Perception of risk and treatment decisions in the management of differentiated thyroid cancer.

BACKGROUND AND OBJECTIVES: The recent de-escalation of care for differentiated thyroid cancer (DTC) has broadened the range of initial treatment options. We examined the association between physicians' perception of risk and their management of DTC. METHODS: Thyroid specialists were surveyed with four clinical vignettes: (1) indeterminate nodule (2) tall cell variant papillary thyroid cancer (PTC), (3) papillary thyroid microcarcinoma (mPTC), and (4) classic PTC. Participants judged the operative risks and likelihood of structural cancer recurrence associated with more versus less aggressive treatments. A logistic mixed effect model was used to predict treatment choice. RESULTS: Among 183 respondents (13.4% response rate), 44% were surgical and 56% medical thyroid specialists. Risk estimates and treatment recommendation varied markedly in each case. Respondents' estimated risk of 10-year cancer recurrence after lobectomy for a 2.0-cm PTC ranged from 1% to 53% (interquartile range [IQR]: 3%-12%), with 66% recommending lobectomy and 34% total thyroidectomy. Respondents' estimated 5-year risk of metastastic disease during active surveillance of an 0.8-cm mPTC ranged from 0% to 95% (IQR: 4%-15%), with 36% choosing active surveillance. Overall, differences in perceived risk reduction explained 10.3% of the observed variance in decision-making. CONCLUSIONS: Most of the variation in thyroid cancer treatment aggressiveness is unrelated to perceived risk of cancer recurrence.

Trends in Adjuvant External Beam Radiation Therapy for Nonanaplastic Thyroid Cancer in California, 2003-2017.

BACKGROUND: External beam radiation therapy (EBRT) is rarely used to treat patients with differentiated or medullary thyroid cancer. Although EBRT is generally administered to patients with high-risk or unresectable diseases, neither its indications for the use nor the associated outcomes are well-defined. We used a statewide cohort to assess the trends in EBRT use and postradiation outcomes in California. METHODS: A population-based study of patients within the California Cancer Registry who underwent EBRT after surgery for nonanaplastic thyroid cancer (2003-2017) was conducted. The primary outcome was the annual utilization rate of EBRT. The secondary outcomes included Kaplan-Meier analysis for cause-specific survival and identifying factors associated with improved survival after EBRT. RESULTS: Among the 57 607 patients with nonanaplastic thyroid cancer from 2003 to 2017, 344 (0.6%) patients received EBRT. EBRT was utilized in 0.4% of papillary, 1.1% of follicular, and 7.7% of medullary thyroid cancers in California. Overall, 99 (28.8%) patients treated with EBRT died of thyroid cancer. The 10-year cause-specific survival of all patients with thyroid cancer after EBRT was 61.5% (95% CI: 54.8%-69.1%) and that of patients without distant disease was 80.3% (95% CI: 73.5%-87.8%). The survival outcomes varied by tumor size, histology, disease stage, patient age at diagnosis, and the presence of extrathyroidal extension (P < .05). CONCLUSIONS: The use of adjuvant EBRT for nonanaplastic thyroid cancer remained stable and low in California from 2003 to 2017. The comparative efficacy of EBRT was not discernible in this study, but disease control appeared durable in select patients. Well-controlled observational studies and/or prospective studies are needed to better define which patients benefit from EBRT.

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma.

OBJECTIVE: Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine. METHODS: We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs. RESULTS: Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin. CONCLUSION: Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.

Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer in children, adolescents and young adults.

