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Adrenal insufficiency in pregnancy: Physiology, diagnosis, management and areas for future research

Abstract

Adrenal insufficiency requires prompt diagnosis in pregnancy, as untreated, it can lead to serious consequences such as adrenal crisis, intrauterine growth restriction and even foetal demise. Similarities between symptoms of adrenal insufficiency and those of normal pregnancy can complicate diagnosis. Previously diagnosed adrenal insufficiency needs monitoring and, often, adjustment of adrenal hormone replacement. Many physiological changes occur to the hypothalamic–pituitary–adrenal (HPA) axis during pregnancy, often making diagnosis and management of adrenal insufficiency challenging. Pregnancy is a state of sustained physiologic hypercortisolaemia; there are multiple contributing factors including high plasma concentrations of placental derived corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and increased adrenal responsiveness to ACTH. Despite increased circulating concentrations of CRH-binding protein (CRH-BP) and the major cortisol binding protein, corticosteroid binding globulin (CBG), free concentrations of both hormones are increased progressively in pregnancy. In addition, pregnancy leads to activation of the renin–angiotensin–aldosterone system. Most adrenocortical hormone diagnostic thresholds are not applicable or validated in pregnancy. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid and at times mineralocorticoid replacement, especially in the last trimester. In this review, we describe pregnancy induced changes in adrenal function, the diagnosis and management of adrenal insufficiency in pregnancy and areas requiring further research.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

AD:

Addison’s disease

AI:

Adrenal insufficiency

APS:

Autoimmune polyendocrine syndrome

CAH:

Congenital adrenal hyperplasia

CBG:

Corticosteroid binding globulin

CRH:

Corticotropin releasing hormone

CRH-BP:

Corticotropin releasing hormone binding protein

HPA :

Hypothalamic–pituitary–adrenal

NCCAH :

Non-classic congenital adrenal hyperplasia

pCRH:

Placental corticotropin releasing hormone

PNMT:

Phenylethanolamine N-methyltransferase

PRA:

Plasma renin activity

RAAS:

Renin-angiotensin-aldosterone system

11β-HSD1:

11 Beta hydroxysteroid dehydrogenase type 1

11β-HSD2:

11 Beta hydroxysteroid dehydrogenase type 2

11- DOC:

11 Deoxycorticosterone

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Lee, J.H., Torpy, D.J. Adrenal insufficiency in pregnancy: Physiology, diagnosis, management and areas for future research. Rev Endocr Metab Disord (2022). https://doi.org/10.1007/s11154-022-09745-6

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Keywords

  • Adrenal insufficiency
  • Pregnancy
  • Primary adrenal insufficiency
  • Secondary adrenal insufficiency
  • Corticosteroid binding globulin