Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology.

PURPOSE OF REVIEW: Targeting specific steroidogenic enzymes is effective in decreasing testosterone synthesis, resulting in significant antitumor effects in prostate cancer. Such treatments result in disruptions of complicated and intertwining pathways with systemic physiologic consequences via effects on the adrenal gland and renin-angiotensin-aldosterone axis. This review highlights some of these aspects that need to be taken into consideration when treating patients with androgen biosynthesis inhibitors. RECENT FINDINGS: Targeting CYP17A1, a key enzyme involved in androgen biosynthesis, is a well established treatment in prostate cancer. More recently, efforts are underway to target a gatekeeper enzyme of steroidogenesis, CYP11A1. This enzyme mediates conversion of cholesterol to pregnenolone, the first step in steroid hormone biogenesis. Studies are beginning to demonstrate antitumor effects of ODM-208, a CYP11A1 inhibitor in prostate cancer. Although anticipated to have a therapeutic role in prostate cancer, there are potential downstream effects of CYP11A1 targeting arising from suppression of the entire adrenal cortex, including long-term adrenal insufficiency and possibly cardiovascular dysregulation. SUMMARY: Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.

Cost Effectiveness of Definitive Treatment Strategies for Autonomously Functioning Thyroid Nodules.

OBJECTIVE: Autonomously functioning thyroid nodules (AFTN) can be treated with antithyroid drugs, radioactive iodine (RAI), thyroid lobectomy or radiofrequency ablation (RFA). Although surgery is most definitive, some patients require lifelong hormone supplementation. RFA avoids this sequela, but its efficacy depends on nodule size. This study aims to compare the relative cost-effectiveness of RAI, RFA and lobectomy for treatment of AFTNs. STUDY DESIGN: A Markov analysis model was created to simulate clinical outcomes, costs and utilities for three AFTN treatments: (1) thyroid lobectomy, (2) RAI, and (3) RFA. PATIENTS: This mathematical model was created using published literature and modeling. MEASUREMENTS: Transition probabilities, utilities and costs were extracted from published literature, Medicare, and RedBook. The willingness to pay threshold was set to $100,000 per quality-adjusted life year. The model simulated 2-year outcomes, reflecting RFA literature. Sensitivity analyses were conducted to account for uncertainty in model variables. RESULTS: In the base model, RAI dominated both lobectomy and RFA, with lower estimated cost ($2000 vs. $9452 and $10,087) and higher cumulative utility (1.89 vs. 1.82 and 1.78 quality-adjusted life years). One-way sensitivity analyses demonstrated that relative cost-effectiveness between surgery and RFA was driven by the probability of euthyroidism after RFA and hypothyroidism after lobectomy. RFA becomes more cost-effective than surgery if the rate of euthyroidism after ablation is higher than 69% (baseline 54%). CONCLUSION: Based on published data, RAI is most cost-effective in treating most AFTN. Surgery is more cost-effective than RFA in most scenarios, but RFA may be more resource-efficient for smaller nodules with a high likelihood of complete treatment.

An Assessment of Diversity, Inclusion, and Health Equity Training in Endocrinology Fellowship Programs in the United States.

CONTEXT: The Accreditation Council for Graduate Medical Education has instituted common program requirements related to diversity, equity, and inclusion (DEI) for postgraduate trainees in the United States; however, the extent to which DEI training is being incorporated across endocrinology fellowship programs is unknown. OBJECTIVES: To describe the sociodemographic representation and DEI training experiences within endocrinology fellowship programs. DESIGN, SETTING, AND PARTICIPANTS: National cross-sectional survey study of fellows and fellowship program leaders in the United States whose fellowships were members of the Association of Program Directors in Endocrinology and Metabolism. MAIN OUTCOME MEASURES: (1) Demographics of fellows and program leaders and (2) programs' experience, confidence, and interest in formal DEI training. RESULTS: A total of 108 and 106 fellow and faculty responded to the survey, respectively. The majority of fellows and faculty are female. Less than 3% of fellows and 3.7% of faculty identify as Black. More than 90% of fellows/faculty are heterosexual and no respondents identified as transgender/nonbinary; however, 5% and 2% of all respondents preferred not to disclose their sexual orientation and gender identity, respectively. While 85% of faculty received institutional diversity and inclusion training, 67.6% of fellows did. Fellows are more likely to have received training in health equity than program leaders. Both fellows and program leaders express a high interest in health equity curriculum. CONCLUSIONS: Within the diversity of endocrinology training programs, Black physicians are underrepresented in medicine, which persists in endocrinology fellowships. Fellowship programs express enthusiasm for national diversity and health equity curricula, with the majority of programs reporting institutional DEI training.

