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Early introduction to essential communication skills is important. We sought to determine if a handoff curriculum (HC) would improve confidence, decrease anxiety, and increase participation in clinical handoffs during the surgical clerkship.A multi-center prospective cohort study was performed at two medical schools. Training in the intervention group (HC) consisted of a didactic lecture, video review, and practice session. Students completed a pre-clerkship knowledge test and confidence/anxiety/handoff experience questionnaire pre- and post-clerkship.There were no significant differences in pre-clerkship handoff experiences between institutions except having previously witnessed a verbal handoff (School A 96.4% versus School B 76.2%, P = 0.01). While there were no significant differences in post-clerkship confidence or anxiety, HC students were significantly more involved with written sign-outs (52.9% versus 18.2%, P = 0.02) and verbal handoffs (29.4% versus 4.6%, P = 0.03).Medical students exposed to handoff training shared similar confidence and anxiety scores compared to those that were not, however, they were more involved in handoff experiences during their surgical clerkship. Early introduction to handoff skills may encourage greater participation during subsequent clinical experiences.

Introduction: Acquired adrenal insufficiency is a known risk of unilateral adrenalectomy. However, the rates of early and prolonged adrenal insufficiency following unilateral adrenalectomy are not well defined in the literature. Patients and Methods: We reviewed a case series of 184 consecutive patients to determine the likelihood of steroid supplementation at 30 days and 1 year following adrenalectomy. 109 lesions were non-functional and 75 (41%) demonstrated functionality, including 33 pheochromocytomas, 20 cortisol-producing adenomas, 19 aldosteronomas, and 3 cases of cortisol-secreting hyperplasia. No patients with a nonfunctional lesion, pheochromocytoma, or aldosteronoma required steroid supplementation following surgery. Eleven of 23 patients (48%) with primary adrenal Cushing syndrome required cortisol supplementation at 30 days, and only 1 patient (4%) necessitated supplementation one year following surgery. Discussion: Approximately 50% of patients with cortisol-producing lesions in the adrenal gland will require supplementation 30-days following surgery. Only 4% will require persistent exogenous steroids at 1-year. Conversely, less than 1% of patients with different types of functional or non-functional tumors required supplementation after surgery. Conclusion: The incidence of adrenal insufficiency following unilateral adrenalectomy is low. A large majority of patients requiring steroid supplementation 30 days following surgery are able to wean off this requirement by 1 year. With this information, we can better counsel our patients and set clearer expectations for the potential need of cortisol supplementation following adrenalectomy

Objective Thyroid and parathyroid surgery is performed by both general surgeons and otolaryngologists. We describe the proportion of surgeries performed by specialty, providing data to support decisions about when and to whom to direct research, education, and quality improvement interventions. Methods We tabulated case numbers for privately insured patients undergoing thyroid and parathyroid surgery in Marketscan: 2010–2016 and trainee case logs for residents and fellows in general surgery and otolaryngology. Summary statistics and tests for trends and differences were calculated. Results Marketscan data captured 114 500 thyroid surgeries. The proportion performed by each specialty was not significantly different. Otolaryngologists performed 58 098 and general surgeons performed 56 402. Otolaryngologists more commonly performed hemithyroidectomy (n = 25 148, 43.29% of all thyroid surgeries performed by otolaryngologists) compared to general surgeons (n = 20 353, 36.09% of all thyroid surgeries performed by general surgeons). Marketscan data captured 21 062 parathyroid surgeries: 6582 (31.25%) were performed by otolaryngologists, and 14 480 (68.75%) were performed by general surgeons. The case numbers of otolaryngology and general surgery trainees completing residency and fellowship varied 6- to 9-fold across different sites. The wide variation may reflect both the level of exposure a particular training program offers and trainee level of interest. Conclusion Thyroid surgical care is equally provided by general surgeons and otolaryngologists. Both specialties contribute significantly to parathyroid surgical care. Both specialties should provide input into and be targets of research, quality, and education interventions.

Objectives To establish a time frame for postoperative improvements in neurocognitive function in patients who undergo parathyroidectomy for primary hyperparathyroidism by utilizing repeat neuropsychological assessment at multiple time points before and after surgery. Study Design Prospective cohort study. Methods A prospective study was conducted at a tertiary academic medical center between August 2014 and December 2015, including 50 patients with primary hyperparathyroidism who underwent parathyroidectomy. A panel of neurocognitive tests was administered at two separate time points: preoperative and 1-week postoperative. Validated neuropsychological assessment tools were utilized, including Rey Auditory-Verbal Learning Test, Trail Making Test A and B, Benton Controlled Oral Word Association, WAIS-IV Digit Span, Hospital Anxiety and Depression Scale, Positive and Negative Affect Schedule, and Insomnia Severity Index. Barona Information Sheet was used to collect demographic data. Paired t tests were to compare pre- and postoperative scores. Results Thirty-five patients completed the preoperative and 1-week postoperative testing. In cognitive testing, significant improvement was noted in immediate recall (P < 0.001), working memory (P = 0.011), and attention (P = 0.008) at 1-week postoperative. In mood testing, depression (P < 0.001), anxiety (P < 0.001), and negative affect (P = 0.001) scores were significantly improved at 1-week postoperative. Insomnia scores also were significantly improved at 1 week (P < 0.001). Conclusion Objective improvements in neurocognitive function following parathyroidectomy for primary hyperparathyroidism were noted as early as 1 week after surgery, which is earlier than previously reported. Level of Evidence 2b. Laryngoscope, 2017

