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Cushing’s Syndrome during Pregnancy: Personal Experience and Review of the Literature
Abstract
Cushing's syndrome (CS) occurs rarely during pregnancy. We investigated and treated four patients with pituitary-dependent Cushing's syndrome during pregnancy over a 15-yr period at the National Institutes of Health. Except for preservation of menses before conception, our patients presented with typical clinical features, increased urinary free cortisol, and loss of diurnal variation of cortisol. The diagnosis was facilitated, without complications, by the use of CRH testing and inferior petrosal sinus sampling in three women. Transsphenoidal pituitary surgery achieved remission in three women, but there were two fetal/neonatal deaths. This experience and review of 136 previous reports suggest that: 1) urinary free cortisol in CS patients overlaps the normal pregnant range; 2) ACTH levels are not suppressed in adrenal causes of CS, which may be identified by the 8-mg dexamethasone test; 3) inferior petrosal sinus sampling and transsphenoidal pituitary surgery, the optimal diagnostic test and treatment for nonpregnant patients with pituitary-dependent Cushing's syndrome, can safely facilitate the management of pregnant patients; and 4) surgery may achieve remission during pregnancy, but the prognosis for the fetus remains guarded. It is likely that earlier recognition and treatment would improve outcome. There is a need for development of criteria for interpretation of diagnostic tests and increased consideration of CS in pregnancy.
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In the citing paper
“During the second trimester, UFC also increases, leading to an approximately 1.4-fold increase during the second trimester and a 1.6-fold increase during the third trimester.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
In the citing paper
“Fetal morbidity includes rates of spontaneous abortion, perinatal death, premature birth, and intrauterine growth retardation (see Figure 4).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
In the citing paper
“The biochemical diagnosis of CS during pregnancy can also be more challenging because of normal physiologic changes that occur during pregnancy, including activation of the HPA axis.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
In the citing paper
“Suppression of serum and plasma cortisol by dexamethasone is blunted during pregnancy; therefore, making the DST difficult to interpret in these patients (3, 90, 92).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
In the citing paper
“Early diagnosis and management of CS during pregnancy are important because of associated fetal and maternal morbidity.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
In the citing paper
“Starting in the first trimester, there is an increase in estrogen and CRH produced by the placenta, which can lead to an increase in corticosteroid-binding globulin, a plasma cortisol transport protein.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
In the citing paper
“Maternal morbidity caused by CS includes hypertension, preeclampsia, wound breakdown, diabetes, fractures, and opportunistic infections (2, 92).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
In the citing paper
“This in combination with the rise in placental CRH and ACTH cause an increase in total plasma cortisol levels.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [92]
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“Patient with adrenal Cushing may be identified with this test as they don’t suppress, but the test may misclassify those with Cushing disease, as three of seven cases failed to suppress in small series (Lindsay et al., 2005).”
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“Although metyrapone is not FDA approved for use during pregnancy, it has been found in the literature to be suitable for monotherapy in pregnant patients (Gormley et al., 1982; Lindsay et al., 2005).”
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“There are reports indicating that individuals with suspected Cushing ’ s syndrome in the early stages of pregnancy received a de fi nitive diagnosis of Cushing ’ s disease through the use of high-resolution MRI and bilateral inferior petrosal sinus sampling (BIPSS) (14).”
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“There are also very few reports of patients becoming pregnant after being diagnosed with CS (2).”
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“Second, the clinical signs of hypercortisolism (weight gain, fatigue, hypertension, and hyperglycemia) overlap with the physiological changes that characterize pregnancy [2,5].”
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InfluentialCushing’s Syndrome and a Dead Fetus in Pregnancy: A Clinical Case and Behavior Report
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“13 14 Diagnosing Cushing’s syndrome during pregnancy is complex due to the physiological elevation in cortisol driven by multiple mechanisms.”
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“This discrepancy in etiology patterns is likely due to the lower incidence of suppression of the hypothalamic-pituitary-adrenal (HPA) axis in adrenal CS [5].”
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“This is remarkable, as not only hypercortisolism (38, 39) but also exposure to DDT and its isomers may affect fertility and pregnancy outcomes negatively (40 – 42).”
