Latest Progress in Risk-Adapted Surgery for Medullary Thyroid Cancer.

(1) Background: The wider adoption of a preoperative ultrasound and calcitonin screening complemented by an intraoperative frozen section has increased the number of patients with occult sporadic medullary thyroid cancer (MTC). These advances offer new opportunities to reduce the extent of the initial operations, minimizing operative morbidity and the risk of postoperative thyroxin supplementation without compromising the cure. (2) Methods: This systematic review of the international literature published in the English language provides a comprehensive update on the latest progress made in the risk-adapted surgery for sporadic and hereditary MTC guided by an intraoperative frozen section. (3) Results: The current evidence confirms the viability of a hemithyroidectomy for desmoplasia-negative sporadic MTC. To add an extra safety margin, the hemithyroidectomy may be complemented by a diagnostic ipsilateral central node dissection. Despite the limited extent of the surgery, all the patients with desmoplasia-negative sporadic tumors achieved a biochemical cure with excellent clinical outcomes. A hemithyroidectomy decreases the need for postoperative thyroxine substitution, but a total thyroidectomy may be required for bilateral nodular thyroid disease. Hereditary MTC is a different issue. Because each residual thyroid C cell carries its own risk of malignant progression, a total thyroidectomy remains mandatory for hereditary MTC. (4) Conclusion: In experienced hands, a hemithyroidectomy, which minimizes morbidity without compromising the cure, is an adequate therapy for desmoplasia-negative sporadic MTC.

Accelerated MEN2A in homozygous RET carriers in the context of consanguinity.

BACKGROUND: Homozygous mutations, 2 identical gene versions (alleles), 1 from each biological parent, are exceptional. Clinical descriptions of affected families, comprising few carriers only, are scattered throughout the literature, hindering evidence generation. METHODS: Included in this literature analysis were 5 RET families with ≥1 homozygous carrier and ≥3 heterozygous carriers per family. RESULTS: In consanguineous families with first-degree cousins, homozygotes presented with node-positive medullary thyroid cancer and pheochromocytoma in their mid-teens, whereas heterozygotes presented in their end-30s and early 40s. Homozygotes developed node-positive medullary thyroid cancer 27.4 years and pheochromocytoma 23 years earlier than heterozygotes. These age differences were smaller in the 15 families carrying founder mutation p.Leu666delinsAsnSer, whereas homozygotes developed node-positive medullary thyroid cancer in their mid-40s, 6 years earlier than heterozygotes in their early 50s. CONCLUSION: These results, limited in scope and size and modulated by extent of consanguinity, are consistent with moderate dose-response effects accelerating MEN2A development.

Late recurrence of a single gland primary hyperparathyroidism-Atypical parathyroid adenoma or misdiagnosed parathyroid carcinoma.

Key Clinical Message: This case report aims to raise awareness of differential diagnoses of hypercalcemia and primary hyperparathyroidism, including parathyroid carcinoma and atypical adenoma, and to highlight the diagnostic challenges. Abstract: Parathyroid carcinoma is a rare and often fatal cause of primary hyperparathyroidism and hypercalcemia. To date, there is still no clear-cut diagnostic pathway for parathyroid carcinoma established, which results in major diagnostic ambiguity and complexity. Clinical differentiation between benign parathyroid adenoma and carcinoma is challenging and ultimately the diagnosis remains histopathological. We present a case of a 58-year-old female patient with parathyroid tumor recurrence after parathyroidectomy because of primary hyperparathyroidism. The first tumor was histologically classified as an atypical parathyroid adenoma by a specialized endocrine pathologist. Eleven years after the primary tumor resection a new tumor recurred. Retrospectively, after the tumor recurrence, the primary diagnosis of the atypical adenoma was questioned, and the tumor was temporarily classified to rather be a parathyroid carcinoma. This case aims to raise awareness for the diagnostic challenge of parathyroid carcinomas as a rare cause of primary hyperparathyroidism and therewith to improve treatment and prognosis.

Sexual dimorphism in medullary thyroid cancer aggressiveness.

