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      An extremely rare case of calcinosis cutis in human Cushing’s disease

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          Abstract

          Summary

          Cushing’s disease or pituitary adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is considered a rare condition. It is caused by hypersecretion of the ACTH by a pituitary adenoma that ultimately induces endogenous hypercortisolism by stimulating the adrenal glands. It is responsible for significant morbidity and mortality. The clinical signs and symptoms of hypercortisolism are usually common and non-specific including obesity, moon face, hypertension, hirsutism and facial plethora. The association between Cushing’s disease and calcinosis cutis which is defined as dystrophic calcium deposition in the skin and subcutaneous tissues is extremely rare. To the best of our knowledge, it has never been described previously in humans, probably like a symptom or complication of chronic and severe hypercortisolism. In this paper, we report a case of a 30-year-old female diagnosed with Cushing’s disease and presented bilateral leg’s calcinosis cutis complicated with ulceration. The evolution was favorable and the complete cicatrization was obtained 12 months following the suppression of systemic glucocorticoid excess.

          Learning points
          • Calcinosis cutis is common in autoimmune connective diseases. However, to our knowledge, it has never been reported in humans with Cushing’s disease.

          • Given the rarity of this association, the diagnostic approach to calcinosis cutis must exclude the other etiologies.

          • Calcinosis cutis is challenging to treat with no gold standard therapy. In our case, the use of the combination of colchicine and bisphosphonates does not significantly improve the patient’s outcomes. In fact, we suppose that without treating the endogenous hypercortisolism, the calcinosis cutis will not resolve.

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          Most cited references12

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          Epidemiology of Cushing’s Syndrome

          Overt Cushing’s syndrome is a rare disorder with an annual incidence of 2–3/million of which benign adrenal adenomas account for 0.6/million. The female:male ratio is 3:1. Preliminary data indicate a high proportion of subclinical Cushing’s syndrome in certain risk populations such as patients with type 2 diabetes or osteoporosis. The clinical implications of these observations are presently unclear. Surgery remains first line treatment for overt disease and initial cure or remission is obtained in 65–85% of patients with Cushing’s disease. Late recurrences, however, occur in up to 20% and the risk does not seem to plateau even after 20 years of follow-up. A 2- to 3-fold increase in mortality is observed in most studies, and this excess mortality seems confined to patients in whom initial cure was not obtained. Cushing’s syndrome continues to pose diagnostic and therapeutic challenges and life-long follow-up is mandatory.
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            Calcinosis in rheumatic diseases.

            Calcinosis, or dystrophic soft-tissue calcification, occurs in damaged or devitalized tissues in the presence of normal calcium/phosphorus metabolism. It is often noted in the subcutaneous tissues of connective tissues diseases--primarily systemic lupus erythematosus, scleroderma, or dermatomyositis--and may involve a relatively localized area or be widespread. The calcinotic accumulations may lead secondarily to muscle atrophy, joint contractures, and skin ulceration complicated by recurrent episodes of local inflammation and infection. To review the classification, pathogenesis, clinical features, and treatment of calcinosis in rheumatic diseases. A MEDLINE search of articles from 1972 to 2004 was conducted utilizing the index word "calcinosis" with the coindexing terms "scleroderma," "lupus," "dermatomyositis," and "dystrophic calcification." Calcinosis may be the source of both pain and disability in connective tissue disease patients. Illustrative cases of patients with severe calcinosis are described. The literature available was critically reviewed. While warfarin, colchicine, probenecid, bisphosphonates, diltiazem, minocycline, aluminum hydroxide, salicylate, surgical extirpation, and carbon dioxide laser therapies have been used, no treatment has convincingly prevented or reduced calcinosis. Calcinosis is common in the conditions reviewed and a number of agents have been used for treatment. However, the approach to calcinosis management is disorganized, beginning with the lack of a generally accepted classification and continuing with a lack of systematic study and clinical therapeutic trials.
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              Cushing's disease.

              Cushing's syndrome refers to the clinical manifestations induced by chronic exposure to excess glucocorticoids. There are three pathological conditions that can result in the chronic overproduction of endogenous cortisol in man: the most frequent is Cushing's disease where adrenocorticotropic hormone (ACTH) is overproduced by a pituitary corticotroph adenoma, rarely ACTH can be produced in an 'ectopic' manner by a non-pituitary tumour, finally cortisol can be directly over-secreted by one or (rarely) the two adrenals that have become tumourous, either benign or malignant. The positive diagnosis of Cushing's syndrome requires that chronic hypercortisolism is unequivocally demonstrated biologically, using 24-h urinary cortisol, late-evening plasma or salivary cortisol, midnight 1-mg or the classic 48-h-low-dose dexamethasone suppression test, etc., all with essentially the same diagnosis potencies. The search for the responsible tumour then relies on the assessment of the corticotroph function, and imaging: suppressed ACTH plasma levels indicate an 'adrenal' Cushing, and the responsible unilateral adrenocortical tumour is always visible at computed tomography (CT) scan, whereas its benign or malignant nature may be difficult to diagnose before surgery. Imaging can suspect bilateral 'adrenal' Cushing, when the two adrenals are small, as in the primary pigmented nodular adrenal dysplasia associated with Carney complex, or enlarged, as in the ACTH-independent macronodular adrenocortical hyperplasia. Measurable or increased ACTH plasma levels indicate either Cushing's disease or the ectopic ACTH syndrome. When the dynamics of the corticotroph function (high-dose dexamethasone suppression test, the CRH test) are equivocal, and/or the imaging is non-contributive, it may be difficult to distinguish between the two. This is the situation where sampling ACTH plasma levels in the inferior petrosal sinus may be necessary. The best treatment option of Cushing's disease is when the responsible corticotroph adenoma can be entirely removed by the trans-sphenoidal approach, with sufficient skill to preserve the normal anterior pituitary function. When it fails, all other options directed towards the pituitary (radiation therapies), or the adrenals (medications or surgery), have numerous side effects. There is at present no recognised efficient medical treatment towards the corticotroph adenoma -still an orphan disease.

                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
                10 May 2022
                2022
                : 2022
                : 21-0113
                Affiliations
                [1 ]Department of Diabetology and Endocrinology , Mohammed VI Hospital
                [2 ]Laboratory of Epidemiology , Clinical Research and Public Health
                [3 ]Department of Dermatology , Mohammed VI Hospital, Faculty of Medicine and Pharmacy, Mohamed Ist University, Oujda, Morocco
                Author notes
                Correspondence should be addressed to N Rbiai; Email: najwarbiai@ 123456gmail.com
                Author information
                http://orcid.org/0000-0002-8490-3885
                Article
                EDM210113
                10.1530/EDM-21-0113
                9254282
                35670257
                c22c862f-210a-4323-ab7d-3176ae03f706
                © The authors

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

                History
                : 05 May 2022
                : 10 May 2022
                Categories
                Adult
                Female
                Other
                Sri Lanka
                Adrenal
                Pituitary
                Skin
                Adrenal
                Bone
                Mineral
                Neuroendocrinology
                Dermatology
                Unique/Unexpected Symptoms or Presentations of a Disease
                Unique/Unexpected Symptoms or Presentations of a Disease

                adult,female,other,sri lanka,adrenal,pituitary,skin,bone,mineral,neuroendocrinology,dermatology,unique/unexpected symptoms or presentations of a disease,june,2022

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