Advertisement

Journal of Endocrinological Investigation

, Volume 31, Issue 5, pp 436–444 | Cite as

Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients

  • L. Vilar
  • M. C. Freitas
  • L. A. Naves
  • L. A. Casulari
  • M. Azevedo
  • R. MontenegroJr
  • A. I. Barros
  • M. Faria
  • G. C. Nascimento
  • J. G. Lima
  • L. H. Nóbrega
  • T. P. Cruz
  • A. Mota
  • A. Ramos
  • A. Violante
  • A. Lamounier Filho
  • M. R. Gadelha
  • M. A. Czepielewski
  • A. Glezer
  • M. D. Bronstein
Original Articles

Abstract

Objective: The aim of the study was to evaluate clinical and laboratorial features of 1234 patients with different etiologies of hyperprolactinemia, as well as the response of 388 patients with prolactinomas to dopamine agonists. Design, setting, and patients: A total of 1234 hyperprolactinemic patients from 10 Brazilian endocrine centers were enrolled in this retrospective study. Main outcome measure: PRL measurement, thyroid function tests, and screening for macroprolactin were conducted. Results: Patients were subdivided as follows: 56.2% had prolactinomas, 14.5% drug-induced hyperprolactinemia, 9.3% macroprolactinemia, 6.6% non-functioning pituitary adenomas, 6.3% primary hypothyroidism, 3.6% idiopathic hyperprolactinemia, and 3.2% acromegaly. Clinical manifestations were similar irrespective of the etiology of the hyperprolactinemia. The highest PRL levels were observed in patients with prolactinomas but there was a great overlap in PRL values between all groups. However, PRL>500 ng/ml allowed a clear distinction between prolactinomas and the other etiologies. Cabergoline (CAB) was more effective than bromocriptine (BCR) in normalizing PRL levels (81.9% vs 67.1%, p<0.0001) and in inducing significant tumor shrinkage and complete disappearance of tumor mass. Drug resistance was observed in 10% of patients treated with CAB and in 18.4% of those that used BCR (p=0.0006). Side-effects and intolerance were also more common in BCR-treated patients. Conclusion: Prolactinomas, drug-induced hyperprolactinemia, and macroprolactinemia were the 3 most common causes of hyperprolactinemia. Although PRL levels could not reliably define the etiology of hyperprolactinemia, PRL values >500 ng/ml were exclusively seen in patients with prolactinomas. CAB was significantly more effective than BCR in terms of prolactin normalization, tumor shrinkage, and tolerability.

