Perioperative Management of Calciphylaxis: Literature Review and Treatment Recommendations.

Calciphylaxis is a serious and rare medical condition that leads to substantial clinical manifestations including pain, creating perioperative and treatment challenges. No standard treatment protocol exists nor are comprehensive guidelines available for perioperative management of patients with calciphylaxis. In this review, we evaluate existing literature (January 2000 to May 2021) with the aim to offer guidance for treating patients with this challenging disease through the perioperative period. Although no therapies are currently considered standard for treating calciphylaxis, multiple interventions are available for improving symptoms. Preoperative and intraoperative management involves monitoring and optimizing patient comorbid conditions and any possible electrolyte imbalances. Postoperative management can be challenging when potential calciphylaxis triggers are indicated, such as warfarin and corticosteroids. In addition, poor wound healing and difficult pain control are common. Therefore, a multifactorial approach to controlling postoperative pain is recommended that includes the use of nerve blocks, renal-sparing opioids, benzodiazepines, and/or ketamine. We present preoperative, intraoperative, and postoperative recommendations for treating calciphylaxis with levels of evidence when appropriate.

Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19.

SARS-CoV-2 is the causative viral pathogen driving the COVID-19 pandemic that prompted an immediate global response to the development of vaccines and antiviral therapeutics. For antiviral therapeutics, drug repurposing allows for rapid movement of the existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. One effective antiviral treatment strategy used early in symptom onset is to prevent viral entry. SARS-CoV-2 enters ACE2-expressing cells when the receptor-binding domain of the spike protein on the surface of SARS-CoV-2 binds to ACE2 followed by cleavage at two cut sites by TMPRSS2. Therefore, a molecule capable of inhibiting the protease activity of TMPRSS2 could be a valuable antiviral therapy. Initially, we used a fluorogenic high-throughput screening assay for the biochemical screening of 6030 compounds in NCATS annotated libraries. Then, we developed an orthogonal biochemical assay that uses mass spectrometry detection of product formation to ensure that hits from the primary screen are not assay artifacts from the fluorescent detection of product formation. Finally, we assessed the hits from the biochemical screening in a cell-based SARS-CoV-2 pseudotyped particle entry assay. Of the six molecules advanced for further studies, two are approved drugs in Japan (camostat and nafamostat), two have entered clinical trials (PCI-27483 and otamixaban), while the other two molecules are peptidomimetic inhibitors of TMPRSS2 taken from the literature that have not advanced into clinical trials (compounds 92 and 114). This work demonstrates a suite of assays for the discovery and development of new inhibitors of TMPRSS2.

Pediatric intraoperative nerve monitoring during thyroid surgery: A review from the American Head and Neck Society Endocrine Surgery Section and the International Neural Monitoring Study Group.

Children are more likely to experience recurrent laryngeal nerve (RLN) injury during thyroid surgery. Intraoperative nerve monitoring (IONM) may assist in nerve identification and surgical decision making. A literature review of pediatric IONM was performed and used to inform a monitoring technique guide and expert opinion statements. Pediatric IONM is achieved using a variety of methods. When age-appropriate endotracheal tubes with integrated surface electrodes are not available, an alternative method should be used. Patient age and surgeon experience with laryngoscopy influence technique selection; four techniques are described in detail. Surgeons must be familiar with the nuances of monitoring technique and interpretation; opinion statements address optimizing this technology in children. Adult IONM guidelines may offer strategies for surgical decision making in children. In some cases, delay of second-sided surgery may reduce bilateral RLN injury risk.

Clarifying optimal outcome measures in intermittent and continuous laryngeal neuromonitoring.

BACKGROUND: Intraoperative neuromonitoring (IONM) techniques have evolved over the past decade into intermittent IONM (I-IONM) and continuous IONM (C-IONM) modes of application. Despite many prior publications on both types of IONM, there remains uncertainty about what outcomes should be measured for each form of IONM. The primary objective of this paper is to define categories of benefit for I-IONM/C-IONM and to clarify and standardize their reporting outcomes. METHODS: Expert review consensus statement utilizing modified Delphi methodology. RESULTS: I-IONM provides diagnosis, classification, and prevention of nerve injury through accurate and early nerve identification. C-IONM provides real-time information on nerve functional integrity and thus may prevent some types of nerve injury but cannot assist in nerve localization. Sudden mechanisms of nerve injury cannot be predicted or prevented by either technique. CONCLUSIONS: I-IONM and C-IONM are complementary techniques. Future studies evaluating the utility of IONM should focus on outcomes that are appropriate to the type of IONM being utilized.

