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Pituitary Pathology (Biochemical Tests for Pituitary Function (Combined…
Pituitary Pathology
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Causes:
- Growth hormone cell (somatotroph) adenoma
Diagnosis:
- 1. Serial GH measurements
- 2. Oral glucose tolerance test (dynamic test)
- Glucose: suppressor of GH secretion
- Paired measurements (before & after oral glucose)
- 3. Insulin-like growth factor 1 test
- 4. Thyrotropin releasing hormone test
- If there is a paradoxical rise in GH in acromegaly
Clinical Features:
- Appearance:
- Enlarged viscera (thyroid, heart, liver, adrenals)
- Prognathism (protrusion of enlarged jaw)
- Hyperostosis (increased bone density) of hip & spine
- Enlarged hands & feet with sausage fingers
- Pathological effects:
- Gonadal dysfunction
- Diabetes mellitus
- Hypertension
- Arthritis
- Congestive heart failure
- Muscle weakness
Overview
Anterior Pituitary (Adenohypophysis)
- GHRH, 2. Somatostatin --> GH
- Stimulated linear growth, metabolism
- CRH --> ACTH
- Stimulates cortisol synthesis by adrenal cortex
- GnRH --> FSH, LH
- Stimulates ovulation, spermatogenesis
- Stimulates oestrogen and testosterone synthesis
- TRH --> TSH (thyrotrophin)
- Stimulates T3, T4 synthesis by thyroid gland
- Dopamine --> (Inhibits) Prolactin
- Stimulates breast milk production
- Hypothalamic control of AP hormone secretion is hormonal in nature
- Hypothalamic hormones secretion into hypophysial portal venous system to be carried to pituitary gland
Posterior Pituitary (Neurohypophysis)
- Vasopressin (ADH)
- Stimulated free water absorption by renal medullary collecting ducts
- Oxytocin
- Stimulates milk ejection and uterine contraction
- Hypothalamic control of PP hormone secretion is neuronal in nature
- Hormones are synthesised within hypothalamic neurons found in the paraventricular and supraoptic nucleus
- Hormones are then carried via axonal transport into the neurons' axonal processes (which make up the posterior pituitary) for storage
- Subsequent release of hormones in the axonal endings is triggered by a stimulus to the hypothalamus
Cushing Syndrome
- Excessive cortisol levels
Causes:
- ACTH-dependent:
- Pituitary adenoma (Cushing's disease)
- Ectopic ACTH production
- Paraneoplastic syndrome of gastric, pancreatic & lung malignancies
- Ectopic CRH production
- Ectopic bombesin (gastrin-releasing peptide) production (as bombesin mimics effects of cortisol)
- ACTH-independent
- Adrenal adenoma/carcinoma/hyperplasia
- Long-term exogenous cortisol administration
- Pseudo-Cushing's syndrome
- Depression, obesity, alcoholism
Establishing diagnosis of Cushing's syndrome:
- Low-dose dexamethasone suppression test
- 0.5mg dexamethasone, 6-hourly, for 48 hours
- Failure to suppress serum cortisol levels below 50 mol/L indicates presence of Cushing's syndrome
- Overnight dexamethasone suppression test
- 1mg dexamethasone at midnight, measure at 8am the next morning
- Urinary free cortisol
- 24 hr measurement of conjugated cortisol excreted in urine
- High dose dexamethasone suppression test
- Success in suppressing cortisol levels --> Pituitary adenoma
- Failure to suppress cortisol levels --> Ectopic ACTH production or adrenal adenoma
- Basal plasma ACTH test
- Inferior petrosal sinus sampling (CRH test)
HypopituitarismCauses:1. Pituitary adenoma
- May be functional or non-functional (causes panhypothyroidism)
- Causes hypopituitarism by mass effect (pressure atrophy of normal tissue)
2. Infiltrative Diseases:
- Hemochromatosis
- Lymphocytic hypophysitis
- Sarcoidosis
3. Infections:
- Tuberculosis
- Brucellosis
- Syphilis
- Mycosis (fungal infections)
4. Trauma
- Traumatic brain injury
- Subarachnoid hemorrhage
5. Post-operative6. Pituitary apoplexy
- Sudden haemorrhage into pituitary gland, often occurring into a pituitary adenoma
- Causes sudden onset of an excruciating headache, diplopia & hypopituitarism
7. Ischemic necrosis
*Due to any cause of impaired pituitary perfusion
- Sheehan syndrome: obstetric complication in which hemorrhagic shock during parturition precipitates an acute ischemic necrosis of the pituitary gland
8. Hypothalamic lesions
- Damage to hypothalamic neurons producing regulatory hormones or damage to pituitary stalk (conveys the hypophyseal portal venous plexus)
- Note: All affected ant pituitary hormones will be decreased except prolactin (increased)