Late Recovery of Parathyroid Function After Total Thyroidectomy: A Case-Control Study

Abstract

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i. e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i. e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3–6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3–6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time.

Key words

permanent hypoparathyroidism - recovery of parathyroid function - calcium - calcitriol

Publikationsverlauf

Eingereicht: 10. Februar 2021

Angenommen nach Revision: 15. August 2021

Artikel online veröffentlicht:
13. September 2021

• References

• 1 Iglesias P, Diez JJ. Endocrine complications of surgical treatment of thyroid cancer: an update. Exp Clin Endocrinol Diabetes 2017; 125: 497-505
• 2 Orloff LA, Wiseman SM, Bernet VJ. et al. American thyroid association statement on postoperative hypoparathyroidism: Diagnosis, prevention, and management in adults. Thyroid 2018; 28: 830-841
• 3 Harsløf T, Rolighed L, Rejnmark L. Huge variations in definition and reported incidence of postsurgical hypoparathyroidism: A systematic review. Endocrine 2019; 64: 176-183
• 4 Bollerslev J, Schalin-Jantti C, Rejnmark L. et al. Unmet therapeutic, educational and scientific needs in parathyroid disorders. Eur J Endocrinol 2019; 181: P1-P19
• 5 Paek SH, Lee YM, Min SY. et al. Risk factors of hypoparathyroidism following total thyroidectomy for thyroid cancer. World J Surg 2013; 37: 94-101
• 6 Wang JB, Sun HL, Song CY. et al. Association between decreased serum parathyroid hormone after total thyroidectomy and persistent hypoparathyroidism. Med Sci Monit 2015; 21: 1223-1231
• 7 Villarroya-Marquina I, Sancho J, Lorente-Poch L. et al. Time to parathyroid function recovery in patients with protracted hypoparathyroidism after total thyroidectomy. Eur J Endocrinol 2018; 178: 103-111
• 8 Diez JJ, Anda E, Sastre J. et al. Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: A multicentric and nation-wide retrospective analysis. Endocrine 2019; 66: 405-415
• 9 Loncar I, Dulfer RR, Massolt ET. et al. Postoperative parathyroid hormone levels as a predictor for persistent hypoparathyroidism. Eur J Endocrinol 2020; 183: 149-159
• 10 Song CM, Jung JH, Ji YB. et al. Relationship between hypoparathyroidism and the number of parathyroid glands preserved during thyroidectomy. World J Surg Oncol 2014; 12: 200
• 11 Al-Dhahri SF, Mubasher M, Mufarji K. et al. Factors predicting post-thyroidectomy hypoparathyroidism recovery. World J Surg 2014; 38: 2304-2310
• 12 Kim BW, Kim SY, Lee YS. et al. Parathyroid score can predict the duration of required calcium supplementation after total thyroidectomy. PLoS One 2017; 12: e0174088
• 13 Filho EBY, Machry RV, Mesquita R. et al. The timing of parathyroid hormone measurement defines the cut-off values to accurately predict postoperative hypocalcemia: A prospective study. Endocrine 2018; 61: 224-231
• 14 Su A, Gong Y, Wu W. et al. Does the number of parathyroid glands autotransplanted affect the incidence of hypoparathyroidism and recovery of parathyroid function? Surgery 2018 S0039-6060(17)30928-5
• 15 Bollerslev J, Rejnmark L, Marcocci C. et al. European society of endocrinology clinical guideline: treatment of chronic hypoparathyroidism in adults. Eur J Endocrinol 2015; 173: G1-G20
• 16 Brandi ML, Bilezikian JP, Shoback D. et al. Management of hypoparathyroidism: summary statement and guidelines. J Clin Endocrinol Metab 2016; 101: 2273-2283
• 17 Stack BC, Bimston DN, Bodenner DL. et al. American association of clinical endocrinologists and American college of endocrinology disease state clinical review: postoperative hypoparathyroidism - definitions and management. Endocr Pract 2015; 21: 674-685
• 18 Ritter K, Elfenbein D, Schneider DF. et al. Hypoparathyroidism after total thyroidectomy: incidence and resolution. J Surg Res 2015; 197: 348-353
• 19 Kim SM, Kim HK, Kim KJ. et al. Recovery from permanent hypoparathyroidism after total thyroidectomy. Thyroid 2015; 25: 830-833
• 20 Lorente-Poch L, Sancho JJ, Ruiz S. et al. Importance of in situ preservation of parathyroid glands during total thyroidectomy. Br J Surg 2015; 102: 359-367
• 21 Sitges-Serra A, Ruiz S, Girvent M. et al. Outcome of protracted hypoparathyroidism after total thyroidectomy. Br J Surg 2010; 97: 1687-1695
• 22 Cusano NE, Anderson L, Rubin MR. et al. Recovery of parathyroid hormone secretion and function in postoperative hypoparathyroidism: a case series. J Clin Endocrinol Metab 2013; 98: 4285-4290
• 23 Youngwirth L, Benavidez J, Sippel R. et al. Parathyroid hormone deficiency after total thyroidectomy: incidence and time. J Surg Res 2010; 163: 69-71
• 24 Edafe O, Antakia R, Laskar N. et al. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br J Surg 2014; 101: 307-320
• 25 Almquist M, Hallgrimsson P, Nordenstrom E. et al. Prediction of permanent hypoparathyroidism after total thyroidectomy. World J Surg 2014; 38: 2613-2620
• 26 Sitges-Serra A, Gomez J, Barczynski M. eti al. A nomogram to predict the likelihood of permanent hypoparathyroidism after total thyroidectomy based on delayed serum calcium and iPTH measurements. Gland Surg 2017; 6: S11-S19
• 27 Cantley LK, Russell J, Lettieri D. et al. 1,25-Dihydroxyvitamin D3 suppresses parathyroid hormone secretion from bovine parathyroid cells in tissue culture. Endocrinology 1985; 117: 2114-2119
• 28 Ritter CS, Brown AJ. Suppression of PTH by the vitamin D analog eldecalcitol is modulated by its high affinity for the serum vitamin D-binding protein and resistance to metabolism. J Cell Biochem 2011; 112: 1348-1352
• 29 Clarke BL. Epidemiology and complications of hypoparathyroidism. Endocrinol Metab Clin North Am 2018; 47: 771-782
• 30 Bilezikian JP. Hypoparathyroidism. J Clin Endocrinol Metab 2020; 105: 1722-1736
• 31 Mannstadt M, Bilezikian JP, Thakker RV. et al. Hypoparathyroidism. Nat Rev Dis Primers 2017; 3: 17055