Predictors of Severe COVID-19 in Patients With Diabetes: A Multicenter Review.

OBJECTIVE: Diabetes is an independent risk factor for severe SARS-CoV-2 infections. This study aims to elucidate the risk factors predictive of more severe outcomes in patients with diabetes by comparing the clinical characteristics of those requiring inpatient admissions with those who remain outpatient. METHODS: A retrospective review identified 832 patients-631 inpatients and 201 outpatients-with diabetes and a positive SARS-CoV-2 test result between March 1 and June 15, 2020. Comparisons between the outpatient and inpatient cohorts were conducted to identify risk factors associated with severity of disease determined by admission rate and mortality. Previous dipeptidyl peptidase 4 inhibitor use and disease outcomes were analyzed. RESULTS: Risk factors for increased admission included older age (odds ratio [OR], 1.04 [95% CI, 1.01-1.06]; P = .003), the presence of chronic kidney disease (OR, 2.32 [1.26-4.28]; P = .007), and a higher hemoglobin A1c at the time of admission (OR, 1.25 [1.12-1.39]; P < .001). Lower admission rates were seen in those with commercial insurance. Increased mortality was seen in individuals with older age (OR, 1.09 [1.07-1.11]; P < .001), higher body mass index number (OR, 1.04 [1.01-1.07]; P = .003), and higher hemoglobin A1c value at the time of diagnosis of COVID-19 (OR, 1.12 [1.01-1.24]; P = .028) and patients requiring hospitalization. Lower mortality was seen in those with hyperlipidemia. Dipeptidyl peptidase 4 inhibitor use prior to COVID-19 infection was not associated with a decreased hospitalization rate. CONCLUSION: This retrospective review offers the first analysis of outpatient predictors for admission rate and mortality of COVID-19 in patients with diabetes.

THE PHYSIOLOGY BEHIND DIABETES MELLITUS IN PATIENTS WITH PHEOCHROMOCYTOMA: A REVIEW OF THE LITERATURE.

OBJECTIVE: This paper reviews the physiologic mechanisms responsible for glucose intolerance and diabetes mellitus in patients with pheochromocytoma. METHODS: Google Scholar and PubMed were searched using the following key words: "diabetes," "pheochromocytoma," "adrenoreceptors," and "hyperglycemia." All the articles that were retrieved and reviewed were in the English language. RESULTS: Glucose intolerance and diabetes mellitus, resulting from high circulating levels of catecholamines, are mainly the product of compromised insulin secretion from the ß-cells in the pancreas, decreased glucose uptake in the peripheral tissues, and increased insulin resistance. CONCLUSION: As pheochromocytomas mainly present with cardiovascular and autonomic hyperfunctioning, it is important to understand the metabolic disorders associated with this rare disease. Hyperglycemia is an associated metabolic abnormality which can drastically improve after tumor resection, and significant downscaling of anti-hyperglycemic therapy is often required. ABBREVIATIONS: GLUT4 = glucose transporter type 4 HbA1c = hemoglobin A1c IL = interleukin OGTT = oral glucose tolerance test.

Is metformin safe in pregnancy: a focus on offspring outcomes.