OBJECTIVE: Recombinant human TSH (rhTSH) is commonly used to prepare patients for postoperative radioiodine (I-131) ablation after surgery for differentiated thyroid cancer (DTC). In adults, rhTSH is associated with equivalent oncologic efficacy in comparison to thyroid hormone withdrawal (THW), but its use has not been well studied in children. We aimed to measure time to disease progression after rhTSH stimulation vs. THW in paediatric patients under the age of 21 with DTC following total thyroidectomy. DESIGN: Retrospective cohort study (March 2001-July 2018). PATIENTS: Sixteen children and adolescents (75% female, median age, 17.4 years) who received rhTSH were compared to 29 historical controls (72% female, median age, 18.5 years) prepared with THW, followed for a median of 2.4 years (range, 0.5-14). MEASUREMENTS: Stimulated serum TSH concentrations prior to I-131 ablation and time to disease progression, as determined by a component outcome variable encompassing both structural and biochemical disease persistence/recurrence. RESULTS: No differences were observed in tumour characteristics and I-131 dose (median 2.3 [1.8-2.90] mCi/kg rhTSH) between groups. Patients who received rhTSH achieved a similar median stimulated TSH level (163 [127-184] mU/L), compared to those who underwent THW (136 [94.5-197] mU/L; p = .20). Both groups exhibited similar time to progression (p = .13) and disease persistence/recurrence rates (rhTSH 31% vs. THW 59%, p = .14). CONCLUSION: In this cohort of children and adolescents with DTC, we observed similar time to disease progression among those who received rhTSH or underwent THW prior to postoperative I-131 ablation.

Pathologic Features Associated With Molecular Subtypes of Well-Differentiated Thyroid Cancer.

OBJECTIVE: To determine the association between pathologic features and molecular classes (BRAF-like, RAS-like, and non-BRAF-like non-RAS-like [NBNR]). METHODS: Retrospective review of a merged database containing 676 patients, 84% (571/676) were assigned to a molecular class from publicly accessible sequenced data of thyroid neoplasms. RESULTS: The merged cohort included 571 neoplasms: 353 (62%) BRAF-like, 172 (30%) RAS-like, and 46 (8.1%) NBNR. Lymph node metastasis (any N1 disease) was present in 166/337 (49%) of BRAF-like, 23/164 (14%) of RAS-like, and 0/46 (0%) of NBNR and are significantly different (P < .001). Gross extra-thyroidal extension was observed in 27 patients, including 24/331 (7%) of BRAF-like, 2/160 (1%) of RAS-like, and 1/46 (2%) of NBNR (P = .01). N1B lymph node metastases or T4 disease was present in 74/333 (22%) of BRAF-like, 10/160 (6%) of RAS-like, and 1/46 (2%) of NBNR (P < .0001). Distant metastasis was present in 4/151 (2.6%) of BRAF-like, 2/50 (4%) of RAS-like and 0/46 for NBNR (P = .627). Angioinvasion was present in 0/81 (0%) of BRAF-like, 3/53 (6%) of RAS-like, and 3/46 (7%) of NBNR (P = .08); and multifocality was present in 27/81 (33%) of BRAF-like, 9/53 (17%) of RAS-like, and 1/46 (2%) for NBNR (P = .0001). CONCLUSION: Pathological features of metastasis, gross extra-thyroidal extension, and multifocality were more prevalent in BRAF-like samples compared to RAS-like and NBNR. A trend towards increased frequency of angioinvasion in RAS-like and NBNR cancers compared to BRAF-like samples was observed. Further studies are needed to evaluate if preoperative knowledge of molecular mutations in thyroid tumors aids in decision-making regarding extent of surgery.

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer.

OBJECTIVE: To determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC). METHODS: This retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models. RESULTS: Postoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines. CONCLUSION: More than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.

Normocalcaemic primary hyperparathyroidism: An update on diagnostic and management challenges.

Normocalcaemic primary hyperparathyroidism is a condition that can present with intermittent hypercalcemia or may evolve into hypercalcemic primary hyperparathyroidism. This milder biochemical entity remains incompletely understood because of a lack of long-term health outcomes regarding both medical and surgical approaches to its management. Medical therapies have shown some efficacy. A limited number of studies have found that bisphosphonates increase bone mineral density, and calcimimetics may decrease the risk of nephrolithiasis in patients with normocalcaemic primary hyperparathyroidism. Studies have also described patient outcomes after applying the same surgical criteria used for patients with hypercalcaemic primary hyperparathyroidism to those with the normocalcaemic form of the disease. These studies suggest that parathyroid surgery appears to be effective in normalizing elevated serum parathyroid hormone concentrations and decreasing adverse renal and skeletal outcomes in patients with normocalcaemic hyperparathyroidism. Given the available data and overall lack of consensus regarding the optimal management of these patients, a reasonable approach is to tailor treatment to the individual patient by considering their risk factors for new or accelerated bone loss, kidney stones, diminished quality of life, and cardiovascular disease.

