Approach of Acromegaly during Pregnancy

Abstract

Acromegaly-related sub/infertility, tidily related to suboptimal disease control (1/2 of cases), correlates with hyperprolactinemia (1/3 of patients), hypogonadotropic hypogonadism—mostly affecting the pituitary axis in hypopituitarism (10−80%), and negative effects of glucose profile (GP) anomalies (10−70%); thus, pregnancy is an exceptional event. Placental GH (Growth Hormone) increases from weeks 5−15 with a peak at week 37, stimulating liver IGF1 and inhibiting pituitary GH secreted by normal hypophysis, not by somatotropinoma. However, estrogens induce a GH resistance status, protecting the fetus form GH excess; thus a full-term, healthy pregnancy may be possible. This is a narrative review of acromegaly that approaches cardio-metabolic features (CMFs), somatotropinoma expansion (STE), management adjustment (MNA) and maternal-fetal outcomes (MFOs) during pregnancy. Based on our method (original, in extenso, English—published articles on PubMed, between January 2012 and September 2022), we identified 24 original papers—13 studies (3 to 141 acromegalic pregnancies per study), and 11 single cases reports (a total of 344 pregnancies and an additional prior unpublished report). With respect to maternal acromegaly, pregnancies are spontaneous or due to therapy for infertility (clomiphene, gonadotropins or GnRH) and, lately, assisted reproduction techniques (ARTs); there are no consistent data on pregnancies with paternal acromegaly. CMFs are the most important complications (7.7−50%), especially concerning worsening of HBP (including pre/eclampsia) and GP anomalies, including gestational diabetes mellitus (DM); the best predictor is the level of disease control at conception (IGF1), and, probably, family history of 2DM, and body mass index. STE occurs rarely (a rate of 0 to 9%); some of it symptoms are headache and visual field anomalies; it is treated with somatostatin analogues (SSAs) or alternatively dopamine agonists (DAs); lately, second trimester selective hypophysectomy has been used less, since pharmaco-therapy (PT) has proven safe. MNA: PT that, theoretically, needs to be stopped before conception—continued if there was STE or an inoperable tumor (no clear period of exposure, preferably, only first trimester). Most data are on octreotide > lanreotide, followed by DAs and pegvisomant, and there are none on pasireotide. Further follow-up is required: a prompt postpartum re-assessment of the mother’s disease; we only have a few data confirming the safety of SSAs during lactation and long-term normal growth and developmental of the newborn (a maximum of 15 years). MFO seem similar between PT + ve and PT − ve, regardless of PT duration; the additional risk is actually due to CMF. One study showed a 2-year median between hypophysectomy and pregnancy. Conclusion: Close surveillance of disease burden is required, particularly, concerning CMF; a personalized approach is useful; the level of statistical evidence is expected to expand due to recent progress in MNA and ART.

Keywords: acromegaly; cabergoline; diabetes mellitus; growth hormone; lanreotide; octreotide; pegvisomant; pituitary; pregnancy; prolactin; somatostatin; somatotropinoma.

Figure 1

GH amid physiological and acromegalic pregnancy. In non-acromegalic pregnancy pituitary GH is inhibited by the increasing placental GH which takes control of IGF1 levels. In acromeglaic pregnancy, somatotropinoma continues to produce GH, but its actions are antagonized due to estrogen-induced blockade. Abbreviations: GH = Growth Hormone (see references [30,31,32,33,34,35,36,37,38,39,40,41,42,43]).

Figure 2

This is a 34-year-old acromegalic patient with suggestive facial (left) and hand (right) features for GH excess.

Figure 3

Magnetic resonance imaging of the somatotropinoma (2.4 by 3.3 by 2.5 cm) at initial diagnostic. (A) Coronal post-contrast aspect. (B) Sagittal post-contrast aspect. (C) Post-operatory aspect (2 months since selective trans-sphenoidal hypophysectomy)—a somatotropinoma of 2.4 by 3.1 by 2.2 cm.

Figure 3

Magnetic resonance imaging of the somatotropinoma (2.4 by 3.3 by 2.5 cm) at initial diagnostic. (A) Coronal post-contrast aspect. (B) Sagittal post-contrast aspect. (C) Post-operatory aspect (2 months since selective trans-sphenoidal hypophysectomy)—a somatotropinoma of 2.4 by 3.1 by 2.2 cm.

Figure 4

Magnetic resonance imaging of the somatotropinoma during follow-up. (A) Before second pituitary surgery (5 years postpartum)—a somatotropinoma of 3.8 by 0.8 by 1.1 cm, with superior and right extension and invasion at the level of cavernous sinus. (B) During follow-up: 2 months since second neurosurgery—a pituitary macroadenoma of 2.8 by 0.8 by 1.0 cm with right cavernous sinus invasion. (C) The most recent evaluation under triple medical therapy—6 years since the second pituitary intervention (status quo versus 3.B.)

Figure 4

Magnetic resonance imaging of the somatotropinoma during follow-up. (A) Before second pituitary surgery (5 years postpartum)—a somatotropinoma of 3.8 by 0.8 by 1.1 cm, with superior and right extension and invasion at the level of cavernous sinus. (B) During follow-up: 2 months since second neurosurgery—a pituitary macroadenoma of 2.8 by 0.8 by 1.0 cm with right cavernous sinus invasion. (C) The most recent evaluation under triple medical therapy—6 years since the second pituitary intervention (status quo versus 3.B.)