INTRODUCTION: Metformin has been part of treatment algorithms for type 2 diabetes mellitus (T2DM) for decades. While it has formal approval in the U.S.A. for treatment of T2DM, it is used off-label in gestational diabetes mellitus (GDM), polycystic ovarian syndrome (PCOS), and ovarian hyperstimulation prevention. Its role as an insulin sensitizer has made it an attractive therapeutic to address the insulin resistance seen in these syndromes. In 2022, the European Union approved metformin as the only oral antidiabetic medication for diabetes in pregnancy. While its safety and benefits for the mother are well documented, it does cross the placenta with plasma concentrations comparable between mother and child at delivery. AREAS COVERED: This special report will focus on major randomized control trials investigating metformin use in pregnancies impacted by PCOS, GDM, T2DM, and obesity and their offspring follow up trials. EXPERT OPINION: For the mother, metformin can be beneficial, with reduction in insulin therapeutic burden, weight gain, hypoglycemia and in certain situations, pre-eclampsia. For the neonate, benefits may include reduction in hypoglycemia and no increased risk of congenital anomalies. It is the long-term data in the offspring that remains unknown with some areas of concerns (SGA, altered anthropometrics) requiring continued research.

Insulin Autoimmune Syndrome (Hirata's Disease) Caused by Methimazole in a 47-Year-Old Man.

Insulin autoimmune syndrome (IAS), or Hirata's disease, is a rare disease characterized by episodes of hypoglycemia with elevated levels of insulin secondary to high concentrations of insulin autoantibodies. The use of methimazole is a risk factor for the development of Hirata's disease. We report a case of a 47-year-old man being treated for thyroid storm initially with methimazole and other agents. Medical management was stopped, as the patient was refractory to treatment. Ultimately, the patient underwent plasmapheresis and thyroidectomy. While the patient was initially noted to have hyperglycemia during his hospital stay, requiring a regular insulin drip, he subsequently developed hypoglycemia even after cessation of insulin therapy. Lab work was positive for insulin autoantibodies, and the patient was diagnosed with IAS. IAS should be considered in patients with hypoglycemia who have been exposed to specific agents.

Improving Access to Eye Care Through Community Health Screenings Using Artificial Intelligence.

PURPOSE: To the best of our knowledge, implementation of artificial intelligence (AI)-based vision screening in community health fair settings has not been previously studied. This prospective cohort study explored the incorporation of AI in a community health fair setting to improve access to eyecare. METHODS: Vision screening was implemented during a community health fair event using an AI-based non-mydriatic fundus camera. In addition, a questionnaire was provided to survey the various barriers to eyecare and assess eye health literacy. RESULTS: A total of 53 individuals were screened at this event. Notably, about 88% of participants had follow-up appointments scheduled accordingly with an approximate 62% attendance rate. The most reported barrier to eyecare was lack of health insurance followed by transportation. CONCLUSION: The addition of AI-based vision screening in community health fairs may ultimately help improve access to eye care.

Challenges of Gender-Affirming Care in Incarcerated Transgender People.

Social and health disparities among transgender people may result in increased rates of incarceration, particularly among Black transgender women. The World Professional Association for Transgender Health states that all recommendations for gender-affirming care made in the Standards of Care-8 be applied equally to people living in institutions. Understanding the structural challenges to gender-affirming care in the corrections environment will allow the endocrinologist to navigate the complex correctional health care system. The barriers to gender-affirming care and surgery will be highlighted in this article.

The Effect of Telemedicine in Glycemic Control in Adult Patients with Diabetes during the COVID-19 Era-A Systematic Review.

Telemedicine can be an effective tool for managing chronic diseases. The disruption in traditional diabetes care resulting from the COVID-19 pandemic led to global interest in telemedicine. With this manuscript, we evaluated the use of telemedicine for the management of diabetes during the pandemic and its impact on glycemic control, focusing on retrospective and prospective studies which included adult, non-pregnant patients with diabetes. We evaluated whether there was an improvement in HbA1c, time in range (TIR), glucose management indicator (GMI), mean glucose values, hypoglycemic episodes, time below range (TBR), or hospitalizations for hypoglycemia/DKA, depending on the available information provided. This review article highlights the benefits of telemedicine during the global state of emergency, which altered the standard of healthcare delivery. Across the studies reported in this review, telemedicine was shown to be an effective tool for the management of diabetes, illustrating its potential to be the new standard of care. Although these improvements may be confounded by potential extraneous factors present during the pandemic, telemedicine was shown to positively impact glycemic control. Overall, this article highlights the benefits of telemedicine on glycemic control during the global state of emergency, which altered the standard of care. With the rollback of COVID-19 restrictions, and a return to the office, this article emphasizes the necessity to study how telemedicine can be best utilized for diabetes management when compared to the traditional standard of care.

