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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During the second trimester, UFC increases approximately 1.4-fold, and during the third trimester, approximately 1.6-fold.
“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]
Fetal morbidity associated with CS in pregnancy includes spontaneous abortion, perinatal death, premature birth, and intrauterine growth retardation.
“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]
The biochemical diagnosis of CS during pregnancy can be more challenging because of normal physiologic changes that occur during pregnancy, including activation of the HPA axis.
“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]
Suppression of serum and plasma cortisol by dexamethasone is blunted during pregnancy, making the DST difficult to interpret.
“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]
Early diagnosis and management of CS during pregnancy are important because of associated fetal and maternal morbidity.
“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]
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.
“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]
Maternal morbidity caused by CS in pregnancy includes hypertension, preeclampsia, wound breakdown, diabetes, fractures, and opportunistic infections.
“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]
The rise in placental CRH and ACTH causes an increase in total plasma cortisol levels.
“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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The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.
Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., Stewart, P. M., & Montori, V. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0125 · Cited by 2,718 · see citing works
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Pivonello, R., Leo, M. D., Cozzolino, A., & Colao, A. A. L. (2015) · Endocrine Reviews · doi:10.1210/er.2013-1048 · Cited by 471 · see citing works
Tritos, N. A., Biller, B. M. K., & Swearingen, B. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.12 · Cited by 212 · see citing works
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BackgroundBERTAGNA, X. Y., Guignat, L., Groussin, L., & Bertherat, J. Y. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2009.06.001 · Cited by 221 · see citing works
The diagnosis of Cushing’s syndrome
Carroll, T. B., & Findling, J. W. (2010) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-010-9143-3 · Cited by 95 · see citing works
Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases
Caimari, F., Valassi, E., Garbayo, P., Steffensen, C. H., Santos, A., Corcoy, R., & Webb, S. (2017) · Endocrine · doi:10.1007/s12020-016-1117-0 · Cited by 114 · see citing works
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Feelders, R. A., Newell-Price, J. D. C., Pivonello, R., Nieman, L. K., Hofland, L. J., & Lacroix, A. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30155-4 · Cited by 160 · see citing works
Self-citationPofi, R., & Tomlinson, J. (2019) · Obstetric Medicine · doi:10.1177/1753495x19847832 · Cited by 63 · see citing works
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ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy
Luger, A., Broersen, L. H. A., Biermasz, N. R., Biller, B. M. K., Buchfelder, M., Chanson, P., Jørgensen, J. O. L., Keleştimur, F., Llahana, S., Maiter, D. M., et al. (2021) · European Journal of Endocrinology · doi:10.1530/eje-21-0462 · Cited by 104 · see citing works
Cushing's syndrome in pregnancy: an overview
Vilar, L., Freitas, M. D. C., Lima, L. H. C., Lyra, R., & Kater, C. E. (2007) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302007000800015 · Cited by 75 · see citing works
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Daniel, E., & Newell-Price, J. D. C. (2015) · European Journal of Endocrinology · doi:10.1530/eje-14-1014 · Cited by 88 · see citing works
Eculizumab for Atypical Hemolytic Uremic Syndrome in Pregnancy
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Adrenal Disorders in Pregnancy
Abdelmannan, D. K., & Aron, D. C. (2011) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2011.09.001 · Cited by 31 · see citing works
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Keller-Wood, M., Feng, X.-D., Wood, C., Richards, E., Anthony, R., Dahl, G., & Tao, S. (2014) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00530.2013 · Cited by 51 · see citing works
Perlman, J. E., Johnston, P. C., Hui, F., Mulligan, G., Weil, R. J., Recinos, P. F., Yogi-Morren, D., Salvatori, R., Mukherjee, D., Gallia, G., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab012 · Cited by 50 · see citing works
The diagnosis and management of Cushing's syndrome in pregnancy
Hamblin, R., Coulden, A., Fountas, A., & Karavitaki, N. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13118 · Cited by 59 · see citing works
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Morton, A., & Teasdale, S. (2021) · Clinical Endocrinology · doi:10.1111/cen.14624 · Cited by 49 · see citing works
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BackgroundBoronat, M., Marrero, D., López-Plasencia, Y., Barber, M. Á., Schamann, Y., & Novoa, F. J. (2010) · Gynecological Endocrinology · doi:10.3109/09513590.2010.521268 · Cited by 47 · see citing works
“However, as previously known from patients with diagnosis de novo during pregnancy, physiologic changes of gestation, specifically the increase in levels of plasma and urine cortisol, complicate the interpretation of clinical and biochemical investigations [1], and postoperative diagnostic work-up in our case led to t…”
BackgroundInfluentialPituitary disorders during pregnancy.
