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      Pregnancy during the course of Cushing’s syndrome: a case report and literature review

      research-article
      1 , 1 , 2 , 3 , 1
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd
      Pregnant adult, Female, Hispanic or Latino - other, Peru, Adrenal, Adrenal, Cortisol, ACTH, Insulin, Adrenocortical adenoma, Cushing's syndrome, Hypokalaemia, Hypertension, Hyperglycaemia, Facies - moon, Dorsal gibbus*, Rash, Hirsutism, Alopecia, Weight gain, Hypokalaemia, Hypercortisolaemia, Hypertension, Hyperglycaemia, Ecchymoses, Myasthaenia, Headache, Striae, Ultrasound scan, Blood pressure, Potassium, Transaminase, Urinary free cortisol, Cortisol (midnight), Cortisol (9am), Cortisol (serum), MRI, Histopathology, ACTH, Laparoscopic adrenalectomy, Prednisone, Potassium chloride, Insulin, Methyldopa*, General practice, Obstetrics, Unique/unexpected symptoms or presentations of a disease, April, 2020

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          Abstract

          Summary

          Cushing’s syndrome is an endocrine disorder that causes anovulatory infertility secondary to hypercortisolism; therefore, pregnancy rarely occurs during its course. We present the case of a 24-year-old, 16-week pregnant female with a 10-month history of unintentional weight gain, dorsal gibbus, nonpruritic comedones, hirsutism and hair loss. Initial biochemical, hormonal and ultrasound investigations revealed hypokalemia, increased nocturnal cortisolemia and a right adrenal mass. The patient had persistent high blood pressure, hyperglycemia and hypercortisolemia. She was initially treated with antihypertensive medications and insulin therapy. Endogenous Cushing’s syndrome was confirmed by an abdominal MRI that demonstrated a right adrenal adenoma. The patient underwent right laparoscopic adrenalectomy and anatomopathological examination revealed an adrenal adenoma with areas of oncocytic changes. Finally, antihypertensive medication was progressively reduced and glycemic control and hypokalemia reversal were achieved. Long-term therapy consisted of low-dose daily prednisone. During follow-up, despite favorable outcomes regarding the patient’s Cushing’s syndrome, stillbirth was confirmed at 28 weeks of pregnancy. We discuss the importance of early diagnosis and treatment of Cushing’s syndrome to prevent severe maternal and fetal complications.

          Learning points:
          • Pregnancy can occur, though rarely, during the course of Cushing’s syndrome.

          • Pregnancy is a transient physiological state of hypercortisolism and it must be differentiated from Cushing’s syndrome based on clinical manifestations and laboratory tests.

          • The diagnosis of Cushing’s syndrome during pregnancy may be challenging, particularly in the second and third trimesters because of the changes in the maternal hypothalamic-pituitary-adrenal axis.

          • Pregnancy during the course of Cushing’s syndrome is associated with severe maternal and fetal complications; therefore, its early diagnosis and treatment is critical.

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          Most cited references17

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          The hypothalamic-pituitary-adrenal axis in pregnancy: challenges in disease detection and treatment.

          Pregnancy dramatically affects the hypothalamic-pituitary-adrenal axis leading to increased circulating cortisol and ACTH levels during gestation, reaching values in the range seen in Cushing's syndrome (CS). The cause(s) of increased ACTH may include placental synthesis and release of biologically active CRH and ACTH, pituitary desensitization to cortisol feedback, or enhanced pituitary responses to corticotropin-releasing factors. In this context, challenges in diagnosis and management of disorders of the hypothalamic-pituitary-adrenal axis in pregnancy are discussed. CS in pregnancy is uncommon and is associated with fetal morbidity and mortality. The diagnosis may be missed because of overlapping clinical and biochemical features in pregnancy. The proportion of patients with primary adrenal causes of CS is increased in pregnancy. CRH stimulation testing and inferior petrosal sinus sampling can identify patients with Cushing's disease. Surgery is a safe option for treatment in the second trimester; otherwise medical therapy may be used. Women with known adrenal insufficiency that is appropriately treated can expect to have uneventful pregnancies. Whereas a fetal/placental source of cortisol may mitigate crisis during gestation, unrecognized adrenal insufficiency may lead to maternal or fetal demise either during gestation or in the puerperium. Appropriate treatment and management of labor are reviewed.
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            Cushing's syndrome during pregnancy: personal experience and review of the literature.

            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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              Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                12 April 2020
                2020
                : 2020
                : 20-0022
                Affiliations
                [1 ]Division of Endocrinology, Guillermo Almenara Irigoyen National Hospital , Lima, Peru
                [2 ]National University of Trujillo , School of Medicine, Trujillo, Peru
                [3 ]Metabolism and Reproduction Unit , Division of Endocrinology, Guillermo Almenara Irigoyen National Hospital, Lima, Peru
                Author notes
                Correspondence should be addressed to C J Benites-Moya; Email: cjbenitesmoya@ 123456gmail.com
                Article
                EDM200022
                10.1530/EDM-20-0022
                7159255
                a5a301ae-fc76-4f89-9fde-dc6de997175a
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 14 March 2020
                : 23 March 2020
                Categories
                Pregnant adult
                Female
                Hispanic or Latino - other
                Peru
                Adrenal
                Adrenal
                Cortisol
                ACTH
                Insulin
                Adrenocortical Adenoma
                Cushing's Syndrome
                Hypokalaemia
                Hypertension
                Hyperglycaemia
                Facies - Moon
                Dorsal Gibbus*
                Rash
                Hirsutism
                Alopecia
                Weight Gain
                Hypokalaemia
                Hypercortisolaemia
                Hypertension
                Hyperglycaemia
                Ecchymoses
                Myasthaenia
                Headache
                Striae
                Ultrasound Scan
                Blood Pressure
                Potassium
                Transaminase
                Urinary Free Cortisol
                Cortisol (Midnight)
                Cortisol (9am)
                Cortisol (Serum)
                Mri
                Histopathology
                ACTH
                Laparoscopic Adrenalectomy
                Prednisone
                Potassium Chloride
                Insulin
                Methyldopa*
                General Practice
                Obstetrics
                Unique/Unexpected Symptoms or Presentations of a Disease
                Unique/Unexpected Symptoms or Presentations of a Disease

                pregnant adult,female,hispanic or latino - other,peru,adrenal,cortisol,acth,insulin,adrenocortical adenoma,cushing's syndrome,hypokalaemia,hypertension,hyperglycaemia,facies - moon,dorsal gibbus*,rash,hirsutism,alopecia,weight gain,hypercortisolaemia,ecchymoses,myasthaenia,headache,striae,ultrasound scan,blood pressure,potassium,transaminase,urinary free cortisol,cortisol (midnight),cortisol (9am),cortisol (serum),mri,histopathology,laparoscopic adrenalectomy,prednisone,potassium chloride,methyldopa*,general practice,obstetrics,unique/unexpected symptoms or presentations of a disease,april,2020

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