Hormonal Workup for Pituitary Macroadenoma
When evaluating a pituitary macroadenoma, check testosterone in men, estradiol in women (premenopausal and postmenopausal), FSH, LH, and prolactin as the essential sex steroid panel. 1
Core Sex Hormone Testing
All patients with pituitary macroadenomas require comprehensive evaluation of gonadal function as part of the initial workup 1:
In Men
- Testosterone (total): Essential to detect both hypogonadism from pituitary compression and rare cases of hypersecretion from functional gonadotroph adenomas 1, 2, 3
- Free testosterone: Should be measured alongside total testosterone, as elevated levels have been documented in functional gonadotroph adenomas 2
- FSH and LH: Critical for distinguishing primary gonadal failure from secondary hypogonadism and identifying gonadotroph adenomas 1, 2, 3
In Women
- Estradiol: Must be checked in all women with pituitary macroadenomas to assess gonadal function 1, 4
- FSH and LH: Essential for characterizing the type of hypogonadism and detecting gonadotroph adenomas 1, 3
- Progesterone: Important as women with hypopituitarism show markedly reduced levels 4
Universal Testing
- Prolactin: Mandatory in all patients, as macroadenomas can cause stalk compression leading to hyperprolactinemia (typically <150-200 μg/L), and prolactinomas are the most common functional adenomas 1, 5
Additional Steroid Precursors to Consider
While not always part of routine workup for pituitary adenomas, certain steroid precursors may be relevant:
- DHEA-S: Women with hypopituitarism, particularly those with ACTH deficiency, show severely reduced DHEA levels 4
- Androstenedione: Similarly depleted in women with combined pituitary deficiencies 4
- 17α-OH-progesterone: Reduced in women with hypopituitarism 4
Critical Clinical Context
Functional gonadotroph adenomas are rare but important to identify. Although most gonadotroph adenomas are classified as "non-functioning," approximately one-third secrete FSH and/or LH 1, 2. In exceptional cases, these can cause secondary hypersecretion of testosterone in men, though this rarely produces recognizable clinical symptoms 2, 3. The clinical presentation typically remains dominated by mass effects (visual field defects, headaches) rather than hormonal symptoms 2, 3.
Women with hypopituitarism from macroadenomas face particularly severe sex steroid deficiency. Those with combined gonadotropin and ACTH deficiency demonstrate markedly lower concentrations of all sex hormones compared to those with isolated gonadotropin deficiency 4. This broad hormonal deficiency may contribute to the increased morbidity and mortality observed in women with hypopituitarism 4.
Practical Testing Algorithm
Measure prolactin first to distinguish prolactinomas (which may respond to medical therapy) from other adenoma types 1, 5
Check gonadal axis: Testosterone (total and free) in men; estradiol in women; FSH and LH in all patients 1, 2, 3
Assess for hypopituitarism: Include thyroid function (TSH, free T4) and adrenal function (morning cortisol, ACTH) as macroadenomas commonly cause multiple pituitary hormone deficiencies 1
Consider GH/IGF-1 if acromegaly features are present 1
Measure ACTH and cortisol to evaluate for Cushing's disease or secondary adrenal insufficiency 1
Important Caveats
Do not assume "non-functioning" based on lack of clinical symptoms alone. Elevated FSH, LH, or sex hormones may be present without obvious clinical manifestations, particularly in men with testosterone hypersecretion 2, 3. The hormonal profile serves as a "fingerprint" for postoperative monitoring and helps guide replacement therapy decisions 1.
Postoperative hormonal reassessment is essential. Many patients develop new or worsening hypopituitarism after surgery, requiring lifelong hormone replacement 1, 2. Women with combined deficiencies require particularly careful monitoring and consideration for comprehensive sex hormone replacement 4.