Informed Consent for Intraoperative Neural Monitoring in Thyroid and Parathyroid Surgery - Consensus Statement of the International Neural Monitoring Study Group.

In the past decade, the use of intraoperative neural monitoring (IONM) in thyroid and parathyroid surgery has been widely accepted by surgeons as a useful technology for improving laryngeal nerve identification and voice outcomes, facilitating neurophysiological research, educating and training surgeons, and reducing surgical complications and malpractice litigation. Informing patients about IONM is not only good practice and helpful in promoting the efficient use of IONM resources but is indispensable for effective shared decision making between the patient and surgeon. The International Neural Monitoring Study Group (INMSG) feels complete discussion of IONM in the preoperative planning and patient consent process is important in all patients undergoing thyroid and parathyroid surgery. The purpose of this publication is to evaluate the impact of IONM on the informed consent process before thyroid and parathyroid surgery and to review the current INMSG consensus on evidence-based consent. The objective of this consensus statement, which outlines general and specific considerations as well as recommended criteria for informed consent for the use of IONM, is to assist surgeons and patients in the processes of informed consent and shared decision making before thyroid and parathyroid surgery.

Recurrent Laryngeal Nerve Preservation Strategies in Pediatric Thyroid Oncology: Continuous vs. Intermittent Nerve Monitoring.

(1) Background: Pediatric thyroidectomy is characterized by considerable space constraints, thinner nerves, a large thymus, and enlarged neck nodes, compromising surgical exposure. Given these challenges, risk-reduction surgery is of paramount importance in children, and even more so in pediatric thyroid oncology. (2) Methods: Children aged ≤18 years who underwent thyroidectomy with or without central node dissection for suspected or proven thyroid cancer were evaluated regarding suitability of intermittent vs. continuous intraoperative neuromonitoring (IONM) for prevention of postoperative vocal cord palsy. (3) Results: There were 258 children for analysis, 170 girls and 88 boys, with 486 recurrent laryngeal nerves at risk (NAR). Altogether, loss of signal occurred in 2.9% (14 NAR), resulting in six early postoperative vocal cord palsies, one of which became permanent. Loss of signal (3.5 vs. 0%), early (1.5 vs. 0%), and permanent (0.3 vs. 0%) postoperative vocal cord palsies occurred exclusively with intermittent IONM. With continuous nerve stimulation, sensitivity, specificity, positive and negative predictive values, and accuracy reached 100% for prediction of early and permanent postoperative vocal cord palsy. With intermittent nerve stimulation, sensitivity, specificity, positive and negative predictive values, and accuracy were consistently lower for prediction of early and permanent postoperative vocal cord palsy, ranging from 78.6% to 99.8%, and much lower (54.2-57.9%) for sensitivity. (4) Conclusions: Within the limitations of the study, continuous IONM, which is feasible in children ≥3 years, was superior to intermittent IONM in preventing early and permanent postoperative vocal cord palsy.

Varied Recurrent Laryngeal Nerve Course Is Associated with Increased Risk of Nerve Dysfunction During Thyroidectomy: Results of the Surgical Anatomy of the Recurrent Laryngeal Nerve in Thyroid Surgery Study, an International Multicenter Prospective Anatomic and Electrophysiologic Study of 1000 Monitored Nerves at Risk from the International Neural Monitoring Study Group.

