Andrew M. Hinson

Is Bisphosphonate-Related Osteonecrosis of the Jaw an Infection? A Histological and Microbiological Ten-Year Summary

The role of infection in the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is poorly understood. Large-scale epidemiological descriptions of the histology and microbiology of BRONJ are not found in the literature. Herein, we present a systematic review of BRONJ histology and microbiology (including demographics, immunocompromised associations, clinical signs and symptoms, disease severity, antibiotic and surgical treatments, and recovery status) validating that infection should still be considered a prime component in the multifactorial disease.

Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT

Objective To evaluate 4-dimensional (4D) computed tomography (CT) for the localization of parathyroid adenomas previously considered nonlocalizing on ultrasound and single-photon emission CT with CT scanning (SPECT-CT). To measure radiation exposure associated with 4D-CT and compared it with SPECT-CT. Study Design Case series with chart review. Setting University tertiary hospital. Subjects and Methods Nineteen adults with primary hyperparathyroidism who underwent preoperative 4D CT from November 2013 through July 2014 after nonlocalizing preoperative ultrasound and technetium-99m SPECT-CT scans. Sensitivity, specificity, predictive values, and accuracy of 4D CT were evaluated. Results Nineteen patients (16 women and 3 men) were included with a mean age of 66 years (range, 39-80 years). Mean preoperative parathyroid hormone level was 108.5 pg/mL (range, 59.3-220.9 pg/mL), and mean weight of the excised gland was 350 mg (range, 83-797 mg). 4D CT sensitivity and specificity for localization to the patient’s correct side of the neck were 84.2% and 81.8%, respectively; accuracy was 82.9%. The sensitivity for localizing adenomas to the correct quadrant was 76.5% and 91.5%, respectively; accuracy was 88.2%. 4D CT radiation exposure was significantly less than the radiation associated with SPECT-CT (13.8 vs 18.4 mSv, P = 0.04). Conclusion 4D CT localizes parathyroid adenomas with relatively high sensitivity and specificity and allows for the localization of some adenomas not observed on other sestamibi-based scans. 4D CT was also associated with less radiation exposure when compared with SPECT-CT based on our study protocol. 4D CT may be considered as first- or second-line imaging for localizing parathyroid adenomas in the setting of primary hyperparathyroidism.

Temporal correlation between bisphosphonate termination and symptom resolution in osteonecrosis of the jaw: a pooled case report analysis.

PURPOSE To investigate whether termination of bisphosphonates (BPs) affects resolution of bone exposure and symptomatic disease in patients with established medication-related osteonecrosis of the jaw (MRONJ). PATIENTS AND METHODS The studied population included 84 patients with established MRONJ who discontinued BP therapy before treatment (n = 21), at treatment initiation (n = 38), or later (or never) in the treatment course (n = 25). These 3 groups were compared using Kaplan-Meier curves and log-rank tests for differences in the respective times to resolution of 1) bone exposure for any treatment modality, 2) bone exposure not requiring radical surgery, and 3) disease symptoms. RESULTS Patients who continued BPs after the start of treatment exhibited significantly delayed resolution of symptoms (median 12 months; 95% confidence interval 8 to 15) compared with those who discontinued BPs before (3 months; 2 to 5) and at (6 months; 3 to 7) presentation (P < .005). CONCLUSIONS Independent of treatment modality and MRONJ stage at presentation, discontinuing BP before or at treatment initiation is associated with faster resolution of MRONJ symptoms compared with continuing the drug throughout jaw treatment. Patients should be counseled that continuing their BP medication after an established MRONJ diagnosis (compared to stopping the BP at diagnosis) may delay resolution of maxillofacial symptoms by approximately 6 months.

Comparison of Intraoperative versus Postoperative Parathyroid Hormone Levels to Predict Hypocalcemia Earlier after Total Thyroidectomy

Objective To determine differences in the mean parathyroid hormone (PTH) levels for normocalcemic and hypocalcemic total thyroidectomy patients who were tested for PTH during the intraoperative or early postoperative period. Data Sources MEDLINE, the Cochrane Database, and other databases from 1960 to 2014 in the English language and specific to humans for relevant articles. Review Methods Studies were included if PTH was obtained within 24 hours of thyroidectomy. Studies were excluded (1) if only a hemithyroidectomy was performed, (2) if means of studied PTH values were not reported in the article, or (3) if the time of the PTH draw fell outside of defined “intraoperative” or “early postoperative” windows. PTH values were divided into 3 groups: preoperative (control group), intraoperative (ie, discharge decisions were based on PTH values drawn in the operating room), and early postoperative (ie, PTH values at 1 to 4 hours after surgery were used as a guide). Results The reported means of perioperative PTH levels and percentage of patients who developed hypocalcemia were collected from 14 studies. PTH evaluated at both the intraoperative and early postoperative periods was significantly lower in patients who became hypocalcemic versus patients who remained normocalcemic. There was no significant difference when PTH was measured intraoperatively or early postoperatively. Conclusion Intraoperative PTH has no significant disadvantage versus early postoperative PTH when used as a clinical guide for discharge after thyroidectomy.

Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults.

To measure the effect of proton pump inhibitors (PPIs), with and without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and calcium.

Postoperative Calcium Management in Same-Day Discharge Thyroid and Parathyroid Surgery.

