Medical treatment of acromegaly in pregnancy, highlights on new reports.

Abstract

In this issue of Endocrine, van der Lely et al. [1] provided a well-written, extensive review of all reported cases of pegvisomant use in pregnancy, (mother and father) from a large safety database. Acromegaly is a relatively rare disease, caused by a growth hormone (GH) secreting pituitary adenoma [2]; however, reports now suggest disease incidence might be higher than previously reported, with women and men equally affected [2–4]. Hypogonadism is reported in approximately 70 % of patients with acromegaly [2]. The decreased rate of fertility in women with acromegaly is multifactorial. Gonadotrope reserve can be lower due to mass tumor effect, stalk effect or subsequent to surgery or radiation [5]. The hyperprolactinemia in mixed tumors also plays a role, while GH/insulin-like growth factor 1 (IGF-1) excess per se has been noted to have direct effect on the ovaries. Nevertheless, over the last two decades, more women with acromegaly achieve successful pregnancy [5]. This is due to improved outcomes after transsphenoidal surgery, use of medical therapy as a first line treatment in many patients, and delegation of pituitary radiation to a third line treatment, and of course advances in fertilization techniques. How to better care for women with acromegaly is complex and not well studied [5]. Management of acromegaly in patients desiring pregnancy should include optimizing biochemical control and maximizing tumor shrinkage before becoming pregnant [5–8]. After becoming pregnant, most reports recommend stopping all medical treatment for acromegaly [5, 9, 10] and restarting only if severe symptoms (headache for example), visual changes, or tumor growth are present. Interestingly, acromegaly symptoms usually improve during pregnancy. A diagnosis of new onset acromegaly while pregnant is problematic due to the complex issue of measuring GH, which includes placental GH and GH resistance in the presence of high estrogen [5]. The focus of this editorial will be medical treatment of acromegaly during pregnancy, with a review of new data regarding pegvisomant use during pregnancy, published in this issue [1]. Rather than summarizing study-related findings, comments will focus on current, if somewhat limited data on outcomes after acromegaly treatment in pregnancy. For example, do physicians need to treat and if yes, which approach should be pursued? Pregnancy has not been found to change the course of acromegaly, other than, in rare cases of asymptomatic tumor enlargement, which may or may not be related to physiologic pituitary hyperplasia [5, 9]. Tumor enlargement may also be theoretically triggered by somatostatin receptor ligand (SRL) discontinuation at pregnancy onset. The literature indicates an increased risk of gestational diabetes and gravid hypertension in women with noncontrolled GH/IGF-1 hypersecretion before gestation, which must be appropriately and aggressively treated, but in most patients, specific acromegaly therapy can be delayed until after delivery. Based on experience with dopamine agonists (DAs) in prolactinomas, bromocriptine and cabergoline have constituted the initial treatment of choice for acromegaly in pregnancy; however, efficacy is limited outside of mild cases. & Maria Fleseriu fleseriu@ohsu.edu