What is the workup for adrenal insufficiency and hypopituitarism differentials?

Diagnostic Workup for Adrenal Insufficiency and Hypopituitarism

The diagnostic workup for adrenal insufficiency and hypopituitarism should include comprehensive hormonal testing, imaging studies, and dynamic testing to establish the diagnosis and determine the underlying cause. 1

Adrenal Insufficiency Workup

Initial Laboratory Testing

• Evaluate morning (8 AM) ACTH and cortisol levels - this is essential for distinguishing between primary and secondary adrenal insufficiency 1, 2
• Obtain a basic metabolic panel to assess for electrolyte abnormalities (hyponatremia, hyperkalemia) which are common in primary adrenal insufficiency 1, 3
• Consider ACTH stimulation test for indeterminate results or when morning cortisol levels are in the intermediate range (5-10 μg/dL) 1, 2

Confirmatory Testing

• For suspected primary adrenal insufficiency (high ACTH, low cortisol), perform adrenal CT to evaluate for metastasis, hemorrhage, or other structural abnormalities 1, 4
• In cases with low or normal ACTH and low cortisol, further evaluation for secondary adrenal insufficiency (hypopituitarism) is warranted 1

Additional Considerations

• Evaluate for precipitating causes of adrenal crisis such as infection 1
• If the patient is on corticosteroids for other conditions, laboratory confirmation of adrenal insufficiency should be deferred until treatment can be safely discontinued 1

Hypopituitarism Workup

Initial Laboratory Testing

• Evaluate all anterior pituitary axes as the prevalence of hypopituitarism in patients with pituitary abnormalities is high 1
• Test for central adrenal insufficiency: low ACTH with low cortisol 1, 5
• Test for central hypothyroidism: low or normal TSH with low free T4 1, 6
• Test for hypogonadism: low testosterone or estradiol with low LH and FSH 1, 5
• Check for diabetes insipidus: hypernatremia and volume depletion 1, 3

Imaging Studies

• MRI of the brain with pituitary/sellar cuts is recommended in patients with multiple endocrine abnormalities, especially with headaches or visual changes 1, 6

Additional Testing

• Routine prolactin testing is recommended to rule out hypersecretion that might not be clinically suspected 1
• Routine IGF-1 evaluation is recommended to rule out growth hormone deficiency or hypersecretion 1

Special Considerations

Immune Checkpoint Inhibitor-Related Endocrinopathies

• For patients on immune checkpoint inhibitors, monitor thyroid function (TSH, free T4) before each treatment cycle 1
• Consider routine monitoring with early morning ACTH and cortisol levels (every month for 6 months, then every 3 months for 6 months, then every 6 months for 1 year) 1
• For suspected immune-related hypophysitis, obtain MRI of the sella and comprehensive pituitary hormone testing before administering steroids 1

Adrenal Incidentaloma Evaluation

• For patients with adrenal incidentalomas, screen for autonomous cortisol secretion with 1 mg dexamethasone suppression test 1
• Screen for primary aldosteronism with aldosterone-to-renin ratio in patients with hypertension and/or hypokalemia 1
• Screen for pheochromocytoma with plasma or 24-hour urinary metanephrines in patients with adrenal masses >10 HU on non-contrast CT or with symptoms of catecholamine excess 1

Pitfalls to Avoid

• Do not perform adrenal mass biopsy routinely for the workup of adrenal incidentalomas 1
• Do not start thyroid hormone replacement before glucocorticoid replacement in patients with multiple hormone deficiencies, as this may precipitate adrenal crisis 1, 7
• Be aware that concurrent treatment with IV hydrocortisone can lead to false-negative results on ACTH stimulation testing 7
• Do not overlook hypopituitarism as a cause of severe hyponatremia, as it is frequently missed and can be life-threatening 3

Treatment Considerations

• For primary adrenal insufficiency, replacement therapy includes both glucocorticoids and mineralocorticoids (fludrocortisone) 8, 2
• For secondary adrenal insufficiency (hypopituitarism), glucocorticoid replacement alone is typically sufficient 2, 5
• All patients with adrenal insufficiency should be educated on stress dosing and provided with a medical alert bracelet 1, 4