QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
ENDOCRINE GLANDS
Controls many body functions
exerts control by releasing special chemical substances into the blood called
Hormones
Hormones affect other endocrine glands or body systems
Ductless glands
Secrete hormones directly into bloodstream
Hormones are quickly distributed by bloodstream throughout the body
HORMONES
Chemicals produced by endocrine glands.
Act on target organs elsewhere in body.
Control/coordinate widespread processes:
Homeostasis.
Reproduction.
Growth & Development.
Metabolism.
Response to stress - Overlaps with the Sympathetic Nervous System
Hormones are classified as:
Proteins (Thyroid Hormone)
Polypeptides (Pituitary, Panreatic Parathyroid)
Lipids (fatty acid derivatives or steroids) (Adrenal Cortical, Gonadal)
Amount of hormone reaching target tissue directly correlates with concentration of
hormone in blood.
Constant level hormones: Thyroid hormones
Variable level hormones: Epinephrine (adrenaline) release
Cyclic level hormones: Reproductive hormones
Regulation of hormone release
Feedback
Negative
Positive (only narrow dose range)
Nerve regulation
pain, emotions, sex, injury, stress,...
e.g. oxytocin with nipple stimulation
THE ENDOCRINE SYSTEM
Consists of several glands located in various parts of the body
Specific Glands
Hypothalamus
Pituitary
Thyroid
Parathyroid
Adrenal
Kidneys
Pancreatic Islets
Ovaries
Testes
Hormones doesnt just secrete from glands but also cell
Heart (ANP), kidney (renin), liver (angiotensin), stomach (gastrin)
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
HYPOTHALAMUS
Part of brain
Regulates ANS, emotions, feeding/satiety, thirst, body temperature, etc.
Hormones related to these functions
Releasing hormones
Axonal transport to posterior lobe
Mention the releasing hormone and function of each hormone.
Posterior part of nervous system, not endocrine
Produces several releasing and inhibiting factors that stimulate or inhibit anterior
pituitarys secretion of hormones.
Produces hormones that are stored in and released from posterior pituitary.
Also responsible for:
Regulation of water balance
Esophageal swallowing
Body temperature regulation (shivering)
Food/water intake (appetite)
Sleep-wake cycle
Autonomic functions (heart rate, digestion)
Hypothalamic Releasing Hormones
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
Characteristics of Hypothalamic releasing hormones
Secretion in pulses
Act on specific membrane receptors
Transduce signals via second messengers
Stimulate release of stored pituitary hormones
Stimulate synthesis of pituitary hormones
Stimulates hyperplasia and hypertophy of target cells
Regulates its own receptor
Releasing hormone will be stimulated by stimulating hormone.
PITUITARY GLAND
ZIES
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
Small gland located on stalk hanging from base of brain.
The Master Gland
Primary function is to control other glands.
Produces many hormones.
Secretion is controlled by hypothalamus in base of brain.
Weight 600 mg
Is located within the bony cavity of the sphenoid bone
Sella Turcica (Turkish Chair)
Anatomically and functionally distinct anterior and posterior
lobes
Anterior Pituitary-adenohypophysis
Posterior pituitary-neurohypophysis
TRH - TSH
Cortico relasing acth
(check balik)
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
Histology of the PG
Anterior pituitary cells were originally classified as
Acidophils cells
Basophils cells
Chromophope cells
Now with immunocytochemical and electron microscopic techniques, classified
cells by their secretary products
Somatotrophs cells
GH secreting cells
Account about 50% of anterior P.G
Acidophilic stained ( red-pinkish)
Lactotrophic
Prl secreting cells
acidophilic stained
10-15% of anterior PG
Thyrotrophis
TSH secreting cells
basophilic cells (blue)
< 10% of anterior PG
Corticotrophs
ACTH secretary cells
basophilic cells
15-20% of anterior PG
Gonadotrophs
LH,FSH secretary cells
basophilic staining
10-15% of anterior PG
Yellow MSH (skin colour) and endrophine (pain hormone carry stimulation to brain)
ANTERIOR
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
Adrenocorticotropic hormone(ACTH)
Thyroid-stimulating hormone(TSH)
Growth hormone, Prolactin
Luteinizing hormone,
Follicle stimulating hormone
melanocytestimulating hormones
POSTERIOR
