Fumarate Hydratase Variants and Their Association With Paraganglioma/Pheochromocytoma.

OBJECTIVE: To clarify the link between germline variants in fumarate hydratase (FH), hereditary leiomyomatosis and renal cell cancer (HLRCC), and paraganglioma (PGL) and pheochromocytoma (PCC) we utilize a well-annotated hereditary cancer testing database. METHODS: Records of 120,061 patients receiving germline testing were obtained. FH variants were classified into 4 categories: autosomal dominant (AD) HLRCC variants, autosomal recessive (AR) fumarase deficiency (FMRD), variants, previously reported as PGL/PCC FH variants, and variants of unknown significance (VUS) not previously associated with PGL/PCC (NPP-VUS). Rates of PGL/PCC were compared with those with negative genetic testing. RESULTS: About 1.3% of individuals carried FH variants which were more common among individuals with PGL/PCC compared to those without (3.1% vs 1.3%, P < .0001). PGL/PCC rates were higher among individuals with PGL/PCC FH variants compared to those with negative genetic testing (22.2% vs 0.9%, P < .0001). Neither AD HLRCC variants (0.3% vs 0.9%, P = .35) nor AR FMRD variants (1.4% vs 0.9%, P = .19) carried an increased prevalence of PGL/PCC. An increased prevalence of PGL/PCC was detected in those with NPP-VUS (2.0% vs 0.9%, P = .0023). CONCLUSIONS: Certain FH variants confer an increased risk of PGL/PCC, but not necessarily HLRCC. While universal screening for PGL/PCC among all individuals with FH variants does not appear warranted, it should be considered in select high-risk PGL/PCC FH variants.

Thyroid Cancer and Pesticide Use in a Central California Agricultural Area: A Case Control Study.

OBJECTIVE: To examine environmental factors that influence risk of thyroid cancer. METHODS: We performed a case-control study utilizing thyroid cancer cases from the California Cancer Registry (1999-2012) and controls sampled in a population-based manner. Study participants were included if they were diagnosed with thyroid cancer, lived in the study area at their time of diagnosis, and were ≥35 years of age. Controls were recruited from the same area and eligible to participate if they were ≥35 years of age and had been living in California for at least 5 years prior to the interview. We examined residential exposure to 29 agricultural use pesticides, known to cause DNA damage in vitro or are known endocrine disruptors. We employed a validated geographic information system-based system to generate exposure estimates for each participant. RESULTS: Our sample included 2067 cases and 1003 controls. In single pollutant models and within a 20-year exposure period, 10 out of 29 selected pesticides were associated with thyroid cancer, including several of the most applied pesticides in the United States such as paraquat dichloride [odds ratio (OR): 1.46 (95% CI: 1.23, 1.73)], glyphosate [OR: 1.33 (95% CI: 1.12, 1.58)], and oxyfluorfen [OR: 1.21 (95% CI: 1.02, 1.43)]. Risk of thyroid cancer increased proportionately to the total number of pesticides subjects were exposed to 20 years before diagnosis or interview. In all models, paraquat dichloride was associated with thyroid cancer. CONCLUSIONS: Our study provides first evidence in support of the hypothesis that residential pesticide exposure from agricultural applications is associated with an increased risk of thyroid cancer.

Three Patients with Lithium-Associated Hyperparathyroidism: Literature Review Regarding Medical and Surgical Management.

Lithium (Li) carbonate has been established as a mood stabilizer and an efficacious treatment for bipolar disorder since its discovery by Dr. John Cade in 1948. Li interacts significantly with organ systems and endocrine pathways. One of the most challenging side effects of Li to manage is its effect on the parathyroid glands. Dysregulation of parathyroid signaling due to Li results in hypercalcemia due to increased vitamin D3 generation, increased calcium absorption from the gut, and bone resorption, occasionally resulting in concomitant hypercalciuria. However, hypercalciuria is not a definitive feature for hyperparathyroidism, and normal calcium excretion might be seen in these patients. Hypercalcemia may also result from volume contraction and decreased renal clearance, which are commonly seen in these patients. Anatomically the parathyroid abnormalities can present as single or multiglandular disease. We report 3 cases where the patients developed multiple side effects of Li therapy as well as hypercalcemia due to hyperparathyroidism. The literature is reviewed with regard to medical and surgical management of Li-associated hyperparathyroidism in the context of these 3 presented cases.

