Follow-up intervals in patients with Cushing's disease: recommendations from a panel of experienced pituitary clinicians.

PURPOSE: Follow-up guidelines are needed to assess quality of care and to ensure best long-term outcomes for patients with Cushing's disease (CD). The purpose of this study was to assess agreement by experts on recommended follow-up intervals for CD patients at different phases in their treatment course. METHODS: The RAND/UCLA modified Delphi process was used to assess expert consensus. Eleven clinicians who regularly manage CD patients rated 79 hypothetical patient scenarios before and after ("second round") an in-person panel discussion to clarify definitions. Scenarios described CD patients at various time points after treatment. For each scenario, panelists recommended follow-up intervals in weeks. Panel consensus was assigned as follows: "agreement" if no more than two responses were outside a 2 week window around the median response; "disagreement" if more than two responses were outside a 2 week window around the median response. Recommendations were developed based on second round results. RESULTS: Panel agreement was 65.9% before and 88.6% after the in-person discussion. The panel recommended follow-up within 8 weeks for patients in remission on glucocorticoid replacement and within 1 year of surgery; within 4 weeks for patients with uncontrolled persistent or recurrent disease; within 8-24 weeks in post-radiotherapy patients controlled on medical therapy; and within 24 weeks in asymptomatic patients with stable plasma ACTH concentrations after bilateral adrenalectomy. CONCLUSIONS: With a high level of consensus using the Delphi process, panelists recommended regular follow-up in most patient scenarios for this chronic condition. These recommendations may be useful for assessment of CD care both in research and clinical practice.

BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.

OBJECTIVE: Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. METHODS: Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. RESULTS: Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). CONCLUSION: Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. ABBREVIATIONS: BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Micronutrient deficiencies in patients with gastrointestinal cancer: To treat or not to treat.

Nutrition supplements are widely used among patients with cancer. The general public perceives supplements as more natural anticancer and antitoxicity agents, and often supplements are used without the knowledge of the treating physician. In the clinical setting, there are concerns that supplements may decrease effectiveness of chemotherapy and/or radiotherapy and, as a result, supplementation is avoided. There is a body of literature evaluating micronutrient deficiencies, supplementation, and cancer risk; however, little is known about the risks of treatment of micronutrient deficiencies in specific cancers. Of the types of cancers, patients with gastrointestinal cancers are at high risk of developing malnutrition and, subsequently, possible micronutrient deficiencies. This review aims to evaluate the effects of supplementation of specific micronutrients in patients with cancer of the digestive tract.

Concentrated Grape Powder Consumption Modulates Cholesterol Metabolism and Homeostasis in Healthy Subjects.

SCOPE: Four weeks' of concentrated grape powder (GP) consumption reduces circulating cholesterol in healthy free-living subjects consuming a low-fiber/low-polyphenol diet. Here, the study aims to investigate the underlying mechanisms for cholesterol reduction by evaluating biomarkers of cholesterol de novo biosynthesis, intestinal absorption, miRNA involved in transcriptional regulation of cholesterol metabolism, as well as cholesterol oxidation. METHODS AND RESULTS: Fasting plasma samples collected from 19 healthy free-living subjects at baseline and week 4 of GP consumption are used in this study. Gas chromatography-mass (GC-MS) analysis of plasma samples shows that lathosterol, a precursor of cholesterol synthesis, is significantly decreased after GP consumption indicating reduced cholesterol de novo biosynthesis. Markers of intestinal absorption, campesterol, and ß-sitosterol are not changed. Realtime PCR shows that plasma exosomal miRNA-1 is increased after GP consumption. GC-MS also shows that GP consumption reduces the plasma cholesterol oxidation product 27-hydroxycholesterol (27-HC). CONCLUSIONS: This study enhances the understanding of the mechanisms of the cholesterol lowering effects of GP, and provides new insights into the potential health benefits of grape consumption.

Micronutrient Deficiency as a Confounder in Ascertaining the Role of Obesity in Severe COVID-19 Infection.

