Postoperative Hypoparathyroidism After Total Thyroidectomy in Children.

BACKGROUND: Postoperative hypocalcemia because of hypoparathyroidism is the most common complication of total thyroidectomy in children. We hypothesized that most children with postoperative hypocalcemia would be eucalcemic by 12 mo and sought to define risk factors for permanent hypoparathyroidism. METHODS: We retrospectively reviewed children who underwent total thyroidectomy at a single children's hospital from 2012 to 2019. Patients with prior neck surgery were excluded. Indication for operation, final pathologic diagnosis, and postoperative serum calcium up to 12 mo were recorded. Permanent hypoparathyroidism was defined as supplemental calcium requirement beyond 1 y postoperatively. RESULTS: Sixty-eight patients underwent total thyroidectomy. Graves' disease was the most common benign indication for surgery (38 patients). Twenty-six patients (38%) had cancer on final pathology. Central lymph node dissection (CLND) was performed in 12 cancer patients. Twenty-eight patients (41%) had postoperative hypocalcemia. Eight patients (12%) had hypocalcemia at 6 mo. Risk factors for hypoparathyroidism at 6 mo were a cancer diagnosis (odds ratio [OR] 6.7; P = 0.02), CLND (OR 12.6; P < 0.01), and parathyroid tissue in the surgical specimen on pathologic analysis (OR 19.5; P < 0.01). Only two patients (3%) developed permanent hypoparathyroidism, both of whom had thyroidectomy for cancer and underwent CLND. CONCLUSIONS: Children with thyroid cancer are at high risk for postoperative hypocalcemia after total thyroidectomy. The risk is further increased by CLND, which should be performed selectively. A majority of patients with hypoparathyroidism at 6 mo postoperatively regain normal parathyroid function by 1 y. Permanent hypoparathyroidism in children after total thyroidectomy at a pediatric endocrine surgery center is rare.

Surgical Hypoparathyroidism.

Surgical hypoparathyroidism is the most common cause of hypoparathyroidism and the result of intentional or inadvertent extirpation, trauma, or devascularization of the parathyroid glands. Surgical hypoparathyroidism may present as a medical emergency. Pediatric patients, those with Graves disease, and those undergoing extensive neck dissections or reoperative neck surgery are at particular risk for this complication. Extensive surgical expertise, immediate or delayed autotransplantation, and prophylactic and postoperative calcium/vitamin D supplementation in select patients are associated with a reduction in the risk of surgical hypoparathyroidism. Intraoperative parathyroid imaging is among novel strategies being investigated to mitigate surgical hypoparathyroidism in the intraoperative setting.

NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018.

The NCCN Guidelines for Neuroendocrine and Adrenal Tumors provide recommendations for the management of adult patients with neuroendocrine tumors (NETs), adrenal gland tumors, pheochromocytomas, and paragangliomas. Management of NETs relies heavily on the site of the primary NET. These NCCN Guidelines Insights summarize the management options and the 2018 updates to the guidelines for locoregional advanced disease, and/or distant metastasis originating from gastrointestinal tract, bronchopulmonary, and thymus primary NETs.

How Many Lymph Nodes Are Enough? Assessing the Adequacy of Lymph Node Yield for Papillary Thyroid Cancer.

PURPOSE: Patients who undergo surgery for papillary thyroid cancer with only a limited lymph node examination are thought to be at risk for potentially harboring occult disease. However, this risk has not been objectively quantified and may have implications for subsequent management and surveillance. METHODS: Data from the National Cancer Database (1998 to 2012) were used to characterize the distribution of nodal positivity of adult patients diagnosed with localized ≥ 1-cm papillary thyroid cancer who underwent thyroidectomy with one or more lymph nodes (LNs) examined. A ß-binomial distribution was used to estimate the probability of occult nodal disease as a function of total number of LNs examined and pathologic tumor stage. RESULTS: A total of 78,724 patients met study criteria; 38,653 patients had node-positive disease. The probability of falsely identifying a patient as node negative was estimated to be 53% for patients with a single node examined and decreased to less than 10% when more than six LNs were examined. To rule out occult nodal disease with 90% confidence, six, nine, and 18 nodes would need to be examined for patients with T1b, T2, and T3 disease, respectively. Sensitivity analyses limited to patients likely undergoing prophylactic central neck dissection resulted in three, four, and eight nodes needed to provide comparable adequacy of LN evaluation. CONCLUSION: To our knowledge, our study provides the first empirically based estimates of occult nodal disease risk in patients after surgery for papillary thyroid cancer as a function of primary tumor stage and number of LNs examined. Our estimates provide an objective guideline for evaluating adequacy of LN yield for surgeons and pathologists in the treatment of papillary thyroid cancer, and especially intermediate-risk disease, for which use of adjuvant radioactive iodine and surveillance intensity are not currently standardized.

