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Exp Clin Endocrinol Diabetes 2017; 125(08): 497-505
DOI: 10.1055/s-0043-106441
Review
© Georg Thieme Verlag KG Stuttgart · New York

Endocrine Complications of Surgical Treatment of Thyroid Cancer: An Update

Pedro Iglesias
1   Department of Endocrinology. Hospital Ramón y Cajal, Madrid (Spain)
,
Juan José Díez
1   Department of Endocrinology. Hospital Ramón y Cajal, Madrid (Spain)
2   Department of Medicine and Medical Specialities, University of Alcalá, Alcalá de Henares, Madrid (Spain)
› Author Affiliations
Further Information

Publication History

received 02 January 2017
revised 06 March 2017

accepted 15 March 2017

Publication Date:
25 April 2017 (online)

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Abstract

Postoperative hypoparathyroidism (HypoPT) and hypothyroidism (HypoT) are the main endocrine complications after the surgical treatment for thyroid cancer. Postsurgical HypoPT can be transient, protracted or permanent. Its frequency varies according to the underlying cervical pathology, surgical technique, and mainly the experience of the surgeon. Risk factors for HypoPT include aggressiveness of the tumor, extent of surgery, the presence of parathyroid gland in the pathologic specimen, and surgeon experience. Clinical manifestations of postsurgical HypoPT can be acute or chronic. An adequate surgical technique that minimizes trauma and preserve the vascularization of the parathyroid glands is the better procedure to reduce the risk of postoperative HypoPT. Acute hypocalcemia may be managed with intravenous or oral calcium supplements, according to the level of serum calcium and the presence of signs and symptoms. Patients with permanent HypoPT require lifelong calcium and vitamin D supplementation. Calcitriol is the vitamin D metabolite of preference because of its high activity and short half-life. Both PTH (1–34) and intact PTH (1–84) have demonstrated to be attractive options in hypoparathyroid patients who cannot maintain stable serum and urinary calcium levels with calcium and vitamin D supplementation. However, the long-term safety of these preparations has not been established. Postsurgical HypoT is an unavoidable consequence of total or near-total thyroidectomy for thyroid cancer. Replacement and suppressive therapy are necessary in these patients. Thyroid hormone suppression therapy has shown to be accompanied by a decreased risk of disease progression and recurrence; however, it may also be associated with increased risk of dysrhythmia and loss of bone mass. Therefore, the intensity of TSH suppression must be established in a personalized way after balancing risk and benefits, according to the severity of the thyroid cancer, the response to therapy, and the individual risk factors for adverse events.

Key words

hypoparathyroidism - hypothyroidism - hypocalcemia - thyroid cancer - calcium - vitamin D - parathyroid hormone - levothyroxine
 

