Hypertension in a Patient With Polycystic Kidney Disease Complicated by Concomitant Pheochromocytoma.

Background: Due to the high prevalence of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD) and advanced chronic kidney disease, diagnosing secondary hypertension poses challenges. We present a rare case of pheochromocytoma in an ADPKD patient to highlight the diagnostic difficulties in identifying secondary hypertension due to pheochromocytoma/paraganglioma (PPGL) in end-stage renal disease (ESRD) patients. Case Report: A 48-year-old female with ADPKD and ESRD experienced recurrent hypertensive crises (up to 220/135 mmHg) accompanied by palpitations and tremors that recurred over the past 2 years. Introduction of a betablocker to the antihypertensive therapy aggravated her symptoms. The initial documentation of elevated urinary metanephrines was interpreted as false positive finding due to renal failure. Subsequent measurements of free plasma metanephrines revealed significant elevations raising suspicion of PPGL. Magnetic resonance imaging identified a 29 mm right adrenal mass. The patient underwent right adrenalectomy resulting in resolution of the hypertensive crises. Discussion: The diagnosis of PPGLs can present significant challenges and is further complicated in ESRD due to nonspecific clinical symptoms and diagnostic pitfalls. Less than 20 PPGL cases have been reported in patients with ESRD. The intolerance of beta-blocker therapy, as well as the use of a scoring system for the likelihood of PPGL should have raised suspicion. Conclusion: PPGL should be considered in all patients with uncontrolled hypertension and beta-blockers intolerance, even in the presence of other etiologic mechanisms such as ESRD. Measuring free plasma metanephrines provides the most reliable biochemical screening in the context of impaired renal function.

Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section.

Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery. Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

Consumptive hypothyroidism in a patient with malignant rhabdoid tumor of the kidney: case report on a newly found association.

Introduction: Consumptive hypothyroidism is a rare paraneoplastic condition most commonly associated with infantile hemangiomas. It is caused by overexpression of deiodinase type 3 (D3), which leads to preferential conversion of thyroxine to the metabolically inactive reverse triiodothyronine (rT3), paralleled by a decrease of the biologically active T3. Case presentation: A 46-year-old male patient with previously normal thyroid function was diagnosed with a renal carcinoma with rhabdoid differentiation. He was treated with sunitinib, followed by the immune checkpoint inhibitors ipilimumab and nivolumab, and he developed primary hypothyroidism secondary to thyroiditis. Substitution with unusually high doses of levothyroxine as high as 4.3 µg/kg/day did not normalize his thyroid function. Poor compliance was refuted because there was no improvement after observed administration. He had no malabsorption. Although tyrosine kinase inhibitors can increase the expression of D3, this effect tends to be modest. Therefore, the suspicion of tumor-related consumptive hypothyroidism was raised and supported by low free T3 and elevated rT3 levels. The therapy could not be further modified because the patient opted for palliative care and passed away 12 days later. Immunohistochemistry of the tumor from a sample obtained prior to systemic therapy documented abundant expression of D3, corroborating the diagnosis of consumptive hypothyroidism. Conclusions: This observation extends the spectrum of malignancies overexpressing D3. Although rare, increased awareness of this paraneoplastic syndrome is key, if persistent hypothyroidism cannot be explained by compliance issues or malabsorption. Substitution with high doses of levothyroxine, and combination therapy with liothyronine, can correct hypothyroidism in these patients.

Is there a role for diagnostic scans in the management of intermediate-risk thyroid cancer?

Radioiodine (RAI) is selectively recommended for intermediate-risk differentiated thyroid carcinomas (DTC). The information gleaned from pretherapy stimulated thyroglobulin levels (sTg) and diagnostic 131I whole-body scans (DxWBS) to guide therapy remains controversial. The present study aimed at evaluating the impact of preablation sTg and DxWBS in the management of intermediate-risk DTC. A retrospective analysis of 301 intermediate-risk DTC patients submitted to total thyroidectomy and RAI therapy was performed. Pretherapy sTg and DxWBS and post-therapy WBS (RxWBS) findings were analyzed and compared to outcomes. Fifty-two patients (17.3%) had metastases diagnosed by DxWBS and/or RxWBS. The DxWBS identified 10.6% of patients with functioning metastases, including unexpected distant metastases. If combined with SPECT-CT, DxWBS detected RAI-avid metastases more frequently, particularly lymph node metastases (13.1% vs 4.2% planar WBS, P = 0.015). The DxWBS findings modified patient management in 8.3%. A pretherapy sTg <1 ng/mL was associated with a low false-negative rate for the presence of metastases (5.2%), and its performance in excluding metastasis was improved by a negative DxWBS (2.7% of patients with both negative exams had metastases in RxWBS). A sTg <1 ng/mL predicted statistically significant lower rates of recurrent/persistent disease and biochemical/structural incomplete responses. In conclusion, preablation sTg and DxWBS contribute to the detection of unknown or persistent metastatic disease in intermediate-risk DTC patients. A sTg <1 ng/mL in combination with a negative DxWBS is highly suggestive of the absence of remaining malignant disease, and one may consider deferring RAI ablation if both exams are negative. A stunning effect is rarely observed and it does not impair proper treatment of metastases.