BackgroundCushing’s Disease in Pregnancy and Cabergoline Use: Obstetric and Neonatal Outcomes
Murillo, N. B., Ramacciotti, C. F., Otta, C. F., & Cecenarro, L. A. (2023) · Advances in Obstetrics and Gynecology Research · doi:10.26689/aogr.v1i1.4947
“This is the reason they are contraindicated during pregnancy (Table 2) ([5,15]).”
BackgroundL’ipertensione arteriosa in gravidanza
Sabbadin, C., & Armanini, D. (2023) · L Endocrinologo · doi:10.1007/s40619-023-01266-x
“La diagnosi eziologica non è raccomandata per mancanza di dati sui test di II livello in gravidanza e per gli effetti teratogeni delle indagini strumentali [18].”
BackgroundCushing Syndrom in der Schwangerschaft, eine diagnostische Herausforderung – Case Report
Semrl, N., Obermayer-Pietsch, B. M., Feigl, S., Ragossnig, M., Wölfler, M. M., Taumberger, N., Kirchhoff, E., Hochstätter, R., Kurleto, M., & Kollmann, M. (2022) · Geburtshilfe und Frauenheilkunde · doi:10.1055/s-0042-1750254
Endocrine diseases and pregnancy
Brietzke, S. (2021) · CRC Press eBooks · doi:10.1201/9781003222590-20
“or carpopedal or laryngospasm) should be treated with intravenous infusion of 10% calcium gluconate, 20mL intravenously over 10minutes, followed by continuous intravenous drip infusion of calcium 0.5 to 2mg/kg/hr, adjusted to keep the plasma calcium level at 8 to 9mg/dL (97).”
InfluentialThree Successful Pregnancies in a Patient with Recurrent Cushing’s Disease
Benothman, W., Saad, G., Kacem, M., & Ach, K. (2021) · Case Reports in Endocrinology · doi:10.1155/2021/5517303 · Cited by 1
“*e most frequently stated maternal complications in CS are hypertension (68%), diabetes (25%), preeclampsia (14%), osteoporosis and fractures (5%), heart failure (3%), and maternal death (2%) [21, 22].”
Gli adenomi ipofisari in gravidanza
Betella, N., Vena, W., Biamonte, E., Lavezzi, E., & Lania, A. G. (2020) · L Endocrinologo · doi:10.1007/s40619-020-00765-5
Cushing’s syndrome during pregnancy with different clinical courses: Two case reports
Umemiya, M., Chigusa, Y., Minamiguchi, S., Horie, A., Mandai, M., & Kondoh, E. (2020) · Hypertension Research in Pregnancy · doi:10.14390/jsshp.hrp2019-019
Management of Obstetric Umbilical Cord Complications
Bressman, P. L. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.006
Leftwich, H. K. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.018
Thromboembolic Complications of Pregnancy
Kuhlmann, Z. C. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.052
Davis, G. H. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.007 · Cited by 1
Metadata
- Authors
- Lindsay, J. R., Jonklaas, J., Oldfield, E. H., & Nieman, L. K.
- Affiliations
- National Institutes of Health (US)
- Georgetown University Medical Center (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- Corresponding author
- Nieman, Lynnette K.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-05
- Volume
- 90
- Issue
- 5
- Pages
- 3077-3083
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2142121727
- Cited by
- 343
- References
- 0
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 13 · 2023: 11 · 2022: 16 · 2021: 17 · 2020: 16 · 2019: 15 · 2018: 18 · 2017: 68 · 2016: 11 · 2015: 26 · 2014: 15 · 2013: 10 · 2012: 18
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Keywords
- Cushing's syndrome, pregnancy, pituitary-dependent Cushing's syndrome, transsphenoidal microsurgery, inferior petrosal sinus sampling, CRH stimulation test, urinary free cortisol, diurnal cortisol rhythm, ACTH, dexamethasone suppression test, fetal outcomes, adrenal Cushing's syndrome
- MeSH terms
- Adrenocorticotropic Hormone, Adult, Cushing Syndrome, Diagnosis, Differential, Female, Humans, Hydrocortisone, Pregnancy, Pregnancy Complications
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