BACKGROUND Our goal was to elucidate the differences in degree of technical difficulty of thyroidectomy in patients with autoimmune thyroid diseases. METHODS Charts of adult patients who had undergone thyroidectomy were reviewed. Patients with Hashimoto's Thyroiditis (HT) or Graves' Disease (GD) were individually compared to a control group of patients with early stage malignancy or goiter. RESULTS The HT (n = 65) group was significantly more likely to have friable (P = .001) and fibrotic (P

Adrenalectomy is performed to treat functional pathology and remove tumors of malignant concern. The National Surgical Quality Improvement Program (NSQIP) risk calculator predicts 30-day complications and length of stay following index surgical procedures. We assess whether this tool accurately predicts complications following adrenalectomy procedures at a tertiary care academic medical center. A retrospective review was performed for all adrenalectomies at a single institution from 2004 to 2016. 197 patients underwent adrenalectomy without concurrent resections. Predicted risk for NSQIP complications was calculated for each patient. The mean predicted and observed risks (%) at 30 days across all patients within each category were determined, and these were compared with two-sided one-sample t tests. Of 197 adrenalectomies, 180 were laparoscopic and 17 were open. For laparoscopic adrenalectomy, ten (5.5%) complications were observed including nine (5%) graded Clavien III or greater. All observed complication rates were significantly different than predicted (p values for all

Secondary hyperparathyroidism is a systemic metabolic derangement that leads to massive expansion of parathyroid tissue and overproduction of parathyroid hormone. Accurate biochemical diagnosis is crucial to establishing a plan of care for these patients. Indications and timing of surgical intervention once refractory to medical management are best established through multidisciplinary care including an expert parathyroid surgeon. Principles of careful parathyroid surgery including identification of all parathyroid tissue in a bloodless field allow for the appropriate management of parathyroid excision. Subtotal resection of parathyroid tissue and total parathyroidectomy with immediate parathyroid autotransplantation are equivalent options. Hypocalcemia is the most common postoperative occurrence and should be anticipated and managed aggressively.

Purpose Patients with primary hyperparathyroidism routinely undergo preoperative imaging to localize the abnormal gland to facilitate a guided parathyroidectomy. These techniques include neck ultrasound (US), dual phase planar technetium-99 m (99mTC) sestamibi (MIBI) scans, single photon emission computed tomography (SPECT), combined SPECT/CT, and four dimensional CT scans (4D CT). Despite appropriate preoperative imaging, non-localization of abnormal glands does occur. This study aims to determine whether non-localization is the result of radiologic interpretive error or a representation of a subset of truly non-localizing parathyroid adenomas. Materials and methods A retrospective study was performed; two senior radiologists reinterpreted the preoperative imaging (US and MIBI scans) of 30 patients with initially non-localizing studies. All patients underwent parathyroidectomy for primary hyperparathyroidism at a tertiary referral center. Both radiologists were blinded to the scores of his colleague. The results were compared for inter-reader reliability using Cohen’s kappa test. Results Twenty-nine of thirty nuclear studies were found to be negative on reinterpretation. The readers agreed in 86.67% of their observations, with a kappa (κ) value of 0.706 (SE = ± 0.131, 95% confidence interval for κ = 0.449–0.962). One of eighteen ultrasounds had positive localizations on reexamination, however, the inter-observer agreement was only 55.6%, with a kappa value of 0.351 (SE = ± 0.139, and 95% confidence interval for κ = 0.080–0.623). Overall, no statistically significant difference in preoperative and retrospective interpretation was found. Conclusion This study identifies a subset of parathyroid adenomas that do not localize on preoperative imaging despite sound radiographic evaluation.

BACKGROUND: The American Association of Endocrine Surgeons initiated a fellowship match in 2007. The profile of applicants who successfully match into an endocrine surgery (ES) fellowship has not previously been characterized. METHODS: An institutional review board-approved, web-based survey was distributed to recent and current ES fellows. RESULTS: The survey response rate was 62% (56/90). The overall mean age was 33 years (standard deviation 63), 54% were female, and 37% self-identified as non-white. Only 5% entered their surgical training with the aim of specializing in ES. During residency, respondents were exposed to high volumes of index ES cases. Sixty-two percent had dedicated research time. At the time of fellowship application, the median number of publications was 5 (range, 0 to 25), and 30% of respondents had additional advanced degrees. CONCLUSION: Entering ES fellows has diverse backgrounds, with strong academic credentials. These data help inform the career mentoring of aspiring ES applicants.