Selective use of Molecular Testing Based on Sonographic Features of Cytologically Indeterminate Thyroid Nodules: A Decision Analysis.

BACKGROUND: Molecular diagnostics can allow some patients with indeterminate thyroid nodule cytopathology to avoid diagnostic hemithyroidectomy; however, the testing is costly. We hypothesized that molecular testing with the intention of preventing unnecessary diagnostic hemithyroidectomy would be cost-effective if this test was applied selectively based on sonographic risk of malignancy. METHODS: A Markov model was constructed depicting a 40-year-old patient with a cytologically indeterminate thyroid nodule. Molecular testing of fine needle aspiration material was compared to a strategy of immediate diagnostic hemithyroidectomy. Data from a single tertiary-referral health system were reviewed to estimate the outcomes of molecular testing of indeterminate nodules stratified by the American Thyroid Association sonographic classification system. Other outcome probabilities and their utilities were derived from literature review. Costs were estimated with Medicare reimbursement data. A $100,000/QALY threshold for cost-effectiveness was applied. Sensitivity analysis was employed to examine uncertainty in the model's assumptions. RESULTS: Of 123 patients who underwent molecular testing for indeterminate cytology, 12 (9.8%) were classified as high sonographic suspicion, 49 (40%) were intermediate suspicion, and 62 (50%) were low or very low suspicion. Molecular testing was only cost-effective when the pretest probability of a negative test was greater than 31%. The model was most sensitive to the cost of molecular testing and the quality adjustment factor for hypothyroidism. CONCLUSIONS: In hypothetical modeling, molecular testing is only cost-effective for cytologically indeterminate thyroid nodules with sonographic features that are intermediate or low suspicion for malignancy. In nodules with high sonographic suspicion, molecular testing is rarely negative and appears to add minimal value.

Surgery for Primary Hyperparathyroidism: Adherence to Consensus Guidelines in an Academic Health System.

OBJECTIVE: To determine the extent to which consensus guidelines for surgery in patients with primary hyperparathyroidism (PHPT) are followed within an academic health system. BACKGROUND: Previous studies have shown that adherence to consensus guidelines in community practice is low. METHODS: Adults with biochemically confirmed PHPT who received primary care within an academic health system were identified from 2005 to 2015. Multivariable logistic regression was used to analyze predictors of parathyroidectomy (PTx). RESULTS: In 617 patients, the overall PTx rate was 30.8%. When individual consensus criteria were examined, age <50 (P<0.01), serum calcium >11.3 mg/dL (P < 0.01), and hypercalciuria (P = 0.02) were associated with PTx; while nephrolithiasis (P = 0.07) and osteoporosis (P = 0.34) did not affect the PTx rate. The PTx rate increased with the number of consensus criteria satisfied (1 criterion, 33%; 2 criteria, 45%; 3 or more criteria, 82%, P < 0.01). Independent predictors of PTx included male sex [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.8], increasing serum parathyroid hormone (OR 1.1 per 10 pg/mL 95% CI 1.05-1.13), and endocrinologist evaluation (OR 1.6, 95% CI 1.1-2.4); while Black race (OR 0.4, 95% CI 0.2-0.8), lack of 24-hour urine calcium measurement (OR 0.5, 95% CI 0.3-0.8), Charlson Comorbidity Index ≥ 2 (OR 0.6, 95% CI 0.4-0.9), and age ≥80 years (OR 0.2, 95% CI 0.1-0.4) predicted against PTx. CONCLUSION: Within an academic health system, consensus guidelines do appear to influence the decision for surgery in patients with PHPT. However, the level of compliance is generally low, and similar to that observed in community practice.

Biochemical and Skeletal Outcomes of Parathyroidectomy for Normocalcemic (Incipient) Primary Hyperparathyroidism.

