Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism is Associated with Improved Bone Mineral Density Regardless of Postoperative Parathyroid Hormone Levels.

BACKGROUND: Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. METHODS: Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. RESULTS: Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p = 0.014), more bilateral cervical explorations (22% vs. 13%, p = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p = 0.002) and TH (1.64%, p = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. - 0.83%, p = 0.017). There was no difference in improvement at the LS or FN (p = NS). CONCLUSION: Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.

A Multidisciplinary Head-to-Head Comparison of American College of Radiology Thyroid Imaging and Reporting Data System and American Thyroid Association Ultrasound Risk Stratification Systems.

BACKGROUND: Ultrasound plays a critical role in evaluating thyroid nodules. We compared the performance of the two most popular ultrasound malignancy risk stratification systems, the 2015 American Thyroid Association (ATA) guidelines and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS). MATERIALS AND METHODS: We retrospectively identified 250 thyroid nodules that were surgically removed from 137 patients. Their ultrasound images were independently rated using both ATA and ACR TI-RADS by six raters with expertise in ultrasound interpretation. For each system, we generated a receiver operating characteristic curve and calculated the area under the curve (AUC). RESULTS: Sixty-five (26%) nodules were malignant. There was "fair agreement" among raters for both ATA and ACR TI-RADS. Our observed malignancy risks for ATA and ACR TI-RADS categories were similar to expected risk thresholds with a few notable exceptions including the intermediate ATA risk category and the three highest risk categories for ACR TI-RADS. Biopsy of 226 of the 250 nodules would be indicated by ATA guidelines based on nodule size and mean ATA rating. One hundred forty-six nodules would be biopsied based on ACR TI-RADS. The sensitivity, specificity, and negative and positive predictive values were 92%, 10%, 79%, and 27%, respectively, for ATA and 74%, 47%, 84%, and 33%, respectively, for ACR TI-RADS. The AUC for ATA was 0.734 and for ACR TI-RADS was 0.718. CONCLUSION: Although both systems demonstrated good diagnostic performance, ATA guidelines resulted in a greater number of thyroid biopsies and exhibited more consistent malignancy risk prediction for higher risk categories. IMPLICATIONS FOR PRACTICE: With the rising incidence of thyroid nodules, the need for accurate detection of malignancy is important to avoid the overtreatment of benign nodules. Ultrasonography is one of the key tools for the evaluation of thyroid nodules, although the use of many different ultrasound risk stratification systems is a hindrance to clinical collaboration in everyday practice and the comparison of data in research. The first step toward the development of a universal thyroid nodule ultrasound malignancy risk stratification system is to better understand the strengths and weaknesses of the current systems in use.

Beyond the three P's: adrenal involvement in MEN1.

Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.

Advances in Endocrine Surgery.

Recent changes in the landscape of endocrine surgery include a shift from total thyroidectomy for almost all patients with papillary thyroid cancer to the incorporation of thyroid lobectomy for well-selected patients with low-risk disease; minimally invasive parathyroidectomy with, and potentially without, intraoperative parathyroid hormone monitoring for patients with well-localized primary hyperparathyroidism; improvement in the management of parathyroid cancer with the incorporation of immune checkpoint blockade and/or targeted therapies; and the incorporation of minimally invasive techniques in the management of patients with benign tumors and selected secondary malignancies of the adrenal gland.

Pheochromocytoma recurrence in hereditary disease: does a cortical-sparing technique increase recurrence rate?