Inherited endocrinopathies are rare tumor predisposition syndromes associated with significant morbidity and mortality and have implications for both patients and their families. Prior studies suggest that early diagnosis of inherited endocrinopathies may reduce morbidity and mortality. Although genetic counseling and testing can help inform the appropriate management of at-risk relatives, barriers to care still exist. We explored patient perceptions to identify barriers and promote the uptake of genetic counseling.An anonymous survey of patients from a multidisciplinary inherited endocrinopathy clinic at a tertiary care, university-based medical center was conducted. Data collected and analyzed included demographics, socioeconomic status, perceived risks, benefits, and both motivating and dissuading factors to genetic counseling and testing.Our study suggests barriers to genetic testing include concerns regarding cost and the potential for discrimination with respect to employers and insurers.This highlights the importance of genetic counseling to discuss benefits of genetic testing, while dispelling misperceptions. Knowledge of the common barriers to genetic counseling and testing can guide initiatives and education to foster genetic testing of at-risk relatives in the inherited endocrinopathy population.FMTC = familial medullary thyroid carcinoma GINA = Genetic Information Nondiscrimination Act MEN1 = multiple endocrine neoplasia 1 MEN2A = multiple endocrine neoplasia 2A MEN2B = multiple endocrine neoplasia 2B MTC = medullary thyroid cancer PGL-PCC = paraganglioma-pheochromocytoma.

Aim Serrated polyposis is a condition of the colon characterized by multiple serrated polyps. This review aims to provide a practical guide to the day-to-day management of serrated polyposis, including diagnosis, endoscopic identification of serrated polyps, surveillance, the role of endoscopic and surgical management and the screening of family members. Method The literature was searched using PubMed and MEDLINE databases for the terms “serrated polyp”, “serrated polyposis” and “hyperplastic polyposis”. English-language abstracts were read and the full article was retrieved if relevant to the review. Expert opinion from the authors was also sought. Results Advances in our knowledge of the molecular pathways involved in serrated polyposis and an improved clinical picture of the disease from retrospective studies have led to better understanding of its pathogenesis and natural history. However, there are still areas not answered by the literature, and hence empirical management or expert opinion has to be followed. Conclusion Improvements in our understanding of serrated polyposis, together with improvements in endoscopic equipment and technique, have enabled the endoscopist to be at the forefront of managing this condition from diagnosis to endoscopic surveillance and control of the polyps.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder that presents with renal tumors, pulmonary cysts with spontaneous pneumothoraces, and skin hamartomas. We present a case of a 67-year-old female with multiple endocrinopathies and a history of BHD syndrome. In 2011, a thyroidectomy with a four-gland parathyroidectomy was performed for toxic multinodular goiter (TMNG) and parathyroid hyperplasia. On frozen section, a tumor was identified next to a hypercellular parathyroid. After being worked up, this tumor was determined to be an adult rhabdomyoma. This represents the first time that both TMNG and parathyroid hyperplasia have been present in a BHD patient. Additionally, this is the first adult rhabdomyoma reported in a patient with BHD syndrome. Adult rhabdomyomas have no reported associations; however, potential colocation of the mutation in BHD syndrome and translocation in adult rhabdomyomas on chromosome 17p suggests a possible connection. Further work is needed to better understand this connection.

Primary hyperparathyroidism (PHPT) is a prevalent and costly disease. This chapter discusses recent health services and health economics research related to PHPT. We cover first the epidemiology of PHPT in the USA, using primary data from the Truven Health MarketScan database. We then discuss several dimensions of costs of management. We review the evidence regarding medical approaches to managing PHPT relative to surgical approaches, showing that definitive surgical management soon after diagnosis appears to yield cost savings. We then examine the costs associated with surgical management, comparing economic implications of alternative surgical approaches, including limited exploration after preoperative gland localization, which appears to have reasonable evidence in favor of cost-effectiveness, and intraoperative adjuncts, for which cost-effectiveness evidence is weak. We finally review the economic evidence for medical management of patients who are not good candidates for surgery.

Background Little is known about costs associated with differentiated thyroid cancer (DTC) and follow-up care. This study used data from the Surveillance Epidemiology and End Results (SEER) database to examine cumulative costs attributable to disease stage and treatment options of DTC in elderly patients over 5 years. Methods We identified 2,823 patients aged >65 years with DTC and 5,646 noncancer comparison cases from SEER Medicare data between 1995 and 2005. Cumulative costs were obtained by estimating average costs/patient in each month up to 60 months after diagnosis. We performed multivariate analyses of costs by fitting each monthly cost to linear models, controlling for demographics and comorbidities. Marginal effects of covariates were obtained by summing coefficients over 60 months. Results Cumulative costs were $17,669/patient the first year and $48,989/patient 5 years after diagnosis. Regional disease was associated with higher costs at 1 year ($9,578) and 5 years ($8,902). Distant disease was associated with 1-year costs of $28,447 and 5-year costs of $20,103. Patients undergoing surgery and radiation had a decrease in cost of $722 at 5 years. Conclusion DTC in the elderly is associated with significant economic burden largely attributable to patient demographics, stage of disease, and treatment modalities.

In some patients, papillary thyroid carcinoma (PTC) lymph-node metastases are noted to be black (dark) in color at the time of surgical removal. The goal of this project was to determine histological, genetic, and clinical features that are associated with regional black PTC metastasis.Fifteen patients with black PTC metastases (black-PTC) were compared to a control cohort of 15 patients with nonblack PTC metastasis (nonblack PTC). Each sample was evaluated for the histological characteristics, BRAF V600E mutational status, and associated patient clinical data.The degree of cystic degeneration (80% vs. 27%, p=0.004), percent hemosiderin deposition (20% vs. 6%, p=0.001), and presence of classical variant (100% vs. 67%, p=0.018) were significantly greater in black PTC than nonblack PTC (α=0.05). Other results were not significantly different.This study demonstrates that black compared to nonblack metastases have a greater degree of cystic degeneration and hemosiderin deposition leading to discoloration, and a trend toward an increased incidence in BRAF V600E mutations. This study is the first of its kind to describe the clinical, pathological, and genetic features associated with black PTC lymph-node metastasis.

