ORIGINAL ARTICLE
Clinical Profile and Changing Etiological Spectrum of Hyperprolactinemia at a Tertiary Care Endocrine Facility
Üçüncü Basamak Bir Endokrin Kuruluşunda Hiperprolaktineminin Klinik Profili ve Değişen Etiyolojik Spektrumu
Received Date : 09 Jul 2020
Accepted Date : 16 Nov 2020
Available Online : 10 Dec 2020
Junaid Rashid DAR, Moomin Hussain BHAT*, Javaid Ahmad BHAT, Raiz Ahmad MISGAR*, Shariq Rashid MASOODI*, Mir Iftikhar BASHIR*, Arshad Iqbal WANI*
Department of Endocrinology, GMC Srinagar, Jammu & Kashmir, INDIA
*Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu & Kashmir, INDIA
Doi: 10.25179/tjem.2020-77992 - Makale Dili: EN
Turk J Endocrinol Metab. 2020;24:308-313
ABSTRACT
Objective: Hyperprolactinemia is the most common disorder of the hypothalamic-
pituitary axis. It is most commonly caused by a pituitary adenoma.
Due to the recent easy availability of over-the-counter medication,
many drugs, including herbals have commonly been related to this disorder.
Our purpose was to study the clinical presentation and etiology of
hyperprolactinemia and to address any changing trend in the etiological
profile of this disorder. Material and Methods: This study was a crosssectional
observational study on the etiologic spectrum and clinical profile
of hyperprolactinemia. A total of 100 consecutive non-pregnant and
non-lactating patients attending or referred to the out-patient department
of Endocrinology at SKIMS, Srinagar were included. Hyperprolactinemia
was confirmed by a serum prolactin level of >25 ng/mL
(normal range=1-20 ng/mL). Patients with suspicion of drug-related hyperprolactinemia
were advised to stop drug consumption for a minimum
of three days (if medically feasible) and retest for prolactin levels as per
the Institutional protocol. Hyperprolactinemia in patients whose prolactin
levels normalized after stopping drug consumption was labeled as druginduced
hyperprolactinemia. Young patients with pituitary adenoma were
evaluated for multiple endocrine neoplasia syndrome (MEN 1). The results
were compared with those of a study conducted two decades ago
at the same center. Results: Galactorrhea was the most common presenting
symptom occurring in 64% of subjects (all females), followed
by oligomenorrhea or amenorrhea in 60 patients. Both menstrual abnormalities
and galactorrhea were seen in 35 patients. Drug-induced hyperprolactinemia
was the most common cause seen in 59 patients,
followed by pituitary adenoma seen in 31 patients and idiopathic cause
seen in only 4% of cases. However, in the study done two decades ago
at the same center, microprolactinoma was the most common cause
(35.8%), followed by idiopathic hyperprolactinemia (27.8%), with drugs
being responsible in only 5% of the cases. Domperidone and levosulpride
constituted about 88% of drug-induced hyperprolactinemia. Microprolactinoma
was demonstrated in 15 patients, macroadenoma in 16
patients, hypothyroidism in 4% cases, and only one patient had the polycystic
ovarian disease. In four patients, no apparent cause could be determined.
Conclusion: In our study, drug-induced hyperprolactinemia
was the most frequent identifiable etiology, with prokinetics being the
most common cause; contrary to previous studies, where pituitary adenoma
followed by neuroleptic drugs was found to be the most common.
Discontinuation of the offending drug resolved HP in all the patients.
Keywords: Hyperprolactinemia; galactorrhea; domperidone; drug-induced hyperprolactinemia
ÖZET
Amaç: Hiperprolaktinemi, hipotalamus-hipofiz aksının en sık görülen
bozukluğudur. En yaygın nedeni ise hipofiz adenomudur. Son zamanlarda
reçetesiz satılan ilaçların kolay bulunabilirliği nedeniyle,
bitkiler de dahil olmak üzere birçok ilaç bu bozuklukla ilişkilendirilmiştir.