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.

Adipocyte Browning and Higher Mitochondrial Function in Periadrenal But Not SC Fat in Pheochromocytoma.

CONTEXT: Patients with pheochromocytoma (pheo) show presence of multilocular adipocytes that express uncoupling protein 1 within periadrenal (pADR) and omental (OME) fat depots. It has been hypothesized that this is due to adrenergic stimulation by catecholamines produced by the pheo tumors. OBJECTIVE: To characterize the prevalence and respiratory activity of brown-like adipocytes within pADR, OME, and SC fat depots in human adult pheo patients. DESIGN: This was an observational cohort study. SETTING: The study took place in a university hospital. PATIENTS: We studied 46 patients who underwent surgery for benign adrenal tumors (21 pheos and 25 controls with adrenocortical adenomas). MAIN OUTCOME MEASURE: We characterized adipocyte browning in pADR, SC, and OME fat depots for histological and immunohistological features, mitochondrial respiration rate, and gene expression. We also determined circulating levels of catecholamines and other browning-related hormones. RESULTS: Eleven of 21 pheo pADR adipose samples, but only one of 25 pADR samples from control patients exhibited multilocular adipocytes. The pADR browning phenotype was associated with higher plasma catecholamines and raised uncoupling protein 1. Mitochondria from multilocular pADR fat of pheo patients exhibited increased rates of coupled and uncoupled respiration. Global gene expression analysis in pADR fat revealed enrichment in ß-oxidation genes in pheo patients with multilocular adipocytes. No SC or OME fat depots exhibited aspects of browning. CONCLUSION: Browning of the pADR depot occurred in half of pheo patients and was associated with increased catecholamines and mitochondrial activity. No browning was detected in other fat depots, suggesting that other factors are required to promote browning in these depots.

Increased rates of advanced thyroid cancer in California.

BACKGROUND: We have noted an unusually high rate of advanced thyroid cancers presenting from across California. We examined the rates of thyroid cancer presentation throughout California for potential geographic clustering. MATERIALS AND METHODS: A total of 26,983 patients with a new diagnosis of thyroid cancer (1999-2008) were abstracted from the California Cancer Registry and the Office of Statewide Health Planning and Development registry. Percentages of advanced thyroid cancer rates were calculated within each county (defined as those with distant metastatic stage; regional and/or distant metastatic stage [RM]) as well as those with well-differentiated thyroid cancer diagnosed before age 30. National averages were taken from Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: There was no obvious clustering of advanced cases within certain regions in California; however, on average, the entire state of California had significantly higher rates of distant metastatic thyroid cancer (6.73%) and RM (34.92%) than the national SEER averages (4%, 29%, respectively, P < 0.001). Of the 47 California counties, 20 had significantly higher percentages of distant metastatic thyroid cancer than the national SEER average (range, 6%-13% versus 4%, P < 0.05), and 20 had a higher percentage of RM than the national SEER average (range, 35%-48% versus 29%, P < 0.05). Two California counties had higher rates of young patients with well-differentiated thyroid cancer (range, 14.29%-17.9%) than the national SEER average (12%). CONCLUSIONS: California exhibits more advanced thyroid cancers than the national SEER population average. Further studies are warranted to better understand etiologies for these disparities, which may include environmental impacts and/or delays in diagnosis.

Medical Students' Perceptions of Surgeons: Implications for Teaching and Recruitment.