Background: The recurrent laryngeal nerve (RLN) can be injured during thyroid surgery, which can negatively affect a patient's quality of life. The impact of intraoperative anatomic variations of the RLN on nerve injury remains unclear. Objectives of this study were to (1) better understand the detailed surgical anatomic variability of the RLN with a worldwide perspective; (2) establish potential correlates between intraoperative RLN anatomy and electrophysiologic responses; and (3) use the information to minimize complications and assure accurate and safe intraoperative neuromonitoring (IONM). Methods: A large international registry database study with prospectively collected data was conducted through the International Neural Monitoring Study Group (INMSG) evaluating 1000 RLNs at risk during thyroid surgery using a specially designed online data repository. Monitored thyroid surgeries following standardized IONM guidelines were included. Cases with bulky lymphadenopathy, IONM failure, and failed RLN visualization were excluded. Systematic evaluation of the surgical anatomy of the RLN was performed using the International RLN Anatomic Classification System. In cases of loss of signal (LOS), the mechanism of neural injury was identified, and functional evaluation of the vocal cord was performed. Results: A total of 1000 nerves at risk (NARs) were evaluated from 574 patients undergoing thyroid surgery at 17 centers from 12 countries and 5 continents. A higher than expected percentage of nerves followed an abnormal intraoperative trajectory (23%). LOS was identified in 3.5% of NARs, with 34% of LOS nerves following an abnormal intraoperative trajectory. LOS was more likely in cases of abnormal nerve trajectory, fixed splayed or entrapped nerves (including at the ligament of Berry), extensive neural dissection, cases of cancer invasion, or when lateral lymph node dissection was needed. Traction injury was found to be the most common form of RLN injury and to be less recoverable than previous reports. Conclusions: Multicenter international studies enrolling diverse patient populations can help reshape our understanding of surgical anatomy during thyroid surgery. There can be significant variability in the anatomic and intraoperative characteristics of the RLN, which can impact the risk of neural injury.

Training Courses in Laryngeal Nerve Monitoring in Thyroid and Parathyroid Surgery- The INMSG Consensus Statement.

Intraoperative neural monitoring (IONM) is now an integral aspect of thyroid surgery in many centers. Interest in IONM and the number of institutions that perform monitored thyroidectomies have increased throughout the world in recent years. For surgeons considering the introduction of IONM in their practice, specific training in IONM devices and procedures can substantially shorten the learning curve. The International Neural Monitoring Study Group (INMSG) has been at the forefront of IONM technology and procedural adoption since the introduction of neural monitoring in thyroid and parathyroid surgery. The purpose of this document is to define the INMSG consensus on essential elements of IONM training courses. Specifically, this document describes the minimum training required for teaching practical application of IONM and consensus views on key issues that must be addressed for the safe and reliable introduction of IONM in surgical practice. The intent of this publication is to provide societies, course directors, teaching institutions, and national organizations with a practical reference for developing IONM training programs. With these guidelines, IONM will be implemented optimally, to the ultimate benefit of the thyroid and parathyroid surgical patients.

Superior Laryngeal Nerve Signal Attenuation Influences Voice Outcomes in Thyroid Surgery.

OBJECTIVES/HYPOTHESIS: The objective was to identify whether injury of the external branch of the superior laryngeal nerve (EBSLN) or changes in EBSLN parameters after dissection during thyroidectomies correlate with changes in voice quality postoperatively. STUDY DESIGN: Prospective multicenter case series. METHODS: A prospective multicenter study was conducted on patients undergoing thyroidectomies with intraoperative nerve monitoring. Electromyography waveforms of EBSLN stimulation before (S1) and after superior pole dissection (S2) were evaluated using endotracheal tube (ETT) and cricothyroid intramuscular (CTM) electrodes. Voice outcomes were assessed using Voice-Related Quality of Life Surveys and Voice Handicap Index. RESULTS: A total of 131 at-risk EBSLNs were evaluated in 80 patients. Two nerves showed loss of CTM twitch coupled with an absent S2 signal response. Complete EBSLN loss of signal was more likely with: 1) Cernea EBSLN anatomic classification Type 2B; 2) with a longer distance from the sternothyroid muscle insertion site; and 3) with larger lobar volumes (P < .05). Patients who experienced a more than 50% decrement in CTM amplitudes of S2 (n = 7) by CTM electrodes had a statistically significant decline in their voice outcomes compared to those who did not (n = 69) (P < .05). CONCLUSIONS: Patients experienced worse voice outcomes when at least one EBSLN response amplitude decreased by more than 50% after dissection when measured by CTM needle electrodes. CTM needle electrodes have an ability to measure finer amplitude changes compared to ETT electrodes, may represent a safe method to deduce subtle EBSLN injuries, and may serve to optimize voice outcomes during thyroidectomy. CTM needle electrodes are safe and tolerated well. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1436-1442, 2021.

Clinically significant anticardiolipin antibodies associated with COVID-19.

