Joyce Shin

Circulating thyrotropin receptor mRNA as a novel marker of thyroid cancer: clinical applications learned from 1758 samples.

Objectives:Since thyroglobulin, no new blood tests for differentiated thyroid cancer (DTC) have been introduced into routine clinical practice. In initial studies, the detection of circulating DTC cells by thyrotropin receptor (TSHR) mRNA measurement distinguished benign from malignant thyroid diseases. This prospective validation study tests the ability of TSHR mRNA to diagnose DTC preoperatively and to detect cancer recurrence. Methods:TSHR mRNA was measured by quantitative RT-PCR from blood drawn perioperatively in patients undergoing thyroid surgery (n = 526), postoperatively in patients undergoing DTC follow-up (n = 418) and in patients monitored for known benign disease (n = 151). The reference range and applications for TSHR mRNA were previously defined from 663 samples from patients with normal, benign, and malignant thyroid disease. Results:In patients with follicular neoplasms or suspicious cytology, preoperative TSHR mRNA >1 ng/&mgr;g had 96% predictive value for DTC, whereas 95% of patients with undetectable mRNA and benign thyroid sonography had benign disease. In patients with DTC, elevated TSHR mRNA levels became undetectable in all patients (n = 64) on the first postoperative day, except in 5 who manifested persistent or recurrent cervical disease within the year. In long-term follow-up of DTC patients with thyroglobulin antibodies, 96% with undetectable TSHR mRNA also had no evidence of cancer recurrence. Conclusions:TSHR mRNA provides an additional clinical tool for the evaluation of patients with thyroid nodules. It is particularly useful in guiding appropriate initial surgery for follicular neoplasms. TSHR mRNA also represents a new blood test to aid assessment of disease status in thyroid cancer follow-up.

The phenotype of primary hyperparathyroidism with normal parathyroid hormone levels: How low can parathyroid hormone go?

BACKGROUND While normocalcemic hyperparathyroidism is well recognized in primary hyperparathyroidism (PHP), less is known about patients with high calcium but normal intact parathyroid hormone (iPTH). We aimed to describe this entity and designated it normohormonal primary hyperparathyroidism (NHPHP). METHODS From a prospectively maintained database of patients undergoing bilateral parathyroid exploration for PHP, we identified and compared those with preoperative iPTH levels below (NHPHP) and above (typical PHP) normal reference peak (60 pg/mL). RESULTS NHPHP occurred in 46 of 843 patients (5.5%) undergoing initial parathyroidectomy for PHP. All had hypercalcemia (11.1 mg/dL). Regarding preoperative iPTH, 7 patients (15%) had values <40 pg/mL, 19 (41%) had values <60 pg/mL; and 20 (44%) had intermittent values >60 pg/mL. Unlike patients with elevated iPTH, nearly all NHPHP patients had additional testing delaying the operation. Imaging correctly localized NHPHP parathyroid disease in 80%. At the time of operation, 74% of NHPHP patients had single adenomas. Intraoperatively postmobilization, using the same assay that was used preoperatively, 82% had PTH levels >60 pg/mL (mean, 279 pg/mL). During the follow-up period, iPTH levels remained lower among NHPHP patients (21 pg/mL) compared to 41 pg/mL for patients with preoperative iPTH 60 to 100 pg/mL and 56 pg/mL for patients with preoperative iPTH 100 to 200 pg/mL (P < .0001). CONCLUSION Lower PTH set points may exist in some patients with otherwise typical PHP features. Although high normal iPTH is inappropriate for hypercalcemia and should suggest PHP, this disorder may occur with iPTH levels as low as 5 pg/mL. Awareness of the unusual phenotype of NHPHP may facilitate earlier diagnosis and surgery.

