Faculty Bibliography

Introduction The primary receptor for SARS-CoV-2 infection, angiotensin-converting enzyme-2 (ACE-2), is expressed in the gastrointestinal tract and liver parenchyma. The involvement of the gastrointestinal tract with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has remained unclear. The following study retrospectively reviews gastrointestinal symptoms and liver function tests at the time of hospital admission to identify patient outcomes including prolonged hospital stay, the requirement for intensive care, and all-cause in-hospital 30-day mortality. Methods A retrospective review of patient charts at the Woodhull Medical and Mental Health Center (WMC) was conducted at the time of hospital admission, using a pre-determined selection criterion. All adult patients, both inpatient and outpatient, were included from March 2020 till May 2020. A 95% confidence interval was used to estimate the odds ratio (OR) for patient outcomes. Results Of the 520 patients, gastrointestinal symptoms including nausea (OR = 0.375, p = 0.015), and nausea and vomiting in combination (OR = 0.400, p = 0.016) had an inverse protective relationship with all-cause in-hospital 30-day mortality among COVID-19 patients. Gastrointestinal symptoms including diarrhea (OR = 1.008, p < 0.001), and nausea and vomiting (OR = 1.291, p = 0.043) had a mild impact on the length of hospital stay. Conclusion Elevated liver transaminases including alanine transaminase (ALT) and aspartate transaminase (AST) at the time of hospital admission can predict critical care requirement and all-cause 30-day hospital mortality in patients with COVID-19 infection. Presence of gastrointestinal symptoms is associated with worsened outcomes.

Tacrolimus is a reversible calcineurin inhibitor. It is commonly used as an immunosuppressive drug in the treatment of T cell mediated diseases such as polymyositis, graft rejection in solid organ transplant, graft-versus-host disease in hematopoietic stem cell transplant, and is postulated to have diabetogenic potential. Fluconazole, on the other hand, is frequently prescribed antifungal therapy. Fluconazole increases the serum level of tacrolimus into the supratherapeutic range, thus developing drug toxicity if the dose is unadjusted. Diabetic ketoacidosis is a rare adverse drug effect reported with the use of tacrolimus. In this report, we present a case of DKA in a 60-year-old woman with polymyositis on low dose corticosteroids and tacrolimus, precipitated by the use of fluconazole. We highlight the pathophysiologic mechanisms underlying the effect of fluconazole on tacrolimus levels causing an accelerated development of DKA along with the review of literature on this potentially life-threatening condition.

Background/UNASSIGNED:Ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of ovarian stimulation occurring during assisted reproduction technologies (ART). It is characterized by increased vascular permeability and hypercoagulable states resulting in strokes and peripheral ischemia. Acute myocardial infarction and cardiac thrombosis, however, have been rarely reported complications of OHSS. Methods/UNASSIGNED:A literature search was performed for reports on myocardial infarction and cardiac thrombosis associated with ovarian stimulation with a summary of their clinical characteristics. Results/UNASSIGNED:A total of twelve published cases were reviewed with 5 out of 12 (41.67%) of the reported cases were 35 years of age or older. Myocardial infarction was reported in 10 out of the 12 cases (83.3%). Two of the cases were pregnant at presentation (16.67%). The mean duration between starting ovarian stimulation medications and clinical presentation was 23 days. Chest pain was the most common presenting symptom (66.67%), 2 cases presented with stroke (16.67%) and 2 cases presented with abdominal distention (16.67%). A total of 8 patients underwent coronary angiography with 2 of these cases were treated with percutaneous coronary intervention. No mortality reported in any of the twelve cases. Conclusion/UNASSIGNED:Women of a relatively younger age undergoing ovarian stimulation may be at risk for developing myocardial infarction and cardiac thrombosis. Once thrombosis is suspected, initiating appropriate therapy in a timely manner is crucial.

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.

The differential diagnosis of adrenal incidentalomas includes primary hyperaldosteronism, Cushing's syndrome, and pheochromocytoma, and, when the first 3 have been excluded,-non-classic adrenal hyperplasia (NCAH). We have previously shown that insulin-sensitizing interventions ameliorate the expression of both classic and non-classic CAH. The patient is a 56 year-old African-American man who was referred to Endocrine in 2002 for hypertension with a 3.0x2.8x2.1 cm, well circumscribed, ovoid, hypodense, soft tissue mass in the medial limb of the right adrenal first noted in 2001. Endocrine evaluation was negative for primary hyperaldosteronism, Cushing's syndrome, and pheochromocytoma, however plasma renin activity (PRA) by liquid chromatography tandem mass spectrometry (LC/MS/MS) was low at 0.52 ng/ml/hr., at least suggesting the possibility of a deoxycorticosterone-secreting adenoma (DOComa). Unstimulated serum deoxycorticosterone by LC/MS/MS on 9/20/11 was 38 ng/dl (3.5-11.5). Both hypo- and hyperkalemia were occasionally noted, but not at DOC or aldosterone sampling times. Unstimulated serum 11-deoxycortisol by LC/MS/MS on 1/31/08 was 130 ng/dl (<76). Serum 17-OH-pregnenolone was normal and serum 17-OH-progesterone by LC/MS/MS was low at 43 ng/dl (61-334). Metformin 500 mg daily after supper was started on 5/6/08, following which serum 11- deoxycortisol fell to 84 ng/dl. After this the patient was lost to follow-up for several years and ran out of metformin. On 6/13/12 his serum 25-OH-Vitamin D by immunoassay (IA) was 6 ng/ml (30-100). Between 1/8/08 and 6/8/12 the patient had lost 2.3 kg, after which he underwent right below knee amputation due to peripheral arterial disease with gangrene. On 7/15/16 serum 11-deoxycortisol fell to 53 ng/dl (<42), serum deoxycorticosterone normalized to 6ng/dl (2-19), serum 25-OH-Vitamin D was 14.4 ng/ml (30.0-100.0). On 8/5/16 serum 11-deoxycortisol fell to 47 ng/dl, DOC was 5.2 ng/dl, and 25-OH-Vitamin D was 36.3 ng/ml. The right adrenal mass has not changed in size or appearance since 2001. This case illustrates the importance of considering NCAH in the differential diagnosis of adrenal incidentaloma and again illustrates the potential benefit of improvement of insulin sensitivity by both weight loss and correction of hypovitaminosis D in NCAH