Thyroid cancer is the only nonreproductive cancer with striking female predominance, although men with thyroid cancer develop more aggressive disease. This study aimed to quantify sex-specific differences in medullary thyroid cancer (MTC) spread after controlling for primary thyroid tumor size. Included in this retrospective analysis were all patients with unilateral solitary MTC who underwent initial neck surgery at a tertiary referral center. A total of 565 patients, 255 men and 310 women, were identified, of whom 467 had sporadic and 98 hereditary MTC. When stratified by sex, and after correction for multiple testing, men had higher preoperative basal calcitonin levels (medians of 655 vs 181 pg/mL; P < 0.001), more frequent extrathyroid extension (25 vs 9%; P < 0.001) and node metastasis (53 vs 27%; P < 0.001) with more involved nodes (medians of 2 vs 0 nodes; P < 0.001) than women but achieved less often biochemical cure (53 vs 74%; P < 0.001). Although absent in patients with very small (≤5 mm) thyroid tumors, sex disparities were immediately apparent in patients with 5.1-40 mm (node metastasis and biochemical cure) and 10.1-40 mm (extrathyroid extension) large thyroid tumors but were lost in patients with thyroid tumors >40 mm as women caught up. Sex disparities were strongest for node metastasis with a 27-41% (overall 24.0%) point difference, followed by biochemical cure with a -15-35% (overall -20.3%) point difference and extrathyroid extension with a 17-24% (14.2% overall) point difference. These findings indicate that the male predominance in MTC aggressiveness is largely biologically driven, warranting further research.

[Individualization of treatment in sporadic and hereditary medullary thyroid cancer]. / Therapieindividualisierung beim sporadischen und hereditären medullären Schilddrüsenkarzinom.

BACKGROUND: Routine preoperative assessment of the tumor marker calcitonin for medullary thyroid cancer (MTC) and the generally improved diagnostics with high-resolution ultrasound, elastography and Doppler function as well as functional imaging, enable the earlier detection of organ-limited, non-metastasized MTC. Thereby, a new treatment option arises for surgical de-escalation in sporadic MTC, moving from routine thyroidectomy with bilateral central lymph node dissection towards unilateral thyroidectomy with ipsilateral central lymph node dissection. MATERIAL AND METHODS: A search was carried out in PubMed for surgical approaches and selection of publications with results from limited resection in sporadic MTC. RESULTS: In selected patient cohorts limited resection surgery can achieve adequate oncological results but requires long-term follow-up. DISCUSSION: When sporadic unifocal primary tumors are identified and intraoperative frozen section pathological investigation is consistently employed for assessing the grade of desmoplasia and breach of the tumor capsule, the extent of resection can be intraoperatively adapted. Pivotal prerequisites for this personalized concept include consideration of preoperative clinical criteria and intraoperative surgical assessment in conjunction with the intraoperative frozen section examination in order to achieve an adequate oncological tumor resection and a biochemical cure.

Multiple endocrine neoplasia type 2: towards a risk-based approach integrating molecular and biomarker results.

PURPOSE OF REVIEW: Significant advances have transformed our understanding of the molecular biology and natural history of multiple endocrine neoplasia type 2 (MEN2). This progress enacted a paradigm shift with regard to routine neck dissection for medullary thyroid cancer and total adrenalectomy for pheochromoytoma. The purpose of this review is to summarize key molecular and clinical data underpinning the current risk-based approach to MEN2 that integrates molecular and biomarker results. RECENT FINDINGS: Early identification and biochemical monitoring of rearranged during transfection ( RET ) carriers yield important lead time. Within these ' windows of opportunity ', total thyroidectomy alone, avoiding incremental morbidity from node dissection; ' tissue-sparing ' subtotal adrenalectomy, balancing risks of steroid dependency with pheochromocytoma recurrence in adrenal remnants; and parathyroidectomy of enlarged glands only, weighing risks of postoperative hypoparathyroidism against hyperactive parathyroid glands left behind, are adequate therapies. SUMMARY: All that is needed to determine a RET carriers' risk of medullary thyroid cancer, pheochromocytoma and/or primary hyperparathyroidism in the molecular era is patient age, underlying RET mutation, and biomarker levels. As broader testing begins to penetrate healthcare, the needle on population genomic screening and education needs to be moved forward to complete the transition from symptom-based to preventive healthcare.

Comparing nodal with primary tumor desmoplasia uncovers metastatic patterns in multiple endocrine neoplasia 2B.

