Growth of a microprolactinoma to a macroprolactinoma during estrogen therapy

Abstract

Following presentation and diagnosis, microprolactinomas usually follow a benign course and rarely progress to macroprolactinomas. However, clinically significant enlargement of prolactinomas during pregnancy, presumably related to estrogen stimulation, has been reported. This report describes a patient with amenorrhea and hyperprolactinemia and a microadenoma by computed tomography scan who developed a macroprolactinoma within 10 months after being placed on estrogen therapy. We propose that exogenous estrogen administration in this patient most likely promoted growth from a microprolactinoma to a macroprolactinoma. This case emphasizes the primary role of dopaminergic agonist therapy in the management of pathological hyperprolactinemia and suggests that estrogen therapy should not be casually given to patients with known prolactinomas to avoid the possibility of promoting tumor growth. A correlate of this approach is that caution regarding estrogen therapy should also be exercised in patients with idiopathic hyperprolactinemia who might have an occult microprolactinoma which could grow following estrogen stimulation. If estrogen treatment is deemed necessary, dopaminergic agonist therapy should also be used prophylactically to prevent potential tumor growth due to estrogen. The patient should then be carefully monitored with periodic serum PRLs and for the development of clinical manifestations suggesting pituitary growth. An imaging study should be performed when there is a significant increase in serum PRL or the development of new clinical manifestations.

Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals

“…There are reports of the development of prolactinemia in a male to female transsexual receiving massive doses of estrogen [19]. There is evidence of growth of microprolactinoma to a macroprolactinoma during estrogen therapy [20]. Women taking oral estrogen contraceptive showed higher PRL levels [21].…”

Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk

“…Thus, the number of lactotroph cells increases during pregnancy (1). Prolactinomas occur more frequently in women and increase in size during pregnancy or estrogen treatment (2,3), and, at least in human prolactinomas, estrogen receptor (ER) expression is positively related to size (4). Dominant-negative ER inhibits growth of lactotroph cells in nude mice (5).…”

Role of Protein Kinase C-Ras-MAPK p44/42 in Ethanol and Transforming Growth Factor-β3-Induced Basic Fibroblast Growth Factor Release from Folliculostellate Cells

“…Alcohol drinking and estrogen exposure have both been considered risk factors for the development of prolactin-secreting pituitary tumors known as prolactinomas in humans and laboratory animals (Gooren et al, 1988;Garcia and Kapcala, 1995;De et al, 2002). There are several reports showing evidence of high levels of prolactin in chronic alcoholic men and women (Mello et al, 1988;Vä limä ki et al, 1990;Seki et al, 1991;Gavaler, 1994;Teoh et al, 1994).…”