ObjectiveData from the Surveillance Epidemiology and End Results Medicare-linked database were used to estimate the incidence of and risk factors associated with recurrent thyroid cancer, and to assess the impact of recurrence on mortality following diagnosis, controlling for mortality as a competing risk.DesignWe identified 2883 patients over 65 years of age diagnosed with a single, primary well-differentiated thyroid cancer between 1995 and 2007. A recurrence was considered if the patient had evidence of I-131 therapy, imaging for metastatic thyroid carcinoma, or complete thyroidectomy beyond 6 months of diagnosis. Competing risk regressions were performed using Cox proportional hazards models with 1- and 2-year landmarks.ResultsRecurrence was observed in 1117 (39%) of the 2883 patients in the cohort. Age, stage, and treatment status were significant risk factors for developing recurrent disease (PP=0.03) than patients with no recurrence.ConclusionsThe rate of recurrence of well-differentiated thyroid carcinomas in this sample of elderly patients was 39%. Extent of disease and older age negatively impacted the risk of recurrence from differentiated thyroid cancer. In these data, patients with follicular histology and a recurrence were less likely to die, suggesting that mortality and recurrence are competing risks. These data should be taken into account with individualized treatment strategies for elderly patients with recurrent malignant thyroid disease.

Background and Aims It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis. Methods Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. Results The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. Conclusions The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.

We conducted a retrospective study to compare operating times and costs in patients who underwent guided parathyroidectomies with either (1) technetium-99m ((99m)Tc) multiplex ion-beam imaging (MIBI) parathyroid scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT) fusion images or (2) sestamibi dual-phase (99m)Tc MIBI planar parathyroid scintigraphy alone preoperatively. Our study population was made up of the first 24 patients at our facility who had undergone SPECT/CT parathyroid imaging with technetium-99m ((99m)Tc) MIBI and a group of 24 patients who had undergone MIBI planar imaging alone. Patient demographics, preoperative laboratory test results, operating times, and hospital charges were analyzed. We found that less operating time was required for the planar MIBI group than in the SPECT/CT group (mean: 135 vs. 158 min), although the difference was not statistically significant. Likewise, the total cost of treatment was lower in the planar MIBI group (mean: $10,035 vs. $11,592); the difference was statistically significant by one measure (p × 0.02, Wilcoxon rank sum test) but not by another (p × 0.06, Student t test). Although SPECT/CT is efficient for patients with small and difficult-to-localize adenomas, it has yet to demonstrate greater efficacy or cost-effectiveness than planar MIBI for routine parathyroidectomy in patients with primary hyperparathyroidism when an easily identifiable parathyroid adenoma is localized.

Background Sentinel lymph node biopsy (SNLB) is the standard of care in staging of melanoma and other skin cancers. Early studies used lymphazurin (LZ) for SLNB. A national shortage of LZ promoted methylene blue (MB) as an alternate stain. Objective This study compares complication rates between LZ and MB in SLNB patients, and the reliability dyes in locating sentinel lymph nodes. Methods Charts were reviewed for patients who underwent SLNB for skin cancers between September 2006 and November 2008 at Penn State Hershey Medical Center. The type and quantity of dye, the presence of blue stained sentinel nodes, and any complications were recorded. Results Ninety-three patients underwent SLNB (46 LZ, 47 MB). The amount of dye used was similar (avg. 0.93 ml LZ, 1.24 ml MB). The complication rate of LZ was 8.7%, and MB was 25.5%. There was significantly more (P = 0.003) skin graft complications in the MB patients (6/12) versus LZ (0/15). Conclusions There is a higher rate of complications with MB, especially with skin grafting. The reported risk of anaphylaxis with LZ has not been reported in volumes

Prolonged therapeutic exposure to lithium compounds can have adverse consequences on calcium homeostasis. A unique form of hyperparathyroidism appears to be causally linked to chronic lithium exposure. We provide a comprehensive review of relevant literature using a structured, evidence-based approach. Published data were identified from systematic electronic literature searches. References are assigned a level of evidence according to a validated classification schema. Level III and V evidence supports an etiologic link between sustained lithium therapy and both hypercalcemia and hyperparathormonemia (grade C recommendation). Level V evidence supports the use of preoperative parathyroid imaging if a focused exploration is planned (grade C recommendation). Level V evidence supports the use of intraoperative parathyroid hormone monitoring to guide appropriate surgical therapy (grade C recommendation). There is conflicting and equally weighted level V evidence supporting a routine preoperative plan of bilateral neck exploration versus selective unilateral exploration (no recommendation). There may be a role for calcimimetic drug therapy as an alternate, nonsurgical means of controlling lithium-associated hyperparathyroidism (grade C recommendation). Evidence-based recommendations support screening of patients on chronic lithium therapy for hypercalcemia. Appropriate surgical therapy may consist of either a bilateral or a unilateral approach when performed by an experienced endocrine surgeon. Focused approaches should be guided by preoperative imaging and intraoperative hormone monitoring. Calcimimetic therapy is a potential alternative to parathyroidectomy.

