What are the treatment options for adrenal gland disorders?

Treatment Options for Adrenal Gland Disorders

The treatment of adrenal disorders depends fundamentally on whether the problem is hormone excess or deficiency, with adrenal insufficiency requiring lifelong glucocorticoid replacement (hydrocortisone 15-25 mg daily in divided doses) plus mineralocorticoid replacement (fludrocortisone 50-200 μg daily) for primary cases, while adrenal crisis demands immediate IV hydrocortisone 100 mg bolus with rapid saline infusion. 1

Primary Adrenal Insufficiency (Addison's Disease)

Maintenance Therapy

Glucocorticoid replacement is the cornerstone of treatment:

• Hydrocortisone 15-25 mg daily in divided doses is the preferred agent 1
• Common dosing schedules: 10 mg upon waking + 5 mg midday + 2.5 mg afternoon 1
• The first dose must be taken immediately upon waking, and the last dose at least 6 hours before bedtime to avoid sleep disturbances 1
• Alternative: Cortisone acetate 18.75-31.25 mg daily in divided doses 2

Mineralocorticoid replacement is essential in primary adrenal insufficiency:

• Fludrocortisone 50-200 μg once daily taken in the morning 1
• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during the third trimester of pregnancy when progesterone counteracts mineralocorticoids 2, 1
• Patients should consume salt and salty foods without restriction and avoid potassium-containing salt substitutes 2, 1

Acute Adrenal Crisis Management

Treatment must never be delayed for diagnostic procedures 2, 1. This is a life-threatening emergency with 6-8 crises per 100 patient-years 2.

Immediate interventions:

• Hydrocortisone 100 mg IV bolus immediately, followed by 100-300 mg/day as continuous infusion or IV/IM boluses every 6 hours 2, 1
• Rapid IV administration of 0.9% saline at 1 L/hour initially, followed by 3-4 L over 24-48 hours with frequent hemodynamic monitoring 2, 1
• Draw blood for cortisol, ACTH, electrolytes, and glucose before treatment if possible, but do not delay therapy 2
• Taper parenteral glucocorticoids over 1-3 days to oral maintenance therapy as the patient's condition improves 2, 1
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 2

Common precipitating factors include vomiting/diarrhea, infections, surgical procedures, injuries, myocardial infarction, severe allergic reactions, and severe hypoglycemia in diabetic patients 2, 1.

Stress Dosing

During minor illnesses with fever: Double or triple the usual glucocorticoid dose 1

Major surgery: 100 mg hydrocortisone IM before anesthesia, followed by 100 mg IM every 6 hours until able to take oral medications 1

Minor surgery: 100 mg hydrocortisone IM before anesthesia, then double oral dose for 24 hours 1

Monitoring and Follow-up

Annual assessments should include:

• Blood pressure (supine and standing) to detect postural hypotension indicating insufficient mineralocorticoid therapy 2, 1
• Weight monitoring (weight loss suggests insufficient glucocorticoid dosing or additional disease) 2, 1
• Serum sodium, potassium, glucose, and HbA1c 1
• Screening for associated autoimmune conditions, particularly thyroid dysfunction (TSH, FT4, TPO-Ab) and vitamin B12 levels 1

Signs of under-replacement: Weight loss, fatigue, postural hypotension, salt craving, hyperpigmentation 1

Signs of over-replacement: Weight gain, hypertension, peripheral edema 1

Drug Interactions

Medications that may increase hydrocortisone requirements:

• Anti-epileptic drugs and barbiturates 2, 1
• Antituberculosis medications 2
• Antifungal drugs 2, 1
• Etomidate 2
• Topiramate 2

Medications that may decrease hydrocortisone requirements:

• Grapefruit juice 2, 1
• Licorice 2, 1

Medications to avoid with fludrocortisone:

• Diuretics 2, 3
• Acetazolamide 2, 3
• NSAIDs 2, 3
• Carbenoxolone and licorice 2, 3

Drospirenone-containing contraceptives may require higher fludrocortisone doses 2, 3

Prevention of Future Crises

Critical patient education components:

• All patients must wear medical alert identification jewelry 1
• Patients must be empowered to increase steroid doses during intercurrent illnesses, vomiting, injuries, or other stressors 2, 1
• Patients should be prescribed injectable hydrocortisone (100 mg IM) for emergency self-administration 4
• Seek medical help before reaching a state of being unable to self-care 2

Common pitfalls leading to recurrent crises:

• Under-replacement with mineralocorticoids is common and predisposes to recurrent crises 2, 1, 3
• Low salt consumption 2
• Poor compliance and inadequate patient education 2

Secondary Adrenal Insufficiency

Key differences from primary adrenal insufficiency:

• Mineralocorticoid replacement (fludrocortisone) is not required because aldosterone production remains intact 4
• Glucocorticoid replacement follows the same principles as primary adrenal insufficiency 4
• DHEA levels are typically low or low-normal 4

Critical warning: When treating patients with both secondary adrenal insufficiency and hypothyroidism, corticosteroids must be started several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 5

Glucocorticoid-Induced Adrenal Insufficiency

This is the most common form of adrenal insufficiency 4.

Risk factors:

• Any patient taking ≥20 mg/day prednisone or equivalent for at least 3 weeks 5
• Prolonged use of supraphysiological doses of glucocorticoids 4

Management approach:

• Gradual tapering of exogenous glucocorticoids to minimize drug-induced secondary adrenocortical insufficiency 6
• During tapering, patients may require stress-dose coverage for months after discontinuation 6
• Salt and/or mineralocorticoid may need to be administered concurrently during the recovery period 6

Adrenal Androgen Replacement (Optional)

For female patients with primary adrenal insufficiency:

• DHEA 10-50 mg daily (typically 25 mg as a single morning dose) can be considered for persistent lack of libido and/or low energy despite optimized glucocorticoid and mineralocorticoid replacement 2
• A pragmatic approach is a 6-month trial, continuing only if clinically effective 2
• Guided by serum DHEA sulfate, androstenedione, and testosterone levels measured in the morning prior to DHEA ingestion 2
• Long-term effects are not well established, so use with caution 2

Disorders of Adrenal Hormone Excess

While the provided evidence focuses primarily on adrenal insufficiency, other adrenal disorders mentioned include:

Hypercortisolism (Cushing's syndrome): Causes muscle weakness and behavioral disturbances including emotional lability and depression 7, 8

Primary hyperaldosteronism: Affects 6% of hypertensive patients and may cause weakness from hypokalemia 7, 8

Pheochromocytoma: Causes excessive catecholamine secretion with primarily cardiovascular symptoms 7, 9

Adrenocortical carcinoma and metastases: Require imaging studies and may necessitate surgical intervention 9

Special Populations

Pregnancy:

• Hydrocortisone dose typically remains unchanged 2
• Fludrocortisone requirements may increase, particularly in the third trimester due to progesterone's anti-mineralocorticoid effects 2, 3

Children:

• Growth and development must be carefully monitored on prolonged corticosteroid therapy 6
• Higher fludrocortisone doses (up to 500 μg daily) may be required 2, 1
• Hypoglycemia is more common in children with adrenal insufficiency 2, 10