  • References

  • 1 Christou N, Mathonnet M. Complications after total thyroidectomy. J Visc Surg 2013; 150: 249-256
    CrossrefPubMedGoogle Scholar
  • 2 Daher R, Lifante JC, Voirin N. et al. Is it possible to limit the risks of thyroid surgery?. Ann Endocrinol (Paris) 2015; 76 (Suppl. 01) 1S16-1S26
    PubMedGoogle Scholar
  • 3 Stack Jr BC, Bimston DN, Bodenner DL. et al. American Association of Clinical Endocrinologist and American College of Endocrinology disease state clinical review: Postoperative hypoparathyroidism – definitions and management. Endocr Pract 2015; 21: 674-685
    CrossrefPubMedGoogle Scholar
  • 4 Schafer AL, Shoback DM. Hypocalcemia: Diagnosis and treatment. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM. et al. (eds.). Endotext. South Dartmouth (MA): MDText.com, Inc; 2000
    Google Scholar
  • 5 Sitges-Serra A, Ruiz S, Girvent M. et al. Outcome of protracted hypoparathyroidism after total thyroidectomy. Br J Surg 2010; 97: 1687-1695
    CrossrefPubMedGoogle Scholar
  • 6 Lorente-Poch L, Sancho JJ, Munoz-Nova JL. et al. Defining the syndromes of parathyroid failure after total thyroidectomy. Gland Surg 2015; 4: 82-90
    PubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 Bilezikian JP, Khan A, Potts Jr JT. et al. Hypoparathyroidism in the adult: Epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res 2011; 26: 2317-2337
    CrossrefPubMedGoogle Scholar
  • 9 Wang X, Xing T, Wei T. et al. Completion thyroidectomy and total thyroidectomy for differentiated thyroid cancer: Comparison and prediction of postoperative hypoparathyroidism. J Surg Oncol 2016; 113: 522-525
    CrossrefPubMedGoogle Scholar
  • 10 Coimbra C, Monteiro F, Oliveira P. et al. Hypoparathyroidism following thyroidectomy: Predictive factors. Acta Otorrinolaringol Esp 2017; 68: 106-111
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 Powers J, Joy K, Ruscio A. et al. Prevalence and incidence of hypoparathyroidism in the united states using a large claims database. J Bone Miner Res 2013; 28: 2570-2576
    CrossrefPubMedGoogle Scholar
  • 13 Underbjerg L, Sikjaer T, Mosekilde L. et al. Cardiovascular and renal complications to postsurgical hypoparathyroidism: A danish nationwide controlled historic follow-up study. J Bone Miner Res 2013; 28: 2277-2285
    CrossrefPubMedGoogle Scholar
  • 14 Underbjerg L, Sikjaer T, Mosekilde L. et al. The epidemiology of nonsurgical hypoparathyroidism in denmark: A nationwide case finding study. J Bone Miner Res 2015; 30: 1738-1744
    CrossrefPubMedGoogle Scholar
  • 15 Lee YS, Nam KH, Chung WY. et al. Postoperative complications of thyroid cancer in a single center experience. J Korean Med Sci 2010; 25: 541-545
    CrossrefPubMedGoogle Scholar
  • 16 Hu J, Zhao N, Kong R. et al. Total thyroidectomy as primary surgical management for thyroid disease: Surgical therapy experience from 5559 thyroidectomies in a less-developed region. World J Surg Oncol 2016; 14: 20 doi:10.1186/s12957-016-0772-1
    PubMedGoogle Scholar
  • 17 Giordano D, Valcavi R, Thompson GB. et al. Complications of central neck dissection in patients with papillary thyroid carcinoma: Results of a study on 1087 patients and review of the literature. Thyroid 2012; 22: 911-917
    CrossrefPubMedGoogle Scholar
  • 18 Polistena A, Monacelli M, Lucchini R. et al. Surgical morbidity of cervical lymphadenectomy for thyroid cancer: A retrospective cohort study over 25 years. Int J Surg 2015; 21: 128-134
    CrossrefPubMedGoogle Scholar
