Chapter 14

Endocrine Hormones

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Chapter Objectives

Upon completion of this chapter, the student will be able to:

 Define terms related to endocrine hormones.
 Classify hormones
 Describe the metabolism of hormones
 Discuss the mechanisms of action (organ/system level), control and regulation

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Chapter Objectives

Upon completion of this chapter, the student will be able to:

 Describe the source, chemical nature, and mechanism of action of:
• Posterior pituitary hormones, ADH, oxytocin
• Anterior pituitary hormones
• Adrenocortical hormones
• Gonadal hormones
• Adrenomedullary Hormones
• Parathyroid Hormones
• Calcitonin
• Pancreatic Hormones
• Gastrointestinal hormones
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Definition and Classification of endocrine hormones
Definition of basic terms

 Endocrinology - science that deals with a group of ductless glands and the action
of their secretions which are transported via bloodstream.

 Hormones - any substance normally produced by specialized cells in some part of

the body, carried by the bloodstream to another from which it affects the body as a
whole.

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Hormones
 Endocrine system:-They are produced at one site in the body and exert their
action(s) at distant sites
E.g. insulin, thyroxine, and cortisol
 Paracrine system:- exert locally through what is termed the
E.g. Neurotransmitters and neurohormones
 Autocrine system:-exert their action on the cells of origin, regulating their
own synthesis and secretion
E.g. certain growth factors

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Definition and Classification of endocrine hormones
 Functions of Hormones
• Maintain homeostasis
• Regulate growth/development
• Promote sexual maturation, and sexual rhythms and facilitate
reproduction
• Regulate energy production
• Adapt/adjust the body to stressful/emergency situations
✓ Stress – dehydration – starvation – hemorrhage – temperature extremes
• Promote/inhibit the production or release of other hormones
• Helps regulate the immune system.

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Definition and Classification of endocrine hormones
 Classification of Hormones
a) Amines
▪ Amino acid derivatives

▪ Poorly soluble in plasma

▪ Enter their target cell, penetrate the nuclei, and react with the DNA to promote
or suppress gene action

 Examples:
 Thyroid hormones, Epinephrine, Norepinephrine

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Definition and Classification of endocrine hormones
 Classification of Hormones
b) Protein/peptide
▪ Soluble in plasma

▪ Interact with target cell membrane receptor to trigger the production/release of

adenyl cyclase resulting in the production of cyclic-AMP
 Cyclic-AMP diffuses throughout the cell to respond to the hormone
in a characteristic manner
 Cyclic guanosine monophosphate is believed to have the opposite
effect on regulating cell activities

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Definition and Classification of endocrine hormones
 Classification of Hormones
b) Protein/peptide
 Short-term effects
 Examples:
 Releasing hormones eg. thyroid releasing hormone
 Oxytocin
 Antidiuretic hormone
 Insulin
 Glucagon
 Parathyroid hormone
 Calcitonin

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Definition and Classification of endocrine hormones
 Classification of Hormones
C) Steroid ring structured hormones
 Lipid soluble, chemically derived from cholesterol
 Pass through cell membranes and interact with intracellular receptors
 Require time to initiate/terminate processes
 Examples:
• Aldosterone, Cortisol, Androgens—Testosterone, Calcitrol,
Estrogen, Progesterone

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Comparison of Steroidal and Non-steroidal Transport

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Functional types of hormones
a. Releasing factors
1) From the hypothalamus
2) Stimulate anterior pituitary
b. Inhibitory hormones
 Come from the hypothalamus or GI tract; suppress the secretion of particular
hormones.
[Link] hormones
 Come from the anterior pituitary gland and have as their target the other
endocrine glands.

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Functional types of hormones
d. Non-tropic or effector hormones
 Secreted by non-pituitary endocrine glands

 Act on tissue cells

 Exert a feedback effect upon either the hypothalamus or anterior pituitary glands
• Negative feedback: an increase in the product causes a decrease
in the system
• Positive feedback: an increase in the product causes an increase in
the activity of the system

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 Neural and Sensory input

Hypothalamus
(Releasing and inhibiting factors) _
+ LFL
Pituitary _ Thyroxine
(Tropic hormone)
+ SFL
Thyroid gland
(Secretory hormones)
Thyroxine

Target tissue
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Mechanisms of action (organ/system level), control and regulation
of endocrine hormones
Hormonal secretion is stimulated by:
1. The nervous system
Example: the sympathetic nervous system causes the release of
norepinephrine from the adrenal medulla.
2. Chemical changes in the blood
Example: a decrease in the level of calcium in the blood will trigger the
release of PTH
3. Other hormones
Example: releasing hormones from the hypothalamus will in turn cause the
release of hormones from the adenohypophysis

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Mechanisms of action (organ/system level), control and regulation
of endocrine hormones