Key-words

Prolactin hyperprolactinemia diagnosis treatment macroprolactin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Vilar L, Gadelha MR, Une K. Diagnostic evaluation of hyperprolactinemia. In: Vilar L, Kater CE, Naves LA. Endocrinologia Clínica (Clinical Endocrinology). 3rd ed. Rio de Janeiro: Guanabara Koogan. 2006, 29–38.Google Scholar
  2. 2.
    Molitch ME. Disorders of prolactin secretion. Endocrinol Metab Clin North Am 2001, 30: 585–610.PubMedCrossRefGoogle Scholar
  3. 3.
    Vilar L, Naves LA, Gadelha M. Pitfalls in the diagnosis of hyperprolactinemia. Arq Brasil Endocrinol Metab 2003, 47: 347–57.Google Scholar
  4. 4.
    Sinha YN. Structural variants of prolactin: occurrence and physiological significance. Endocr Rev 1995, 16: 354–69.PubMedCrossRefGoogle Scholar
  5. 5.
    Vieira JGH. Macroprolactinemia. Arq Brasil Endocrinol Metab 2002, 46: 45–50.CrossRefGoogle Scholar
  6. 6.
    Hattori N, Inagaki C. Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia: bioassay and clearance studies of PRL-immunoglobulin G complex. J Clin Endocrinol Metab 1997, 82: 3107–10.PubMedGoogle Scholar
  7. 7.
    Glezer A, Soares CRJ, Vieira JG, et al. Human macroprolactin displays low biological activity via its homologous receptor in a new sensitive bioassay J Clin Endocrinol Metab 2006, 91: 1048–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Gibney J, Smith TP, McKenna TJ. The impact on clinical practice of routine screening for macroprolactin. J Clin Endocrinol Metab 2005, 90: 3927–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 2006, 65: 265–73.CrossRefGoogle Scholar
  10. 10.
    Vilar L, Naves L, Freitas MC, Oliveira S, Leite V, Canadas V. Medical treatment of pituitary tumors. Part I: Prolactinomas and GH secreting adenomas. Arq Bras Endocrinol Metab 2000, 44: 367–81.Google Scholar
  11. 11.
    Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev 2006, 27: 485–534.PubMedCrossRefGoogle Scholar
  12. 12.
    Colao A, Di Sarno A, Landi ML, et al. Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab 2000, 85: 2247–52.PubMedGoogle Scholar
  13. 13.
    Colao A, Di Sarno A, Landi ML, et al. Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 1997, 82: 3574–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Vilar L, Burke CW. Quinagolide efficacy and tolerability in hyperprolactinaemic patients who are resistant to or intolerant of bromocriptine. Clin Endocrinol (Oxf) 1994, 41: 821–6.CrossRefGoogle Scholar
  15. 15.
    Di Sarno A, Landi ML, Cappabianca P, et al. Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab 2001, 86: 5256–61.PubMedCrossRefGoogle Scholar
  16. 16.
    Molitch ME. Dopamine resistance of prolactinomas. Pituitary 2003, 6: 19–27.PubMedCrossRefGoogle Scholar
  17. 17.
    Vieira JG, Tachibana TT, Obara LH, Maciel RM. Extensive experience and validation of polyethylene glycol precipitation as a screening method for macroprolactinemia. Clin Chem 1998, 44: 1758–9.PubMedGoogle Scholar
  18. 18.
    Colao A, Loche S, Cappa M, et al. Prolactinomas in children and adolescents. Clinical presentation and long-term follow-up. J Clin Endocrinol Metab 1998, 83: 2777–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Colao A, Di Sarno A, Cappabianca P, et al. Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol 2003, 148: 325–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Jackson RD, Wortsman J, Malarkey W. Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses. J Clin Endocrinol Metab 1985, 61: 258–64.PubMedCrossRefGoogle Scholar
  21. 21.
    Hauache OMG, Rocha AJ, Maia ACM Jr, Maciel RMB, Vieira JGH. Screening for macroprolactinaemia may prevent unnecessary pituitary imaging studies. Clin Endocrinol (Oxf) 2002, 57: 327–31.CrossRefGoogle Scholar
  22. 22.
    Alfonso A, Rieniets KI, Vigersky RA. Incidence and clinical significance of elevated macroprolactin levels in patients with hyperprolactinemia. Endocr Pract 2006, 12: 275–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Vallette-Kasic S, Morange-Ramos I, Selim A, et al. Macroprolactinemia revisited: A study on 106 patients. J Clin Endocrinol Metab 2002, 87: 581–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Strachan MW, Teoh WL, Don-Wauchope AC, Seth J, Stoddart M, Beckett GJ. Clinical and radiological features of patients with macroprolactinaemia. Clin Endocrinol (Oxf) 2003, 59: 339–46.CrossRefGoogle Scholar
  25. 25.
    Vilar L, Moura E, Canadas V, et al. Prevalence of macroprolactinemia among 115 patients with hyperprolactinemia. Arq Brasil Endocrinol Metab 2007, 51: 86–91.CrossRefGoogle Scholar
  26. 26.
    Toldy E, Locsei Z, Szabolcs I, et al. Macroprolactinemia: the consequences of a laboratory pitfall. Endocrine 2003, 22: 267–73.PubMedCrossRefGoogle Scholar
  27. 27.
    Bevan JS, Burke CW, Esiri MM, Adams CBT. Misinterpretation of prolactin levels leading to management errors in patients with sellar enlargement. Am J Med 1987, 82: 29–32.PubMedCrossRefGoogle Scholar
  28. 28.
    Albuquerque FC, Hinton DR, Weiss MH. Excessively high prolactin level in a patient with a nonprolactin-secreting adenoma. J Neurosurg 1998, 89: 1043–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Smith MV, Laws ER Jr. Magnetic resonance imaging measurements of pituitary stalk compression and deviation in patients with nonprolactin-secreting intrasellar and parasellar tumors: lack of correlation with serum prolactin levels. Neurosurgery 1994, 34: 834–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Vilar L, Czepielewski MA, Naves LA, Rollin GAFS, Casulari LA, Coelho CE. Marked shrinkage of cosecreting GH/prolactin adenomas with cabergoline. Endocr Pract 2007, 13: 396–402.PubMedCrossRefGoogle Scholar
  31. 31.
    Freda PU, Reyes CM, Nuruzzaman AT, Sundeen RE, Khandji AG, Post KD. Cabergoline therapy of growth hormone and growth hormone/prolactin secreting pituitary tumors. Pituitary 2004, 7: 21–30.PubMedCrossRefGoogle Scholar
  32. 32.
    Fahie-Wilson M. In hyperprolactinemia, testing for macroprolactin is essential. Clin Chem 2003, 49: 1434–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Honbo KS, van Herle AJ, Kellett KA. Serum prolactin levels in untreated primary hypothyroidism. Am J Med 1978, 64: 782–7.PubMedCrossRefGoogle Scholar
  34. 34.
    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.PubMedCrossRefGoogle Scholar
  35. 35.
    Molitch ME. Medication-induced hyperprolactinemia. Mayo Clin Proc 2005, 80: 1050–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Bandyopadhyay P. Drug-induced hyperprolactinemia. Drugs Today (Barc) 2006, 42: 103–19.CrossRefGoogle Scholar
  37. 37.
    Melkersson K. Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry 2005, 66: 761–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhoea. Cabergoline Comparative Study Group. N Engl J Med 1994, 331: 904–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Pascal-Vigneron V, Weryha G, Bosc M, Leclere J. Hyperprolactinemic amenorrhea: treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study. Presse Med 1995, 24: 753–7.PubMedGoogle Scholar
  40. 40.
    Delgrange E, Maiter D, Donckier J, Tourniaire J. Influence of age on the clinical presentation of prolactinomas in male patients. Gerontology 1999, 45: 160–4.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2008