  • 19 Urken ML, Milas M, Randolph GW. et al. Management of recurrent and persistent metastatic lymph nodes in well-differentiated thyroid cancer: A multifactorial decision-making guide for the thyroid cancer care collaborative. Head Neck 2015; 37: 605-614
    CrossrefPubMedGoogle Scholar
  • 20 Ritter K, Elfenbein D, Schneider DF. et al. Hypoparathyroidism after total thyroidectomy: Incidence and resolution. J Surg Res 2015; 197: 348-353
    CrossrefPubMedGoogle Scholar
  • 21 Youngwirth L, Benavidez J, Sippel R. et al. Parathyroid hormone deficiency after total thyroidectomy: Incidence and time. J Surg Res 2010; 163: 69-71
    CrossrefPubMedGoogle Scholar
  • 22 Al-Dhahri SF, Mubasher M, Mufarji K. et al. Factors predicting post-thyroidectomy hypoparathyroidism recovery. World J Surg 2014; 38: 2304-2310
    CrossrefPubMedGoogle Scholar
  • 23 Karamanakos SN, Markou KB, Panagopoulos K. et al. Complications and risk factors related to the extent of surgery in thyroidectomy. results from 2,043 procedures. Hormones (Athens) 2010; 9: 318-325
    CrossrefPubMedGoogle Scholar
  • 24 Almquist M, Hallgrimsson P, Nordenstrom E. et al. Prediction of permanent hypoparathyroidism after total thyroidectomy. World J Surg 2014; 38: 2613-2620
    CrossrefPubMedGoogle Scholar
  • 25 Chow TL, Choi CY, Chiu AN. et al. monitoring of hypocalcemia expedites discharge after thyroidectomy. Am J Otolaryngol 2014; 35: 736-740
    CrossrefPubMedGoogle Scholar
  • 26 Nawrot I, Pragacz A, Pragacz K. et al. Total thyroidectomy is associated with increased prevalence of permanent hypoparathyroidism. Med Sci Monit 2014; 20: 1675-1681
    CrossrefPubMedGoogle Scholar
  • 27 Tohme JF, Bilezikian JP. Hypocalcemic emergencies. Endocrinol Metab Clin North Am 1993; 22: 363-375
    CrossrefPubMedGoogle Scholar
  • 28 Reber PM, Heath 3rd H. Hypocalcemic emergencies. Med Clin North Am 1995; 79: 93-106
    CrossrefPubMedGoogle Scholar
  • 29 Hurley K, Baggs D. Hypocalcemic cardiac failure in the emergency department. J Emerg Med 2005; 28: 155-159
    CrossrefPubMedGoogle Scholar
  • 30 Mitchell DM, Regan S, Cooley MR. et al. Long-term follow-up of patients with hypoparathyroidism. J Clin Endocrinol Metab 2012; 97: 4507-4514
    CrossrefPubMedGoogle Scholar
  • 31 Underbjerg L, Sikjaer T, Mosekilde L. et al. Postsurgical hypoparathyroidism – risk of fractures, psychiatric diseases, cancer, cataract, and infections. J Bone Miner Res 2014; 29: 2504-2510
    CrossrefPubMedGoogle Scholar
  • 32 Bohrer T, Pasteur I, Lyutkevych O. et al. Permanent hypoparathyroidism due to thyroid cancer surgical procedures in patients exposed to radiation in the chernobyl, ukraine, nuclear reactor accident. Dtsch Med Wochenschr 2005; 130: 2501-2506
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Khan MI, Waguespack SG, Hu MI. Medical management of postsurgical hypoparathyroidism. Endocr Pract 2011; 17 (Suppl. 01) 18-25
    PubMedGoogle Scholar
  • 34 Brandi ML, Bilezikian JP, Shoback D. et al. Management of hypoparathyroidism: Summary statement and guidelines. J Clin Endocrinol Metab 2016; 101: 2273-2283
    CrossrefPubMedGoogle Scholar
  • 35 Rathod A, Bonny O, Guessous I. et al. Association of urinary calcium excretion with serum calcium and vitamin D levels. Clin J Am Soc Nephrol 2015; 10: 452-462
    CrossrefPubMedGoogle Scholar
  • 36 Hesswani C, Noureldin YA, Elkoushy MA. et al. Combined vitamin D and calcium supplementation in vitamin D inadequate patients with urolithiasis: Impact on hypercalciuria and de novo stone formation. Can Urol Assoc J 2015; 9: 403-408
    CrossrefPubMedGoogle Scholar
