Jellybeans/Juice/Biscuits/etc.)
Dizziness) OR – IM/IV Glucagon
CNS – (Confusion, Drowsiness, Visual
Disturbances, Seizures, Coma)
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Chronic Complications:

Caused by chronic exposure to Vascular:

Hyperglycaemia & Dyslipidaemia in the Macrovascular:
Insulin Insensitive Tissues Heart Disease/Coronary Artery
Disease/Atherosclerosis
Stroke
Peripheral Vascular Disease
Microvascular:
Retinopathy
Neuropathy
Nephropathy
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The ‘Somogyi’ Effect:

Where Circadian Elevations in Counter-Regulatory hormones (GH & Cortisol) cause
Hyperglycaemia early in the morning→ →
Patient Increases Insulin Dose @ Bedtime
→
Sustained Hypo all night →
Body releases Glucagon, Adrenaline & Cortisol Hyper @ Dawn

Possible Causes of Chronic Complications:

The ‘Polyol Pathway’:

Hyperglycaemia →↑ Glucose
Accumulation in Insulin
Independent Tissues
Much Glucose → Converted to
Sorbitol→ Slowly converted to
Fructose.
However, Sorbitol is Osmotically
Very Active → Sorbitol
Accumulation →
Osmotic Cell Injury
Affects Ion Pumps
Affects Some Cellular
Secondary Messenger
Pathways
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Hyperglycosylation of Proteins:

↑Glucose → ‘Glycosylation’ of proteins (Ie: Linkage of Glucose to Free Amino Groups in

Proteins)
Eg: HbA 1C (Glycosylated Haemoglobin)
Affects proteins in Blood Vessel Walls & Basement Membranes → Can stimulate
Inflammation.
Includes Collagen, Fibronectin, etc.
Leads to formation of ‘Advanced Glycosylated End-Products’ (AGE’s):
Can form cross-linkages between peptides → Forms a “Mesh” → Traps Other Molecules:
Eg: LDL Trapping → Cholesterol Deposition → Atherosclerosis
Eg: Immunoglobulins & Complement → Inflammation
Can form binding-sites for other proteins (eg: Albumin)
→
Inactivate Nitric Oxide Reduce Vasodilation
Stimulate Growth-Factor & Cytokine Secretion
↑ Vascular Permeability
↑ →
Clotting Activity Stroke/Embolus/etc.
↑ Extra-Cellular Matrix Deposition.

Reactive Oxygen Species:

↑Hyperglycaemia → ↑O₂ Free-Radical Production.

Compounded by ↑Immune Cell Activation
 ENDOCRINE SYSTEM

CALCIUM &
PHOSPHATE
BALANCE DISORDERS
 ENDOCRINE SYSTEM

CALCIUM &
PHOSPHATE
BALANCE
DISORDERS

Disorders of Calcium & Phosphate Regulation:

Hypercalcaemia: Hypercalcaemia:

Caused By: Caused by:

Hyperparathyroidism Vit-D Deficiency/Disorders of Vit-D
Malignancy (Eg: BRCA, Multiple Metabolism (Activation) →↓ Active Vit-D →
Myeloma) Rickets
Vit D Excess Eg: Lack of sunlight
Secondary Renal Eg: Lack of Dietary Vit-D
Hyperparathyroidism Eg: Chronic Kidney Failure
Hypoparathyroidism – (Because PTH is
required for Vit-D Activation in the Kidneys)
Acquired/Congenital

Rickets:

What is it?:
→
A Vit-D Deficiency Resulting in a Calcium/Phosphate Deficiency.
Note: Clinical Signs occur after a few months (Once the Bone’s Ca/P Reservoirs are
Depleted)
Effects:
↑
Marked PTH Secretion → Extreme Osteoclastic Activity:
→ ↑↑ Plasma Calcium
→ ↓↓ ↑
Plasma Phosphate (Due to Renal Excretion)
Tetany – Once the Bone’s Ca+ Reservoir is Depleted, Plasma Ca+ falls to dangerous
levels.
Treatment:
Dietary Calcium Supplements
Exogenous Vit-D Administration.
 ENDOCRINE SYSTEM

