Prevalence and predictors of hyperprolactinemia in subclinical hypothyroidism

  • Lokesh Kumar Sharma
    Department of Biochemistry, Post Graduate Institute of Medical Education & Research (PGIMER) & Dr. Ram Manohar Lohia (RML) Hospital, 1 Baba Kharak Singh Marg, New Delhi 110001, India
    Search for articles by this author
  • Neera Sharma
    Department of Biochemistry, Post Graduate Institute of Medical Education & Research (PGIMER) & Dr. Ram Manohar Lohia (RML) Hospital, 1 Baba Kharak Singh Marg, New Delhi 110001, India
    Search for articles by this author
  • Adesh Kisanji Gadpayle
    Post Graduate Institute of Medical Education & Research (PGIMER) and Dr. Ram Manohar Lohia (RML) Hospital, 1 Baba Kharak Singh Marg, New Delhi 110001, India
    Search for articles by this author
  • Deep Dutta
    Corresponding author at: Endocrinology Clinic, Nursing Home Annex, Department of Endocrinology, Post-graduate Institute of Medical Education & Research (PGIMER) and Dr. Ram Manohar Lohia (RML) Hospital, 1 Baba Kharak Singh Marg, New Delhi, 110001, India.
    Department of Endocrinology, Post Graduate Institute of Medical Education & Research (PGIMER) and Dr. Ram Manohar Lohia (RML) Hospital, 1 Baba Kharak Singh Marg, New Delhi 110001, India
    Search for articles by this author


      • Hyperprolactinemia was common in primary (42.19%) and subclinical hypothyroidism (ScH) (34.93%)
      • In ScH, hyperprolactinemia was especially common in TSH>7.5mIU/L (≈50%)
      • TSH followed by free T4 were best predictors of serum prolactin
      • TSH ≥ 7.51mIU/L (♀) and ≥ 8.33mIU/L (♂) had sensitivity & specificity of ≈ 50% & > 90% in detecting hyperprolactinemia


      Background and aims

      Hyperprolactinemia has been reported in 0–57% of primary hypothyroidism. Data on hyperprolactinemia in subclinical hypothyroidism (ScH) is scant and inconsistent. This study aimed to determine the prevalence and predictors of hyperprolactinemia in ScH.


      Consecutive patients diagnosed to have normal thyroid function, ScH or overt primary hypothyroidism underwent serum prolactin, gonadotropins, testosterone and estradiol estimation. Patients with pregnancy, pituitary adenomas, secondary hypothyroidism, hyperthyroidism, comorbid states and drug-induced hyperprolactinemia were excluded.


      From initially screened 4950 patients, hormonal data from 2848 individuals who fulfilled all criteria were analyzed. The occurrence of hyperprolactinemia (females:males) was highest in primary hypothyroidism (42.95%:39.53%) (n = 192), followed by ScH (35.65%:31.61%) (n = 770) and euthyroid individuals (2.32%:2.02%) (n = 1886) (P < 0.001). Hyperprolactinemia in ScH with TSH 5–7.5, 7.5–10 and >10 mIU/L (females: males) was 25.56%:20.73%, 49.07%:50% and 61.43%:35.71% respectively (P < 0.001). Significant positive correlation between TSH and prolactin was noted in ScH and primary hypothyroidism. In females, testosterone was lowest in patients with primary hypothyroidism. In males, serum estradiol was significantly higher, and testosterone significantly lower in men with ScH and primary hypothyroidism. Regression analysis revealed serum TSH followed by free T4, to be best predictors of serum prolactin in both sexes.


