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      Glucocorticoid-induced adrenal insufficiency: an uncommon cause of hypercalcaemia

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          Abstract

          Summary

          Long-term use of exogenous glucocorticoids leads to the suppression of the hypothalamic–pituitary–adrenal axis. Therefore, if the glucocorticoid is withdrawn abruptly, patients will develop adrenal insufficiency. Hypercalcaemia is a rare but well-known complication of adrenal insufficiency. However, hypercalcaemia is a rare presentation of glucocorticoid-induced adrenal insufficiency (GI-AI). A 62-year-old patient with a past history of diabetes mellitus, ischaemic heart disease, stroke, hypertension and dyslipidaemia presented with polyuria, loss of appetite, malaise and vomiting for a duration of 2 months. His ionized calcium level was high at 1.47 mmol/L. Intact parathyroid hormone was suppressed (4.3 pg/mL) and vitamin D was in the insufficient range (24.6 ng/mL). Extensive evaluation for solid organ or haematological malignancy including contrast-enhanced CT chest, abdomen, pelvis, multiple myeloma workup and multiple tumour markers were negative. His synacthan-stimulated cortisol was undetectable thus confirming adrenal insufficiency. His adrenocorticotrophic hormone level was 3.82 pg/mL (4.7–48.8) excluding primary adrenal insufficiency. His MRI brain and other pituitary hormones were normal. Further inquiry revealed that the patient had taken over-the-counter dexamethasone on a regular basis for allergic rhinitis for more than 2 years and had stopped 2 weeks prior to the onset of symptoms. Therefore, a diagnosis of GI-AI leading to hypercalcemia was made. The patient was resuscitated with intravenous fluids and replacement doses of oral hydrocortisone were started with a plan of prolonged tailing off to allow the endogenous adrenal function to recover. His calcium normalized and he made a complete recovery.

          Learning points
          • Long-term use of glucocorticoids leads to the suppression of the hypothalamic–pituitary–adrenal axis.

          • If the glucocorticoid is withdrawn abruptly, patients will develop adrenal insufficiency which is known as glucocorticoid-induced adrenal insufficiency.

          • Adrenal insufficiency should be considered in the differential diagnosis of parathyroid hormone-independent hypercalcaemia.

          • A thorough clinical history is of paramount importance in arriving at the correct diagnosis.

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          Most cited references15

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          Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment.

          Suppression of the adrenal response is an unpredictable consequence of glucocorticoid treatment. To investigate the kinetics of the adrenal response after short-term, high-dose glucocorticoid treatment, we measured the adrenal response to the low-dose (1 microg) corticotropin stimulation test. We studied 75 patients who received the equivalent of at least 25 mg prednisone daily for between 5 days and 30 days. After discontinuation of glucocorticoid treatment, 1 microg corticotropin was administered intravenously, and stimulated plasma cortisol concentrations were measured 30 min later. In patients with a suppressed response to 1 microg corticotropin, the test was repeated until stimulated plasma cortisol concentrations reached the normal range. The adrenal response to 1 microg corticotropin was suppressed in 34 patients and normal in 41. Subsequent low-dose corticotropin tests showed a steady recovery of the adrenal response within 14 days. In two patients, the adrenal response remained suppressed for several months. There was no correlation between plasma cortisol concentrations and the duration or dose of glucocorticoid treatment. Suppression of the adrenal response is common after short-term, high-dose glucocorticoid treatment. The low-dose corticotropin test is a sensitive and simple test to assess the adrenal response after such treatment.
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            Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone.

            To assess the status of the hypothalamic-pituitary-adrenal (HPA) axis in cortico-steroid-treated patients whose prednisone dose had been tapered to physiologic doses. The design of the study was a retrospective chart review of 50 consecutive patients receiving 10 mg or less of prednisone daily at a university teaching hospital rheumatology clinic. Patients were given a rapid adrenocorticotropic hormone stimulation test, with cortisol levels obtained at baseline and after intravenous administration of cosyntropin. Charts were reviewed for duration of therapy, highest, current, and total cumulative steroid dose, and average daily steroid dose in each month of the preceding 2 years. Current steroid dose was the only significant indicator of HPA axis function. Patients receiving less than 5 mg of prednisone daily had a normal HPA axis response, whereas those receiving 5 mg or more had widely varied responses. Neither the total, the highest prednisone dose, nor the duration of therapy was a significant indicator of HPA axis recovery. Spontaneous recovery of the HPA axis is usual for patients who are taking prednisone at daily doses of 5 mg or less. Return of normal HPA axis function can be achieved without alternate-day therapy in patients whose disease allows tapering to daily prednisone doses of 5 mg or less.
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              New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2

              Stanniocalcin, a glycosylated peptide hormone, first discovered in a bony fish has originally been shown to play critical role in calcium and phosphate homeostasis. Two paralogs of stanniocalcin (STC1 and STC2) identified in mammals are widely expressed in variety of tissues. This review provides historical perspective on the discovery of fish and mammalian stanniocalcin, describes molecular regulation of STC2 gene, catalogs distribution as well as expression of STC2 in tissues, and provides key structural information known till date regarding mammalian STC2. Additionally, this mini review summarizes pivotal functions of STC2 in calcium and phosphate regulation, cytoprotection, cell development, and angiogenesis. Finally, STC2's role as a novel marker for human cancers has also been outlined. Reviewing these studies will provide an opportunity to understand STC2's structure, biological functions as well as key molecular pathways involving STC2, which will help us design innovative therapeutic interventions using this novel hormone.

                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
                04 April 2022
                2022
                : 2022
                : 21-0177
                Affiliations
                [1 ]University Medical Unit , National Hospital of Sri Lanka, Colombo, Sri Lanka
                [2 ]Department of Clinical Medicine , Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
                Author notes
                Correspondence should be addressed to S D N De Silva; Email: neomalde@ 123456gmail.com
                Author information
                http://orcid.org/0000-0003-3763-2020
                Article
                EDM210177
                10.1530/EDM-21-0177
                9175604
                35510507
                ee48d240-7164-4c3a-83f8-d730effac0a5
                © The authors

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

                History
                : 02 February 2022
                : 04 April 2022
                Categories
                Adult
                Male
                Asian - other
                Sri Lanka
                Adrenal
                Bone
                Adrenal
                Unique/Unexpected Symptoms or Presentations of a Disease
                Unique/Unexpected Symptoms or Presentations of a Disease

                adult,male,asian - other,sri lanka,adrenal,bone,unique/unexpected symptoms or presentations of a disease,may,2022

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