BACKGROUND: Normocalcemic (incipient) primary hyperparathyroidism (PHPT) is characterized by inappropriately elevated parathyroid hormone (PTH) levels in the setting of normal serum calcium. The biochemical and skeletal outcomes after parathyroidectomy for normocalcemic PHPT are not well-described. METHODS: All patients who underwent parathyroidectomy for normocalcemic PHPT at a single institution were retrospectively reviewed (2006-2016). Pre- and postoperative calcium, PTH, and bone mineral density (BMD) were compared between patients with normalized versus persistently elevated PTH levels > 6 months after parathyroidectomy. Multivariable Cox regression was used to identify risk factors associated with persistently elevated PTH levels after parathyroidectomy. RESULT: Parathyroidectomy was performed in 71 patients with normocalcemic PHPT, of whom 38 (53.5%) had multi-gland disease. No patients became hypercalcemic, with a median follow-up of 23.1 months. Persistently elevated PTH levels were noted in 33 (46.5%) patients. In multivariable analysis, preoperative PTH > 100 pg/mL was associated with persistently elevated PTH levels after parathyroidectomy. In 38 patients with available pre- and postoperative BMD measurements, the mean preoperative BMD improved + 5.6% (p < 0.01) in patients with normalized PTH, while no significant change was observed in patients with persistently elevated PTH levels (- 2.2%, p = 0.47). CONCLUSIONS: Elevated PTH levels are common after parathyroidectomy for normocalcemic PHPT. Improvements in BMD may be predicated on long-term normalized PTH levels following surgery.

Risk Factors for Readmission After Parathyroidectomy for Renal Hyperparathyroidism.

BACKGROUND: Patients with renal hyperparathyroidism (RHPT) are susceptible to major electrolyte fluctuations following parathyroidectomy, which may predispose them to early readmission. The purpose of this study is to evaluate risk factors for readmission in patients undergoing parathyroidectomy for RHPT. METHODS: Patients with renal failure who underwent parathyroidectomy were abstracted from the California Office of Statewide Health Planning and Development (1999-2012). Multivariable logistic regression was used to identify risk factors for readmission within 30 days of discharge. RESULTS: The cohort included 4411 patients, of whom 17% were readmitted. Procedures included subtotal parathyroidectomy (74% of cases) and total parathyroidectomy with autotransplantation (26%). Median time to readmission was 9 days (interquartile range 4-16 days). Electrolyte disturbances including hypocalcemia were present in 36% of readmissions and were the most common cause for readmission. Independent risk factors for readmission included Black race [odds ratio (OR) 1.26, 95% confidence interval (CI) 1.00-1.57], Hispanic race (OR 1.38, 95% CI 1.12-1.71), disposition with home health (OR 1.94, 95% CI 1.35-2.77), disposition to a skilled nursing facility (OR 2.30, 95% CI 1.58-3.35), and total parathyroidectomy with autotransplantation (OR 1.27, 95% CI 1.06-1.52). Advancing age (OR 0.98, 95% CI 0.98-0.99) and surgery at a high-volume hospital (OR 0.53, 95% CI 0.36-0.77) were protective against readmission. CONCLUSIONS: Patients undergoing parathyroidectomy for RHPT have a high readmission rate, most frequently for metabolic complications. Increased postoperative vigilance, which may include outpatient laboratory monitoring, may be indicated in patients with risk factors for readmission.

BIOCHEMICAL DYNAMICS OF UNTREATED PRIMARY HYPERPARATHYROIDISM: AN OBSERVATIONAL STUDY.

