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141 acromegalic pregnancies per study), and 11 single cases reports (a total of 344 pregnancies and an additional prior unpublished report).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.
摘要：
肢端肥大症相关亚/不孕症，与疾病控制欠佳相关(1/2的病例)，与高催乳素血症相关（1/3的患者），低促性腺激素性性腺功能减退-主要影响垂体功能减退中的垂体轴（10-80％），以及葡萄糖分布(GP)异常的负面影响(10-70%)；因此，怀孕是一个特殊的事件。胎盘GH（生长激素）从第5-15周增加，在第37周达到峰值，刺激肝脏IGF1并抑制正常垂体分泌的垂体GH，不是生长激素瘤。然而,雌激素诱导GH抗性状态，保护胎儿形成GH过量；因此足月，健康的怀孕是可能的。这是接近心脏代谢特征（CMFs）的肢端肥大症的叙述性综述，生长激素瘤扩大（STE），妊娠期管理调整（MNA）和母胎结局（MFOs）。根据我们的方法(原始，简而言之，在PubMed上发表的英文文章，2012年1月至2022年9月)，我们确定了24篇原始论文-13项研究（每项研究3至141例肢端肥大症妊娠），和11个单一病例报告(总共344例怀孕和一份先前未公布的额外报告)。关于产妇肢端肥大症，怀孕是自发的或由于不孕症的治疗(克罗米芬，促性腺激素或GnRH)和，最近,辅助生殖技术（ARTs）；关于父体肢端肥大症的妊娠没有一致的数据。CMFs是最重要的并发症（7.7-50％），特别是关于HBP（包括先兆/子痫）和GP异常的恶化，包括妊娠期糖尿病（DM）;最好的预测指标是怀孕时的疾病控制水平（IGF1），and,可能,2型糖尿病家族史,和体重指数。STE很少发生（发生率为0％至9％）；其中一些症状是头痛和视野异常；用生长抑素类似物（SSAs）或多巴胺激动剂（DAs）治疗；最近，孕中期选择性垂体切除术的使用较少，因为药物治疗（PT）已被证明是安全的。MNA：PT，理论上,需要在受孕前停止-如果有STE或无法手术的肿瘤(没有明确的暴露期，最好是,只有前三个月)。大多数数据是关于奥曲肽和gt;lanreotide，其次是DAs和pegvisomant，Pasireotide上没有。需要进一步的随访：及时对母亲的疾病进行产后重新评估；我们只有少数数据证实了哺乳期SSA的安全性以及新生儿的长期正常生长和发育（最长为15年）。PT+ve和PT-ve之间的MFO似乎相似，无论PT持续时间如何；额外的风险实际上是由于CMF。一项研究显示，垂体切除术和妊娠之间的中位数为2年。结论:需要密切监测疾病负担,特别是,关于CMF；个性化方法是有用的；由于MNA和ART的最新进展，统计证据的水平预计将扩大。
