What is hypopituitarism, its diagnosis, and treatment?

Hypopituitarism: Diagnosis and Treatment

Hypopituitarism is defined as partial or complete loss of one or more pituitary hormones, requiring hormone replacement therapy tailored to the specific deficiencies and close lifelong monitoring to optimize morbidity, mortality, and quality of life outcomes.

Definition and Etiology

Hypopituitarism refers to insufficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary 1. The clinical presentation varies depending on the number and severity of hormone deficiencies.

Common causes include:

• Pituitary adenomas (most common cause in adults, ~50% of cases) 2
• Pituitary surgery or radiotherapy 3
• Traumatic brain injury
• Infiltrative diseases
• Genetic mutations (more common in children) 2
• Immune-related hypophysitis (increasingly recognized with immunotherapy) 4

Clinical Presentation

Symptoms depend on which hormones are deficient:

• ACTH deficiency (central hypocortisolism): Fatigue, weakness, nausea, hypotension, hypoglycemia
• TSH deficiency (central hypothyroidism): Fatigue, cold intolerance, weight gain, constipation
• Gonadotropin deficiency (LH/FSH):
  • Males: Decreased libido, erectile dysfunction, infertility
  • Females: Amenorrhea, infertility, vaginal dryness
• GH deficiency: Decreased muscle mass, increased fat mass, reduced exercise capacity
• ADH deficiency (diabetes insipidus): Polyuria, polydipsia
• Prolactin abnormalities: Both high and low levels can occur

Diagnosis

Diagnosis involves a combination of baseline hormone measurements and dynamic stimulation tests:

1. Baseline measurements:

   • Morning cortisol
   • Free T4 and TSH
   • LH, FSH, estradiol (women) or testosterone (men)
   • IGF-1
   • Prolactin

2. Dynamic testing (required for certain deficiencies):

   • ACTH deficiency: ACTH stimulation test (250 μg cosyntropin)
   • GH deficiency: Insulin tolerance test, glucagon stimulation test, or GHRH-arginine test

3. Imaging:

   • MRI of pituitary with contrast (protocol specifically for pituitary visualization)

Treatment Approach

1. Hormone Replacement Therapy

Critical: Always start corticosteroid replacement before thyroid hormone replacement to avoid precipitating adrenal crisis 5.

Corticosteroid Replacement

• Initial dose: Hydrocortisone 15-20 mg/day divided (typically 10-15 mg in morning, 5-10 mg in afternoon) 5
• "Sick day rules" education is essential - double or triple dose during minor illness, 100 mg IV/IM for major illness 5

Thyroid Hormone Replacement

• Start levothyroxine at 1.6 μg/kg/day (lower in elderly or those with cardiac issues) 5
• Monitor with free T4 levels, not TSH (which is unreliable in central hypothyroidism) 5

Sex Hormone Replacement

• Males: Testosterone replacement via injections, gels, or patches 5
• Females: Estrogen with progestogen (if uterus present) or estrogen-only (if hysterectomized); transdermal 17β-estradiol (50-100 μg daily) preferred 5

Growth Hormone Replacement

• Conventional replacement dose: 0.025 mg/kg per day 5
• Improves body composition, exercise capacity, lipid profile, and quality of life 5

Desmopressin for Diabetes Insipidus

• Administered as nasal spray, oral tablets, or sublingual formulation based on patient needs 5

2. Management of Immune-Related Hypophysitis

For hypophysitis related to immune checkpoint inhibitors 4:

• Severe symptoms (severe headache, visual disturbance, severe hypoadrenalism):

  • IV methylprednisolone 1 mg/kg after pituitary axis assessment
  • Withhold immunotherapy
  • MRI pituitary protocol
  • Endocrinology consultation

• Moderate symptoms (headache without visual disturbance, stable hemodynamics):

  • Oral prednisolone 0.5-1 mg/kg after pituitary axis assessment
  • Withhold immunotherapy
  • Endocrinology consultation

• Mild/vague symptoms:

  • Await pituitary axis results to confirm diagnosis
  • Continue immunotherapy with appropriate hormone replacement if needed

Long-Term Monitoring

• Annual review including assessment of health and well-being, weight, blood pressure, and serum electrolytes 5

• Hormone replacement monitoring:

  • Cortisol day curve for glucocorticoid adequacy
  • Free T4 levels for thyroid replacement
  • Sex hormone levels
  • IGF-1 for growth hormone adequacy

• MRI surveillance post-treatment at 3 and 6 months, then at 1,2,3, and 5 years 5

Critical Considerations and Pitfalls

1. Adrenal crisis prevention: All patients must wear medical alert identification, carry a steroid alert card, have supplies for self-injection of parenteral hydrocortisone 5

2. Avoid starting thyroid hormone before corticosteroids - can precipitate adrenal crisis 5

3. Don't rely on TSH to monitor thyroid replacement - use free T4 levels instead 5

4. Don't overlook stress dosing education - inadequate stress dosing is a common cause of adrenal crisis 5

5. Recognize that hypopituitarism is associated with excess mortality, with cortisol deficiency being a key risk factor 3

6. Understand that pituitary function can be dynamic - it may progress or rarely show recovery, requiring ongoing monitoring 1