Objective: The natural biochemical history of untreated primary hyperparathyroidism (PHPT) is poorly understood. The purpose of this study was to determine the extent of biochemical fluctuations in patients with PHPT. Methods: Retrospective cohort study from January 1, 1995, to December 31, 2014. Serum calcium and parathyroid hormone (PTH) levels in patients with classic (Ca >10.5 mg/dL, PTH >65 pg/mL) and nonclassic (Ca >10.5 mg/dL, PTH 40 to 65 pg/mL) PHPT were followed longitudinally at 1, 2, and 5 years. Biochemical profiles in follow-up were ranked in descending biochemical severity as classic PHPT, nonclassic PHPT, normal calcium with elevated PTH (Ca <10.5 mg/dL, PTH >65 pg/mL), possible PHPT (Ca >10.5 mg/dL, PTH 21 to 40 pg/mL), or absent PHPT (Ca >10.5 mg/dL, PTH <21 pg/mL or Ca <10.5 mg/dL, PTH <65 pg/mL). Results: Of 10,598 patients, 1,570 were treated with parathyroidectomy (n = 1,433) or medications (n = 137), and 4,367 were censored due to study closure, disenrollment, or death. In the remaining 4,661 untreated patients with 5 years of follow-up, 235 (5.0%) progressed to a state of increased biochemical severity, whereas 972 (20.8%) remained the same, and 3,454 (74.1%) regressed to milder biochemical states. In 2,522 untreated patients with classic PHPT, patients most frequently transitioned to the normal calcium with elevated PTH group (n = 1,257, 49.8%). In 2,139 untreated patients with nonclassic PHPT, patients most frequently transitioned to the absent PHPT group (n = 1,354, 63.3%). Conclusion: PHPT is a biochemically dynamic disease with significant numbers of patients exhibiting both increases and decreases in biochemical severity. Abbreviations: IQR = interquartile range; KPSC = Kaiser Permanente Southern California; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; PTx = parathyroidectomy.

Cost Effectiveness of Routine Laryngoscopy in the Surgical Treatment of Differentiated Thyroid Cancer.

BACKGROUND: Some surgeons perform flexible fiberoptic laryngoscopy (FFL) in all patients prior to thyroid cancer operations. Given the low likelihood of recurrent laryngeal nerve (RLN) or aerodigestive invasion in clinically low-risk thyroid cancers, the value of routine FFL in this group is controversial. We hypothesized that routine preoperative FFL would not be cost effective in low-risk differentiated thyroid cancer (DTC). METHODS: A decision model was constructed comparing preoperative FFL versus surgery without FFL in a clinical stage T2 N0 DTC patient without voice symptoms. Total thyroidectomy and definitive hemithyroidectomy were both modeled as possible initial surgical approaches. Outcome probabilities and their corresponding utilities were estimated via literature review, and costs were estimated using Medicare reimbursement data. Sensitivity analysis was conducted to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: When the initial surgical strategy was total thyroidectomy, routine preoperative FFL produced an incremental cost of $183 and an incremental effectiveness of 0.000126 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) for routine FFL prior to total thyroidectomy was $1.45 million/QALY, exceeding the $100,000/QALY threshold for cost effectiveness. Routine FFL became cost effective if the preoperative probability of asymptomatic vocal cord paralysis increased from 1.0% to 4.9%, or if the cost of preoperative FFL decreased from $128 to $27. Changing the extent of initial surgery to hemithyroidectomy produced a higher ICER for routine FFL of $1.7 million/QALY. CONCLUSION: Routine preoperative FFL is not cost effective in asymptomatic patients with sonographically low-risk DTC, regardless of the initial planned extent of surgery.

Endocrinopathies with use of cancer immunotherapies.

BACKGROUND: Immunomodulatory therapies, including CTLA-4 and PD-1 inhibitors, provide a directed attack against cancer cells by preventing T cell deactivation. However, these drugs also prevent the downregulation of auto-reactive T cells, resulting in immune-related adverse events (IRAEs). Reports show a varied incidence of endocrine IRAEs, ranging from 0% to 63%. OBJECTIVE: To describe the frequency and clinical characteristics of endocrine IRAEs in patients taking cancer immunomodulatory therapies. DESIGN: Retrospective cohort study. PATIENTS: A total of 388 patients aged ≥18 years who were prescribed ipilimumab, nivolumab and/or pembrolizumab between 2009 and 2016 at our institution. MEASUREMENTS: Biochemical criteria were used to define endocrine IRAEs, including thyroid, pituitary, pancreas and adrenal dysfunction, following use of immunomodulatory therapies. RESULTS: Fifty endocrine IRAEs occurred in our cohort, corresponding to a rate of 12.9%. The most common endocrine IRAEs were thyroid dysfunction (11.1%), with a lower incidence of pituitary dysfunction (1.8% of patients). CONCLUSIONS: Over 12% of patients receiving ipilimumab, nivolumab and/or pembrolizumab in our study sample developed an endocrine IRAE. Patients who undergo treatment with immunomodulatory therapies should be monitored for the development of endocrine IRAEs.

