Thyroid cancer can be largely classified as well-differentiated, poorly differentiated, medullary and anaplastic. Differentiated thyroid cancer (DTC) includes follicular and papillary subtypes, with the incidence of papillary thyroid cancer (PTC) on the rise. The mainstay of treatment for DTC includes a combination of surgery, radioactive iodine (RAI) and levothyroxine suppression. DTC portends a favorable prognosis, even in the presence of distant metastases, with a 50% rate of 5-year survival largely due to tumor cell’s sensitivity to RAI therapy influencing disease outcome. In radioactive iodine refractory differentiated thyroid cancer (RAI-refractory DTC) there is a lower survival rate prompting the use of other therapeutic options available. RAI refractoriness is more common in older patients (age >40), large metastases and lesions that are fluorodeoxyglucose (FDG) avid on position emission tomography (PET). Over the past decade, Identification of genetic mutations in the signaling pathway involved in thyroid tumorigenesis has led to the approval of tyrosine kinase inhibitors (TKIs); Sorafenib and Lenvatinib in RAI-refractory DTC. Similarly, metastatic medullary thyroid cancer (MTC) implies an unfavorable 10-year survival rate of only 20% as the principal treatment options focuses on loco regional control via surgical and/or non-surgical options. The approval of TKIs such as Cabozantinib and Vandetanib has introduced an encouraging, novel, systemic therapeutic option for metastatic MTC. Lastly, anaplastic thyroid cancer (ATC) carries the worst prognosis with high recurrence rates. Treatment includes surgery, chemotherapy and external beam radiation. The FDA recently approved Dabrafenib plus trametinib for BRAF V600E mutated ATC. Considering the modality of chemotherapy and the expanding field of targeted therapies, the role of the oncologist and interaction with endocrinologist in the management of thyroid cancer needs further clarification aiming at collaborative management plans more than ever. This review summarizes the key phase III trials that led to the approval of TKIs in the treatment of DTC and metastatic MTC. Additionally, the review aims to clarify the patient selection criteria for initiation of TKIs and examine the implications, considerations and adverse effects prior to utilizing targeted therapy. Clinical trials are ongoing with promising results and may contribute to the addition of several targeted molecules and immune check point inhibitors to the therapeutic armamentarium for RAI-refractory DTC, medullary and anaplastic thyroid cancer.

Introduction: A relationship between hyperglycemia and outcomes in patients with COVID-19 has been proposed, however there is a paucity of literature on this. In this study, we examined the effect of admission glucose in diabetics and non-diabetics on outcomes in patients hospitalized with COVID-19. Our study uniquely examines this association in a largely African American cohort, a population disproportionately affected by COVID-19. Methods: In this retrospective cohort study, we analyzed all adults admitted with COVID-19 to a designated COVID hospital in Brooklyn, NY from March 1 to May 15, 2020. Diabetics were compared to non-diabetics, and were further stratified based on admission glucoses of 140 and 180 mg/dL. Diagnosis of diabetes was based on history and/or Hba1c > 6.5%. Univariate, multiple and logistic regressions were used for analyses, examining outcomes of mortality, intubation, ICU admission, acute kidney injury (AKI), and length of stay based on admission glucose levels, while controlling for age, gender, lab values (serum creatinine and WBC), and comorbidities including hypertension, cardiovascular disease, and obesity. Outcomes are presented as an adjusted odds ratio (OR) with 95% confidence interval (95% CI). Results: 708 patients were analyzed; 54% diabetics, 83.5% non-Hispanic Blacks, 51% male with a mean age of 68, BMI of 29 kg/m2 and crude mortality rate of 40%. The length of hospital stay was greater in diabetics than non-diabetics, (13±26 days vs 9.5±18.5 days, p<0.05). Diabetics with an admission glucose > 140 mg/dL (vs<140 g/dL) had a 2.4-fold increased odds of both intubation and ICU admission (95% CI: 1.2, 4.5; 1.3, 4.6). Diabetics with admission glucoses > 180 mg/dL (vs <180 g/dL) had a 1.8-fold increased mortality (95% CI: 1.2, 2.9). Non-diabetics with admission glucoses >140 mg/dL (vs<140 g/dL) had a two-fold increased mortality (95% CI: 1.2, 3.5), 3.5-fold increased odds of ICU admission (95% CI: 1.8,6.6) and a 2.3-fold increased odds of both intubation and AKI (95% CI: 1.3, 4.2; 1.3,4.2). Non-diabetics with a glucose >180 mg/dL (vs <180 g/dL) had a four-fold increased mortality (95% CI: 1.8, 8.8), 2.7-fold increased odds of intubation (95% CI: 1.3, 5.6) and 2.9-fold increased odds of ICU admission (95% CI: 1.3, 6.2). Conclusion: Our results show hyperglycemia portends worse outcomes in diabetics and non-diabetics with COVID-19. Elevated admitting glucoses >180 mg/dL increased odds of mortality four-fold in non-diabetics and 1.8- fold in diabetics. In COVID-19, diabetic patients had a 37% greater length of hospital stay than non-diabetics. Whether hyperglycemia is a marker or a cause of more severe COVID-19 is unknown. These findings suggest that patients presenting with hyperglycemia require closer observation and more aggressive therapies. This raises the testable hypothesis that intensive glucose control may improve outcomes in patients with COVID-19.