  • 37 Mitchell DM, Regan S, Cooley MR. et al. Long-term follow-up of patients with hypoparathyroidism. J Clin Endocrinol Metab 2012; 97: 4507-4514
    CrossrefPubMedGoogle Scholar
  • 38 Levy I, Licht C, Daneman A. et al. The impact of hypoparathyroidism treatment on the kidney in children: Long-term retrospective follow-up study. J Clin Endocrinol Metab 2015; 100: 4106-4113
    CrossrefPubMedGoogle Scholar
  • 39 Hermann M, Ott J, Promberger R. et al. Kinetics of serum parathyroid hormone during and after thyroid surgery. Br J Surg 2008; 95: 1480-1487
    CrossrefPubMedGoogle Scholar
  • 40 Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med 2005; 20: 3-17
    CrossrefPubMedGoogle Scholar
  • 41 Grober U, Schmidt J, Kisters K. Magnesium in prevention and therapy. Nutrients 2015; 7: 8199-8226
    CrossrefPubMedGoogle Scholar
  • 42 Hu M, Hoff A, Gagel R. Short-term use of teriparatide in the treatment of postoperative hypocalcemia. Journal of Bone Mineral Research 2006; 21: S438 Abstract M429
    PubMedGoogle Scholar
  • 43 Shah M, Bancos I, Thompson GB. et al. Teriparatide therapy and reduced postoperative hospitalization for postsurgical hypoparathyroidism. JAMA Otolaryngol Head Neck Surg 2015; 141: 822-827
    CrossrefPubMedGoogle Scholar
  • 44 Palermo A, Mangiameli G, Tabacco G. et al. PTH(1–34) for the primary prevention of postthyroidectomy hypocalcemia: The THYPOS trial. J Clin Endocrinol Metab 2016; 101: 4039-4045
    CrossrefPubMedGoogle Scholar
  • 45 Porter RH, Cox BG, Heaney D. et al. Treatment of hypoparathyroid patients with chlorthalidone. N Engl J Med 1978; 298: 577-581
    CrossrefPubMedGoogle Scholar
  • 46 Shoback D. Clinical practice. hypoparathyroidism. N Engl J Med 2008; 359: 391-403
    CrossrefPubMedGoogle Scholar
  • 47 Cusano NE, Rubin MR, Irani D. et al. Use of parathyroid hormone in hypoparathyroidism. J Endocrinol Invest 2013; 36: 1121-1127
    CrossrefPubMedGoogle Scholar
  • 48 Kim ES, Keating GM. Recombinant human parathyroid hormone (1–84): A review in hypoparathyroidism. Drugs 2015; 75: 1293-1303
    CrossrefPubMedGoogle Scholar
  • 49 Marcucci G, Della Pepa G, Brandi ML. Natpara for the treatment of hypoparathyroidism. Expert Opin Biol Ther 2016; 16: 1417-1424
    CrossrefPubMedGoogle Scholar
  • 50 Winer KK, Ko CW, Reynolds JC. et al. Long-term treatment of hypoparathyroidism: A randomized controlled study comparing parathyroid hormone-(1–34) versus calcitriol and calcium. J Clin Endocrinol Metab 2003; 88: 4214-4220
    CrossrefPubMedGoogle Scholar
  • 51 Gafni RI, Brahim JS, Andreopoulou P. et al. Daily parathyroid hormone 1–34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure. J Bone Miner Res 2012; 27: 1811-1820
    CrossrefPubMedGoogle Scholar
  • 52 Puig-Domingo M, Diaz G, Nicolau J. et al. Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide. Eur J Endocrinol 2008; 159: 653-657
    CrossrefPubMedGoogle Scholar
  • 53 Winer KK, Zhang B, Shrader JA. et al. Synthetic human parathyroid hormone 1–34 replacement therapy: A randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. J Clin Endocrinol Metab 2012; 97: 391-399
    CrossrefPubMedGoogle Scholar
  • 54 Santonati A, Palermo A, Maddaloni E. et al. PTH(1–34) for surgical hypoparathyroidism: A prospective, open-label investigation of efficacy and quality of life. J Clin Endocrinol Metab 2015; 100: 3590-3597
    CrossrefPubMedGoogle Scholar
  • 55 Mannstadt M, Clarke BL, Vokes T. et al. Efficacy and safety of recombinant human parathyroid hormone (1–84) in hypoparathyroidism (REPLACE): A double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol 2013; 1: 275-283
    CrossrefPubMedGoogle Scholar