Oxytocin,
Antidiuretic hormone
Anterior Pituitary Hormones
Thyroid-Stimulating Hormone (TSH)
stimulates release of hormones from Thyroid
-- thyroxine (T4) and triiodothyronine (T3): stimulate metabolism of all cells
-- calcitonin: lowers the amount of calcium in the blood by inhibiting
breakdown of bone
released when stimulated by TSH
abnormal conditions
-- hyperthyroidism: too much TSH release
-- hypothyroidism: too little TSH release
Growth Hormone (GH)
stimulates growth of all organs and increases blood glucose concentration
-- decreases glucose usage
-- increases consumption of fats as an energy source
Adreno-Corticotrophic Hormone (ACTH)
stimulates the release of adrenal cortex hormones
Follicle Stimulating Hormone (FSH)
females - stimulates maturation of ova; release of estrogen
males - stimulates testes to grow; produce sperm
Luteinizing Hormone (LH)
females - stimulates ovulation; growth of corpus luteum
males - stimulates testes to secrete testosterone
Prolactin
stimulates breast development during pregnancy; milk production after
delivery
Melanocyte Stimulating Hormone (MSH)
stimulates synthesis, dispersion of melanin pigment in skin
Posterior Pituitary Hormones
Stores, releases two hormones produced in hypothalamus
Antidiuretic hormone (ADH)
Oxytocin
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
Antidiuretic hormone (ADH)
Stimulates water retention by kidneys: reabsorb sodium and water
Abnormal conditions
-- Undersecretion: diabetes insipidus (water diabetes)
-- Oversecretion: Syndrome of Inappropriate Antidiuretic Hormone
(SIADH)
Oxytocin
Stimulates contraction of uterus at end of pregnancy (Pitocin); release of
milk from breast
Pineal Gland
Located within the Diencephalon
Melatonin
Inhibits ovarian hormones
May regulate the bodys internal clock
ANTERIOR PITUITARY INSUFFICIENCY
Etiology
Reduced pituitary function can result from inhereited disorders more commonly,
It is acquired and reflects the mass effects of tumors or the consequences of
inflamation or vascular damage.
Most common is hypo and hyper
Why pituitary not secrete enough hormone? 2 reason: congenital (due to genetic,
during pregnancy) or acquired.
Developmental and Genetic Causes of Hypopituitarism
3 most common causes: *
Non secretory adenoma of anterior pituitary
Sheehans syndrome (postpartum pituitary necrosis)
Empty sella syndrome (pituitary gland becom shrinks or becomes flattened)
Also happen because of :
Developmental Hypotalamic Dysfunction:
Kallmann Syndrome (Hypogonadotropic hypogonadism)
Laurence-Moon-Bardet-Biedl Syndrome (involves many body systems)
Causes of Hypopituitarism
Tumours (tu)
Pituitary tumor
Adenoma,craniopharyngioma
Cerebral tumor
Hypothalamic disorders
Tumor
Functional disturbance-
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
Eg -Anorexia nervosa
Isolated GH and GnH secretion due to impaired secretion of hypothalamic
releasing hormones
Miscellaneous
Sarcoidosis (inflammation of L.N)
Histocytosis X (abnormal increase in the number of immune cells )
Haemochromatosis
Vascular ds
Necrosis (Sheehans synd)
Infarction
Severe hypotension
Cranial arteritis (inflammation of artery)
Trauma
Infection
Meningitis esp TB, syphilis
Iatrogenic
Surgery (remove tumor)
Irradiation
Prolonged rx with glucocorticoid or thyroid hormones-isolated ACTH or TSH
suppression
Partial hypopituitarism is more frequent than complete loss of pit functions
Sx/signs do not manifest until > 75% of ant lobe is destroyed
GH secretion is an early feature of pit failure-effects > dramatic in children but less
significant in adults
LH/ FSH are affected before ACTH
Hypothyroidism is an uncommon presenting feature of pit failure
GH- LH/FSH ACTH - THYROID
Clinical Features
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
POSTERIOR PITUITARY HYPOFUNCTION
ADH production cranial diabetes insipidus (DI)
Causes of cranial DI
Tumours-craniopharyngioma, secondary tumours (metastatic CA), pituitary tumours
with suprasella extension.
Granulomatous disease.
Meningitis, abscess and encephalitis.
Vascular disorders. (sheehan syndrome)
Trauma.
Surgery.
Idiopathic.
Effects
Polyuria-uncontrolled renal water excretion, tendency to dehydration
Polydipsia-excessive thirst, dehydration stimulate thirst centre resulting in increase water
intake
Water take sodium and potassium
Lead to hypotension .
