Concise Notes on Adrenal Glands and Disorders

Adrenal Glands

• Small, triangular glands on top of kidneys.
• Produce hormones regulating metabolism, immune system, blood pressure, stress response, and other functions.

Adrenal Cortex

• Produces steroid hormones:
  • Mineralocorticoids: Aldosterone
  • Glucocorticoids: Cortisol
  • Androgens: Dehydroepiandrosterone (DHEA)
• Synthesis stimulated by ACTH & controlled by plasma cortisol levels.

Aldosterone (Mineralocorticoid)

• Synthesis controlled by the Renin-Angiotensin system.
• Stimulates sodium exchange for potassium and hydrogen ions in kidneys.
• Important for sodium and water homeostasis.
• Inactivated by hepatic conjugation & excreted in urine.

Cortisol

• Naturally occurring glucocorticoid.
• Stimulates gluconeogenesis and breakdown of protein and fat.
• Opposes insulin actions.
• Maintains ECF volume and normal blood pressure.
• 95% bound to protein (transcortin), 5% unbound and active.

Adrenal Androgens

• Main: dehydroepiandrosterone (DHEA).
• Most DHEA bound to albumin.
• Secreted episodically, followed by cortisol secretion.
• Highest episodes in the morning, lowest in the evening.
• Loss of circadian rhythm is an early feature of Cushing’s syndrome.

Cushing’s Syndrome (↑↑ Cortisol)

• Clinical features: obesity (moon face), impaired glucose tolerance, increased protein catabolism, skin thinning, hypertension, androgen excess, psychiatric problems.
• Earliest feature: loss of diurnal variation.
• Causes: ACTH-dependent (↑ ACTH) or ACTH-independent (N/↓ ACTH).
• ACTH-dependent causes: Cushing’s disease (pituitary adenoma), ectopic ACTH-producing tumor.
• ACTH-independent causes: Adrenal tumor, exogenous glucocorticoids, ectopic cortisol-producing tumor.
• Pseudo-Cushing’s: psychological/physical stress, malnutrition, intense exercise, depression, obesity.

Lab Investigation of Suspected Cushing’s Syndrome

1. Assess abnormal Cortisol Secretion by:
   • Plasma cortisol level (morning/afternoon)
   • 24-hour Urinary free-cortisol estimation.
   • Late-night salivary cortisol.
2. Low-dose overnight Dexamethasone Suppression test:
   • Dexamethasone inhibits ACTH & thus cortisol secretion
3. High-Dose Dexamethasone Suppression test:
   • Negative feedback on pituitary adenomas
4. Insulin suppression test:
   • Differentiate Cushing’s from hypercortisolaemia due to depression or obesity.

Hypocortisolaemia

• Low Cortisol due to:
  • Problem in adrenals (Addison’s disease; primary).
  • Low ACTH (secondary).
  • Problem in hypothalamus (secondary/tertiary).

Addison’s Disease (Primary Adrenocortical hypofunction)

• Bilateral destruction of adrenal cortex (↓ cortisol).
• Causes: autoimmune, TB, amyloidosis, infections.
• Deficient hormones: Mineralocorticoids, Glucocorticoids, Androgens.
• Pigmentation due to high ACTH.

2nd Adrenocortical hypofunction (ACTH deficiency)

• Disorders of hypothalamus or anterior pituitary.
• Symptoms: weight loss, tiredness, hypoglycaemia, nausea, vomiting, hypotension, hyponatraemia.
• Absent pigmentation (low ACTH).

Investigation of Adrenocortical Hypofunction

• Urea, Electrolytes & Random Plasma cortisol level.
• Plasma ACTH assay: differentiate between 1° or 2°.
• Insulin-induced hypoglycaemia dynamic test.
• Short tetracosactrin test: (ACTH stimulation test).
• Combined pituitary stimulation test.

Congenital Adrenal Hyperplasia (CAH)

• Hyperplasia of adrenal cortex.
• Increase in cortisol precursors due to enzyme block (CYP21A2).
• Low cortisol, high ACTH.
• Increased androgen production (virilization).
• Decrease in Aldosterone synthesis (21α-hydroxylase deficiency): loss of sodium, vomiting, hyperkalaemia, hyponatraemia.

Diagnosis of 21⍺-hydroxylase deficiency

• Plasma 17-OH progesterone = ↑ in CAH
• Plasma androstenedione concentration = ↑ if patient with excessive androgen synthesis
• Check hormone profiles & kidney functions