Pre-term birth in women exposed to Cushing’s disease: the baby-cush study

in European Journal of Endocrinology
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  • 1 Service d’Endocrinologie, L’institut du thorax, CHU de Nantes, Nantes, Pays de la Loire, France
  • 2 Endocrinologie, Diabétologie et Maladies Métaboliques, CHU de Grenoble, Grenoble, France
  • 3 Service d’Endocrinologie, Hôpital Larrey, Toulouse, France
  • 4 Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse and Université Paris-Saclay, Univ. Paris-Sud, Inserm, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Le Kremlin-Bicêtre, Paris, France
  • 5 Service d’Endocrinologie-Diabète et Maladies Métaboliques, Hôpital de la Cavale Blanche, CHU de Brest, Brest, France
  • 6 Service Endocrinologie, Diabétologie et Nutrition, Institut Mitovasc, CHU d’Angers, Angers, France
  • 7 Service d’Endocrinologie et Médecine de la Reproduction, IE3M, Hôpital Universitaire Pitié Salpêtrière, Sorbonne Université, Paris, France
  • 8 Service d’Endocrinologie, CHU de Nice, Nice, France
  • 9 Service des Maladies Métaboliques et Endocriniennes, CHU Nîmes, Nimes, France
  • 10 Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Marseille, France
  • 11 Assistance Publique-Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France

Correspondence should be addressed to F Castinetti; Email: frederic.castinetti@ap-hm.fr
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Design

Hypercortisolism during pregnancy is a risk factor for prematurity. Long-term exposure to hypercortisolism may lead to permanent comorbidities, such as hypertension or diabetes, even after remission. Our aim was to determine whether women with a history of Cushing’s disease (and being eu-, hypo- or hypercortisolic at the time of pregnancy) had the same risks of comorbidities, and especially prematurity, during pregnancy.

Methods

It was a retrospective multicentric study focusing on mothers with a history of Cushing’s disease or diagnosed during pregnancy, followed in French tertiary referral centers. We compared the outcomes of pregnancies depending on the cortisolic status at the time of pregnancy.

Results

A total of 60 patients (78 pregnancies including 21 with hypercortisolism, 32 with hypocortisolism and 25 in eucortisolism in 25) were evaluated. The overall rate of preterm birth was 24.3%, with a peak in women diagnosed during pregnancy (62.5%), a high risk in hypercortisolic (33%) and hypocortisolic (19.3%), and a low risk (8%) in eucortisolic women Gestational diabetes and hypertension were observed in 21% and 10.4% of the whole cohort, with a higher risk in hypercortisolic women. Cesarean delivery was performed in 33.7% of the cohort.

Conclusions

Being non-eucortisolic at the time of pregnancy increases the risk of prematurity and comorbidities compared to the general population. Women with a history of Cushing’s disease should thus be carefully monitored during pregnancy. The high rate of cesarean delivery emphasizes the fact that these pregnancies should always be considered at risk.

Supplementary Materials

    • Additional table 1 : Characteristics of the 6 patients who had a diagnosis of Cushing’s disease during pregnancy. NA, not available.

 

     European Society of Endocrinology

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  • 1

    Bronstein MD, Machado MC & Fragoso MCBV MANAGEMENT OF ENDOCRINE DISEASE: Management of pregnant patients with Cushing’s syndrome. European Journal of Endocrinology 2015 173 R85R 91. (https://doi.org/10.1530/EJE-14-1130)

    • Search Google Scholar
    • Export Citation
  • 2

    Brue T, Amodru V & Castinetti F MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing’s syndrome during pregnancy: solved and unsolved questions. European Journal of Endocrinology 2018 178 R259R266. (https://doi.org/10.1530/EJE-17-1058)

    • Search Google Scholar
    • Export Citation
  • 3

    Lindsay JR & Nieman LK The hypothalamic-pituitary-adrenal axis in pregnancy: challenges in disease detection and treatment. Endocrine Reviews 2005 26 775799. (https://doi.org/10.1210/er.2004-0025)

    • Search Google Scholar
    • Export Citation
  • 4

    Caimari F, Valassi E, Garbayo P, Steffensen C, Santos A, Corcoy R & Webb SM Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases. Endocrine 2017 55 555563. (https://doi.org/10.1007/s12020-016-1117-0)

    • Search Google Scholar
    • Export Citation
  • 5

    Tang K, Lu L, Feng M, Zhang H, Chen K, Sun X, Zhu H, Wang R & Lu Z The incidence of pregnancy-associated Cushing’s disease and its relation to pregnancy: a retrospective study. Frontiers in Endocrinology 2020 11 305. (https://doi.org/10.3389/fendo.2020.00305)

    • Search Google Scholar
    • Export Citation
  • 6

    Abbassy M, Kshettry VR, Hamrahian AH, Johnston PC, Dobri GA, Avitsian R, Woodard TD & Recinos PF Surgical management of recurrent Cushing’s disease in pregnancy: a case report. Surgical Neurology International 2015 6 S640S 645. (https://doi.org/10.4103/2152-7806.170472)

    • Search Google Scholar
    • Export Citation
  • 7

    Berwaerts J, Verhelst J, Mahler C & Abs R Cushing’s syndrome in pregnancy treated by ketoconazole: case report and review of the literature. Gynecological Endocrinology 1999 13 175182. (https://doi.org/10.3109/09513599909167552)