BACKGROUND: While primary tumor desmoplasia is a powerful biomarker of node metastases in sporadic medullary thyroid cancer (MTC), information for hereditary MTC is sparse. METHODS: This proof-of-concept study, comprising 3 consecutive children with multiple endocrine neoplasia 2B, evaluated simultaneously the metastatic behavior of multiple primary thyroid tumors of disparate size and extent of desmoplasia within patients. RESULTS: Altogether, MTC typically involved the ipsilateral central neck before spreading to the ipsilateral lateral and the contralateral neck. Medullary thyroid cancer in the upper thyroid lobe leaped the ipsilateral central neck to invade the ipsilateral lateral neck. Unlike the desmoplasia-positive 6-mm high-grade and 7-mm low-grade primary thyroid tumors, the desmoplasia-negative 8-, 11-, and 16-mm low-grade primary thyroid tumors did not spread to ipsilateral neck nodes. With extranodal growth, the extent of nodal desmoplasia was greater than with intranodal growth. CONCLUSION: This proof-of-concept study suggests that primary tumor desmoplasia is an equally powerful biomarker of node metastasis in hereditary MTC.

Sporadic noninvasive medullary thyroid neoplasm: A desmoplasia-negative unifocal nonmetastatic tumor cured by hemithyroidectomy.

BACKGROUND: The absence of primary tumor desmoplasia, a marker of node metastases, on frozen section may help reduce the extent of surgery without compromising the biochemical cure. We aimed to clarify whether hemithyroidectomy with diagnostic ipsilateral central neck dissection can replace total thyroidectomy with routine central neck dissection in patients with sporadic medullary thyroid cancer. METHODS: We retrospectively evaluated data collected from patients who had undergone primary neck surgery for hypercalcitoninemic sporadic medullary thyroid cancer between January 2017 and December 2022 at one institution. RESULTS: Of the 25 patients we examined, 19 had desmoplasia-negative and 6 desmoplasia-positive primary thyroid tumors on frozen section. The desmoplasia-negative patients had undergone less surgery with fewer nodes removed than the desmoplasia-positive patients (medians of 6 vs 31 nodes, P < .001). The desmoplasia-negative patients had predominantly undergone hemithyroidectomy with ipsilateral central neck dissection. None of the desmoplasia-negative tumors was multifocal (0 of 19 desmoplasia-negative vs 2 of 6 desmoplasia-positive or 0% vs 33%, P = .050) or node-positive (0 of 19 vs 6 of 6 patients or 0% vs 100%; medians of 0 vs 3.5 node metastases; both P < .001). Despite limited surgery, all desmoplasia-negative patients attained and maintained biochemical cure. CONCLUSION: Hemithyroidectomy combined with diagnostic ipsilateral central neck dissection is a viable risk-reducing and curative strategy for desmoplasia-negative and node-negative, nonmetastatic unifocal tumors, for which we propose the term sporadic noninvasive medullary thyroid neoplasm (SNMTP).

Axillary Node Metastases of Medullary Thyroid Cancer: A Hallmark of Terminal Disease.

Little is known about axillary node metastasis of medullary thyroid cancer (MTC). To address this, a comparative study of patients with and without axillary node metastases of MTC was conducted. Among 1215 consecutive patients with MTC, 482 patients had node-negative MTC and 733 patients node-positive MTC. Among the 733 patients with node-positive MTC, 4 patients (0.5%) had axillary node metastases, all of which were ipsilateral. Patients with axillary node metastases had 5.7-6.9-fold more node metastases removed, both at the authors' institution (medians of 34.5 vs. 5 metastases; p=0.011) and in total (medians of 57 vs. 10 metastases; p=0.013), developed more frequently distant metastases (3 of 4 vs. 178 of 729 patients, or 75 vs. 24%; p=0.049), specifically to bone (2 of 4 vs. 67 of 729 patients, or 50 vs. 9%; p=0.046) and brain (1 of 4 vs. 4 of 729 patients, or 25 vs. 0.5%; p=0.027), and more often succumbed to cancer-specific death (3 of 4 vs. 52 of 729 patients, or 75 vs. 14%; p=0.005). Altogether, patients with axillary node metastases revealed 4-8-fold more node metastases in the ipsilateral lateral neck (medians of 11 vs. 3 metastases; p=0.021) and in the ipsilateral central neck (medians of 8 vs. 1 metastases; p=0.079) patients without axillary node metastases. Cancer-specific survival of patients with vs. patients without axillary node metastases of MTC was significantly shorter (means of 41 vs. 224 months; plog-rank<0.001). These findings show that patients with axillary node metastases of MTC have massive metastatic dissemination with poor survival.