Molitch, M. (2006) · Endocrinology and metabolism clinics of North America (Print) · doi:10.1016/j.ecl.2005.09.011 · Cited by 48 · see citing works
“Slightly more than 100 cases of Cushing’s syndrome in pregnancy have been reported [61–76].”
BackgroundInfluentialMANAGEMENT OF ENDOCRINE DISEASE: Management of pregnant patients with Cushing's syndrome.
Bronstein, M. D., Machado, M., & Fragoso, M. C. V. (2015) · European Journal of Endocrinology · doi:10.1530/eje-14-1130 · Cited by 47 · see citing works
Cabergoline Therapy for Cushing Disease Throughout Pregnancy
Woo, I., & Ehsanipoor, R. (2013) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e31829e398a · Cited by 47
The Hypothalamic-Pituitary-Adrenal Axis and the Fetus
Morsi, A., DeFranco, D. B., & Witchel, S. F. (2018) · Hormone Research in Paediatrics · doi:10.1159/000488106 · Cited by 50 · see citing works
Updates in adrenal steroidogenesis inhibitors for Cushing’s syndrome – A practical guide
Varlamov, E. V., Han, A. J., & Fleseriu, M. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101490 · Cited by 55 · see citing works
Dopamine Agonists for Pituitary Adenomas
Cooper, O., & Greenman, Y. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00469 · Cited by 43 · see citing works
Medical Management of Cushing’s Syndrome: Current and Emerging Treatments
Hinojosa‐Amaya, J. M., Ramos, D. C., & Fleseriu, M. (2019) · Drugs · doi:10.1007/s40265-019-01128-7 · Cited by 53 · see citing works
Changes in biochemical tests in pregnancy and their clinical significance
Teasdale, S., & Morton, A. (2018) · Obstetric Medicine · doi:10.1177/1753495x18766170 · Cited by 53 · see citing works
Sammour, R., Saiegh, L., Matter, I., Gonen, R., Shechner, C., Cohen, M., Ohel, G., & Dickstein, G. (2012) · European Journal of Obstetrics, Gynecology, and Reproductive Biology · doi:10.1016/j.ejogrb.2012.05.030 · Cited by 42
“Prematurity and intrauterine growth restriction seem to be significantly increased, with rates as high as 43% [26] and 37% [3], respectively.”
BackgroundInfluentialImitators of preeclampsia: A review
Morton, A. (2016) · Pregnancy Hypertension · doi:10.1016/j.preghy.2016.02.001 · Cited by 43 · see citing works
“Eight pregnant subjects have undergone transphenoidal resection of pituitary tumours during pregnancy [24].”
BackgroundStewart, P. M., & Krone, N. P. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00015-8 · Cited by 44 · see citing works
Nieman, L. K., Castinetti, F., Newell-Price, J. D. C., Valassi, E., Drouin, J., Takahashi, Y., & Lacroix, A. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00588-w · Cited by 73 · see citing works
Self-citationCurrent management of Cushing's disease
Tritos, N. A., & Biller, B. M. K. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12975 · Cited by 56 · see citing works
Adrenally Directed Medical Therapies for Cushing Syndrome
Tritos, N. A. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa778 · Cited by 51 · see citing works
Primary aldosteronism and pregnancy
Morton, A. (2015) · Pregnancy Hypertension · doi:10.1016/j.preghy.2015.08.003 · Cited by 69 · see citing works
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BackgroundMel'nichenko, G. A., Dedov, I. I., Belaya, Z. E., Rozhinskaya, L. Y., Vagapova, G. R., Волкова, Н. И., Grigor’ev, A. Y., Grineva, E. N., Marova, E. I., Mkrtumayn, A. M., et al. (2015) · Problems of Endocrinology · doi:10.14341/probl201561255-77 · Cited by 50 · see citing works
Human adrenal cortex hyperfunction due to LH/hCG.
