MEN1 in a Patient With Nonsyndromic Familial Nonmedullary Thyroid Carcinoma.

Clinical syndromes involving multiple endocrine glands have been well recognized for over a century. Multiple reports describing hereditary multiple endocrine neoplasia (MEN) syndromes involving pituitary, parathyroid, and pancreatic neuroendocrine tumors have been published. Differentiated (nonmedullary) thyroid cancer can also present as a hereditary syndrome with or without a specific genetic predisposition. We report the case of a man with nonsyndromic familial nonmedullary thyroid carcinoma, a pituitary adenoma, hyperparathyroidism, an adrenal adenoma, and pancreatic adenocarcinoma. Genetic testing did not reveal mutations in the commonly reported genes associated with MEN syndromes. MEN1 is characterized by endocrine neoplasia in at least 2 of the following glands: pituitary, parathyroid, and the gastro-entero-pancreatic (GEP) tract. Co-occurrence of MEN1 with familial nonmedullary thyroid carcinoma, however, has not been reported in the medical literature. This unique case of MEN1 co-existing in a patient with nonsyndromic familial thyroid carcinoma was not associated with any common MEN syndrome germline mutations.

Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies.

OBJECTIVE: Detection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer. METHODS: We performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb-) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years. RESULTS: Patients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis. CONCLUSION: We conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.

Myxedema Coma Associated with Macroprolactinoma: Case Report and Review of the Literature.

Myxedema coma is a rare life-threatening presentation of severe hypothyroidism associated with a high mortality rate. Although most cases are due to primary thyroid failure, a minority have central hypothyroidism as the underlying cause. We report the case of a 69-year-old man who presented with obtundation, hypoglycemia, and hyponatremia. The patient's initial thyroid-stimulating hormone (TSH) was within normal limits. Subsequent evaluation revealed critical anterior pituitary insufficiency due to a macroprolactinoma and a diagnosis of myxedema coma after appropriate workup The finding of a normal serum TSH should not eliminate the possibility of myxedema coma.

The Evolving Role of the Orthopaedic Surgeon in Combat Zones and Austere Deployed Locations Since the 2012 Troop Drawdown.

The purpose of this study was to evaluate the operative experience of orthopaedic surgeons in the various deployment locations since 2012. We also evaluated the implications of humanitarian surgical care and the impact of deployment on an orthopaedic practice. An emailed survey was sent to orthopaedic surgeons deployed after 2012. The survey was 48 questions. Most cases in Iraq, Afghanistan and Syria were emergent traumas. In other locations, however, most cases were elective/non-emergent cases. Of surgeons surveyed, 44% performed less than 10 cases during their deployment, and 50% considered humanitarian surgery part of their mission. Six weeks was needed to prepare for deployment, and 4.4 weeks to re-build a practice. Disparity exists in surgical case volume and types of cases performed by orthopaedic surgeons that is dependent on deployed location. This dichotomy in operative experience places surgeons deployed to such locations at risk of losing surgical skills. (Journal of Surgical Orthopaedic Advances 29(3):182-186, 2020).

A BRAF V600E Mutation in RET-Negative Medullary Thyroid Cancer.

We report the case of a woman with a sporadic medullary thyroid carcinoma. Genomic analysis found that her tumor did not contain any common RET mutations but did harbor a BRAF V600E mutation. Only one other well-confirmed example of the BRAF V600E mutation has been reported in an MTC patient. We conclude that this common BRAF mutation may independently drive neoplastic transformation of human parafollicular C cells.

Features of Multiple Endocrine Neoplasia Type 1 and 2A in a Patient with Both RET and MEN1 Germline Mutations.

The coexistence of multiple endocrine neoplasia type 1 (MEN1) and type 2A (MEN2A) is a rare occurrence and has been reported only twice in the literature. We present a patient with primary hyperparathyroidism and medullary thyroid cancer with strong family history of both MEN1- and MEN2A-associated conditions. Genetic testing showed the patient had a novel MEN1 loss-of-function mutation, c0.525_526insTT (p.Ala176Leufs*10), and an uncommon Cys630Tyr RET mutation. This case highlights the importance of obtaining a detailed family history when heritable endocrine disorders are suspected.

