Hyperprolactinemia resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mydah Sajid, MD[2]


Hyperprolactinemia is defined as high circulating levels of prolactin in the blood. The cut-off values of serum prolactin for hyperprolactinemia are greater than 20 ng/ml in men and postmenopausal women and greater than 30ng/ml in premenopausal women.[1] Prolactin hormone is produced by lactotroph cells located in the anterior lobe of the pituitary gland. It is responsible for lactation and the development of breasts in females during pregnancy. Elevated levels of prolactin cause galactorrhea, menstrual irregularities, and failure to conceive in females and erectile dysfunction, hypogonadism, and infertility in males. This section provides a short and straight to the point overview of the hyperprolactinemia.


Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

Common Causes


Shown below is an algorithm summarizing the diagnosis of hyperprolactinemia according to an Endocrine Society Clinical Practice guidelines:[1][11]

Inquire about any present illness like hypothyroidism, chronic renal failure, and the use of medications known to cause hyperprolactinemia.
Measure serum prolactin. Elevated serum prolactin
Mesure serum TSH. TSH levels elevated?
Perform the MRI with the contrast of the brain. Does it show any mass in the hypothalamic-pituitary region?
Levels of TSH and prolactin should be reassessed after 6-12 weeks.
The levels of other pituitary hormones should be evaluated: Plasma corticotropins (ACTH), Serum TSH, Insulin-like growth factors, Follicle-stimulating hormone, Luteinizing hormone, Estradiol/ Testosterone


Shown below is an algorithm summarizing the treatment of hyperprolactinemia:[1][12][13][14]

The prolactinoma are treated in the following patients:
The drug of choice for prolactinoma are:
Transsphenoidal surgery is done in:
  • Patients with unsuccessful treatment with dopamine agonists.
  • A female patient with a known history of lactotroph macroadenoma who wishes to conceive.
    • The preferred initial dose of cabergoline for microadenoma is 0.25mg twice a week or 0.5mg once a week.
    • The medicine should be given at dinner or bedtime to reduce the incidence of nausea and drowsiness.
    Transsphenoidal surgery has a high success rate in reducing serum prolactin to a normal level.


    • While assessing serum prolactin levels "hook effect” should be considered. Patients with macroadenoma can have artifactually low values of serum prolactin between 20 to 200 mcg/L in patients with high levels of serum prolactin i.e. 5000 mcg/L.[15] This artifact is avoided by repeating the assay by dilution of serum.
    • Cabergoline is preferred by women who wish to conceive as it is safe in early pregnancy.[16] Though bromocriptine is also a safe choice with more evidence of reduced events of congenital defects.[17]
    • Physician should monitor patients with hyperprolactinemia with normal serum prolactin levels for regular intervals after discontinuing cabergoline. There is a chance of recurrence of hyperprolactinemia in patients after disconticontinuing cabergoline.[18]