Hormonal Interactions
➢ Permissive
✓ Exposure to one hormone enhances action of second hormone
➢ Synergistic
✓ Two or more hormones are required for one effect
➢ Antagonistic
✓ Two hormones have opposing actions

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Regulation of Hormones
 It is achieved primarily by controlling the rate of synthesis rather than the rate
of degradation
a. Primary control = hypothalamus
✓ Small gland adjacent to the pituitary gland
✓ Connected to pituitary via “pituitary stalk”
✓ Synthesize ADH (vasopressin) and oxytocin
✓ These hormones are stored and released from the posterior
pituitary gland

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Regulation of Hormones

b. Pituitary gland
 Tropic hormones secreted
ACTH
TSH
FSH
LH
 Effector hormones secreted work on tissues
GH (somatotropin)
Prolactin

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NOTE: The blood supply to the anterior pituitary passes through the hypothalamus first
where it picks up regulating hormones that control the release of hormones from the
anterior pituitary.
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Hormones of the hypothalamus
➢ Thyrotropin-releasing hormone (TRH) – stimulates the release of TSH

➢ Lactotroph- stimulates the release of Prolactin

➢ Corticotropin-releasing hormone (CRH)- stimulates the release of ACTH and

MSH

➢ Gonadotropin-releasing hormone (GnRH)- stimulates the release of LH and

FSH
➢ Growth hormone-releasing hormone/ Somatotroph (GHRH ) – Stimulates
the release of GH
➢ Somatostatin- inhibits the production of GH and TSH
➢ Dopamine- inhibits the release of prolactin
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The Posterior Pituitary Lobe
Nature of posterior pituitary hormones
Two peptide hormones are released from the posterior pituitary lobe:
1. OT (oxytocin)
• In females, contracts the uterine wall smooth muscles
• helps to eject milk when lactating
• can have some antidiuretic effects
2. ADH (antidiuretic hormone or vasopressin)
• antidiuretic; decreases urine formation by renal conservation of water contract smooth
muscle cells,
• Regulated by hypothalamic osmoreceptors (>284 mOsm/kg) and vascular baroreceptors (<10%
of arterial bp)
Note: No hormones are made here. They are made in the hypothalamus and
stored and released here.
Transported to the neurohypophysis via the pituitary stalk

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Major abnormalities (diseases) associated with posterior
pituitary hormones
Diabetes insipidus (DI) : vasopressin deficiency.
 characterized by copious production of urine (polyuria)
 intense thirst (polydipsia)
Causes:-
✓ Autoimmunity to vasopressin-secreting neurons,
✓ Trauma,
✓ Diseases affecting pituitary stalk function, and
✓ Various central nervous system or pituitary tumors
Diagnosis:
✓ Inappropriately low vasopressin level
✓ Elevated plasma osmolality
✓ Decreased urine osmolality
✓ Water deprivation test

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Major abnormalities (diseases) associated with posterior
pituitary hormones
Syndrome of inappropriate ADH Secretion (SIADH):
: Hypersecretion of ADH, excessive water retention
 characterized by low urine volume (anuria)

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Anterior Pituitary Hormones

❖Tropic hormones
– TSH
– ACTH
– Gonadotrophins (LH & FSH )
– MSH

❖Effector Hormones: those work on tissues

GH
Prolactin

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Anterior Pituitary Hormones
Human Growth Hormone

 Structurally related to other hormones

 Causes body cells to grow (mainly muscle and bone)

 Has an effect on:

 protein synthesis

 fat catabolism

 Carbohydrate metabolism (hyperglycemia of the blood)

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Human Growth Hormone
 The release of Growth Hormone from the pituitary is stimulated by the
GHRH.
 Secreted in pulses with an average interval of 2-3 hrs.
 Peak occurring at the onset of sleep
 The secretion is inhibited by somatostatin (SS)
 Causes body cells to grow (mainly muscle and bone)
 Causes cells to:
✓ Increase their uptake of amino acids, and rate of protein synthesis.
✓ Decrease the use of proteins for energy (promotes fat catabolism)
✓ Stop burning glucose, and stop up taking glucose, leading to hyperglycemia of the
blood (this is referred to as the diabetogenic effect)

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Clinical Significance of GH
 Gigantism
 Hypersecretion of growth hormone in growth years
 Rapid, prolonged bone growth & Normal body proportions
 Acromegaly
 Hypersecretion of hGH in adult years
 Abnormal body proportions
 Affects Soft tissue of face & Bones of face, hands & feet
 Pituitary Dwarfism
 Hyposecretion of growth hormone
 Slow bone & organ growth, reduced adult height & abnormal body proportions

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Detection of GH
 Random testing is rarely diagnostic
 Definitive testing for acromegaly relies on the normal compressibility of GH
by oral glucose loading (100gm)
 Then GH was measured at 0, 60, and 120 mins.
 In normal individuals GH is undetectable after oral glucose ingestion
 Acromegaly patients will fail to suppress and may even have a rise in GH.
 Testing for deficiency
 Combination infusions of GHRH and AA L-arginine or infusion of L-arginine
coupled with oral L-DOPA is the most common
 If the GH level will rise above 3-5ng/mL it is unlikely the patient is hormone deficient