The ability to accurately stratify patients with thyroid nodules (TNs) preoperatively is imperative because most TNs are benign. The reliability of fine-needle aspiration biopsy (FNAB) in large TNs has been questioned in recent literature.To determine whether TN size affects the reliability of FNAB results, and to determine the rates of malignant disease of each Bethesda class at Penn State Medical Center.Retrospective electronic medical record review of patients undergoing FNAB followed by thyroidectomy from March 2010 through December 2013 at an academic, tertiary referral center. A total of 297 patients with 326 TNs were identified as part of a consecutive series.The primary outcome was to determine the rate of malignant disease of TNs smaller than 3.0 cm or 3.0 cm or larger and of each Bethesda class. Statistical analysis included χ(2) tests. The secondary outcome was to develop logistic regression models to estimate the probability of malignant disease on final pathologic diagnosis as predicted by TN size as well as TN size in conjunction with Bethesda class.Of the 297 patients, 233 were female (78.4%). The mean (SD) age was 51.0 (15.4) years. Of the 326 TNs, 143 were malignant on surgical histopathologic analysis (43.7%). The mean TN size was 2.0 (1.4) cm. Rates of malignant disease for Bethesda classes 1 to 6 were 0% (95% CI, 0%-26.0%), 6.0% (95% CI, 1.7%-14.6%), 30.2% (95% CI, 18.3%-44.3%), 23.5% (95% CI, 14.8%-34.2%), 72.4% (95% CI, 52.8%-87.3%), and 98.8% (95% CI, 93.5%-99.9%), respectively. Overall sensitivity and specificity (excluding class 1 TNs) were 97.2% and 36.8%, respectively. The false-negative rate of benign cytologic results was 6.0% (95% CI, 1.7%-14.6%); only 1 false-negative result occurred in TNs 3.0 cm or greater. Of the TNs smaller than 3.0 cm, 48.4% were malignant compared with 33.3% of TNs 3.0 cm or greater (P = .049). Both Bethesda class and TN size were significant variables (P .05) within our logistic regression models indicating that higher Bethesda class and TN size smaller than about 2.0 cm were associated with increased probabilities of malignant disease.Our results suggest that smaller TNs (smaller than about 2.0 cm) are associated with increased probabilities of malignant disease irrespective of Bethesda class. Routine diagnostic thyroid lobectomy solely owing to TN size of 3.0 cm or greater need not be performed.

Background Chronic lithium therapy may cause hyperparathyroidism (HPT). The utility of intraoperative parathyroid hormone monitoring (IOPTH) in these patients is unknown. The authors' hypothesis was that multiglandular disease is more common in these patients, and the ability of IOPTH to predict cure may be limited. Methods Twelve patients had HPT during chronic lithium therapy and underwent parathyroidectomy with IOPTH. Criteria for curative resection were a decrease ≥50% from baseline and into the normal range. Calcium and PTH levels were measured during follow-up. Results Preoperatively, mean calcium was 11.0 ± 0.1 mg/dL, and PTH was 116 ± 14 pg/mL. Fifty percent of patients had multiglandular disease confirmed by IOPTH levels. Mean IOPTH decrease from baseline was 74 ± 4%. Although 10 of 12 patients met criteria for curative resection, only 8 remain normocalcemic. The 2 patients who did not meet criteria remain normocalcemic. Mean postoperative calcium for all patients was 9.5 ± 0.2 mg/dL. Of the 10 normocalcemic patients, 4 also have hyperparathormonemia (mean PTH, 119 ± 19 pg/mL). Conclusions The incidence of multiglandular disease in HPT after chronic lithium exposure is higher than standard HPT. The ability of IOPTH to predict durable normocalcemia is limited. Bilateral neck exploration should be considered for these patients regardless of whether IOPTH monitoring is used.

The relationship between polycythemia vera (PV) and primary hyperparathyroidism is not well understood. Remission or improvement of PV following parathyroidectomy in the setting of primary hyperparathyroidism has previously been described; however, long-term outcomes are not well characterized. We describe a patient with JAK2 mutation negative PV and primary hyperparathyroidism, with a dramatic, but ultimately transient, improvement in hemoglobin following resection of a parathyroid adenoma. While screening for hyperparathyroidism may be useful in the setting of PV, indications for parathyroidectomy should be driven by symptomatology or established criteria, not the desire to affect the clinical course of PV.

The regulation of LH and FSH subunit gene expression is under the control of GnRH. Physiological changes in the frequency of pulsatile GnRH release from the hypothalamus result in differential stimulation of α-, LHβ-, and FSHβ-gene expression. Previous studies indicate that the GnRH receptor couples to G proteins of the Gq/11 family, with phosphoinositide turnover and its resultant increase in intracellular calcium concentration and protein kinase C (PKC) activation, to stimulate secretion of LH and FSH. However, the molecular mechanisms by which GnRH mediates its transcriptional effects remain largely unknown. We used GH3 cells, constitutively expressing the rat GnRH receptor (GGH3-1′ cells) and transiently transfected with a luciferase reporter gene controlled by either the α, LHβ, or FSHβ gene regulatory region (αLUC, LHβLUC, and FSHβLUC, respectively), to examine the roles of several signal transduction pathways in the GnRH-mediated stimulation of gonadotropin subunit gene expression. Activation of PK...