Lose of water, plasma lose (50%) blood will be more concentrated lead to blood clot
Clinical Feautures
Hypotension
Decreased pulse pressure
Tachycardia
Increased Hbg,hct
Increased UOP
Poor skin turgor
Irritablilty
Decreased cognition
Hyperthermia
Lethargy leading to coma
HYPOPITUITARISM
Diagnosis
Biochemical diagnosis of pituitary insufficiency
- Demonstrating low levels of trophic hormones in the setting of low target
hormone levels.
Hormone Replacement *
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
HYPERPITUITARISM (PITUITARY HYPERFUNCTION)
Hyperpituitarism - Excessive production of adenohypophyseal hormones
Causes
Pituitary adenoma
Carcinoma (rare)
Hypothalamic disorder-excess stimulation of the pituitary (rare)
Order of frequency with which hormone secretion occurs in pituitary tumour is
prolactin (relatively common) GH ACTH gonadotrophin TSH
Pathogenesis
Excessive Secretion of prolactin secretion of GnRH gonadotrophins
In men: impotency, decreased libido
In women: amenorrhea, galactorrhea
Excessive Secretion of somatotrophine (growth hormone)
acromegaly (in adults)
gigantism (in adolescent whose epiphysseal plates havent closed)
Pathomechanism involved:
The usual GH baseline secretion pattern is lost (as are sleep related GH peaks)
GH secretion is slightly elevated somatomedin to stimulation of growth
(in adolescent)
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
In adults
Connective tissue proliferation
Bony proliferation characteritics appearance of acromegaly
Phosphate reabsorbtion in renal tubules hyperphosphatemia
Impairement of carbohydrate tolerance
Metabolic rate
Hyperglycemia - it is a result of GH inhibition of peripheral glucose uptake and
increase hepatic glucose production compensatory hyperinsulinism insulin
resistance diabetes mellitus
Excessive Secretion of corticotrophin (ACTH) central form of Cushing syndrome
(Cushing disease)
Chronic hypercortisolism is the main disturbance of ACTH
Symptoms and signs:
Weight gain: - accumulation of adipose tissue in the
cervical areas (truncal obesity, moon face, buffalo hump)
weight gain from Na and water retention
Glucose intolerance DM type 2
Polyuria: osmotic polyuria due to glycosuria
trunk, facial, and
-
Protein Wasting: due to catabolic effects of cortisol on peripheral tissue
(muscle wasting muscle atrophy and weakness thin lower extremities)
in bone: - loss of protein matrix osteoporosis
blood calcium concentration renal stones
in skin: - loss of collagen thin, weakened integumentary tissues purple
striae; rupture of small vessel
- thin, atrophic skin is easily damaged, leading to skin breaks and
ulceration
Hyperpigmentation: due to very high levels of ACTH - manifestation in: mucous membranes,
hair, and skin.
Hypertension: results from permissive effect of cortisol on the actions of the catecholamines
(KA) vascular sensitivity to KA vasoconstriction hypertension
Suppression of the immune system susceptibility to infections
Alteration of mental status - from irritability and depression up to schizophrenia.
Symptoms and signs of adrenal androgens level in women:
hair growth (especially facial hair)
acne
oligoamenorrhea
changes of the voice
Hyperglycemia, glycosuria, hypokalemia, metabolic alkalosis.
Excessive Secretion Of Thyreotrophin and Gonadotrophins is rare
QPT20603: PATHOPHYSIOLOGY OF ENDOCRINE
PITUITARY GLAND DISEASES
ZIES
Measurement of anterior pituitary hormones
Measured in serum by immunoassay
Dynamic tests/ functional tests are important tools in pituitary functions and other
endocrine organs.
Basic principle of dynamic tests:
Hypofunction - stimulation tests
Hyperfunction-suppression tests
Magnetic resonance imaging (MRI)
Treatment
MedicationDrugs may be used to shrink large tumors.
1. Dopamine inhibits prolactin secretion. Bromocriptine and cabergoline are
dopamine agonists (drugs that behave like dopamine) and can shrink
prolactinomas and return secretions of prolactin to normal levels.
2.
Patients with acromegaly may be treated with somastatin analogs to lower
growth hormone levels and shrink tumors.
3. Dopamine agonists may also be used alone or in combination with somastatin
analog
Surgery: Removing the underlying tumor surgically is the chosen treatment.
Radiation, by itself or following surgery, might be done to decrease the size of the
tumor, or keep it from coming back.