Failure of radioactive iodine in the treatment of hyperthyroidism.

BACKGROUND: Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. METHODS: We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis. RESULTS: Of the 325 patients analyzed, 74 patients (22.8 %) failed initial RAI treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses <12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (hazard ratio [HR] 1.13; 95 % confidence interval [CI] 1.02-1.26; p = 0.02) and methimazole treatment (HR 2.55; 95 % CI 1.22-5.33; p = 0.01) were associated with failure. CONCLUSIONS: Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.

Minimal benefit to subsequent intraoperative parathyroid hormone testing after all four glands have been identified.

BACKGROUND: Modern tools, such as intraoperative parathyroid hormone (IoPTH) assay, reduce operative time and extent of parathyroidectomy. However, the utility of a subsequent final set of IoPTH after all four glands are visualized remains questionable. This study was designed to determine the added value of IoPTH assay following parathyroidectomy with four-gland visualization in patients with primary hyperparathyroidism (PHPT). METHODS: A retrospective review of patients who underwent parathyroidectomy for PHPT between July 2001 and February 2012 by two experienced endocrine surgeons was performed. Included were patients with operative reports indicating that all four parathyroid glands were identified. Following four-gland visualization a subsequent final set of IoPTH was measured to confirm cure. Cure was defined as at least 50 % fall by 5, 10, or 15 min postexcision compared with preincision levels. RESULTS: Of 1,838 patients that underwent parathyroidectomy, four glands were visualized in 238 cases (13 %). Of those patients meeting inclusion criteria with four glands visualized, the final set of IoPTH fell to cure criteria in 235 patients (98 %). An inadequate drop was documented in three (2 %) patients all of which were found to have multigland disease. Only in one patient (0.4 %) was a fifth parathyroid gland identified and resected. In all three cases, the subsequent final IoPTH did not affect the ultimate outcome or cure rate. CONCLUSIONS: When experienced surgeons visualize all four parathyroid glands, drawing a subsequent final set of IoPTH rarely changes the operative course and therefore serves a limited role.

Multigland disease and slower decline in intraoperative PTH characterize mild primary hyperparathyroidism.

BACKGROUND: Many patients with primary hyperparathyroidism (PHPT) present with less severe biochemical parameters. The purpose of this study was to compare the presentation, operative findings, and outcomes of these patients with "mild" PHPT to patients with "overt" disease. METHODS: A retrospective review of a prospectively collected parathyroid database was performed to identify cases of PHPT undergoing an initial neck operation. Patients were classified as mild when either the preoperative calcium or PTH was within the normal limits. Comparisons were made with the Student's t test, Chi-squared test, or Wilcoxon rank-sum test where appropriate. Kaplan-Meier estimates were plotted for disease-free survival and compared by the log-rank test. RESULTS: Of the 1,429 patients who met inclusion criteria, 1,049 were classified as overt and 388 (27.1 %) were mild. Within the mild group, 122 (31.4 %) presented with normocalcemic PHPT and 266 (68.6 %) had a normal PTH. The two groups had similar demographics and renal function. Interestingly, the mild group had more than double the rate of kidney stones (3.1 vs. 1.3 %, p = 0.02). The mild group was less likely to localize on sestamibi scan (62.4 vs. 78.7 %, p < 0.01). Intraoperatively, more mild patients exhibited multigland disease (34.3 vs. 14.1 %, p < 0.01). When examining intraoperative PTH (IoPTH) kinetics where single adenomas were excised, the IoPTH fell at a rate of 6.9 pg/min in mild patients compared with 11.5 pg/min in the overt group (p < 0.01). Accordingly, 62.2 % of patients in the overt group and 53.3 % in the mild group were cured at 5 min postexcision (p < 0.01). There was no difference in the rates of persistence or recurrence between the groups, and disease-free survival estimates were identical (p = 0.27). CONCLUSIONS: Patients with mild PHPT were more likely to have multigland disease and a slower decline in IoPTH, but these patients can be successfully treated with surgery.

Significance of rebounding parathyroid hormone levels during parathyroidectomy.

