Prolactin

Overview:

First test for work-up of galactorrhea (inappropriate lactation). Pituitary function test useful in the detection of prolactin-secreting pituitary tumors (microadenomas, macroadenomas) with or without galactorrhea, with or without structural evidence of sellar enlargement. An adult female premenopausal patient having amenorrhea and galactorrhea is highly suspect of pituitary prolactinoma and is a candidate for radiologic evaluation of the pituitary as well as serum prolactin levels. Elevated prolactin may be associated with corpus luteum insufficiency or anovulation. Sequelae of hyperprolactinemia include amenorrhea, anovulation, and decreased bone density.

When determining prolactin, it should be remembered that the measured concentration is dependent upon when the blood sample was taken, since the secretion of prolactin occurs in episodes and is also subject to a 24-hour cycle.

The release of prolactin is promoted physiologically by suckling and stress. In addition, elevated serum prolactin concentrations are caused by a number of pharmaceuticals (eg, dibenzodiazepines, phenothiazine), TRH, and estrogen.1-3 The release of prolactin is inhibited by dopamine, L-dopa, and ergotamine derivatives.

In patients receiving therapy with high biotin doses (ie, >5 mg/day), no sample should be taken until at least eight hours after the last biotin administration.4 As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or who have received them for diagnostic purposes.4 In rare cases, interference due to extremely high titers of antibodies to ruthenium can occur.4 Extremely high titers of antibodies to streptavidin can occur in isolated cases and cause interference.4

Levels rise during pregnancy and are elevated during lactation, in postpartum subjects, and following bilateral oophorectomy. Destructive pituitary diseases cause low levels. Hypothalamic lesions may be associated with increased values. Many pituitary tumors which previously were called chromophobe adenomas are now recognizable as prolactinomas.

Patients with hyperprolactinemia may have the multiple endocrine neoplasia syndrome, MEN-1.5 Provocative tests used in work-up of hyperprolactinemia include metyrapone stimulation of ACTH-2 and TRH provocative test.6

Antipsychotic drugs may elevate serum prolactin. Antipsychotics block dopamine, thereby elevating serum prolactin levels. Hyperprolactinemia is present in many patients receiving neuroleptics with an occasional patient developing amenorrhea, galactorrhea, and/or decreased libido. Amoxapine, a dibenzoxazepine type of tricyclic with antidepressant and antipsychotic characteristics, has been found to cause galactorrhea and oligomenorrhea with hyperprolactinemia. Amoxapine may have a dopamine blocking action.7 The prolactin level may rise significantly but only briefly. Point prolactin level determinations during therapy may be within normal range while total integrated 24-hour secretion is significantly increased. It has been recommended that patients who develop amenorrhea and/or galactorrhea during neuroleptic therapy should be observed regularly for possible emergence of a pituitary tumor.

Persistent elevations of plasma prolactin levels may be observed with, and after withdrawal from, chronic cocaine abuse, and may reflect a cocaine-induced derangement in the neural dopaminergic regulatory systems.8

1. Frantz AG. Prolactin. N Engl J Med. 1978 Jan 26; 298(4):201-207. PubMed 339087

2. Müller EE, Locatelli V, Cella S, Peñalva A, Novelli A, Cocchi D. Prolactin-lowering and -releasing drugs, mechanism of action and therapeutic applications. Drugs. 1983 Apr; 25(4):399-432. PubMed 6133737

3. Pontiroli AE, Falsetti L, Bottazzo G, et al. Clinical, endocrine, roentgenographic, and immune characterization of hyperprolactinemic women. Int J Fert. 1987 Jan-Feb; 32(1):81-85. PubMed 2880822

4. Prolactin on Elecsys 1010/2010 and Modular Analytics E170. [Package insert] 2007-09, V 2, Indianapolis, Ind: Roche Diagnostics; 2007.

5. Levine JH, Sagel J, Rosebrock G. Prolactin-secreting adenoma as part of the multiple endocrine neoplasia—type 1 (MEN-1) syndrome. Cancer. 1979 Jun; 43(6):2492-2496. PubMed 36978

6. Randall RV, Laws ER Jr, Abboud CF, Ebersold MJ, Kao PC, Scheithauer BW. Transsphenoidal microsurgical treatment of prolactin-producing pituitary adenomas. Results in 100 patients. Mayo Clin Proc. 1983 Feb; 58(2):108-121. PubMed 6681646

7. Gelenberg AJ, Cooper DS, Doller JC, Maloof F. Galactorrhea and hyperprolactinemia associated with amoxapine therapy. Report of a case. JAMA. 1979 Oct 26; 242(17):1900-1901. PubMed 573343

8. Mendelson JH, Teoh SK, Lange U, et al. Anterior pituitary, adrenal, and gonadal hormones during cocaine withdrawal. Am J Psychiatry. 1988 Sep; 145(9):1094-1098. PubMed 3414852

Baskin HJ. Endocrinologic evaluation of impotence. South Med J. 1989 Apr; 82(4):446-449. PubMed 2495570

Berczi I, Cosby H, Hunter T, Baragar F, McNeilly AS, Friesen HG. Decreased bioactivity of circulating prolactin in patients with rheumatoid arthritis. Br J Rheumatol. 1987 Dec; 26(6):433-436. PubMed 3690137

Burrow GN, Wortzman G, Rewcastle NB, Holgate RC, Kovacs K. Microadenomas of the pituitary and abnormal sellar tomograms in an unselected autopsy series. N Engl J Med. 1981 Jan 15; 304(3):156-158. PubMed 7442734

Fujimoto VY, Clifton DK, Cohen NL, Soules MR. Variability of serum prolactin and progesterone levels in normal women: The relevance of single hormone measurements in the clinical setting. Obstet Gynecol. 1990 Jul; 76(1):71-78. PubMed 2359568

Kelly PA, Djiane J, Postel-Vinay MC, Edery M. The prolactin/growth hormone receptor family. Endocr Rev. 1991 Aug; 12(3):235-251. PubMed 1935820

Kletzky OA, Davajan V. Hyperprolactinemia: Diagnosis and treatment. In: Mishell DR Jr, Davajan V, eds. Infertility, Contraception and Reproductive Endocrinology. 2nd ed. Oradell, NJ: Medical Economics Books;1986:275-301.

Schlechte J, Dolan K, Sherman B, Chapler F, Luciano A. The natural history of untreated hyperprolactinemia: A prospective analysis. J Clin Endocrinol Metab. 1989 Feb; 68(2):412-418. PubMed 2918052

Smith CR, Butler J, Hashim I, Norman MR. Serum prolactin bioactivity and immunoactivity in hyperprolactinaemic states. Ann Clin Biochem. 1990 Jan; 27(Pt 1):3-8. PubMed 2310154

Tippet PD, Simon JA, Rifka SM, Falk RJ. Luteal phase hyperprolactinemia during ovulation induction with human menopausal gonadotropins: Incidence, recurrence, and effect on pregnancy rates. Obstet Gynecol. 1989 Apr; 73(4):613-616. PubMed 2494621

Veldhuis JD, Evans WS, Stumpf PG. Mechanisms that subserve estradiol's induction of increased prolactin concentrations: Evidence of amplitude modulation of spontaneous prolactin secretory bursts. Am J Obstet Gynecol. 1989 Nov; 161(5):1149-1158. PubMed 2589434