Should patients with Cowden syndrome undergo prophylactic thyroidectomy

BACKGROUND Cowden syndrome (CS) is dominantly inherited and predisposes patients to tumors in multiple organs. We characterized CS-associated malignant and benign thyroid disease. METHODS Of data from 3,477 prospectively recruited CS patients with known genetic analysis, we analyzed 225 PTEN mutation+ patients whose treatment occurred at our center (n = 25) or other hospitals nationwide (n = 200). RESULTS A total of 32 of 225 PTEN mutation+ patients (14%) had thyroid cancer: 52% papillary, 28% follicular-variant papillary, 14% follicular, and 6% anaplastic. Median age at diagnosis was 35 years compared with 49 years for Surveillance Epidemiology and End Results population data. Initial thyroid ultrasonography in 16 of 25 patients revealed thyroiditis/goiters in all >13 years age, leading to FNA in 7 (64%), thyroidectomy in 3 (27%), and new cancer diagnosis in 2 (18%). Three with severe autism required intraoperative sedation for ultrasonography. A total of 9 of 25 patients were monitored after multiple partial thyroidectomies for goiters by age 42 (n = 5), thyroiditis, or cancer detected by age 36 (n = 3). CONCLUSION PTEN mutation+ patients with CS have an enormous prevalence of thyroid disease. Earlier screening may be advisable because thyroiditis and nodules are seen by the time patients reach adolescence, and cancer diagnosis occurs on average 14 years earlier than expected. Furthermore, the risks observed may justify prophylactic total thyroidectomy in select, if not all, patients, particularly those with developmental disorders.

Characteristics of Benign and Malignant Thyroid Disease in Familial Adenomatous Polyposis Patients and Recommendations for Disease Surveillance

BACKGROUND Familial adenomatous polyposis (FAP) is a hereditary colon cancer syndrome that involves multiple extracolonic organs, including the thyroid. Several studies have estimated the rate of thyroid cancer in FAP to occur at five times the rate of the general population, but no current consensus defines screening for thyroid cancer in this cohort. This study seeks to define the features of benign and malignant thyroid disease in FAP patients, to compare thyroid cancer cases found through screening with those found incidentally, and to propose disease surveillance recommendations. METHODS Prospective screening for early thyroid cancer detection with thyroid ultrasound (US) was performed on FAP patients at the time of annual colonoscopy since November 2008. Clinical and US data were reviewed to characterize the observed thyroid nodules. Nonscreening-detected cases (NSD) were found through review of the colon cancer registry database. RESULTS Eighteen NSD were found, compared with 15 screening-detected (SD) cases, out of 205 total patients screened (Mage=42 years; 55% female). The mean tumor size was larger in the NSD group than the SD group (p=0.04), and they tended to demonstrate more positive lymph nodes and more complications than the SD group. In the screened cohort, at least one thyroid nodule was detected in 106 (51.7%) patients, with 90% of these seen on initial exam. A total of 40/106 (37.7%) patients required fine-needle aspiration biopsy of a dominant nodule (Msize=14 mm), and 28/40 (70%) of these were performed at the first US visit. Suspicious US features were present in 16/40 (40%) patients, including five sub-centimeter nodules. Cytology and/or nodule US was abnormal in 15/205 screened patients, leading to surgery and revealing 14 papillary and one medullary thyroid cancer. CONCLUSIONS Given the age and sex distribution of the screened cohort, this study reveals a higher-than-expected prevalence of both benign and malignant thyroid disease in the FAP population. Additionally, SD cases seemed to consist of smaller-sized cancers that required less radical therapy compared to NSD cases. Since it was found that the initial US in the screening program accounted for the majority of detected nodules (90%) and biopsies (70%), baseline and subsequent thyroid US surveillance is recommended in all FAP patients.

Impact of localization studies and clinical scenario in patients with hyperparathyroidism being evaluated for reoperative neck surgery

BACKGROUND Previous studies have focused on the success of localization studies (LSs) in patients undergoing reoperative parathyroid surgery; however, patients who did not undergo reexploration surgery have been excluded from analysis. In addition, the concept of whether clinical scenario (CS) suggests single- vs multiple-gland disease in reoperative strategy is often underemphasized. OBJECTIVE To evaluate how LSs and CS direct operative strategy in patients being considered for reexploration. DESIGN Retrospective review of a prospective database. SETTING Tertiary referral center. PATIENTS Two hundred three patients with hyperparathyroidism who underwent previous neck surgery. The CS stratified patients as candidates for single- or multiple-site exploration (or unknown). MAIN OUTCOME MEASURE Ability of CS and LSs to direct successful reexploration. RESULTS Of 203 patients, 27 were not explored owing to nonlocalizing studies. Of the remaining 176 patients, LSs accurately guided reexploration in 85%. However, when including the 27 nonexplored patients, the success of LSs decreased to 73%. The cure rate in reoperated patients was 96% but was reduced to 83% when including nonexplored patients. Of the reoperated patients, 83% had single-site disease and 17% had multiple-site disease. The positive predictive value of LSs in predicting single- or multiple-site disease was 92% and 73%, respectively. However, when stratified by CS, the positive predictive value increased to 95% for single-site disease and to 100% for multiple-site disease. CONCLUSIONS Failure to cure patients was 4 times more likely to be due to nonlocalizing studies than to a failed reexploration. Stratification by CS was useful in the interpretation of LSs and in determining the most accurate reoperative approach.

