Prolactinomas

Symptoms

Symptoms depend on sex, age, adenoma size, and prolactin levels. In women, prolactinoma manifests as menstrual irregularities (absence or delay of periods), infertility, and lactation. In men, it results in testosterone deficiency, reduced libido, erectile dysfunction, impotence, decreased beard growth, and rarely breast pain and lactation. In children, puberty is additionally delayed. In a large adenoma, symptoms such as headache and visual disturbances may be added due to mechanical compression of the cranial nerves. Possible complications include decreased bone density, increased risk of fracture, and anemia. Malignant pituitary tumors are extremely rare.

Causes

Prolactinomas are benign glandular tumors (adenomas) that arise from the lactotroph cells of the anterior pituitary gland and result in increased release of the hormone prolactin and hyperprolactinemia. The sexual dysfunction is due to the increased prolactin concentration in the blood, as prolactin inhibits GnRH release. Prolactinomas are classified according to size: Microprolactinomas are smaller than 10 mm, and macroprolactinomas are 10 mm or larger. Prolactin levels are often proportional to the size of the adenoma. The disease can occur at any age, but most commonly affects women between 20 and 60 years of age.

Diagnosis

Diagnosis is made by medical treatment on the basis of the clinical picture, laboratory chemical methods (e.g., measurement of elevated prolactin levels in the blood, sex hormones), and imaging methods (MRI, CT). Other possible causes of hyperprolactinemia, including pregnancy, must be excluded.

Nonpharmacologic treatment

Asymptomatic prolactinomas do not necessarily require treatment. Physician-prescribed and controlled observational waiting (“watchful waiting”) may be recommended for some patients. Because drug therapy is usually well effective, only a minority of patients need to undergo surgical treatment (minimally invasive transsphenoidal pituitary surgery) or radiation therapy as a 2nd-choice method.

Drug treatment

The release of prolactin is physiologically inhibited by dopamine, called prolactin inhibiting factor PIF. Therefore, the dopamine agonists bromocriptine, cabergoline, or quinagolide are used for drug treatment. Pergolide is also mentioned in the literature, but is not approved for this indication in many countries. The Parkinson’s drug pramipexole is also not approved in this indication. Dopamine agonists are considered 1st-line agents for microadenomas and macroadenomas, normalizing prolactin and abolishing symptoms. They also lead to a significant reduction in adenoma size. The most common possible adverse effects include headache, drowsiness, low blood pressure, fatigue, nausea, vomiting, indigestion, chest pain, hot flashes, depression, and hallucinations. Symptoms often resume after discontinuation of the medication, so follow-up visits are necessary. Cabergoline has a long half-life and can be administered as a single weekly dose. It is the 1st choice drug according to most publications. Bromocriptine and quinagolide, on the other hand, must be taken daily.