Clinical features of hyperprolactinemia in children: modern methods of diagnosis and treatment




hyperprolactinemia, prolactinoma, dopamine receptor agonists, treatment, review


Hyperprolactinemia is a common endocrine disease that can be associated with significant morbidity and disability in the population. A systematic review of literature sources on the diagnosis and treatment results in patients with hyperprolactinemia, including drug-resistant micro- and macroadenomas of the pituitary gland, was carried out in order to highlight the most significant practical recommendations. The purpose of this literature review is to provide algorithms for differential diagnosis and clinical observation of patients, to compare the efficacy and side effects of drugs, surgeries, and radiation therapy in the treatment of hyperprolactinemia. Prolactinomas are the most common pituitary adenomas in older children. Their share in the structure of pituitary adenomas is about 50 %. The clinical picture depends on the age, sex of the child, volume and characteristics of tumor growth. The leading clinical manifestations of hyper­prolactinemia are disorders of the reproductive system, including signs of the development of secondary hypogonadotropic hypogonadism, sexual dysfunction, psychoemotional disorders, and endocrine and metabolic disorders. The main criterion for the diagnosis of hyperprolactinemia is the concentration of prolactin in the blood serum, which is above the upper limit of the physio­logical norm. The primary step in the treatment of patients with pituitary macroadenoma is to control the compression effects of the tumor, including compression of the optic chiasm, followed by restoration of gonadal function. The main areas of treatment for hyperprolactinemia are restoration and maintenance of the normal function of the gonads; restoration of fertility; prevention of osteoporosis. Dopamine receptor agonists are the gold standard in the treatment of hyperprolactinemia. However, some people do not respond satisfactorily to these drugs. In this case, in the presence of pituitary tumors, in addition to drug treatment, surgery and radiation therapy are used. But surgery and radiation therapy are not the primary methods of choice for the management of patients with prolactin-secreting pituitary adenomas; first of all, preference is given to drug therapy. The prognosis of the course of prolactinomas is favorable and is based on the results of dynamic observation and the presence of markers of the aggressiveness of this adenoma.


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Abaturov OE, Nikulina AO, Petrenko LL. Acromegaly and pituitary gigantism in children. Kyiv: Logos; 2020. 98 p. (in Ukrainian).

Tronko MD, Antipkin YG, Kaminsky VV, et al. National Consensus on the Management of Patients with Hyperprolactinemia 2016. Medical aspects of women's health. 2017;(106):32-42. (in Ukrainian).

Baldari S, Ferraù F, Alafaci C, et al. First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment. Pituitary. 2012 Dec;15 Suppl 1:S57-60. doi: 10.1007/s11102-011-0373-5.

Barlier A, Jaquet P. Quinagolide-a valuable treatment option for hyperprolactinaemia. Eur J Endocrinol. 2006 Feb;154(2):187-95. doi: 10.1530/eje.1.02075.

Bengtsson D, Schrøder HD, Andersen M, et al. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab. 2015 Apr;100(4):1689-98. doi: 10.1210/jc.2014-4350.

Bolyakov A, Paduch DA. Prolactin in men's health and disease. Curr Opin Urol. 2011 Nov;21(6):527-34. doi: 10.1097/MOU.0b013e32834bdf01.

Capozzi A, Scambia G, Pontecorvi A, Lello S. Hyperprolactinemia: pathophysiology and therapeutic approach. Gynecol Endocrinol. 2015 Jul;31(7):506-10. doi: 10.3109/09513590.2015.1017810.

Chaurasia PK, Singh D, Meher S, Saran RK, Singh H. Epistaxis as first clinical presentation in a child with giant prolactinoma: Case report and review of literature. J Pediatr Neurosci. 2011 Jul;6(2):134-7. doi: 10.4103/1817-1745.92840.

Cookson J, Hodgson R, Wildgust HJ. Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis. J Psychopharmacol. 2012 May;26(5 Suppl):42-51. doi: 10.1177/0269881112442016.

Cooper O, Mamelak A, Bannykh S, et al. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors. Endocrine. 2014 Jun;46(2):318-27. doi: 10.1007/s12020-013-0093-x.

Drummond J, Roncaroli F, Grossman AB, Korbonits M. Clinical and Pathological Aspects of Silent Pituitary Adenomas. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2473-2489. doi: 10.1210/jc.2018-00688.

Eren E, Yapıcı Ş, Çakır ED, Ceylan LA, Sağlam H, Tarım Ö. Clinical course of hyperprolactinemia in children and adolescents: a review of 21 cases. J Clin Res Pediatr Endocrinol. 2011;3(2):65-9. doi: 10.4274/jcrpe.v3i2.14.

Fukuoka H, Cooper O, Mizutani J, et al. HER2/ErbB2 receptor signaling in rat and human prolactinoma cells: strategy for targeted prolactinoma therapy. Mol Endocrinol. 2011 Jan;25(1):92-103. doi: 10.1210/me.2010-0353.