OBJECTIVE: The purpose of this study was to assess first-year medical students' implicit perceptions of surgeons, focusing on the roles of gender and demeanor (communal = supportive, associated with women; agentic = assertive, associated with men). DESIGN: Survey study. Each survey had 1 of 8 possible scenarios; all began with a short description of a surgeon who was described as accomplished and well trained, then varied by surgeon gender (male/female), surgeon demeanor (agentic/communal), and type of surgery (breast cancer/lung cancer). Using a 0 to 5 scale, respondents rated their perception of the surgeon through 5 questions. These 5 items were averaged to create a composite perception score scaled from 0 to 5. SETTING: Surveys were administered at the University of California, San Francisco, and the University of California, Los Angeles. PARTICIPANTS: We administered surveys to 333 first-year medical students who could read English and voluntarily agreed to participate. RESULTS: A total of 238 students responded (71.5%). They preferred the communal vs agentic surgeon (4.2 ± 0.7 vs 3.9 ± 0.7, p = 0.002) and male medical students perceived surgeons more favorably than female medical students did (4.2 ± 0.6 vs 4.0 ± 0.8, p = 0.036). The preference score did not differ according to surgeon gender (female 4.12 vs male 3.98, p = 0.087). There were no significant interactions between the factors of student gender, surgeon gender, or demeanor. Students who reported an interest in surgery as a career did not perceive surgeons more favorably than the students interested in other fields (4.3 ± 0.7 vs 4.0 ± 0.7 respectively, p = 0.066). CONCLUSIONS: Based on our findings, surgeon educators would likely find success in teaching and recruiting medical students by employing a communal demeanor in their interactions with all students, regardless of the students' gender or stated interest in surgery.

Dynamic Parathyroid Computed Tomography (4DCT) Facilitates Reoperative Parathyroidectomy and Enables Cure of Missed Hyperplasia.

BACKGROUND: Four-dimensional computed tomography (4DCT) is an emerging imaging modality in the evaluation of primary hyperparathyroidism (PHPT). We assessed the role of 4DCT in patients presenting for reoperative parathyroidectomy. METHODS: A prospective database of patients with persistent or recurrent PHPT undergoing reoperative parathyroidectomy during the years 2006-2014 was analyzed. Patients treated before versus after the advent of 4DCT were compared for operative eligibility, operative success, operative time, and concordance of imaging results with surgical findings. RESULTS: Ninety patients were included in the study (61 before 4DCT, 29 after 4DCT). The post-4DCT group had a higher rate of surgical concordance with imaging results (63 vs. 90 %, p < 0.01) and shorter operative time (114 vs. 76 min, p < 0.05). The operative success rate was not different (87 vs. 86 %). A similar pattern was observed in the subset of sestamibi-negative patients, with post-4DCT patients having a higher rate of surgical concordance (12 vs. 83 %, p < 0.0001) and shorter operative time (181 vs. 89 min, p < 0.05). Among patients ultimately found to have parathyroid hyperplasia, 4DCT correctly identified multiple enlarged glands in 80 % (4 of 5) and correctly lateralized one or more glands in 100 % (5 of 5) of cases, facilitating successful subtotal parathyroidectomy in the reoperative setting. CONCLUSIONS: 4DCT enables successful and efficient reoperative parathyroidectomy. These benefits extend to difficult cases, including sestamibi-negative patients and those with missed hyperplasia.

Reproductive outcomes and nononcologic complications after radioactive iodine ablation for well-differentiated thyroid cancer.

BACKGROUND: Radioactive iodine (RAI) ablation is frequently performed after initial surgery for well-differentiated thyroid cancer (WDTC). We examined the frequency and timing of childbirth as well as nononcologic complications after RAI ablation for WDTC on a population level. METHODS: A retrospective cohort study of 25,333 patients (18,850 women) with WDTC was performed using the California Cancer Registry and California Office of Statewide Health Planning and Development database, 1999-2008. The primary outcomes were birthrate and median time to first live birth among women of childbearing age. Secondary outcomes were nononcologic diagnoses occurring outside the acute setting (>30 days) after ablation. RESULTS: RAI ablation did not affect birthrate among women in the full dataset. However, in subgroup analyses, birthrate among women age 35-39 was significantly decreased in those who received RAI versus those who did not (11.5 versus 16.3 births per 1000 woman-years, p<0.001). Median time to first live birth after diagnosis of WDTC was prolonged among women who received RAI compared to those who did not (34.5 versus 26.1 months; p<0.0001). When 5-year age groups were examined individually, delay to first live birth was observed in women age 20-39 (p<0.05). This remained significant after adjustment for tumor characteristics, socioeconomic status, and marital status. The only nononcologic, nonreproductive adverse effect associated with RAI ablation was an increased rate of nasolacrimal stenosis (RR 3.44, p<0.0001). CONCLUSIONS: RAI ablation is associated with delayed childbearing in women across most of the reproductive lifespan, and with decreased birthrate in the late reproductive years. The underlying mechanism likely involves physician recommendation to delay pregnancy, as well as a potential impact of RAI on both reproductive choice and reproductive health. Further investigation is merited.

