What are the diagnostic and treatment approaches for Conn's (Primary Aldosteronism) syndrome, Addison's disease, and other similar endocrinological syndromes?

Key Findings in Conn's, Addison's, and Related Endocrinological Syndromes

Primary aldosteronism (Conn's syndrome) and primary adrenal insufficiency (Addison's disease) represent opposite ends of the adrenal dysfunction spectrum, with distinct diagnostic approaches and treatment strategies based on their underlying pathophysiology.

Primary Aldosteronism (Conn's Syndrome)

Diagnostic Approach

• Screening: Measure plasma aldosterone and renin activity; aldosterone-to-renin ratio >30 suggests primary aldosteronism 1
• Confirmatory testing: Saline suppression test or salt loading test 1
• Laboratory findings: Elevated aldosterone, suppressed renin, hypokalemia, metabolic alkalosis 1
• Imaging: Adrenal CT or MRI to identify adenoma vs. bilateral hyperplasia 1
• Adrenal vein sampling: Gold standard for distinguishing unilateral adenoma from bilateral hyperplasia, especially important in patients >40 years 1

Treatment Algorithm

1. Unilateral adenoma:

   • Laparoscopic adrenalectomy (preferred) 1
   • Expect normalization of potassium levels post-surgery, though hypertension may persist in ~45% of patients 2

2. Bilateral adrenal hyperplasia:

   • Medical management with mineralocorticoid receptor antagonists:
     • Spironolactone 12.5-100 mg/day 3
     • Eplerenone as alternative 1

3. Malignant hyperaldosteronism (rare):

   • Warning signs: tumor >4 cm, very high aldosterone/renin ratio, severe hypokalemia (<2.0 mmol/L) 4
   • Treatment: Open adrenalectomy (not laparoscopic) due to risk of tumor rupture 1, 4

Clinical Pearls

• Monitor for hypokalemia-induced complications including rhabdomyolysis 5
• CT has ~82% sensitivity for detecting aldosteronomas 6
• Residual hypertension persists in approximately 45% of patients after successful surgery 2

Primary Adrenal Insufficiency (Addison's Disease)

Diagnostic Approach

• Initial testing: Morning serum cortisol and plasma ACTH 1
• Confirmatory testing: ACTH stimulation test (cosyntropin 0.25 mg IV/IM) with cortisol measurement at 30 and 60 minutes; normal response >550 nmol/L 1, 7
• Etiologic diagnosis: Measure 21-hydroxylase antibodies (21OH-Ab); positive result indicates autoimmune etiology (85% of cases) 1
• If 21OH-Ab negative: Consider CT adrenals to evaluate for hemorrhage, tumor, tuberculosis 1

Treatment Algorithm

1. Glucocorticoid replacement:

   • Hydrocortisone 15-25 mg daily in divided doses (first dose upon waking, last dose ≥6 hours before bedtime) 1, 7
   • Children: 6-10 mg/m² of body surface area 1

2. Mineralocorticoid replacement:

   • Fludrocortisone 50-200 μg daily as single dose 1, 8
   • Higher doses may be needed in children and younger adults 1
   • Monitor blood pressure and electrolytes for dose adjustments 7

3. Adrenal crisis management:

   • Immediate IV/IM hydrocortisone 100 mg, followed by 100 mg every 6-8 hours until recovered 1, 7
   • Isotonic saline infusion at initial rate of 1 L/hour until hemodynamic improvement 1, 7
   • Identify and treat underlying precipitant (e.g., infection) 1

Stress Dosing Protocol

• Minor illness/stress: Double or triple usual daily dose 7
• Moderate stress: Hydrocortisone 50-75 mg/day in divided doses 7
• Severe stress: Hydrocortisone 100 mg IV immediately, followed by 100-300 mg/day continuous infusion or divided doses every 6 hours 7

Clinical Pearls

• All patients should wear medical alert identification, carry steroid alert card, and receive education on stress dosing 7
• Annual monitoring for development of other autoimmune disorders, particularly hypothyroidism 1
• Avoid medications that interact with fludrocortisone (diuretics, NSAIDs, licorice) 7

Differentiating Primary vs. Secondary Adrenal Insufficiency

Type	ACTH Level	Cortisol Level	Electrolytes
Primary	High	Low	↓Na, ↑K
Secondary	Low	Low	Normal

Cushing Syndrome

Diagnostic Approach

• Screening: Overnight 1 mg dexamethasone suppression test with 8 am plasma cortisol or repeated midnight salivary cortisols 1
• Laboratory findings: Elevated cortisol, possible hypokalemia, hyperglycemia 1
• ACTH levels: Determine source (adrenal vs. pituitary vs. ectopic) 1

Treatment Algorithm

• ACTH-independent (adrenal source):

  • Benign adrenal adenoma: Adrenalectomy 1
  • Malignant adrenal tumor: Open adrenalectomy with adjuvant therapy 1

• ACTH-dependent (pituitary or ectopic source):

  • Pituitary tumor: Transsphenoidal surgery 1
  • Ectopic tumor: Remove primary tumor if possible 1
  • If unresectable: Bilateral adrenalectomy or medical management 1

Clinical Pearls

• Suspect malignancy if tumor >5 cm, inhomogeneous with irregular margins, or local invasion 1
• Symptoms include weight gain, muscle weakness, hypertension, psychiatric disturbances, hirsutism, and central obesity 1

Pheochromocytoma

Diagnostic Approach

• Screening: Fractionated plasma-free metanephrines 1
• Confirmatory testing: 24-hour urine catecholamines if plasma metanephrines elevated 1
• Imaging: Adrenal protocol CT or MRI 1

Treatment

• Rule out pheochromocytoma before any adrenal biopsy or surgery 1
• Surgical resection after appropriate alpha-blockade 1