Thyroid and Breast Cancer in 2 Sisters With Monoallelic Mutations in the Ataxia Telangiectasia Mutated (ATM) Gene.

The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of the breast at 44 and 42 years. The 2 children of the younger sister developed ataxia-telangiectasia; the son also developed lymphoblastic lymphoma and his sister died secondary to acute lymphoblastic leukemia (ALL). They were found to be compound heterozygous for ataxia telangiectasia mutated (ATM) gene mutations (c.3848T>C, p.L1283P; and c.802C>T, p.Q268X). Exome sequencing of the 2 sisters (mother and aunt of the children with ataxia-telangiectasia) led to the detection of the pathogenic monoallelic ATM mutation in both of them (c.3848T>C; minor allele frequency [MAF] < 0.01) but detected no other variants known to confer a risk for PTC or breast cancer. The findings suggest that monoallelic ATM mutations, presumably in conjunction with additional genetic and/or nongenetic factors, can confer a risk for developing PTC and breast cancer.

What's in a Name? A Cost-Effectiveness Analysis of the Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features' Nomenclature Revision.

Background: The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. Objective: To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC. Methods: A cost-effectiveness analysis was performed by creating Markov models to simulate two management strategies for NIFTP: (i) de-escalated management of the tumor as NIFTP involving lobectomy with reduced follow-up, (ii) management of the tumor as eFVPTC involving completion thyroidectomy/radioactive iodine ablation for some patients, and follow-up recommended for carcinoma. The model was simulated for 5 and 20 years following diagnosis of NIFTP. Aggregate costs and quality-life years were measured. One-way sensitivity analysis was performed for all variables. Results: Over a five-year simulation period, de-escalated management of NIFTP had a total cost of $12,380.99 per patient while the more aggressive management of the tumor as eFVPTC had a total cost of $16,264.03 per patient (saving $3883.05 over five years). Management of NIFTP provided 5.00 quality-adjusted life years, whereas management as eFVPTC provided 4.97 quality-adjusted life years. Sensitivity analyses showed that management of NIFTP always resulted in lower costs and greater quality-adjusted life years (QALYs) over the sensitivity ranges for individual variables. De-escalated management for NIFTP is expected to produce ∼$6-42 million in cost savings over a five-year period for these patients, and incremental 54-370 QALYs of increased utility in the United States. Conclusion: The degree of cost savings and improved patient utility of de-escalated NIFTP management compared with traditional management was estimated to be $3883.05 and 0.03 QALYs per patient. We demonstrate that these findings persisted in sensitivity analysis to account for variability in recurrence rate, surveillance approaches, and other model inputs. These findings allow for greater understanding of the economic and QOL impact of the NIFTP reclassification.

Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases.

Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team.

[Anaplastic thyroid carcinoma : new therapeutic approaches]. / Carcinome anaplasique de la thyroïde : nouvelles approches thérapeutiques.

Anaplastic thyroid cancer (ATC) is among the most aggressive cancers with a median overall survival of 4 months and a disease-specific mortality of close to 100%. As soon as the diagnosis is suspected or established, urgent referral to an experienced multidisciplinary center is imperative. Chemotherapy has limited efficacy. Molecular analyses, together with the availability of novel targeted therapies and immunotherapies, now permit to improve outcomes. In particular, targeted therapy with dabrafenib and trametinib is indicated as first-line therapy for BRAF V600E-mutated ATC.