Clinical Features in Differentiated Thyroid Carcinoma Stratified By Lymph Node Status.

OBJECTIVE: Cervical lymph node (CLN) metastases (mets) often occur in differentiated thyroid cancer (DTC), especially in the central compartment, and are a major predictor of local recurrence. We examined clinical endpoints in three groups of patients based on status of lymph node involvement: those with definite lymph node involvement (N1), negative lymph nodes (N0), and no lymph nodes resected (Nx). We correlated these endpoints with clinical and pathologic features of these patients. METHODS: Medical records of 261 patients with DTC who underwent thyroidectomy between 2006 and 2018 at our center were reviewed. Lymph node status of patients was categorized based on American Joint Committee on Cancer (AJCC) 8th edition criteria as N1, N0, and Nx. We performed statistical analysis to assess the differences among these groups, using one-way analysis of variance. When significant differences were found, pairwise comparisons were conducted among the three groups. Statistical significance was defined as 2-tailed P<.05 for all tests. RESULTS: There were significant differences among the groups in tumor multicentricity, tumor category/size, AJCC stage, and the presence of thyroglobulin auto-antibodies (TgAbs). There were no difference in age, gender, or histopathology. N1 patients had a higher incidence of multicentricity, larger tumor sizes, and were more likely to have elevated TgAbs. There were no significant differences between the N0 and Nx groups. CONCLUSION: This study shows that larger and multi-centric tumors are associated with increased likelihood of CLN mets in DTC. We suggest increased vigilance for CLN mets in tumors >2 cm, multicentric tumors, and patients with elevated TgAbs. ABBREVIATIONS: AJCC = American Joint Committee on Cancer; CLN = cervical lymph node; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; mets = metastases; N0 = no cancer in any lymph nodes; N1 = cancer in a lymph node; N1a = cancer in a central compartment lymph node; N1b = cancer in a lateral neck lymph node; Nx = lymph nodes not resected or examined; PTC = papillary thyroid cancer; TgAb = thyroglobulin auto-antibody.

Comparison of Direct Patient Care Costs and Quality Outcomes of the Teaching and Nonteaching Hospitalist Services at a Large Academic Medical Center.

PURPOSE: To compare costs of care and quality outcomes between teaching and nonteaching hospitalist services, while testing the assumption that resident-driven care is more expensive. METHOD: Records of inpatients with the top 20 Medicare Severity Diagnosis-Related Groups admitted to the University Teaching Service (UTS) and nonteaching hospitalist service (NTHS) at Houston Methodist Hospital from 2014-2015 were analyzed retrospectively. Direct costs of care, length of stay (LOS), in-hospital mortality (IHM), 30-day readmission rate (30DRR), and consultant utilization were compared between the UTS and NTHS. Propensity score matching and case mix index (CMI) were used to mitigate differences in baseline characteristics. To compare outcomes between matched groups, the Wilcoxon rank sum test and chi-square test were used. A sensitivity analysis was conducted using multivariable regression analysis. RESULTS: From the overall study population of 8,457 patients, 1,041 UTS and 3,123 NTHS patients were matched. CMI was 1.07 for each group. The UTS had lower direct costs of care per case ($5,028 vs. $5,502, P = .006), lower LOS (4.7 vs. 5.2 days, P = .0002), and lower consultant utilization (1.0 vs. 1.6, P ≤ .0001) versus the NTHS. The UTS and NTHS 30DRR (17.2% vs. 19.3%, P = .110) and IHM (2.9% vs. 3.7%, P = .206) were comparable. The multivariable regression analysis validated the matched data and identified an incremental cost savings of $333/UTS patient. CONCLUSIONS: Patients of an academic hospitalist service had significantly shorter LOS, fewer consultants, and lower direct care costs than comparable patients of a nonteaching service.

PANCREAS METASTASES FROM PAPILLARY THYROID CARCINOMA: A REVIEW OF THE LITERATURE.