2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.

BACKGROUND: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. METHODS: The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. RESULTS: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. CONCLUSIONS: One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer.

CONTEXT: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The long-term prognosis is generally excellent. Due to a paucity of data, debate exists regarding the benefit of adjuvant radioactive iodine therapy (RAI) for intermediate-risk patients. OBJECTIVE: The objective of the study was to examine the impact of RAI on overall survival in intermediate-risk PTC patients. DESIGN/SETTING: Adult patients with intermediate-risk PTC who underwent total thyroidectomy with/without RAI in the National Cancer Database, 1998-2006, participated in the study. PATIENTS: Intermediate-risk patients, as defined by American Thyroid Association risk and American Joint Commission on Cancer disease stage T3, N0, M0 or Mx, and T1-3, N1, M0, or Mx were included in the study. Patients with aggressive variants and multiple primaries were excluded. MAIN OUTCOME MEASURES: Overall survival (OS) for patients treated with and without RAI using univariate and multivariate regression analyses was measured. RESULTS: A total of 21 870 patients were included; 15 418 (70.5%) received RAI and 6452 (29.5%) did not. Mean follow-up was 6 years, with the longest follow-up of 14 years. In an unadjusted analysis, RAI was associated with improved OS in all patients (P < .001) as well as in a subgroup analysis among patients younger than 45 years (n = 12 612, P = .002) and 65 years old and older (median OS 140 vs 128 mo, n = 2122, P = .008). After a multivariate adjustment for demographic and clinical factors, RAI was associated with a 29% reduction in the risk of death, with a hazard risk 0.71 (95% confidence interval 0.62-0.82, P < .001). For age younger than 45 years, RAI was associated with a 36% reduction in risk of death, with a hazard risk 0.64 (95% confidence interval 0.45- 0.92, P = .016). CONCLUSION: This is the first nationally representative study of intermediate-risk PTC patients and RAI therapy demonstrating an association of RAI with improved overall survival. We recommend that this patient group should be considered for RAI therapy.

Papillary thyroid microcarcinoma: an over-treated malignancy?

BACKGROUND: The clinical importance of papillary thyroid microcarcinoma (PTMC) remains controversial, with current guidelines suggesting that thyroid lobectomy alone is sufficient. The purpose of this study was to identify population-level treatment patterns in the USA for PTMC. METHODS: Patients with PTMC in SEER (1998-2010) were included; demographic, clinical (extent of surgery, administration of post-operative radioactive iodine [RAI]), and pathologic characteristics were examined. Outcomes of interest were 5- and 10-year overall survival (OS) and disease-specific survival (DSS). RESULTS: The cohort consisted of 29,512 patients. Mean age at diagnosis was 48.5 years; mean tumor size was 0.53 cm. Overall, 73.4 % of patients underwent total thyroidectomy, and RAI was administered to 31.3 %. In multivariate analysis, total thyroidectomy was more frequently performed in patients with multifocal (odds ratio [OR] 2.55), 'regional', or 'distant' PTMC (OR 2.90 and 2.59). Non-operative management was associated with male patients (OR 4.24) and those aged ≥65 years (OR 6.31). Post-operative RAI was associated with multifocal PTMC (OR 2.57). Overall, 5- and 10-year DSS was 99.6 and 99.3 %, respectively, with no difference in DSS between patients who underwent partial versus total thyroidectomy. OS of patients with PTMC who underwent any thyroid operation was similar to that of the general population of the USA. CONCLUSIONS: An increasing number of patients are undergoing total thyroidectomy and RAI for PTMC. While there may be a subset of patients for whom more aggressive therapy is indicated, many patients with PTMC may be over-treated, with no demonstrable benefit to survival.

Optimal surgical management of well-differentiated thyroid cancer arising in struma ovarii: a series of 4 patients and a review of 53 reported cases.