Le cancer anaplasique de la thyroïde (CAT) compte parmi les cancers les plus agressifs avec une survie médiane de 4 mois et une mortalité spécifique à la maladie proche de 100 %. Dès que le diagnostic est suspecté ou établi, une orientation urgente vers un centre multidisciplinaire expérimenté est essentielle. La chimiothérapie a une efficacité limitée. Les analyses moléculaires, ainsi que la disponibilité de nouvelles thérapies ciblées et d'immunothérapies, permettent désormais d'améliorer les résultats. En particulier, le CAT avec mutation BRAF V600E bénéficie d'une combinaison de thérapies ciblées par dabrafénib et tramétinib en traitement de première ligne.

Denosumab for the Treatment of Hypercalcemia in a Patient With Parathyroid Carcinoma: A Case Report.

Background: Refractory hypercalcemia is one of the major complications of parathyroid carcinoma. Case report: An 84-year old female patient presented with an acute confusional state due to hypercalcemia. This led to the diagnosis of primary hyperparathyroidism for which she underwent surgery. The initial histological diagnosis was interpreted as atypical parathyroid adenoma; the resection was microscopically incomplete. One year later, the patient presented with elevated calcium levels up to 3.89 mmol/l. Recurrent severe hypercalcemia required multiple hospitalizations. Review of the histology slides revealed that the initially resected lesion was in fact a parathyroid carcinoma. Treatment with the calcimimetic drug cinacalcet was poorly tolerated. Repeated administration of zoledronic acid only had transient effects on calcium levels, and bisphosphonate treatment was ultimately discontinued because of chronic renal failure. The patient then received denosumab (60 or 120 mg) when needed (nine doses over twenty months), the last dose in November 2020, which led to a reduction and control of here calcium levels. Currently, at three years after initial surgery, calcium levels are stable between 2.7-2.8 mmol/l and the patient has not required hospitalization for hypercalcemia for 10 months. Discussion: In case of parathyroid carcinoma, en-bloc resection is the first treatment. Denosumab has proven its efficiency in treating hypercalcemia in malignancy. Several case reports studied denosumab in hypercalcemia due to parathyroid carcinoma, and the treatment were efficient to decrease levels of calcium when repeated as needed or monthly. We report another case of refractory hypercalcemia treated with several doses of denosumab in a patient with parathyroid carcinoma.

Incidence trends of lung and gastroenteropancreatic neuroendocrine neoplasms in Switzerland.

The incidence of neuroendocrine neoplasms (NENs) seems to increase worldwide. Long-term, population-based series that consider tumor differentiation are, however, sparse. We assessed the incidence trend of lung and gastroenteropancreatic (GEP) NENs according to the latest International Agency for Research on Cancer/World Health Organization classification over a 41-year time period in two Swiss regions. All cases of lung and GEP NENs recorded in the Vaud and Neuchâtel Cancer Registries from 1976 to 2016 were included. NENs were stratified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Changes in annual age-standardized incidence rates were calculated for lung and GEP NETs and NECs by sex. Of 4,141 patients diagnosed with NENs, 65% were men. The incidence of lung NETs among men and women increased by 3.9%/year (95% CI: -5.3, 14.1%) and 4.9%/year (0.1, 9.9%), respectively, between 1976 and 2016. The incidence of lung NECs decreased by 2.6%/year (-3.1,-1.8%) in men from 1985 to 2016 whereas it increased in women between 1976 and 1998 by 6%/year (4.2, 7.9%). For GEP NETs, a steady annual increase in incidence occurred between 1976 and 2016 with a magnitude of 1.7% (0.7, 2.7%) in men and 1.3% (0.5, 2.1%) in women. No significant trend in incidence of GEP NECs was found for both sexes. The incidence trends of lung NECs in men and women parallel changes in smoking prevalence in the population. Causes of the increase in incidence of GEP NETs are likely multifactorial. Our study supports the importance of evaluating the epidemiology of NENs by tumor differentiation.

Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/ß-catenin pathway.

OBJECTIVE: Genomic alterations in Hürthle cell carcinomas (HCC) include chromosomal losses, mitochondrial DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/ß-catenin pathways. This study aimed at characterizing the mutational profile of HCC. METHODS: Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/ß-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/recurrent disease, but there were no cancer-related deaths. RESULTS: Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/ß-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features. CONCLUSIONS: This series of HCC presents a wide range of mutations in the Wnt/ß-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/ß-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/ß-catenin pathway plays a critical role in this distinct thyroid malignancy.

The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System.