Burada, hiperprolaktineminin klinik prezentasyonunun ve etiyolojisinin
incelenmesi ve bu bozukluğun etiyolojik profilindeki
değişen eğilimlerin ele alınması amaçlanmıştır. Gereç ve Yöntemler:
Bu çalışma, hiperprolaktineminin etiyolojik spektrumu ve klinik profili
üzerine kesitsel, gözlemsel bir çalışmadır. Srinagar'daki SKIMS endokrinoloji
polikliniğine gelen veya bu polikliniğe sevk edilen, gebe
olmayan ve emzirmeyen toplam 100 hasta çalışmaya dahil edilmiştir.
Hiperprolaktinemi, serum prolaktin seviyesinin >25 ng/mL olması
ile doğrulanmıştır (normal aralık=1–20 ng/mL). İlaçla ilişkili hiperprolaktinemi
şüphesi olan hastalara, en az üç gün süreyle ilaç kullanmayı
bırakmaları (tıbbi olarak uygunsa) ve kurum protokolüne göre
prolaktin seviyelerini yeniden test ettirmeleri tavsiye edilmiştir. İlaç
kullanmayı bıraktıktan sonra prolaktin seviyeleri normale dönen hastalardaki
hiperprolaktinemi, ilaca-bağlı hiperprolaktinemi olarak etiketlenmiştir.
Hipofiz adenomlu genç hastalar multipl endokrin
neoplazi sendromu (MEN 1) açısından değerlendirilmiştir. Elde edilen
sonuçlar, aynı merkezde yirmi yıl önce yapılan bir araştırmanın sonuçlarıyla
karşılaştırılmıştır. Bulgular: Galaktore, katılımcıların
%64'ünde (tümü kadın) gözlenen en yaygın başvuru semptomuydu.
Bunu oligomenore veya amenore izliyordu (60 hasta). 35 hastada
hem menstrual anomaliler hem de galaktore görüldü. İlaca bağlı hiperprolaktinemi
en sık neden iken (59 hasta), bunu hipofiz adenomu
(31 hasta) ve idiyopatik neden (vakaların sadece %4'ü) izlemekteydi.
Oysaki, 20 yıl önce aynı merkezde yapılan çalışmada mikroprolaktinoma
en sık nedendi (%35,8), bunu idiyopatik hiperprolaktinemi
(%27,8) izliyordu ve vakaların sadece %5'inden ilaçlar sorumluydu.
Domperidon ve levosulpirid, ilaca bağlı hiperprolaktineminin yaklaşık
%88'ini oluşturmaktaydı. 15 hastada mikroprolaktinoma, 16 hastada
makroadenom, vakaların %4’ünde hipotiroidizm ve sadece bir hastada
polikistik over hastalığı tespit edildi. 4 hastada belirgin bir neden
saptanamadı. Sonuç: Çalışmamızda, ilaca bağlı hiperprolaktinemi en
sık saptanabilir etiyolojiydi ve prokinetikler en sık nedendi. Daha önceki
çalışmalarda ise hipofiz adenomu ve onun ardından nöroleptik
ilaçlar en yaygın nedenler olarak bulunmuştu. Sorumlu olan ilacın kesilmesiyle
tüm hastalarda hiperprolaktinemi ortadan kalktı.
Anahtar Kelimeler: Hiperprolaktinemi; galaktore; domperidon; ilaca-bağlı hiperprolaktinemi
KAYNAKLAR
- Serri O, Chik CL, Ur E, Ezzat S. Diagnosis and management of hyperprolactinemia. CMAJ. 2003;169:575-581. [PubMed] [PMC]
- Lundberg PO, Osterman PO, Wide L. Serum prolactin in patients with hypothalamus and pituitary disorders. J Neurosurg. 1981;55:194-199. [Crossref] [PubMed]
- Zargar AH, Wani AI, Masoodi SR, Laway BA, Salahuddin M. Epidemiologic and etiologic aspects of primary infertility in the Kashmir region of India. Fertil Steril. 1997;68:637-643. [Crossref] [PubMed]
- Melmed S. Disorders of the anterior pituitary and hypothalamus In: Braunwald EG, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's Principles of Internal Medicine (15th ed). New York: McGraw Hill; 2001;2029-2052.
