What laboratory tests should be ordered in the initial work‑up of a patient with a suspected pituitary adenoma?

Laboratory Work-Up for Suspected Pituitary Adenoma

Order a comprehensive anterior pituitary hormone panel in all patients with suspected pituitary adenoma, including prolactin, IGF-1, TSH with free T4, morning (8 AM) cortisol with ACTH, and gonadal hormones (testosterone/LH/FSH in men; estradiol/LH/FSH in women), along with basic electrolytes and renal function. 1, 2

Essential Hormone Testing

Prolactin

• Measure serum prolactin in every patient regardless of symptoms, as hyperprolactinemia occurs in 25-65% of nonfunctioning adenomas due to stalk compression. 2
• Prolactin levels >200 ng/mL strongly suggest a prolactinoma, while modest elevations (typically mean ~39 ng/mL) in nonfunctioning adenomas reflect stalk effect. 3
• Prolactinomas account for 32-66% of all pituitary adenomas and may remain clinically silent, particularly in men, until mass effect develops. 1, 4

IGF-1 (Insulin-Like Growth Factor 1)

• Obtain IGF-1 in all patients to screen for clinically silent growth hormone hypersecretion, as up to 45-46% of presumed nonfunctioning adenomas show GH immunostaining without overt acromegaly. 1, 2
• Growth hormone-secreting tumors account for 8-16% of adenomas and typically present as microadenomas in their secretory phase. 4, 5

Thyroid Axis

• Measure TSH and free T4 simultaneously to detect central hypothyroidism, which presents with low free T4 and inappropriately low or normal TSH (unlike primary hypothyroidism where TSH is elevated). 3, 2
• Central hypothyroidism occurs in 8-81% of patients with pituitary adenomas. 1, 3

Adrenal Axis

• Obtain morning (8 AM) cortisol and ACTH levels to assess for secondary adrenal insufficiency. 3, 2
• Cortisol <3 μg/dL confirms adrenal insufficiency; >15 μg/dL excludes it; values between 3-15 μg/dL require a 1 mcg cosyntropin stimulation test for confirmation. 3, 2
• Adrenal insufficiency occurs in 17-62% of patients with pituitary adenomas. 1, 3
• Critical: Perform all dynamic testing before initiating glucocorticoid therapy to avoid false-negative results. 3

Gonadal Axis

• In men: Measure morning testosterone, LH, and FSH. Hypogonadism occurs in 36-96% of male patients with pituitary adenomas. 2
• In women: Measure LH, FSH, and estradiol. Hypogonadism occurs in 36-96% of female patients. 2
• In premenopausal women, hormone-secreting adenomas commonly manifest with menstrual irregularities and galactorrhea. 1

Additional Baseline Tests

• Measure serum sodium and osmolality to screen for diabetes insipidus or SIADH, though diabetes insipidus occurs in only ~7% of patients at presentation. 1, 3
• Obtain glucose and HbA1c for baseline glycemic assessment. 3

Understanding Hypopituitarism Prevalence

• Hypopituitarism is present in 37-85% of patients with pituitary adenomas, making comprehensive screening mandatory. 3, 2
• The growth hormone axis is most commonly affected (61-100% of patients), followed by gonadal axis (36-96%), adrenal axis (17-62%), and thyroid axis (8-81%). 1, 3
• Panhypopituitarism (≥3 hormone deficiencies) occurs in 6-29% of patients. 1, 3

Dynamic Testing Indications

• 1 mcg cosyntropin stimulation test: Indicated when morning cortisol is equivocal (3-15 μg/dL) to confirm or exclude adrenal insufficiency. 3
• GH stimulation testing: Consider for confirming GH deficiency, though patients with ≥3 pituitary hormone deficiencies are highly likely to have GH deficiency and may not require additional testing. 3

Critical Clinical Pitfalls

• Never initiate thyroid hormone replacement before confirming adequate cortisol replacement, as this can precipitate an adrenal crisis in patients with unrecognized adrenal insufficiency. 3
• Do not rely on symptoms alone to guide hormone testing, as many hormone deficiencies and excesses are clinically silent, particularly GH excess and early hypopituitarism. 2
• Always assess adrenal and thyroid function preoperatively in macroadenomas, as unrecognized deficiencies cause perioperative complications. 2
• Replacement for adrenal insufficiency and significant hypothyroidism is mandatory preoperatively before any surgical intervention. 1, 3

Coordination with Imaging

• High-resolution MRI of the sella with and without intravenous contrast should be performed together with the full anterior pituitary hormone panel as the gold-standard imaging study. 1
• Thin-section T1-weighted coronal and sagittal sequences before and after gadolinium maximize detection of microadenomas (<10 mm), which appear as hypo-enhancing lesions. 1

Endocrinology Referral

• Coordinate with endocrinology for interpretation of pituitary hormone testing, particularly for dynamic testing that may be needed in selected cases and for preoperative hormonal optimization when surgery is planned. 1, 3