BACKGROUND: Well-differentiated thyroid cancer arising in struma ovarii is rare. The optimal management of this entity remains undefined. Unilateral cystectomy, unilateral salpingo-oophorectomy (USO), or total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO), in addition to total thyroidectomy and radioactive iodine (RAI) ablation, have been employed by various groups. We hypothesized that in patients with thyroid cancer arising within struma ovarii, pelvic surgery alone would be sufficient, provided there is no evidence of gross extra-ovarian extension. METHODS: We review a series of four patients from a single institution and 53 cases from the literature, comparing the extent of treatment and outcomes. Our literature review focused on low-risk patients with struma ovarii confined to the ovary, without evidence of gross extra-ovarian spread or distant metastases. Cumulative recurrence rate was determined by using the Kaplan-Meier method. RESULTS: We report the treatment of four patients with well-differentiated thyroid cancer arising within struma ovarii. Patients underwent USO, BSO, or TAH/BSO. One patient underwent prophylactic total thyroidectomy in anticipation of RAI treatment, and was found to have a synchronous papillary thyroid carcinoma. All patients clinically remain without evidence of disease at a median follow-up of 9 (range 0.8-13) years. Treatment strategies in 53 cases from a review of the literature varied. The pooled cumulative recurrence rate of 57 cases with struma ovarii confined to the ovary was 7.5% at 25 years. CONCLUSIONS: Thyroid cancer arising in struma ovarii is rare. Controversy exists regarding the extent of pelvic resection and management of the thyroid gland. In our series of four patients, all patients are alive without evidence of disease, and the 25-year recurrence rate of 57 cases was low (7.5%), despite a variety of approaches to surgical resection and adjuvant treatment. Extensive pelvic surgery and prophylactic total thyroidectomy to facilitate RAI therapy may be reserved for patients with gross extra-ovarian extension or distant metastases.

Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.

OBJECTIVE: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. METHODS: The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. RESULTS: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. CONCLUSIONS: One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.

BACKGROUND: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. METHODS: The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. RESULTS: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. CONCLUSIONS: One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

To supplement or not to supplement: a cost-utility analysis of calcium and vitamin D repletion in patients after thyroidectomy.

BACKGROUND: Postoperative hypocalcemia is the most common complication after thyroidectomy; prevention and treatment remain areas of ongoing debate. The purpose of this study was to determine the incremental cost utility of routine versus selective calcium and vitamin D supplementation after total or completion thyroidectomy. METHODS: A cost-utility analysis using a Markov decision model was performed for a hypothetical cohort of adult patients after thyroidectomy. Routine or selective supplementation of oral calcium carbonate, vitamin D (calcitriol), and intravenous calcium gluconate, when required, was used. Selective supplementation was determined by serum intact parathyroid hormone levels. The incremental cost utility, measured in U.S. dollars per quality-adjusted life-year (QALY), was calculated. RESULTS: In the base-case analysis, the cost of routine supplementation was $102 versus $164 for selective supplementation. Patients in the routine arm gained 0.002 QALYs compared to patients in the selective arm (0.95936 QALYs vs. 0.95725 QALYs). At the population level, this translates into a savings of $29,365/QALY (95% confidence interval, -$66,650 to -$1,772) for routine supplementation. Sensitivity analyses demonstrated that the model was most sensitive to the utility of the hypocalcemic state, postoperative rates of hypocalcemia, and cost of serum parathyroid hormone testing. CONCLUSIONS: Routine oral calcium and calcitriol supplementation in patients after thyroidectomy seems to be less expensive and results in higher patient utility than selective supplementation. Surgeons who have very low rates of hypocalcemia in their patients may benefit less from routine supplementation.

Medullary thyroid cancer: are practice patterns in the United States discordant from American Thyroid Association guidelines?

BACKGROUND: Surgery is the mainstay of treatment for medullary thyroid cancer (MTC), with long-term patient outcomes associated with adequacy of resection. This study benchmarked national practice patterns against 2009 American Thyroid Association (ATA) guidelines for MTC regarding use of thyroidectomy, lymphadenectomy, radioactive iodine (RAI), and external-beam radiotherapy (EBRT). METHODS: This is a cross-sectional, retrospective cohort study of MTC patients in the Surveillance, Epidemiology, and End Results Program database, 1973 to 2006. ATA recommendations 61 to 66 (extent of surgery), 85 (RAI), and 93 (EBRT) were analyzed. Outcome of interest was practice accordance with these recommendations. Predictors of accordance were determined and Kaplan-Meier survival analyses were performed. RESULTS: A total of 2033 patients with MTC were identified. Fifty-nine percent were women; 78% were white. Forty-one percent of patients did not receive appropriate surgical therapy (recommendations 61 to 63). Most patients with distant metastatic disease had less aggressive surgery and more EBRT (P < 0.001) (recommendations 64 to 66). Four percent of patients received inappropriate RAI (recommendation 85). Two hundred nine patients had gross incomplete resections, with 33% receiving postoperative EBRT (recommendation 93). Statistically significant predictors of receiving surgery discordant with ATA recommendations in multivariate analysis were patient age >65, female sex, earlier year of diagnosis (1988 to 1997), geographic region, intrathyroidal tumor extent, and tumor size of

Treatment patterns of aging Americans with differentiated thyroid cancer.

