What is the primary treatment approach for an adult patient with hypopituitarism (underactive pituitary gland)?

Treatment of Hypopituitarism in Adults

The primary treatment for adult hypopituitarism is hormone replacement therapy targeting each deficient axis, with glucocorticoid replacement being the absolute first priority before any other hormone is initiated. 1

Critical First Step: Glucocorticoid Replacement

Never start thyroid hormone before glucocorticoid replacement—this is the most dangerous error and can precipitate adrenal crisis. 1 This represents the single most important safety principle in hypopituitarism management.

Glucocorticoid Protocol

• Hydrocortisone 20-30 mg/day in divided doses: 20 mg morning, 10 mg noon, 10 mg evening 1
• For severe symptoms with acute presentation, initiate IV methylprednisolone 1 mg/kg, then convert to oral prednisolone 1
• All patients must receive a medical alert bracelet and education on "sick day rules" for stress dosing 1

Sequential Hormone Replacement After Glucocorticoid Initiation

Thyroid Hormone Replacement

• Only after glucocorticoid replacement is established, initiate levothyroxine (thyroxine) 2, 3
• Monitor free T4 every 1-2 weeks until stable, then every 6-8 weeks 1
• Target normal free T4 levels, not TSH (which will be low in central hypothyroidism) 2

Sex Steroid Replacement

• Men: Testosterone replacement therapy 2, 3
• Women: Estrogen replacement therapy 2, 3
• When fertility is desired, use gonadotropin therapy (FSH/LH) rather than sex steroid replacement 3

Growth Hormone Replacement

• Consider GH replacement in adults with confirmed GH deficiency, as it improves body composition, exercise capacity, cardiac function, and quality of life 4
• Daily subcutaneous recombinant human GH administration 4, 3
• GH replacement should be considered routine management based on current evidence 4

Posterior Pituitary (ADH Deficiency)

• Desmopressin for central diabetes insipidus 2, 3

Monitoring Schedule

Initial Phase (First 6 Months)

• ACTH and cortisol: monthly 1
• Free T4: every 1-2 weeks until stable 1
• Clinical assessment: energy level, weight, blood pressure 1

Maintenance Phase

• ACTH and cortisol: every 3-6 months 1
• Free T4: every 6-8 weeks 1
• Annual screening for autoimmune disorders, thyroid function, plasma glucose, and HbA1c 1

Treatment of Underlying Cause

While hormone replacement addresses the consequences of hypopituitarism, the underlying cause requires specific management:

• Pituitary macroadenomas with mass effect: Trans-sphenoidal surgical resection is preferred 1
• Post-surgical reassessment: Pituitary function should be reassessed 6-12 months after surgery, as hormone deficiencies may persist or worsen 1
• Hypophysitis with severe symptoms: High-dose glucocorticoids (methylprednisolone 1 mg/kg IV) 1

Note that the evidence for surgical management of nonfunctioning pituitary adenomas shows improved hypopituitarism in only 35-50% of patients, with many requiring lifelong hormone replacement 5

Critical Management Pitfalls to Avoid

• Mineralocorticoid replacement is rarely necessary in hypopituitarism, unlike primary adrenal insufficiency, because the renin-angiotensin-aldosterone system remains intact 1
• Both adrenal insufficiency and hypothyroidism are typically permanent, requiring lifelong replacement in most cases 1
• Adequate salt intake is critical, as low salt consumption can predispose to recurrent adrenal crises 1
• For unaccustomed intense exercise, patients should take an extra 5 mg hydrocortisone before activity and increase fluid and salt intake 1

Patient Education Requirements

• Emergency injectable hydrocortisone use 1
• When to seek immediate medical attention for impending adrenal crisis (even mild gastrointestinal upset can precipitate crisis) 1
• Stress dosing protocols for illness, surgery, or trauma 1
• Medical alert bracelet wearing at all times 1

Long-Term Considerations

Hypopituitarism is associated with excess mortality, with cortisol deficiency being a key risk factor 2. Lifelong follow-up with an endocrinologist is required 6, with annual consultations assessing quality of life, adequacy of replacement therapy, and any previous adrenal crises 1. Physical examination should focus on skin color, postural hypotension, and weight changes, which indicate adequacy of replacement 1.