Trends in the frequency and quality of parathyroid surgery: analysis of 17,082 cases over 10 years.

OBJECTIVE: To examine trends in the frequency and quality of surgery for primary hyperparathyroidism (PHPT) in California during the period of 1999 to 2008. BACKGROUND: The quality of surgery for PHPT can be measured by the complication rate and the success rate of surgery. A fraction of patients with failed initial surgery undergo reoperation. METHODS: Data on patients undergoing parathyroidectomy (PTx) were obtained from the California Office of Statewide Health Planning and Development. Renal transplant recipients and dialysis patients were excluded. Hospitals were categorized by case volume: Very low: 1 to 4 operations annually; Low: 5 to 9; Medium, 10 to 19; High: 20 to 49; Very high: 50 or more. Complication rates and the percentage of cases requiring reoperation were analyzed. RESULTS: A total of 17,082 cases were studied. Annual case volume grew from 990 to 2746 (177% increase) over the study period, corresponding to a 147% increase in the per capita PTx rate. The proportion of cases performed by very high-volume hospitals increased from 6.4% to 20.5% (P < 0.001). The overall complication rate declined from 8.7% to 3.8% (P < 0.001). Complication rates were inversely related to hospital volume (very high volume, 3.9% vs very low volume, 5.2%, P < 0.05). Reoperation was performed in 363 patients (2.1%). The reoperation rate increased from 0.91% to 2.73% during the study period (P < 0.01). The reoperation rate was inversely and nonlinearly related to hospital volume, as described by the equation % reoperation = 100/(total hospital case volume). CONCLUSIONS: Surgery for PHPT has grown safer and more common over time. High-volume centers have lower rates of complication and reoperation.

Surgery is associated with improved survival for adrenocortical cancer, even in metastatic disease.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but lethal tumor. Predictors of survival include earlier stage at presentation and complete operative resection. We assessed effect of treatment and demographic variables on survival. METHODS: ACC cases were abstracted from the California Cancer Registry and Office of Statewide Health Planning and Development (1999-2008). Predictors included patient demographics, comorbidities, tumor size, stage, and treatment (none, surgery, chemotherapy and/or radiation [CRT], and surgery plus CRT). RESULTS: We studied 367 patients with median tumor size of 10 cm. At presentation, 37% had localized, 17% had regional, and 46% had metastatic disease. Median survival was 1.7 years (7.4 years local, 2.6 years regional, and 0.3 years metastatic, P < .0001). One-year and 5-year survival was: 92%/62% (local); 73%/39% (regional); and 24%/7% (metastatic). Increased age (hazard ratio [HR] 1.16) and Cushing's syndrome (HR 1.66) worsened survival (P < .05). Low socioeconomic status worsened survival in local and regional disease (P < .05). In multivariable regression, both surgery (regional HR 0.13; metastatic HR 0.52) and surgery plus CRT (regional HR 0.15; metastatic HR 0.31) improved survival compared with no treatment (P < .02). CONCLUSION: In ACC, surgery is associated with improved survival, even in metastatic disease. Surgery should be considered for select patients as part of multimodality treatment.

Utility of serum thyroglobulin measurements after prophylactic thyroidectomy in patients with hereditary medullary thyroid cancer.