The novel coronavirus strain known as SARS-CoV-2 has rapidly spread around the world creating distinct challenges to the healthcare workforce. Coagulopathy contributing to significant morbidity in critically ill patients with SARS-CoV-2 has now been well documented. We discuss two cases selected from patients requiring critical care in April 2020 in New York City with a unique clinical course. Both cases reveal significant thrombotic events noted on imaging during their hospital course. Obtaining serial inflammatory markers in conjunction with anti-phospholipid antibody testing revealed clinically significant Antiphospholipid syndrome (APS). This case series reviews the details preceding APS observed in SARS-CoV-2 and aims to report findings that could potentially further our understanding of the disease.

Intraoperative nerve monitoring in thyroid surgery-shifting current paradigms.

Over the past two decades, intraoperative neural monitoring (IONM) has matured into a powerful risk minimization tool. Meta-analyses of studies, most of which were limited by poor study designs and the sole use of intermittent nerve stimulation, failed to demonstrate superiority of IONM over anatomic recurrent laryngeal nerve (RLN) dissection in the absence of IONM. With the advent of continuous IONM (CIONM), intraoperative nerve electromyographic tracings, registered almost in real time during the operation, accurately predict postoperative vocal fold function when International Neural Monitoring Study Group quality standards are adhered to. CIONM aids in avoiding permanent traction-related nerve injury by urging surgeons to reverse harmful surgical maneuvers. CIONM also forms an integral part in the surgical concept of staged thyroidectomy. Delaying completion surgery on the other side until nerve function has recovered mitigates the risk of bilateral vocal fold palsy. CIONM has greatly furthered our understanding of functional RLN injury, enabling conception of effective risk minimization strategies tailored to the individual patient. The review summarizes the advances of continuous IONM technology that caused a quantum leap in risk minimization for thyroid surgery, shifting current paradigms.

Thyroid Carcinoma: Do We Need to Treat Men and Women Differently?

BACKGROUND: For differentiated thyroid carcinoma, gender-specific differences exist in regard to incidence, age at onset, tumor stage, and recurrence, but causative factors remain to be elucidated. Possible and likely contributors are genetic and hormonal differences. While some of these factors are known to be differently distributed between the sexes, like, for example, BRAF-mutation and estrogen levels, their role in thyroid cancer initiation or promotion awaits further investigation. SUMMARY: Apart from generally accepted risk factors for differentiated thyroid carcinoma, an apparent gender disparity of thyroid cancer with a general female predominance, an age-dependent difference in growth acceleration during the reproductive years, and a peak at the time of entering menopause have been demonstrated. Hormonal status and hormonal receptor mediation seem to be most likely to contribute to the differences in thyroid cancer phenotypes of males and females. However, specific cause-and-effect pathways have not yet been determined. KEY MESSAGES: Female gender is overrepresented in the incidence of differentiated thyroid carcinoma, as it is in the more favorable tumor stages. Besides the assumption of gender-specific differences in general health awareness and behavior, hormonal age-dependent and gender-specific factors appear to be contributory. In the advanced stage of thyroid cancer, males are overrepresented. Therefore, the real cause of gender differences in thyroid cancer is likely due to a mixed effect. Present knowledge does not favor different treatment modalities of thyroid carcinoma according to gender.

Serum levels of advanced glycation end products and their receptors sRAGE and Galectin-3 in chronic pancreatitis.

BACKGROUND: /Objectives: AGE and their receptors like RAGE and Galectin-3 can activate inflammatory pathways and have been associated with chronic inflammatory diseases. Several studies investigated the role of AGE, Galectin-3 and sRAGE in pancreatic diseases, whereas no comprehensive data for chronic pancreatitis (CP) are available. METHODS: Serum samples from CP patients without an active inflammatory process (85 ACP; 26 NACP patients) and 40 healthy controls were collected. Levels of AGE, sRAGE and Galectin-3 were measured by ELISA. To exclude potential influences of previously described RAGE SNPs on detected serum levels, we analyzed variants rs207128, rs207060, rs1800625, and rs1800624 by melting curve technique in 378 CP patients and 338 controls. RESULTS: AGE and Galectin-3 serum levels were significantly elevated in both ACP and NACP patients compared to controls (AGE: 56.61 ± 3.043 vs. 31.71 ± 2.308 ng/mL; p < 0.001; Galectin-3: 16.63 ± 0.6297 vs. 10.81 ± 0.4835 ng/mL; p < 0.001). In contrast, mean serum sRAGE levels were significantly reduced in CP patients compared to controls (sRAGE: 829.7 ± 37.10 vs. 1135 ± 55.74 ng/mL; p < 0.001). All results were consistent after correction for gender, age and diabetes mellitus. No genetic association with CP was found. CONCLUSIONS: Our extensive analysis demonstrated the importance of aging related pathways in the pathogenesis of CP. As the results were consistent in ACP and NACP, both entities most likely share common pathomechanisms. Most probably the involved pathways are a general hallmark of an inflammatory state in CP that is even present in symptom-free intervals.

