Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

OBJECTIVE: The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States. METHODS: The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSION: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

OBJECTIVE: To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the US. METHODS: The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSIONS: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.

PERSONALIZED CARE OF PATIENTS WITH ADRENOCORTICAL CARCINOMA: A COMPREHENSIVE APPROACH.

A concerted effort has been made in the past decade to better differentiate benign from malignant adrenocortical tumors. Of those tumors found to be adrenocortical carcinomas (ACCs) and through the use of multiple modalities including biochemical, radiologic, and genomic analysis, significant strides have been made in understanding what drives ACC development, how various treatments may result in different outcomes, which ACCs are more likely to respond to various treatments, and overall prognosis. While most patients will have recurrence of their ACC and succumb to their disease, the disease course is highly variable; it is therefore imperative that each patient is treated with individualized attention paid to their particular ACC. This article highlights and discusses specific, important, and many times subtle features that may impact the evaluation, management, treatment selection, and outcome of patients with ACC. ABBREVIATIONS: ACC = adrenocortical carcinoma; CT = computed tomography; XRT = external beam radiation therapy.

Outcomes of total thyroidectomy with therapeutic central and lateral neck dissection with a single dose of radioiodine in the treatment of regionally advanced papillary thyroid cancer and effects on serum thyroglobulin.

BACKGROUND: Achieving an undetectable serum thyroglobulin (Tg) level (<1.0 ng/mL) after surgical and radioiodine treatment for papillary thyroid cancer (PTC) is associated with low recurrence rates and has been termed biochemical remission. This study aimed to determine the effectiveness of total thyroidectomy with therapeutic central and lateral neck dissection for regionally advanced (T1-4bN1bM0) PTC with regard to posttreatment Tg levels. METHODS: This is a single-institution retrospective cohort study of patients with regionally advanced PTC initially treated with total thyroidectomy and therapeutic levels 2-7 neck dissection from 2002 to 2012. Pathologic findings, complications, serum Tg levels, and outcomes were analyzed. RESULTS: Sixty-one patients were initially treated with total thyroidectomy and therapeutic central and lateral neck dissection for PTC involving the lateral cervical nodes (N1b). The median number of lymph nodes excised and positive was 27 (range 5-112) and 9 (range 1-67), respectively. Extranodal extension occurred in 48 %. Radioiodine was administered after surgery with a median total dose of 150 mCi (range 30-244 mCi). Recurrent or persistent cervical disease occurred in 8 (13 %) and 3 (5 %) patients, respectively, and required additional radioiodine treatment in 2 and reoperative neck dissection in 10. Three patients developed new distant metastasis, and 1 died during the median follow-up of 20 months (range 1-109 months). Undetectable unstimulated Tg (<1.0 ng/mL) without clinically detectable recurrence was experienced in 68 % of patients with initial treatment. CONCLUSIONS: Biochemical remission can be experienced in most patients presenting with regionally advanced PTC with total thyroidectomy and compartment based therapeutic neck dissection followed by a single dose of radioiodine.

Potential effects of molecular testing of indeterminate thyroid nodule fine needle aspiration biopsy on thyroidectomy volume.

BACKGROUND: Increasing utilization of genetic expression profiling (GEP) for thyroid nodules with indeterminate fine needle aspiration (FNA) results will potentially decrease the number of patients requiring diagnostic thyroidectomy. This study sought to determine the potential effects of GEP for indeterminate thyroid FNA results on thyroidectomy volume. METHODS: A retrospective review of thyroidectomy procedures performed over 1 year at the University of Michigan in the endocrine surgery division evaluated the indications for thyroidectomy, FNA Bethesda classification, and final surgical pathology to determine how application of GEP on indeterminate FNA results would affect decision for surgery and subsequent thyroidectomy volume. RESULTS: During the study period, 358 thyroidectomies were performed. The indication for procedure included: FNA findings, n = 122; symptomatic multinodular goiter, n = 85; nodule >4 cm, n = 30; Graves', n = 26; other, n = 95. FNA was performed in 231 patients. Bethesda classification included: benign, n = 69; malignant, n = 55; follicular lesion of undetermined significance, n = 59; follicular neoplasm, n = 20; suspicious for malignancy, n = 16; nondiagnostic, n = 12. If standard GEP was performed for all indeterminate FNA results, it would have influenced the decision for surgery in 68 (19 %) patients. Assuming 38 % of indeterminate FNA specimens will have benign results on genetic profiling, 27 patients would not have undergone thyroidectomy, translating into a 7.2 % decrease in overall thyroidectomy volume over a year. CONCLUSIONS: In an academic endocrine surgery program, the most common indication for thyroidectomy is an FNA result; however, standard application of GEP for all indeterminate thyroid FNAs would result in a minimal reduction in overall thyroidectomy volume.

