Cabergoline-Resistant Recurrent Macroprolactinoma During Pregnancy: A Case Report and Review of the Literature

Abstract

We report a rare case of cabergoline-resistant recurrent macroprolactinoma during pregnancy. A 34-year-old woman, 17 weeks pregnant, presented with a four-week history of headache and a one-day history of visual disturbance. The medical history was significant for a macroprolactinoma with pituitary apoplexy, which was treated with an emergent pituitary resection approximately two years and four months before this presentation. At that time, postoperative prolactin levels improved but remained elevated despite gradually escalating cabergoline doses up to 6 mg per week. Our patient met the established criteria for cabergoline resistance, with persistently elevated prolactin levels despite high-dose cabergoline therapy. She was dealing with resistant hyperprolactinemia, causing infertility. The patient decided to conceive, and pre-pregnancy counseling was done by reproductive endocrinology, maternal-fetal medicine, and a genetic counselor. Before conception, magnetic resonance imaging (MRI) of the pituitary showed postoperative changes from transsphenoidal hypophysectomy and expanded partial sella, with no clear tumor, and the prolactin level was 228 ng/mL (non-pregnant normal reference range: 3-30 ng/mL). She had in vitro fertilization done, and cabergoline was discontinued on confirmation of pregnancy. On presentation, MRI of the pituitary revealed a recurrent pituitary macroadenoma (29 × 29 × 27 mm). She developed symptomatic tumor recurrence within three months of stopping cabergoline, and her prolactin level was 1,669.8 ng/mL (normal reference range in pregnancy: 10-209 ng/mL). She was treated with steroids, and cabergoline was restarted. However, the tumor continued to grow, causing symptoms necessitating repeat urgent pituitary resection in the second trimester of pregnancy. She remained on cabergoline through the rest of her pregnancy and delivered a healthy male neonate via cesarean section, done for breech presentation at 39 weeks. The postpartum, fetal, and neonatal stages were all uneventful. This case highlights the complexities of managing dopamine agonist-resistant macroprolactinomas during pregnancy and underscores the importance of individualized, multidisciplinary decision-making to optimize maternal and fetal outcomes.

Keywords: cabergoline resistance; hyperprolactinemia; macroprolactinoma; recurrent macroprolactinoma in pregnancy; transsphenoidal pituitary surgery.

Figure 1. MRI of the pituitary on admission showing recurrent pituitary macroadenoma (29 × 29 × 27 mm) with central hemorrhagic component, compression of the optic chiasm, suprasellar cistern extension, and projection into the right cavernous sinus.

MRI: magnetic resonance imaging

Figure 2. MRI of the pituitary five days after treatment showing a pituitary mass measuring 30 × 25 × 20 mm.

MRI: magnetic resonance imaging

Figure 3. Trends in serum prolactin levels over time in relation to diagnosis, treatment, and reproductive events.

Prolactin levels (ng/mL) from 2021 to 2024 are plotted against the clinical timeline. At diagnosis in 2021, prolactin was markedly elevated (1,603 ng/mL). Following TSS, levels decreased to 428 ng/mL, and while on cabergoline, prolactin level was 228 ng/mL before in vitro fertilization in 2023. Discontinuation of cabergoline during early pregnancy was associated with an increase in prolactin (1,669 ng/mL at 17 weeks), which peaked at 2,713 ng/mL prior to repeat TSS during pregnancy. Postoperatively, prolactin levels decreased but remained above the reference range (224 ng/mL). At three months postpartum, prolactin levels continued to be elevated (120 ng/mL) but lower compared to preoperative pregnancy levels, consistent with persistent biochemical disease despite ongoing dopamine agonist therapy. TSS: transsphenoidal surgery