The utility of serum 25-hydroxyvitamin D in predicting post-thyroidectomy hypocalcemia in thyrotoxic subjects: a single-center cohort study


  • Poongkodi Karunakaran Department of Endocrine Surgery, Madras Medical College, Chennai, Tamil Nadu, India
  • Deepak Thomas Abraham Department of Endocrine Surgery, Christian Medical College, Vellore, Tamil Nadu, India



Euthyroid, Hyperthyroidism, Postoperative hypocalcemia, Thyroidectomy, Thyrotoxicosis, 25-hydroxycholecalciferol, Vitamin D deficiency


Background: The role of preoperative vitamin D deficiency as a predictor of post-thyroidectomy hypocalcemia in thyrotoxic subjects is controversially reported. This prospective cohort study determined the utility of serum 25-hydroxyvitamin D (25OHD) levels in predicting transient hypocalcemia in thyrotoxic and euthyroid patients undergoing total thyroidectomy (TT).

Methods: Subjects with new-onset hyperthyroidism (n=97; age=median (Inter-Quartile Range); 38 (18) years; M:F=25:72) and age; sex-matched euthyroid cohorts (n=231; age=37 (18) years; M:F=40:191) undergoing TT were evaluated for serum corrected-calcium, intact parathormone and 25OHD levels at baseline, 48-hour and 6-months post-TT, p value <0.05 was considered significant.

Results: The incidence of transient hypocalcemia in thyrotoxic subjects was 58.8% (57/97) versus 22.5% (52/179) in euthyroid cohorts. In receiver operating characteristic analysis predicting transient hypocalcemia for the test-variable preoperative 25OHD, the area under curve (AUC) among euthyroid subjects was 0.725 (95% CI: 0.641-0.809; p<0.001) with a threshold of 17.6 ng/mL with sensitivity and specificity of 65.4% and 64.2% respectively. In thyrotoxic subjects, the AUC was 0.573 (95% CI; 0.452-0.694; p=0.222) with poorer predictability and was less than that of euthyroid subjects.

Conclusions: Preoperative 25OHD below 17.6 ng/ml was reliable in predicting transient postoperative hypocalcemia in euthyroid subjects though with a limited sensitivity and specificity but unreliable in thyrotoxic subjects undergoing TT.

Author Biographies

Poongkodi Karunakaran, Department of Endocrine Surgery, Madras Medical College, Chennai, Tamil Nadu, India

Civil Surgeon and Assistant Professor of Endocrine Surgery, Department of Endocrine surgery

Deepak Thomas Abraham, Department of Endocrine Surgery, Christian Medical College, Vellore, Tamil Nadu, India

Professor and Head, Department Of Endocrine Surgery


Liu ZW, Masterson L, Fish B. Thyroid surgery for Graves’ disease and Graves’ ophthalmopathy. Cochrane Database Systematic Rev. 2015:CD010576.

Thomusch O, Machens A, Sekulla C. The impact of surgical technique on postoperative hypoparathyroidism in bilateral thyroid surgery: a multivariate analysis of 5846 consecutive patients. Surg. 2003;133:180-5.

Thomusch O, Machens A, Sekulla C. Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany. World J Surg. 2000;24:1335-41.

Bott KJ, Markogiannakis H, Skandarajah A. Preoperative vitamin D deficiency predicts postoperative hypocalcemia after total thyroidectomy. World J Surg. 2011;35:10-2.

Unsal IO, Calapkulu M, Sencar ME. Preoperative vitamin D levels as a predictor of transient hypocalcemia and hypoparathyroidism after parathyroidectomy. Scientific Reports. 2020;10:95-8.

Kim WW, Chung SH, Ban EJ. Is preoperative vitamin D deficiency a risk factor for postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing total thyroidectomy plus central compartment neck dissection? Thyroid. 2015;25:911-8.

Wang X, Zhu J, Liu F. Preoperative vitamin D deficiency and postoperative hypocalcemia in thyroid cancer patients undergoing total thyroidectomy plus central compartment neck dissection. Oncotarget. 2017;8:78113-9.

Manzini G, Malhofer F, Weber T. Can preoperative vitamin D deficiency predict postoperative hypoparathyroidism following thyroid surgery? Langenbeck’s Arch Surg. 2019;404:55-61.

Lee GH, Ku YH, Kim H. Vitamin D level is not a predictor of hypocalcemia after total thyroidectomy. Langenbeck’s Arch Surg. 2015;10:1007-11.

Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocrine Metab Dis. 2017;18:24-31.

Edafe O, Antakia R, Laskar N. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. British J Surg. 2014;101:307-20.

Edafe O, Balasubramanian SP. Incidence, prevalence and risk factors for post-surgical hypocalcaemia and hypoparathyroidism. Gland Surg. 2017;8:09-13.

Michie W, Duncan T, Hodges DW. Mechanism of hypocalcaemia after thyroidectomy for thyrotoxicosis. Lancet. 1971;297:508-14.

Dembinski TC, Yatscoff RW, Blandford DE. Thyrotoxicosis and hungry bone syndrome-a cause of posttreatment hypocalcemia. Clinical Biochem. 1994;27:69-74.

See ACH, Soo KC. Hypocalcaemia following thyroidectomy for thyrotoxicosis. British J Surg. 1997;84:95-7.

Nicholls JJ, Brassill MJ, Williams GR. The skeletal consequences of thyrotoxicosis. J Endocrinol. 2012;213:209-21.

Karunakaran P, Maharajan C, Ramalingam S. Is hungry bone syndrome a cause of postoperative hypocalcemia after total thyroidectomy in thyrotoxicosis? a prospective study with bone mineral density correlation. Surg. 2018;163:367-72.

Holick MF, Binkley NC, Ferrari HA. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-30.

Sousa AA, Salles JMP, Soares JMA. Predictors factors for post-thyroidectomy hypocalcaemia. Revista Colegio Brasileiro Cirurgioes. 2012;39:10-2.

Eismontas V, Slepavicius A, Janusonis V. Predictors of postoperative hypocalcemia occurring after a total thyroidectomy: results of prospective multicenter study. BMC Surg. 2018;18:87-9.

D’Orazi V, Sacconi A, Trombetta S. May predictors of difficulty in thyroid surgery increase the incidence of complications? Prospective study with the proposal of a preoperative score. BMC Surg. 2019;18:447-52.

Cho JN, Park WS, Min SY. Predictors and risk factors of hypoparathyroidism after total thyroidectomy. Int J Surg. 2016;34:47-52.

Yamashita H, Murakami T, Noguchi S. Postoperative tetany in Graves disease: important role of vitamin D metabolites. Annals Surg. 1999;229:237-45.

Qubaisi M, Haigh PI. Hypocalcemia after total thyroidectomy in graves disease. The Permanente Journal. 2019;10:812-8.

Nelson KL, Hinson AM, Lawson BR. Postoperative calcium management in same-day discharge thyroid and parathyroid surgery. Otolaryngol Head Neck Surg. 2016;154:854-60.

Mazeh H, Khan Q, Schneider DF. Same-day thyroidectomy program: eligibility and safety evaluation. Surg. 2012;152:1133-41.

Reinhart HA, Snyder SK, Stafford SV. Same day discharge after thyroidectomy is safe and effective. Surg. 2018;10:101-6.

Arer IM, Kus M, Akkapulu N. Prophylactic oral calcium supplementation therapy to prevent early post thyroidectomy hypocalcemia and evaluation of postoperative parathyroid hormone levels to detect hypocalcemia: a prospective randomized study. Int J Surg. 2017;38:9-14.

Langner E, Tincani AJ, Negro A. Use of prophylactic oral calcium after total thyroidectomy: a prospective study. Arch Endocrinol Metabol. 2017;61:447-54.

Rodríguez MD, Ramírez LM, Gallardo LG. Hungry bone syndrome related to hyperythyroidism. Anales Med Interna. 2006;23:326-8.

Loredana D, Pasquale GG. Hungry bone syndrome after parathyroidectomy for primary hyperthyroidism. Surg. 2014;10:417-22.

Ronde W, Have SMTH, Daele PLA. Hungry bone syndrome, characterized by prolonged symptomatic hypocalcaemia, as a complication of the treatment of hyperthyroidism. Nederlands Tijdschrift. 2004;148:231-4.

Karunakaran P, Maharajan C, Mohamed KN. Rapid restoration of bone mass after surgical management of hyperthyroidism: a prospective case control study in Southern India. Surg. 2016;159:771-6.

Karunakaran P, Maharajan C, Chockalingam R. The effect of total thyroidectomy on the recovery of bone mineral density in subjects with hyperthyroidism. Surg. 2019;165:80-4.






Original Research Articles