Fusco A, Lugli F, Sacco E, et al. Efficacy of the combined cabergoline and octreotide treatment in a case of a dopamine-agonist resistant macroprolactinoma. Pituitary. 2011 Dec;14(4):351-7. doi: 10.1007/s11102-008-0162-y.

Gao H, Xue Y, Cao L, et al. ESR1 and its antagonist fulvestrant in pituitary adenomas. Mol Cell Endocrinol. 2017 Mar 5;443:32-41. doi: 10.1016/j.mce.2016.12.029.

Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev. 2006 Aug;27(5):485-534. doi: 10.1210/er.2005-9998.

Gordon CM, Ackerman KE, Berga SL, et al. Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 May 1;102(5):1413-1439. doi: 10.1210/jc.2017-00131.

Heidari Z, Hosseinpanah F, Shirazian N. Achievement of fertility in an infertile man with resistant macroprolactinoma using high-dose bromocriptine and a combination of human chorionic gonadotropin and an aromatase inhibitor. Endocr Pract. 2010 Jul-Aug;16(4):669-72. doi: 10.4158/EP10026.CR.

Li Q, Zhu Y, Chen M, et al. Development and Validation of a Deep Learning Algorithm to Automatic Detection of Pituitary Microadenoma From MRI. Front Med (Lausanne). 2021 Nov 29;8:758690. doi: 10.3389/fmed.2021.758690.

Li Z, Liu Q, Li C, et al. The role of TGF-β/Smad signaling in dopamine agonist-resistant prolactinomas. Mol Cell Endocrinol. 2015 Feb 15;402:64-71. doi: 10.1016/j.mce.2014.12.024.

Loeffler JS, Shih HA. Radiation therapy in the management of pituitary adenomas. J Clin Endocrinol Metab. 2011 Jul;96(7):1992-2003. doi: 10.1210/jc.2011-0251.

Maiter D. Management of Dopamine Agonist-Resistant Prolactinoma. Neuroendocrinology. 2019;109(1):42-50. doi: 10.1159/000495775.

Melmed S, Casanueva FF, Hoffman AR, et al. Endocrine Society. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273-88. doi: 10.1210/jc.2010-1692.

Molitch ME. Diagnosis and Treatment of Pituitary Adenomas: A Review. JAMA. 2017 Feb 7;317(5):516-524. doi: 10.1001/jama.2016.19699.

Molitch ME. Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma. Eur J Endocrinol. 2015 May;172(5):R205-13. doi: 10.1530/EJE-14-0848.

Molitch ME. Management of medically refractory prolactinoma. J Neurooncol. 2014 May;117(3):421-8. doi: 10.1007/s11060-013-1270-8.

Recouvreux MV, Camilletti MA, Rifkin DB, et al. The pituitary TGFβ1 system as a novel target for the treatment of resistant prolactinomas. J Endocrinol. 2016 Mar;228(3):R73-83. doi: 10.1530/JOE-15-0451.

Shimazu S, Shimatsu A, Yamada S, et al. Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels. Eur J Endocrinol. 2012 Mar;166(3):383-90. doi: 10.1530/EJE-11-0656.

Shimon I, Sosa E, Mendoza V, et al. Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas. Pituitary. 2016 Aug;19(4):429-36. doi: 10.1007/s11102-016-0723-4.

Trott JF, Schennink A, Petrie WK, Manjarin R, VanKlompenberg MK, Hovey RC. Triennial Lactation Symposium: Prolactin: The multifaceted potentiator of mammary growth and function. J Anim Sci. 2012 May;90(5):1674-86. doi: 10.2527/jas.2011-4682.

Vasilev V, Daly AF, Vroonen L, Zacharieva S, Beckers A. Resistant prolactinomas. J Endocrinol Invest. 2011 Apr;34(4):312-6. doi: 10.1007/BF03347092.

Vilar L, Abucham J, Albuquerque JL, et al. Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism. Arch Endocrinol Metab. 2018 Mar-Apr;62(2):236-263. doi: 10.20945/2359-3997000000032.

Vilar L, Vilar CF, Lyra R, Freitas MDC. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia. Neuroendocrinology. 2019;109(1):7-19. doi: 10.1159/000499694.

Wang AT, Mullan RJ, Lane MA, et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev. 2012 Jul 24;1:33. doi: 10.1186/2046-4053-1-33.

Wang S, Wang A, Zhang Y, et al. The role of MAPK11/12/13/14 (p38 MAPK) protein in dopamine agonist-resistant prolactinomas. BMC Endocr Disord. 2021 Nov 23;21(1):235. doi: 10.1186/s12902-021-00900-9.

Wang Z, Gao L, Guo X, Feng C, Deng K, Lian W, Xing B. Identification of microRNAs associated with the aggressiveness of prolactin pituitary tumors using bioinformatic analysis. Oncol Rep. 2019 Aug;42(2):533-548. doi: 10.3892/or.2019.7173.



How to Cite

Abaturov, A., Nikulina, A., & Alieinykova, T. (2022). Clinical features of hyperprolactinemia in children: modern methods of diagnosis and treatment. CHILD`S HEALTH, 17(1), 28–36.



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