Management of High LH and Prolactin Levels
Patients with persistently elevated prolactin levels of unknown etiology should undergo endocrinologic evaluation, and dopamine agonist therapy—preferably cabergoline—is the first-line treatment for confirmed prolactinomas. 1, 2
Diagnostic Workup
Confirm and Characterize the Hyperprolactinemia
Repeat prolactin measurement in the morning while fasting to exclude stress-induced or pulsatile elevation before proceeding with further evaluation. 2, 3
For modestly elevated levels, consider serial measurements 20-60 minutes apart using an indwelling cannula to differentiate stress-related hyperprolactinemia from organic disease. 2, 3
Rule out the "hook effect" in patients with large pituitary lesions (≥3 cm) but only modestly elevated prolactin by requesting serum dilutions (1:100) for prolactin measurement—this can unmask falsely low values in massive prolactinomas. 3, 4
Screen for macroprolactinemia in patients with mildly elevated prolactin, especially if asymptomatic, as this represents 10-40% of hyperprolactinemia cases and may not require treatment. 2, 3, 4
Evaluate Secondary Causes
Review all medications, particularly antipsychotics and dopamine antagonists, which are common causes of drug-induced hyperprolactinemia. 3
Screen for pregnancy, primary hypothyroidism, liver disease, renal failure, and intracranial hypotension. 3, 4
Measure LH and Additional Hormones
Measure serum LH levels in all patients with confirmed hyperprolactinemia to establish the etiology of any concurrent testosterone deficiency and guide treatment decisions. 1, 3
The combination of high LH with high prolactin suggests primary gonadal failure with concurrent hyperprolactinemia (hypergonadotropic hypogonadism), whereas low/normal LH with high prolactin indicates hypothalamic-pituitary dysfunction. 1
Measure estradiol in male patients presenting with breast symptoms or gynecomastia, and refer to endocrinology if baseline estradiol is elevated. 1
Evaluate IGF-1 levels to rule out mixed prolactin and growth hormone hypersecretion. 3
Imaging
Obtain pituitary MRI when prolactin levels are significantly elevated (>250 ng/mL strongly suggests prolactinoma) or when prolactin remains persistently elevated after excluding secondary causes. 3, 4
Men with total testosterone <150 ng/dL combined with low/normal LH should undergo pituitary MRI regardless of prolactin levels, as non-secreting adenomas may be present. 1, 3
Treatment Strategy
First-Line Pharmacologic Therapy
Dopamine agonists are the first-line treatment for prolactinomas to reduce serum prolactin, restore gonadal function, and induce tumor shrinkage. 2, 3, 5
Cabergoline is preferred over bromocriptine due to superior effectiveness (better prolactin suppression and restoration of gonadal function) and better tolerability, with dosing once or twice weekly versus daily for bromocriptine. 2, 3, 5, 6
Use the lowest effective dose of cabergoline for hyperprolactinemic disorders and periodically reassess the need for continuing therapy. 7
Special Considerations for Fertility
Testosterone-deficient patients with low or low/normal LH levels are candidates for selective estrogen receptor modulator (SERM) use as treatment, particularly those wishing to preserve fertility. 1
Men with testosterone deficiency interested in fertility should have a reproductive health evaluation, including testicular exam and FSH measurement, performed prior to treatment. 1
For patients with hypogonadotropic hypogonadism (low LH, low testosterone), referral to endocrinology or male reproductive specialist is encouraged, as spermatogenesis can be initiated with exogenous gonadotropins or pulsatile GnRH. 1
Monitoring and Follow-Up
Measure prolactin levels 1-3 months after initiating treatment and every 3-6 months until stabilized to assess treatment response. 2
Perform echocardiographic surveillance every 6-12 months for patients on standard doses of cabergoline (≤2 mg/week) to monitor for cardiac valvulopathy, as postmarketing cases have been reported. 2, 7
Discontinue cabergoline if echocardiogram reveals new valvular regurgitation, valvular restriction, or valve leaflet thickening. 7
For macroprolactinomas, repeat MRI 3-6 months after starting treatment; for microprolactinomas, re-imaging depends on clinical and biochemical follow-up. 3
Monitor for signs of fibrotic complications including pleuro-pulmonary disease (dyspnea, persistent cough, chest pain), retroperitoneal fibrosis (back pain, lower limb edema, renal insufficiency), and cardiac manifestations. 7, 8
Critical Pitfalls to Avoid
Do not miss macroprolactinemia—present in 10-40% of hyperprolactinemia cases, up to 40% may have hypogonadism symptoms, but many do not require treatment. 2, 3, 4
Do not overlook the hook effect—falsely low prolactin in large tumors due to assay saturation; always request diluted samples for large pituitary masses with unexpectedly normal prolactin. 2, 3, 4
Do not use cabergoline in patients with a history of cardiac or extracardiac fibrotic disorders, and obtain baseline cardiovascular evaluation including echocardiogram before initiating therapy. 7
Refer to endocrinology for persistently elevated prolactin of unknown etiology after excluding common causes, or for men with testosterone <150 ng/dL and low/normal LH. 1, 3
Prolactin values >250 ng/mL are highly suggestive of prolactinomas, while most drug-induced hyperprolactinemia, macroprolactinemia, or systemic diseases present with levels <100 ng/mL—though exceptions occur in up to 25% of microprolactinomas or cystic macroprolactinomas. 4