What is the treatment for a patient with suspected adrenal hyperplasia?

Treatment of Adrenal Hyperplasia

The treatment of adrenal hyperplasia depends entirely on the underlying etiology: congenital adrenal hyperplasia (CAH) requires glucocorticoid and mineralocorticoid replacement, while bilateral adrenal hyperplasia from primary aldosteronism is treated medically with mineralocorticoid receptor antagonists, and ACTH-dependent bilateral hyperplasia requires addressing the pituitary source. 1

Initial Diagnostic Workup to Guide Treatment

Before initiating treatment, you must determine the specific cause of adrenal hyperplasia, as this fundamentally changes management:

• Measure 17-hydroxyprogesterone levels to screen for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency—the most common form of CAH 1
• Assess for primary aldosteronism by measuring plasma aldosterone concentration, plasma renin activity, and calculating the aldosterone-to-renin ratio (typically >30 in primary aldosteronism) 2, 1
• Measure ACTH levels to distinguish ACTH-dependent causes (elevated ACTH indicates pituitary or ectopic sources driving bilateral hyperplasia) from ACTH-independent causes 2, 1
• Rule out metastatic disease if the patient has a known malignancy elsewhere, as this would fundamentally alter management 1

Treatment Algorithm by Etiology

Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)

For classical CAH, initiate both glucocorticoid and mineralocorticoid replacement immediately to prevent life-threatening salt-wasting crisis and suppress excessive adrenal androgens 3, 4, 5:

Glucocorticoid Replacement

• Hydrocortisone is the preferred glucocorticoid for children and adults with CAH 3, 5
• Standard dosing: Administer hydrocortisone in divided doses throughout the day to mimic physiologic cortisol secretion 3, 5
• Monitor treatment adequacy through growth rate, body weight, blood pressure, physical examination for virilization, and biochemical measurements of adrenal androgens 5

Critical pitfall: Avoid chronic overtreatment with glucocorticoids, as high doses and potent synthetic long-acting glucocorticoids (dexamethasone, prednisone) increase risk of obesity, insulin resistance, osteoporosis, and reduced quality of life 3, 6

Mineralocorticoid Replacement

• Fludrocortisone is required in salt-wasting forms of CAH to normalize electrolytes and plasma renin activity 4, 7
• Monitor adequacy by checking serum electrolytes, blood pressure, and plasma renin activity 5

Stress Dosing

• Triple the daily glucocorticoid dose during febrile illness, significant trauma, or major physiologic stress 5
• For major surgery: Administer 100 mg hydrocortisone IM/IV just before anesthesia, then continue 100 mg every 6 hours until the patient can take oral medications 8

Non-Classical CAH

• Glucocorticoid therapy is recommended only if the patient has inappropriately early and rapidly progressing pubarche, accelerated bone age progression, or overt virilization 5
• For stress dosing: Hydrocortisone is recommended for major surgery, trauma, or childbirth only if the patient has a suboptimal cortisol response to ACTH stimulation testing 5

Primary Aldosteronism with Bilateral Adrenal Hyperplasia (Idiopathic Hyperaldosteronism)

Medical management with mineralocorticoid receptor antagonists is first-line therapy for bilateral adrenal hyperplasia causing primary aldosteronism 1, 9:

• Spironolactone 100-400 mg daily is the FDA-approved treatment for long-term maintenance therapy in patients with bilateral micro or macronodular adrenal hyperplasia 9
• Eplerenone is an alternative mineralocorticoid receptor antagonist with fewer side effects 1

Critical pitfall: Do not perform bilateral adrenalectomy for primary aldosteronism without first attempting adequate medical therapy, as two-thirds of primary aldosteronism cases are bilateral hyperplasia requiring medical rather than surgical management 1

Important consideration: If medical therapy fails to control hypertension or hypokalemia, obtain adrenal venous sampling to exclude unilateral autonomous function developing within bilateral hyperplasia, which may be amenable to unilateral adrenalectomy 1

ACTH-Dependent Bilateral Adrenal Hyperplasia (Cushing's Disease)

Address the pituitary source rather than the adrenal glands when bilateral adrenal hyperplasia is secondary to ACTH excess 1:

• Transsphenoidal resection of the pituitary adenoma is the definitive treatment for Cushing's disease, which addresses the root cause of adrenal hyperplasia 1
• Medical management with adrenostatic agents (ketoconazole, mitotane) is reserved for patients with unresectable pituitary tumors 10, 1

Bilateral adrenalectomy should be considered only for severe, refractory Cushing's disease or life-threatening emergencies requiring immediate cortisol control 1

Management After Bilateral Adrenalectomy

If bilateral adrenalectomy is performed for any reason, lifelong glucocorticoid and mineralocorticoid replacement is mandatory 10, 1:

• Immediate postoperative management: Administer stress-dose hydrocortisone (100 mg IV/IM every 6-8 hours) until the patient is stable, then transition to maintenance therapy 10
• Maintenance therapy: Hydrocortisone 15-20 mg daily in divided doses plus fludrocortisone 50-200 μg daily 10
• Patient education is non-negotiable: All patients must carry a steroid emergency card, wear medical alert identification, and be prescribed emergency injectable hydrocortisone with clear instructions for use 10

Recognition and Treatment of Adrenal Crisis

Adrenal crisis is a life-threatening emergency that occurs in 6-8 per 100 patient-years in patients with adrenal insufficiency 8:

Clinical Recognition

• Symptoms include: Malaise, fatigue, nausea, vomiting, abdominal pain (sometimes with peritoneal irritation), muscle pain or cramps, dehydration leading to hypotension and shock 8
• Impaired cognitive function including confusion, loss of consciousness, and coma is not uncommon 8
• Laboratory findings: Hyponatremia, hyperkalemia, increased creatinine from prerenal renal failure, and sometimes hypoglycemia (especially in children) 8

Emergency Treatment

Treatment must not be delayed by diagnostic procedures 8:

1. Draw blood for serum cortisol, ACTH, electrolytes, glucose, and cultures (if infection suspected) 8
2. Immediately administer 100 mg hydrocortisone IV or IM, followed by 100 mg every 6-8 hours until recovered 8
3. Rapidly infuse 0.9% saline at 1 L per hour initially until hemodynamic improvement 8
4. Identify and treat the precipitating cause (infection, trauma, surgery, myocardial infarction, severe allergic reaction) 8

Critical rationale: The 100 mg hydrocortisone dose saturates 11β-hydroxysteroid dehydrogenase type 2, providing the desired mineralocorticoid effect in addition to glucocorticoid replacement 8

Long-Term Monitoring

Annual clinical assessment is mandatory for all patients with adrenal hyperplasia on hormone replacement 8, 10:

• Assess: Health and well-being, weight, blood pressure, and serum electrolytes 8, 10
• Monitor for new autoimmune disorders (particularly hypothyroidism) in patients with autoimmune adrenal insufficiency 8
• Bone mineral density should be checked every 3-5 years in patients on glucocorticoid replacement to assess for osteoporosis 8, 10
• Repeat imaging at 6-12 months if initial post-operative imaging shows any abnormality 10