Makindo Medical Notes

Related Subjects: |Adrenal Physiology |Addisons Disease |Phaeochromocytoma |Adrenal Adenomas |Adrenal Cancer |Cushing's Syndrome |Cushing's Disease |Congenital Adrenal hyperplasia |Primary hyperaldosteronism (Conn's syndrome) |ACTH |McCune Albright syndrome

Aldosterone induces sodium and water retention, but this is followed within a few days by a spontaneous diuresis called aldosterone escape. This process returns excretion to the level of intake and partially lowers the extracellular fluid volume toward normal, thus avoiding any clinically significant edema.

📖 About

• Excess production of aldosterone may cause up to 5% of cases of hypertension (HTN).

🧬 Aetiology

• High aldosterone → suppressed renin → sodium retention, potassium (K⁺) and hydrogen (H⁺) loss.
• Main clues: hypertension, hypokalaemia, metabolic alkalosis.

⚡ Causes of Primary Hyperaldosteronism

• Conn’s Adenoma (~75%)
  • Benign adrenal adenoma (<25 mm), yellow on imaging (cholesterol-rich).
  • Age 30–60, more common in women.
  • 🔧 Treatment: laparoscopic adrenalectomy (HTN cured ~70%). Spironolactone pre-op may be used.
• Bilateral Adrenal Hyperplasia (~25%)
  • Usually in >50 years, bilateral (macro- or micronodular).
  • 🔧 Treatment: medical management with spironolactone or eplerenone. Surgery not usually indicated.
• Adrenal Carcinoma (rare)
  • More common in elderly; tumours >4 cm, invasive.
  • May co-secrete cortisol, androgens, or oestrogens.
  • 🔧 Treatment: surgical resection ± adjuvant mitotane. Prognosis poor.
• Glucocorticoid-Remediable Hyperaldosteronism (rare, genetic)
  • Autosomal dominant; early-onset HTN in childhood.
  • Family history; bilateral zona glomerulosa hyperplasia.
  • ↑ 18-hydroxycortisol & 18-oxocortisol.
  • 🔧 Treatment: low-dose glucocorticoids (e.g., dexamethasone) + MR antagonists/amiloride.

🩺 Clinical Features

• Hypertension (often resistant).
• Headaches, general weakness.
• Muscle weakness, cramps, myopathy (from hypokalaemia).

🧾 Indications for Screening

• HTN with hypokalaemia (not diuretic-induced).
• Resistant HTN (uncontrolled on ≥3 agents).
• HTN + adrenal incidentaloma.
• Severe HTN (>160/100 mmHg).

🔍 Investigations (off diuretics, ACEi, ARBs)

ARR (aldosterone:renin ratio) >30 with aldosterone >300 pmol/L = highly suggestive (99% sensitive, 79% specific).

• Electrolytes: mild hypernatremia, hypokalaemia, hypomagnesemia; metabolic alkalosis (but >50% normokalaemic).
• Plasma renin & aldosterone: high aldosterone, suppressed renin. ARR >20–30 diagnostic.
• Saline suppression test: 2L saline over 4h. Normal → aldosterone <200 pmol/L; failure to suppress = primary hyperaldo.
• Imaging: adrenal CT/MRI to localise adenomas or hyperplasia.
• Adrenal venous sampling: differentiates unilateral vs bilateral disease.
• 131-Iodocholesterol scan: may help localise adenomas.
• Echocardiogram: LVH from longstanding HTN.
• Genetic testing: for glucocorticoid-remediable hyperaldosteronism.

🧾 Differential Diagnosis

• Glucocorticoid-remediable hyperaldosteronism.
• Apparent mineralocorticoid excess (licorice ingestion).
• Liddle’s syndrome (low aldosterone, high ENaC activity).
• Congenital adrenal hyperplasia (enzyme defects).
• Gordon’s syndrome (HTN + hyperkalaemia).

💊 Management

• Surgical
  • Conn’s adenoma → laparoscopic adrenalectomy (70% cure/improvement).
  • Adrenal carcinoma → surgical resection ± mitotane (poor prognosis).
• Medical
  • Bilateral hyperplasia or non-surgical → MR antagonists:
    • Spironolactone 25–100 mg/day.
    • Eplerenone 50–100 mg/day (more selective).
    • Amiloride also an option.
  • Glucocorticoid-remediable → low-dose dexamethasone ± MR antagonists.

📚 References

• Screening for Conn’s Syndrome (Primary Aldosteronism)

Cases — Primary Hyperaldosteronism (Conn’s Syndrome)

• Case 1 — Hypertension with hypokalaemia 💊: A 42-year-old woman presents with resistant hypertension despite 3 antihypertensives. Bloods: K⁺ 2.7 mmol/L, metabolic alkalosis. Plasma aldosterone:renin ratio is raised. CT adrenal: left adrenal adenoma. Diagnosis: Conn’s syndrome due to adrenal adenoma. Managed with laparoscopic adrenalectomy.
• Case 2 — Bilateral adrenal hyperplasia 🧬: A 55-year-old man with long-standing hypertension develops muscle weakness and polyuria. Bloods: persistent hypokalaemia, suppressed renin, raised aldosterone. Adrenal vein sampling: bilateral secretion. Diagnosis: primary hyperaldosteronism due to bilateral adrenal hyperplasia. Managed medically with mineralocorticoid receptor antagonists (spironolactone, eplerenone).
• Case 3 — Incidentaloma ⚠️: A 48-year-old woman investigated for an incidental adrenal mass found on CT for renal colic. She has mild hypertension but normal potassium. Screening shows elevated aldosterone:renin ratio. Diagnosis: subclinical primary hyperaldosteronism. Managed with further endocrine evaluation and treatment depending on lateralisation studies (surgery if unilateral, medication if bilateral).

Teaching Point 🩺: Primary hyperaldosteronism = autonomous aldosterone secretion, causing hypertension, hypokalaemia, and metabolic alkalosis. Causes: adrenal adenoma (Conn’s), bilateral adrenal hyperplasia, rarely carcinoma. Investigations: aldosterone:renin ratio (screening), confirmatory suppression tests, CT/MRI, adrenal vein sampling. Management: unilateral = surgery, bilateral = medical (spironolactone/eplerenone).