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  • Review Article
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Adrenal disorders in pregnancy

Nature Reviews Endocrinology volume 8, pages 668–678 (2012)Cite this article

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Abstract

Pregnancy is marked by alterations in a number of endocrine systems, including activation of the renin–angiotensin–aldosterone system and the hypothalamic–pituitary–adrenal axis. The placenta, the fetal adrenal glands and the liver constitute an interactive endocrine entity, known as the fetoplacental unit. In the fetoplacental unit, the fetal adrenal glands are the primary source of dehydroepiandrosterone sulphate, which is further metabolized by the fetal liver and placenta to produce a variety of oestrogens. Several disorders can affect both the fetal and maternal adrenal glands during pregnancy. The most common fetal adrenal disorder, steroid 21-hydroxylase deficiency, leads to abnormalities in sexual development and can be life threatening for the neonate. Although rare, maternal adrenal disorders are associated with considerable maternal mortality and morbidity if not promptly recognized and treated. However, diagnosis is often difficult to establish because of the endocrine changes occurring during normal pregnancies and the lack of reference values for the majority of the adrenal steroids. This Review provides an overview of adrenal steroid metabolism during pregnancy and focuses on diagnosis and treatment of the most common fetal and maternal adrenal disorders.

Key Points

  • Adrenal disorders are rare in pregnancy but are associated with considerable maternal and fetal mortality and morbidity if not promptly diagnosed and treated

  • CYP21A2 deficiency is the most common cause of congenital adrenal hyperplasia, which causes fetal androgen excess and female fetus virilization; however, the placenta protects the mother against androgen exposure

  • The most frequent cause of Cushing syndrome during pregnancy is an adrenocortical adenoma; surgical treatment is recommended to improve fetal and maternal outcomes

  • Primary aldosteronism can improve spontaneously during pregnancy and is often successfully controlled with medical therapy

  • If pheochromocytoma is diagnosed during pregnancy, adrenalectomy should always be considered, as untreated pheochromocytoma is associated with maternal mortality as high as 48%

  • Adrenal insufficiency can be undiagnosed during pregnancy because circulating levels of cortisol increase twofold to threefold in pregnant women, such that plasma and urinary cortisol values within the nonpregnant normal range are misinterpreted as normal

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Figure 1: Adrenal gland histology.
Figure 2: Steroidogenic enzyme expression pattern in the unique fetal adrenal zones and the steroids produced.
Figure 3: The placenta, in concert with the fetal adrenal glands and liver, constitutes an interactive endocrine entity, known as fetoplacental unit.
Figure 4: The diagnosis and treatment of primary aldosteronism during pregnancy.
Figure 5: The diagnosis and treatment of Cushing syndrome during pregnancy.
Figure 6: The diagnosis and treatment of pheochromocytoma during pregnancy.

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Authors and Affiliations

  1. Department of Physiology, Georgia Health Sciences University, 1120 15th Street, Augusta, 30912, GA, USA

    Silvia Monticone & William E. Rainey

  2. Division of Metabolism, Department of Internal Medicine, Endocrinology and Diabetes, University of Michigan Medical School, Room 5560A, MSRBII, 1150 West Medical Center Drive, Ann Arbor, 48109, MI, USA

    Richard J. Auchus

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  1. Silvia Monticone
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  2. Richard J. Auchus
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All authors contributed equally to all aspects of the article (researching data for the article, discussion of the content, writing the manuscript, and review or editing of the manuscript before submission).

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Correspondence to William E. Rainey.

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Supplementary information

Supplementary Table 1

Adrenal-related hormone levels in pregnant and non-pregnant women (DOC 46 kb)

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Monticone, S., Auchus, R. & Rainey, W. Adrenal disorders in pregnancy. Nat Rev Endocrinol 8, 668–678 (2012). https://doi.org/10.1038/nrendo.2012.155

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