Carlson, H. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.06.014 · Cited by 39 · see citing works
Adrenal Cushing's syndrome during pregnancy.
Andreescu, C., Alwani, R., Hofland, J., Looijenga, L., de Herder, W. D., Hofland, L., & Feelders, R. (2017) · European Journal of Endocrinology · doi:10.1530/eje-17-0263 · Cited by 37
Cabergoline treatment for recurrent Cushing’s disease during pregnancy
Nakhleh, A., Saiegh, L., Reut, M., Ahmad, M. S., Pearl, I. W., & Shechner, C. (2016) · HORMONES · doi:10.14310/horm.2002.1685 · Cited by 37 · see citing works
Pivonello, R., Martino, M. C. D., Auriemma, R. S., Alviggi, C., Grasso, L. F. S., Cozzolino, A., Leo, M. D., Placido, G. D., Colao, A. A. L., & Lombardi, G. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-013-0019-8 · Cited by 40 · see citing works
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BackgroundInfluentialPituitary disorders in pregnancy
Chrisoulidou, A., Boudina, M., Karavitaki, N., Bill, E., & Wass, J. (2015) · HORMONES · doi:10.1007/bf03401382 · Cited by 34 · see citing works
Adrenal Disorders in Pregnancy
Lindsay, J. R., & Nieman, L. K. (2006) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2005.09.010 · Cited by 59 · see citing works
“nodular adrenal disease and adrenocorticotropic hormone (ACTH)-independent hyperplasia, caused possibly by aberrant receptor stimulation, accounted for eight cases of the pregnancies [1].”
BackgroundMethodResultInfluentialSelf-citationAdrenal disorders in pregnancy
Monticone, S., Auchus, R. J., & Rainey, W. E. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.155 · Cited by 53 · see citing works
Chui, M. H., Özbey, N., Ezzat, S., Kapran, Y., Erbil, Y., & Asa, S. L. (2009) · Endocrine Pathology · doi:10.1007/s12022-009-9090-2 · Cited by 39 · see citing works
“Approximately 130 cases have been reported in the literature, with the majority (50–60%) attributable to adrenal neoplasms and a significant proportion (30%) to adrenocorticotropic hormone (ACTH) hypersecretion from pituitary adenomas [ 1 ].”
BackgroundTuberculum sellae meningioma symptomatic during pregnancy: pathophysiological considerations
Ebner, F., Bornemann, A., Wilhelm, H., Ernemann, U., & Honegger, J. (2008) · Acta Neurochirurgica · doi:10.1007/s00701-007-1417-5 · Cited by 31
“uncommon during pregnancy [4, 6, 12, 18–21].”
Cushing's Syndrome During Pregnancy: Personal Experience and Review of the Literature
Molitch, M. (2006) · doi:10.1016/s0084-3741(08)70475-x · Cited by 30
Surgical management of recurrent Cushing's disease in pregnancy: A case report
Abbassy, M., Kshettry, V., Hamrahian, A., Johnston, P., Dobri, G. A., Avitsian, R., Woodard, T. D., & Recinos, P. (2015) · Surgical neurology international · doi:10.4103/2152-7806.170472 · Cited by 29 · see citing works
“[4,25] Prior studies have demonstrated superior maternal and fetal outcomes in addition to a higher rate of live births when medical treatment is implemented in the second trimester compared to no intervention during pregnancy.[25,29] The second trimester is considered the optimal time for surgical intervention becaus…”
BackgroundInfluentialAACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease
Hamrahian, A. H., Yuen, K. C. J., & Hoffman, A. R. (2014) · Endocrine Practice · doi:10.4158/ep14147.ra · Cited by 27 · see citing works
Martin, M. D., Giraldi, F. P., & Cavagnini, F. (2006) · Pituitary · doi:10.1007/s11102-006-0407-6 · Cited by 35 · see citing works
Pregnancy‐induced Cushing’s syndrome in recurrent pregnancies: Case report and literature review
Achong, N., d'Emden, M., Fagermo, N., & Mortimer, R. H. (2012) · Australian and New Zealand journal of obstetrics and gynaecology · doi:10.1111/j.1479-828x.2011.01388.x · Cited by 26
Pregnancy in Patients with Cushing's Syndrome.