Impact of continuous intraoperative vagus stimulation on intraoperative decision making in favor of or against bilateral surgery in benign goiter.

The advent of continuous vagus stimulation (CVS), eliminating lag time between nerve preparation with potential trauma and stimulation, has transformed the intraoperative surgical strategy in thyroid surgery. Continuous intraoperative nerve monitoring empowers the surgeon to be optimally aware of traction-related injury to the recurrent laryngeal nerve (RLN). Electromyographic precursor lesions, called combined events, prompt surgeons to cease harmful surgical maneuvers and release the nerve before damage to the nerve is established. Complete RLN recovery, defined as restitution of the nerve amplitude to ≥50% of baseline, assures the surgeon that it is safe to pursue completion surgery of the contralateral side in one procedure. If this restitution is incomplete or absent (<50% of amplitude baseline) immediate vocal cord paralysis is likely and it is advisable to delay completion surgery until the nerve has fully recovered. This review summarizes the tremendous progress made in this dynamic field, delineating the extent to which CVS has changed the landscape: tailoring intraoperative decision making to determine the safest course of action for patients with benign goiter.

Prediction of Postoperative Vocal Fold Function After Intraoperative Recovery of Loss of Signal.

OBJECTIVES/HYPOTHESIS: This multicenter study aimed to 1) evaluate early postoperative vocal fold function in relation to intraoperative amplitude recovery, and 2) determine optimal absolute and relative thresholds of intraoperative amplitude recovery heralding normal early postoperative vocal fold function, both after segmental type 1 and after global type 2 loss of signal (LOS). STUDY DESIGN: Prospective outcome study. METHODS: This study, encompassing nine surgical centers from four countries, correlated intraoperative amplitude recovery with early postoperative vocal fold function using receiver operating characteristic analysis. RESULTS: Included in this study were 68 patients, 48 women and 20 men, who sustained transient recurrent laryngeal nerve injury during thyroid surgery under continuous intraoperative nerve monitoring. Early transient vocal fold palsy was seen in 18 (64%) of 28 patients with ipsilateral segmental LOS type 1, and in 10 (25%) of 40 patients with ipsilateral global LOS type 2. On receiver operating characteristic analysis, relative amplitude thresholds were superior to absolute amplitude thresholds in predicting vocal fold function after LOS type 2 (area under the curve [AUC]: 0.83 vs. 0.65; P = .01 vs. P = .15; Youden index 44% and 253 µV) and LOS type 1 (AUC: 0.96 vs. 0.97; P < .001 each; Youden index 49% and 455 µV). Amplitude recovery ≥50% of baseline after LOS always indicated intact vocal fold function. CONCLUSIONS: When the nerve amplitude recovers ≥50% of baseline after segmental LOS type 1 or global LOS type 2, it is appropriate to extend completion thyroidectomy to the other side during the same session. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:525-531, 2019.

Anterior laryngeal electrodes for recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: New expanded options for neural monitoring.

