The diagnosis and management of Cushing's syndrome in pregnancy

Abstract

Endogenous Cushing's syndrome (CS) is rarely encountered during pregnancy. Clinical and biochemical changes in healthy pregnancy overlap with those seen in pregnancy complicated by CS; the diagnosis is therefore challenging and can be delayed. During normal gestation, adrenocorticotrophic hormone, corticotrophin-releasing hormone, cortisol, and urinary free cortisol levels rise. Dexamethasone administration fails to fully suppress cortisol in pregnant women without CS. Localisation may be hindered by non-suppressed adrenocorticotrophic hormone levels in a large proportion of those with adrenal CS; smaller corticotroph adenomas may go undetected as a result of a lack of contrast administration or the presence of pituitary hyperplasia; and inferior petrosal sinus sampling is not recommended given the risk of radiation and thrombosis. Yet, diagnosis is essential; active disease is associated with multiple insults to both maternal and foetal health, and those cured may normalise the risk of maternal-foetal complications. The published literature consists mostly of case reports or small case series affected by publication bias, heterogeneous definitions of maternal or foetal outcomes or lack of detail on severity of hypercortisolism. Consequently, conclusive recommendations, or a standardised management approach for all, cannot be made. Management is highly individualised: the decision for surgery, medical control of hypercortisolism or adoption of a conservative approach is dependent on the timing of diagnosis (respective to stage of gestation), the ability to localise the tumour, severity of CS, pre-existing maternal comorbidity, and, ultimately, patient choice. Close communication is a necessity with the patient placed at the centre of all decisions, with risks, benefits, and uncertainties around any investigation and management carefully discussed. Care should be delivered by an experienced, multidisciplinary team, with the resources and expertise available to manage such a rare and challenging condition during pregnancy.

Keywords: Cushing's syndrome; pregnancy; adrenal adenoma; hypercortisolism; pituitary tumour.

FIGURE 1

Aetiology of 213 gestations with active Cushing's syndrome (CS) (data reported by Caimari et al.⁵). Includes both those with active disease during pregnancy and those newly diagnosed with CS within 12 months of pregnancy. Abbreviations: ACTH, adrenocorticotrophic hormone

FIGURE 2

Treatment algorithm for management of Cushing's syndrome (CS) in pregnancy. Given limited evidence, this should be used as a guide only. Abbreviations: AA, adrenal adenoma; TSS, transsphenoidal surgery

FIGURE 3

Schematic highlighting the challenges associated with a diagnosis of Cushing's syndrome (CS) in pregnancy. Abbreviations: ACTH, adrenocorticotrophic hormone; CRH, corticotrophin‐releasing hormone; IPSS, inferior petrosal sinus sampling; UFC, urinary free cortisol