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Anterior pituitary hormones
Prolactin
✓ Hypothalamic regulation is tonic inhibition rather than intermittent
stimulation

✓ Inhibited by dopamine

✓ Stimulation of breasts, as in nursing, causes the release of prolactin

✓ the physiologic effect of prolactin is lactation

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Major abnormalities (diseases) associated with anterior
pituitary hormones

 Clinical Significance of prolactin

• Hyperprolactinemia
Causes
• A prolactinoma
• Pituitary stalk interruption
Symptoms
 Premenopausal women ..menstrual irregularity/amenorrhea, infertility, or
galactorrhea
 Man may present with reduced libido or complaints of erectile dysfunction
 b/c prolactin-induces hypogonadism

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Major abnormalities (diseases) associated with anterior
pituitary hormones

Hypopituitarism

• Panhypopituitarism

Causes

✓ Pituitary tumors

✓ Hypothalamic tumors

✓ Infectious organism

• Monohypopituitarism
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Adrenal hormones
 Two small, triangular-shaped glands located atop the upper portion of each
kidney
1. Outer cortex
• Outermost zona glomerulosa
✓ Synthesis site of mineralocorticoids
• Central zona fasciculata
✓ Synthesis site of glucocorticoids
• Inner zona reticularis
✓ Synthesis site of adrenal sex steroid hormones

2. Inner medulla
• Chromaffin cells (pheochromocytes)
✓ Synthesis site of catecholamines
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Adrenocortical hormones

Adrenal function
 The primary function of the adrenal glands is to produce the adrenal
hormones (> 50 hormones)
✓ Mineralocorticoids

✓ Glucocorticoids

✓ Sex hormones

✓ Catecholamines
 Only two adrenal hormones are essential for human life: cortisol and
aldosterone
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Adrenocortical hormones

 The adrenal cortical steroid hormones are derived from the cholesterol
nucleus via a branched metabolic pathway

✓ Inborn errors of metabolism are caused by specific enzyme deficiencies in the adrenal
steroid hormone synthetic pathway

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Adrenal steroid synthesis

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Adrenocortical hormones
Glucocorticoid release
 Corticotropin-releasing hormone (CRH)
• A polypeptide synthesized and secreted by the hypothalamus

• Stimulates the synthesis and release of the 39 amino acid polypeptide

adrenocorticotropic hormone (ACTH) from the anterior pituitary
✓ ACTH in turn stimulates the synthesis and secretion of cortisol from the adrenal cortex

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CNS stimuli

Hypothalamic hormone CRH

Anterior pituitary hormone
ACTH

Target gland
Adrenals

Target hormones Glucocorticoids
Mineralocorticoids
Sex steroids
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Adrenocortical hormones
Glucocorticoids
 Most important glucocorticoid hormone - cortisol
 Target organ - every cell of the body
 Effects
✓ Regulation of carbohydrate, protein, and lipid metabolism;
✓ maintenance of blood pressure and
✓ suppression of the immune response
 General characteristics
 Steroids, lipid-soluble, protein-bound, slow effects

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Adrenocortical hormones
Glucocorticoid regulation
 Glucocorticoid homeostasis is maintained through:-

 A cortisol-negative feedback loop at the level of both the hypothalamus

and pituitary

 Additionally, CRH release is subjected to CNS controls and negative

feedback from ACTH

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Adrenocortical hormones
Glucocorticoid transport
 The lipid-soluble glucocorticoids are transported in circulation bound to
carrier proteins
• Cortisol is 90-97% protein-bound
✓ Cortisol-binding globulin (CBG) – major transport protein
✓ Albumin
✓ Sex-hormone binding globulin (SHBG)
• Conditions that change the level of binding protein affect the level of total
hormone, but not of the biologically active free hormone
✓ Causes of increased CBG
 Estrogen, hyperthyroidism, etc.
✓ Causes of decreased CBG
 Malnutrition, chronic liver disease, hypothyroidism, androgens, etc.
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Adrenocortical hormones
Glucocorticoid variation
 ACTH and cortisol both exhibit a diurnal variation pattern with the highest
levels occurring in the early morning – 8 am and lowest levels in the late
evening
✓ Diurnal variation pattern is related to sleep-wake cycles

✓ Stress is a powerful regulator of cortisol, able to override the diurnal variation pattern
and negative feedback regulation

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 ACTH diurnal variation

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Adrenocortical hormones
Mineralocorticoids
 Most important mineralocorticoid hormone – aldosterone
 Target organs - kidneys, sweat and salivary glands and GI tract
 Effects: Aldosterone regulates electrolyte balance and extracellular fluid
balance
✓ Through its effects on renal sodium absorption, it regulates blood volume and
blood pressure
✓ In the kidney, aldosterone causes active sodium reabsorption, potassium excretion,
and passive water reabsorption
 Characteristics – poorly protein bound