Machado, M., Fragoso, M., & Bronstein, M. (2018) · Endocrinology and metabolism clinics of North America (Print) · doi:10.1016/j.ecl.2018.02.004 · Cited by 25 · see citing works
Cushing's syndrome in pregnancy with a severe maternal complication: A case report
Choi, W., Jung, T., & Paik, W. (2011) · The journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2010.01339.x · Cited by 25
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Tritos, N. A., & Biller, B. M. K. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2018.01.006 · Cited by 24 · see citing works
Zieleniewski, W., & Michalak, R. (2017) · Gynecological Endocrinology · doi:10.1080/09513590.2017.1290070 · Cited by 24 · see citing works
“reported cases, a specific treatment for hypercortisolism was not introduced [7].”
BackgroundInfluentialPregnancy does not accelerate corticotroph tumor progression in Nelson's syndrome.
Jornayvaz, F., Assié, G., Bienvenu-Perrard, M., Coste, J., Guignat, L., Bertherat, J., Silvéra, S., Bertagna, X., & Legmann, P. (2011) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2010-2235 · Cited by 24 · see citing works
Tritos, N. A., & Biller, B. M. K. (2014) · Handbook of clinical neurology · doi:10.1016/b978-0-444-59602-4.00015-0 · Cited by 45 · see citing works
Cushing's Disease and Pregnancy
Polli, N., Giraldi, F. P., & Cavagnini, F. (2004) · Pituitary · doi:10.1007/s11102-005-1479-4 · Cited by 27 · see citing works
“Treatment of choice for ACTH-secreting pituitary adenomas is removal of the pituitary tumor and, in fact, transsphenoidal surgery has been performed in a number of pregnant women with Cushing’s disease [25,27,43].”
BackgroundMethodInfluentialMachado, M. C., Fragoso, M. C. B. V., Moreira, A. C., Boguszewski, C. L., Vieira Neto, L., Naves, L. A., Vilar, L., Araújo, L. A. D., Czepielewski, M. A., Gadelha, M. R., et al. (2016) · Archives of Endocrinology and Metabolism · doi:10.1590/2359-3997000000174 · Cited by 21 · see citing works
Emerging diagnostic methods and imaging modalities in cushing’s syndrome
Wright, K. E., van Rossum, E. F. C., Zan, E., Werner, N. L., Harris, A. G., Feelders, R. A., & Agrawal, N. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1230447 · Cited by 25 · see citing works
“UFC levels modestly increase in the second and third trimester and, although UFC levels of more than 3 times the upper limit of normal (ULN) are indicative of CS, it can be dif fi cult to distinguish CS from physiological activation of the HPA-axis when UFC levels are mildly elevated (11, 28).”
BackgroundEndogenous Cushing’s syndrome during pregnancy
Younes, N., St-Jean, M., Bourdeau, I., & Lacroix, A. (2022) · Reviews in Endocrine & Metabolic Disorders · doi:10.1007/s11154-022-09731-y · Cited by 22 · see citing works
“1 3 CS from ACTH-dependent CS in pregnancy [10]; in their series including 122 pregnant women with CS, using the cut-off for serum cortisol suppression at > 80%, they correctly diagnosed all cases of adrenal CS, but missed 3 out of 7 cases of CD [10].”
BackgroundMethodResultInfluentialSurgical indications for pituitary tumors during pregnancy: a literature review
Graillon, T., Cuny, T., Castinetti, F., Courbière, B., Cousin, M., Albarel, F., Morange, I., Bruder, N., Brue, T., & Dufour, H. (2019) · Pituitary · doi:10.1007/s11102-019-01004-3 · Cited by 22 · see citing works
Klibanski, A., Stephen, A., Greene, M., Blake, M., & Wu, C.-L. (2006) · New England Journal of Medicine · doi:10.1056/nejmcpc069027 · Cited by 22 · see citing works
Recognition of Nonneoplastic Hypercortisolism in the Evaluation of Patients With Cushing Syndrome
Findling, J. W., & Raff, H. (2023) · Journal of the Endocrine Society · doi:10.1210/jendso/bvad087 · Cited by 30 · see citing works
“Serum-free and salivary cortisol increase during pregnancy [88, 89].”