INTRODUCTION: Prophylactic thyroidectomy can be curative for patients with hereditary medullary thyroid cancer (MTC) caused by RET proto-oncogene mutations. Calcitonin is a sensitive tumor marker used to follow patients. We suggest that thyroglobulin (Tg) levels should also be monitored postoperatively in these patients. METHODS: We reviewed patients with RET mutations who underwent prophylactic thyroidectomy between 1981 and 2011 at an academic endocrine surgery center. Patients were excluded if they had no postoperative Tg levels recorded. RESULTS: Of the 22 patients who underwent prophylactic thyroidectomy, 14 were included in the final analysis. The average age at thyroidectomy was 9.8 years (range, 4-29). Tg levels were detectable 1.5 months to 31 years postoperatively in 11 patients (79%), all of whom were <15 years old at thyroidectomy. Median thyroid-stimulating hormone (TSH) was 2.5 mIU/L and 13.4 mIU/L in patients with undetectable and detectable Tg, respectively. Of those with detectable Tg, 5 had cervical ultrasonographic examination: Two showed no residual tissue in the thyroid bed, and 3 showed remnant thyroid tissue. CONCLUSION: Tg levels can identify patients with remnant thyroid tissue after prophylactic thyroidectomy. Ultrasonography can determine whether thyroid tissue remains posterolaterally that is at risk of MTC recurrence. Maintaining normal TSH may prevent growth of remaining thyroid follicular cells.

Risk-based ultrasound screening for thyroid cancer in obese patients is cost-effective.

BACKGROUND: A higher body mass index (BMI) is associated with more advanced stages of thyroid cancer. Screening obese patients for thyroid cancer has been proposed but has yet to be examined for cost-effectiveness. The objective of this study was to assess the cost-effectiveness of ultrasound (US) screening of obese patients for thyroid cancer. METHODS: A decision-tree model compared cost savings for the following: (i) base case scenario of an obese patient with thyroid nodule found by palpation, (ii) universal US screening of all obese patients, and (iii) risk-based US screening in obese patients. Risk-based screening consisted of patients who had at least one of four major identified risk factors for thyroid cancer (family history of thyroid cancer, radiation exposure, Hashimoto's thyroiditis, and/or elevated thyrotropin). Patients with nodules underwent established treatment and management guidelines. The model accounted for recurrence, complications, and long-term treatment/follow-up for five years. Outcome probabilities were identified from a literature review. Costs were estimated using a third-party payer perspective. Sensitivity analyses were performed to examine the impact of risk factor prevalence and US cost on the model. RESULTS: The resulted costs per patient were $210.73 in the base case scenario, $434.10 in the universal US screening arm, and $166.72 in the risk-based screening arm. Risk-based screening remained cost-effective until more than 14% of obese patients had risk factors and with a wide variation of US costs ($0-$1113). CONCLUSION: Risk-based US screening in selected obese patients with risk factors for thyroid cancer is cost-effective. Recommendations for screening this subgroup will result in cost savings and a likely decreased morbidity and mortality in this subpopulation with more aggressive disease.

Thyroglobulin antibody levels do not predict disease status in papillary thyroid cancer.

BACKGROUND: Thyroglobulin antibodies (TgAb) are present in approximately 20% of patients with papillary thyroid cancer (PTC) and invalidate the serum thyroglobulin (Tg) level as a tumour marker. We examined whether trends in the TgAb level could serve as a surrogate marker of disease status in the surveillance of patients with PTC. METHODS: All patients found to have a least one positive postoperative TgAb level (determined by the Beckman-Coulter Access Assay) after undergoing initial surgery for PTC from 2000 to 2010 at a single institution were included. Log-log transformation and linear regression were applied to longitudinal TgAb levels, yielding patient-specific regression coefficients that categorized as follows: highly negative, moderately negative and positive/no trend. The recurrence rate in each category was then assessed. RESULTS: Ninety-three of 967 patients with PTC were included. Recurrent disease was detected in 19 patients (20%) after a mean follow-up time of 51 months. Regression coefficients in the highly negative and moderately negative groups were not different, and hence these groups were pooled. The proportion of recurrent cases in the negative trend group was similar to that in the positive/no trend group (19.7% vs 21.9%, NS). The mean regression coefficients were similar for recurrent and nonrecurrent cases within both the negative trend group (-0.89 vs -0.80, NS) and the positive/no trend group (0.08 vs 0.33, NS). CONCLUSION: Trends in the TgAb level do not predict disease status in PTC in our experience. In the context of most commercially available TgAb assays, surveillance of TgAb-positive patients will hinge on high-quality imaging until a valid alternative serum marker to Tg is identified.

Racial and socioeconomic disparities in presentation and outcomes of well-differentiated thyroid cancer.