Anaplastic thyroid cancer (ATC) is a rare, but extremely aggressive, form of cancer with a high mortality rate. Differentiated thyroid cancer (DTC), on the other hand, including papillary and follicular subtypes, are relatively common and typically follows a more indolent course. Cases have been reported in which ATC transforms from DTC, and where DTC and ATC exist simultaneously. Given the low incidence of such cases, they have not been well studied, and the optimal treatment regimen has yet to be determined. We present a case of a 77year-old woman who was initially presented with papillary thyroid cancer (PTC) with focal ATC. Five months after undergoing total thyroidectomy, she returned with a new right sided neck mass. Fine needle aspiration (FNA) with biopsies of the mass and lymph node at one level revealed a smear pattern consistent with ATC. However, lymph node biopsy taken from a different level revealed a smear pattern consistent with PTC. Mutation analysis was performed and results were positive for metastatic BRAF V600-mutant ATC. The patient was then started on dabrafenib/trametinib chemotherapy. Seven months later, she was tolerating treatment well. These unique clinical features including the initial presentation and the relatively favorable survival, that is more than double that of the median survival rate for ATC, suggests that those with synchronous PTC and ATC may have a more indolent course with better prognosis than those with ATC alone. It is also possible that the relatively longer survival in our patient is due to the use of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib in this case with concurrent ATC and PTC. While patients with both PTC and ATC have been documented to have mutations in the BRAF V600 gene, the objective of this report is to present the relatively favorable outcomes when a therapeutic regimen is guided by mutation analysis. Future research into advanced treatment options including targeted therapy and /or immunotherapy for both DTC and ATC is needed. Somatic mutation testing may also be helpful to identify oncogenic kinase abnormalities that will inform therapeutic decision making.

The incidence of HIV-associated Hodgkin lymphoma has risen during the era of combined antiretroviral therapy (ART) despite the proven, protective effects of ART as treatment for HIV. The clinical presentation of Hodgkin Lymphoma may also resemble disseminated mycobacterial infection-in symptoms, laboratory findings, and even bone marrow biopsy. This is a case report of a patient with HIV who was suspected to have disseminated mycobacterial infection after a first bone marrow biopsy showed granulomatous inflammation and was later found to have HIV-associated Hodgkin lymphoma on a repeat biopsy.

IntroductionThe purpose of this study is to examine the effect of admission glucose in patients hospitalized with COVID-19 with and without diabetes mellitus in a largely African American cohort.Design and methodsThis study included 708 adults (89% non-Hispanic Black) admitted with COVID-19 to an urban hospital between 1 March and 15 May 2020. Patients with diabetes were compared with those without and were stratified based on admission glucose of 140 and 180 mg/dL. Adjusted ORs were calculated for outcomes of mortality, intubation, intensive care unit (ICU) admission, acute kidney injury (AKI), and length of stay based on admission glucose levels.ResultsPatients with diabetes with admission glucose >140 mg/dL (vs <140 g/dL) had 2.4-fold increased odds of intubation (95% CI 1.2 to 4.6) and 2.1-fold increased odds of ICU admission (95% CI 1.0 to 4.3). Patients with diabetes with admission glucose >180 mg/dL (vs <180 g/dL) had a 1.9-fold increased mortality (95% CI 1.2 to 3.1). Patients without diabetes with admission glucose >140 mg/dL had a 2.3-fold increased mortality (95% CI 1.3 to 4.3), 2.7-fold increased odds of ICU admission (95% CI 1.3 to 5.4), 1.9-fold increased odds of intubation (95% CI 1.0 to 3.7) and 2.2-fold odds of AKI (95% CI 1.1 to 3.8). Patients without diabetes with glucose >180 mg/dL had 4.4-fold increased odds of mortality (95% CI 1.9 to 10.4), 2.7-fold increased odds of intubation (95% CI 1.2 to 5.8) and 3-fold increased odds of ICU admission (95% CI 1.3 to 6.6).ConclusionOur results show hyperglycemia portends worse outcomes in patients with COVID-19 with and without diabetes. While our study was limited by its retrospective design, our findings suggest that patients presenting with hyperglycemia require closer observation and more aggressive therapies.