The Endocrine Surgery Job Market: A Survey of Fellows, Department Chairs, and Surgery Recruiters

INTRODUCTION Fifty endocrine surgery (ES) fellows have completed their training since the American Association of Endocrine Surgeons initiated a formal match process in 2007. This study was designed to better understand the job prospects of current and future endocrine surgeons and to evaluate the evolution of ES practices nationwide. METHODS Three surveys were conducted of former fellows, surgery department chairs, and surgery recruiters. RESULTS Of former fellows, 90% are working in academic centers and 10% in private practice. Average number of job interviews was 3.1 and job offers was 2.2. Eighty-eight percent have a practice that attends to ≥50% ES cases, and 45% practice entirely ES. Ninety-eight percent are satisfied with their job. Subjectively, 57% believe that there are not enough job opportunities for young endocrine surgeons, and 50% believe that there are too many ES fellowships. Department chair survey showed that the average number of endocrine surgeons in their department increased from 1.3 to 2.2 in the past decade. A recognized ES section exists in 49% of centers, and 39% of chairs feel that they will need to recruit another endocrine surgeon in the next 2 years. Only 3 of 10 recruiters were familiar with ES, and all had<5 of their hiring institutions asking for endocrine surgeons. CONCLUSIONS To date, there have been adequate job opportunities to sustain currently trained endocrine surgeons. This contrasts with their subjective belief of limited job prospects. This information can guide the optimal number of fellowship positions and alerts the American Association of Endocrine Surgeons to the opportunity to promote the creation of formal ES sections.

Calculating an individual maxPTH to aid diagnosis of normocalemic primary hyperparathyroidism.

BACKGROUND We aimed to validate a nomogram for diagnosing primary hyperparathyroidism (PHP), particularly when normocalcemic PHP and vitamin D (VitD25) deficiency coexist. METHODS The nomogram calculates maximal upper limit of normal PTH unique for each person by maxPTH = 120 - [6*calcium] - [½*VitD25] + [¼*age]. PHP is suspected when serum PTH exceeds maxPTH. Normocalcemic PHP (NCPHP) was defined as always normal serum calcium (8.5-10.5 mg/dL) with PTH >60 pg/mL preoperatively and VitD25 deficiency as <31 ng/mL. RESULTS A total of 477 patients had operatively and histologically proven PHP. Overall and including those with classical presentation (high serum levels of calcium and PTH), the nomogram predicted PHP in 97% patients. A total of 66 had NCPHP: 47 with low VitD25 levels (20 ± 0.4 ng/mL) made initial PHP diagnosis challenging; 19 had normal VitD25 status. Although the level of serum calcium concentrations were equivalent in these 2 groups (10.1 ± 0.4 mg/dL), PTH was greater in patients with concurrent VitD25 deficiency (129 vs 97 pg/mL, P = .04). However, when used to calculate maxPTH, the nomogram predicted PHP correctly in all 66 NCPHP patients (100%). CONCLUSION The maxPTH nomogram functions as expected to classify patients with PHP and may aid in the diagnosis of NCPHP regardless of vitamin D status and repletion, reassuring primary providers and surgeons alike to embark on appropriate and timely PHP management.