Sustained Growth of a University-Based Endocrine Surgery Program Over 10 Years.

BACKGROUND: Endocrine surgery continues to mature as a subspecialty field. We describe the clinical performance of an academic endocrine surgery program (ESP) over its first 10 years. METHODS: We examined all endocrine procedures performed during the 10-year period (2006-2015) following the inception of the ESP. Institutional and state-level data on case volume, patient geographic origin, and hospital-side costs were obtained. RESULTS: Endocrine case volume increased by approximately ninefold over the study period (from 102 cases in 2006 to 919 cases in 2015). The rate of growth remained approximately linear, and was driven by geographic expansion of referral regions coupled with transitioning low- to moderate-acuity operations to venues outside of the main tertiary care hospital. Market share across the eight-county Southern California region grew by more than twofold over the study period. Increased utilization of outpatient surgery led to cost reductions, averaging 11.1% per case by 2015. CONCLUSIONS: Establishment of an academic ESP can lead to sustained clinical growth and a fundamental shift in regional referral patterns. The nation's continued need for skilled high-volume endocrine surgeons represents opportunities for medical centers to institute their own dedicated endocrine surgery programs.

Incidence of abnormal liver biochemical tests in hyperthyroidism.

OBJECTIVE: Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen the severity of the abnormal serum liver biochemistries. There is a wide range of the incidence of these abnormalities in the published literature. The aim of this study was to assess the risks factors and threshold of thyrotoxicosis severity for developing an abnormal liver biochemical test upon the diagnosis of new thyrotoxicosis. DESIGN: Single-institution retrospective cohort study. PATIENTS: Patients of ≥18 years old receiving medical care at a large, academic, urban US medical centre between 2002-2016. MEASUREMENTS: Inclusion criteria were a serum thyroid stimulating hormone (TSH) concentration of <0·3 mIU/l or ICD-9 code for thyrotoxicosis, with thyrotoxicosis confirmed by either a concurrent elevated serum triiodothyronine (T3) or thyroxine (T4) concentration ([total or free] within 3 months), and an available liver biochemical test(s) within 6 months of thyrotoxicosis. The biochemical liver tests assessed were serum aspartate transaminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), total bilirubin, and conjugated bilirubin concentrations. RESULTS: In this cohort of 1514 subjects, the overall incidence of any biochemical liver test abnormality within 6 months of thyrotoxicosis was 39%. An initial serum TSH concentration <0·02 mIU/l, male gender, and African-American race were significant predictors of an abnormal serum liver biochemical test within 6 months of the diagnosis of new-onset untreated thyrotoxicosis. CONCLUSIONS: This study identifies risk factors for patients who develop an abnormal serum liver biochemical test result within 6 months of a diagnosis of untreated thyrotoxicosis.

Single-incision retroperitoneoscopic adrenalectomy: a North American experience.