- Lamberts SW, de Herder WW, Kwekkeboom DJ, vd Lely AJ, Nobels FR, Krenning EP. Current tools in the diagnosis of pituitary tumours. Acta Endocrinol (Copenh). 1993;129 Suppl 1:6-12. [PubMed]
- Molitch ME, Thorner MO, Wilson C. Management of prolactinomas. J Clin Endocrinol Metab. 1997;82:996-1000. [Crossref] [PubMed]
- Touraine P, Plu-Bureau G, Beji C, Mauvais-Jarvis P, Kuttenn F. Long-term follow-up of 246 hyperprolactinemic patients. Acta Obstet Gynecol Scand. 2001;80:162-168. [Crossref] [PubMed]
- Kulshreshtha B, Pahuja I, Kothari D, Chawla I, Sharma N, Gupta S, Mittal A. Menstrual cycle abnormalities in patients with prolactinoma and drug-induced hyperprolactinemia. Indian J Endocrinol Metab. 2017;21:545-550. [Crossref] [PubMed] [PMC]
- Zargar AH, Laway BA, Masoodi SR, Bhat MH, Wani AI, Bashir MI, Salahuddin M, Rasool R. Clinical and etiological profile of hyperprolactinemia--data from a tertiary care centre. J Assoc Physicians India. 2005;53:288-290. [PubMed]
- Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA; Endocrine Society. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:273-288. [Crossref] [PubMed]
- Franks S, Nabarro JD. Prevalence and presentation of hyperprolactinaemia in patients with "functionless" pituitary tumours. Lancet. 1977;1:778-780. [Crossref] [PubMed]
- Thorner MO, Besser GM. Bromocriptine treatment of hyperprolactinaemic hypogonadism. Acta Endocrinol Suppl (Copenh). 1978;216:131-146. [PubMed]
- Kemmann E, Jones JR. Hyperprolactinemia and headaches. Am J Obstet Gynecol. 1983;145:668-671. [Crossref] [PubMed]
- Petit A, Piednoir D, Germain ML, Trenque T. [Drug-induced hyperprolactinemia: a case-non-case study from the national pharmacovigilance database]. Therapie. 2003;58:159-163. [Crossref] [PubMed]
- Melkersson K. Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry. 2005;66:761-767. [Crossref] [PubMed]
- Bushe C, Shaw M. Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics. J Psychopharmacol. 2007;21:768-773. [Crossref] [PubMed]
- Ou Horng-Yih, Hsiao Shu-Hwa,Yu Eugene-Hsin,Wu Ta-Jen. Etiologies and clinical manifestations of hyperprolactinemia in a medical centre in Southern Taiwan. J Intern Med Taiwan. 2004;15:19-24. [Link]
- Bronstein MD. Disorders of prolactin secretion and prolactinomas. In: Jameson JL, De Groot LJ, eds. Endocrinology (6th ed). Philadelphia: Saunders Elsevier; 2010;333-357. [Crossref]
- Jacobs LS, Snyder PJ, Wilber JF, Utiger RD, Daughaday WH. Increased serum prolactin after administration of synthetic thyrotropin releasing hormone (TRH) in man. J Clin Endocrinol Metab. 1971;33:996-998. [Crossref] [PubMed]
- Vilar L, Freitas MC, Naves LA, Casulari LA, Azevedo M, Montenegro R Jr, Barros AI, Faria M, Nascimento GC, Lima JG, Nóbrega LH, Cruz TP, Mota A, Ramos A, Violante A, Lamounier Filho A, Gadelha MR, Czepielewski MA, Glezer A, Bronstein MD. Diagnosis and management of hyperprolactinemia: results of a Brazilian multicenter study with 1234 patients. J Endocrinol Invest. 2008;31:436-444. [Crossref] [PubMed]
- Thorner MO, Edwards CRW, Hanker JP, Abraham G, Besser GM. Prolactin and gonadotropin interaction in the male. In: Troen P, Nankin HR, eds. Testis Norm Infertile Men. New York: Raven Press; 1977;351-366.
- Luciano AA, Chapler FK, Sherman BM. Hyperprolactinemia in polycystic ovary syndrome. Fertil Steril 1984;41:719-725. [Crossref]
- Szosland K, Pawlowicz P, Lewiński A. Prolactin secretion in polycystic ovary syndrome (PCOS). Neuro Endocrinol Lett. 2015;36:53-58. [PubMed]