PROLACTINOMA – HYPERPROLACTINEMIA

♦ PHYSIOLOGY: Prolactin is a polypeptide hormone secreted by the lactotrophic cells of the pituitary gland. Its secretion is regulated by the hypothalamus through stimulatory and inhibitory stimuli. In contrast to the other anterior pituitary hormones, the primary tonic effect of the hypothalamus on prolactin secretion is inhibitory. The main substance of hypothalamic origin with an inhibitory effect on the secretion of prolactin is dopamine. Normal baseline blood prolactin levels range from 100-500 mU/L (2.8-29.2 ng/ml) during the day, and nearly double during the night when lactotroph cell secretory activity is most intense. The main physiological action of prolactin in women is its participation in milk production during lactation, while in men it remains unclear.

♦ DEFINITION

Hyperprolactinemia is defined as the constant and repeated finding of elevated serum prolactin values, in periods other than pregnancy or lactation. There is no complete consensus on the upper normal limit of prolactin values. Thus, the upper normal limits vary among laboratories from 360-700 mU/I (18-29 ng/ml), which is explained not only by differences in the applied radioimmunoassay method, but also by differences in the way the normal range is defined prolactin values in the normal population.

♦ CAUSE OF HYPERPROLACTINEMIA

Hyperprolactinemia is the most common hypothalamic-pituitary disorder. Causes of hyperprolactinemia are the following:

• Prolactinoma
• Hypothalamic-pituitary tumors
• Medicines

– Major sedatives (phenothiazines, haloperidol)

– Dopamine antagonists (metoclopramide)

– Antidepressants (imipramine, amitriptyline)

– Antihypertensives (α-methyldopa, reserpine, verapamil)

– Estrogens

– Opioids

– Cimetidine

• Hypothyroidism
• Chronic kidney failure.

♦ WHEN HYPERPROLACTINEMIA INDICATES PROLACTINOMA

Excluding drug-induced hyperprolactinemia, prolactinoma a pituitary adenoma that oversecretes prolactin, is the most common cause of pathological hyperprolactinemia. In clinical practice, once medication and hypothyroidism are excluded, prolactinoma is the most common cause of hyperprolactinemia. In theory, the best indication that hyperprolactinemia is due to a prolactin-hypersecreting pituitary adenoma would be radiological demonstration of the adenoma by sensitive radiological methods such as computed tomography or magnetic resonance imaging. It should be noted, however, that the finding of a radiological picture compatible with a pituitary microadenoma is particularly common in normal women of reproductive age and is observed in rates ranging up to 36-42%. Therefore, the practical value of the radiological investigation consists mainly in finding or not macroadenoma, and not in indicating microadenoma. In a significant proportion of patients, and usually in cases with low hyperprolactinemia (prolactin levels <2000 mU/I or 100 ng/ml), detailed radiological examination of the pituitary gland, even with sensitive methods, may be negative. These cases are described as "idiopathic or functional hyperprolactinemia", although this term is disputed by most researchers.

In the case of radiological evidence of a large macroadenoma, it is necessary to differentiate between a prolactinoma and a non-hormone-secreting adenoma or other space-occupying lesion of the hypothalamic-pituitary region causing hyperprolactinemia from pituitary stalk pressure (pseudoprolactinoma). In these cases, serum prolactin levels help in the differential diagnosis. If prolactin levels are >5000 mU/L (250 ng/ml) the diagnosis of macroprolactinoma is considered almost certain, while prolactin levels <2000 mU/L (100 ng/ml) make the diagnosis of prolactinoma rather unlikely. However, for prolactin values between 2000-5000 mU/L (100-250 ng/ml) in the presence of a large pituitary macroadenoma, the differential diagnosis between macroprolactinoma and non-hormone-secreting macroadenoma is difficult without histological confirmation.

♦ CLINICAL EVENTS

Prolactinoma in premenopausal women is one of the most common causes of menstrual disorders (15-20% of amenorrhea cases) and infertility. It also causes galactorrhea (spontaneous or after pressure). In men and postmenopausal women, it is diagnosed with a significantly lower frequency, with the most common manifestations being a decrease in libido, impotence (in men), and not infrequently, symptomatology of space-occupying damage.

 ♦ THERAPEUTIC TREATMENT

The goals of prolactinoma treatment are: 1) control of invasive processing and its complications and 2) control of hyperprolactinaemic hypogonadism and its effects (sterility, menstrual disorder, impotence, osteoporosis). Therapeutic agents used in the treatment of prolactinomas include: 1) the administration of dopamine agonists, 2) transsphenoidal removal of the adenoma, and 3) radiation therapy. The best predictor of prolactinoma response to therapy is the size of the adenoma. For this reason, the reference to the treatment of choice for prolactinomas is listed by adenoma size category.

GRADUATE COURSES IN ENDOCRINOLOGY AND DIABETES- DEPARTMENT OF ENDOCRINOLOGY DIABETES AND METABOLISM OF EVANGELISMOS GENERAL HOSPITAL OF ATHENS- 2004