What is the management of panhypopituitarism?

Management of Panhypopituitarism

The management of panhypopituitarism requires systematic hormone replacement therapy with glucocorticoids first, followed by thyroid hormone, sex hormones, and growth hormone, along with comprehensive patient education on stress dosing and emergency management. 1

Diagnosis and Initial Assessment

• Evaluate for specific hormone deficiencies:

  • Morning cortisol and ACTH levels
  • TSH and free T4 levels
  • LH, FSH, testosterone (males) or estradiol (females)
  • IGF-1 and growth hormone stimulation testing
  • Serum sodium, osmolality for diabetes insipidus

• MRI of the sella with pituitary cuts to identify underlying etiology (e.g., pituitary adenoma, empty sella syndrome, immune checkpoint inhibitor therapy) 2, 1

Hormone Replacement Therapy

1. Glucocorticoid Replacement (FIRST priority)

• Initial dose: Hydrocortisone 15-20 mg daily in divided doses (typically 10-15 mg in morning, 5 mg in afternoon) 1
• Alternative: Prednisone 5 mg daily for patients unable to adhere to multiple daily dosing 1
• Never start thyroid hormone before corticosteroids as this can precipitate adrenal crisis 1

2. Thyroid Hormone Replacement

• Levothyroxine dosing based on weight: 1.6 μg/kg/day in adults 1, 3
• Target free T4 in upper half of reference range 1
• Do not use TSH to monitor therapy in central hypothyroidism; rely on free T4 levels 1

3. Sex Hormone Replacement

• Males: Testosterone replacement via injections, gels, or patches 1
• Females: Estrogen with progestogen (if uterus present) or estrogen-only (if hysterectomized)
  • Transdermal 17β-estradiol (50-100 μg daily) preferred due to better safety profile 1
  • Progestogen should be given with estrogen to protect the endometrium in women with intact uterus 2

4. Growth Hormone Replacement

• Consider in adults with confirmed GH deficiency 1, 4
• Benefits include improved body composition, exercise capacity, lipid profile, and quality of life 1, 4
• Conventional replacement doses: 0.025 mg/kg per day 2
• GH deficiency is the most common pituitary deficit following surgical or radiotherapeutic treatment 2

5. Desmopressin for Diabetes Insipidus

• If posterior pituitary dysfunction is present 1

Stress Dosing Protocol

• Minor illness: Double or triple daily hydrocortisone dose 1

• Major illness or surgery:

  • Hydrocortisone 100 mg IV before surgery
  • 50-100 mg every 6-8 hours, tapering to maintenance over 5-7 days 1

• Adrenal crisis management:

  • Immediate treatment with IV/IM hydrocortisone 100 mg
  • Follow with 100 mg every 6-8 hours until recovered
  • Administer isotonic saline solution 1

Patient Education and Safety Measures

• All patients must:

  • Wear medical alert identification
  • Carry a steroid alert card
  • Have supplies for self-injection of parenteral hydrocortisone 1
  • Receive education on managing daily medications and concurrent illnesses 1

• Dietary recommendations:

  • Take salt and salty foods ad libitum
  • Avoid licorice and grapefruit juice 1

Monitoring and Follow-up

• Annual review should include:

  • Assessment of health and well-being
  • Weight and blood pressure measurement
  • Serum electrolytes
  • Monitoring for development of new autoimmune disorders 1

• Hormone replacement monitoring:

  • Cortisol day curve for glucocorticoid adequacy
  • Free T4 levels (not TSH) for thyroid replacement
  • Sex hormone levels
  • IGF-1 for growth hormone adequacy 1

• Bone mineral density assessment every 3-5 years 1

Special Considerations

• Hypophysitis from immune checkpoint inhibitors:

  • Approximately 50% present with panhypopituitarism (adrenal insufficiency plus hypothyroidism plus hypogonadism) 2
  • MRI may show pituitary enlargement that resolves within two months 2
  • Both adrenal insufficiency and hypothyroidism typically represent long-term sequelae requiring lifelong hormonal replacement 2

• Perioperative management:

  • High-dose steroid coverage essential (hydrocortisone 100 mg IV before surgery)
  • Continue thyroid replacement throughout perioperative period
  • Monitor closely for hemodynamic instability 5

Prognosis and Mortality Risk

• Increased mortality risk (2.19 times higher in men, 2.86 times higher in women)
• Primary causes: cardiovascular disease, infections, and malignancies 1
• Proper hormone replacement, especially GH in adults with confirmed deficiency, may improve outcomes 4