BACKGROUND: Using minimally invasive parathyroidectomy (MIP), most surgeons require a 50% decline in intraoperative parathyroid hormone (IoPTH) to determine cure, but the significance of IoPTH kinetics occurring after this drop remains unknown. The aim of this study was to determine the impact of IoPTH levels that first meet criteria for cure, but then increase again, or rebound, between 10 and 15 min postexcision. METHODS: We conducted a retrospective review of patients undergoing initial parathyroidectomy for primary hyperparathyroidism at our institution from 2001 to 2011. Rebound IoPTH was defined as an increase in parathyroid hormone ≥5 pg/mL after achieving the 50% drop required for cure. Comparisons were evaluated with the Student t-test, chi-square test, or Fisher exact test where appropriate. RESULTS: Of the 1386 patients who met selection criteria, 86 (6.2%) patients exhibited rebound IoPTH. The mean magnitude of rebound was 13.8 ± 3.6 pg/mL. Compared with those not displaying rebound, more patients with rebound IoPTH were treated with open parathyroidectomy rather than MIP (10.8% versus 4.5%, P < 0.01). The recurrence rate among those with rebound IoPTH was more than double that of the patients without rebound IoPTH (5.8% versus 2.2%, P = 0.03). Magnitude of rebound, however, did not correlate with recurrence. The rate of persistent disease was not different between those with and without rebound IoPTH. Rebound was a much better indicator of recurrence than patients whose final IoPTH levels were not within the normal range. CONCLUSIONS: Rebound IoPTH is more common in patients who develop recurrent hyperparathyroidism. Therefore, surgeons should closely monitor patients with rebound IoPTH for disease recurrence.

Remnant uptake as a postoperative oncologic quality indicator.

BACKGROUND: The purpose of this study was to examine the utility of remnant uptake on postoperative radioiodine scans as an oncologic indicator after thyroidectomy for differentiated thyroid cancer (DTC). METHODS: We conducted a retrospective review of patients undergoing total thyroidectomy for DTC and subsequent radioactive iodine (RAI) treatment. Of the eight surgeons included, three were considered high volume, performing at least 20 thyroidectomies per year. Patients with distant metastases at diagnosis or poorly differentiated variants were excluded. To control for the effect of varying RAI doses, the remnant uptake was analyzed as a ratio of the percentage uptake to the dose received (uptake to dose ratio [UDR]). Multivariate logistic regression was used to determine the influence of UDR on recurrence. RESULTS: Of the 223 patients who met inclusion criteria, 21 patients (9.42%) experienced a recurrence. Those with a recurrence had a 10-fold higher UDR compared with those who did not (0.030 vs. 0.003, p=0.001). Similarly, patients with increasing postoperative thyroglobulin measurements (0.339 vs. 0.003, p<0.001) also had significantly greater UDRs compared with those with stable thyroglobulin. The UDRs of high-volume surgeons were significantly smaller than low-volume surgeons (0.003 vs. 0.025, p=0.002). When combined with other known predictors for recurrence, UDR (OR 3.71 [95%CI 1.05-13.10], p=0.041) was significantly associated with recurrence. High-volume surgeons maintained a low level of permanent complications across all UDRs, whereas low-volume surgeons had greater permanent complications associated with higher uptake. CONCLUSIONS: Remnant uptake is a useful postoperative oncologic quality indicator that can predict a patient's risk of disease recurrence and indicate the completeness of resection.

Using body mass index to predict optimal thyroid dosing after thyroidectomy.

BACKGROUND: Current postoperative thyroid replacement dosing is weight based, with adjustments made after thyroid-stimulating hormone values. This method can lead to considerable delays in achieving euthyroidism and often fails to accurately dose over- and underweight patients. Our aim was to develop an accurate dosing method that uses patient body mass index (BMI) data. STUDY DESIGN: A retrospective review of a prospectively collected thyroid database was performed. We selected adult patients undergoing thyroidectomy, with benign pathology, who achieved euthyroidism on thyroid hormone supplementation. Body mass index and euthyroid dose were plotted and regression was used to fit curves to the data. Statistical analysis was performed using STATA 10.1 software (Stata Corp). RESULTS: One hundred twenty-two patients met inclusion criteria. At initial follow-up, only 39 patients were euthyroid (32%). Fifty-three percent of patients with BMI >30 kg/m(2) were overdosed, and 46% of patients with BMI <25 kg/m(2) were underdosed. The line of best fit demonstrated an overall quadratic relationship between BMI and euthyroid dose. A linear relationship best described the data up to a BMI of 50. Beyond that, the line approached 1.1 µg/kg. A regression equation was derived for calculating initial levothyroxine dose (µg/kg/d = -0.018 × BMI + 2.13 [F statistic = 52.7, root mean square error of 0.24]). CONCLUSIONS: The current standard of weight-based thyroid replacement fails to appropriately dose underweight and overweight patients. Body mass index can be used to more accurately dose thyroid hormone using a simple formula.