Surgical Management of Primary Aldosteronism.

Hypertension leads to multiple comorbidities and increased risk for mortality. Endocrine disorders contribute to the development of hypertension, including primary aldosteronism (PA). This article discusses the evaluation and management of PA.

Efficacy and safety of near-infrared fluorescence identification of the thoracic duct during left lateral neck dissection.

BACKGROUND: Thoracic duct leaks occur in up to 5% of left lateral neck dissections. No one imaging modality is routinely used to identify the thoracic duct intraoperatively. The goal of our study was to evaluate the efficacy and safety of indocyanine green lymphangiography for intraoperative identification of the thoracic duct compared to traditional methods using ambient and evaluate the optimal timing of indocyanine green administration. METHODS: We enrolled all patients who underwent left lateral neck dissection at our institution from 2018 to 2022 in this prospective clinical trial. After indocyanine green injection into the dorsum of the foot, we performed intraoperative imaging was performed with a near-infrared fluorescence camera. We reported the data using descriptive statistics. RESULTS: Of the 42 patients we enrolled, 14 had prior neck surgery, and 3 had prior external beam radiation. We visualized the thoracic duct with ambient light in 48% of patients and with near-infrared fluorescence visualization in 64%. In 17% of patients, we could identify the thoracic duct only using near-infrared fluorescence visualization, which occurred within 3 minutes of injection, and were required to re-dose 5 patients. We visualized the thoracic duct with near-infrared fluorescence in all patients with prior neck radiation and 77% of patients with prior neck surgery. One adverse reaction occurred (hypotension), and 5 intraoperative thoracic duct injuries occurred that were ligated. There with no chylous fistulas postoperatively. CONCLUSION: This trial demonstrates that near-infrared fluorescence identification of the thoracic duct is feasible and safe with indocyanine green lymphangiography, even in patients with prior neck surgery or radiation.

Clinical characteristics and outcomes of adrenal hemorrhage.

BACKGROUND: Although uncommon, adrenal hemorrhage has multiple etiologies. Because clinical characteristics, management, and outcomes of patients with adrenal hemorrhage are inadequately described, we examined the underlying etiology, need for intervention, evolution of imaging characteristics, and adequacy of subsequent evaluation. METHODS: We performed a retrospective review of patients diagnosed with adrenal hemorrhage (radiologist-confirmed density consistent with hemorrhage on computed tomography) from 2005 to 2021 at a university-based institution. Demographic characteristics, hemorrhage etiology, and subsequent follow-up were analyzed. RESULTS: Of 193 adrenal hemorrhage patients, the mean age was 49.2 ± 18.3 years, and 35% were female. Clinical presentations included trauma (47%), abdominal or flank pain (28%), incidental findings on imaging acquired for other reasons (12%), postoperative complication (8%), or shock (3%). Hemorrhage outside of the gland was present in 62% of patients. Unilateral hemorrhage was more frequent (93%) than bilateral (7%). A total of 12% of patients had nodules, but only 70% of these were identified on initial imaging, and only 43% had hormonal evaluation. Of 7 patients who had adrenalectomy or biopsy, pathology was either benign (57%) or nonadrenal malignancy (43%). No adrenocortical carcinomas were identified. Follow-up imaging was performed in 56% of patients and revealed decreased, stable, resolved, or increased adrenal hemorrhage size in 39%, 19%, 30%, and 12% of patients, respectively. CONCLUSION: Adrenal hemorrhage is secondary to multiple etiologies, most commonly trauma. In the setting of adrenal hemorrhage, many adrenal nodules were not identified on initial imaging. Only a minority of patients with nodules underwent "complete" biochemical evaluation. Follow-up imaging may improve the identification of underlying nodules needing hormonal evaluation.