Total thyroidectomy is more cost-effective than radioactive iodine as an alternative to antithyroid medication for Graves' disease.

BACKGROUND: Patients with Graves' disease treated with radioactive iodine report worse quality of life than those treated by thyroidectomy. However, radioactive iodine is often selected due to lower risk of complications and lower cost. The objective of this study was to estimate the cost-effectiveness of radioactive iodine versus total thyroidectomy for treatment of Graves' disease. METHODS: A Markov decision-analytic model was created to simulate clinical outcomes and costs of medication-refractory Graves' disease treated with radioactive iodine or total thyroidectomy. Complication rates and utilities were derived from published data. Costs were extracted from national Medicare reimbursement rates. We conducted 1-way, 2-way, and probabilistic sensitivity analyses to identify factors that influence cost-effectiveness and reflect uncertainty in model parameters. The willingness-to-pay threshold was set at $100,000/quality-adjusted life-years. RESULTS: Total thyroidectomy yielded 23.6 quality-adjusted life-years versus 20.9 quality-adjusted life-years for radioactive iodine. The incremental cost-effectiveness ratio was $2,982 per quality-adjusted life-years, indicating that surgery is highly cost-effective relative to radioactive iodine. Surgery was more cost effective than radioactive iodine in 88.2% of model simulations. Sensitivity analyses indicate that the model outcomes are driven predominantly by posttreatment quality of life, with contributing effects from rates of treatment complications and the impact of these complications on quality of life. CONCLUSION: For patients with Graves' disease who either cannot tolerate or are refractory to antithyroid drugs, thyroidectomy is more cost-effective than radioactive iodine. Future research should validate reported differences in quality of life between these 2 treatment modalities.

Effects of Electroconvulsive Therapy on Glycemic Control in Type 1 Diabetes.

Electroconvulsive therapy (ECT) is a treatment modality for refractory depression and other severe psychiatric diseases. Depression is a common comorbid condition of diabetes. Yet, evidence regarding the effect of ECT on glycemic control in patients with diabetes is limited and conflicting, with reports of both exacerbation and amelioration of hyperglycemia. A 52-year-old Caucasian man with a history of type 1 diabetes mellitus (T1DM) was admitted for ECT therapy in the setting of worsening depression refractory to medical treatment. Pre-admission glycemic control was poor. He had significant glycemic variability during his hospitalization with hyper- and hypoglycemia. He required near-daily adjustment of insulin doses and distinct "ECT day" and "non-ECT day" insulin regimens. By the conclusion of his ECT course, in addition to achieving favorable psychiatric recovery, he had a marked improvement in glycemic control. This suggests that the treatment of depression may have beneficial effects on improving glycemic control in patients with T1DM.

Open-source automated insulin delivery systems for the management of type 1 diabetes during pregnancy.

A 40-year-old woman used an open-source automated insulin delivery system to manage her type 1 diabetes (T1D) prior to conception. The code for building the iPhone application called 'Loop' that carried the software for the hybrid closed-loop controller was available online. Her glycated hemoglobin before conception was 6.4%. Between 6 and 12 weeks gestation, she spent 66% time-in-range (TIR), 28% time-above-range (TAR) and 6% time-below-range (TBR). Between 18 and 24 weeks gestation, she spent 68% TIR, 27% TAR and 5% TBR. During her third trimester, she spent 72% TIR, 21% TAR and 7% TBR. She delivered a healthy infant with no neonatal complications. Clinicians should be aware of this technology as it gains traction in the T1D community and seeks Food and Drug Administration approval.

Thyroid carcinoma discovered incidentally during surgical resection of head and neck squamous cell carcinoma: A case series.