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Adrenocortical hormones
Mineralocorticoids release

 Three release stimulators

✓ Renin-angiotensin system (RAS) – primary stimulation
✓ Extracellular potassium and sodium
✓ ACTH

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Adrenocortical hormones
Mineralocorticoids release

 Renin-angiotensin system
 The juxtaglomerular apparatus- a volume/osmoreceptor located in the
kidney, releases the proteolytic enzyme renin
✓ Release is stimulated by a decrease in blood volume, an increase in plasma
potassium, or a negative sodium balance
 Renin converts angiotensinogen to angiotensin I
 Pulmonary angiotensin-converting enzyme (ACE) converts angiotensin I
to angiotensin II - a potent vasoconstrictor to raise BP
 Angiotensin II stimulates the adrenal synthesis of aldosterone

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 Angiotensinogen Angiotensin I

ACE Lung

Renin Angiontensin II

Adrenal Cortex Aldosterone  Na and H2O

reabsorption
(- Feedback) K
reabsorption

Kidney (Juxtaglomerular apparatus)

49 Hyperkalemia Sodium depletion Hypotension  ECF volume

Adrenocortical hormones
Mineralocorticoids regulation
 Aldosteronehas negative feedback on the
juxtaglomerular apparatus of the kidney

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Adrenocortical hormones
Catecholamines
 Catecholamines – epinephrine, norepinephrine and dopamine
• Epinephrine is the major adrenal catecholamine (80-90%)
✓ Affects metabolism (mobilizes energy stores) and increases heart rate and blood pressure in
times of stress
✓ Functions as a neurotransmitter
• Norepinephrine (10-20%) and dopamine function solely as neurotransmitters
 Catecholamine release
• Catecholamine adrenal release is stimulated by stressors such as fear and pain - “fight
or flight”

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Adrenocortical hormones
Catecholamines synthesis
 The adrenal medullary catecholamines are derived from the amino acid
tyrosine

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Adrenocortical hormones
Adrenal hormone catabolism

 The liver, and to a lesser extent, the kidneys and GI, metabolize adrenal

steroid hormones

 Adrenal catecholamines are metabolized by the liver and kidneys and also

taken up by sympathetic neurons

✓ Catcholamine metabolites – metanephrine, normetanephrine, homovanillic aicd (HVA)

and vanillylmandelic acid (VMA)

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Adrenocortical hormones
Classes of sex steroids
 Androgens
• Dehydroepiandrosterone (DHEA), DHEAS, testosterone (C19 steroid), dihydrotestosterone
(DHT), androstenedione
✓ The predominate adrenal androgens are DHEA and DHEAS

 Estrogens:-C18 steroid
✓ Estradiol:- Major hormone in non-pregnant
✓ Estriol:- Major hormone in pregnant
✓ Estrone
 Progestins
✓ Progesterone:-C21 steroid
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Adrenocortical hormones
Clinical Significance of Adrenal Hormones
 Adrenal hyperfunction
✓ Glucocorticoid—Cushing’s syndrome
✓ Mineralocorticoid—Conne’s syndrome
✓ Medullary—pheochromocytoma
 Adrenal hypofunction
✓ Glucocorticoid
Addison’s disease-
✓ Mineralocorticoid
Autoimmune destruction
✓ Medullary

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Glucocorticoid hyperfunction
 Cushing’s Syndrome - excessive glucocorticoids
✓ Either endogenous or exogenous (chronic long-term glucocorticoid therapy) in origin
A. Endogenous Cushing’s Syndrome
 Causes
• Primary
✓ Adrenal adenoma or carcinoma (15%)
• Secondary (Cushing’s Disease)
✓ ACTH-secreting pituitary tumor (70%)
✓ Failure of normal negative feedback mechanism results in bilateral adrenal hyperplasia
✓ Ectopic Sources – lung, pancreas, or thymus
B. Exogenous Cushing’s Syndrome
 chronic long-term glucocorticoid therapy

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Glucocorticoid hyperfunction
Cushing’s Syndrome features
 Cushingoid appearance (truncal obesity, moon facies, buffalo hump, purple striae,
excessive bruising, thin skin)

 Poor wound healing

 Osteopenia

 Glucose intolerance

 Psychiatric symptoms (euphoria, mania, depression)

 Muscle weakness

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 Hypercortisolism

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Hyperacortisolism

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Correlation of Results with Cushing’s
 Increased  Decreased
• Cortisol • Potassium
• Glucose • Eosinophils
• Hematocrit • Lymphocytes
• Calcium
• Bicarbonate
• Bone turnover markers

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Specimens for Cortisol

 Serum

 Hepararinized plasma

• Multiple timed specimens

 24-hour urine

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Determination of Cushing’s Syndrome
 Random serum cortisol
• Limitations – pulsatile secretion and diurnal variation
 24 hour urinary free cortisol
• Most sensitive screening test
• normalizes the diurnal variation
 Plasma ACTH
• Differentiate Cushing’s Disease and Syndrome
 Urinary steroids
• Rarely used

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Interpretation of Cortisol Results
Serum or hepararinized plasma cortisol
 Reference intervals reflect diurnal variation
 Reference intervals (Tietz)
• 0800 h 5 – 23 g/dL
• 1600 h 3 – 16 g/dL
• 2000 h  50% of 0800 h
Compare patient results to reference ranges to assess for hyper or hypocortisolism.