    1. 1.0 1.1 1.2 Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA; et al. (2011). "Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 96 (2): 273–88. doi:10.1210/jc.2010-1692. PMID 21296991.
    2. Morley JE, Dawson M, Hodgkinson H, Kalk WJ (1977). "Galactorrhea and hyperprolactinemia associated with chest wall injury". J Clin Endocrinol Metab. 45 (5): 931–5. doi:10.1210/jcem-45-5-931. PMID 562902.
    3. 3.0 3.1 Tyson JE, Hwang P, Guyda H, Friesen HG (1972). "Studies of prolactin secretion in human pregnancy". Am J Obstet Gynecol. 113 (1): 14–20. doi:10.1016/0002-9378(72)90446-2. PMID 5024994.
    4. 4.0 4.1 Kleinberg DL, Noel GL, Frantz AG (1977). "Galactorrhea: a study of 235 cases, including 48 with pituitary tumors". N Engl J Med. 296 (11): 589–600. doi:10.1056/NEJM197703172961103. PMID 840242.
    5. David SR, Taylor CC, Kinon BJ, Breier A (2000). "The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia". Clin Ther. 22 (9): 1085–96. doi:10.1016/S0149-2918(00)80086-7. PMID 11048906.
    6. McCallum RW, Sowers JR, Hershman JM, Sturdevant RA (1976). "Metoclopramide stimulates prolactin secretion in man". J Clin Endocrinol Metab. 42 (6): 1148–52. doi:10.1210/jcem-42-6-1148. PMID 777023.
    7. Sowers JR, Sharp B, McCallum RW (1982). "Effect of domperidone, an extracerebral inhibitor of dopamine receptors, on thyrotropin, prolactin, renin, aldosterone, and 18-hydroxycorticosterone secretion in man". J Clin Endocrinol Metab. 54 (4): 869–71. doi:10.1210/jcem-54-4-869. PMID 7037817.
    8. Steiner J, Cassar J, Mashiter K, Dawes I, Fraser TR, Breckenridge A (1976). "Effects of methyldopa on prolactin and growth hormone". Br Med J. 1 (6019): 1186–8. doi:10.1136/bmj.1.6019.1186. PMC 1639736. PMID 1268617.
    9. Newey PJ, Gorvin CM, Cleland SJ, Willberg CB, Bridge M, Azharuddin M; et al. (2013). "Mutant prolactin receptor and familial hyperprolactinemia". N Engl J Med. 369 (21): 2012–2020. doi:10.1056/NEJMoa1307557. PMC 4209110. PMID 24195502.
    10. Snyder PJ, Jacobs LS, Utiger RD, Daughaday WH (1973). "Thyroid hormone inhibition of the prolactin response to thyrotropin-releasing hormone". J Clin Invest. 52 (9): 2324–9. doi:10.1172/JCI107421. PMC 333037. PMID 4199418.
    11. Majumdar A, Mangal NS (2013). "Hyperprolactinemia". J Hum Reprod Sci. 6 (3): 168–75. doi:10.4103/0974-1208.121400. PMC 3853872. PMID 24347930.
    12. Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD; et al. (2006). "Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas". Clin Endocrinol (Oxf). 65 (2): 265–73. doi:10.1111/j.1365-2265.2006.02562.x. PMID 16886971.
    13. Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF (1994). "A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group". N Engl J Med. 331 (14): 904–9. doi:10.1056/NEJM199410063311403. PMID 7915824.
    14. Randall RV, Laws ER, Abboud CF, Ebersold MJ, Kao PC, Scheithauer BW (1983). "Transsphenoidal microsurgical treatment of prolactin-producing pituitary adenomas. Results in 100 patients". Mayo Clin Proc. 58 (2): 108–21. PMID 6681646.
    15. Petakov MS, Damjanović SS, Nikolić-Durović MM, Dragojlović ZL, Obradović S, Gligorović MS; et al. (1998). "Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect". J Endocrinol Invest. 21 (3): 184–8. doi:10.1007/BF03347299. PMID 9591215.
    16. Robert E, Musatti L, Piscitelli G, Ferrari CI (1996). "Pregnancy outcome after treatment with the ergot derivative, cabergoline". Reprod Toxicol. 10 (4): 333–7. doi:10.1016/0890-6238(96)00063-9. PMID 8829257.
    17. Turkalj I, Braun P, Krupp P (1982). "Surveillance of bromocriptine in pregnancy". JAMA. 247 (11): 1589–91. PMID 7062462.
    18. Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G (2003). "Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia". N Engl J Med. 349 (21): 2023–33. doi:10.1056/NEJMoa022657. PMID 14627787.
    19. Dogansen SC, Cikrikcili U, Oruk G, Kutbay NO, Tanrikulu S, Hekimsoy Z; et al. (2019). "Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study". J Clin Endocrinol Metab. 104 (7): 2527–2534. doi:10.1210/jc.2018-02202. PMID 30848825.

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