Opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia
Open accessAbstract
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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Less common but well-recognized manifestations of cortisol deficiency include hypercalcemia and hypoglycemia.
“As well as common symptoms of cortisol deficiency, such as fatigue, nausea/vomiting, musculoskeletal pain, weight loss, headache, and light-headedness (119), less common but well recognized manifestations, such as hypercalcemia (123) and hypoglycemia (124) have been described.”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [123]
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- Authors
- Lee, A. S., & Twigg, S. M.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Twigg, Stephen M
- Venue
- Endocrinology, Diabetes & Metabolism Case Reports
- Publisher
- Bioscientifica
- Published
- 2015-07-01
- Volume
- 2015
- Pages
- 150035-150035
- ISSN
- 2052-0573 (ISSN-L)
- PMC
- PMC4496564
- OpenAlex
- W856920266
- Cited by
- 31
- References
- 10
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 1
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Endocrinology Diabetes and Metabolism Case Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Keywords
- secondary adrenal insufficiency, hypercalcemia, methadone, opioid side effects, glucocorticoid replacement therapy, adrenal insufficiency, critical illness, opioid withdrawal
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