Hyperprolactinemia resident survival guide

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

Overview

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.

Causes

Life Threatening Causes

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

  • Severe burns on the chest can cause hyperprolactinemia due to neural stimulation similar to suckling. [2]

Common Causes

  • Pregnancy
  • Lactation
  • Prolactinoma
  • Injury to dopaminergic neurons in the hypothalamus (sarcoidosis, craniopharyngioma, and metastatic brain carcinoma)
  • Section of the hypothalamic-pituitary stalk
  • Antipsychotics (risperidone, haloperidol, and phenothiazine)
  • Selective serotonin reuptake inhibitors
  • Metoclopramide
  • Domperidone
  • Methyldopa
  • Verapamil
  • Familial hyperprolactinemia
  • Hypothyroidism
  • Chronic renal failure
  • macroprolactinomas
  • Exercise

Diagnosis

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

 
 
 
Suggestive symptoms including headache, oligomenorrhea, infertility, hypogonadism, erectile dysfunction, and galactorrhea
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Detailed history and physical examination should be performed to rule out hypothyroidism, chronic renal failure, and the use of medications known to cause hyperprolactinemia.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum prolactin measured. 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.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MRI with the contrast of brain should be performed to rule out any mass in the hypothalamic-pituitary region.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The levels of other pituitary hormones should be evaluated. The following hormone levels should be evaluated: Plasma corticotropins (ACTH), Serum TSH, Insulin-like growth factors, Follicle-stimulating hormone, Luteinizing hormone, Estradiol/ Testosterone
 
 
 

Treatment

 
 
 
The prolactinoma are treated in the following patients[3][1][4]:
  • A macroadenoma causing neurological symptoms such as headache and visual impairment due to compression of the optic chiasm.
  • Hypogonadism and galactorrhea due to increased prolactin secretion.
  • Infertility in women with disrupted luteal phase.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The drug of choice for prolactinoma are dopamine agonists as they decrease prolactin secretion and reduce the size of the prolactinoma.[5][6] Cabergoline is the preferred drug because of its efficacy and lower incidence of nausea and side effects compared to bromocriptine.[7][8]
 
 
 
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.
  • Transsphenoidal surgery has a high success rate in reducing serum prolactin to a normal level.[9] [10]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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.[1]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cabergoline is also preferred by women who wish to conceive as it is safe in early pregnancy.[11] Though bromocriptine is also a safe choice with more evidence of reduced events of congenital defects.[12]
 
 
 
 

Do's

  • The content in this section is in bullet points.

Don'ts

  • Certain medications like risperidone, domperidone, methyldopa, metoclopramide, verapamil, and cimetidine raise serum prolactin levels. These medications can blunt the effects of dopamine agonists.
  • The patients should be monitored for side effects. Cabergoline treatment in prolactinoma patients for more than three months can result in impulse control disorders. Hypersexuality is common in males and compulsive eating disorders in females.[13]

References

  1. 1.0 1.1 1.2 1.3 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. 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.
  4. Melmed S (2020). "Pituitary-Tumor Endocrinopathies". N Engl J Med. 382 (10): 937–950. doi:10.1056/NEJMra1810772. PMID 32130815 Check |pmid= value (help).
  5. Vance ML, Evans WS, Thorner MO (1984). "Drugs five years later. Bromocriptine". Ann Intern Med. 100 (1): 78–91. doi:10.7326/0003-4819-100-1-78. PMID 6229205.
  6. Wang AT, Mullan RJ, Lane MA, Hazem A, Prasad C, Gathaiya NW; et al. (2012). "Treatment of hyperprolactinemia: a systematic review and meta-analysis". Syst Rev. 1: 33. doi:10.1186/2046-4053-1-33. PMC 3483691. PMID 22828169.
  7. 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.
  8. Biller BM, Molitch ME, Vance ML, Cannistraro KB, Davis KR, Simons JA; et al. (1996). "Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline". J Clin Endocrinol Metab. 81 (6): 2338–43. doi:10.1210/jcem.81.6.8964874. PMID 8964874.
  9. Feigenbaum SL, Downey DE, Wilson CB, Jaffe RB (1996). "Transsphenoidal pituitary resection for preoperative diagnosis of prolactin-secreting pituitary adenoma in women: long term follow-up". J Clin Endocrinol Metab. 81 (5): 1711–9. doi:10.1210/jcem.81.5.8626821. PMID 8626821.
  10. 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.
  11. Ricci E, Parazzini F, Motta T, Ferrari CI, Colao A, Clavenna A; et al. (2002). "Pregnancy outcome after cabergoline treatment in early weeks of gestation". Reprod Toxicol. 16 (6): 791–3. doi:10.1016/s0890-6238(02)00055-2. PMID 12401507.
  12. "Reorganized text". JAMA Otolaryngol Head Neck Surg. 141 (5): 428. 2015. doi:10.1001/jamaoto.2015.0540. PMID 25996397.
  13. 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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