Department of Internal Medicine, School of Medicine, Marmara University, Istanbul, Turkey
Vallatte-Kasic S, Morange-Ramos I, Selim A, et al. The macroprolactin problem. J Clin Endocrinol Metabol 2002;87:581-588
PRLs main role is to induce lactation. Hyperprolactinemia, resulting from hypersecretion of PRL by lactotroph cells, occurs as a result of some physiological or pathological conditions.
Physiologic causes of hyperprolactinemia include pregnancy and lactation. Pathologic hyperprolactinemia can be caused by a lactotroph adenoma, hypothalamic or pituitary tumors, D2 dopamin reseptor antagonist drugs or hypothyroidism. Additionally, despite hormonal and radiological workup, in some hyperprolactinemic patients the etiology can not be assessed. These conditions are called Idiopathic hyperprolactinemia.
PRL circulates in different forms. Normally, human PRL is synthesized as a pre-hormone with a molecular weight of 23000 kDa (Little PRL). Serum also contains big PRL(50000 kDa) and lesser amounts of big big PRL (molecular weight greater than 100000 kDa). Big big PRL consist of antigen-antibody complex of monomeric PRL and IgG. When the serum of a patient with hyperprolactinemia contains mostly big or big big PRL fraction, this condition is termed Macroprolactinemia. Recent studies have shown that macroprolactin has normal bioactivity in the NB2 bioassay. But the large PRL-Ig complex may fail to reach receptors because of a limited capacity to cross-vascular endothelium. Therefore big big PRL has decreased bioavailability.
SV Kasic and colleagues reported a prospective study of 1106 hyperprolactinemic patients from 1990 to 1999. These patients were evaluated and 368 cases were suggested to have macroprolactinemia. (These cases have no typical symptoms of hyperprolactinemia or pituitary lesions at MRI evaluation or no decrease in PRL level after medical or surgical treatment). Molecular chromatography was performed in these 368 cases.
As a result of the,chromatographic evaluation, 106 patients (%29) had macroprolactinemia. (Of all hyperprolactinemic patients, %10 have macroprolactinemia.). 37 of macroprolactinemic women (%39) had menstrual disorders, 44 (%46) had galactorea and 25(%26) had infertility. When macroprolactinemic patients compared with the hyperprolactinemic patients, menstrual disorders, galactorea and infertility were significantly less frequent in the first group. This finding shows that macroprolactin has weak bioactivity in vivo.
A pituitary MRI was performed on 81 macroprolactinemic patients. Of these patients, 3 had rarely, microadenoma, 2 had macroadenoma and 5 intrasellar pituitary cyst were found. It is known that macroprolactinemia may be associated with any other causes of hyperprolactinemia, such as autoimmune thyroid disorders, pituitary adenoma..) This association may be coincidental. The previous studies showed that about %10 of the normal population have radiographic findings of pitultary adenoma.
This study reported that;
1-Macroprolactinemia is a common and overlooked cause of hyperprolactinemia (10% of all hyperprolactinemic cases).
2-Some of the symptoms of hyperprolactinemia may be present in macroprolactinemia patients
3-Pituitary lesions (eg.prolactinoma) may be found in macroprolactinemic patients..
4-Dopaminergic treatment may be beneficial in a small group of macroprolactinemic patients. (But this treatment is still under investigation)
If macroprolacinemia is diagnosed there is no need for repeated hormonal and radiological investigations and no treament is needed.