[Misleading diagnosis of hyperprolactinemia in women]

Prolactin is a major hormone, involved in gonadotroph axis regulation. Hyperprolactinemia induces gonadotropin deficiency and therefore hypogonadotropic hypogonadism. It should be suspected in front of menstrual cycle abnormalities, infertility and/or galactorrhea. If drugs and/or PRL adenoma represent the vast majority of causes of hyperprolactinemia, other etiologies and misleading diagnosis of hyperprolactinemia should be searched for. After eliminating a pregnancy, in women of childbearing age, the first step is to interpret the result of hyperprolactinemia, according to the assay technique used. Indeed, the major active form of prolactin is the 23kDA non-glycosylated prolactin. However, some assays interfere with macroprolactinemia, an inactive form of prolactin, including glycosylated prolactin bound to an IgG immunoglobulin. Its presence in the serum is misleading as it may induce increased levels of prolactin, usually below 100 ng/mL. The diagnosis of macroprolactinemia has major issues as pituitary MRI does not need to be performed. Furthermore, neither treatment nor follow-up of patients with macroprolactinemia are necessary. It should be suspected in the presence of normal menstrual cycles. Drugs inducing hyperprolactinemia usually raise prolactin levels below 100 ng/mL. If prolactin level is higher than 250 ng/mL, the main diagnosis is pituitary macro-adenoma. If prolactin ranges between 100 and 250 ng/mL, it is usually related to a micro-adenoma or a necrotic macro-adenoma. A mixed PRL/GH should always be suspected. If prolactin level is below 150 ng/mL, in the presence of a large hypothalamic-pituitary tumor, the major diagnosis is hyperprolactinemia due to pituitary disconnection. Ectopic secretions of prolactin remain very rare. A new etiology of hyperprolactinemia is loss of function mutation of prolactin receptor.