OBJECTIVES/HYPOTHESIS: Intraoperative neural monitoring is a useful adjunct for the laryngeal nerve function assessment during thyroid and parathyroid surgery. Typically, monitoring is performed by measurement of electromyographic responses recorded by endotracheal tube (ETT) surface electrodes. Tube position alterations during surgery can cause displacement of the electrodes relative to the vocal cords, leading to false positive loss of signal. Numerous reports have denoted monitoring equipment-related issues, especially endotracheal tube displacement, as the dominant source of false positive error. The false positive error may result in inappropriate decisions by the surgeon. This study tests the hypothesis that anterior laryngeal electrodes (ALEs) can help reduce this error. Placement of ALEs directly onto the thyroid cartilage represent an adjunctive and possible alternative method to standard ETT surface electrodes. STUDY DESIGN: Retrospective review. METHODS: Fifteen consecutive patients undergoing thyroid and parathyroid surgery with intraoperative neuromonitoring using both ETT electrodes and ALEs were studied. Data collected included site of neural stimulation, laterality, and electromyographic parameters. RESULTS: With vagal and recurrent laryngeal nerve stimulation, the ALEs recorded mean vocalis muscle waveform amplitude within 83% of that recorded with standard ETT electrodes. The latency measurements with the anterior laryngeal and endotracheal electrodes were similar, with both electrodes recording significantly longer latency for the left vagus nerve as compared to the right vagus nerve. With superior laryngeal nerve stimulation, the ALEs recorded a 800% greater mean amplitude than the ETT electrodes. The ALEs demonstrated similar sensitivity to stimulation at low current as ETT electrodes and provided stable intraoperative monitoring information. CONCLUSIONS: Compared to ETT surface electrodes, the ALEs provide similar and stable electromyographic responses with equal sensitivity for recording evoked responses during neural monitoring in thyroid and parathyroid surgery. The ALEs offer significantly more robust monitoring of the external branch of the superior laryngeal nerve. Furthermore, ALEs are contained within the operative field, are totally surgeon controlled, and are unaffected by the potential vicissitudes of ETT position during surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2910-2915, 2018.

International neural monitoring study group guideline 2018 part I: Staging bilateral thyroid surgery with monitoring loss of signal.

This publication offers modern, state-of-the-art International Neural Monitoring Study Group (INMSG) guidelines based on a detailed review of the recent monitoring literature. The guidelines outline evidence-based definitions of adverse electrophysiologic events, especially loss of signal, and their incorporation in surgical strategy. These recommendations are designed to reduce technique variations, enhance the quality of neural monitoring, and assist surgeons in the clinical decision-making process involved in surgical management of recurrent laryngeal nerve. The guidelines are published in conjunction with the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope, 128:S1-S17, 2018.

International neuromonitoring study group guidelines 2018: Part II: Optimal recurrent laryngeal nerve management for invasive thyroid cancer-incorporation of surgical, laryngeal, and neural electrophysiologic data.

The purpose of this publication was to inform surgeons as to the modern state-of-the-art evidence-based guidelines for management of the recurrent laryngeal nerve invaded by malignancy through blending the domains of 1) surgical intraoperative information, 2) preoperative glottic function, and 3) intraoperative real-time electrophysiologic information. These guidelines generated by the International Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical decision-making process involved in recurrent laryngeal nerve management during thyroid surgery by incorporating the important information domains of not only gross surgical findings but also intraoperative recurrent laryngeal nerve functional status and preoperative laryngoscopy findings. These guidelines are presented mainly through algorithmic workflow diagrams for convenience and the ease of application. These guidelines are published in conjunction with the INMSG Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of Signal. Level of Evidence: 5 Laryngoscope, 128:S18-S27, 2018.

Disease impacts more than age on operative morbidity in children with Graves' disease after total thyroidectomy.

BACKGROUND: In pediatric Graves' disease, operative morbidity after total thyroidectomy remains ill defined. The present study aimed to clarify whether total thyroidectomy entails greater operative morbidity in children with Graves' disease, in particular when they are very young, as compared with an age-matched reference group of children with hereditary C-cell disease who underwent total thyroidectomy at the same time. METHODS: Operative morbidity after total thyroidectomy for Graves' disease was determined in relation to the child's age and in comparison with a reference group of age-matched children with hereditary C-cell disease. RESULTS: Included in the study were 58 children with Graves' disease (51 girls and 7 boys) and 108 children with hereditary C-cell disease (59 girls and 49 boys). When children with Graves' disease and children with hereditary C-cell disease were compared across and within the 4 age increments (≤ 3, 4-6, 7-12, and 13-18 years), operative mortality did not differ significantly among and within age increments. Children with Graves' disease had a 1.7-fold greater overall risk of transient hypoparathyroidism (29% versus 17%; P = .073) than children with hereditary C-cell disease. Permanent hypoparathyroidism was nil in either group. Transient recurrent laryngeal nerve palsy, wound hemorrhage, and wound infections were infrequent (≤ 3% each), resolving spontaneously and after reoperation, respectively. CONCLUSION: Disease impacts more than age on operative morbidity in children with Graves' disease after total thyroidectomy but is fairly low overall and rarely permanent in experienced hands.