THYMIC HYPERPLASIA in Graves’ disease (GD) is a known entity, but massive thymic hyperplasia in GD is a rare phenomenon described in few case reports, in which about half of the patients underwent unnecessary invasive diagnostic interventions to rule out a malignancy. In previous studies, the molecular pathogenesis of thymic hyperplasia in GD has been related to thyrotropin receptors (TSHR) in thymus tissue that can be engaged by the stimulating autoimmune antibodies present in GD. Furthermore, hyperthyroidism may have an independent, hyperplastic effect on thymic tissue that is evident from regression of thymic hyperplasia with appropriate medical or operative treatment of hyperthyroidism. Understanding the benign course of thymic hyperplasia in GD may prevent unnecessary operations on these patients.

Angiotensin II (AII) receptor binding assays were performed in rat adipocytes from three separate anatomic depots. Fat cells were isolated by collagenase digestion, and plasma membranes were prepared from the epididymal, mesenteric, and retroperitoneal fat depots of male Sprague-Dawley rats at 100 days of age. Binding of 125I-labeled [Sar1,Ile8]AII was rapid, saturable, and specific in membranes from all depots, identifying a receptor with a similar affinity of approximately 1 nM. Site-associated differences in receptor number were observed, with epididymal and mesenteric fat cell membranes exhibiting significantly more receptors than retroperitoneal fat cells when binding was expressed per unit of membrane protein. When corrected for cell volume, the number of receptors per cell ranked epididymal > retroperitoneal > mesenteric. Inhibitory constants for the peptide agonists AII and AIII and the peptide antagonist [Sar1,Ala8]AII indicated similar affinities in all three depots. Because the receptor has been classified pharmacologically into two subtypes, the AT1 selective antagonist losartan, and the AT2 selective antagonist PD 123,319 were used to classify the adipocyte receptor, indicating an AT1 subtype with an affinity for losartan in the mesenteric and retroperitoneal adipocytes that was significantly greater than the epididymal. Similar studies were performed in adipocyte membranes obtained from human omental and subcutaneous adipose tissue, revealing the presence of an AII receptor in both depots with an affinity of approximately 10 nM for losartan. These data indicate site-specific differences in AII receptor number in fat cell membranes from rats and the existence of human adipocyte AII receptors, suggesting that the adipocyte is significant for the peripheral metabolism of components of the renin-angiotensin system.

Adipose tissue possesses considerable growth potential, and excess adipose tissue mass is associated with noninsulin dependent diabetes mellitus (NIDDM). Adipose tissue is a significant source of angiotensinogen, the precursor of angiotensin II (All), a vasoactive peptide with in vitro mitogenic effects. The renin-angiotensin system remains only partially identified in adipose tissue, however, and knowledge of whether All has a physiologic role in this tissue is dependent in part upon other components of the system being characterized. We have chosen to further investigate aspects of the renin-angiotensin system in separate adipose tissue depots of rats during growth and development of the tissue. Either epididymal or retroperitoneal adipose tissue was examined in young lean, or adult obese male Sprague-Dawley rats. Adipose tissue was subjected to collagenase digestion, yielding separate vascular and fat cell fractions. Each fraction was analyzed for angiotensin converting enzyme (ACE) activity and All receptor binding capacity. ACE activity was significantly greater when expressed per gram of adipose tissue in the young lean rats. Vascular and fat cell fractions exhibited All receptors of high affinity, with a greater density of receptors observed in the epididymal adipose tissue fractions. Incubation of adipocytes with exogenous All was associated with the release of prostaglandin into the medium, and analyses of adipocyte cytosol indicated the presence of angiotensinogen. Growing rats given oral losartan, an All receptor antagonist, once daily (15 mg/kg) for 2 weeks exhibited reductions in body weight gain, fat mass, fat cell volume, and All receptor number. These data further document the presence of a peripheral renin-angiotensin system in anatomically distinct adipose tissue depots at different stages of growth. While the characterization of the effects of All upon adipose tissue development remains incomplete, future investigations with agents affecting the adipocyte renin-angiotensin system could provide additional information on the role of this system in adipose tissue growth.

Objective To discuss the implications of a young age at diagnosis in a family member with hyperparathyroidismjaw tumor syndrome, the youngest published case to date, due to a mutation of the CDC73 gene (formerly known as HRPT2); to review this family with regard to modifications of guidelines for surveillance of hyperparathyroidism and other associated features in affected and at-risk relatives; and to discuss surgical recommendations in this syndrome. Methods A review of English-language publications in PubMed and a review of GeneReviews were conducted pertaining to the subject of familial hyperparathyroidism. A case is described, and the family pedigree is discussed. Results Review of the literature revealed that CDC73-related disorder has not previously been reported in patients younger than 10 years. This finding has been the basis for the recommendation for initiation of surveillance for disease manifestations at that age. Review of the family history of our current patient revealed a 7-yearold nephew with hypercalcemia attributable to primary hyperparathyroidism. Conclusion Surveillance of hyperparathyroidism in affected persons and genetic testing of relatives at risk are currently recommended to start at 10 years of age. We recommend that these be conducted at a younger age, preferably 5 to 10 years before the earliest diagnosis of hyperparathyroidism within the family, and potentially at birth in families with a known mutation of the CDC73 gene, in light of the malignant potential of the disease. (Endocr Pract. 2011;17:602-609)

