Hyperprolactinemia: Etiology, Diagnosis, and Management

 

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ABSTRACT

Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. A prolactinoma is the most common cause of chronic hyperprolactinemia once pregnancy, primary hypothyroidism, and drugs that elevate serum prolactin levels have been excluded. Patients can present with hypogonadism, infertility, galactorrhea, osteopenia, and mass effects of the tumor. When hyperprolactinemia is confirmed, a cause for the disorder needs to be sought. This involves a careful history and examination, followed by laboratory tests and diagnostic imaging of the sella turcica. The goals of treatment are to normalize prolactin levels, restore gonadal function, and reduce the effects of chronic hyperprolactinemia. Dopamine agonists are the treatment of choice for the majority of patients. Transsphenoidal surgery is usually reserved for patients who are intolerant of or resistant to dopamine agonists or when hyperprolactinemia is caused by non-prolactin-secreting tumors compressing the pituitary stalk. Cabergoline has been shown to be more effective and better tolerated than bromocriptine. However, there are more data on the safety of the latter drug during pregnancy and bromocriptine, therefore, remains the treatment of choice in hyperprolactinemic women wishing to conceive.

REFERENCES

• 1 Delitala G. Hyperprolactinaemia: causes, biochemical diagnosis and tests of prolactin secretion. In: Grossman A, ed. Clinical Endocrinology Oxford, UK: Blackwell Science 1998: 138-147
  Google Scholar
• 2 Molitch M E. Disorders of prolactin secretion.  Endocrinol Metab Clin North Am . 2001;  30 585-610
  CrossrefPubMedGoogle Scholar
• 3 Molitch M E. Management of prolactinomas during pregnancy.  J Reprod Med . 1999;  44 (suppl 12) 1121-1126
  PubMedGoogle Scholar
• 4 Biller B M, Luciano A, Crosignani P G. Guidelines for the diagnosis and treatment of hyperprolactinemia.  J Reprod Med . 1999;  44 (suppl 12) 1075-1084
  PubMedGoogle Scholar
• 5 Luciano A A. Clinical presentation of hyperprolactinemia.  J Reprod Med . 1999;  44 (suppl 12) 1085-1090
  PubMedGoogle Scholar
• 6 Webster J, Scanlon M F. Prolactinomas. In: Sheaves R, Jenkins PJ, Wass JA, eds. Clinical Endocrine Oncology Oxford, UK: Blackwell Science 1997: 189-194
  Google Scholar
• 7 Bevan J S, Webster J, Burke C W, Scanlon M F. Dopamine agonists and pituitary tumor shrinkage.  Endocr Rev . 1992;  13 220-240
  CrossrefPubMedGoogle Scholar
• 8 Klibanski A, Neer R M, Beitins I Z, Ridgway E C, Zervas N T, McArthur J W. Decreased bone density in hyperprolactinemic women.  N Engl J Med . 1980;  303 1511-1514
  PubMedGoogle Scholar
• 9 Biller B M, Baum H B, Rosenthal D I, Saxe V C, Charpie P M, Klibanski A. Progressive trabecular osteopenia in women with hyperprolactinemic amenorrhea.  J Clin Endocrinol Metab . 1992;  75 692-697
  CrossrefPubMedGoogle Scholar
• 10 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
  PubMedGoogle Scholar
• 11 Biller B M. Hyperprolactinemia.  Int J Fertil Womens Med . 1999;  44 74-77
  PubMedGoogle Scholar
• 12 Jenkins R C, Ross R JM. Protocols for common endocrine tests. In: Grossman A, ed. Clinical Endocrinology Oxford, UK: Blackwell Science 1998: 1117-1134
  Google Scholar
• 13 Martin T L, Kim M, Malarkey W B. The natural history of idiopathic hyperprolactinemia.  J Clin Endocrinol Metab . 1985;  60 855-858
  PubMedGoogle Scholar
• 14 Schlechte J, Dolan K, Sherman B, Chapler F, Luciano A. The natural history of untreated hyperprolactinemia: a prospective analysis.  J Clin Endocrinol Metab . 1989;  68 412-418
  PubMedGoogle Scholar
• 15 Jeffcoate W J, Pound N, Sturrock N D, Lambourne J. Long-term follow-up of patients with hyperprolactinaemia.  Clin Endocrinol (Oxf) . 1996;  45 299-303
  CrossrefPubMedGoogle Scholar
• 16 Nishioka H, Ito H, Haraoka J, Hirano A. Growth potential of female prolactinomas.  Surg Neurol . 2001;  55 213-217
  PubMedGoogle Scholar
• 17 Tyrrell J B, Lamborn K R, Hannegan L T, Applebury C B, Wilson C B. Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results.  Neurosurgery . 1999;  44 254-261
  CrossrefPubMedGoogle Scholar
• 18 Turner H E, Adams C B, Wass J A. Trans-sphenoidal surgery for microprolactinoma: an acceptable alternative to dopamine agonists?.  Eur J Endocrinol . 1999;  140 43-47
  CrossrefPubMedGoogle Scholar
• 19 Wilson C B. Surgical management of pituitary tumors.  J Clin Endocrinol Metab . 1997;  82 2381-2385
  CrossrefPubMedGoogle Scholar
• 20 Bevan J S, Adams C B, Burke C W. Factors in the outcome of transsphenoidal surgery for prolactinoma and non-functioning pituitary tumour, including pre-operative bromocriptine therapy.  Clin Endocrinol (Oxf) . 1987;  26 541-556
  PubMedGoogle Scholar