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24 hour urinary free cortisol
 Adult reference interval (Tietz)
 50 g/day
 In the absence of stress, a urinary-free cortisol
> 250 g/day is indicative of Cushing’s Syndrome
❖ Correlation of Plasma ACTH results with Cushing’s Syndrome

1o Cushing’s  cortisol  ACTH

2o Cushing’s  cortisol  ACTH
Ectopic  cortisol  ACTH
Exogenous  cortisol  ACTH

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Cushing’s dynamic testing
 CRH stimulation test
• IV administration of 1.0 mg/kg CRH
• Measure ACTH and cortisol at baseline and 60 and 180 minutes post
• Cushing’s Disease
✓ Exaggerated response
• Adrenal tumors or ectopic ACTH-producing neoplasms
✓ No response but elevated ACTH baseline
➢ Insulin-induced hypoglycemia--Exaggerated response
• Both of these stimulation tests show a response in Cushing’s disease but not with
other forms of Cushing’s Syndrome
 Dexamethasone suppression tests
• Potent cortisol analogue that suppresses pituitary ACTH secretion
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Adrenal cortical hypofunction

 Primary
• Destruction of the entire adrenal cortex causing deficiency of all adrenal steroids

• Most common cause

 Secondary

 Tertiary

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Adrenal cortical hypofunction
 Mineralocorticoid effects
• Hyponateremia

• Hyperkalemia

• Metabolic acidosis

• Edema

 Sex steroid effects

• Female: amenorrhea, hirsutism

• Male: impotence, gynecomastia

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Features of adrenal insufficiency

Related to glucocorticoid deficiency –

 Weakness,  abdominal pain,

 weight loss,  hypotension,
 fatigue,  hypoglycemia,
 anorexia,  hyponatremia
 nausea, (inappropriate ADH
 vomiting, production),
 diarrhea or constipation,  eosinophilia,
 lymphocytosis
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Features of adrenal insufficiency
 Related to ACTH excess – Hyperpigmentation of skin and mucous
membranes

 Related to mineralocorticoid deficiency – Postural hypotension,

dehydration, hyponatremia, hyperkalemia, non-anion gap metabolic
acidosis,

 Related to sex steroid deficiency – Infertility, loss of body hair, in

children, delayed development of secondary sex characteristics

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Primary adrenal insufficiency

 Acute
• Adrenal hemorrhage, infection, uncontrolled anticoagulant therapy, adrenalectomy
 Chronic
• Addison’s Disease
✓ Rare autoimmune-mediated destruction of the adrenal cortex
• Tuberculosis, metastatic carcinoma, amyloidosis

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Addison’s lab results
 Related to glucocorticoid deficiency
• Hypoglycemia,
• hyponatremia,
• eosinophilia,
• lymphocytosis
 Related to mineralocorticoid deficiency
• Hyponatremia,
• hyperkalemia,
• non-anion gap metabolic acidosis

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Addison’s test results
 Random serum cortisol
• Confirmation: < 2 g/dL
 Cosyntropin (potent synthetic fragment of ACTH) stimulation test
• Normal: serum cortisol > 18 – 20 g/dL at 30 - 60 minutes post
  Serum and urine aldosterone
  Plasma ACTH
  Serum Na,  serum K,  urine sodium
 Other stimulation tests
• CRH, insulin hypoglycemia, metyrapone (a glucocorticoid synthesis inhibitor
by inhibits 11-beta-hydroxylase)

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Clinical Significance of Mineralocorticoids
 Hyperaldosteronism
• Primary – Conn’s Syndrome
✓ Aldosterone-producing adrenal adenomas,
✓ bilateral idiopathic hyperplasia of the zona glomerulosa or adrenal carcinoma
• Secondary
✓ Renal artery stenosis, chronic renal failure, renin-secreting tumor, CHF, nephrotic syndrome,
cirrhosis and malignant hypertension
• Other
✓ Ectopic Cushing’s Syndrome or congenital adrenal hyperplasia due to enzyme deficiency
Clinical features
 Hypertension
• Cause of 1-2% of hypertension cases
 Muscle weakness and fatigue

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Laboratory Findings in Primary Hyperaldosteronism