      Hyperprolactinemia is common in ScH, especially in those with TSH > 7.5 mIU/L. ROC analysis confirmed that TSH ≥ 7.51 mIU/L in females and ≥8.33 mIU/L in males had a sensitivity of ≈50% with a very high specificity of >90% in detecting hyperprolactinemia. Prolactin screening may be warranted in ScH with TSH > 7.5mIU/L, and may form an indication for treating ScH.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Mancini T.
        • Casanueva F.F.
        • Giustina A.
        Hyperprolactinemia and prolactinomas.
        Endocrinol Metab Clin North Am. 2008; 37: 67-99
        • Josimovich J.B.
        • Lavenhar M.A.
        • Devanesan M.M.
        • Sesta H.J.
        • Wilchins S.A.
        • Smith A.C.
        Heterogeneous distribution of serum prolactin values in apparently healthy young women, and the effects of oral contraceptive medication.
        Fertil Steril. 1987; 47: 785-791
        • Tyson J.E.
        • Hwang P.
        • Guyda H.
        • Friesen H.G.
        Studies of prolactin secretion in human pregnancy.
        Am J Obstet Gynecol. 1972; 113: 14-20
        • Vilar L.
        • Fleseriu M.
        • Bronstein M.D.
        Challenges and pitfalls in the diagnosis of hyperprolactinemia.
        Arq Bras Endocrinol Metabol. 2014; 58: 9-22
        • Misra M.
        • Papakostas G.I.
        • Klibanski A.
        Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism.
        J Clin Psychiatry. 2004; 65: 1607-1618
        • Fernandez A.
        • Karavitaki N.
        • Wass J.A.
        Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK).
        Clin Endocrinol (Oxf). 2010; 72: 377-382
        • Kleinberg D.L.
        • Noel G.L.
        • Frantz A.G.
        Galactorrhea: a study of 235 cases, including 48 with pituitary tumors.
        N Engl J Med. 1977; 296: 589-600
        • Klibanski A.
        • Biller B.M.
        • Rosenthal D.I.
        • Schoenfeld D.A.
        • Saxe V.
        Effects of prolactin and estrogen deficiency in amenorrheic bone loss.
        J Clin Endocrinol Metab. 1988; 67: 124-130
        • Raber W.
        • Gessl A.
        • Nowotny P.
        • Vierhapper H.
        Hyperprolactinaemia in hypothyroidism: clinical significance and impact of TSH normalization.
        Clin Endocrinol (Oxf). 2003; 58: 185-191
        • Notsu K.
        • Ito Y.
        • Furuya H.
        • Ohguni S.
        • Kato Y.
        Incidence of hyperprolactinemia in patients with Hashimoto's thyroiditis.
        Endocr J. 1997; 44: 89-94
        • Meier C.
        • Christ-Crain M.
        • Guglielmetti M.
        • Huber P.
        • Staub J.J.
        • Müller B.
        Prolactin dysregulation in women with subclinical hypothyroidism: effect of levothyroxine replacement therapy.
        Thyroid. 2003; 13: 979-985
        • Z
        • Kafesçiler S.
        • Güçlü F.
        • Ozmen B.
        The prevalence of hyperprolactinaemia in overt and subclinical hypothyroidism.
        Endocr J. 2010; 57: 1011-1015
        • Bahar A.
        • Akha O.
        • Kashi Z.
        • Vesgari Z.
        Hyperprolactinemia in association with subclinical hypothyroidism.
        Caspian J Intern Med. 2011; 2: 229-233
        • Samson S.L.
        • Hamrahian A.H.
        • Ezzat S.
        American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.
        Endocr Pract. 2015; 21: 1427-1435
        • Poppe K.
        • Velkeniers B.
        • Glinoer D.
        Thyroid disease and female reproduction.
        Clin Endocrinol (Oxf). 2007; 66: 309-321
        • Lu K.H.
        • Chen H.I.
        • Grandison L.
        • Huang H.H.
        • Meites J.
        Reduced luteinizing hormone release by synthetic luteinizing hormone releasing hormone (LHRH) in postpartum lactating rats.
        Endocrinology. 1976; 98: 1235-1240
        • Mazziotti G.
        • Chiavistelli S.
        • Giustina A.
        Pituitary diseases and bone.
        Endocrinol Metab Clin North Am. 2015; 44: 171-180
        • Asa S.L.
        • Ezzat S.
        The pathogenesis of pituitary tumours.
        Nat Rev Cancer. 2002; 2: 836-849
        • Carlson H.E.
        • Jacobs L.S.
        • Daughaday W.H.
        Growth hormone, thyrotropin, and prolactin responses to thyrotropin releasing hormone following diethylstilbestrol pretreatment.
        J Clin Endocrinol Metab. 1973; 37: 488-490
        • Katznelson L.
        • Riskind P.N.
        • Saxe V.C.
        • Klibanski A.
        Prolactin pulsatile characteristics in postmenopausal women.
        J Clin Endocrinol Metab. 1988; 83: 761-764
        • Seri O.
        • Chik C.L.
        • Ur E.
        • Ezzat S.
        Diagnosis and management of hyperprolactinemia.
        CMAJ. 2003; 169: 575-581
        • Foord S.M.
        • Peters J.R.
        • Dieguez C.
        • Jasani B.
        • Hall R.
        • Scanlon M.F.
        Hypothyroid pituitary cells in culture: an analysis of thyrotropin and prolactin response to dopamine (DA) and DA receptor binding.
        Endocrinology. 1984; 115: 407-415
        • Davis J.R.
        • Lynam T.C.
        • Franklyn J.A.
        • Docherty K.
        • Sheppard M.C.
        Tri-iodothyronine and phenytoin reduce prolactin messenger RNA levels in cultured rat pituitary cells.
        J Endocrinol. 1986; 109: 359-364
        • Cave Jr., W.T.
        • Paul M.A.
        Effects of altered thyroid function on plazma prolactin clearance.
        Endocrinology. 1980; 107: 85-91
        • Hapon M.B.
        • Gamarra-Luques C.
        • Jahn G.A.
        Short term hypothyroidism affects ovarian function in the cycling rat.
        Reprod Biol Endocrinol. 2010 Feb 11; 8: 14
        • Kumar A.
        • Chaturvedi P.K.
        • Mohanty B.P.
        Hypoandrogenaemia is associated with subclinical hypothyroidism in men.
        Int J Androl. 2007; 30: 14-20
        • Hatsuta M.
        • Abe K.
        • Tamura K.
        • Ryuno T.
        • Watanabe G.
        • Taya K.
        • et al.
        Effects of hypothyroidism on the estrous cycle and reproductive hormones in mature female rat.
        Eur J Pharmacol. 2004; 486: 343-348
        • Tohei A.
        Studies on the functional relationship between thyroid, adrenal and gonadal hormones.
        J Reprod Dev. 2004; 50: 9-20
        • Mattheij J.A.
        • Swarts J.J.
        • Lokerse P.
        • van Kampen J.T.
        • Heide Van der D.
        Effect of hypothyroidism on the pituitary–gonadal axis in the adult female rat.
        J Endocrinol. 1995; 146: 87-94
        • Jaya Kumar B.
        • Khurana M.L.
        • Ammini A.C.
        • Karmarkar M.G.
        • Ahuja M.M.
        Reproductive endocrine functions in men with primary hypothyroidism: effect of thyroxine replacement.
        Horm Res. 1990; 34: 215-218
        • Velazquez E.M.
        • Arata G.B.
        Effects of thyroid status on pituitary gonadotropin and testicular reserve in men.
        Arch Androl. 1997; 38: 85-92
        • Donnelly P.
        • White C.
        Testicular dysfunction in men with primary hypothyroidism; reversal of hypogonadotrophic hypogonadism with replacement thyroxine.
        Clin Endocrinol (Oxf). 2000; 52: 197-201