Authors and Affiliations

  • L. Vilar
    • 1
  • M. C. Freitas
    • 1
  • L. A. Naves
    • 2
  • L. A. Casulari
    • 2
  • M. Azevedo
    • 2
  • R. MontenegroJr
    • 3
  • A. I. Barros
    • 3
  • M. Faria
    • 4
  • G. C. Nascimento
    • 4
  • J. G. Lima
    • 5
  • L. H. Nóbrega
    • 5
  • T. P. Cruz
    • 6
  • A. Mota
    • 7
  • A. Ramos
    • 7
  • A. Violante
    • 8
  • A. Lamounier Filho
    • 8
  • M. R. Gadelha
    • 8
  • M. A. Czepielewski
    • 9
  • A. Glezer
    • 10
  • M. D. Bronstein
    • 10
  1. 1.Division of Endocrinology, Hospital das ClínicasFederal University of PernambucoRecife
  2. 2.Division of EndocrinologyBrasilia University HospitalBrasilia
  3. 3.Division of EndocrinologyFederal University of CearáFortaleza
  4. 4.Division of EndocrinologyFederal University of MaranhaoSao Luiz
  5. 5.Division of EndocrinologyNatal Institute of EndocrinologyNatal
  6. 6.Division of EndocrinologyFederal University of BahiaSalvador
  7. 7.Division of EndocrinologyFederal University of ParaibaCampina Grande
  8. 8.Division of EndocrinologyFederal University of Rio de JaneiroRio de Janeiro
  9. 9.Division of EndocrinologyFederal University of Rio Grande do SulPorto Alegre
  10. 10.Neuroendocrine Unit, Division of Endocrinology and MetabolismUniversity of Sao Paulo Medical SchoolSao PauloBrazil

Personalised recommendations