Reoperative lymph node dissection for recurrent papillary thyroid cancer and effect on serum thyroglobulin.

BACKGROUND: Papillary thyroid cancer (PTC) has an excellent prognosis with current treatment methods. However, the rates of locoregional recurrence after initial surgical management remain significant. This study evaluates the effect of reoperative neck dissection for locoregional recurrence of PTC after initial total thyroidectomy and radioiodine therapy on the incidence of cervical recurrence and postoperative serum thyroglobulin (Tg) levels. METHODS: This is a retrospective cohort study conducted in a single academic medical center of patients with recurrent or persistent PTC isolated to the neck after previous total thyroidectomy with or without lymph node dissection and adjuvant I(131) therapy who were treated with reoperative lymph node dissection. Outcomes including operative complications, pathologic findings, and effect of surgery on Tg levels and rates of recurrent disease were analyzed. RESULTS: From 2001 to 2010, a total of 61 patients had reoperative neck dissections for recurrent cervical PTC with a complication rate of 5 %. Seventy-two percent of patients were clinically free of detectable disease, and 28 % of patients had recurrent, persistent, or newly metastatic disease detected during the follow-up period. All patients had significant decreases in Tg levels, with a median 98 % reduction in preoperative levels. However, only 21 % of patients had an undetectable stimulated Tg (<0.5 ng/mL) during the follow-up period of 15.5 months. CONCLUSIONS: Reoperative treatment of recurrent or persistent PTC can be performed with low complication rates, and Tg levels greatly decrease in most patients; however, few achieve undetectable stimulated Tg.

Evaluation of postoperative radioactive iodine scans in patients who underwent prophylactic central lymph node dissection.

BACKGROUND: Prophylactic central lymph node dissection (CLND) accompanying total thyroidectomy for papillary thyroid cancer (PTC) remains controversial. Our hypothesis is that CLND may help select patients who benefit from postoperative radioactive iodine (RAI). METHODS: A total of 119 patients who were clinically node-negative underwent total thyroidectomy/bilateral CLND for papillary thyroid cancer (PTC) > 1 cm during 2002-2010. Pathology results, RAI results, and outcomes were compared between node-positive (NP) and node-negative (NN) patients. RESULTS: NP and NN patients were similar in age, gender, tumor size, and MACIS score. Median number of nodes excised was six. The rate of permanent hypocalcemia was 1.7% without permanent recurrent laryngeal nerve injuries. Thirteen of 52 (25%) NN patients and 24 of 67 (36%) NP patients had suspicious nodes by intraoperative inspection. The node assessment negative predictive value was 75%; positive predictive value was 36%. Fifty-six percent (67/118) were NP; 100 patients were treated with RAI. Fourteen of 62 NP patients had abnormal postoperative RAI scans aside from the thyroid remnant versus 4 of 38 NN patients (23 vs. 11%, p = 0.18). Median 1-year stimulated thyroglobulin (Tg) level was 0.0 for both (range 0.0-1.2, NN; 0.0-22.7, NP; p = 0.1). NP patients received higher doses of RAI (150 vs. 30 mCi, p < 0.001). Rate of recurrent or persistent disease was 3.4%. CONCLUSIONS: Few node-negative patients have abnormal RAI scans outside of the thyroid bed. Node-positive patients had greater variability in stimulated 1-year Tg levels after higher doses of RAI. CLND may identify the patients most likely to have persistently elevated stimulated Tg after initial therapy for PTC.

Worsening central sarcopenia and increasing intra-abdominal fat correlate with decreased survival in patients with adrenocortical carcinoma.