CONTEXT: Racial/ethnic minorities suffer disproportionate morbidity and mortality from chronic diseases. OBJECTIVE: Our objective was to assess racial and socioeconomic status (SES) disparities in well-differentiated thyroid cancer (WDTC) patients. DESIGN AND PARTICIPANTS: We conducted a retrospective cohort study on 25 945 patients with WDTC (1999-2008) from the California Cancer Registry (57% white, 4% black, 24% Hispanic, and 15% Asian-Pacific Islander [API]). MAIN OUTCOMES: We evaluated effect of race and SES variables on stage of cancer presentation and overall/disease-specific survival. RESULTS: Significant differences in stage of presentation between all racial groups were found (P<.001), with minority groups presenting with a higher percentage of metastatic disease as compared with white patients (black, odds ratio [OR]=1.36 with confidence interval [CI] 1.01-1.84; Hispanic, OR=1.89 [CI, 1.62-2.21], API, OR=1.82 [CI, 1.54-2.15]). Hispanic (OR=1.59, [CI, 1.48-1.72]) and API (OR=1.32 [1.22-1.44]) patients also presented with higher odds of regional disease. Patients with the lowest SES presented with metastatic disease more often than those with the highest SES (OR=1.45 [CI, 1.16-1.82]). Those that were poor/uninsured and/or with Medicaid insurance had higher odds of presenting with metastatic disease as compared with those with private insurance (OR=2.41, [CI, 2.10-2.77]). Unadjusted overall survival rates were higher among API and Hispanic patients and lower among black patients (P<.001 vs white patients). Adjusted overall survival also showed a survival disadvantage for black patients (hazard ratio=1.4, [CI, 1.10-1.73]) and survival advantage for API patients (hazard ratio=0.83, [CI, 0.71-0.97]). In disease-specific survival analyses, when only those patients with metastatic disease were analyzed separately, black patients again had the lowest survival rates, and Hispanic/API patients had the highest survival rates (P<.04). CONCLUSION: Black patients and those with low SES have worse outcomes for thyroid cancer. API and Hispanic patients may have a protective effect on survival despite presenting with more advanced disease.

Effect of reoperation on outcomes in papillary thyroid cancer.

BACKGROUND: The influence of lymph node recurrences of papillary thyroid carcinoma (PTC) on overall prognosis is uncertain. We performed a population-based, longitudinal analysis to evaluate the impact of reoperation on mortality. METHODS: Patients who underwent initial operation for PTC >1 cm were abstracted from the California Cancer Registry database (1999-2008). Reoperation was defined as any lymph node dissection after total or near-total thyroidectomy. RESULTS: Of the 11,986 patients included in the study, 222 (1.9%) underwent one or more reoperations. The median time to reoperation was 8.7 months, with 58.6% and 83.8% of reoperations being performed within 1 and 2 years of initial thyroidectomy, respectively. The mortality rate from PTC was 2.3% (271 patients). After we adjusted for age, sex, tumor size, stage, and radioactive iodine treatment, we found that reoperation was associated with an increased risk of all-cause mortality in patients ≥45 years of age (hazard ratio [HR] 1.51, P < .05). Reoperation was associated with an increased risk of disease-specific mortality in both patients <45 (HR 6.22, P < .01) and ≥45 (HR 2.49, P < .001). CONCLUSION: Reoperation is independently associated with mortality in PTC. Most reoperations are performed soon after initial thyroidectomy and likely reflect persistent rather than recurrent disease.

Three-phase parathyroid 4-dimensional computed tomography initial experience: inexperienced readers have high accuracy and high interobserver agreement.

OBJECTIVE: Multiphase multidetector contrast-enhanced parathyroid CT (4-dimensional computed tomography [4D-CT]) is an emerging tool for evaluating patients with primary hyperparathyroidism. Our goal was to describe the initial performance of 2 inexperienced readers in interpretation of 4D-CT. METHODS: Twenty-three subjects who received 4D-CT and successful surgical exploration were studied (14 initial and 9 repeat explorations; 15 single-gland disease and 8 multigland disease) A staff neuroradiologist prospectively interpreted all studies, and a neuroradiology fellow retrospectively interpreted all studies; their results were compared with the surgical findings for each side of the neck separately. RESULTS: The prospective readings were 78% accurate overall, 97% accurate in the subset of single-gland disease cases, and 89% accurate in re-exploration cases. There was 91% concordance in interpretation between observers, with κ of 0.83. CONCLUSIONS: Initial results after implementation of 4D-CT show high accuracy of interpretation for inexperienced observers, comparable to published data, and high interobserver agreement.

