Persistent calcium dependence after total thyroidectomy: a hypothesis of bone hunger syndrome with parathyroid reserve insufficiency in the setting of normalized parathyroid hormone - a case report and literature review.

BACKGROUND: Restoration of parathyroid hormone (PTH) to the normal range following total thyroidectomy is conventionally regarded as an indicator of functional recovery of the parathyroid glands. Nevertheless, a subset of patients develop hypocalcemia upon withdrawal of supplementation. This report describes a case in which PTH normalized postoperatively yet calcium supplements could not be discontinued for three years, and discusses the underlying mechanisms and management strategy.

CASE SUMMARY: A 40-year-old woman with multifocal papillary thyroid carcinoma harboring the BRAF V600E mutation underwent total thyroidectomy with bilateral level VI lymph node dissection. The patient had a background of Hashimoto's thyroiditis (thyroglobulin antibody 225.30 IU/mL, thyroid peroxidase antibody 144.40 IU/mL). Preoperative serum calcium and PTH were within normal limits, but 25-hydroxyvitamin D was severely deficient (12.8 ng/mL). On postoperative day 1, hypocalcemic symptoms accompanied by a decline in serum calcium occurred and resolved after intravenous calcium administration. PTH transiently rose to 70.8 pg/mL on postoperative day 3 but fell to 3.0 pg/mL by one month after surgery. At three months postoperatively, PTH recovered to 26.7 pg/mL and remained consistently normal over the subsequent three years. However, repeated attempts to taper or discontinue calcium and active vitamin D at 3, 5, and 18 months postoperatively, as well as on multiple later occasions-provoked numbness of the hands and perioral region within 4-7 days. Emergency laboratory evaluations consistently revealed decreased serum calcium without a compensatory rise in PTH. At three years after surgery, the patient still depends on oral calcium supplementation to maintain normocalcemia.

CONCLUSION: Normal basal PTH levels do not exclude parathyroid reserve insufficiency. In this patient, preoperative vitamin D deficiency may have predisposed to an osteomalacic state, potentially generating a persistent skeletal calcium demand when combined with a limited PTH stress response. We hypothesize that this represents a phenotype of 'bone hunger syndrome with parathyroid reserve insufficiency'. Such patients require long-term individualized calcium replacement, and assessment of the calcium stress response facilitates precise phenotyping. However, further studies with objective biomarkers are needed to validate this hypothesis.