Background

In the vast majority of prolactin deficiency states, the deficiency occurs secondary to general anterior pituitary dysfunction. The most commonly associated condition is postpartum pituitary necrosis (Sheehan syndrome); however, prolactin deficiency can also be caused by anterior pituitary impairment secondary to pituitary (or extrapituitary) tumor or treatment of tumor, parasellar diseases, head injury, infection (eg, tuberculosis, histoplasmosis), or infiltrative diseases (eg, sarcoidosis, hemochromatosis, lymphocytic hypophysitis).^{[1, 2, 3]}

Partial isolated prolactin deficiency is rare, and case reports of total isolated prolactin deficiency are rarer still and may have a genetic component (ie, familial puerperal alactogenesis).^{[4, 5, 6]}Although the endocrine and metabolic function of prolactin is not fully understood, the clinical manifestation of prolactin deficiency is probably limited to puerperal alactogenesis.^[4]

Pathophysiology

Prolactin deficiency is characterized by the inability of pituitary lactotrophs to secrete prolactin and by the resulting lack of puerperal lactogenesis. Other pathophysiologic mechanisms have not been fully established. Prolactin is principally regulated by tonic inhibition rather than by intermittent stimulation. Its principal inhibitory regulator is dopamine. Prolactin enhances dopamine secretion and thus exhibits feedback inhibition of its own secretion. The only other known physiologic inhibitors include triiodothyronine (T3) and somatostatin.^[7]

Menstrual disorders, delayed puberty, infertility, and subfertility have been associated with hypoprolactinemia, through mechanisms that are not entirely clear. Prolactin concentration in follicular fluid during in vitro fertilization (IVF) correlates with the oocyte maturation level and fertilization rate. Further, in a randomized human trial, bromocriptine-induced hypoprolactinemia during IVF resulted in decreased fertilization and cleavage rate compared with a hyperprolactinemic cycle group. A partial prolactin deficiency may result in inadequate lactation. Further, a possibility exists that male factor infertility may be associated with hypoprolactinemia. Serum prolactin levels that were suppressed by bromocriptine resulted in decreased spermatogenesis and decreased testosterone production in healthy male volunteers.^[8]

Some data support the idea that prolactin is also an immunoregulating hormone. Prolactin receptors have been found on human T lymphocytes and B lymphocytes, and some data support T-lymphocyte dependence on prolactin for maintenance of immune competence.^[9]In research using a mouse model, inhibition of prolactin release impaired lymphocyte function and depressed macrophage activation.^[10]Further, the study's mice had a decreased tolerance for bacterial exposure; this reduced tolerance was manifested by death from a normally nonlethal dose of bacteria.

Part of the immunosuppressive effects of cyclosporine may be mediated through a competitive antagonistic action at the prolactin receptor site. Further evidence is found in the observation of the immunosuppressant effects of bromocriptine, which has been shown to be an effective adjuvant (immunosuppressant) in patients after transplantation and in patients with autoimmune disease.^{[11, 12]}

Because prolactin release is inversely related to dopamine levels in the anterior pituitary, critically ill patients on prolonged dopamine infusion have resultant prolactin deficiency. It has been hypothesized that this causes impairment of the T-lymphocyte proliferation response; this impairment occurs in patients in intensive care units (ICUs) and may be an important cause of infection susceptibility in this group. However, no data support the hypothesis that lack of prolactin in otherwise healthy patients results in immunodeficiency.

Several studies have found a correlation in preterm infants between hypoprolactinemia and increased mortality.^[13]The precise pathophysiologic mechanism is unknown, but it is speculated to be associated with the effects of prolactin on surfactant synthesis, whole-body water regulation, or gastrointestinal maturation.^[14]

Frequency

United States

In association with other anterior pituitary dysfunction, prolactin deficiency is uncommon except with pituitary infarction (Sheehan syndrome). In isolation, partial prolactin deficiency occurs rarely, and total isolated prolactin deficiency is limited to case reports.^{[5, 6]}

Mortality/Morbidity

No fatalities resulting from prolactin deficiency in adults have been documented. In preterm infants, however, increased mortality may be associated with hypoprolactinemia.^[13]

Race

No race predilection exists for prolactin deficiency.

Sex

Clinical manifestations occur only in females (puerperal alactogenesis). Excluding women with Sheehan syndrome, incidence in males and females is probably equal.

Age

The prevalence of hypoprolactinemia parallels the prevalence of all causes of hypopituitarism. Obviously, Sheehan syndrome is possible only in women of reproductive age.

Clinical Presentation

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