Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency: Experience from a Multicenter Survey

Abstract

Context Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Objective Multicenter survey on current clinical approaches in managing AI during pregnancy. Design Retrospective anonymized data collection from 19 international centers from 2013 to 2019. Setting and Patients 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Results Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. Conclusions This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

Case Report: Late-Onset Congenital Adrenal Hyperplasia and Acute Covid-19 Infection in a Pregnant Woman: Multidisciplinary Management

“…By suppressing ACTH production, glucocorticoids can normalise the excessive androgen production and can be used in symptomatic patients to increase fertility and during pregnancy ( 3 , 5 – 7 ). However, during pregnancy and especially in NCAH, most experts do not recommend dexamethasone, a category C drug that passes the placenta and has potential adverse effects on both mother and fetus ( 3 , 6 , 8 ).…”

Clinical Unmet Needs in the Treatment of Adrenal Crisis: Importance of the Patient’s Perspective

“…Pregnancy can be considered as a state of hypercortisolism due to general increase in the activity of the HPA-axis, and is associated with a gradual but significant increase of corticosteroid-binding globulin and total serum cortisol concentrations. During the third trimester, free cortisol concentrations rise, altogether explaining the need for higher hydrocortisone doses in AI patients (2.5 to 10mg increase of daily dose, 20 to 40% between different studies) ( 1 , 73 ). Since serum progesterone has anti-mineralocorticoid effects, fludrocortisone dose often needs also to be increased in the third trimester in patients with primary AI ( 74 ).…”

“…Since serum progesterone has anti-mineralocorticoid effects, fludrocortisone dose often needs also to be increased in the third trimester in patients with primary AI ( 74 ). Although literature on the incidence of adrenal crisis among pregnant AI patients is scarce, a recent multicenter study of Bothou et al described the course of 128 pregnancies among 113 women with different AI etiology ( 73 ). In this report, glucocorticoid dose was increased in 57% of patients during pregnancy, whereas mineralocorticoid dose was increased only in a minority of patients.…”

“…In this report, glucocorticoid dose was increased in 57% of patients during pregnancy, whereas mineralocorticoid dose was increased only in a minority of patients. Moreover, adrenal crisis was reported in 9 out of 128 patients (7%) during pregnancy, which was triggered by hyperemesis gravidarum in a significant proportion of patients ( 73 ).…”

Risk of miscarriage in women with chronic diseases in Norway: A registry linkage study

“…Various studies of specific illnesses have suggested an association with risk of miscarriage. These include systemic lupus erythematosus [7], type 1 diabetes [8,9], celiac disease [10,11], asthma/allergies [12], thyroid disorders [13][14][15][16], Addison disease [17,18], type 2 diabetes [9,19,20], parathyroid disorders [21,22], Cushing syndrome [23], migraine [24], and epilepsy [25,26]. These scattered findings suggest that immunological, metabolic, or endocrinological mechanisms might be linked to miscarriage risk, any of which is biologically plausible since all play a role in development and function of the placenta [27][28][29][30].…”