BackgroundUse of cabergoline for the management of persistent Cushing’s disease in pregnancy
Sek, K., Deepak, D., & Lee, K. (2017) · BMJ Case Reports · doi:10.1136/bcr-2016-217855 · Cited by 21
Advances in the Medical Treatment of Cushing Disease
Tritos, N. A., & Biller, B. M. K. (2020) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2020.05.003 · Cited by 25 · see citing works
Endocrine causes of hypertension in pregnancy.
Affinati, A. H., & Auchus, R. (2020) · Gland surgery · doi:10.21037/gs.2019.12.04 · Cited by 20 · see citing works
“For adrenal CS, abdominal ultrasound and adrenal MRI without contrast are the preferred imaging studies (50).”
BackgroundEndocrine oncology in pregnancy.
Lansdown, A., & Rees, D. (2011) · Best practice & research. Clinical endocrinology & metabolism · doi:10.1016/j.beem.2011.06.011 · Cited by 20 · see citing works
Chronic maternal hypercortisolemia in late gestation alters fetal cardiac function at birth.
Antolic, A. T., Wood, C., & Keller-Wood, M. (2018) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00296.2017 · Cited by 19 · see citing works
“Our data indicate that this biphasic relationship also holds true for the effects of cortisol on the developing heart, with effects that could contribute to the increase in stillbirth rates associated with chronic maternal stress or Cushing’s syndrome in late pregnancy (18, 35, 37, 61, 67).”
BackgroundPituitary Disorders in Pregnancy.
Woodmansee, W. (2019) · Neurologic clinics · doi:10.1016/j.ncl.2018.09.009 · Cited by 18 · see citing works
Surgery for Cushing's disease in pregnancy: our experience and a literature review.
Jolly, K., Darr, A., Arlt, W., Ahmed, S., & Karavitaki, N. (2019) · Annals of the Royal College of Surgeons of England · doi:10.1308/rcsann.2018.0175 · Cited by 18
“To date, approximately 200 cases of Cushing’s syndrome in pregnancy have been reported.(3,4) Of these, 40–50% had adrenal adenoma, 30% had Cushing’s disease and 10% had either adrenal carcinoma, adrenocorticotrophic hormone (ACTH)-independent hyperplasia or ectopic ACTH secretion.”
BackgroundAdrenal disorders in pregnancy, labour and postpartum – an overview
Manoharan, M., Sinha, P., & Sibtain, S. (2020) · Journal of Obstetrics and Gynaecology Research · doi:10.1080/01443615.2019.1648395 · Cited by 17 · see citing works
“(Gicquel et al. 2000; Dackiw et al. 2001; Abiven-Lepage et al. 2010) Previous studies have shown that hypercortisolism is itself associated with frequent maternal morbidity and poor fetal prognosis (Lindsay et al. 2005).”
BackgroundMethodInfluentialPituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?
Petersenn, S., Christ‐Crain, M., Droste, M., Finke, R., Flitsch, J., Kreitschmann‐Andermahr, I., Luger, A., Schopohl, J., & Stalla, G. K. (2019) · Geburtshilfe und Frauenheilkunde · doi:10.1055/a-0794-7587 · Cited by 21 · see citing works
“Surgery during pregnancy may be considered in a few cases, particularly for patients with progressive deterioration of vision and reduced visual field acuity for whom glucocorticoid therapy was ineffective [38].”
InfluentialPituitary disease and pregnancy.
Valassi, E. (2020) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2020.07.007 · Cited by 16 · see citing works
Fahrleitner-Pammer, A., Wagner, D., Krisper, P., Amrein, K., & Dimai, H. (2016) · Osteoporosis International · doi:10.1007/s00198-016-3858-2 · Cited by 16
Antolic, A. T., Feng, X.-D., Wood, C., Richards, E., & Keller-Wood, M. (2015) · Physiological Reports · doi:10.14814/phy2.12548 · Cited by 16 · see citing works
“Higher doses of glucocorticoids administered to the mother have been found to reduce growth (Johnson et al. 1981), as does maternal Cushing’s syndrome (Lindsay et al. 2005).”
