The cortex of the gland secretes mainly cortisol, aldosterone and androgens. The medulla secrets epinephrine and not epinephrine.
Control of cortisol secretion:
- Higher centre Negative feedback control: through corticotropin-releasing hormone (CRH) from the hypothalamus and ACTH from the anterior pituitary.
- Response to stress: e.g. physical and emotional stress lead to sudden large increase in CRH and ACTH.
- Diurnal rhythm: values of plasma cortisol are higher in the morning than at midnight. This depends also on CRH and ACTH secretions which are related to the rhythm of an individual’s sleeping-waking cycle.
In the circulation, cortisol is mainly bound (90%) to cortisol-binding globulin (CBG). The biologically active fraction, free cortisol (10%) is in equilibrium with the protein-bound cortisol.
This is the principal mineralocorticoid, its functions is to conserve Na+ mainly by enhancing the reabsorption of Na+ and reciprocal K+ or H+ secretion in distal renal tubule and in other epithelial cells.
Regulation of aldosterone secretion is achieved by:
- Renin-angiotensin system: renin is released in response to fall in blood volume or renal perfusion pressure, and by loss of Na+.
- Potassium: increase in plasma K+ stimulates aldosterone Secretion.
- ACTH has a little role in aldosterone regulation.
Their production is determined by the rate of synthesis of precursors and is controlled by ACTH.
Disorders of supra-renal cortical functions
A) Hyperfunction: Cushing's syndrome:
This results from pituitary hyperplasia (Cushing disease), adenoma, carcinoma of the suprarenal, iatrogenic or ectopic production of ACTH or CRH.
* Screening tests:
- Elevation of urinary free cortisol.
- Low dose dexomethasone suppression test: normally dexamethasone causes suppression of CRH, ACTH and cortisol secretion by negative feedback. Failure of this suppression occurs in Cushing's disease.
* Confirmatory tests:
- Elevation of serum cortisol with loss of diurnal rhythm.
- Insulin hypoglycemia test: insulin induced hypoglycemia is a sensitive stress test for the integrity of the hypotholamo-pituitary-adrenal axis. Induction of sufficient hypoglycemia causes marked elevation of serum cortisol in normal subjects. In Cushing's syndrome, basal cortisol levels are high with no further increase after adequate hypoglycemia. This test should be performed under careful observation in hospital.
Tests to assess the cause:
- Plasma ACTH: low in cases due to primary suprarenal pathology e.g. tumor, raised in cases of pituitary origin. Very high plasma ACTH, in ectopic production.
- High-dose dexamethasone suppression test: Patients with Cushing’s disease due to hyperplasia respond to this test by a fall of serum cortisol or urinary free cortisol to less than 50% of the basal level. Patients with suprarenal tumors or ectopic ACTH production do not show suppression.
Other laboratory finding:
- Hypokalemic alkalosis.
- Impaired glucose tolerance (steroid diabetes).
- Tumor markers may be positive in ectopic ACTH production.
Primary chronic suprarenal cortex insufficiency (Addison's disease) arises due to autoimmune disorder, infections especially T.B, CMV, congenital adrenal hypoplasia or hyperplasia or to post-partum hemorrhage secondary hypofunction due to pituitary disease.
Diagnosis is based on:
Screening tests: serum cortisol is usually low and fails to rise thirty min. after I.M. injections of synacthen (Synthetic ACTH short synacthen test).
Tendency for hyponatremia and hyperkalemia.
Depot (long) synacthen test: serum cortisol is measured on basal sample and on further samples taken between five and eight hours after I.M. injection of 1.0 mg synacthen for three successive days. The cortisol fails to rise in Addison’s disease while stepwise increase in cortisol response occurs in secondary adrenocortical insufficiency.
Tests to assess the cause: ACTH values are high in primary and low in secondary hypofunction.
Tests for adrenal antibodies.
Disorders of suprarenal medulla
The suprarenal medulla secretes the catecholamines (adrenaline and noradrenaline). Tumours at this site secrete excessive amounts of either noradrenaline or adrenaline, together with increased excretion of their metabolites in urine.
Tumours causing these effects are pheochromocytoma and neuroblastoma.
Laboratory diagnosis is based on:
- Measurement of plasma catecholamines.
- Measurement of urinary catecholamines and their metabolites: metadrenaline normetadrenaline and 4-hydroxy, 3-methoxymandelic acid (HMMA), which are commonly referred to as vanilyl mandelic acid (VMA). These analytes are sensitive to drugs (azothioprine) and certain dietary constituents (vanilline and bannana). In patients with paroxysmal attacks of hypertension basal measurements should be made at the time of the attack and in-between.