How should I diagnose and initially treat an adult with hypopituitarism?

Diagnosis and Initial Treatment of Adult Hypopituitarism

Begin with comprehensive hormonal screening including morning (8-9 AM) cortisol, ACTH, TSH, free T4, LH, FSH, sex steroids (testosterone in men, estradiol in premenopausal women), IGF-1, and prolactin, followed by MRI sella with contrast using high-resolution pituitary protocols, and immediately initiate hydrocortisone replacement if cortisol deficiency is confirmed before addressing any other hormonal deficits. 1, 2, 3

Diagnostic Approach

Initial Hormonal Assessment

Baseline hormone measurements can diagnose most pituitary deficiencies except growth hormone and ACTH deficiency, which typically require dynamic testing. 4, 3

• Measure morning (8-9 AM) cortisol and ACTH to assess the adrenal axis 1, 2
• Obtain TSH and free T4 to evaluate for central hypothyroidism 1, 2
• Check LH, FSH, and sex hormones (testosterone in men, estradiol in premenopausal women) for hypogonadotropic hypogonadism 1, 2
• Measure IGF-1 for growth hormone deficiency screening 1, 2
• Assess prolactin levels 1, 2
• Include basic metabolic panel to evaluate sodium and potassium 5

Dynamic Testing When Indicated

If morning cortisol is indeterminate (typically between 3-15 µg/dL), perform cosyntropin (ACTH) stimulation test to clarify adrenal reserve. 5, 4

• Peak cortisol <18 µg/dL after stimulation confirms adrenal insufficiency 5
• Peak cortisol >18-20 µg/dL effectively excludes it 5
• Dynamic tests are mandatory for proper diagnosis of GH and ACTH deficiency when basal levels are equivocal 4, 6

Imaging Protocol

MRI using high-resolution pituitary protocols with gadolinium contrast is the gold standard for evaluating hypopituitarism. 1, 7

• Obtain pre-contrast (T1 and T2) and post-contrast T1-weighted thin-sliced sequences 1
• Include post-contrast volumetric gradient echo sequences for increased sensitivity in detecting microadenomas 1
• Use 2 mm slice thickness with coronal and sagittal views 1, 7
• Dynamic contrast-enhanced imaging increases sensitivity for small adenomas 7
• MRI directly visualizes the pituitary gland, stalk abnormalities, and can detect mass effect on the optic chiasm 1, 5

Initial Treatment Algorithm

Critical First Step: Cortisol Replacement

If cortisol deficiency is confirmed or strongly suspected, initiate hydrocortisone replacement IMMEDIATELY before any other hormone replacement, as this is life-saving and prevents adrenal crisis. 1, 5, 3

Severe Hypoadrenalism (hypotension, severe electrolyte disturbance, acute illness):

• Start IV methylprednisolone 1 mg/kg after sending blood for pituitary axis assessment 1
• Do not delay treatment waiting for laboratory results if patient is acutely unwell 1
• Convert to oral prednisolone and wean over 4 weeks to maintenance dose 1

Confirmed Hypoadrenalism (stable patient):

• Replace with hydrocortisone 20/10 mg (morning/afternoon dosing) 1
• Alternative regimen: hydrocortisone 20/10/10 mg if 9 AM cortisol <250 nmol/L or random cortisol <150 nmol/L 1

Second Step: Thyroid Hormone Replacement

Always replace cortisol for at least 1 week before initiating thyroid hormone replacement to avoid precipitating adrenal crisis. 1

• If TSH is falling with low or low-normal free T4, initiate levothyroxine replacement 1
• Monitor thyroid function tests every 1-2 weeks initially 1
• Central hypothyroidism is present in up to 48% of hypopituitarism cases 2

Subsequent Hormone Replacement

After stabilizing cortisol and thyroid axes, address sex hormone and growth hormone deficiencies based on individual patient needs. 3, 8

• Consider testosterone or estrogen replacement if sex hormones are low 1
• Growth hormone replacement requires careful benefit-risk evaluation in adults 8
• Mineralocorticoid replacement is rarely necessary in hypopituitarism 1

Critical Management Considerations

Patient Education and Safety

All patients with confirmed adrenal insufficiency require "sick day rules" education, prescription for emergency IM hydrocortisone, and medical alert identification. 1

• Provide written instructions for stress-dose steroids during illness 1
• Consider medical alert card or bracelet 1
• Educate on signs of adrenal crisis requiring emergency care 1

Common Pitfalls to Avoid

• Never initiate thyroid hormone replacement before cortisol replacement - this can precipitate life-threatening adrenal crisis 1, 3
• Do not stop corticosteroids abruptly once initiated 1
• Do not rely solely on TSH levels - in central hypothyroidism, TSH may be normal, low, or even slightly elevated despite low free T4 2, 3
• Do not miss the diagnosis by failing to perform dynamic testing when basal cortisol is indeterminate 5, 4

Follow-Up Requirements

Long-term endocrinological follow-up is mandatory to monitor hormone replacement regimens and avoid under- or over-treatment. 4, 6

• Repeated pituitary function assessment at regular intervals is needed for slowly evolving hypopituitarism 3
• Approximately 30-40% of patients with empty sella demonstrate hypopituitarism, often requiring lifelong hormone replacement 1, 2, 5
• Hypopituitarism is associated with increased mortality and morbidity, particularly from untreated cortisol deficiency 3, 8