BackgroundSíndrome de Cushing: situaciones especiales
Iriarte, M. J. G. (2009) · Endocrinología y Nutrición · doi:10.1016/s1575-0922(09)71408-1 · Cited by 13 · see citing works
Cushing’s syndrome in pregnancy
Nassi, R., Ladu, C., Vezzosi, C., & Mannelli, M. (2015) · Gynecological Endocrinology · doi:10.3109/09513590.2014.984680 · Cited by 16 · see citing works
“To date, only a few cases have been reported in literature [1,2].”
Fertility issues in aggressive pituitary tumors
Marques, J. V. O., & Boguszewski, C. L. (2020) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09530-y · Cited by 18 · see citing works
“Tumor enlargement is less important as cause of gonadal dysfunction in Cushing’s disease, as most patients harbor mic roadenomas and , consequen t l y, agg r e s s i ve corticotropinomas is rarely seen associated with pregnancy [18, 43, 44].”
BackgroundWang, W., Yuan, F., & Xu, D.-Y. (2015) · Frontiers in Medicine · doi:10.1007/s11684-015-0407-x · Cited by 15
A successful case of Cushing's disease pregnancy treated with ketoconazole
Costenaro, F., Rodrigues, T., de Lima, P. B., Ruszczyk, J., Rollin, G. A. F., & Czepielewski, M. (2015) · Gynecological Endocrinology · doi:10.3109/09513590.2014.995615 · Cited by 15
“For the fetus, maternal CS increases the rates of spontaneous abortion, intrauterine growth restriction, perinatal death and premature birth [2,4].”
BackgroundInfluentialEarly severe pre-eclamptic findings in a patient with Cushing's syndrome
Delibaşı, T., Ustun, I., Aydin, Y., Berker, D., Erol, H., Gul, K., Unal, M., & Guler, S. (2006) · Gynecological Endocrinology · doi:10.1080/09513590601069447 · Cited by 15
“Plasma cortisol, cortisol-binding protein and urinary free cortisol all increase during the second and third trimesters of normal pregnancy [2,3].”
BackgroundInfluentialAdrenal Cushing Syndrome Diagnosed During Pregnancy: Successful Medical Management With Metyrapone
Azzola, A., Eastabrook, G. D. M., Matsui, D. M., Berberich, A. J., Tirona, R. G., Gray, D., Gallego, P., & Uum, S. H. M. V. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa167 · Cited by 23 · see citing works
“Cushing syndrome (CS) during pregnancy is rare, with only about 200 cases reported in the literature [1].”
BackgroundTang, K.-Y., Lu, L., Feng, M., Zhang, H.-L., Chen, K., Sun, X., Zhu, H., Wang, R.-Z., & Lu, Z.-L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00305 · Cited by 14
Diagnosis and treatment outcomes of Cushing’s disease during pregnancy
Sridharan, K., Sahoo, J., Palui, R., Patil, M., Kamalanathan, S., Ramesh, A., & Kubera, N. (2021) · Pituitary · doi:10.1007/s11102-021-01142-7 · Cited by 13 · see citing works
Pregnancy during the course of Cushing’s syndrome: a case report and literature review
Ildefonso-Najarro, S., Plasencia-Dueñas, E., Benites-Moya, C. J., Carrion-Rojas, J., & Concepción-Zavaleta, M. (2020) · Endocrinology, Diabetes & Metabolism Case Reports · doi:10.1530/edm-20-0022 · Cited by 13
Evaluation and Management of Endocrine Hypertension During Pregnancy.
Corsello, S., & Paragliola, R. (2019) · Endocrinology and metabolism clinics of North America (Print) · doi:10.1016/j.ecl.2019.08.011 · Cited by 13 · see citing works
Zhang, X., Liao, H., Zhu, X., Shi, D., & Chen, X.-P. (2019) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-019-2262-2 · Cited by 13 · see citing works
- 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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