Prolactin is another peptide pituitary hormone. It stimulates lactation (galactorrhea) in females, but its function in males is less certain. The major regulatory mechanism for prolactin secretion is an inhibitory effect exerted by the hypothalamus, with one known pathway being under control of dopamine. There is also a hypothalamic stimulating effect, although a specific prolactin-stimulating hormone has not yet been isolated. TRH stimulates release of prolactin from the pituitary as well as release of TSH. Dopamine antagonists such as chlorpromazine or reserpine block the hypothalamic inhibition pathway, leading to increased prolactin secretion. Serum prolactin is measured by immunoassay. Prolactin secretion in adults has a diurnal pattern much like that of GH, with highest levels during sleep.

Some Conditions Associated With Generalized Retardation or Acceleration of Bone Maturation Compared to Chronologic Age (as Seen on Hand-Wrist X-ray Films
Bone age retarded
Hypopituitarism with GH deficiency
Constitutional growth delay
Gonadal dysgenesis (Turner’s syndrome)
Primary Hypothyroidism (20%-30% of patients)
Cushing’s syndrome
Severe chronic disease (renal, inflammatory gastrointestinal [GI] disease, malnutrition, chronic
anemia, cyanotic congenital heart disease)
Poorly controlled severe type I diabetes mellitus
Bone age accelerated
Excess androgens (adrenogenital syndrome; tumor; iatrogenic)
Excess estrogens (tumor; iatrogenic)
Albright’s syndrome (polyostotic fibrous dysplasia)

Prolactin assay

Prolactin-secreting pituitary tumors. Prolactin assay has aroused interest for two reasons. First, about 65% of symptomatic pituitary ad enomas (literature range, 25%-95%), including both microadenomas (<1 cm) and adenomas, produce elevated serum levels of prolactin. The pituitary cell type most often associated with hyperprolactinemia is the acidophil cell adenoma, but chromophobe adenomas (which are by far the most frequent adenoma type) are also involved. In addition, about 20%-30% of women with postpubertal (secondary) amenorrhea (literature range, 15%-50%) have been found to have elevated serum prolactin levels. The incidence of pituitary tumors in such persons is 35%-45%. Many patients have been cured when pituitary adenomas were destroyed or when drug therapy directed against prolactin secretion was given. Hyperprolactinemia has also been reported to be an occasional cause of male infertility.

Some reports indicate that extension of a pituitary adenoma outside the confines of the sella turcica can be detected by assay of cerebrospinal fluid (CSF) prolactin. Prolactin in CSF rises in proportion to blood prolactin levels but is disproportionately elevated when tumor extension from the sella takes place. A CSF/plasma prolactin ratio of 0.2 or more suggests suprasellar extension of a pituitary tumor. Simultaneously obtained CSF and venous blood specimens are required.

Not all pituitary tumors secrete prolactin. Autopsy studies have demonstrated nonsymptomatic pituitary adenomas in 2.7%-27% of patients. Theoretically, nonfunctional tumors should have normal serum prolactin levels. Reports indicate, however, that some tumors that do not secrete prolactin may be associated with elevated serum prolactin levels, although the values are usually not as high as levels found with prolactin-secreting tumors.

Prolactin assay drawbacks. Elevated serum prolactin levels may be associated with conditions other than pituitary tumors, idiopathic pituitary hyperprolactinemia, or hypothalamic dysfunction. Some of these conditions are listed in the box. Especially noteworthy are the empty sella syndrome, stress, and medication. The empty sella syndrome is associated with an enlarged sella turcica on x-ray film. Serum prolactin is elevated in some of these patients, although the elevation is most often not great; and the combination of an enlarged sella plus elevated serum prolactin level could easily lead to a false diagnosis of pituitary tumor. Stress is important since many conditions place the patient under stress. In particular, the stress of venipuncture may itself induce some elevation in serum prolactin levels, so some investigators place an indwelling heparin lock venous catheter and wait as long as 2 hours with the patient resting before the sample is drawn. Estrogens and other medications may contribute to diagnostic problems. In general, very high prolactin levels are more likely to be due to pituitary adenoma than to other causes, but there is a great deal of overlap in the low- and medium-range elevations, and only a minority of pituitary adenomas display marked prolactin elevation. Statistics depend on the diagnostic cutoff level being used. The level of 100 ng/ml (100 µg/L) is most frequently quoted; the majority (45%-81%) of pituitary adenomas are above this level, but only 25%-57% of patients with prolactin levels above 100 ng/ml are reported to have a pituitary adenoma. A value of 300 ng/ml gives clear-cut separation but includes only about one third of the adenomas (literature range, 12%-38%).

Conditions Associated With Increased Serum Prolactin (% With Elevation Varies)
Stress (including exercise, trauma, illness)
Nursing infant
Pregnancy and estrogens
Pituitary adenoma
Hypothalamic space-occupying, granulomatous, or destructive diseases
Chronic renal failure
Certain medications
Postpartum amenorrhea syndrome
Postpill amenorrhea-galactorrhea syndrome
Empty sella syndrome
Addison’s disease (Nelson’s syndrome)
Polycystic ovary (PCO) disease
Ectopic prolactin secretion (nonpituitary neo-plasms)

Prolactin stimulation and suppression tests Several stimulation and suppression tests have been used in attempts to differentiate pituitary adenoma from other causes of hyperprolactinemia. For example, several investigators have reported that pituitary adenomas display a normal response to levodopa but a blunted response to chlorpromazine. Normally there is a considerable elevation of prolactin level (at least twofold) after TRH or chlorpromazine administration and a decrease of the prolactin level after levodopa administration. In pituitary insufficiency there typically is failure to respond to TRH, chlorpromazine, or levodopa. In hypothalamic dysfunction there typically is normal response to TRH (which directly stimulates the pituitary), little, if any, response to chlorpromazine, and blunted response to levodopa. Pituitary adenomas are supposed to give a blunted response to TRH and chlorpromazine but a normal decrease with levodopa. Unfortunately, there are sufficient inconsistent results or overlap in adenoma and nonadenoma response that most investigators believe none of these tests is sufficiently reliable. There have also been some conflicting results in differentiating hypothalamic from pituitary disease. Diseases such as hypothyroidism and other factors that affect pituitary function or prolactin secretion may affect the results of these tests.