Intravenous calcitriol: a critical intervention for severe postoperative hypoparathyroidism when oral administration is not feasible

Abstract

Iatrogenic hypoparathyroidism is a serious complication that can arise from neck surgery, predominantly during thyroidectomy, parathyroidectomy, and laryngectomy; it can be transient or permanent, requiring lifelong treatment. Early detection and treatment are crucial to prevent severe hypocalcemia, which is potentially fatal. This case report describes a 59-year-old male with a history of well-differentiated squamous cell carcinoma of the vocal cords who developed severe postoperative hypoparathyroidism following total laryngectomy with right hemithyroidectomy. Despite initial treatment with cholecalciferol by nasogastric tube, the patient experienced recurrent severe hypocalcemia, requiring intravenous administration of calcitriol due to his inability to swallow. This case highlights the risk factors for triggering postoperative hypoparathyroidism, such as previous surgery or radiotherapy in the cervical region, underlines the importance of careful monitoring of postoperative hypoparathyroidism and proposes the use of intravenous calcitriol as an effective strategy in acute treatment when oral administration is not feasible.

Keywords

Hypoparathyroidism / iatrogenic / intravenous calcitriol / laryngectomy / hypocalcemia / vitamin D

References

[1] Balasubramanian SP. Iatrogenic/post-surgical hypoparathyroidism: where do we go from here? Endocrine. 2014; 47: 357-9.

[2] Costanzo M, Marziani A, Condorelli F, Migliore M, Cannizzaro MA. Post-thyroidectomy hypocalcemic syndrome: predictive value of early PTH. Preliminary results. Ann Ital Chir. 2010; 81: 301-5.

[3] Gervasi R, Orlando G, Lerose MA, Amato B, Docimo G, Zeppa P, et al. Thyroid surgery in geriatric patients: a literature review. BMC Surg. 2012; 12: S16.

[4] Velicescu C, Bilha SC, Teleman A, Vitelariu A, Teodoriu L, Florescu A, et al. Incidence of transient and chronic hypoparathyroidism after total thyroidectomy - the experience of a tertiary center. Arch Clin Cases. 2024; 11: 93-7.

[5] Cocchiara G, Cajozzo M, Fazzotta S, Palumbo VD, Geraci G, Maione C, et al. Risk factors’ analysis of transient and permanent hypoparathyroidism after thyroidectomy. Clin Ter. 2017; 168: e271-7. Italian.

[6] Pepe J, Colangelo L, Biamonte F, Sonato C, Danese VC, Cecchetti V, et al. Diagnosis and management of hypocalcemia. Endocrine. 2020; 69: 485-95.

[7] Orloff LA, Wiseman SM, Bernet VJ, 3rd TJF, Shaha AR, Shindo ML, et al. American Thyroid Association Statement on Postoperative Hypoparathyroidism: Diagnosis, Prevention, and Management in Adults. Thyroid. 2018; 28: 830-41.

[8] Kumar R, Drinnan M, Robinson M, Meikle D, Stafford F, Welch A, et al. Thyroid gland invasion in total laryngectomy and total laryngopharyngectomy: a systematic review and meta-analysis of the English literature. Clin Otolaryngol. 2013; 38: 372-8.

[9] Pasha HA, Wasif M, Ikram M, Hammad M, Ghaloo SK, Rashid Z. Frequency of Thyroid Gland Invasion by Laryngeal Squamous Cell Carcinoma: The Role of Subglottic Extension. Int Arch Otorhinolaryngol. 2022; 26: e574-8.

[10] Marcocci C, Cianferotti L. The parathyroids. In: Miccoli P, Terris DJ, Minuto MN, Seybt MW, editors. Thyroid surgery: preventing and managing complications. John Wiley and Sons; 2012. pp. 227-36.

[11] Stack BC Jr, Bimston DN, Bodenner DL, Brett EM, Dralle H, Orloff LA, 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: 674-85. Erratum in: Endocr Pract. 2015; 21:1187.

[12] Edafe O, Antakia R, Laskar N, Uttley L, Balasubramanian SP. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br J Surg. 2014; 101: 307-20.

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

[14] Cianferotti L, Marcucci G, Brandi ML. Causes and pathophysiology of hypoparathyroidism. Best Pract Res Clin Endocrinol Metab. 2018; 32: 909-25.

[15] Negm H, Mosleh M, Fathy H, Awad A. Thyroid and parathyroid dysfunction after total laryngectomy in patients with laryngeal carcinoma. Eur Arch Otorhinolaryngol. 2016; 273: 3237-41.

[16] Edafe O, Sandler LM, Beasley N, Balasubramanian SP. Systematic review of incidence, risk factors, prevention and treatment of post-laryngectomy hypoparathyroidism. Eur Arch Otorhinolaryngol. 2021; 278: 1337-44.

[17] Edafe O, Tan ET, Jackson R, Sionis S, Balasubramanian SP, Beasley N. Evaluation of hypoparathyroidism following laryngectomy. Ann R Coll Surg Engl. 2023; 105: 62-7.

[18] Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006; 92: 4-8.

[19] Wimalawansa SJ. Physiology of Vitamin D-Focusing on Disease Prevention. Nutrients. 2024; 16: 1666.

[20] Edafe O, Mech CE, Balasubramanian SP. Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism. Cochrane Database Syst Rev. 2019; 5: CD012845.

[21] Bilezikian JP, Clarke BL, Mannstadt M, Rothman J, Vokes T, Lee H, et al. Safety and Efficacy of Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism Randomly Assigned to Receive Fixed 25-μg or 50-μg Daily Doses. Clin Ther. 2017; 39: 2096-102.

[22] Yeh C, Wu J, Su L, Yang P, Lee P, Chen K, et al. Intravenous calcitriol administration regulates the renin-angiotensin system and attenuates acute lung injury in obese mice complicated with polymicrobial sepsis. Biomed Pharmacother. 2021; 141: 111856.

[23] Fernandez E, Llach F. Guidelines for dosing of intravenous calcitriol in dialysis patients with hyperparathyroidism. Nephrol Dial Transplant. 1996; 11 Suppl 3: 96-101.

[24] McCarty EB, Chao TN. Dysphagia and Swallowing Disorders. Med Clin North Am. 2021; 105: 939-54.

[25] Pludowski P, Takacs I, Boyanov M, Belaya Z, Diaconu CC, Mokhort T, et al. Clinical Practice in the Prevention, Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement. Nutrients. 2022; 14: 1483.

[26] Almirall J, Torregrosa V, Arrizabalaga P, Cases A, Oliva J. [Intravenous calcitriol in the treatment of the refractory secondary hyperparathyroidism of terminal chronic kidney failure]. Med Clin (Barc). 1994; 102: 325-8. Spanish.

[27] Dressler R, Laut J, Lynn RI, Ginsberg N. Long-term high dose intravenous calcitriol therapy in end-stage renal disease patients with severe secondary hyperparathyroidism. Clin Nephrol. 1995; 43: 324-31.

[28] Yeh C, Wu J, Yang P, Lee P, Chen K, Huang C, et al. Intravenous calcitriol administration modulates mesenteric lymph node CD4⁺ T-cell polarization and attenuates intestinal inflammation in obese mice complicated with polymicrobial sepsis. JPEN J Parenter Enteral Nutr. 2022; 46: 1371-83.

[29] Jones AS, Warren AM, Bach LA, Sztal-Mazer S. The challenges of post-bariatric surgery hypocalcaemia in pre-existing hypoparathyroidism. Endocrinol Diabetes Metab Case Rep. 2020; 2020: 20-0103.