Hypoparathyroidism: Hyperparathyroidism:

What is it?: What is it?:

When the Parathyroid Glands don’t When the Parathyroid Glands secrete
secrete sufficient PTH. an inappropriate excess of PTH.
Effects: Effects:
↓ Resorption of exchangeable ↑↑ Extreme Osteoclastic activity in
Calcium→ Hypocalcaemia bones.
When Ca+ falls too low, Tetany can → Hypercalcaemia
→
develop (Can occur in larynx → Hypophosphataemia (Due to
obstructs respiration) ↑ Renal Excretion)

Osteoporosis:

What is it?:
Decreased Bone Decreased Bone Matrix (Not decreased bone calcification) (Not
decreased bone calcification)
Possible Causes:
→↓
Usually due to poor Osteoblastic Activity Osteoid Deposition.
Can be due to ↑↑ Osteoclastic Activity→↑ Osteoid Resorption.
→
Inactivity Lack of physical stress on bones
Malnutrition
↓
Postmenopausal Lack of Oestrogen (Oestrogen normally Osteoclast Activity)
Cushing’s Syndrome - ↑↑ ↓
Glucocorticoids cause Protein deposition throughout the
body.
 ENDOCRINE SYSTEM

PARATHYROID DISORDERS:

HYPERPARATHYROIDISM:

What is it?:
When the Parathyroid Glands secrete ↑↑PTH.
Effects of↑↑ PTH:
↑↑ →
Extreme Osteoclastic activity in bones Hypercalcaemia
↑↑ Renal Phosphate Excretion→ Hypophosphataemia

Types:
Primary Hyperparathyroidism – Autonomous, Spontaneous Overproduction of PTH:
Aetiologies/Pathogeneses:
Adenoma(Sporadic or MEN)/Hyperplasia/Carcinoma → ↑↑ PTH
Clinical Features:
F>>M
Hypercalcaemia Triad – “Bones, Moans & Abdominal Groans”:
1- Bone: Pain/Osteoporosis/Fractures
2- Moans: Depression/Lethargy/Seizures
3- Abdo: Constipation/Nausea/Ulcers/Gallstones
+ (Renal: Renal Stones)
+ (Heart: Aortic/Mitral Calcification)
Diagnosis:
↑ PTH
↑ Serum Calcium
↓ Serum Phosphate
Treatment:
Surgical Excision
Secondary Hyperparathyroidism – Secondary to Chronic Renal Insufficiency:
Aetiology:
Secondary to Renal Failure→ HypOcalcaemia
(Others incl. Dietary Calcium Deficiency, Vit-D Deficiency)
Pathogenesis:
Renal Failure→ →↑
Hypocalcaemia →
PTH to Compensate Hyperplasia
Clinical Features:
Symptoms of Chronic Renal Failure
Osteoporosis
Treatment:
Vitamin D + Calcium Supplementation
Partial Parathyroidectomy
 ENDOCRINE SYSTEM

Blackburn, Miriam and Terry H Diamond. “Primary hyperparathyroidism and familial hyper
parathyroid syndromes.” Australian family physician 36 12 (2007): 1029-33 .

HYPOPARATHYROIDISM:

Effects:
↓ Resorption of exchangeable Calcium → Hypocalcaemia
Aetiologies:
Iatrogenic – Surgery (Eg: Thyroidectomy/Lymphadenectomy/Over-resection in 1ᴼ HyperPT)
Genetic – (Autoimmune/Familial/Congenital Absence of Gland)

Clinical Features:
*Hypocalcaemia
*Hallmark = Tetany:
→ Neuromuscular Irritability
→ Distal Paraesthesias
→ Carpopedal Spasm
→ *Laryngospasm (Life-Threatening)
→ Seizures
CNS: Confusion/Depression/Hallucinations/Psychosis
Eyes: Cataracts (Calcification of Lenses)
CVS: Characteristic Prolonged QT-Interval
ENDOCRINE SYSTEM
 ENDOCRINE SYSTEM

