Adrenal Cortical Hyperfunction: Cushing Syndrome, Hyperaldosteronism and Adrenogenital Syndrome

4th Year MBBS • ENDOCRINE + REPRODUCTION

Connect adrenal hormone regulation, hormone excess, diagnostic patterns and treatment principles for rapid revision.

Prepared according to the supplied AIM Concept Integration structure. :contentReference[oaicite:0]{index=0}

1. THE TOPIC IN ONE CONNECTED FLOW

The adrenal cortex produces aldosterone, cortisol and adrenal androgens. Disease develops when one pathway becomes autonomous, excessively stimulated or enzymatically blocked. The resulting hormone pattern explains the clinical presentation, guides the investigation and determines whether treatment should remove the source, inhibit hormone synthesis, block its receptor or replace a deficient hormone.

1. Normal adrenal organization

Glomerulosa → aldosterone
Fasciculata → cortisol
Reticularis → androgens

→

2. Regulation changes

ACTH mainly drives cortisol/androgens
RAAS + K⁺ mainly drive aldosterone

→

3. Pathway becomes abnormal

Cortisol excess
Aldosterone excess
Enzyme block → androgen excess

→

4. Functional effects

Catabolism + insulin resistance
Na⁺ retention + K⁺ loss
ACTH-driven androgen production

→

5. Clinical syndromes

Cushing phenotype
Hypertension ± hypokalaemia
Virilization / precocious androgen effects

→

6. Diagnostic clue

Cortisol testing → ACTH
Aldosterone relative to renin
Steroid precursor pattern

→

7. Treatment point

Remove autonomous source
Block synthesis/receptor
Replace deficient steroid

2. KEY CLINICAL CONNECTIONS

Cortisol Excess

Cortisol excess
→ protein catabolism + altered fat distribution
→ proximal weakness, thin skin, easy bruising and central obesity.

Confirm hypercortisolism
→ measure ACTH
→ suppressed ACTH suggests an autonomous adrenal source; non-suppressed ACTH suggests ACTH-dependent disease.

Aldosterone Excess

Excess aldosterone
→ increased Na⁺ reabsorption + K⁺/H⁺ secretion
→ hypertension ± hypokalaemia and metabolic alkalosis.

Bilateral adrenal hyperplasia
→ mineralocorticoid receptor blockade
→ spironolactone reduces aldosterone-mediated effects but may cause hyperkalaemia and endocrine adverse effects.

Adrenogenital Syndrome

Cortisol-synthesis enzyme defect
→ reduced negative feedback → increased ACTH
→ adrenal hyperplasia + increased androgen production.

21-hydroxylase deficiency
→ possible salt wasting;
11β-hydroxylase deficiency
→ mineralocorticoid-active precursors
→ hypertension.

3. AIM HIGH-YIELD INTEGRATION REVIEW

⭐ Zona fasciculata → cortisol → ACTH control; autonomous adrenal cortisol production raises cortisol but suppresses ACTH by negative feedback.

⭐ Cushing syndrome → catabolic cortisol effects → proximal myopathy, thin skin, bruising and osteoporosis; insulin resistance explains hyperglycaemia.

Dexamethasone → glucocorticoid negative feedback → reduced ACTH; failure of appropriate cortisol suppression supports pathological hypercortisolism.

⭐ Primary hyperaldosteronism → aldosterone high relative to renin → hypertension with suppressed renin; hypokalaemia strengthens the clue but is not obligatory.

Spironolactone → mineralocorticoid receptor blockade → reduced aldosterone effect; watch for hyperkalaemia and antiandrogen-related adverse effects.

⭐ 21-hydroxylase deficiency → low cortisol → high ACTH → androgen excess; severe deficiency also reduces aldosterone and may produce salt wasting.

Metyrapone, ketoconazole and aminoglutethimide → reduced steroid synthesis; mifepristone differs because it blocks glucocorticoid action at the receptor.

Long-term glucocorticoids → CRH/ACTH suppression → reduced endogenous cortisol production; abrupt withdrawal can therefore precipitate adrenal insufficiency.

AIM Exam Trap: Cushing syndrome describes cortisol excess from any cause, whereas Cushing disease specifically refers to a pituitary ACTH-secreting adenoma.