BACKGROUND: Accurate prediction of survival from adrenocortical carcinoma (ACC) is difficult and current staging models are unreliable. Central sarcopenia as part of the cachexia syndrome is a marker of frailty and predicts mortality. This study seeks to confirm that psoas muscle density (PMD), lean psoas muscle area (LPMA), lumbar skeletal muscle index (LSMI), and intra-abdominal (IA) or subcutaneous fat (SC) can be used in combination to more accurately predict survival in ACC patients. METHODS: PMD, LPMA, IA, and SC fat were measured on serial CT scans of patients with ACC. Clinical outcome was correlated with quantitative data from patients with ACC and analyzed. A linear regression model was used to describe the relationship between PMD, LPMA, LSMI, IA, and SC fat, time to recurrence, and length of survival according to tumor stage. RESULTS: One hundred twenty-five ACC patients (94 females) were treated from 2005 to 2011. Significant morphometric predictors of survival include PMD, LPMA, and IA fat (p ≤ 0.0001, ≤ 0.0024, <0.0001, respectively) and improve prediction of survival compared to using stage alone. A 100-mm(2) increase in LPMA confers an 8 % lower hazard of death. LSMI does not change significantly between stages (p = 0.3196). CONCLUSION: Decreased PMD, LPMA, and increased IA fat suggest decreased survival in ACC patients and correlate with traditional staging systems. A more precise prediction of survival may be achieved when staging systems and morphometric measures are used in combination. Serial measurements of morphometric data are possible. The rate of change of these variables over time may be more important than the absolute value.

Paraganglioma: not just an extra-adrenal pheochromocytoma.

PURPOSE: Pheochromocytoma (PCC) and paraganglioma (PG) are evaluated and treated similarly. This study evaluates the hypothesis that tumor characteristics and outcome of patients with PCC and PG are equivalent. METHODS: Records of patients from a single institution undergoing resection of PCC or PG from 1999 to 2010 were reviewed. Data were collected for demographics, operative records, laboratory and pathologic results, adjuvant and palliative therapy given, recurrence, and length of survival. Descriptive statistics were used to describe differences between patients with benign and malignant PCC and PG. Analysis was performed using the Wilcoxon-Mann-Whitney test with p = 0.05 considered as significant. RESULTS: One hundred fifteen patients were identified (106 PCC and nine PG). Of the tumors, 5.2% were bilateral and 10.4% were malignant. Forty-three of the 115 patients underwent genetic testing; 21 out of 37 (56.8%) PCC and five out of six (83.3%) PG had a genetic mutation. Twelve patients (seven PCC and five PG) had malignant tumors. Malignant PG (mPG) exhibited more invasive pathologic characteristics. The median sizes of benign and malignant PCC (mPCC) were 4.0 (0.7-14 cm) and 5.5 cm (3.7-11.2 cm), respectively, p = 0.03. The median sizes of benign and mPG were 4.1 (2.7-5.4 cm) and 5.8 cm (4-6.2 cm), respectively, p = 0.11. Sites of recurrence were similar between the groups. Patients with mPG received chemotherapy more often than those with mPCC. With a median follow-up of 54.7 months (2.0-185.3), two out of five mPG and zero out of seven mPCC had died of the disease. CONCLUSION: Tumor size does not appear to correlate with malignancy in a clinically significant manner. Malignant paraganglioma may be more aggressive than malignant pheochromocytoma and is frequently offered more adjuvant therapy. PCC and PG should be evaluated separately in future analyses of these diseases.

Adrenal Near-Infrared Autofluorescence.