Background: Metformin use has been associated with a decreased risk of cancer and improvement in overall cancer survival rates. However, scant data available regarding metformin's role in the risk of Gastrointestinal (GI) malignancies in patients with type II diabetes. Our study aimed to conduct a meta-analysis to evaluate the association of metformin use and GI cancer risk. Methods:We conducted electronic search by two independent investigators using the PubMed and Cochrane library databases. Studies were assessed for design and quality, and a meta-analysis was conducted to quantify the effect of metformin on the odds of developing specifi c GI malignancies. The fi nal papers that met our prespecifi ed inclusion criteria included 4 case-control studies that address metformin's effect on pancreatic cancer, and 4 case-control studies that address metformin's effect on colorectal cancer in patients with type II DM.Results: Of 2258 articles screened, 8 eligible studies were identifi ed comprising 483,561 participants diagnosed with DM. Our analysis showed that metformin use was not associated with a signifi cant effect on the odds of developing pancreatic cancer (OR .98; 95% CI 0.82-1.17, P=0. 83). Metformin use was associated with signifi cantly lower odds of having Colorectal Cancer (CRC); (OR 0.84; 95% CI 0.81-0.87, p < 0.01). Suffi cient data were not available to conduct analyses on the impact of metformin dose and duration. Conclusion:Our fi ndings suggest that metformin could be a useful neoadjuvant agent for CRC cancer and as a possible preventive therapy for other infl ammatory conditions related to colorectal pathologies such as adenomatous polyps and infl ammatory bowel disease. Further research is warranted to elucidate the role of metformin on the risk of developing pancreatic cancer, given the complex nature of the organ's regulation on insulin production.

Background: Cushing syndrome (CS) is well known to be associated with metabolic syndrome, venous thromboembolism, hypertension, left ventricular hypertrophy, and rarely dilated cardiomyopathy. The pathophysiological effects of hypercortisolism on the myocardium results in cardiomyocyte hypertrophy, myofibrillolysis, myocardial fibrosis, global longitudinal and circumferential strain. Our patient presents an example of CS in the setting of chronic heart failure with reduced ejection fraction, multiple thromboembolic events, and diabetes mellitus in a young adult. Clinical Case: A 34-year male with a past medical history of dilated cardiomyopathy with biventricular failure and left ventricle ejection fraction of 10%, pulmonary embolism, diabetes mellitus, and gout presented with shortness of breath. On physical exam he presented with symptoms of CS: moon facies, supraclavicular fat pads, dorsal fat pads, purple striae of abdominal skin, truncal obesity, ecchymosis, and skin atrophy. Labs showed elevated morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 8.6 mcg/dl, n&lt; 5 mcg/dl), repeat morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 5.7 mcg/dl, n&lt; 5 mcg/dl), and ACTH-concentrations &lt;5 pg/ml. CT-scan was insignificant for adrenal hyperplasia. He was admitted and treated for acute congestive heart failure exacerbation with plans for definitive treatment of CS outpatient with further imaging studies. Conclusion: The occurrence of CS induced heart failure results in increased mortality. There have been numerous accounts of resolution of cardiomyopathy after surgical treatment for CS secondary to adrenal adenoma. Our patient had a 10-year history of chronic dilated cardiomyopathy prior to cushingoid symptoms and confirmatory endocrinological data. The definitive treatment for CS syndrome in our patient would eventually be surgery targeting the source of hypercortisolism, however his cardiovascular risk factors would make him a poor surgical candidate. Severely reduced ejection fraction is a contraindication for generalized anesthesia needed for surgery. When surgery is contraindicated in CS medical management is recommended according to guidelines that target pituitary-directed medical treatments for Cushing’s disease and targeted therapies to treat ectopic ACTH syndrome. To our knowledge there have been few studies that demonstrate the effects of CS treatment on chronic conditions such as dilated cardiomyopathy. Studies have shown that surgical treatment for CS have reversed cardiomyopathy caused by CS but it still remains to be answered whether this same effect is achieved to some degree in chronic dilated cardiomyopathy.

With its alarmingly rising prevalence worldwide, type 2 diabetes has become a leading cause of morbidity and mortality around the planet. Efforts to prevent progression to diabetes in individuals at risk could have a significant positive public health impact. Multiple trials examining cardiovascular outcomes of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors revealed, in secondary analysis, a significantly reduced risk of new onset diabetes in participants receiving these agents. This glycemic protective effect is attributed to the known implication of RAAS in the development of insulin resistance and type 2 diabetes. The DREAM trial and the NAVIGATOR trial were two large randomized controlled studies examining, as primary outcome, the effect of Ramipril and Valsartan respectively on the incidence of diabetes in patients with prediabetes. Their results confirmed a favorable glycemic effect of RAAS inhibition agents and suggested a possible added benefit of diabetes prevention to their other several cardiovascular and blood pressure benefits.