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      Opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia

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      1 , 2 , 1 , 2 ,
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd

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          Summary

          Adrenal insufficiency is a rare cause of hypercalcaemia and should be considered when more common causes such as primary hyperparathyroidism and malignancy are excluded. Opioid therapy as a cause of adrenal insufficiency is a possibly under-recognised endocrinopathy with potentially life-threatening adverse effects. We report on a case of opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia. The patient was a 25-year-old man who developed hypercalcaemia during the recovery stage after a period of critical illness. Systematic investigation of his hypercalcaemia found it to be due to secondary adrenal insufficiency, developing as a consequence of methadone opioid analgesia. Treatment with i.v. saline and subsequent glucocorticoid replacement led to resolution of the hypercalcaemia. The hypoadrenalism resolved when opioids were subsequently weaned and ceased. These two interacting endocrinopathies of opioid-induced adrenal insufficiency and consequent hypercalcaemia highlight the importance of maintaining awareness of the potentially serious adverse clinical outcomes which can occur as a result of opioids, particularly considering that symptoms of hypoadrenalism can overlap with those of concomitant illness. Treatment with hydration and glucocorticoid replacement is effective in promptly resolving the hypercalcaemia due to hypoadrenalism. Hypoadrenalism due to prescribed and recreational opioids may be more common than is currently recognised.

          Learning points

          • Opioid therapy can cause clinically significant secondary adrenal insufficiency, and this may be more common than is currently recognised.

          • Adrenal insufficiency is reversible after discontinuation of the opioid therapy.

          • Hypercalcaemia can occur as a consequence of adrenal insufficiency, and may be the presenting feature.

          • Treatment of hypercalcaemia due to adrenal insufficiency involves i.v. saline and glucocorticoid replacement.

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          Most cited references9

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          Etiology of hypercalcemia in a patient with Addison's disease.

          A case is reported of a hypercalcemic patient with primary Addison's disease. A combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney accounted for the hypercalcemia. The mechanisms responsible for the reduction in calcium removal were decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors were secondary to volume depletion and improved rapidly during rehydration with saline infusion. The enhanced calcium mobilization was probably of skeletal origin. It persisted irrespective of volume status until hydrocortisone treatment was instituted. Serum 1,25-dihydroxyvitamin D3 levels were below 10 pg/ml, even after normalization of the glomerular filtration rate, but returned slowly to the normal range during corticosteroid substitution. Serum 25-hydroxyvitamin D3 and parathyroid hormone levels were within the normal range. Our case report therefore demonstrates that physiological amounts of glucocorticoids reduce bone resorption, normalize serum calcium, and restore the production of 1,25-dihydroxyvitamin D3.
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            Addison's disease--clinical studies. A report fo 108 cases.

            J. Nerup (1974)
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              Effect of oral morphine and naloxone on pituitary-adrenal response in man induced by human corticotropin-releasing hormone.

              To further investigate the role of opioids in the regulation of the pituitary-adrenal axis we studied the effect of morphine and naloxone on human corticotropin-releasing hormone (hCRH)-induced ACTH, immunoreactive (ir) beta-endorphin, and cortisol release in normal subjects. Protocols: 1. 30 mg of a slow-release preparation of morphine or placebo was given orally 3 h prior to administration of hCRH (0.1 mg iv) (N = 7). 2. Naloxone (4 mg as bolus iv) or placebo was given 5 min prior to hCRH (N = 7). 3. Naloxone (4 mg iv as bolus followed by a continuous infusion of 6 mg over 75 min) or placebo was started 15 min prior to hCRH (N = 6). hCRH was injected at 11.00 h (protocol 1, 2) or at 17.00 h (protocol 3). Oral morphine not only suppressed basal hormone levels (P less than 0.02), but also the peak response to hCRH compared with placebo (cortisol: 270 +/- 50 vs 559 +/- 80 nmol/l; ACTH: 5.1 +/- 1.5 vs 13.1 +/- 2.7 pmol/l; ir beta-endorphin: 48.5 +/- 8.7 vs 88 +/- 14 pmol/l; mean +/- SEM, P less than 0.02). Similarly, the maximum incremental changes and the area under the curve were significantly reduced for all three hormones compared with placebo (P less than 0.05). After 4 mg of naloxone in the morning, no significant hormonal changes in response to hCRH were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                edm
                EDM Case Reports
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                18 June 2015
                2015
                : 2015
                : 150035
                Affiliations
                [1 ]Department of Endocrinology, Royal Prince Alfred Hospital , Camperdown, New South Wales, 2050, Australia
                [2 ]Sydney Medical School, Charles Perkins Centre, The University of Sydney , Sydney, New South Wales, 2006, Australia
                Author notes
                Correspondence should be addressed to S M Twigg Email: stephen.twigg@ 123456sydney.edu.au
                Article
                EDM150035
                10.1530/EDM-15-0035
                4496564
                26161260
                442c61b5-58a6-4074-940a-d79a63efed0d
                © 2015 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 6 June 2015
                : 18 June 2015
                Categories
                Unusual Effects of Medical Treatment

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