Endocrine Abstracts

Background: Milk- alkali syndrome (MAS), characterized by the triad of hypercalcemia, metabolic alkalosis, and renal dysfunction, is increasingly recognized as a complication of calcium supplementation, particularly in the management of hypoparathyroidism. Some have proposed should be called calcium- alkali syndrome (CAS). We delineate two cases of CAS and provide a review of relevant literature, emphasizing the endocrine aspects of CAS.

Case Presentations: The first case details a 52-year-old male with iatrogenic hypoparathyroidism post-thyroidectomy, who developed marked hypercalcemia (corrected serum calcium: 13.1 mg/dl) and acute kidney injury (serum creatinine: 2.8 mg/dl) and alkalosis (pH: 7.52, HCO3^-: 33.5 mmol/l, PCO₂: 41mmHg). This was attributed to olmesartan/hydrochlorothiazide, alphacalcidol, calcium carbonate and cholecalciferol. Treatment included intravenous hydration and medication titration, leading to calcium level normalization. The second case involved an 83-year-old woman with a background of hypoparathyroidism, presenting with cognitive impairment and hypercalcemia (corrected serum calcium: 15.36 mg/dl) and acute kidney injury (serum creatinine: 2.6 mg/dl) and alkalosis (pH: 7.51, HCO3: 33.5 mmol/l, PCO₂: 42mmHg) secondary to alfacalcidol, irbesartan and calcium carbonate ingestion; renal function was also compromised. Intravenous fluid administration and medication dose adjustment led to clinical improvement; renal impairment remained.

Discussion: The pathophysiology of CAS is anchored in hypercalcemia-induced nephropathy, precipitated by excessive exogenous calcium intake. This initiates a cascade involving decreased glomerular filtration, enhanced renal calcium reabsorption. Volume depletion promotes tubular reabsorption of bicarbonate creating metabolic alkalosis which in turn decreases renal calcium excretion enhancing metabolic alkalosis. Clinical manifestations are varied, ranging from subacute neuromuscular symptoms to chronic renal insufficiency. Historically associated with antacid overuse, the contemporary landscape of CAS has shifted towards excessive calcium supplementation in the context of osteoporosis, post-surgical hypoparathyroidism, and specific demographics like postmenopausal women or those with renal insufficiency.

Conclusion: These cases highlight the importance of cautious calcium supplementation in hypoparathyroidism management. Endocrinologists and healthcare providers should maintain a high index of suspicion for CAS, especially in predisposed subjects, and advocate for regular serum calcium monitoring. Adjustments in calcium and vitamin D supplementation must be made judiciously to prevent the potentially serious complications of CAS, including irreversible renal damage.