Can a pituitary microadenoma cause low testosterone in an adult male?

Can a Pituitary Microadenoma Cause Low Testosterone?

Yes, a pituitary microadenoma can absolutely cause low testosterone in adult males, most commonly through prolactin hypersecretion (prolactinoma) which suppresses gonadotropin release, or less commonly through direct compression of the pituitary stalk causing secondary hypogonadism. 1

Mechanisms of Testosterone Suppression

Prolactin-Mediated Hypogonadism (Most Common)

• Prolactinomas account for 32-66% of all pituitary adenomas and are the most frequent cause of microadenoma-related hypogonadism in men. 2
• Elevated prolactin directly suppresses pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, leading to secondary hypogonadism with low testosterone levels. 1
• Men with prolactinomas typically present with decreased libido, erectile dysfunction, infertility, and sometimes gynecomastia. 2, 3
• Importantly, some men with prolactinomas can present with testosterone levels in the normal range (≥2.6 ng/ml) despite markedly elevated prolactin, though hypogonadal symptoms may still be present. 4

Direct Stalk Compression (Less Common for Microadenomas)

• While microadenomas (<10 mm) rarely cause mass effect, a 4 mm microadenoma can occasionally compress the pituitary stalk and cause hypopituitarism, though this is uncommon for lesions of this size. 5
• Stalk compression disrupts hypothalamic-pituitary communication, leading to multiple hormonal deficiencies including secondary hypogonadism. 5
• When stalk compression occurs with a microadenoma, it typically requires transsphenoidal surgery to relieve compression and potentially restore pituitary function. 5

Diagnostic Workup Algorithm

Initial Hormonal Assessment

• Measure morning (8-10 AM) total testosterone on at least two separate occasions if levels are subnormal. 1
• Simultaneously measure serum prolactin levels in all men with low testosterone and suspected pituitary pathology. 1
• Check sex hormone-binding globulin (SHBG) and free testosterone by equilibrium dialysis, as obesity-related low SHBG can falsely lower total testosterone while free testosterone remains normal. 1

Secondary Testing Based on Initial Results

• If testosterone is low with concomitantly low or inappropriately normal LH/FSH, this indicates secondary (pituitary-hypothalamic) hypogonadism requiring further evaluation. 1
• Measure serum prolactin and iron saturation to identify reversible causes of pituitary dysfunction. 1
• Obtain high-resolution pituitary MRI with thin-sliced pre- and post-contrast T1-weighted sequences to visualize the adenoma and assess stalk compression. 6, 5

Complete Pituitary Axis Evaluation

• Assess all pituitary axes (thyroid, adrenal, growth hormone) as microadenomas can occasionally affect multiple hormonal pathways. 5, 3
• Perform visual field testing if there is any concern about chiasmal involvement, though this is rare with microadenomas. 2

Treatment Approach

For Prolactinomas (Primary Scenario)

• Dopamine agonists (cabergoline or bromocriptine) are first-line treatment for prolactinomas, even for macroadenomas with visual symptoms. 2, 3
• Cabergoline is preferred over bromocriptine due to superior efficacy, tolerability, and twice-weekly dosing. 7
• Start cabergoline at 0.25 mg twice weekly and titrate upward in 0.5 mg increments until prolactin normalizes and symptoms resolve. 7
• With cabergoline treatment, testosterone levels typically increase significantly (mean increase of 2.34-3.19 ng/ml) and hypogonadal symptoms improve in 83% of symptomatic men. 4, 7
• Prolactin normalization occurs in nearly all patients, with tumor shrinkage or disappearance in the majority of cases within 12 months. 7

For Non-Functioning Adenomas with Stalk Compression

• Transsphenoidal surgery is first-line treatment when a microadenoma causes stalk compression and hormonal deficiency, as surgical decompression can restore pituitary function in 35-50% of cases. 5
• Surgery should be performed by experienced pituitary surgeons in high-volume centers (≥50 pituitary operations per year). 5
• Post-operative MRI surveillance at 3 and 6 months, then annually for 5 years is recommended. 1, 5

Testosterone Replacement Considerations

• Testosterone replacement should be considered when free testosterone by equilibrium dialysis is frankly low on at least two separate occasions and symptoms of hypogonadism are present. 1
• Benefits include improved sexual function, well-being, muscle mass, bone density, and metabolic parameters. 1
• However, address the underlying pituitary pathology first (dopamine agonist for prolactinoma or surgery for compressive lesion) before initiating testosterone replacement, as treating the adenoma may restore endogenous testosterone production. 4, 7
• Be aware that testosterone replacement in older men has been associated with increased cardiovascular events in some studies. 1

Critical Pitfalls to Avoid

• Do not assume normal testosterone excludes a prolactinoma—some men with significant prolactin elevation maintain testosterone in the normal range yet still experience hypogonadal symptoms. 4
• Do not start testosterone replacement without first checking prolactin levels, as this misses the opportunity to treat the underlying adenoma and restore natural testosterone production. 8
• In obese men, always measure free testosterone and SHBG, as low total testosterone may reflect low SHBG rather than true hypogonadism. 1
• Do not perform surgery for prolactinomas as first-line treatment—medical therapy with dopamine agonists is highly effective and should be attempted first, even for macroadenomas with visual symptoms. 2, 3, 7