SAT-826 - Normocalcemic Tertiary Hyperparathyroidism from Chronic Iatrogenic Malabsorption

Background: Iatrogenic malabsorption after bariatric surgery can cause persistent micronutrient deficiencies with skeletal and endocrine adverse consequences. Chronic calcium and vitamin D deficiency typically results in secondary hyperparathyroidism (SHPT), but prolonged stimulation may produce autonomous PTH secretion consistent with tertiary hyperparathyroidism (THPT), prior to development of hypercalcemia (1).

Case: A 64-year-old woman with Roux-en-Y gastric bypass in 2001 and liver transplantation for NASH cirrhosis presented with multiple fragility fractures consistent with clinical osteoporosis and signs and symptoms of osteomalacia. Post-transplant immunosuppression (tacrolimus, mycophenolate mofetil, prednisone) and RYGB-related fat-soluble vitamin malabsorption resulted in vitamin D deficiency (undetectable at diagnosis), low vitamin A, phosphorus, urine calcium, and iron deficiency anemia. Intact PTH (>250 pg/mL) and total alkaline phosphatase were elevated. Serum calcium remained consistently low-normal. All deficiencies were corrected inclusive of a 25-OH vitamin D >30 ng/mL, excluding vitamin D deficiency as the cause of persistent hyperparathyroidism. The differential included SHPT, normocalcemic primary hyperparathyroidism, and normocalcemic THPT.

Over 13 years of follow-up, calcium remained low-normal without an upward trend and without hypercalcemia. PTH demonstrated partial but incomplete suppression (111–170 pg/mL; ~60-70% reduction from baseline) during prolonged high-dose calcium repletion (up to 4800 mg/day) and chlorthalidone. After self-discontinuation of calcium, PTH rebounded to 243.8 pg/mL, failing to normalize, consistent with THPT rather than SHPT.

High-dose calcium and vitamin D supplementation produced marked skeletal improvement without antiresorptive therapy. Lumbar spine and total hip BMD increased ~15% over two years, with substantial suppression of bone turnover markers (BTM: sCTX, P1NP, BSAP), consistent with a PTH-mediated high turnover state responsive to nutritional repletion and partial parathyroid suppression. Rebound of BTM paralleled cessation of supplementation and rising PTH.

Conclusion: This case demonstrates prolonged iatrogenic malabsorption causing severe micronutrient deficiency, SHPT, and biochemical transition to normocalcemic THPT. Calcium challenge literature describes partial suppression of parathyroid hyperplasia (2). Nutritional therapy alone improved BMD despite weight loss. Persistent malabsorption for ~16 years post-RYGB with >25 years of low-normal calcium argues against primary hyperparathyroidism. Long-term follow-up and calcium challenge testing can aid in distinguishing this entity and may avert parathyroidectomy.

References:
1. Mechanick JI et al. Endocr Pract. 2019;25:S1–81.
2. Silverberg SJ et al. J Clin Endocrinol Metab. 1997;82:377–82.

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