 Elevated serum and urine aldosterone

 Suppressed plasma renin activity
 Hypokalemia (if not on low sodium diet)
 Hyperkaluria (if not on low sodium diet)
✓ Urine K > 30 mmol/d
 Metabolic alkalosis
 High normal serum sodium (very rarely hypernatremia is present)

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Specimens for Mineralocorticoids

Aldosterone

 Heparinized or EDTA plasma

 Serum

 24 hour Urine

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Mineralocorticoid testing

 Plasma aldosterone
• Limited diagnostic utility because interpretation is dependent on the patient’s salt
intake and posture at the time of collection

 Captopril (ACE inhibitor) suppression test

• Plasma aldosterone and renin activity measured at baseline and 2 hours post

✓ Normal: plasma aldosterone < 25 ng/dL

✓ Normal: aldosterone/renin activity ratio < 20

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Hyperaldosteronism dynamic tests

 Saline suppression test

• After 4 hour IV infusion of 2 L of normal saline, plasma aldosterone < 10 ng/dL is
normal

 Renin stimulation
• After oral administration of 40-mg of furosemide (stops salt and water reabsorption-
loop diuretics) at 6 pm, midnight and 8 am (or, 80 mg bolus at 8 am)

• Followed by 4 hours of upright ambulatory motion, normal plasma renin activity is > 3
ng/mL/h

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Introduction to Sex steroids
 Predominately produced by the adult male testes and female ovaries
• Adrenal cortex also produces sex steroids

 Effects - secondary sex characteristics

 Characteristics – steroid, lipid-soluble, slow effects, bound to carrier proteins

(SHBG, albumin)

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Regulation of Sex hormones
FSH and LH CRH
 Induce growth and maturation of  Stimulate the release of ACTH from
gonads anterior pituitary gland
 Induce secretion of gonadal ACTH
hormones  Stimulates the release of adrenal sex
 Mature ova and ovulation in female steroids
 Mature spermatozoa in male

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Female Sex Hormones Feedback
 Ovary secretion in response to LH and FSH
A. Estrogens (positive feedback to LH and FSH)
• Normal ovulatory cycle
• Secondary sex characteristics
B. Progesterone (positive feedback to Estrogens)
Suppresses LH (negative feedback)
•
• Suppresses ovulation
• Stimulates uterus for fertilized ovum
 28-35 day cycle

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Male Sex Hormones

 Testicular secretion in response to LH and FSH

• Testosterone

✓ Reproductive cycle

✓ Secondary sex characteristics

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Clinical Significance of sex hormones
 The clinical features of androgen excess depend upon the age of onset and
degree of androgen excess
• Female infant – ambiguous genitalia

• Male child – premature puberty

• Adult male – gynecomastia, infertility, impotence

• Adult female – hirsutism, oligo/amenorrhea, acne (mild); altered body habitus, male
pattern balding, clitoromegaly, deepened voice (severe)

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Methods of Sex Steroid Analysis
Estrogens
 RIA
 Reference Ranges vary with the method and timing of the female cycle
 More useful if tested along with FSH and LH
Testosterone
 RIA
Hirsutism testing
 DHEAS serves as a marker of adrenal androgen production
 Imaging techniques

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Medullary hyperfunction
 Excess levels of catecholamines Features of Pheochromocytoma
produced by pheochromocytomas,  Hypertension

 Chronic or episodic clinical  Other cardiovascular – tachycardia

symptoms
 headache, nausea, weakness,
nervousness, tremors, pallor, flushing,
diarrhea, hyperglycemia

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Medullary testing

 Fractionated urine and plasma catecholamines and their metabolites

• In pheochromocytoma, plasma and urinary catecholamines and their metabolites are
increased (usually > twice the upper reference interval)

 Imaging techniques

 Clonidine (hypotensive agent) suppression test

 Glucagon stimulation test

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Introduction to Thyroid Function
Definition to terms:
 Thyroid gland: small tissue situated in the neck just below the larynx producing
hormones that affect metabolism and growth.
 Thyroxine: 3, 5, 3’, 5’ –tetraiodothyronine or T4; produced by the thyroid gland
 Triiodotyrosine: 3, 5, 3’- triiodotyrosine, T3; produced by the thyroid gland and
peripheral tissues
 Reverse T3: 3, 3’, 5’ triiodotyrosine; inactive T3
 Deiodinazation: biochemical process of removing iodine

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Location of Thyroid Gland

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Thyroid Hormones
1. Thyroxine hormones [ Tetraiodothyronine (T4) and triiodothyronine (T3)] are
produced by follicular cells of the thyroid gland.