Clinical presentation of MEN 2A in index vs. non-index patients.

PURPOSE: Differences in syndromic manifestations of multiple endocrine neoplasia 2 A (MEN2A) between index and non-index patients are ill-defined. METHODS: Cross-sectional analysis of 602 REarranged during Transfection (RET) carriers (156 index and 446 non-index patients) who underwent thyroidectomy, adrenalectomy, and/or parathyroidectomy between 1985 and 2022, stratified by mutational risk. RESULTS: Index patients were 5.8-13.9 years older at thyroidectomy than non-index patients, at which point they had developed 10.6-14.4 mm larger medullary thyroid cancers. Correlations between index status and primary tumor size (ρ = 0.489-0.544) were stronger than correlations between index status and age at thyroidectomy (ρ = 0.359-0.438). For pheochromocytoma and primary hyperparathyroidism, no significant differences were noted. When stratified by time of surgery before vs. in the new millennium, age at thyroidectomy fell significantly only for non-index patients in the new millennium: from 28.6 to 21.2 years (moderate-high risk mutations; P = 0.049) and from 23.1 to 12.3 years (high-risk mutations; P < 0.001). All other inter-millennium comparisons did not reach statistical significance. CONCLUSION: These findings imply that differences between index and non-index patients impact the first syndromic manifestation without extending to subsequent syndromic manifestations. Because they exhibited similar age and tumor characteristics for the secondary and tertiary manifestations of MEN2A, screening for these syndromic components remains an integral element of MEN2A management in index and non-index patients alike. Wider use of population genomic screening may work to diminish the observed disparities between index and non-index patients going forward.

The Changing Face of Multiple Endocrine Neoplasia 2A: From Symptom-Based to Preventative Medicine.

CONTEXT: Early genetic association studies yielded too high risk estimates for multiple endocrine neoplasia (MEN2A), suggesting a need for extended surgery. OBJECTIVE: The objective was to delineate temporal changes in MEN2A presentation by birth cohort analyses. METHODS: Birth cohort analyses (10-year increments; ≤1950 to 2011-2020) of carriers of rearranged during transfection (RET) mutations who underwent surgery for MEN2A. RESULTS: Included in this study were 604 carriers (155 index, 445 nonindex, 4 additional patients), with 237 carriers harboring high-risk mutations, 165 carriers moderate-high risk mutations, and 202 carriers low-moderate risk mutations. With increasing recency of birth cohorts, there was a continual decline in index patients from 41-74% to 0% (P < .001) and of medullary thyroid cancer (MTC) from 96-100% to 0-33% (P < .001). Node metastases diminished from 62-70% to 0% (P ≤ .001; high and low-moderate risk mutations), whereas biochemical cure after thyroidectomy surged from 17-33% to 100% (P ≤ .019; high and low-moderate mutations). Surgical interventions for MEN2A-related tumors were performed increasingly earlier, causing median carrier age to fall: from 51-63 to 3-5 years at thyroidectomy (P < .001); from 46-51 to 24-25 years at first adrenalectomy (P ≤ .013; high and moderate-high risk mutations); and from 43.5-66 to 16.5-32 years at parathyroidectomy. MTC diameters were more effectively decreased from 14-32 to 1-4 mm (P ≤ 002) than pheochromocytoma diameters (nonsignificant). CONCLUSION: These insights into MEN2A presentation, adjusted by birth year, illustrate the shift from reactive to preventative medicine, enabling less extensive risk-reducing surgery.

The internal mammary artery perforator flap for neck reconstruction after palliative resection of advanced anaplastic thyroid cancer: a case report.