Incidence and prevalence of primary hyperparathyroidism in a racially mixed population.

CONTEXT: The epidemiology of primary hyperparathyroidism (PHPT) has generally been studied in Caucasian populations. OBJECTIVE: The aim was to examine the incidence and prevalence of PHPT within a racially mixed population. DESIGN: A descriptive epidemiologic study was performed. PATIENTS/SETTING: The study population included 3.5 million enrollees within Kaiser Permanente Southern California. METHODS: All patients with at least one elevated serum calcium level (>10.5 mg/dL, 2.6 mmol/L) between 1995 and 2010 were included. Cases of PHPT were identified by electronic query of laboratory values using biochemical criteria, after exclusion of secondary or renal and tertiary hyperparathyroidism cases. The incidence and prevalence rates of PHPT were calculated according to sex, race, age group by decade, and year. RESULTS: Initial case finding identified 15,234 patients with chronic hypercalcemia, 13,327 (87%) of which had PHPT as defined by elevated or inappropriately normal parathyroid hormone levels. The incidence of PHPT fluctuated from 34 to 120 per 100,000 person-years (mean 66) among women, and from 13 to 36 (mean 25) among men. With advancing age, incidence increased and sex differences became pronounced (incidence 12-24 per 100,000 for both sexes younger than 50 y; 80 and 36 per 100,000 for women and men aged 50-59 y, respectively; and 196 and 95 for women and men aged 70-79 y, respectively). The incidence of PHPT was highest among blacks (92 women; 46 men, P < .0001), followed by whites (81 women; 29 men), with rates for Asians (52 women, 28 men), Hispanics (49 women, 17 men), and other races (25 women, 6 men) being lower than that for whites (P < .0001). The prevalence of PHPT tripled during the study period, increasing from 76 to 233 per 100,000 women and from 30 to 85 per 100 000 men. Racial differences in prevalence mirrored those found in incidence. CONCLUSIONS: PHPT is the predominant cause of hypercalcemia and is increasingly prevalent. Substantial differences are found in the incidence and prevalence of PHPT between races.

Risk of advanced papillary thyroid cancer in obese patients.

OBJECTIVE To determine whether increasing body mass index (BMI) is associated with more aggressive disease and adverse surgical outcomes in patients with papillary thyroid cancer (PTC). DESIGN Retrospective review of a prospective database. SETTING Single academic tertiary care center. PATIENTS A total of 443 patients older than 18 years who underwent total thyroidectomy for PTC from January 1, 2004, through March 31, 2011, were included in the analysis. Patients were organized into 4 BMI (calculated as weight in kilograms divided by height in meters squared) groups: normal (18.5-24.9), overweight (25-29.9), obese (30-39.9), and morbidly obese (≥40). MAIN OUTCOME MEASURES Disease stage at presentation, histologic subtype, duration of anesthetic induction and extubation, duration of surgery, surgical complications, length of hospital stay, and American Society of Anesthesiologists (ASA) class. RESULTS Ages ranged from 18 to 89 years. Greater BMI was associated with more advanced disease stage at presentation (P < .001) and more aggressive PTC histopathologic subtype (P = .03). Morbidly obese patients presented more frequently with stage III or IV disease (odds ratio, 3.67; P < .001). Greater BMI was also associated with longer duration of anesthetic induction (P < .001), increased length of stay (P < .001), and higher ASA class (P < .001). Duration of surgery was not associated with BMI. There was a trend toward larger tumors with increasing BMI (P = .06). Obese BMI was associated with more preoperative vocal cord paralysis due to local invasion (odds ratio, 9.21; P = .001). CONCLUSIONS Obese patients present with more advanced stage and more aggressive forms of PTC. This finding suggests that obese patients should be screened for thyroid cancer.