➢ Thyroglobulin is a glycoprotein used by the thyroid gland to produce T3 and T4

➢ Activity of thyroid hormone is dependent on the location and number of iodine

atoms

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Thyroid Biochemistry and Metabolic Pathways
 Precursor hormones are:
 Monoiodotyrosine (MIT)
 Diiodotyrosine (DIT)
 Iodine and tyrosine derived

 Circulating thyroid hormones are

 Thyroxine (T4)
 Triiodotyrosine (T3)

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Thyroid Biochemistry and Metabolic Pathways
 Step 1: I- trapped in the thyroid gland
 Step 2: I- oxidized to I2
 Step 3: I2 reacts with tyrosine in thyroid cells → MIT and DIT

 Step 4: 2 DIT→ T4; MIT+ DIT → T3

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Thyroid Anatomy: Cells

 Follicular cells synthesize thyroglobulin and

thyroxine and T3
 Colloid cells provide Iodine
 Capillaries transfer hormones to circulation

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Thyroid Biochemistry and Metabolic Pathways
 Thyroid gland makes T4
 Peripheral tissues make T3 from T4
 Deiodination

 Thyroid makes some reverse T3

 Inactive form
 Thyroid binding globulin
 Binds to the majority of T4 and T3
 Only free T4 and T3 is active

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Function of Thyroid Hormones

Releasing Ant. Pit. Thyroid Action

Hormone Hormone Hormone
TRH TSH T3 and T4 • Increases the metabolic
rate of cells,
• ATP and heat production,
• breakdown of liver
glycogen,
• calorigenic

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Endocrine Control: Thyroid Function

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Clinical Significance: Primary Hyperthyroidism
 Disease of the primary organ (thyroid)
 Increased Free T4 and total T4 and T3
 Decreased TSH
 Symptoms:
 Increased heart rate and metabolism
 Problems with eyes
 Many other symptoms

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Graves disease
 Due to auto antibodies that mimics TSH

 This leads to overproduction of T3 and T4

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Secondary Hyperthyroidism
 Disease of the secondary organ (pituitary)
 Increased Free T4 and total T4 and T3
 Increased TSH
 Symptoms:
 Increased heart rate and metabolism
 Problems with eyes
 Many other symptoms

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Clinical Significance: Primary Hypothyroidism
 Disease of the primary organ (thyroid)
 Decreased Free T4 and total T4 and T3
 Increased TSH
 Symptoms:
 Decreased heart rate and metabolism
 Failure to thrive and retardation in children
 Many other symptoms

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Clinical Significance: Primary Hypothyroidism
Hashimoto's thyroiditis
 Due to antibodies that attacks follicular cells of thyroid gland
 That causes:-
 Decreased Free T4 and total T4 and T3
 Increased TSH
 Symptoms:
 Decreased heart rate and metabolism
 Failure to thrive and retardation in children
 Many other symptoms

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Clinical Significance: Primary Hypothyroidism
Iodine Deficiency Goiter
 Due to the deficiency of iodine in diet
 That causes:-
 Decreased Free T4 and total T4 and T3
 Increased TSH
 Symptoms:
 Decreased heart rate and metabolism
 Failure to thrive and retardation in children
 Many other symptoms

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Clinical Significance: Secondary Hypothyroidism
 Disease of the secondary organ (pituitary)
 Decreased Free T4 and total T4 and T3
 Decreased TSH (and other pituitary hormones)
 Symptoms:
 Decreased heart rate and metabolism
 Many other symptoms

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Principles of Methods: Thyroid Hormone Analysis
 Immunoassay Procedures:
 Radioimmunoassay (RIA)
 Chemilumiscent Immunoassay
 Fluorescence Polarization Immunoassay (FPIA)

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Specimens for Thyroid Analysis
 Serum
 Heparinized or EDTA plasma
 Whole blood from Capillary
 Dried blood spot

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Sources of Error in Thyroid Analysis
 Hemolyzed specimens
 Wrong anticoagulant
 Lipemic
 Turbidity from lipids
 Specimen exposed to heat or sunlight
 Poorly maintained or poorly calibrated instrument.

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Interpretation of Results
Thyroid Hormone Reference Ranges
 T4: adult 5.1 to 11.0 µg/dL(66 -142 nmol/L)
 T3 adult 70 to 200 ng/dL (1.08 to 3.08 nmol/L)
 %T3U: 25 to 35%.
 Free T4: adult 5.6-11.7 g/dL
 Free T3: adult 80-210 ng/dL
 Ranges are method dependent and age adjusted.

 Patient results should be compared with the appropriate reference ranges

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Parathyroid Hormone (PTH)
 PTH maintains plasma Ca2+
 Negative feedback of high Ca2+
 PTH raises Ca2+ directly
o mobilizing calcium from bone
o decreasing renal excretion of Ca 2+ by stimulating tubular reabsorption
o increasing Ca 2+ indirectly by enhancing the renal formation of 1,25 (OH)2 D3
o PTH reduces the phosphate load arising from the bone resorption by
promoting its excretion by the kidney.