BACKGROUND: Thyroid follicular cells have physiologically high levels of reactive oxygen species because oxidation of iodide is essential for the iodination of thyroglobulin (Tg) during thyroid hormone synthesis. Thyroid follicles (the functional units of the thyroid) also utilize incompletely understood autoregulatory mechanisms to defend against exposure to excess iodide. To date, no transcriptomic studies have investigated these phenomena in vivo. Nuclear erythroid factor 2 like 2 (Nrf2 or Nfe2l2) is a transcription factor that regulates the expression of numerous antioxidant and other cytoprotective genes. We showed previously that the Nrf2 pathway regulates the antioxidant defense of follicular cells, as well as Tg transcription and Tg iodination. We, thus, hypothesized that Nrf2 might be involved in the transcriptional response to iodide overload. METHODS: C57BL6/J wild-type (WT) or Nrf2 knockout (KO) male mice were administered regular water or water supplemented with 0.05% sodium iodide for seven days. RNA from their thyroids was prepared for next-generation RNA sequencing (RNA-Seq). Gene expression changes were assessed and pathway analyses were performed on the sets of differentially expressed genes. RESULTS: Analysis of differentially expressed messenger RNAs (mRNAs) indicated that iodide overload upregulates inflammatory-, immune-, fibrosis- and oxidative stress-related pathways, including the Nrf2 pathway. Nrf2 KO mice showed a more pronounced inflammatory-autoimmune transcriptional response to iodide than WT mice. Compared to previously published datasets, the response patterns observed in WT mice had strong similarities with the patterns typical of Graves' disease and papillary thyroid carcinoma (PTC). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also responded to iodide overload, with the latter targeting mRNAs that participate mainly in inflammation pathways. CONCLUSIONS: Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves' disease) and PTC.

Toxicity and cosmetic outcome after hypofractionated whole breast irradiation and boost-IOERT in early stage breast cancer (HIOB): First results of a prospective multicenter trial (NCT01343459).

BACKGROUND AND PURPOSE: To assess the role of intraoperative radiation with electrons (IOERT) as tumor bed boost followed by hypofractionated whole breast irradiation (HWBI) after breast conserving surgery (BCS) of patients with low to intermediate risk breast cancer focusing on acute/late toxicity and cosmetic outcome. MATERIAL AND METHODS: In 2011, a prospective multicenter trial (NCT01343459) was started. Treatment consisted of BCS, IOERT (11.1 Gy) and HWBI (40.5 Gy in 15 fractions). In a single-arm design, 5-year IBR-rates are benchmarked by a sequential ratio test (SQRT) against best published evidences in 3 age groups (35-40 y, 41-50 y, >50 y). Acute/late toxicity and cosmesis were evaluated by validated scorings systems. RESULTS: Of 627 eligible patients, 44 were excluded, leaving 583 to analyze. After a median follow-up (FUP) of 45 months (range 0-74), for acute effects CTCAE-score 0/1 was noted in 91% (end of HWBI) and 92% (4 weeks later), respectively. Late toxicity Grading 0/1 (mean values, ranges) by LENT-SOMA criteria were observed in 92.7% (89-97.3) at 4/5 months, rising to 96.5% (91-100) at 6 years post HWBI. Baseline cosmesis after wound healing prior to HWBI was scored as excellent/good in 86% of cases by subjective (patient) and in 74% by objective (doctor) assessment with no impairment thereafter. CONCLUSIONS: Acute and late treatment tolerance of a combined Boost-IOERT/HWBI regimen is excellent in short/mid-term assessment. Postoperative cosmetic appearance is not impaired after 3 years FUP.

A Survey of American Thyroid Association Members Regarding the 2015 Adult Thyroid Nodule and Differentiated Thyroid Cancer Clinical Practice Guidelines.