GONADAL
DYSFUNCTION
 ENDOCRINE SYSTEM

GONADAL
DYSFUNCTION

MALE HYPOGONADISM:

What is it?
A deficiency in Testosterone due to problems with either:
1) Testes, or - Primary
2) Hypothalamus/Pituitary - Secondary

Primary Hypogonadism (Hypergonadotrophic)

→ ↓↓
Ie: Problem with the Leydig Cells in the Testes Testosterone Production →
↑↑ HypothalamoPituitary release of Gonadotropins (FSH/LH).
Causes:
Trauma/Irradiation of Testes.
Mumps
Klinefelter’s Syndrome (XXY)
Androgen Resistance
Autoimmune
Congenital

Secondary Hypogonadism (Hypogonadotrophic)

Ie: Problem with the Hypothalamo-Pituitary Axis→ ↓↓ Gonadotropin Release (FSH/LH)
→ ↓↓ Testosterone Production
Causes:
Developmental
Pituitary Tumour/Trauma/Pituitary Irradiation/Autoimmune
Genetic Syndromes
 ENDOCRINE SYSTEM

Effects of↓↓ Testosterone:

Infertility (Low Sperm Count),
↓ Libido, Erectile Dysfunction
↓ ↓
Muscle Mass, Bone Mass
↓ Beard/Body Hair
↑ Breast Tissue
↑ Body Fat

Treatment – Testosterone Replacement

Therapy

Salonia, Andrea et al. “Paediatric and adult-onset male

hypogonadism.” Nature Reviews Disease Primers 5 (2019)
 ENDOCRINE SYSTEM

MULTIPE
ENDOCRINE
NEOPLASIA
SYNDROME
 ENDOCRINE SYSTEM

MULTIPE
ENDOCRINE
NEOPLASIA
SYNDROME

Familial Endocrine Neoplasias – MEN Syndromes:

Multiple Endocrine Neoplasia = Genetic Disorders where 2/More Tumours are found in
Endocrine Glands (Parathyroid, Pituitary, Thyroid, & Adrenal Medulla).

MEN Disorders → ↑
Greatly the risk of developing multiple cancerous and noncancerous
tumours in glands such as the parathyroid, pituitary, and pancreas.

Multiple Endocrine Neoplasm Classifications

Type Aetiology Organs Involved Clinical Features

MEN1: Autosomal Dominant 1. Pituitary 60% of Wermer’s Pts have >2x

Wermer’s Genetic Mutation in MEN1 2. Parathyroid of the Following:
Syndrome Tumour Suppressor Gene 3. Pancreas Pituitary Adenoma → Eg:
on Chromosome 11 (Top 2/3 of Body) Prolactinomas/GH
→
Can also Bilateral
Hemianopia
Parathyroid Adenomas →
Hyperparathyroidism
Pancreatic Gastrinoma →
Peptic Ulcer Disease
Pancreatic Insulinoma →
Hypoglycaemia
Pancreatic VIPomas →
↑ →VIP Secretory Diarrhoea
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MEN2a: Autosomal Dominant 1. Thyroid 100% of Pts→ Medullary

Sipple’s Genetic Mutation in MEN2 2. Parathyroid Thyroid Cancer
Syndrome Tumour Suppressor Gene 3. Adrenal 50% of Pts→
on Chromosome 10 Medulla Phaeochromocytoma →
(Lower 2/3 of ↑ Adrenaline
Body) 30% of Pts→ Parathyroid
Hyperplasia→↑ PTH

MEN2b: Autosomal Dominant 1. Thyroid 100% of Pts→ Medullary

Genetic Mutation in MEN2 2. Adrenal Thyroid Cancer
Tumour Suppressor Gene Medulla 50% of Pts→
on Chromosome 10 (Lower 2/3 of Phaeochromocytoma →
Body) ↑ Adrenaline
(Other: Mucosal Neuromas,
Marfanoid Features)
ANATOMY, PHYSIOLOGY & PATHOLOGY NOTES OF THE

ENDOCRINE
SYSTEM