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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]
Citations
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Items 201–239 of 239
Connective Tissue Disorders and Pregnancy
Peterson, J. E. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.045
Perineal Trauma after Vaginal Delivery: Third and Fourth Degree Lacerations and Hematomas
Martinez, A. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.012
Neurological Disease Complicating Pregnancy
Antoniewicz, L. W., & Schneider, K. M. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.039
Dermatologic Disorders and Pregnancy
Stockdale, C. K., & Martini, S. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.046
Diabetes Mellitus in Pregnancy
Hamdi, M. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316662571.044
Pathologie endocrinienne et grossesse (en dehors du diabète sucré)
Gricourt, S., Peigné, M., & Luton, D. (2017) · EMC - Obstétrique · doi:10.1016/s0246-0335(16)73372-2
CushingâÂÂs Syndrome Complicating Pregnancy
Hung, I. K., Ng, H., & Wa, T. K. (2017) · doi:10.4172/2165-7920.1000911
Successful pregnancy outcome in a case of Cushing’s disease
Changede, P., D'Souza, N., Chavan, N., & Nandanwar, Y. (2016) · doi:10.5958/2394-2754.2016.00029.1
“Syndrome, the rate of early spontaneous abortions may be underestimated.(2,7,15) Preterm labour is a common complication in around 60% of pregnancies(2).”
BackgroundInfluentialAnterior and posterior pituitary disease and pregnancy
Molitch, M. (2015) · doi:10.1002/9781118430903.ch11
Tabarin, A., & Nunes, M. (2015) · EMC - Endocrinologie - Nutrition · doi:10.1016/s1155-1941(15)64270-6
Lopes, L. M. L. (2015) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.5.2015.tde-04082015-084833
Marxsen, A. K., Harbeck, B., & Lehnert, H. (2015) · Der Gynäkologe · doi:10.1007/s00129-014-3414-0
Pituitary Disorders - Specific Issues for Women
Fleseriu, M., Yedinak, C., Brzana, J., & McCartney, S. (2013) · doi:10.1002/9781118559406.ch18
Valencia, M. I. B., & Yepes, C. V. (2012) · doi:10.1016/j.rcae.2012.04.001
Adenoma suprarrenal funcional en gestante de 32 semanas programada para cesárea
Valencia, M. I. B., & Yepes, C. V. (2012) · doi:10.1016/j.rca.2012.05.005
Pituitary and Adrenal Disease in Pregnancy
Molitch, M. E., & Peaceman, A. M. (2010) · doi:10.1002/9781444323016.ch13
Life-Threatening Adrenocortical Carcinoma in Pregnancy: Case Report
Hubalewska-Dydejczyk, A., Nowak, W., Matyja, A., Kasperlik-Załuska, A., Kmita, M., Gil, J., & Opalińska, M. (2010) · The Endocrinologist · doi:10.1097/ten.0b013e3181e94730
Cushing's Disease Occurring in Preganacy
Triay, J., & Lambert, A. P. (2010) · Diabetic Medicine · doi:10.1111/j.1464-5491.2009.02877.x
La terapia degli adenomi ipofisari in gravidanza
Cozzi, R., & Attanasio, R. (2007) · doi:10.1007/bf03344589
Morbus Cushing und Prolaktinom
Führer, D. (2006) · doi:10.1055/s-2006-947821
Golounina, O., Dzeranova, L., Zhukova, E., Vorotnikova, S., Tarabrin, E., Lapshina, A., Troshina, E., & Mokrysheva, N. (2024) · Russian Journal of Human Reproduction · doi:10.17116/repro202430061118
Endogenous hypercortisolism in pregnant women
Yukina, M. Y., Чернова, М. О., Belaya, Z. E., Troshina, E. A., Platonova, N. M., & Beltsevich, D. G. (2022) · Russian Bulletin of Obstetrician-Gynecologist · doi:10.17116/rosakush20222202147
Kalinin, P. L., Kutin, M. A., Lubnin, А. Y., Astafieva, L. I., Ахвледиани, К. Н., Ivanov, V. V., Agrba, S. B., Sharipov, O. I., Fomichev, D. V., & Chernov, I. V. (2022) · Russian Journal of Human Reproduction · doi:10.17116/repro202228021110
Evaluation and Management of chronic Hypertension in Pregnancy
Yadav, S., Singh, N., & Pradhan, M. (2021) · Archives of obstetrics and gynaecology · doi:10.33696/gynaecology.2.011
“Although normal pregnancy is associated with increases in urinary free cortisol, levels in pregnant patients with Cushing’s syndrome are significantly higher than the physiologic (100–300 μg/24 h) increase found in normal pregnancy [21,22].”
BackgroundManagement of pituitary tumors in pregnancy
Glezer, A., Jallad, R., Machado, M. C., & Bronstein, M. (2021) · Pituitary Tumors · doi:10.1016/b978-0-12-819949-7.00049-4
Pituitary Physiology During Pregnancy and Lactation
Jallad, R. S., Glezer, A., Machado, M. C., & Bronstein, M. D. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814823-5.00003-9
Hypercorticisme et phéochromocytome pendant la grossesse
Tomaszewski, C., & Dewailly, D. (2019) · Elsevier eBooks · doi:10.1016/b978-2-294-75965-9.00023-4
Cushing Syndrome; Screening and Differential Diagnosis
Lacroix, A., & Nieman, L. K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.65857-9
Self-citationAdrenal Causes of Cushing’s Syndrome
Cavagnini, F., & Giraldi, F. P. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00103-7 · Cited by 5
Other Endocrine Emergencies in Pregnancy
Singh, A., & Singh, S. (2016) · doi:10.1007/978-81-322-2686-4_14
Hormonal Changes and Endocrine Testing in Pregnancy
Molitch, M. E. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00146-3 · Cited by 2
Síndrome de Cushing durante el embarazo: manifestaciones cutáneas secundarias a un tumor suprarrenal
MontserratMolgó, N., DavidMayerson, B., PedroJaramillo, Z., JulioParra, C., & SergioGonzález, B. (2013) · Revista chilena de obstetricia y ginecología · doi:10.4067/s0717-75262013000400013
Spreux, A., Bernard, N., & Vial, T. (2012) · Elsevier eBooks · doi:10.1016/b978-2-294-70624-0.00015-5
Hypercorticisme et phéochromocytome pendant la grossesse
Tomaszewski, C., & Dewailly, D. (2012) · Elsevier eBooks · doi:10.1016/b978-2-294-70154-2.00020-0
[Cortical adrenal adenoma as a cause of Cushing's syndrome during pregnancy].
de Nobrega-Correa, H., Aragón-Charris, J., Torres-Cepeda, D., & Reyna-Villasmil, E. (2011) · doi:10.1016/s2173-5093(11)70056-3
Heazell, A. E. P., Norwitz, E. R., Kenny, L. C., & Baker, P. N. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511902529 · Cited by 8
Pathologie hypothalamohypophysaire et grossesse
Caron, P. (2008) · EMC - Endocrinologie - Nutrition · doi:10.1016/s1155-1941(08)46672-6
Syndrome de Cushing et grossesse
Bertherat, J. (2007) · doi:10.1007/978-2-287-35572-1_7
Alexandraki, K., & Grossman, A. B. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8684-8_9 · Cited by 5
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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