BACKGROUND: The incidence of differentiated thyroid cancer (DTC) increases with age. Total thyroidectomy, often followed by radioactive iodine (RAI), is recommended for patients who have tumors that measure > or =1 cm in greatest dimension. In the current study, the authors assessed the use of thyroidectomy and RAI among elderly patients with DTC and the effects on survival. METHODS: Adults aged > or =45 years with DTC > or =1 cm in the Surveillance, Epidemiology, and End Results database from 1988 to 2003 were included. Bivariate and multivariate analyses were used to measure associations between demographic, clinical, and pathologic characteristics and the likelihood of receiving treatment according to current practice guidelines. RESULTS: Of 8899 patients who were identified, 26% were ages 65 years to 79 years, and 5% were aged > or =80 years. Compared with younger patients, patients aged > or = 65 years were more likely to have larger tumors, stage IV disease, extrathyroid extension, and nonpapillary histology. Elderly patients were less likely to undergo total thyroidectomy (74% vs 80%; P < .001) or to receive RAI (47% vs 54%; P < .001). These trends were most pronounced among those aged > or =80 years. Among the patients who did not undergo surgery, elderly patients did not report higher rates of contraindications to surgery. In multivariate analysis, the groups ages 65 years to 79 years and aged > or =80 years were associated with lower rates of total thyroidectomy (odds ratio, 0.77 and 0.43, respectively; P < .001) and RAI (odds ratio, 0.85 [P < .01] and 0.39 [P < .001], respectively). Among elderly patients, predictors of worse survival included no surgery (hazard ratio, 5.51; P < .001) and no RAI (hazard ratio, 1.36; P < .001). CONCLUSIONS: Elderly patients with DTC received less aggressive surgical and RAI treatment than younger patients despite having more advanced disease and the improved survival associated with these treatments among elderly patients. Long-term outcomes should be measured to determine the impact of this apparent discrepancy in care.

Papillary thyroid cancer.

In summary, PTC is common, although it rarely results in disease-specific mortality. It is being diagnosed increasingly in the subclinical phase as a result of enhanced ultrasound imaging and more aggressive surveillance of smaller thyroid nodules. US-guided FNA is the "gold-standard" for diagnosis. Although controversy continues about the appropriate surgical management of PTC, total thyroidectomy is usually indicated given the frequent multicentricity and metastases of the disease, which in turn, necessitates adjuvant RAI and careful surveillance. An enhanced prognostic classification could better guide initial surgical therapy, standardize surveillance, and reduce the risk of recurrent and persistent disease. Research efforts should focus on the genetic and molecular underpinnings of PTC, as these would facilitate the identification of additional prognostic factors and potential targets for novel therapies.

Assessment and management of patients with abnormal calcium.

Calcium is essential for homeostasis, and normocalcemia should be maintained strictly during the perioperative period. The biochemistry of calcium equilibrium results from the calcium-sensing receptors on the parathyroid glands, which detect changes in calcium concentrations and initiate the proper response. Asymptomatic hypercalcemia is a common metabolic derangement that is often discovered on routine serum screening. The most common etiologies are primary hyperparathyroidism and cancer. Increasingly, parathyroidectomy is the preferred therapy for primary hyperparathyroidism. Severe hypercalcemia ("hypercalcemic crisis") should be managed aggressively with a combination of intravenous fluids, steroids, bisphosphonates, and calcitonin. Some of these patients may require an urgent parathyroidectomy for calcium control. Hypocalcemia needs to be verified, as many cases of hypocalcemia are the artifact of hypoalbuminemia. Severe hypocalcemia occurs after subtotal or total parathyroidectomy with auto transplantation as well as after massive resuscitation or blood transfusion. Strategies aimed at correcting calcium concentrations depend on the severity of symptomatology. If symptoms are mild, oral calcium supplementation can be given; otherwise, intravenous calcium should be administered.