Background: The 2015 American Thyroid Association (ATA) clinical practice guidelines (CPGs) on management of thyroid nodules (TNs) and differentiated thyroid cancer (DTC) in adults were developed to inform clinicians, patients, researchers, and health policy makers about the best available evidence, and its limitations, relating to management of these conditions. Methods: We conducted a cross-sectional electronic survey of ATA members' perspectives of these CPGs, using a standardized survey (Clinician Guidelines Determinant Questionnaire) developed by the Guidelines International Network. A survey link was electronically mailed to members in February of 2019, with reminders sent to nonrespondents 2 and 5 weeks later. Data were descriptively summarized, after excluding missing responses. Results: The overall response rate was 19.8% (348/1761). The effective response rate was 20.2% (348/1720), after excluding a recently deceased member and individuals who had either invalid e-mail addresses or whose e-mails were returned. Of the respondents, 37.9% (132/348) were female, 60.4% (209/346) were endocrinologists, 27.5% (95/346) were surgeons, and 3.5% (12/346) were nuclear medicine specialists. The majority of respondents (71.9%; 250/348) were at a mid- or advanced-career level, and more than half were in academia (57.5%; 195/339). The majority (69.8%; 243/348) practiced in North America. The vast majority of respondents indicated that the CPGs explained the underlying evidence (92.3%; 298/323) and 92.9% (300/323) agreed or strongly agreed with the content. Most respondents stated that they regularly used the CPGs in their practice (83.0%; 268/323). Most respondents (83.0%; 268/323) also agreed or strongly agreed that the recommendations were easy to incorporate in their practice. The most popular CPG format was an electronic desktop file (78.8%; 252/320). Shorter more frequent CPGs were favored by 55.0% (176/320) of respondents, and longer traditional CPGs were favored by 39.7% (127/320). Conclusions: The clinical content and evidence explanations in the adult TN and DTC CPGs are widely accepted and applied among ATA survey respondents. Future ATA CPG updates need to be optimized to best meet users' preferences regarding format, frequency, and length.

Impact of non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) on risk of malignancy in patients undergoing lobectomy/thyroidectomy for suspected malignancy or malignant fine-needle aspiration cytology findings: a systematic review and meta-analysis.

OBJECTIVE: The second version of The Bethesda System for Reporting Thyroid Cytopathology endorsed the introduction of non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) as a distinct entity with low malignant potential into clinical practice. Consequently, the risk of malignancy (ROM) of cytological diagnoses has changed, but the magnitude of the change remains uncertain. The present systematic review was undertaken to obtain more robust information about the true impact of NIFTP on the ROM among patients undergoing surgery following a fine-needle aspiration cytology (FNAC) diagnosis of suspicious for malignancy (Bethesda V) or malignant (Bethesda VI). As they are managed surgically, these two diagnostic categories are the primary entities that are clinically impacted by the advent of NIFTP. DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive literature search of online databases was performed in November 2018. The search was conducted looking for data of histologically proven NIFTP with preoperative FNAC. RESULTS: One-hundred fifty-seven articles were identified and nine were included in the study. Overall, there were 13,752 thyroidectomies with a cancer prevalence of 45.7%. When NIFTP was considered non-malignant, the pooled risk difference for ROM was 5.5%. Applying meta-analysis, the pooled prevalence of NIFTP among nodules with FNAC of Bethesda V or Bethesda VI was 14 and 3%, respectively. CONCLUSION: This meta-analysis shows that the inclusion of NIFTP leads to a reduction in the ROM for the Bethesda V and Bethesda VI FNAC diagnostic categories by 14 and 3%, respectively. Clinicians should be aware of these data to avoid overtreatment.

ECTOPIC ADRENOCORTICOTROPIC HORMONE SYNDROME DUE TO METASTATIC PROSTATE CANCER WITH NEUROENDOCRINE DIFFERENTIATION.

OBJECTIVE: Neuroendocrine differentiation of prostate cancer can result in ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) and Cushing syndrome. The aim of this report is to highlight this unusual mechanism of hypercortisolism and its management. METHODS: We report a 73-year-old patient with a history of prostate adenocarcinoma who presented with severe weakness, hyperglycemia, and hypokalemia caused by EAS. RESULTS: Diagnostic workup showed elevated 24-hour urine cortisol and ACTH levels consistent with EAS. Fluorodeoxyglucose positron emission tomography-computed tomography revealed a hypermetabolic mass in the prostate and metastatic lesions to the liver and bones. Liver biopsy was consistent with small cell carcinoma with positive immunostaining for ACTH. Pleural fluid analysis was consistent with high-grade neuroendocrine carcinoma. The patient underwent chemotherapy with carboplatin and etoposide. Hypercortisolism was treated with ketoconazole, metyrapone, mifepristone, and spironolactone. He suffered complications including opportunistic infections, deep venous thrombosis, and delirium. Given his poor prognosis and clinical decline, the patient opted for comfort measures only in a hospice facility. CONCLUSION: Treatment-related neuroendocrine differentiation of prostate cancer is an emerging entity that may be associated with paraneoplastic syndromes including EAS.

NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018.

The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, Hürthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E-mutated anaplastic thyroid carcinoma.