Context: Parathyroid tissue is one of the few tissues to have strong near-infrared (NIR) autofluorescence, which has been exploited to improve intraoperative parathyroid identification. The US Food and Drug Administration has approved 2 devices for this purpose. Adrenal glands can be difficult to distinguish from surrounding fat, an issue during total adrenalectomy. Objective: We hypothesized adrenal tissue may also possess considerable NIR autofluorescence. Methods: Resected patient adrenal specimens were examined after robotic adrenalectomy with an NIR camera intraoperatively. Patients did not receive fluorescent dye. Images were taken of both gross and sectioned specimens. Post hoc image analysis was performed with ImageJ software. Confocal microscopy was performed on selected tissues using immunofluorescence and hematoxylin-eosin staining. Results: Resected tissue was examined from 22 patients undergoing surgery for pheochromocytomas (6), primary aldosteronism (3), adrenocorticotropin-independent hypercortisolism (10), and a growing or suspicious mass (3). Normal adrenal tissue demonstrated strong NIR autofluorescence. The intensity ratio compared to background (set as 1) for gross images was 2.03 ±â€…0.51 (P < .0001) compared to adjacent adipose of 1.24 ±â€…0.18. Autofluorescence from adrenal tumors was also detected at variable levels of intensity. Cortisol-producing tumors had the highest fluorescence ratio of 3.01 ±â€…0.41. Confocal imaging localized autofluorescence to the cytosol, with the highest intensity in the zona reticularis followed by the zona fasciculata. Conclusion: Normal and abnormal adrenal tissues possess natural NIR autofluorescence. Highest autofluorescence levels were associated with cortisol-producing tumors. Confocal imaging demonstrated the highest intensity in the zona reticularis. NIR cameras may have the potential to improve identification of adrenal tissue during surgery.

An examination of recently revised differentiated thyroid cancer guidelines.

PURPOSE OF REVIEW: To examine the most recent changes in published guidelines by various organizations for the treatment of patients with differentiated thyroid cancer. This document provides a comparison of recommendations for common topics currently found in available thyroid cancer care guidelines. RECENT FINDINGS: Recent changes to guidelines have focused on controversial topics, including extent of thyroidectomy based on tumor size, prophylactic central neck dissection, use of radioactive iodine, and degree of thyrotropin suppression. Regional variations between guidelines exist. Adherence to thyroid cancer guidelines at national levels is less than ideal. SUMMARY: Guidelines for the management of differentiated thyroid cancer should continue to reflect minor regional variations in thyroid cancer treatment based on factors unique to that population while remaining otherwise similar to ensure optimal state-of-the-art patient care and outcomes. In the future, individual patient molecular information will likely play an important role in assessing the risk of tumor recurrence and overall survival. Consideration of multiple patient and tumor factors will allow thyroid cancer specialists to use a risk-adapted approach to patient care, from both a surgical and medical standpoint, to ensure optimal patient outcomes on an individual basis and at a disease level.

Intraoperative parathyroid hormone monitoring in patients with recognized multiglandular primary hyperparathyroidism.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) monitoring reliably predicts cure of primary hyperparathyroidism (PHPT) due to single-gland disease. However, its utility in PHPT caused by multiple-gland disease (MGD) is still debated, for both detection and prediction of adequate resection. Our hypothesis is that once MGD is encountered during an operation, more stringent criteria for determining adequate resection can improve cure rates. METHODS: This was a retrospective cohort study of patients with PHPT who were found to have MGD during the course of focused parathyroidectomy. IOPTH levels after completed multiple parathyroid gland excision were compared between cured patients and those with persistent hyperparathyroidism. RESULTS: Of 1855 patients undergoing focused parathyroidectomy, 243 were found to have MGD. Of the 207 study patients with MGD, 193 were cured and 14 had persistent hyperparathyroidism. After final gland excision, the mean±SEM percentage decrease in IOPTH from the baseline was of significantly greater magnitude for the cured group (90.0±0.5%) than for the persistent group (74.0±3.8%) (p<0.01). The mean±SEM IOPTH after completed multigland excision was higher in the persistent group (44.0±8.4 pg/ml) than in the cured group (34.0±3.5 pg/ml) (p=0.19), although both were within the normal range (12-65 pg/ml). When the groups were analyzed for an incremental fall of IOPTH from the baseline, the criteria of ≥75% drop and into the normal range improved the positive predictive value from 93.2 to 96.6% when compared to the standard criterion of a 50% decrease from the baseline. CONCLUSIONS: When PHPT due to MGD is recognized and focused parathyroidectomy is extended, a final postexcision PTH level that is ≥75% decreased from the baseline PTH level and in the normal range should be used to predict adequate gland resection.