INTRODUCTION: Defects of the neck after palliative resection of exulcerated tumors could be reconstructed with different skin flaps. CASE PRESENTATION: The present report describes the case of a 40-year-old Caucasian female patient with advanced anaplastic thyroid cancer. The exophytically growing, bad-smelling massive exulcerated tumor caused an esthetic defect, neck mobility restrictions, and mental state deterioration. PRIMARY DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: Palliative debulking of the tumor was performed. The 10 × 5 cm skin defect of the neck was successfully reconstructed with an internal mammary artery perforator island flap. The donor site was closed primarily. The patient had an uneventful clinical course; the cosmetic results and mental state were very pleasing. CONCLUSIONS: The present case illustrates that palliative resection of the tumor and plastic reconstruction of the neck defect promoted other treatments such as radiation or chemotherapy due to the improved local situation.

Temporal trends in referrals of RET gene carriers for neck surgery to a tertiary surgical center in the era of international management guidelines.

PURPOSE: Thirty years into the genomic era, this study sought to explore events that helped transform the clinical landscape of hereditary medullary thyroid cancer (MTC). METHOD: This retrospective analysis of prospectively collected data included all RET carriers referred to a tertiary center for neck surgery that was performed between 1986 and 2021, using descriptive statistics and Poisson regression analysis. RESULTS: Altogether, 496 RET carriers were referred for thyroidectomy (388 carriers) or neck reoperation (108 carriers). Of these, 44 carriers had highest risk mutations (p.Met918Thr), 164 carriers high risk mutations (p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr/insHisGluLeuCys), 116 carriers moderate-high risk mutations (p.Cys609/611/618/620/630Arg/Gly/Phe/Ser/Tyr) and 172 carriers low-moderate risk mutations (p.Glu768Asp, p.Leu790Phe, p.Val804Leu/Met, or p.Ser891Ala). Three event clusters drove referral numbers upward: a string of first reports of causative RET mutations between 1993 and 1998; the international consensus guidelines for diagnosis and therapy of MEN type 1 and type 2 in 2001; and the revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma in 2015. Referrals for neck reoperation declined sluggishly over 30 years, ending in 2018. Index patients continued to be referred into 2021. Referrals for thyroidectomy, grouped in 5-year increments, peaked in 1996-2000 for carriers of highest and high risk mutations, and in 2006-2010 for carriers of moderate-high and low-moderate risk mutations, some 10 years later. CONCLUSION: International management guidelines are critical in building and increasing the pressure towards screening of sporadic-appearing disease and offspring of known gene families by encompassing the complete disease spectrum early on.

Superiority of metastatic lymph node ratio over number of node metastases and TNM/AJCC N classification in predicting cancer-specific survival in medullary thyroid cancer.

BACKGROUND: In medullary thyroid cancer (MTC), it is unclear which nodal classification system, metastatic lymph node ratio (MLNR), number of node metastases, or TNM/AJCC N classification, predicts cancer-specific survival best. METHODS: Kaplan-Maier analysis of cancer-specific survival after operation at a tertiary center. RESULTS: Included were 505 MTC patients. The spread of the survival curves was greatest after stratification by MLNR (in 0.20 increments), followed by number of node metastases (in 10-node and 20-node increments) and TNM/AJCC classification (N0, N1a, N1b). After collapsing overlapping survival curves, all adjacent curves (MLNRs ≤0.20 vs. 0.21-0.60 vs. >0.60; 0 vs. 1-20 vs. >20 node metastases; and TNM/AJCC N classification N0/N1a vs. N1b) significantly differed between each other. CONCLUSIONS: In MTC, MLNR, reflecting intensity of lymphatic spread, predicts cancer-specific survival better than number of node metastases or TNM/AJCC N classification. The applicability of these findings to patients with limited neck dissection requires more research.

Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study.

PURPOSE: Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC. PATIENTS AND METHODS: In this prospective single-center, two-arm phase II study, patients received trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days. Redifferentiation was assessed by 123I-scintigraphy. In case of restored radioiodine uptake, 124I-guided 131I therapy was performed. Primary endpoint was the redifferentiation rate. Secondary endpoints were treatment response (thyroglobulin, RECIST 1.1) and safety. Parameters predicting successful redifferentiation were assessed using a receiver operating characteristic analysis and Youden J statistic. RESULTS: Redifferentiation was achieved in 7 of 20 (35%) patients, 2 of 6 (33%) in the BRAF-MUT and 5 of 14 (36%) in the BRAF-WT arm. Patients received a mean (range) activity of 300.0 (273.0-421.6) mCi for 131I therapy. Any thyroglobulin decline was seen in 57% (4/7) of the patients, RECIST 1.1 stable/partial response/progressive disease in 71% (5/7)/14% (1/7)/14% (1/7). Peak standardized uptake value (SUVpeak) < 10 on 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET was associated with successful redifferentiation (P = 0.01). Transient pyrexia (grade 3) and rash (grade 4) were noted in one patient each. CONCLUSIONS: Genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. Subsequent 131I therapy led to a thyroglobulin (Tg) decline in more than half of the treated patients. Low tumor glycolytic rate as assessed by FDG-PET is predictive of redifferentiation success. See related commentary by Cabanillas et al., p. 4164.