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108
Clinical Significance of PTH
 Primary Hyperparathyroidism
 Elevated PTH
 Hypocalcemia due to malignancy
 Normal PTH
 Hypoparathyroidism
 Normal PTH
 Total and ionized calcium testing along with PTH

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Method of Analysis for PTH
 RIA specific to C- terminal or N-terminal
 Establish own reference ranges

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Calcitonin (CT)
 Synthesized in the thyroid gland
 Calcium homeostasis
 CT depresses bone resorption activity of osteoclasts

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Methods of Calcitonin Analysis
 RIA
 diagnostic usefulness has not been established.

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Pancreatic Hormones: Insulin
 Polypeptide produced by the pancreatic β-cells of islets of Langerhans
 Its secretion is stimulated by hyperglycemia
 Its effect is to remove the glucose by
 Increasing Glucose uptake into muscle and adipose cells via hormone-specific
receptors
 Increasing glycolysis [glucose utilization by cells]
 Increasing Glycogenesis
 Increasing Lipogenesis & protein synthesis
 Inhibiting glycogenolysis

 Insulin is the only hormone that decreases blood glucose

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Insulin

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Clinical Significance of Insulin
 Hypoinsulinism
 Diabetes mellitus
 Hyperinsulinism
 Insulinoma

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Methods of Insulin Analysis
 Method: RIA
 Reference Range, fasting: < 20 mU/L
 Glucagon stimulation test:
 Hypoglycemia associated with insulinoma
 Hyperglycemia associated with normal response

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Pancreatic Hormone: Glucagon
Glucagon
▪ Polypeptide secreted by the alpha cells of the pancreas
▪ Increases blood glucose by stimulating hepatic glycogenolysis and
gluconeogenesis
▪ It has no effect on muscle glycogen
▪ Measurement of glucagon has no clinical value

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Gastrointestinal Hormones
 Gastrin
 Secretin
 Somatostatin
 Vasoactive intestinal peptide

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Gastrin
 Stimulates gastric juice secretion
 Overproduction
 Upper GI ulcers
 Gastrinoma
 Non-beta cell tumors of pancreas
 Zollinger-Ellison syndrome

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Vasoactive Intestinal Peptide
 Intestinal hormone
 Over secretion
 Tumor of the intestinal tract
 Pancreatic cholera
 Severe persistent diarrhea

 Measured by RIA

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Self-assessment questions
1. List the major hormones produced by the adrenal outer cortex and inner
medulla
2. Describe the clinical features and expected lab results for the major adrenal
disorders
3. An elevated level of which of the following hormones will inhibit pituitary
secretion of adrenocorticotropic hormone (ACTH)?
A. Aldosterone B. Cortisol C. 17-Estradiol D. Progesterone
4. Which of the following is the major mineralocorticoid?
A. Aldosterone B. Cortisol C. Corticosterone D. Testosterone

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Self-assessment questions
5. Secretion of hormones by the anterior pituitary may be controlled by the
circulating levels of hormones from the respective target gland as well as
hormones secreted by what organ?
A. Posterior lobe of the pituitary gland
B. Intermediate lobe of the pituitary gland
C. Hypothalamus
D. Adrenal medulla
6. Which of the following is the most common cause of adrenogenital syndrome,
congenital adrenal hyperplasia, and which test is used for its diagnosis?
A. 17-Hydroxylase deficiency; progesterone assay
B. 21 -Hydroxylase deficiency; 17-hydroxyprogesterone assay
C. 3- Hydroxysteroid dehydrogenase-isomerase deficiency; 17- hydroxypregnenolone
assay
D. 11- Hydroxylase deficiency; 11-deoxycortisol assay

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Self-assessment questions
7. What would be an example of ectopic hormone production?
A. Prolactin production by pituitary tumors
B. Calcitonin production by thyroid tumors
C. Growth hormone production by lung tumors
D. Cortisol production by adrenal tumors
8. All the following are associated with growth hormones except
A. Somatotropin
B. Secreted by the posterior pituitary
C. Hypersecretion results in acromegaly
D. Effects on lipid, carbohydrate, and protein metabolism

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Self-assessment questions
9. Which of the following is the mechanism causing Cushing's disease?
A. Excess secretion of pituitary ACTH
B. Adrenal adenoma
C. Treatment with corticosteroids
D. Ectopic ACTH production by tumors
10. Which statement below regarding adrenal cortical dysfunction is true?
A. Patients with Cushing's syndrome usually have hyperkalemia.
B. Cushing's syndrome is associated with glucose intolerance.
C. Addison's disease is associated with hypernatremia.
D. Addison's disease is caused by elevated levels of cortisol.

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References
 “ Endocrinology” , Dereje Tekle, MPH, MT (ASCP), CLT (NCA)
 Burtis, Carl A., and Ashwood, Edward R.. Tietz: Fundamentals of Clinical
Chemistry. Philadelphia, 2001
 Arneson, W and J Brickell: Clinical Chemistry: A Laboratory Perspective 1st ed.
2007 FA Davis

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