OFF-LABEL USE AND MISUSE OF TESTOSTERONE, GROWTH HORMONE, THYROID HORMONE, AND ADRENAL SUPPLEMENTS: RISKS AND COSTS OF A GROWING PROBLEM.

Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to "adrenal fatigue," an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men's health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Abbreviations: DHEA = dehydroepiandrosterone; FDA = U.S. Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LT3 = L-triiodothyronine; LT4 = levothyroxine; T3 = total triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Hypercalcemia in histoplasmosis aggravated with antifungal treatment.

INTRODUCTION: Hypercalcemia is a known, but rare complication of histoplasmosis, a granulomatous disease. We present a case of chronic disseminated histoplasmosis, complicated by hypercalcemia, transiently worsening after initiation of antifungal treatment. CASE PRESENTATION: A 61-year-old gentleman presented with shortness of breath, cough, weight loss, but no fever or hemoptysis. His physical exam was unremarkable except for decreased air entry on both lung fields, and axillary and inguinal lymphadenopathies. Computed tomography of the chest showed bilateral cavitary lung lesions, biopsy of which showed non caseating granulomas, and tissue culture showing Histoplasma capsulatum. Itraconazole was started. One month later, patient presented with transient acute renal failure and worsening hypercalcemia. His workup showed a non-PTH mediated hypercalcemia, with a normal PTH-rP, and low calcifediol, but high normal calcitriol level. Hypercalcemia secondary to histoplasmosis was reported in six cases, none of which worsened after antifungal treatment. Several mechanisms have been elucidated. CONCLUSION: We recommend monitoring of serum calcium after initiation of antifungal treatment, especially in patients with underlying hypercalcemia. More studies are needed to understand the pathophysiology.

Glycemic Control and Awareness of Insulin Therapy.

INTRODUCTION: Glycemic control is associated with better health outcomes among patients with diabetes. No previous research has examined the relationship between knowledge of one's insulin dose and glycemic control. This study sought to determine if patients who accurately recalled their insulin dose achieved better glycemic control than patients who could not remember their dose. METHODS: Interviews were conducted with 106 patients. Data were collected during patients' appointments at two endocrinology clinics in Wichita, Kansas from May 29, 2018 to February 15, 2019. Adequate glycemic control was defined as an HbA1c of less than 7.5%. A multiple logistic regression model was developed to identify factors associated with glycemic control. RESULTS: Of the 109 patients asked to participate, 105 agreed to participate in the study. About half (45%, n = 48) were male. Patients' mean age was 50 years (SD = 17). Seventy-seven percent (n = 81) were overweight (body mass index (BMI) of 25 to 29.9) or obese (BMI >30). Patients who correctly stated their insulin dose had a mean Hemoglobin A1c (HbA1c) of 6.9% (SD = 0.98), whereas those who incorrectly stated their dose had a mean HbA1c of 9.5% (SD = 1.9; p <0.0001). CONCLUSIONS: There was a significant relationship between knowledge of one's insulin dose and adequate glycemic control.

Impact of a Community-Based Weight Loss Program on Renal Function.

Introduction Obesity is associated with increased morbidity and mortality and is an independent risk factor for the development and progression of chronic kidney disease (CKD). This study investigated the effect of a community-based, lifestyle-focused, weight-loss intervention on renal function among participants at baseline following 12 weeks of therapy.  Methods A retrospective analysis of adults enrolled in a weight management program from 2009 to 2014 was conducted. Participants consumed at least 800 kilocalories per day in meal replacements, attended weekly behavioral education classes, and expended approximately 300 kilocalories per day in physical activity. The primary outcome was the association of weight loss and changes in glomerular filtration rate (GFR). Secondary outcomes included changes in blood sugar levels, lipid parameters, blood pressure, and the use of medication for hypertension and diabetes mellitus.  Results Of the 71 participants, 63.4% were female, the average weight was 289 pounds, the average body mass index (BMI) of 53, and baseline GFR 47 ml/min/1.73m2. Following 12 weeks of the intervention, 76.1% of participants improved in CKD stage, 22.4% remained within the same stage, and 1.5% progressed to a higher stage (3A to 3B). Analysis revealed a correlation between weight loss and improved GFR (p=0.0006). Improvements were noted in blood sugar levels, blood pressure, and lipids (p<0.05). Medications were reduced in 61.8% of participants for hypertension and 83.3% for diabetes. Conclusions A significant correlation was observed between weight loss and improved renal function, with most participants improving in CKD stage. Participants also improved in markers of chronic disease and required fewer medications. When controlling for both diabetes and hypertension, the effect of improved renal function persisted.

Exceptional Regression of Malignant Pleural Mesothelioma with Pembrolizumab Monotherapy.

The lead author with clinical stage I malignant pleural mesothelioma, epithelioid type, highly programmed cell death ligand 1 (PD-L1) positive, and BAP1 negative, experienced a prompt and exceptionally favorable response to pembrolizumab monotherapy. After cessation of treatment due to immune-related endocrinopathies, complete metabolic response on interim PET/CT scan was achieved. Two years after initial diagnosis, unifocal tumor reactivation was addressed with successful pembrolizumab monotherapy rechallenge. Immunotherapy, typically not used as frontline treatment for malignant pleural mesothelioma, may provide an effective and durable response for some patients. Based on this single case study, epithelioid type tumors with strongly positive PD-L1 and BAP1-negative immunohistochemical markers may be well suited for treatment with immune checkpoint inhibitors such as pembrolizumab.

"Hyper-warburgism," a cause of asymptomatic hypoglycemia with lactic acidosis in a patient with non-Hodgkin's lymphoma.

CONTEXT: In cancer cells, the Warburg effect is defined as the avid consumption of glucose through the glycolytic pathway with concomitant lactate production, even under aerobic conditions. CASE: We report a 64-yr-old woman who was referred to our institution for pancytopenia and hypoglycemia. Physical examination demonstrated hepatosplenomegaly and petechiae. She had no clinical manifestation of neuroglycopenia, despite serum glucose of 26 mg/dl (1.4 mmol/liter) and serum lactate of 28.5 mmol/liter (normal range, 0.5-3.4 mmol/liter). Bone marrow biopsy demonstrated diffuse large B-cell lymphoma. Staging (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed increased FDG avidity in an enlarged spleen and absent FDG uptake in the brain. Despite dextrose infusions up to 30 g/h, there was no increase in serum glucose, but there was a paradoxical increase in serum lactate. Immunochemotherapy improved the hematological and metabolic abnormalities. Follow-up FDG-positron emission tomography/computed tomography showed a decrease in splenic avidity and an increase in brain FDG avidity. The patient refused further chemotherapy and died 1 wk after discharge. METHODS: Literature review of cases of lymphoma with lactic acidosis, with and without hypoglycemia, demonstrated that these combinations occurred in multiple categories of B- and T-cell lymphoma. There was no difference in the mortality rate in those with (75%) or without (74%) concomitant hypoglycemia. CONCLUSION: This case represents an exaggerated Warburg effect, or "hyper-warburgism," characterized by excessive lactate production and overwhelming glucose consumption. We speculate that the decreased brain FDG uptake, despite the lack of neuroglycopenic symptoms, supports the hypothesis that lactate served as a fuel for the brain, thus protecting against hypoglycemia.