Recurrent ipsilateral pheochromocytoma in carriers of RET p.Cys634 missense mutations.

PURPOSE: The objective of this study was to provide RET genotype-specific data on recurrent ipsilateral pheochromocytoma in multiple endocrine neoplasia type 2A (MEN2A), which are sparse. METHODS: Kaplan-Meier analyses were performed to determine the risk of recurrent ipsilateral adrenalectomy after subtotal and total adrenalectomy in 221 carriers of RET p.Cys634 missense mutations. RESULTS: Altogether, pheochromocytoma emerged in 112 of 442 adrenals at risk, for which 63 adrenals underwent total adrenalectomy and 49 adrenals subtotal adrenalectomy. After a mean (median) of 99 (132.9) months, 10 recurrent ipsilateral pheochromocytomas arose in 10 (20.4%) of 49 adrenal remnants. Seven of these 10 adrenal remnants were subjected to total adrenalectomy and 3 to another subtotal adrenalectomy. After 23 and 250 (mean/median 136.5) more months, 2 of the 3 remaining adrenal remnants gave rise to 2 further recurrent ipsilateral pheochromocytomas, which were removed by total adrenalectomy. When the rare publications in which carriers of RET p.Cys634 mutations made up 81-84% of MEN2A patients were combined with the present RET p.Cys634-specific series, the risk of recurrent ipsilateral pheochromocytoma was 6.7% (25 recurrent ipsilateral pheochromocytomas in 375 adrenal remnants), with a mean time interval of 146 months after initial subtotal adrenalectomy. CONCLUSION: Subtotal adrenalectomy is a viable treatment option for many carriers of RET p.Cys634 mutations who develop an initial pheochromocytoma. Although the adrenal remnant may give rise to recurrent ipsilateral pheochromocytoma after 8-11 years in up to 20% of patients, it is manageable very well in experienced hands, buying the patient valuable time off steroids.

Clonidine suppression test for a reliable diagnosis of pheochromocytoma: When to use.

OBJECTIVE: In clinical practice, false-positive results in biochemical testing for suspected pheochromocytoma/paraganglioma (PPGL) are not infrequent and may lead to unnecessary examinations. We aimed to evaluate the role of the clonidine suppression test (CST) in the era of analyses of plasma-free metanephrines for the diagnosis or exclusion of PPGL in patients with adrenal tumours and/or arterial hypertension. DESIGN AND METHODS: This single-centre, prospective trial investigated the use of CST in 60 patients with suspected PPGL associated with out-patient elevations of plasma normetanephrine (NMN) and/or metanephrine (MN), in most cases accompanied with hypertension or an adrenal mass. Measurements of plasma catecholamines and free metanephrines were performed by liquid chromatography with electrochemical detection and tandem mass spectrometry, respectively. RESULTS: Forty-six patients entered final analysis (n = 20 with PPGL and n = 26 with a nonfunctional adrenal mass and/or hypertension). CST reliably excluded false-positive baseline NMN results with a specificity of 100%. The sensitivity of CST improved from 85% to 94% when tumours with isolated MN increase (n = 3) were not considered. In patients with elevated baseline NMN (n = 24), CST correctly identified all patients without PPGL. Patients with falsely elevated baseline NMN results (n = 7, 26.9%) exhibited increases of baseline NMN up to 1.7-fold above the upper reference limit. CONCLUSION: CST qualifies as a useful diagnostic tool for differential diagnosis of borderline elevated plasma-free NMN in patients with suspected PPGL. In this context, CST helps to correctly identify all false-positive NMN screening results.

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.