BACKGROUND: Endoscopic adrenalectomy is currently performed using multiple ports placed either transabdominally or retroperitoneally. We report our initial experience with single-incision retroperitoneoscopic adrenalectomy (SIRA). METHODS: A prospective database of patients undergoing adrenalectomy from December 2013 through March 2016 was analyzed. We adopted conventional retroperitoneoscopic adrenalectomy (CORA) in December 2013 and transitioned to SIRA in March 2015. SIRA was performed using three trocars placed through a single 2-cm incision below the 12th rib. Clinical characteristics and outcomes were compared between patients undergoing SIRA and CORA. RESULTS: One hundred and five adrenalectomies were performed in 102 patients: 34 laparoscopic transperitoneal, 24 CORA, 37 SIRA and 7 open. The SIRA and CORA groups were similar with respect to clinical characteristics (SIRA vs. CORA: mean BMI 27.0 vs. 28.8 kg/m2, maximum BMI 38.9 vs. 44.3 kg/m2; mean nodule size 3.2 vs. 3.2 cm, maximum nodule size 8.0 vs. 6.0 cm). One patient undergoing SIRA required placement of an additional 5-mm port because of extensive adhesions. No patients who underwent SIRA or CORA required conversion to open adrenalectomy. There were no deaths, and blood loss remained <10 mL for all cases. Operative length was similar between SIRA and CORA (105 vs. 92 min, P = 0.26). In multivariable linear regression analysis, nodule size > 5 cm (effect = 1.75, P < 0.001) and pheochromocytoma (effect = 1.30, P = 0.05) were significant predictors of increased operative length for SIRA. BMI and laterality (right vs. left) did not affect operative length. Rates of postoperative temporary abdominal wall relaxation, length of stay and postoperative pain medication use were similar between the two groups. CONCLUSIONS: SIRA is safe and feasible to implement as a refinement of CORA and may be applied to technically challenging cases involving obese patients or large nodules. The use of three ports allows for two-handed dissection, which may shorten the learning curve for many surgeons.

NONOPERATIVE MANAGEMENT OF DIFFERENTIATED THYROID CANCER IN CALIFORNIA: A POPULATION-LEVEL ANALYSIS OF 29,978 PATIENTS.

OBJECTIVE: There has been increasing interest in active surveillance of papillary thyroid microcarcinoma. The objective of this study was to characterize the incidence and outcomes of nonoperatively managed differentiated thyroid cancers (DTCs) in California. METHODS: Biopsy-proven DTCs from the California Cancer Registry were linked to data from the California Office of Statewide Health Planning and Development (2004-2012). Low-risk tumors were defined as localized disease measuring <4 cm without extrathyroidal extension, nodal involvement, or distant metastasis. RESULTS: Of 29,978 patients with DTC, 318 (1.1%) were managed nonoperatively. Compared to operatively managed patients, patients managed nonoperatively were older with more comorbidities, larger tumors (mean size, 2.9 cm vs. 2.0 cm), and an increased rate of distant metastasis (20.4% vs. 3.4%). Independent predictors of nonoperative management included increasing age, larger tumor size, papillary histology, and distant metastases. Of 10,795 patients with low-risk tumors, 161 (1.5%) were managed nonoperatively, with tumor size as follows: <1 cm (15.5%), 1 to 2 cm (50.3%), >2 to 3 cm (24.3%), and >3 to 4 cm (9.9%). There were no disease-specific deaths in the low-risk, nonoperative group (median follow-up [interquar-tile range], 21.3 [5.7 to 51.1] months). The proportion of patients managed nonoperatively remained relatively stable over the study period (mean increase 0.1% per year, P = .09). All P values were <.05 unless otherwise stated. CONCLUSION: The vast majority of patients with DTCs are treated surgically, suggesting active surveillance is rarely practiced in California. Although follow-up was limited, no disease-specific mortality in nonoperatively managed, low-risk DTCs was observed. ABBREVIATIONS: CCI = Charlson Comorbidity Index; CCR = California Cancer Registry; CI = confidence interval; DTC = differentiated thyroid cancer; FTC = follicular thyroid carcinoma; HCC = Hürthle cell carcinoma; IQR = interquartile range; mPTC = papillary thyroid micro-carcinoma; OR = odds ratio; OSPHD = Office of Statewide Health Planning and Development; PTC = papillary thyroid carcinoma.

The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study.

BACKGROUND: The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown. OBJECTIVE: To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT. DESIGN: Retrospective cohort study. SETTING: An integrated health care delivery system. PARTICIPANTS: All enrollees with biochemically confirmed PHPT from 1995 to 2010. MEASUREMENTS: Bone mineral density (BMD) changes and fracture rate. RESULTS: In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and declined progressively in both women and men without these treatments (-6.6% and -7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery. LIMITATION: Retrospective study design and nonrandom treatment assignment. CONCLUSION: Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation. PRIMARY FUNDING SOURCE: National Institute on Aging.