A Rare Case of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Presenting in the Thyroid Gland

BACKGROUND Lymphoma involving the thyroid gland is rare. Diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma are the two most common histologic subtypes of primary thyroid lymphoma. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presenting initially as a thyroid abnormality is extremely rare, with very few reported cases in the literature. SUMMARY We report a case of a patient with a long history of Hashimotos thyroiditis and goiter who presented with a recent enlargement of her thyroid gland. The sonographic finding of a distinct thyroid nodule in the heterogeneous background of chronic lymphocytic thyroiditis led to the performance of a fine-needle aspiration biopsy and flow cytometry, with a high index of suspicion for thyroid lymphoma. Subsequent surgical removal of the thyroid gland, prompted by the patients history of head and neck radiation, confirmed the diagnosis of CLL/SLL. The patients systemic illness was recognized only after the management of her thyroid disease. Although thyroiditis has long been associated with lymphoma arising in the thyroid gland, CLL/SLL involving the thyroid has not been linked to chronic lymphocytic thyroiditis. Therefore, the patient also had coexisting thyroiditis. CONCLUSIONS Due to the rarity of thyroid lymphomas, our experience in the detection and management of this disease is limited. Primary thyroid lymphoma should be suspected in a patient with a history of chronic lymphocytic thyroiditis presenting with a rapidly enlarging neck mass. The initial diagnostic method for thyroid lymphoma should consist of a fine-needle aspiration biopsy with the use of ancillary techniques such as flow cytometry and immunohistochemistry for improved diagnostic accuracy. Although controversial, the treatment of thyroid lymphoma is typically guided by the histologic subtype and extent of disease. CLL/SLL is one of the rarest subtypes of lymphoma that can involve the thyroid gland. Diagnosis of this entity is difficult, particularly before the recognition of systemic involvement, requiring the expertise of a multidisciplinary team for early detection and optimal management.

Mapping endocrine surgery: Workforce analysis from the last six decades

BACKGROUND We analyzed the demographics of high-volume surgeons (HVS) for endocrine operations. METHODS We characterized HVS by region, specialty, gender, teaching-affiliation, American Association of Endocrine Surgeons (AAES) membership, and decade they entered practice. Providers were general surgeons (GS) and otolaryngologists (ENT); fellowship trained (FT) or not FT (NFT). RESULTS We identified 395 HVS in 47 states entering practice between 1958 and 2011. Sixty-eight percent were GS, 35% were FT, and 35% were AAES members. GS, FT surgeons, and endocrine surgery FT surgeons (ES) performed more operations per surgeon. More FT surgeons were in Northeast, West (W), and Midwest than Southeast (SE) and Southwest (SW; P < .0001). More teaching surgeons and AAES members were in the Northeast and Midwest than SE, W, and SW (P < .0001). FT-GS increased over decades (P < .0001) but not FT-ENT (P = .3). Representation of ES, AAES members, and females increased over decades (P < .0001). CONCLUSION The workforce for endocrine operations displayed increased representation of GS, FT surgeons, and women, correlating with the profile of recent AAES fellowship graduates. More insight is needed to understand why most HVS were not AAES members. Regional disparities can guide the placement of endocrine surgeons into both academic and community practices, increasing trainee exposure and patient access to specialty care.

Endocrine surgery fellowship graduates past, present, and future: 8 years of early job market experiences and what program directors and trainees can expect

Background. Given the increasing number of endocrine surgery fellowship graduates, we investigated if expectations and job opportunities changed over time. Methods. American Association of Endocrine Surgeons (AAES) fellowship graduates, surgery department chairs, and physician recruiters were surveyed. Univariate analysis was performed with JMP Pro 12 software. Results. We identified 141 graduates from 2008–2015; survey response rate was 72% (n = 101). Compared to earlier graduates, fewer academic opportunities were available for the recent graduates who intended to join them (P = .001). Unlike earlier graduates, recent graduates expected to also perform elective general surgery, which ultimately represented a greater percentage of their practices (both P < .05). Interview offers increased for recent graduates, but job offers decreased. Overall, 84% of graduates matched their intended practice type and 98% reported being satisfied. Reponses from graduates, department chairs, and physician recruiters highlighted opportunities to improve mentor involvement, job search strategies, and online job board utilization. Conclusion. The endocrine surgery job market has diversified resulting in more graduates entering nonacademic practices and performing general surgery. This rapid evolution supports future analyses of the job market and opportunities for job creation. Almost every graduate reported job satisfaction, which encourages graduates to consider joining both academic and nonacademic practices equally.