To detect the presence in adipose tissue of peptides known to affect tissue growth and to investigate potential regional differences, epididymal and perirenal adipose tissue depots from male Sprague-Dawley rats were separated into adipocyte and stroma-vascular fractions by collagenase digestion, sequential centrifugation and filtration. Identity and integrity of the fractions were demonstrated by light and electron microscopy, while dose-response curves for angiotensin-converting enzyme (ACE) were performed, revealing maintained functional capacity of the stroma-vascular fraction. ACE, atrial natriuretic peptide (ANP), and transforming growth factor-alpha (TGF-alpha) concentrations were significantly greater in epididymal than perirenal stroma-vascular tissue. Adipocyte fractions from both depots contained significant concentrations of ANP and TGF-alpha. There was no detectable ACE in the adipocyte fractions, indicating that no contaminating stromal-vascular cells were present in these fractions. These data show significant concentrations of peptides with effects on growth in subfractions of adipose tissue and demonstrate regional differences in concentrations between fat depots.

Patients with hereditary pheochromocytoma are at risk of the development of bilateral disease. Partial adrenalectomy can preserve adrenal function to avoid the morbidity associated with medical adrenal replacement. Here, we report a multimedia case study of synchronous bilateral partial adrenalectomy by the laparoscopic approach.A 13-year-old patient with von Hippel-Lindau disease was found to have high urinary metanephrines and normetanephrines. Computed tomography showed bilateral adrenal tumors (2.5 cm on the right side and 0.9 cm on the left). MIBG scan showed positive uptake in the right adrenal gland without extra-adrenal uptake. After adequate adrenergic blockade, the patient underwent laparoscopic partial adrenalectomy bilaterally.The left side was approached first with the patient in the right decubitus position. Intraoperative ultrasound was performed to determine the line of tumor excision, which was carefully planned to preserve most of the normal-appearing gland. Both tumors were excised completely with good hemostasis. The main adrenal veins of both sides were precisely preserved. Operative time was 228 minutes. No clinically important hemodynamic fluctuations were noted. Pathologic examination confirmed bilateral entirely excised pheochromocytomas. The patient has not required exogenous corticosteroid replacement at follow-up.Laparoscopic partial adrenalectomy for bilateral pheochromocytomas is safe and technically feasible. It should be considered the treatment of choice for hereditary pheochromocytoma.

Malignant tumours of the adrenal gland are uncommon but are associated with substantial mortality. For most tumours resection is the only opportunity for cure. Advances in diagnostic and surgical techniques have improved the detection and treatment of these tumours. Further advances need new ways to make decisions about the use of laparoscopic resection for malignant, or potentially malignant, adrenal tumours. We review studies on the outcome of laparoscopic adrenalectomy for primary adrenal cancer as well as studies on metastatic disease to the adrenal glands. There are few prospective data because of the rarity of this condition. Careful individual judgment by the surgeon remains the cornerstone of safe and complete resection for adrenal malignant disease.

Minimally invasive approaches have dramatically reduced morbidity associated with adrenalectomy. There has been concern that an increased frequency of adrenal imaging along with the advantages of less morbidity could influence the indications for adrenalectomy. We tested the hypothesis that adrenalectomy has become more common over time and that benign diseases have been increasingly represented among procedural indications. The Nationwide Inpatient Sample (NIS) database was utilized to determine the incidence of adrenalectomy and the associated surgical indications in the United States between 1988 and 2000. All discharged patients were identified whose primary ICD-9-CM procedure code was for adrenalectomy, regardless of the specific surgical approach (laparoscopic adrenalectomy was not reliably coded). This subset was then queried for associated ICD-9-CM diagnostic codes. Linear regression and t-tests were utilized to determine the significance of trends. The total number of adrenalectomies increased significantly, from 12.9 per 100,000 discharges in 1988 to 18.5 per 100,000 discharges in 2000 (p = 0.000003). The total number of adrenalectomies with a primary ICD-9-CM code for malignant adrenal neoplasm did not increase significantly: from 1.2 per 100,000 discharges in 1988 to 1.6 per 100,000 discharges in 2000 (p = 0.47). The total number of adrenalectomies with a primary ICD-9-CM diagnostic code for benign adrenal neoplasm increased significantly, from 2.8 per 100,000 discharges in 1988 to 4.8 per 100,000 discharges in 2000 (p = 0.00002). The average percentage of adrenalectomies performed for malignant neoplasm was significantly higher during the period 1988--1993 when compared to 1994--2000 (11% vs. 9%; p = 0.002). The average percentage of adrenalectomies performed for benign neoplasm was significantly lower during 1988--1993 when compared to 1994--2000 (25% vs. 28%; p = 0.015). Adrenalectomy is being performed with increasing frequency. This is associated with an increase in the proportion of adrenalectomies performed for benign neoplasms. Assuming no significant change in disease prevalence during the study period, these data suggest that indications for adrenalectomy may have changed somewhat over that period.