OBJECTIVE: Although locoregional metastases occur in 5 to 10% of patients with papillary thyroid cancer (PTC), distant metastases are rare, especially to the pancreas. Here we review the literature regarding metastases to the pancreas from PTC and present an illustrative patient. METHODS: The literature search was performed through using the PubMed database. The information regarding our illustrative case was obtained from the medical records of our institution. RESULTS: Since 1991, 11 cases of pancreas metastases of PTC have been reported. The average age at diagnosis was 55.3 years. There were 8 males and 3 females. Three had classic PTC histology, 2 had tall cell variant, and 2 had follicular variant. Four had T4 tumors, and 2 had T3 tumors. Seven had thyroid cancer spread to regional lymph nodes. One had distant metastasis. Pancreas metastases were diagnosed from 1 month to 13 years after primary PTC was detected; the average was 7 years. Our patient was an 84-year-old female diagnosed with PTC with a BRAFV600E mutation following total thyroidectomy. A whole-body scan after radioactive iodine (RAI) remnant ablation was negative for metastases. A pancreatic tumor was identified 2 years later on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan. A biopsy of the tumor was histologically similar to PTC and positive for thyroglobulin, thyroid transcription factor-1, and the BRAFV600E mutation. CONCLUSION: The biological reasons why PTCs metastasize to the pancreas remain to be elucidated. Older patients with non-RAI avid, FDG-PET-positive metastases, and symptoms of pancreatitis are at increased risk of this rare entity. ABBREVIATIONS: FDG = fluorodeoxyglucose FNA = fine-need aspiration PTC = papillary thyroid cancer RAI = radioactive iodine Tg = thyroglobulin TgAb = antithyroglobulin antibodies TNM = tumor-node-metastasis.

Cardiovascular Disease in Acromegaly.

In patients with acromegaly, chronic excess of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) leads to the development of acromegalic cardiomyopathy. Its main features are biventricular hypertrophy, diastolic dysfunction, and in later stages, systolic dysfunction and congestive heart failure. Surgical and/or pharmacological treatment of acromegaly and control of cardiovascular risk factors help reverse some of these pathophysiologic changes and decrease the high risk of cardiovascular complications.

LOWER RATES OF RESIDUAL/RECURRENT DISEASE IN PATIENTS WITH INCIDENTALLY DISCOVERED THYROID CARCINOMA.

OBJECTIVE: Incidentally discovered thyroid cancers (IDTCs) have contributed to the rapid rise in thyroid cancer incidence over the past 20 years. Since death rates from thyroid cancer are not increasing, we hypothesized that IDTCs are less aggressive compared to clinically apparent thyroid cancer (CATC). METHODS: A retrospective study of patients and tumor characteristics of IDTCs and their rates of residual/recurrent (R/R) disease were determined at a median follow-up of 27 months in the setting of a large academic medical center. Patient analysis groups (IDTC [n = 46] and CATC [n = 126]) were based upon how the cancer was initially discovered. Patients were followed clinically and by biochemical testing and ultrasonography. We also compared time to progression between these groups. RESULTS: Patients in the two groups had similar demographic and tumor characteristics. At the close of the study, R/R status in the IDTC group was 6.7%, compared to 20.8% in the CATC group (P = .04). Of the 28 individuals in our overall cohort who had R/R disease, 3 were from the IDTC group and 25 were from the CATC group (P = .04). All three of the IDTC recurrences occurred within the first 6 months of follow-up. Using Kaplan-Meier analysis, there was a nonsignificant trend for longer progression-free survival in the IDTC group (P = .08). CONCLUSION: Compared to CATC patients, IDTC patients have a significantly less aggressive course and a trend toward longer progression-free survival. If confirmed by further studies, it may be reasonable to subject them to less intense surveillance and more conservative therapeutic approaches. ABBREVIATIONS: CATC = clinically apparent thyroid cancers CT = computed tomography HMH = Houston Methodist Hospital IDTC = incidentally discovered thyroid cancer MRI = magnetic resonance imaging PET = positron emission tomography PTMC = papillary thyroid microcarcinoma R/R = residual/recurrent RRA = radioiodine remnant ablation Tg = thyroglobulin TgAb = anti-thyroglobulin antibody TSH = thyroid-stimulating hormone US = ultrasonography.