• 21 Landolt A M, Lomax N. Gamma knife radiosurgery for prolactinomas.  J Neurosurg . 2000;  93 (suppl 3) 14-18
  PubMedGoogle Scholar
• 22 Pan L, Zhang N, Wang E M, Wang B J, Dai J Z, Cai P W. Gamma knife radiosurgery as a primary treatment for prolactinomas.  J Neurosurg . 2000;  93 (suppl 3) 10-13
  PubMedGoogle Scholar
• 23 Webster J. A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation.  Drug Saf . 1996;  14 228-238
  PubMedGoogle Scholar
• 24 Webster J, Piscitelli G, Polli A, Ferrari C I, Ismail I, Scanlon M F. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group.  N Engl J Med . 1994;  331 904-909
  CrossrefPubMedGoogle Scholar
• 25 Morange I, Barlier A, Pellegrini I, Brue T, Enjalbert A, Jaquet P. Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy.  Eur J Endocrinol . 1996;  135 413-420
  PubMedGoogle Scholar
• 26 Webster J, Piscitelli G, Polli A. The efficacy and tolerability of long-term cabergoline therapy in hyperprolactinaemic disorders: an open, uncontrolled, multicentre study. European Multicentre Cabergoline Study Group.  Clin Endocrinol (Oxf) . 1993;  39 323-329
  PubMedGoogle Scholar
• 27 Verhelst J, Abs R, Maiter D. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients.  J Clin Endocrinol Metab . 1999;  84 2518-2522
  CrossrefPubMedGoogle Scholar
• 28 Di Sarno A, Landi M L, Cappabianca P. Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy.  J Clin Endocrinol Metab . 2001;  86 5256-5261
  CrossrefPubMedGoogle Scholar
• 29 Colao A, Di Sarno A, Landi M L. 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 2247-2252
  CrossrefPubMedGoogle Scholar
• 30 Webster J. Clinical management of prolactinomas.  Baillieres Best Pract Res Clin Endocrinol Metab . 1999;  13 395-408
  CrossrefPubMedGoogle Scholar
• 31 Homburg R, West C, Brownell J, Jacobs H S. A double-blind study comparing a new non-ergot, long-acting dopamine agonist, CV 205-502, with bromocriptine in women with hyperprolactinaemia.  Clin Endocrinol (Oxf) . 1990;  32 565-571
  PubMedGoogle Scholar
• 32 Verhelst J A, Froud A L, Touzel R, Wass J A, Besser G M, Grossman A B. Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: a double-blind study.  Acta Endocrinol (Copenh) . 1991;  125 385-391
  PubMedGoogle Scholar
• 33 van der Heijden F P, de Wit W, Brownell J, Schoemaker J, Rolland R. CV 205-502, a new dopamine agonist, versus bromocriptine in the treatment of hyperprolactinaemia.  Eur J Obstet Gynecol Reprod Biol . 1991;  40 111-118
  CrossrefPubMedGoogle Scholar
• 34 Giusti M, Porcella E, Carraro A, Cuttica M, Valenti S, Giordano G. A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients.  J Endocrinol Invest . 1994;  17 51-57
  PubMedGoogle Scholar
• 35 Webster J. Cabergoline and quinagolide therapy for prolactinomas.  Clin Endocrinol (Oxf) . 2000;  53 549-550
  CrossrefPubMedGoogle Scholar
• 36 Di Sarno A, Landi M L, Marzullo P. The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas.  Clin Endocrinol (Oxf) . 2000;  53 53-60
  CrossrefPubMedGoogle Scholar
• 37 Johnston D G, Hall K, Kendall-Taylor P, Patrick D, Watson M, Cook D B. Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Studies with high-definition computerised tomography.  Lancet . 1984;  2 187-192
  PubMedGoogle Scholar
• 38 van't Verlaat W J, Croughs R J. Withdrawal of bromocriptine after long-term therapy for macroprolactinomas: effect on plasma prolactin and tumour size.  Clin Endocrinol (Oxf) . 1991;  34 175-178
  PubMedGoogle Scholar
• 39 Muratori M, Arosio M, Gambino G, Romano C, Biella O, Faglia G. Use of cabergoline in the long-term treatment of hyperprolactinemic and acromegalic patients.  J Endocrinol Invest . 1997;  20 537-546
  PubMedGoogle Scholar
• 40 Karunakaran S, Page R C, Wass J A. The effect of the menopause on prolactin levels in patients with hyperprolactinaemia.  Clin Endocrinol (Oxf) . 2001;  54 295-300
  CrossrefPubMedGoogle Scholar
• 41 Rebar R W. Following patients under treatment for hyperprolactinemia.  J Reprod Med . 1999;  44 (suppl 12) 1100-1104
  PubMedGoogle Scholar
• 42 Corenblum B, Donovan L. The safety of physiological estrogen plus progestin replacement therapy and with oral contraceptive therapy in women with pathological hyperprolactinemia.  Fertil Steril . 1993;  59 671-673
  PubMedGoogle Scholar
• 43 Testa G, Vegetti W, Motta T. Two-year treatment with oral contraceptives in hyperprolactinemic patients.  Contraception . 1998;  58 69-73
  CrossrefPubMedGoogle Scholar
• 44 Camanni F, Ciccarelli E. Prolactinomas. In: Grossman A, ed. Clinical Endocrinology Oxford, UK: Blackwell Science 1998: 148-163
  Google Scholar
• 45 Randeva H S, Davis M, Prelevic G M. Prolactinoma and pregnancy.  Br J Obstet Gynaecol . 2000;  107 1064-1068
  PubMedGoogle Scholar
• 46 Molitch M E. Management of prolactinomas during pregnancy.  J Reprod Med . 1999;  44 (suppl 12) 1121-1126
  PubMedGoogle Scholar