Abstract
Pregnancy in Cushing’s syndrome (CS) is extremely rare due to the influence of hypercortisolism on the reproductive axis. Purpose of this study is to investigate whether the etiology of CS in pregnancy determines a different impact on the fetal/newborn and maternal outcomes. We performed a systematic review of cases published in the literature from January 1952 to April 2015 including the words “Cushing AND pregnancy”. We included 168 manuscripts containing 220 patients and 263 pregnancies with active CS during pregnancy and with a history of CS but treated and cured hypercortisolism at the time of gestation. Adrenal adenoma was the main cause of active CS during pregnancy (44.1 %). Women with active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003), gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs. 2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss in active CS were etiology of hypercortisolism [Odds Ratio –OR—for pregnancy-induced CS 4.7 (95 % Confidence Interval–CI 1.16–18.96), p = 0.03], publication period [OR for “1975–1994” 0.10 (95 % CI 0.03–0.40), p = 0.001] and treatment during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06–1.02), p = 0.052], [OR surgical treatment 0.34 (95 % CI 0.11–1.06), p = 0.063]). The period of diagnosis of CS (before, during or after pregnancy) was the only predictor of overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI 1.37–15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes. Diagnosis of CS during pregnancy was also associated with worse overall fetal morbimortality. Both medical treatment and surgery during pregnancy appeared to be protective in avoiding fetal loss.
Similar content being viewed by others
References
S.T. Sharma, L.K. Nieman, R.A. Feelders, Cushing’s syndrome : epidemiology and developments in disease management. Clin. Epidemiol. 7, 281–293 (2015)
M. Darocas, N. Ruiz, M.T. Bergoglio, A. Cano, A decision dilemma: Cushing syndrome during pregnancy. J. Obstet. Gynaecol. (Lahore) 35(1), 93–94 (2015)
B.A. Laway, S.A. Mir, Pregnancy and pituitary disorders: challenges in diagnosis and management. Indian J. Endocrinol. Metab. 17(6), 996–1004 (2013)
D. Abdelmannan, D.C. Aron, Adrenal disorders in pregnancy. Endocrinol. Metab. Clin. North Am. 40(4), 779–794 (2011)
L. Vilar, M.C. Freitas, L.H. Lima, R. Lyra, C.E. Kater, Cushing’s Syndrome in Pregnancy : an Overview. Arq. Bras. Endocrinol. Metabol. 51(8), 1293–1302 (2007)
P.J. Trainer, Corticosteroids and pregnancy. Semin. Reprod. Med. 20(4), 375–380 (2002)
M.D. Bronstein, M.C. Machado, Fragoso MCBV. management of endocrine disease: Management of the pregnant patient with Cushings. Eur. J. Endocrinol. 173(2), R85–R91 (2015)
M. Kamoun, M.F. Mnif, N. Charfi, F.H. Kacem, B.B. Naceur, F. Mnif et al., Adrenal diseases during pregnancy: pathophysiology, diagnosis and management strategies. Am. J. Med. Sci. 347(1), 64–73 (2014)
D.B. Schwartz, Y. Daoud, P. Zazula, G. Goyert, R. Bronsteen, D. Wright et al., Gestational diabetes mellitus: metabolic and blood glucose parameters in singleton versus twin pregnancies. Am. J. Obstet. Gynecol. 181(4), 912–914 (1999)
M.D. Bronstein, D.B. Paraiba, R.S. Jallad, Management of pituitary tumors in pregnancy. Nat. Rev. Endocrinol. 7(5), 301–310 (2011)
M.A. Buescher, H.D. McClamrock, E.Y. Adashi, Cushing syndrome in pregnancy. Obstet. Gynecol. 79(1), 130–137 (1992)
J.R. Lindsay, J. Jonklaas, E.H. Oldfield, L.K. Nieman, Cushing’s syndrome during pregnancy: personal experience and review of the literature. J. Clin. Endocrinol. Metab. 90(5), 3077–3083 (2005)
N. Polli, F. Pecori Giraldi, F. Cavagnini, Cushing’s syndrome in pregnancy. J. Endocrinol. Invest. 26(10), 1045–1050 (2003)
N. Achong, M.D. Emden, N. Fagermo, R. Mortimer, Pregnancy-induced Cushing ’ s syndrome in recurrent pregnancies : case report and literature review. Aust. New Zeal. J. Obstet. Gynaecol. 52(1), 96–100 (2012)
E. Rask, E. Schvarcz, P. Hellman, J. Hennings, F.A. Karlsson, C.V. Rao, Adrenocorticotropin-independent Cushing ’ s syndrome in hormone / human chorionic gonadotropin receptors. J. Endocrinol. Invest. 32(4), 313–316 (2009)