    • Search Google Scholar
    • Export Citation
  • 8

    Boronat M, Marrero D, López-Plasencia Y, Barber M, Schamann Y & Nóvoa FJ Successful outcome of pregnancy in a patient with Cushing’s disease under treatment with ketoconazole during the first trimester of gestation. Gynecological Endocrinology 2011 27 675677. (https://doi.org/10.3109/09513590.2010.521268)

    • Search Google Scholar
    • Export Citation
  • 9

    Connell JM, Cordiner J, Davies DL, Fraser R, Frier BM & McPherson SG Pregnancy complicated by Cushing’s syndrome: potential hazard of metyrapone therapy. Case report. British Journal of Obstetrics and Gynaecology 1985 92 11921195. (https://doi.org/10.1111/j.1471-0528.1985.tb03037.x)

    • Search Google Scholar
    • Export Citation
  • 10

    Costenaro F, Rodrigues TC, Lima PB de, Ruszczyk J, Rollin G & Czepielewski MA A successful case of Cushing’s disease pregnancy treated with ketoconazole. Gynecological Endocrinology 2015 31 176178. (https://doi.org/10.3109/09513590.2014.995615)

    • Search Google Scholar
    • Export Citation
  • 11

    Jolly K, Darr A, Arlt W, Ahmed S & Karavitaki N Surgery for Cushing’s disease in pregnancy: our experience and a literature review. Annals of the Royal College of Surgeons of England 2019 101 e26e31. (https://doi.org/10.1308/rcsann.2018.0175)

    • Search Google Scholar
    • Export Citation
  • 12

    Leiba S, Weinstein R, Shindel B, Lapidot M, Stern E, Levavi H, Rusecki Y & Abramovici A The protracted effect of o,p′-DDD in Cushing’s disease and its impact on adrenal morphogenesis of young human embryo. Annales d’Endocrinologie 1989 50 4953.

    • Search Google Scholar
    • Export Citation
  • 13

    Lim WH, Torpy DJ & Jeffries WS The medical management of Cushing’s syndrome during pregnancy. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2013 168 16. (https://doi.org/10.1016/j.ejogrb.2012.12.015)

    • Search Google Scholar
    • Export Citation
  • 14

    Giurgescu C Are maternal cortisol levels related to preterm birth? Journal of Obstetric, Gynecologic, and Neonatal Nursing 2009 38 377390. (https://doi.org/10.1111/j.1552-6909.2009.01034.x)

    • Search Google Scholar
    • Export Citation
  • 15

    Mercer BM, Macpherson CA, Goldenberg RL, Goepfert AR, Hauguel-de Mouzon S, Varner MW, Iams JD, Meis PJ, Moawad AH & Miodovnik M Are women with recurrent spontaneous preterm births different from those without such history? American Journal of Obstetrics and Gynecology 2006 194 11761184; discussion 11841185. (https://doi.org/10.1016/j.ajog.2006.01.069)

    • Search Google Scholar
    • Export Citation
  • 16

    Glynn LM, Schetter CD, Chicz-DeMet A, Hobel CJ & Sandman CA Ethnic differences in adrenocorticotropic hormone, cortisol and corticotropin-releasing hormone during pregnancy. Peptides 2007 28 11551161. (https://doi.org/10.1016/j.peptides.2007.04.005)

    • Search Google Scholar
    • Export Citation
  • 17

    Bothou C, Anand G, Li D, Kienitz T, Seejore K, Simeoli C, Ebbehoj A, Ward EG, Paragliola RM & Ferrigno R Current management and outcome of pregnancies in women with adrenal insufficiency: experience from a multicenter survey. Journal of Clinical Endocrinology and Metabolism 2020 105 e2853e2863. (https://doi.org/10.1210/clinem/dgaa266)

    • Search Google Scholar
    • Export Citation
  • 18

    Billionnet C, Mitanchez D, Weill A, Nizard J, Alla F, Hartemann A & Jacqueminet S Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012. Diabetologia 2017 60 636644. (https://doi.org/10.1007/s00125-017-4206-6)

    • Search Google Scholar
    • Export Citation
  • 19

    Blondel B, Coulm B, Bonnet C, Goffinet F, Le Ray CNational Coordination Group of the National Perinatal Surveys. Trends in perinatal health in metropolitan France from 1995 to 2016: results from the French National Perinatal Surveys. Journal of Gynecology Obstetrics and Human Reproduction 2017 46 701713. (https://doi.org/10.1016/j.jogoh.2017.09.002)

    • Search Google Scholar
    • Export Citation
  • 20

    Castinetti F, Guignat L, Bouvattier C, Samara-Boustani D & Reznik Y Group 4: replacement therapy for adrenal insufficiency. Annales d’Endocrinologie 2017 78 525534. (https://doi.org/10.1016/j.ando.2017.10.007)

    • Search Google Scholar
    • Export Citation
  • 21

    Delabaere A, Huchon C, Deffieux X, Beucher G, Gallot V, Nedellec S, Vialard F, Carcopino X, Quibel T & Subtil D et al. Épidémiologie des pertes de grossesse [Epidemiology of loss pregnancy]. Journal de Gynécologie Obstétrique et Biologie de la Reproduction 2014 43 764-775. (https://doi.org/10.1016/j.jgyn.2014.09.011)

    • Search Google Scholar
    • Export Citation
  • 22

    Crépin G & Bréart G Mortalité maternelle et mortalité périnatale des enfants nés à terme en France [Maternal and perinatal mortality of term deliveries in France]. Bulletin de l’Académie Nationale de Médecine 2010 194 15811599. (https://doi.org/10.1016/S0001-4079(1932186-7)

    • Search Google Scholar
    • Export Citation