Background: Adrenal insufficiency (AI) in pregnancy is rare and diagnosis is challenging due to shared symptoms with healthy pregnancy and physiological activation of the hypothalamic–pituitary–adrenal axis (HPAa).Data describing causation in pregnancy is limited.
Methods: A retrospective cohort study of women who delivered at Mater Mothers’ Hospital, Brisbane, Australia, between January 2005 and December 2024. Laboratory databases were screened to identify pregnant women with severe hypocortisolaemia (serum cortisol <100 nmol/L). Biochemical and clinical data were reviewed to determine aetiology and indications for cortisol testing.
Results: Fifty-nine patients with severe hypocortisolaemia were identified among 106, 555 deliveries (1 in 1800 deliveries). Most cortisol samples were collected before 09:00 hours (66%). Iatrogenic factors accounted for 40/59 cases (68%), predominantly post-betamethasone administration (n=35) for fetal lung maturation. HPAa suppression persisted for up to 21 days following betamethasone. Opioid exposure was documented in 11 patients (19%), four with concurrent corticosteroid use. Addison disease was identified in four patients, including one new diagnosis. Single cases of lymphocytic hypophysitis, Sheehan syndrome, and hypocortisolaemia secondary to Ayurvedic therapy were identified. Electrolyte abnormalities, particularly hyponatraemia and/or hyperkalaemia, were the most common indication for cortisol testing.
Conclusions: Severe hypocortisolaemia deficiency in pregnancy predominantly occurs due to iatrogenic HPAa suppression. Hypocortisolaemia may be prolonged following antenatal betamethasone. While non-pharmacological induced hypocortisolaemia is rare, vigilance for HPAa insufficiency is critical, as timely recognition and management may prevent maternal and fetal morbidity and mortality.