A number of case reports and small series have been published suggesting an association between hyperthyroidism and pulmonary artery hypertension (PAH), although such an association is not widely appreciated among endocrinologists, cardiologists, or pulmonologists. Some authors have speculated that PAH in this setting is autoimmune in origin and, thus, likely to occur in Graves' disease, but unlikely to occur in non-autoimmune hyperthyroidism. We evaluated 24 patients with hyperthyroid Graves' disease (GD) - confirmed by the combination of hyperthyroidism with increased titers of thyroid-stimulating immunoglobulin (TSIG) or thyroid peroxidase (TPO) antibody or thyroglobulin antibody - and 3 patients with antibody-negative toxic multinodular goiter (TMG with trans-thoracic 2-D echocardiography while they were hyperthyroid. In a smaller number of patients (3), we were able to repeat their echocardiograms when their hyperthyroidism had either much improved or they had actually become euthyroid. The cardiologist reading the echocardiograms was blinded as to their thyroid status. 54.2 % of the patients with GD and 100% of the patients with TMG had PAH. In the patients with repeat echocardiograms, mean pulmonary artery pressure dropped from 35.8 to 24.3 mmHg. One, previously reported patient closed a patent foramen ovale in association with amelioration of her hyperthyroidism and PAH. We conclude that PAH is common in both GD and TMG. The observation that it was present in a larger percentage of TMG patients than GD patients suggests that the phenomenon is more likely related to hyperthyroidism itself or to upper airway obstruction related to the goiter than to autoimmunity. Future studies involving patients with thyrotoxic adenoma, TSH-dependent hyperthyroidism, and athyreotic patients with iatrogenic hyperthyroidism would be of interest in clarifying the etiology of this common association

An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3-beta-ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.

Heart failure (HF) is a major cardiovascular complication of diabetes mellitus (DM). The greatest risk factor for HF is age, and data indicate that 6 to 10 % of individuals over the age of 65 years suffer from HF. Patients with DM have a 2.5-fold increased risk for developing HF than individuals without DM. The 25 to 40 % of patients with HF who have DM have worse outcome (death from cardiovascular disease or hospitalization for worsening HF) than patients without DM. Hyperglycemia is a risk factor for the development of HF with an increase in incidence of HF rising from 10 % at hemoglobin A1c (HbA1c) 8.0 to 9.0 % to 71 % at a HbA1c > 10 %. Patients with DM and HF are equally distributed between those with low ejection fractions and those with normal ejection fractions. The HF treatment regimens for patients with HF and DM (blockade of angiotensin II synthesis or action, cardioselective beta-adrenergic blockade, mineralocorticoid receptor blockade, and diuretics) are the same as for HF patients without DM, though the benefit on clinical outcomes is not as great. The new angiotensin-neprilysin inhibitors appear to provide increase outcome benefits in both HF patients with or without DM. Glycemic control impacts the clinical outcomes in patients with HF and DM in a U-shaped relationship with poorer survival at low and high mean HbA1c levels. The optimal chronic glycemic control occurs at an HbA1c of 7.5 to 8.0 % for patients with DM who have symptoms of HF.

Cortisol production by hepatocellular carcinoma (HCC) has not been previously reported and dehydroepiandrosterone (DHEA) secretion by HCC is rare. We report a case of a 53-year-old woman admitted with dyspnoea and headache. Serum cortisol by immunoassay (IA) was 42.3 mug/dL, urine free cortisol (UFC) by liquid chromatography mass spectrometry (LC/MS/MS) was 106.1 mug/24 h, serum DHEA by LC/MS/MS was 4886 ng/mL, serum DHEA-S by LC/MS/MS was 4477 ng/mL and plasma adrenocorticotrophic hormone (ACTH) by IA was 10 pg/mL. CT showed likely HCC metastatic to the left adrenal gland, brain and lungs. Liver and adrenal gland biopsies confirmed HCC. ACTH tumour staining was negative. High serum and UFC levels and high serum DHEA and DHEA-S with low-normal plasma ACTH and negative tumour ACTH staining suggested ACTH-independent ectopic Cushing's syndrome (CS); cortisol and DHEA being likely secreted by the HCC. To the best of our knowledge, this is the first reported case of HCC associated with CS.