Endocrine Abstracts

Background: Hypercalcemia, serum calcium above the reference range, is common biochemical finding. When symptomatic, it may present with bone pain, renal colic, constipation, abdominal pain, or neuropsychiatric manifestations-depression. Hypercalcemia is broadly classified into PTH-dependent and PTH-independent causes. PTH-dependent causes include primary hyperparathyroidism, tertiary hyperparathyroidism, and familial hypocalciuric hypercalcemia, while PTH-independent causes are often malignancy, granulomatous diseases (e.g., sarcoidosis, tuberculosis), thiazide use, and less commonly, adrenal insufficiency. The mechanisms underlying hypercalcemia in adrenal insufficiency are not fully understood but are thought to involve increased renal calcium reabsorption and enhanced bone resorption through elevated sclerostin levels. Below is a case of undiagnosed primary adrenal insufficiency presenting with hypercalcemia, hyponatremia, and acute kidney injury.

Clinical Case: A 39-year-old man presented with dizziness, low mood, anorexia, nausea, vomiting, and unintentional weight loss. His past medical history included subclinical hypothyroidism and depression, and was taking sertraline. He was clinically dehydrated, hypotensive with a blood pressure of 93/72 mmHg, and had generalized skin hyperpigmentation. Initial blood tests revealed hyponatremia (Na-126 mmol/l,133–146), hypercalcemia (adjusted calcium 3.05 mmol/l,2.2–2.6), and acute kidney injury with a serum creatinine 143µmol/l (baseline 88). Thyroid studies showed elevated TSH (11.36 mU/l,0.3–5.0) with freeT4 at the lower end of normal(8.9 pmol/l,7.9–16.0). An initial working diagnosis was hypercalcemia-induced dehydration with acute kidney injury. He was commenced on intravenous fluids, and sertraline was discontinued in view of hyponatremia. Further investigations demonstrated suppressed parathyroid hormone (0.3 pmol/l,1.3–9.3), excluding primary hyperparathyroidism. Urine osmolality was 390 mmol/kg with urine sodium of 43 mmol/l. In the context of hypotension, hyponatraemia, and other biochemical abnormalities, adrenal insufficiency was suspected. Morning serum cortisol was <11 nmol/l (185–624), confirming adrenal insufficiency. The patient was commenced on hydrocortisone replacement. Levothyroxine therapy for hypothyroidism was initiated one week later. Both hypercalcemia and hyponatremia resolved with treatment. At follow-up, ACTH was markedly elevated at 1301 ng/l (<50), and adrenal autoantibodies were positive, confirming autoimmune primary adrenal insufficiency. Aldosterone was suppressed(<60 pmol/l,90–700) with normal renin (1.4 nmol/l/hr,0.5–3.5). Curiously, renin was initially normal, an uncommon finding in Addison’s disease. The patient was initially managed without fludrocortisone, with close renin monitoring. Fludrocortisone was introduced at third months when renin levels began to rise.

Conclusion: This case highlights Addison’s disease can present atypically with PTH-independent hypercalcemia, hyponatremia, hypotension, and acute kidney injury. A high index of suspicion will provide prompt diagnosis in patients with unexplained electrolyte disturbances, especially with systemic features such as weight loss and hyperpigmentation. Early glucocorticoid replacement, prior to thyroid hormone initiation, is essential to prevent adrenal crisis³. Renin level may be normal at the initial stage, but mineralocorticoid replacement will always be required. Prompt diagnosis and treatment can fully reverse metabolic abnormalities, including the rare manifestation of hypercalcemia.