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      A Case Report of Cushing’s Disease Presenting With Psychosis and Muscle Weakness Postpartum

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          Abstract

          Cushing’s syndrome is a condition leading to overproducing of cortisol by the adrenal glands. If the pituitary gland overproduces cortisol, it is called Cushing’s disease. Cushing’s syndrome and even Cushing’s disease during and after pregnancy are rare events. There is not enough literature and guidance for managing and treating these patients. The diagnosis of Cushing’s syndrome in pregnancy is often delayed because the symptoms overlap. We presented a thin 31-year-old woman, admitted 2 months after a normal-term delivery, with an atypical presentation of Cushing’s disease, unusual clinical features, and a challenging clinical course. She had no clinical discriminatory features of Cushing’s syndrome. Given that the patient only presented with psychosis and proximal myopathy and had an uncomplicated pregnancy, our case was considered unusual. The patients also had hyperpigmentation and severe muscle weakness which are among the less common presentations of Cushing’s syndrome. Our findings suggest that an early diagnosis of Cushing’s disease is important in pregnancy period for its prevalent fetal and maternal complications, and it should be treated early to optimize fetal and maternal outcomes as there is an increasing trend toward live births in treated participants.

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          Most cited references39

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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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            Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy.

            Adrenocorticotropin (ACTH) and cortisol in plasma were measured weekly from early in gestation through delivery in five women whose pregnancies were normal. During the twelfth week of pregnancy, the concentration of ACTH in plasma of blood samples obtained between 0800 and 0900 hours was 23 +/- 4.6 pg/ml (mean and SEM) and rose progressively to 59 +/- 16 pg/ml at 37 weeks. The levels of ACTH in plasma were significantly lower throughout pregnancy than those found in nonpregnant women. During labor and delivery, ACTH levels rose strikingly to values of 301 +/- 137 pg/ml. As pregnancy advanced, the concentration of cortisol in plasma increased progressively from 149 +/- 34 ng/ml (mean and SEM) at 12 weeks to 352 +/- 90 ng/ml at 26 weeks' gestation but changed minimally thereafter until labor commenced, during which values of 706 +/- 148 ng/ml were achieved. ACTH and cortisol secretory patterns over a 24-hour period were also investigated in one subject during each trimester of pregnancy. Diurnal variations were observed that were qualitatively similar to those seen in nonpregnant women. From the results of these studies, we conclude that ACTH levels are suppressed in plasma of normal pregnant women but are higher in late pregnancy than in early pregnancy. The rise in plasma ACTH concentrations, as pregnancy advances, in spite of increasing levels of plasma cortisol, estrogens, and progesterone, is suggestive of the possibility that a source of ACTH exists that is not subject to negative feedback control, that the clearance of free cortisol increases as pregnancy advances, or that there is an alteration in the metabolism of the ACTH precursor protein produced by the pituitary and/or placenta.
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              Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis.

              The past 45 yr' experience with Cushing's syndrome (CS) has led to the awareness of its complex nature and, by the same token, brought about an increase in the diagnostic and therapeutic dilemmas. We carried out a retrospective multicentre study on the diagnostic work-up and treatment in 426 patients with CS, subdivided as follows: 288 with Cushing's disease (CD), 80 with an adrenal adenoma, 24 with an adrenal carcinoma, 25 with ectopic ACTH and/or CRH secretion, and 9 with ACTH-independent nodular adrenal hyperplasia. Normal urinary free cortisol (UFC) values among multiple collections were recorded in about 10% of patients with CS. In 28% of patients with ACTH-independent CS, basal ACTH concentrations were within the normal range but did not respond to CRH stimulation. Measurement of ACTH levels by immunoradiometric assay, rather than by RIA, offered a greater chance of recognizing patients with ACTH-independent CS or ectopic secretion. A 50% increase in ACTH or cortisol levels after CRH yielded a diagnostic accuracy of 86% and 61%, respectively, in the differential diagnosis of ACTH-dependent CS. An 80% decrease in cortisol levels after 8 mg dexamethasone overnight, or in UFC values after the classical 2-day administration, excluded an ectopic secretion but carried a low negative predictive value given the high number of nonsuppressors among patients with CD. Pituitary imaging identified an adenoma in 61% of patients with CD. At inferior petrosal sinus sampling, an ACTH centre: periphery gradient after CRH less than 3, correctly classified all patients with ectopic secretion but misdiagnosed 15% of 76 patients with CD. Transsphenoidal pituitary surgery, the standard therapy for CD, resulted in complete remission (appearance of clinical signs of adrenal insufficiency associated with low/normal UFC excretion and, when available, low/normal morning plasma ACTH and cortisol levels) in 69% of patients. The overall relapse rate after pituitary surgery was 17%. The probability of relapse-free survival, as assessed by Kaplan-Meier analysis, was 95% at 12 months, 84% at 2 yr, and 80% at 3 yr. Risk of relapse was significantly correlated with postoperative baseline plasma ACTH and cortisol peak after CRH. No relapses were observed among patients who did not respond to CRH. Other therapeutic approaches for CD, such as pituitary irradiation and medical therapy, resulted in normalization of cortisol secretion in about half of treated cases. In summary, an accurate selection of the available diagnostic tools leads to the correct diagnosis in the majority of patients with CS. The therapeutic options for CD, adrenal carcinoma, and ectopic secretion are, as yet, not fully satisfactory. The high incidence of relapse after pituitary surgery calls for a prolonged follow-up.
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                Author and article information

                Journal
                J Investig Med High Impact Case Rep
                J Investig Med High Impact Case Rep
                HIC
                sphic
                Journal of Investigative Medicine High Impact Case Reports
                SAGE Publications (Sage CA: Los Angeles, CA )
                2324-7096
                5 October 2023
                Jan-Dec 2023
                : 11
                : 23247096231204732
                Affiliations
                [1 ]Iran University of Medical Sciences, Tehran, Iran
                [2 ]Tehran University of Medical Sciences, Iran
                Author notes
                [*]Delaram Eskandari, Department of Endocrinology, Rasool Akram Medical Complex, School of Medicine, Iran University of Medical Sciences, Niayesh Street, Sattarkhan Avenue, Tehran 1445613131, Iran. Email: eskandari.@ 123456iums.ac.ir
                Article
                10.1177_23247096231204732
                10.1177/23247096231204732
                10559700
                2ad7ac7d-ebb1-4b12-8d75-1b02696e0bca
                © 2023 American Federation for Medical Research

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 9 August 2022
                : 9 August 2023
                : 19 August 2023
                Categories
                Case Report
                Custom metadata
                January-December 2023
                ts1

                cushing’s disease,pregnancy,cushing’s,cortisol
                cushing’s disease, pregnancy, cushing’s, cortisol

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