M.H. Chui, N.C. Özbey, S.L. Asa, Case Report : adrenal LH/hCG receptor overexpression and gene amplification causing pregnancy-induced Cushing ’ s Syndrome. Endocr. Pathol. 20(4), 256–261 (2009)
L. Tripto-Shkolnik, Z. Blumenfeld, M. Bronshtein, A. Salmon, Pregnancy in a patient with adrenal carcinoma treated with mitotane : a case report and review of literature. J. Clin. Endocrinol. Metab. 98(2), 443–447 (2013)
J.M. Koerten, W.J. Morales, S.R. Washington, T.W. Castaldo, Cushing’s syndrome in pregnancy: a case report and literature review. Am. J. Obstet. Gynecol. 154(3), 626–628 (1986)
S.E. Jones, D. Carr, J. Hoffman, J. Macaulay, P. Tait, Cushing ’ s syndrome in pregnancy due to an adrenocorticotropin secreting islet cell tumour Case report. J. Obstet. Gynaecol. 19(3), 303 (1999)
W.H. Lim, D.J. Torpy, W.S. Jeffries, The medical management of Cushing’s syndrome during pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 168(1), 1–6 (2013)
S. Sam, M.E. Molitch, Timing and special concerns regarding endocrine surgery during pregnancy. Endocrinol Metab Clin North Am. 32(2), 337–354 (2003)
A.H. Mokdad, B.A. Bowman, E.S. Ford, F. Vinicor, J.S. Marks, J.P. Koplan, The continuing epidemics of obesity and diabetes in the United States. JAMA 286(10), 1195–1200 (2001)
A.H. Mokdad, E.S. Ford, B.A. Bowman, D.E. Nelson, M.M. Engelgau, F. Vinicor et al., Diabetes trends in the U.S.: 1990–1998. Diabetes Care 23(9), 1278–1283 (2000)
A. Delabaere, C. Huchon, X. Deffieux, G. Beucher, V. Gallot, S. Nedellec et al., Epidemiology of loss pregnancy. J. Gynecol. Obstet. Biol. Reprod. (Paris) 43(10), 764–775 (2014)
B.S. Buckley, J. Harreiter, P. Damm, R. Corcoy, A. Chico, D. Simmons et al., Gestational diabetes mellitus in Europe: prevalence, current screening practice and barriers to screening. A review. Diabet. Med. 29(7), 844–854 (2012)
E. Abalos, C. Cuesta, G. Carroli, Z. Qureshi, M. Widmer, J.P. Vogel et al., Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG 121(Suppl), 14–24 (2014)
I. Ostlund, U. Hanson, Occurrence of gestational diabetes mellitus and the value of different screening indicators for the oral glucose tolerance test. Acta Obstet. Gynecol. Scand. 82(2), 103–108 (2003)
J. Norman, D. Politz, L. Politz, Hyperparathyroidism during pregnancy and the effect of rising calcium on pregnancy loss: a call for earlier intervention. Clin. Endocrinol. (Oxf). 71(1), 104–109 (2009)
O.M. Dekkers, E. Horváth-Puhó, J.O.L. Jørgensen, S.C. Cannegieter, V. Ehrenstein, J.P. Vandenbroucke et al., Multisystem Morbidity and Mortality in Cushing’s Syndrome: A Cohort Study. J. Clin. Endocrinol. Metab. 98(6), 2277–2284 (2013)
J. Poorolajal, P. Cheraghi, Z. Cheraghi, M. Ghahramani, A.D. Irani, Predictors of miscarriage : a matched case-control study. Epidemiol. Health 36, 1–7 (2014)
K. Pazol, A.A. Creanga, D.J. Jamieson, Abortion Surveillance - United States, 2012. MMWR Surveill. Summ. 64(10), 1–40 (2015)
D. Dong, H. Li, H. Xiao, The diagnosis and management of Cushing syndrome during pregnancy. J. Obstet. Gynaecol. 35(1), 94–96 (2015)
R.N. Sammour, L. Saiegh, I. Matter, R. Gonen, C. Shechner, M. Cohen et al., Adrenalectomy for adrenocortical adenoma causing Cushing’s syndrome in pregnancy: a case report and review of literature. Eur. J. Obstet. Gynecol. Reprod. Biol. 165(1), 1–7 (2012)
A. Klibanski, A.E. Stephen, M.F. Greene, M.A. Blake, C. Wu, Case 36-2006 : A 35-year-old pregnant woman with new hypertension. N. Engl. J. Med. 355(21), 2237–2245 (2006)
A.P.H. Prebtani, D. Donat, S. Ezzat, Worrisome striae. Lancet 355(9), 2000 (2000)
M. Boronat, D. Marrero, Y. López-Plasencia, M. Barber, Y. Schamann, F.J. Nóvoa, Successful outcome of pregnancy in a patient with Cushing’s disease under treatment with ketoconazole during the first trimester of gestation. Gynecol. Endocrinol. 27(9), 675–677 (2011)
N.J. Kassebaum, A. Bertozzi-Villa, M.S. Coggeshall, Ka Shackelford, C. Steiner, K.R. Heuton et al., Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384(9947), 980–1004 (2014)
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Caimari, F., Valassi, E., Garbayo, P. et al. Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases. Endocrine 55, 555–563 (2017). https://doi.org/10.1007/s12020-016-1117-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-016-1117-0