The occurrence of 2 synchronous primary cancers of different origin in the head and neck region is rare. The incidence of thyroid carcinoma found during surgical resection of primary oral squamous cell carcinoma (SCCa) is about 0.3% to 1.9% of patients. Because of the rarity of cases, there is no consensus on management. To clarify significance and management of such lesions, we report 13 cases in which incidental thyroid carcinoma was discovered during surgical resection for primary oral SCCa. A total of 1295 cases of head and neck SCCa from a 4-year period were reviewed, of which we found 13 cases of concurrent thyroid malignancy, providing an incidence rate of approximately 1%. Of these patients, 61.5% received a total or hemithyroidectomy and, of those, 62.5% received radioactive iodine for their thyroid carcinoma; 38.4% did not receive treatment for their thyroid malignancy. The mortality rate for this case series was 23%, of which all deaths were attributed to complications from SCCa. There were no cases where mortality was related to the thyroid carcinoma. Overall, this is consistent with the consensus that incidental thyroid carcinoma found during oral SCCa resection is insignificant compared with the aggressiveness of the primary malignancy.

The use of diazoxide in the management of spontaneous hypoglycemia in patients with ESRD.

Although diabetes remains the number one cause of renal failure nationwide, spontaneous hypoglycemia in patients with CKD has also been described in the absence of exogenous insulin or any other diabetes treatment. Decreased renal gluconeogenesis and impaired renal insulin clearance are underlying mechanisms of hypoglycemia in individuals with ESRD. Diazoxide was originally approved as an anti-hypertensive medication, but also is known to bind ATP-sensitive K channels in the beta cells of the pancreas, ultimately leading to inhibition of insulin release. We detail six cases of ESRD-associated hypoglycemia which responded to treatment with diazoxide therapy.

Diabetes Care for Patients Experiencing Homelessness: Beyond Metformin and Sulfonylureas.

On any given night in the United States, an estimated 553,742 people are homeless. Applying a broader definition of homelessness that includes unstably housed people, an estimated 1.5% of Americans experience homelessness in a given year. Rates of diabetes are increasing among individuals experiencing homelessness. The social, psychological, and physical challenges of homelessness not only contribute to the rate of diabetes, but also complicate management. Unstable housing, limited medical resources, food insecurity, and competing priorities are barriers to diabetes care among patients experiencing homelessness. Homeless patients with diabetes more frequently develop specific comorbidities that require special attention, such as cardiovascular disease, substance abuse, depression, and foot wounds. The Affordable Care Act gave states the option to expand Medicaid to those earning up to 138% of the federal poverty level. This addressed a gap in coverage for low-income individuals not eligible for Medicaid or employer-sponsored insurance. With increased insurance coverage, this has increased the variety of medications available to treat hyperglycemia from type 2 diabetes beyond metformin, sulfonylureas, and insulin. Several of the newer classes of medications have advantages for patients experiencing homelessness, but also have special considerations in this vulnerable patient population. This narrative review will provide a review of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide agonists, sodium glucose cotransporter-2 inhibitors, and thiazolidinediones in individuals experiencing homelessness.

Gestational Diabetes Mellitus: Post-partum Risk and Follow Up.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are at an increased risk for developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. In this review, we will discuss postpartum cardiovascular and diabetes risk in women with a history of GDM and different ways to improve postpartum screening. METHODS: This review involves a comprehensive literature review on gestational diabetes and postpartum risk for cardiovascular disease and diabetes mellitus as well as post-partum screening methods. RESULTS: Cardiovascular risk post-partum is potentiated by increased inflammatory markers leading to worsening atherosclerosis and cardiovascular events downstream. Decreased insulin sensitivity and ß cell compensation, recurrent GDM, maternal factors such as pre and post-partum weight gain and lactation may contribute to T2DM risk. Postpartum glucose testing is essential in screening women as hyperglycemia in pregnancy has long term effects on both cardiovascular disease and diabetes risk on the mother. CONCLUSION: Long and short term improvement to post-partum glucose testing is essential to decreasing cardiometabolic and diabetes risk in women with gestational diabetes mellitus.