Objective To describe a safe and effective postoperative prophylactic calcium regimen for same-day discharge thyroid and parathyroid surgery. Study Design Case series with chart review. Setting Tertiary referral academic institution. Subjects and Methods In total, 162 adult patients who underwent total thyroidectomy, completion thyroidectomy, unilateral parathyroidectomy, parathyroidectomy with bilateral neck exploration, or revision parathyroidectomy were identified preoperatively to be candidates for same-day discharge. All patients in this study were successfully discharged the same day on our standard prophylactic calcium regimen. Results Less than 1% (1/162) of patients re-presented to the hospital within 30 days of surgery, and that patient was successfully discharged from the emergency department after negative workup for hypocalcemia. There was no significant difference between preoperative and postoperative calcium levels in the total/completion thyroidectomy groups (9.3 vs 9.2 mg/dL, respectively; P = .14). The average postoperative calcium level in the parathyroid group was well within normal limits (9.5 mg/dL), and the difference in postoperative calcium levels between revision and primary parathyroidectomy cases was not significantly different (P = .34). Conclusion The reported calcium regimen demonstrates a safe, effective, and objective means of postoperative calcium management in outpatient thyroid and parathyroid surgery in appropriately selected patients.

Evidence-Based Medicine: Approach and References Classification

Evidence-based medicine (EBM) is the process of systematically reviewing, appraising, and applying the best research available to preserve the quality of patient care [1]. In short, the process is daunting, tedious, and, by definition, never-ending. We are reminded of Sisyphus’s eternal task of rolling a large boulder up an even larger hill only to watch the rock roll back down without ever reaching the summit [2]. We begin with two great advantages. First, the task is well defined—we need to only consider four (usually) small glands that reside (usually) in the human neck. Second, unlike Sisyphus, we need not carry the burden alone. While no single person possesses the ability, knowledge, time, or space to classify all present-day therapies, we may be able to accomplish a great deal if we work together.

Domestic Travel and Regional Migration for Parathyroid Surgery Among Patients Receiving Care at Academic Medical Centers in the United States, 2012-2014

IMPORTANCE To improve outcomes after parathyroidectomy, several organizations advocate for selective referral of patients to high-volume academic medical centers with dedicated endocrine surgery programs. The major factors that influence whether patients travel away from their local community and support system for perceived better care remain elusive. OBJECTIVE To assess how race/ethnicity and insurance status influence domestic travel patterns and selection of high- vs low-volume hospitals in different regions of the United States for parathyroid surgery. DESIGN, SETTING, AND PARTICIPANTS A retrospective study was conducted of 36 750 inpatients and outpatients discharged after undergoing parathyroidectomy identified in the University HealthSystem Consortium database from January 1, 2012, to December 31, 2014 (12 quarters total). Each US region (Northeast, Mid-Atlantic, Great Lakes, Central Plains, Southeast, Gulf Coast, and West) contained 20 or more low-volume hospitals (1-49 cases annually), 5 or more mid-volume hospitals (50-99 cases annually), and multiple high-volume hospitals (≥100 cases annually). Domestic medical travelers were defined as patients who underwent parathyroidectomy at a hospital in a different US region from which they resided and traveled more than 150 miles to the hospital. MAIN OUTCOMES AND MEASURES Distance traveled, regional destination, and relative use of high- vs low-volume hospitals. RESULTS A total of 23 268 of the 36 750 patients (63.3%) had parathyroidectomy performed at high-volume hospitals. The mean (SD) age of the study cohort was 71.5 (16.2) years (95% CI, 71.4-71.7 years). The female to male ratio was 3:1. Throughout the study period, mean (SD) distance traveled was directly proportional to hospital volume (high-volume hospitals, 208.4 [455.1] miles; medium-volume hospitals, 50.5 [168.4] miles; low-volume hospitals, 27.7 [89.5] miles; P < .001). From 2012 to 2014, the annual volume of domestic medical travelers increased by 15.0% (from 961 to 1105), while overall volume increased by 4.9% (from 11 681 to 12 252; P = .03). Nearly all (2982 of 3113 [95.8%]) domestic medical travelers had surgery at high-volume hospitals, and most of these patients (2595 of 3113 [83.4%]) migrated to hospitals in the Southeast. Domestic medical travelers were significantly more likely to be white (2888 of 3113 [92.8%]; P < .001) and have private insurance (1934 of 3113 [62.1%]; P < .001). Most patients with private insurance (12 137 of 17 822 [68.1%]) and Medicare (9433 of 15 121 [62.4%]) had surgery at high-volume hospitals, while the largest proportion of patients with Medicaid and those who were uninsured had surgery at low-volume hospitals (1059 of 2715 [39.0%]). CONCLUSIONS AND RELEVANCE Centralization of parathyroid surgery is a reality in the United States. Significant disparities based on race and insurance coverage exist and may hamper access to the highest-volume surgeons and hospitals. Academic medical centers with dedicated endocrine surgery programs should consider strategic initiatives to reduce disparities within their respective regions.

Structural alterations in tumor-draining lymph nodes before papillary thyroid carcinoma metastasis

The purpose of this study was to define and characterize the thyroid tumor‐draining lymph nodes in genetically engineered mice harboring thyroid‐specific expression of oncogenic BrafV600E with and without Pten insufficiency.

Parathyroid Physiology and Molecular Biology

The parathyroid hormone gene has been sequenced in more than ten different species. Phylogenetic analysis has identified an array of homologous domains associated with the synthesis, secretion, and degradation of parathyroid hormone (PTH). These studies are advancing our understanding of the molecular signaling and feedback mechanisms involved in the hormonal control of calcium and phosphate metabolism. This chapter reviews these physiologic processes at the molecular level, which serves as a solid conceptual framework for understanding the pathology discussed in later chapters.