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Cited by 86Adrenal Hormones and DisordersHormonal Regulation and HypertensionThyroid Disorders and Treatments

What is the best diagnostic and therapeutic management strategy for an Addison patient during pregnancy?

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Lebbe, Marie, Arlt, Wiebke·2013·Clinical Endocrinology
DOI 10.1111/cen.12097
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Abstract

Summary: A new diagnosis of primary adrenal insufficiency (PAI) during pregnancy is extremely rare and difficult to recognize as signs and symptoms such as nausea, fatigue and hypotension may resemble features of normal pregnancy. However, if the diagnosis is overlooked and steroid replacement delayed, subsequent adrenal crisis triggered by hyperemesis gravidarum, fever or delivery can cause severe maternal and foetal morbidity and even mortality. In case of clinical suspicion of PAI, we recommend to measure paired samples of cortisol and ACTH and, if clinically feasible, a short synacthen test. We propose trimester‐specific pass cut‐offs for the short synacthen test that take into account the rise of total and also free cortisol during pregnancy. Empirical hydrocortisone treatment should never be delayed if the clinical suspicion is high. All pregnant women with PAI should be monitored by a team of endocrine and obstetric specialists. The third trimester is physiologically associated with a rise not only in total but also free cortisol and thus requires regular adjustment of the glucocorticoid dose. Mineralocorticoid requirements may change during pregnancy due to the anti‐mineralocorticoid properties of progesterone. As plasma renin physiologically increases in pregnancy, monitoring is limited to clinical assessment including blood pressure and serum electrolytes. It is crucial that a pregnant woman with PAI and her partner are well educated regarding the adjustment of glucocorticoid dose in intercurrent illness and that both are trained in hydrocortisone emergency injection techniques. The obstetric staff should be provided with clear and written guidance for hydrocortisone cover during labour and delivery. With the appropriate replacement therapy, PAI patients can expect to have an uneventful pregnancy and deliver a healthy infant.

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Crossref · 10.1111/cen.12097

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  • From week 22 of gestation onward, free cortisol levels increase significantly, with a further rise immediately preterm due to a fall in CBG; cortisol levels return to normal after delivery.

    “From week 22 of gestation onward, free cortisol levels also increase significantly, with a further rise immediately preterm due to a fall in CBG (42, 119); cortisol levels return to normal after delivery (40).”

    From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [40]

    The 'Glucocorticoid synthesis in normal pregnancy' section (p. 2) reports rising free cortisol in the third trimester, and its figure caption describes a rapid drop after delivery. It does not specify an increase beginning at week 22 or a further rise immediately before term caused by falling CBG; instead, it reports that CBG increases during pregnancy and says the mechanism of the late rise in free cortisol is uncertain. (LLM, conf=0.86)

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  • Serum total and free cortisol is normally increased 20-40% in pregnancy.

    “Serum total and free cortisol is normally increased 20 -40% in pregnancy, so it may be advisable to prescribe a higher maintenance dose for women with adrenal insuf fi ciency in the latter stages of pregnancy [4, 33 -37].”

    From Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency (2020) · cites this paper as [37]

    The paper reports that total and free cortisol rise during pregnancy (Glucocorticoid synthesis in normal pregnancy, p. 2). It does not say they rise by 20–40%: that figure is the recommended increase in hydrocortisone dose for women with primary adrenal insufficiency (Points for guidance, p. 5). The paper describes third-trimester cortisol levels as reaching up to threefold those of nonpregnant controls. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Adrenal reserve is appropriately and safely assessed in pregnancy by corticotropin stimulation, if indicated.

    “In addition to a paired sample of cortisol and ACTH, the adrenal reserve is appropriately and safely assessed in pregnancy by corticotropin stimulation, if indicated (40,41).”

    From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [40]

  • It has been suggested to use higher diagnostic cortisol cutoffs of 700 nmol/L, 800 nmol/L, and 900 nmol/L for the first, second, and third trimesters, respectively.

    “Thus, it has been suggested to use higher diagnostic cortisol cutoffs of 700 nmol/L (25 g/ dL), 800 nmol/L (29 g/dL), and 900 nmol/L (32 g/dL) for the first, second, and third trimesters, respectively (40).”

    From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [40]

  • During normal pregnancy, circulating cortisol concentrations are increased 2- to 3-fold, with a continuous increase from the first trimester onward due to increases in CBG levels.

    “During normal pregnancy, circulating cortisol concentrations are increased 2-to 3-fold, with a continuous increase from the first trimester onward due to increases in CBG levels (40,42).”

    From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [40]

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Research works printed but not linked: 3

  1. 18 International Addison's Survey 2003, http://www.addisons.org. uk/topics/2005/02/0011.html
  2. 24 Gradden, C., Lawrence, D., Doyle, P.M., et al. (2011) Uses of error: Addison's disease in pregnancy. Lancet , 357 , 1197.
  3. 28 Agha, A., Tomlinson, J.W., Clark, P.M., et al. (2006) The longterm predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamic-pituitaryadrenal axis. Journal of Clinical Endocrinology and Metabolism , 91 , 43 -47.

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Authors
Lebbe, M., & Arlt, W.
Affiliations
University of Birmingham (GB)
Corresponding author
Arlt, Wiebke
ORCID
Arlt, Wiebke
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2013-03-12
Volume
78
Issue
4
Pages
497-502
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/cen.12097
OpenAlex
W2014845386
Cited by
86
References
30
Citations by year
2026: 2 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 2 · 2019: 11 · 2018: 7 · 2017: 8 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 7
FWCI
3.85
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
Medical Research Council (MR/J011592/1)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Keywords
Addison's disease, pregnancy, hydrocortisone replacement, ACTH stimulation test, free cortisol, ACTH, adrenal crisis, progesterone, plasma renin
MeSH terms
Addison Disease, Female, Glucocorticoids, Humans, Mineralocorticoids, Models, Biological, Pregnancy, Pregnancy Complications, Professional Practice

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