  • 56 Lakatos P, Bajnok L, Lagast H. et al. An open-label extension study of parathyroid hormone rhPTH(1–84) in adults with hypoparathyroidism. Endocr Pract 2016; 22: 523-532
    CrossrefPubMedGoogle Scholar
  • 57 Vahle JL, Sato M, Long GG. et al. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1–34) for 2 years and relevance to human safety. Toxicol Pathol 2002; 30: 312-321
    CrossrefPubMedGoogle Scholar
  • 58 Jolette J, Wilker CE, Smith SY. et al. Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1–84 in a 2-year study in fischer 344 rats. Toxicol Pathol 2006; 34: 929-940
    CrossrefPubMedGoogle Scholar
  • 59 Cardot-Bauters C. Hypoparathyroidism and pregnancy. Ann Endocrinol (Paris) 2016; 77: 172-175
    CrossrefPubMedGoogle Scholar
  • 60 Brabant G. Thyrotropin suppressive therapy in thyroid carcinoma: What are the targets?. J Clin Endocrinol Metab 2008; 93: 1167-1169
    CrossrefPubMedGoogle Scholar
  • 61 McGriff NJ, Csako G, Gourgiotis L. et al. Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med 2002; 34: 554-564
    CrossrefPubMedGoogle Scholar
  • 62 Sawin CT, Geller A, Wolf PA. et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331: 1249-1252
    CrossrefPubMedGoogle Scholar
  • 63 Kahaly GJ, Nieswandt J, Mohr-Kahaly S. Cardiac risks of hyperthyroidism in the elderly. Thyroid 1998; 8: 1165-1169
    CrossrefPubMedGoogle Scholar
  • 64 Sugitani I, Fujimoto Y. Effect of postoperative thyrotropin suppressive therapy on bone mineral density in patients with papillary thyroid carcinoma: A prospective controlled study. Surgery 2011; 150: 1250-1257
    CrossrefPubMedGoogle Scholar
  • 65 Klein Hesselink EN, Klein Hesselink MS, de Bock GH. et al. Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: An observational study. J Clin Oncol 2013; 31: 4046-4053
    CrossrefPubMedGoogle Scholar
  • 66 Diessl S, Holzberger B, Mader U. et al. Impact of moderate vs stringent TSH suppression on survival in advanced differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2012; 76: 586-592
    CrossrefPubMedGoogle Scholar
  • 67 Carhill AA, Litofsky DR, Ross DS. et al. Long-term outcomes following therapy in differentiated thyroid carcinoma: NTCTCS registry analysis 1987–2012. J Clin Endocrinol Metab 2015; 100: 3270-3279
    CrossrefPubMedGoogle Scholar
  • 68 Perros P, Boelaert K, Colley S. et al. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf) 2014; 81 (Suppl. 01) 1-122
    PubMedGoogle Scholar
  • 69 Haugen BR, Alexander EK, Bible KC. et al. 2015; American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016; 26: 1-133
    CrossrefPubMedGoogle Scholar
  • 70 American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer . Cooper DS, Doherty GM, Haugen BR. et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167-1214
    CrossrefPubMedGoogle Scholar
  • 71 Tuttle RM, Tala H, Shah J. et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: Using response to therapy variables to modify the initial risk estimates predicted by the new american thyroid association staging system. Thyroid 2010; 20: 1341-1349
    CrossrefPubMedGoogle Scholar
  • 72 Vaisman F, Momesso D, Bulzico DA. et al. Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clin Endocrinol (Oxf) 2012; 77: 132-138
    CrossrefPubMedGoogle Scholar
  • 73 Vaisman F, Tala H, Grewal R. et al. In differentiated thyroid cancer, an incomplete structural response to therapy is associated with significantly worse clinical outcomes than only an incomplete thyroglobulin response. Thyroid 2011; 21: 1317-1322
    CrossrefPubMedGoogle Scholar