Uterine Fibroid Causing Hyperprolactinemia and Paradoxical Prolactin Rise with Dopamine Agonist: Case Report and Systematic Review

Abstract

Hyperprolactinemia in premenopausal women often presents with amenorrhea, symptoms of estrogen deficiency and subfertility. After exclusion of other common causes and in the context of a normal pituitary MRI scan, hyperprolactinemia is typically deemed "idiopathic." Here we present a case where excess prolactin secretion was attributed to a uterine fibroid and following myomectomy the hyperprolactinemia and its clinical sequelae resolved. Following 6 years of secondary infertility, a 41-year-old woman presented with secondary amenorrhea, expressible galactorrhea, and symptoms of estrogen deficiency. Prolactin levels were consistently raised (1300 mU/L to 2100 mU/L, reference interval < 600 mU/L), and repeated pituitary imaging demonstrated no pituitary abnormality. Prolactin levels demonstrated a paradoxical rise in response to dopamine agonist therapy (2000 mU/L to 5900 mU/L). Imaging demonstrated a uterine fibroid and the patient underwent myomectomy. Following myomectomy, prolactin levels became undetectable, galactorrhea and symptoms of estrogen deficiency resolved, menses returned, and a planned unassisted pregnancy followed. Ectopic prolactin secretion from uterine fibroids is a rare cause of hyperprolactinemia and can result in the same clinical sequelae as pituitary causes. As ectopic prolactin secretion is not under inhibitory control of dopamine, it is usually resistant to, or may rise in response to, dopamine agonist therapy. Prior to a diagnosis of "idiopathic" hyperprolactinemia, ectopic sources of prolactin should be considered.

Prolactinoma or leiomyoma-associated hyperprolactinemia—this is the question, a case report and review of the literature

“…Only a few case reports in the literature presented patients with leiomyoma-associated hyperprolactinemia (Table 1, Ref. [5,6,9,10,[16][17][18][19][20][21]). Common characteristics of all cases were the presence of normal pituitary gland, large uterine fibroids (at least 5.5 cm), mild to moderate prolactin increase with classic clinical symptoms, complete resistance to dopamine agonist treatment, a rapid decrease of the hormonal concentrations after tumour removal, and negative immunostaining for prolactin by an immunohistochemical study of the leiomyomas [9,[16][17][18][19].…”

Prolactin-Secreting Leiomyoma Causing Hyperprolactinaemia Unresponsive to Dopamine Agonist Therapy and Resolution following Myomectomy

“…However, of the 6 leiomyomas reported, only one case reported positive immunostaining for prolactin [ 3 ]. Four cases, including this case, did not exhibit immunostaining for prolactin [ 7 – 9 ], and two were not reported [ 5 , 6 ].…”

“…With regards to pituitary prolactinomas, serum prolactin is generally directly proportionate to the size of the tumour, with a tumour >4 cm correlating to a serum prolactin level of ≥5276 mIU/L [ 20 ]. Each of the six cases including this case reported large leiomyomas >8 cm [ 3 , 9 ], but all with moderately raised prolactin levels (≤5900 mIU/L). This suggests the leiomyomas are likely poorly differentiated with only small focal areas secreting prolactin.…”

“…ere are 8 cases in literature reporting resolution of hyperprolactinaemia after removal of a uterine mass [3][4][5][6][7][8][9][10]. Six of the eight cases revealed leiomyomas on histopathology [3,[5][6][7][8][9].…”

“…ere are 8 cases in literature reporting resolution of hyperprolactinaemia after removal of a uterine mass [3][4][5][6][7][8][9][10]. Six of the eight cases revealed leiomyomas on histopathology [3,[5][6][7][8][9]. Of the two other cases, histopathology revealed a low-grade mesenchymal tumour [4] and a uterine tumour resembling ovarian sex cord tumour [10].…”