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy is an appealing approach for patients with hereditary pheochromocytoma and lends well to cortex preservation. We sought to examine pheochromocytoma recurrence in patients with hereditary pheochromocytoma in the era of posterior retroperitoneoscopic adrenalectomy and evaluate the predictors of recurrence. METHODS: Patients with hereditary pheochromocytoma who underwent adrenalectomy for pheochromocytoma between 1995 and 2020 with biochemical cure and follow-up >1 year were identified. Recurrence was defined as plasma metanephrines above the upper limit of normal with radiographic evidence of disease in the ipsilateral adrenal bed. RESULTS: Seventy-eight hereditary pheochromocytoma patients (median age = 32.4 years; 60.3% women) underwent 114 adrenalectomies for pheochromocytoma. Of these patients, 40 had multiple endocrine neoplasia type 2A (51.3%), 10 had multiple endocrine neoplasia type B (12.8%), 17 had von Hippel-Lindau disease (21.8%), and 11 had neurofibromatosis type 1 (14.1%). Thirty-eight adrenalectomies (33.3%) were performed before the introduction of posterior retroperitoneoscopic adrenalectomy and 76 (66.7%) after. Cortical-sparing technique was performed in 62 (54.4%) adrenalectomies, with no difference in its use before and after posterior retroperitoneoscopic adrenalectomy introduction (P > .05). During a median follow-up of 80.7 months (interquartile range 43.4-151.2), 12 ipsilateral recurrences (10.5%) were identified. There was no difference in recurrence before and after the introduction of posterior retroperitoneoscopic adrenalectomy or by surgical technique or approach of the entire cohort (P > .05). Recurrence was more common in those with RET M918T mutation (23.5% vs 8.2%; P = .05). Patients with RET M918T mutations had a shorter recurrence-free survival (P = .013). On multivariate analysis, only RET M918T mutation was independently associated with an increased recurrence risk (hazard ratio = 4.30; 95% confidence interval, 1.26-14.66; P = .019). CONCLUSION: The introduction of posterior retroperitoneoscopic adrenalectomy did not influence the recurrence rate after adrenalectomy for hereditary pheochromocytoma patients. Patients with a RET M918T germline mutation are at increased risk for pheochromocytoma recurrence and may benefit from initial total adrenalectomy.

Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia.

CONTEXT: Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. OBJECTIVE AND DESIGN: Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD). PARTICIPANTS AND SETTING: Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018. METHODS AND OUTCOMES: Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression. RESULTS: A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates. CONCLUSIONS: In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.

A stepwise analysis of the diagnostic algorithm for the prediction of malignancy in thyroid nodules.

BACKGROUND: The evaluation of the malignancy risk of thyroid nodules involves clinical factors, sonographic characteristics, cytopathology, and molecular profiling. Altogether, this algorithm can be costly and time consuming. We evaluated the stepwise contribution of each diagnostic step toward an accurate prediction of malignancy. METHODS: A retrospective study of dominant nodules of 137 patients who underwent surgical excision was performed. A baseline logistic regression model for predicting malignancy was regressed on clinical factors. In a stepwise fashion, the 2015 American Thyroid Association ultrasound risk stratification, Bethesda classification of fine-needle aspiration biopsies, and molecular profiling were added to the baseline model and the significance of each step analyzed using likelihood ratio test. Receiver operating characteristic curves were calculated for each model. RESULTS: The addition of American Thyroid Association risk stratification and Bethesda classification to preceding models were statistically significant (P < .001). The addition of molecular profiling (as a strategy independent of a particular test) was not significant (P = .812). The areas under the curve of the baseline model and models sequentially including American Thyroid Association stratification, cytopathology, and molecular profiling were 0.76, 0.85, 0.91, and 0.91, respectively. CONCLUSION: Clinical factors, sonographic characteristics, and cytopathology are sufficiently accurate in predicting malignancy risk of most thyroid nodules.

Cross-Sectional Investigation of Acute Changes in Ultrasonographic Markers for Biceps and Supraspinatus Tendon Degeneration After Repeated Wheelchair Transfers in People With Spinal Cord Injury.

OBJECTIVE: The objectives of this work were to investigate how wheelchair transfers influence acute changes in ultrasound markers for biceps and supraspinatus tendon degeneration and to determine how such changes correlate with transfer technique and demographic characteristics. DESIGN: Participants underwent quantitative ultrasound examinations for markers of biceps and supraspinatus tendon degeneration (tendon width, echogenicity, variance, and contrast) before and after a stressful repeated-transfers protocol. The Transfer Assessment Instrument was completed for each participant to identify transfer skills. Linear regression tested whether demographics and transfer skills correlated with ultrasound measures. RESULTS: Sixty-two wheelchair users with spinal cord injury were included (39 with paraplegia and 23 with tetraplegia). Biceps tendon width increased after repeated transfers (P < 0.001). Participants with greater body weight experienced greater increases in biceps width after transfers (ß = 0.109, P < 0.05). Skills evaluating body position relative to the target surface and safe and stable hand and arm positions affected changes in biceps and supraspinatus width and echogenicity (P < 0.05). CONCLUSIONS: Repeated transfers caused measurable changes in biceps tendon width in a subset of participants. Changes in biceps and supraspinatus ultrasound measures were related to body weight and performance of specific transfer skills. Further testing is needed to confirm whether the clinical meaning of the observed relationships and whether using certain transfer skills and reducing body weight can attenuate the development of tendinopathy.