Long-term effects of primary hyperparathyroidism and parathyroidectomy on kidney function.

IMPORTANCE: Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT). OBJECTIVE: To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes. DESIGN: Matched control study. SETTING: A vertically integrated health care system serving 4.6 million patients in Southern California. PARTICIPANTS: 6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016. EXPOSURES: Biochemically confirmed PHPT with varying serum calcium levels. MAIN OUTCOMES: Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74 mmol/L (10.5-11 mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively. RESULTS: Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (−1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (−1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of −1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (−1.5 mL/min/1.73 m2/year, P < .001) and >2.99 mmol/L (−2.1 mL/min/1.73 m2/year, P < .001), comprising 9% and 7% of cases, respectively. In the propensity score­matched population, patients with serum calcium >2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (−2.0 [95% CI: −2.6 to −1.5] to −0.9 [95% CI: −1.5 to 0.4] mL/min/1.73 m2/year). CONCLUSIONS AND RELEVANCE: Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87 mmol/L (11.5 mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87 mmol/L.

Iodine Nutrition in Weaning Infants in the United States.

BACKGROUND: As iodine is a requisite micronutrient for infant brain development, infants are at risk for iodine deficiency during the weaning period when their diet transitions from milk (breast-milk, infant formula, or follow-on formula) to solid food. Dietary iodine intake during this weaning period is likely minimal, as the iodine content of commercial baby food is not regulated, and the addition of salt to baby food is not recommended. This study reports the current status of iodine nutrition among weaning infants in the United States. METHODS: Subjects (n = 60; 50% Caucasian, 30% black) were infants <12 months of age who were fed any combination of formula and/or baby food. Samples of all formula and food consumed in the previous 24 hours and a spot urine sample from each infant were obtained for the measurement of iodine. The estimated quantities of ingested formula and baby food were summed from a food diary recorded by the infants' parents. RESULTS: The mean age of the infants was 6.3 ± 3.5 months. The median urinary iodine concentration (UIC) was 117 µg/L (range 26.9-1302.8 µg/L). Estimated daily iodine intake obtained from the measured iodine content in infant formula/foods was 89 µg (range 0-288 µg). There was a positive correlation between the infants' UIC and the iodine content in the consumed foods (r = 0.4, p < 0.001). CONCLUSIONS: Although the median UIC of infants fed a combination of infant formula and baby food would meet the criteria for iodine sufficiency in a larger sample, those consuming the lowest quartile of iodine-containing nutritional sources had a median UIC <100 µg/L.

Skeletal effects of failed parathyroidectomy.

BACKGROUND: Parathyroidectomy improves bone mineral density and decreases risk for fracture in patients with primary hyperparathyroidism. The aim of this study was to determine skeletal consequences of failed parathyroidectomy. METHODS: A retrospective, cohort study of patients with biochemically confirmed primary hyperparathyroidism within a vertically integrated health system was performed (1995-2014). Failed parathyroidectomy was defined by hypercalcemia within 6 months of initial parathyroidectomy. Time-varying Cox regression was used to estimate the risk for any fracture and hip fracture in 3 comparison groups: observation, successful parathyroidectomy, and failed parathyroidectomy. Bone mineral density changes also were compared. RESULTS: The cohort included 7,169 patients, of whom 5,802 (81%) were observed, 1,228 underwent successful parathyroidectomy (17%), and 137 underwent failed parathyroidectomy (2%). The adjusted risk for any fracture (hazard ratio, 1.28; 95% confidence interval, 0.85-1.92) and hip fracture (hazard ratio, 1.63; 95% CI, 0.77-3.45) associated with failed parathyroidectomy was similar to that associated with observation. Successful parathyroidectomy was associated with a decrease in any fracture (hazard ratio, 0.68; 95% confidence interval, 0.57-0.82) and hip fracture (hazard ratio, 0.43; 95% confidence interval, 0.27-0.68) compared with observation. Bone mineral density changes in the failed parathyroidectomy group paralleled those associated with observation. CONCLUSION: Failed parathyroidectomy is associated with a high risk for fracture similar to that seen with observation.

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.

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.

Population-level predictors of persistent hyperparathyroidism.

BACKGROUND: Systematic study of outcomes of initial surgery for primary hyperparathyroidism (PHPT) has been limited by selection and self-reporting biases. To avoid these biases, we evaluated parathyroidectomy (PTx) outcomes within an integrated health care system encompassing 3.25 million enrollees. METHODS: All patients undergoing PTx for PHPT from 1995 to 2010 were studied. Persistent and recurrent disease were defined by a serum calcium level >10.5 mg/dL before or after 6 months postoperatively, respectively. The effect of demographic, clinical, and hospital volume-related variables was assessed by the use of multivariate logistic regression. RESULTS: A total of 1,190 initial operations for PHPT were performed at 14 hospitals. Follow-up calcium levels were available in 97% of subjects. The overall success rate was 92%, and 5% of patients developed recurrent disease. Age ≥ 70 years was predictive of persistent disease (odds ratio 1.80, P < .05). High-volume hospital (>100 cases) predicted against persistent disease (odds ratio 0.42, P < .05) and carried 96% success rate. Negative or equivocal sestamibi scan was associated with a lower success rate (success rate 89% vs 95% for positive scan, P < .05). Reoperation was performed in 12% of patients with persistent or recurrent PHPT. CONCLUSION: The success rate of PTx is influenced by patient age, hospital volume, and sestamibi scan result. Surgical outcomes may be optimized by designating high-volume centers in the community setting.

Underutilization of parathyroidectomy in elderly patients with primary hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) disproportionately affects older patients, who may face higher thresholds for surgical intervention compared to young patients. OBJECTIVE: The aim was to examine for differences in the utilization of parathyroidectomy attributable to age. DESIGN: We conducted a retrospective cohort study. PARTICIPANTS: Patients with biochemically diagnosed PHPT during the years 1995-2008 were identified within an integrated health care delivery system in Southern California encompassing approximately 3 million individuals. MAIN OUTCOME MEASURES: The outcome measures were parathyroidectomy (PTx) and time interval to surgery. RESULTS: We found 3388 patients with PHPT, 964 (28%) of whom underwent PTx. Patients aged 60+ yr comprised 60% of the study cohort. The likelihood of PTx decreased linearly among patients aged 60+ when compared to patients aged 50-59, an effect that persisted in multivariate analysis: odds ratio 0.68 for ages 60-69 (P < 0.05); 0.41 for ages 70-79 (P < 0.0001), and 0.11 for age 80+ (P < 0.0001). The PTx rate for patients aged 70+ was 14%. Among patients meeting 2002 consensus criteria for surgical treatment, 45% of those aged 60-69 and 24% of those aged 70+ underwent PTx. A Cox proportional hazards model showed that patients aged 60+ experienced significantly longer delays from diagnosis to surgery compared to young patients (P < 0.0001). CONCLUSIONS: PHPT is undertreated in the elderly. We observed a progressive age-related decline in PTx rate that renders patients aged 70+ unlikely to have definitive treatment, irrespective of comorbidity and eligibility for surgery.