Hürthle cell carcinoma of the thyroid presenting as thyrotoxicosis.

OBJECTIVE: To report a case of hyperthyroidism associated with Hürthle cell carcinoma and to review the literature regarding this relationship. METHODS: We describe the clinical, biochemical, radiologic, and pathologic data of a patient with Hürthle cell carcinoma associated with thyrotoxicosis and reversible heart failure. We discuss the mechanistic aspects and review previously reported cases of functional Hürthle cell carcinomas. RESULTS: A 43-year-old woman presented with thyrotoxicosis and nonischemic cardiomyopathy. She had a "hot" nodule in the left lobe of the thyroid on sodium pertechnetate scan. She underwent a left hemithyroidectomy and isthmusectomy. Pathologic findings revealed a minimally invasive Hürthle cell carcinoma. On follow-up, the dilated cardiomyopathy had resolved. The association of thyroid carcinoma with thyrotoxicosis is rare. CONCLUSIONS: Some Hürthle cell carcinomas can be functional and lead to thyrotoxicosis. To our knowledge, we present the first case of reversible dilated cardiomyopathy due to thyrotoxicosis originating from Hürthle cell carcinoma.

The value of positron emission tomography (PET) in the management of patients with thyroid cancer.

For more than a decade, positron emission tomography (PET) has had an important role in the management of thyroid cancer patients. It may be involved in initial, sometimes inadvertent, diagnosis; in postoperative evaluation; in detection of occult metastases; in the evaluation of thyroid nodules; and in prognostication of metastatic disease. In this review we will update the advances in the application of PET scanning to optimal patient management. The majority of the published studies to date have used 18F-fluoro-deoxyglucose (FDG) as the PET isotope, and unless specifically noted, all references to PET scanning will imply that this tracer has been used.

Recombinant human TSH-assisted radioactive iodine remnant ablation achieves short-term clinical recurrence rates similar to those of traditional thyroid hormone withdrawal.

UNLABELLED: Recent studies have confirmed that radioactive iodine therapy after recombinant human TSH (rhTSH) stimulation effectively ablates the normal thyroid remnant. However, no published study has determined the effectiveness of rhTSH preparations on the important endpoint of disease recurrence. METHODS: Disease recurrence was retrospectively assessed a median of 2.5 y after radioiodine remnant ablation (RRA) in 394 consecutive thyroid cancer patients (93% papillary, 71% female, 47+/-15 y old [mean +/- SD], median (131)I dose of 3,996 MBq [108 mCi]). RESULTS: Similar rates of clinically evident disease recurrence (4% rhTSH vs. 7% thyroid hormone withdrawal [THW], P=not statistically significant) and residual thyroid bed uptake without other evidence of persistent disease (4% rhTSH vs. 7% THW, P=not statistically significant) were seen in the 320 patients undergoing rhTSH-assisted RRA and the 74 patients prepared for RRA by THW. When the definition of no clinical evidence of disease included a suppressed thyroglobulin level of less than 1 ng/mL and a stimulated thyroglobulin level of less than 2 ng/mL, rhTSH-assisted RRA was associated with significantly higher rates of no clinical evidence of disease (74% rhTSH vs. 55% THW, P=0.02) and significantly lower rates of persistent disease (19% rhTSH vs. 32% THW, P=0.02) than was RRA after THW. Patients selected for rhTSH-assisted RRA were older (48+/-15 vs. 44+/-15 y, P=0.03) and received a slightly higher administered activity of (131)I (median, 4,033 MBq [109 mCi] vs. 3,811 MBq [103 mCi], P=0.01) but did not differ with respect to sex, histology, disease stage, or mean time to recurrence (19+/-9 mo for rhTSH vs. 20+/-16 mo for THW). CONCLUSION: rhTSH-assisted RRA is associated with rates of clinically evident disease recurrence and persistent uptake in the thyroid bed that are similar to those for traditional THW.