What is the purpose of testing morning cortisol, ACTH, TSH, free T4, prolactin, LH, FSH, and IGF-1 levels in a patient with suspected pituitary disease and a history of epilepsy?

Morning Pituitary Hormone Testing in Suspected Pituitary Disease

All anterior pituitary axes should be evaluated with morning baseline hormone measurements (cortisol, ACTH, TSH, free T4, prolactin, LH, FSH, and IGF-1) because hypopituitarism affects 37-85% of patients with pituitary disorders, and comprehensive screening detects hormone deficiencies that exceed clinical suspicion alone. 1, 2

Why Morning Timing Matters

Morning hormone measurements are essential because they capture peak physiological levels for the hypothalamic-pituitary-adrenal axis and allow proper interpretation of hormone pairs needed to distinguish primary from secondary endocrine dysfunction 2, 3. For example, a low morning cortisol with low ACTH indicates central (pituitary) adrenal insufficiency, whereas low cortisol with elevated ACTH indicates primary adrenal failure 1, 4.

Specific Rationale for Each Test

Cortisol and ACTH (Morning)

• Detects central adrenal insufficiency, which occurs in 17-62% of patients with pituitary adenomas 1
• Morning cortisol below 3 mcg/dL confirms adrenal insufficiency; values between 3-15 mcg/dL require dynamic testing with 1 mcg cosyntropin stimulation 1, 2
• Critical safety point: Adrenal insufficiency must be identified and treated before thyroid hormone replacement to prevent precipitating adrenal crisis 1, 3, 4

TSH and Free T4

• Identifies central hypothyroidism, present in 8-81% of pituitary adenoma patients 1
• Both tests are mandatory because TSH alone is unreliable in pituitary disease—central hypothyroidism presents with low free T4 and inappropriately low or normal TSH 1, 2, 4
• In hypopituitarism, TSH can remain within reference range despite significant hypothyroidism 1

Prolactin

• Rules out prolactinoma, which may masquerade as a nonfunctioning adenoma 1
• Routine prolactin testing is a level II recommendation because hypersecretion often lacks clinical signs 1
• Hyperprolactinemia occurs in 65% of pediatric patients with growth hormone excess due to co-secretion 1

LH and FSH

• Detects hypogonadotropic hypogonadism, affecting 36-96% of pituitary adenoma patients—the second most commonly affected axis 1, 2
• Low testosterone (males) or estradiol (females) with inappropriately low or normal LH/FSH confirms central hypogonadism 2, 4
• Hypogonadism delays bone age in children, extending the window for abnormal growth in GH excess 1

IGF-1

• Screens for clinically silent growth hormone excess, recommended as level III evidence 1
• GH deficiency is the most commonly affected axis (61-100% of patients with nonfunctioning adenomas) 1, 2
• In one study, 45.9% of presumed nonfunctioning adenomas showed GH immunostaining, with 8.1% having elevated IGF-1 1

Special Consideration: Epilepsy History

Prolactin and LH elevations can occur postictally, complicating interpretation 5. Prolactin rises immediately after generalized tonic-clonic seizures and at 20 minutes after complex partial seizures, returning to baseline by 60 minutes 5. LH also elevates after generalized seizures and remains elevated at 60 minutes 5. To avoid false positives, ensure testing occurs at least 24 hours after any seizure activity.

Critical Testing Sequence

1. Obtain all baseline morning hormones simultaneously before any treatment 2, 3
2. If cortisol is low or equivocal, perform cosyntropin stimulation test before starting any steroids 1, 2, 4
3. Always initiate glucocorticoid replacement before thyroid hormone if both deficiencies exist 1, 3, 4
4. Order MRI sella with dedicated pituitary protocol to identify structural lesions 2, 4

Prevalence of Panhypopituitarism

Panhypopituitarism (≥3 hormone deficiencies) occurs in 6-29% of pituitary adenoma patients 1, 2. The hierarchy of axis involvement is: GH axis (61-100%) > gonadal axis (36-96%) > adrenal axis (17-62%) > thyroid axis (8-81%) 2, 4. Diabetes insipidus is uncommon, occurring in only 7% at presentation 1, 2.

Common Pitfall to Avoid

Never rely on TSH alone to assess thyroid function in suspected pituitary disease 1, 3. Central hypothyroidism requires free T4 measurement because TSH remains inappropriately normal despite low thyroid hormone 1, 2, 4. Similarly, never use isolated cortisol or testosterone levels without measuring their corresponding pituitary hormones (ACTH, LH/FSH) to localize the defect 2, 4.