Background Endocrine surgery is a discipline that is dedicated to high-quality care of patients with endocrine surgical disease. The relationship between its “identity” as a separate field and clinical practice patterns is not known. Methods The National Inpatient Sample was searched by the International Classification of Diseases–9th revision–Clinical Modification codes for parathyroidectomy, thyroidectomy, and adrenalectomy for the years 1988 through 2000. The surgeons who performed these operations were profiled by 2 methods: Method A, by the percentage of the total primary International Classification of Diseases–9th revision–Clinical Modification procedure codes that were the selected endocrine procedures; method B, by absolute number of index endocrine procedures performed per year. Only patients with complete coding data for the surgeons were included. Results In this sample, surgeons whose practice was comprised of 25% or less of these endocrine procedures performed 11,071 parathyroidectomies (78% of total), 46,210 thyroidectomies (82% of total), and 4209 adrenalectomies (94% of total). In contrast, surgeons whose practice was comprised of more than 75% of these endocrine procedures performed 769 parathyroidectomies (5% of total), 1560 thyroidectomies (3% of total), and 128 adrenalectomies (3% of total). Conclusion If these data can be extrapolated to indicate generalized practice patterns, the majority of common operations for endocrine disease are performed by surgeons whose practice is not focused on endocrine surgery. However, much of this effect is due to the fact that non–endocrine surgeons far outnumber endocrine surgeons. This understanding of clinical practice patterns will be important to consider during future studies that seek to determine the relationship between surgeon volume and patient outcomes.

Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2.We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line.At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups.In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.

The hypothalamic hormone gonadotropin-releasing hormone (GnRH) plays a critical role in reproductive function by regulating the biosynthesis and secretion of the pituitary gonadotropins. Although it is known that GnRH induces luteinizing hormone beta (LHbeta) gene transcription, the mechanisms by which this occurs remain to be elucidated. We have shown previously that GH3 cells transfected with the rat GnRH receptor cDNA (GGH3-1' cells) support the expression of a cotransfected fusion gene composed of 797 base pairs of rat LHbeta gene 5'-flanking sequence and the first 5 base pairs of the 5'-untranslated region fused to a luciferase reporter (-797/+5LHbetaLUC) and respond to a GnRH agonist with a 10-fold stimulation of activity. Furthermore, we have shown that DNA sequences at -490/-352 confer GnRH responsiveness to the rat LHbeta gene. We have now identified two putative binding sites for Sp1, a three-zinc-finger transcription factor, within this region. Using electrophoretic mobility shift assay, DNase I footprinting, and methylation interference assays, we demonstrate that Sp1 can bind to these sites and that Sp1 is responsible for DNA-protein complexes formed using GGH3-1' and alphaT3-1 nuclear extracts. Mutations of the Sp1 binding sites, which block binding of Sp1, blunt the stimulation of the LHbeta gene promoter by GnRH. These data define GnRH-responsive elements in the LHbeta 5'-flanking sequence and suggest that Sp1 plays an important role in conferring GnRH responsiveness to the LHbeta subunit gene.

GnRH plays a critical role in reproductive development and function by regulating the biosynthesis and secretion of the pituitary gonadotropins, LH and FSH. Although it is known that GnRH induces gonadotropin subunit gene transcription, the mechanism by which this occurs has not been elucidated. Studies have been hindered by the lack of available cell lines that express the LH and FSH subunit genes and respond to GnRH. We have transfected the rat pituitary GH3 cell line with the rat GnRH receptor complementary DNA. These cells, when cotransfected with regulatory regions of the LH or FSH subunit genes fused to a luciferase reporter gene, respond to GnRH with an increase in promoter activity comparable to that seen in primary rat pituitary cells. In this study, we have used this cell model to identify cis-acting elements of the LHβ gene that mediate stimulation by GnRH. Analysis of a series of 5′-deletion and internal deletion constructs has revealed two regions of the rat LHβ gene promoter involved in mediating the response to GnRH, region A (−490/−352) and region B (−207/−82). Fusion of region A upstream of a heterologous minimal promoter linked to the luciferase gene conferred GnRH responsiveness to the promoter, whereas region B did not. However, the presence of both regions A and B conferred a greater GnRH response than region A alone. Electrophoretic mobility shift assay revealed the presence of a protein(s) binding to region A using GH3 as well as αT3–1 nuclear extracts. Thus, region A (−490/−352) confers GnRH responsiveness to the LHβ subunit gene and binds to a protein(s) present in pituitary cell lines. DNA sequences in region B (−207/−82) also contribute to GnRH responsiveness. The identification of putative GnRH response elements in the rat LHβ gene promoter will aid in elucidation of the mechanisms of regulation of gene expression by GnRH.

To better understand the role of the mitogenic vasoactive peptide angiotensin II (AII) in growth and differentiation, we have investigated the existence of membrane receptors for this peptide in rat adipocytes. Following isolation of epididymal fat cells, membrane protein was removed and incubated with varying concentrations of 125I-AII with or without submicromolar concentrations of unlabeled AII. Binding of AII was highly specific, rapid, and reversible. Scatchard analysis indicated that adipocyte membranes contain a high-affinity AII receptor with a Kd of 0.90 nmol/L and a binding site concentration (Bmax) of 53.7 fmol/mg protein. Additional pharmacologic analyses resulted in a rank order potency for peptide agonists and antagonists similar to that reported for the vascular receptor. Determination of subtype specificity with selective organic compounds indicated that the epididymal adipocyte receptor was displaced at low concentrations of DuP753, a selective AT1 subtype antagonist. These studies have successfully identified and characterized a high-affinity membrane receptor for AII in fat cells, further establishing adipose tissue as a peripheral site containing regulatory components of the local renin-angiotensin system.