Food insecurity in the United States has been exacerbated due to the socioeconomic strain of the coronavirus disease 2019 (COVID-19) pandemic. Populations experiencing poverty and, as a consequence, food insecurity in the United States are disproportionately affected by obesity, which was identified early in the pandemic as a major risk factor for increased susceptibility to COVID-19 infection and mortality. Given the focus on obesity and its role in immune dysregulation, it is also important to note the role of micronutrient deficiency, another sequalae of food insecurity. Micronutrients play an important role in the ability of the immune system to mount an appropriate response. Moreover, OBESE individuals are more likely to be micronutrient deficient. This review will explore the role of micronutrients, vitamin A, vitamin D, vitamin C, and zinc in respiratory immunity and COVID-19 and how micronutrient deficiency may be a possible confounder in obesity's association with severe outcomes. By illuminating the role of micronutrients in COVID-19, this paper expands the discussion from food insecurity and obesity to include micronutrient deficiency and how all of these interact in respiratory illnesses such as COVID-19.

The Impact of Obesity on SARS-CoV-2 Pandemic Mortality Risk.

The COVID-19 pandemic has uncovered the increased susceptibility of individuals with obesity to infection and severe disease leading to hospitalization and death. Studies in New York City demonstrated that after advanced age, obesity was the most common risk factor leading to severe disease and death from COVID-19. While the connection has been recognized, there has not been a general recognition of the potential mechanisms for this link between excess body fat and mortality from this viral pandemic including respiratory complications and sequelae of increased activation of the immune system. Despite plans for vaccination of the global population, the risk community spread of COVID-19 and future pandemics will be linked in part to obesity and immunity. This review will detail a number of potential mechanisms through which obesity may contribute to the lethality of this viral infection. These insights will hopefully lead to a greater emphasis on obesity prevention and treatment as part of the global response to this and future pandemic threats.

Association of a Self-Paid Medically Supervised Weight Management Program with Reversal of Obesity-Associated Impaired Fasting Glucose.

AIMS: The progression of prediabetes to T2DM can be delayed through diet modification and weight management. However, the intensive lifestyle program is often not covered by medical insurance. This retrospective analysis evaluates the association of a patient self-paid weight management program on an improvement of blood sugar in overweight and obese patients with impaired fasting glucose (IFG). METHODS: The medical records of 4634 patients who participated in the self-pay UCLA Weight Management Program were reviewed and 2572 patients met the criteria for this retrospective analysis to examine whether this program was associated with the reversal of IFG over 3 months among 1396 patients with normal fasting glucose (NFG) and 1176 with IFG. RESULTS: The patients with IFG lost comparable amounts of weight (10.5 ± 1.3 kg) at three months, as did the subjects with NFG (10.1 ± 1.3 kg). Fasting blood glucose in the IFG group decreased from 108.49 ± 6.4 to 101.8 ± 9.41 mg/dL (p < 0.0001) after three months. There were also significant reductions in triglycerides, and both systolic and diastolic blood pressure in both groups in association with weight loss. CONCLUSION: Our medically supervised self-pay multidisciplinary weight management program was associated with reduced fasting blood glucose levels in patients with IFG over three months with comparable weight loss to patients with NFG.

Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study.

Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equivalent of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metabolism in healthy adults. This study included a 4-week standardization to a low-polyphenol diet, followed by 4 weeks of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 weeks of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addition, there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body composition were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metabolism.

Weight loss for critical care patient to improve lung transplantation candidacy: A case report.

A 47-year-old male with morbid obesity and progressive pulmonary fibrosis was admitted to the intensive care unit (ICU) with worsening hypoxia and nocturnal ventilator dependence. Due to a significant oxygen requirement, the patient could only safely remain in an acute care setting. Unfortunately, he was not eligible for lung transplantation due to having obesity, a relative contraindication to lung transplantation due to potential for post transplantation complications and increased mortality. Therefore, we treated the patient with a modified very low calorie diet (MVLCD) to achieve weight loss. He had successful, sustained weight loss over a period of seven weeks and reached a target weight that made him eligible for transplantation. He subsequently underwent successful bilateral lung transplantation. The patient had improved metabolic parameters and no side effects attributable to the reduced calorie diet. This report shows that in patients with end stage lung disease and a poor prognosis without transplantation, inpatient weight loss is safe and may allow for potentially lifesaving lung transplantation.

Severe Vitamin A Deficiency After Biliopancreatic Diversion.

Biliopancreatic diversion is a surgical procedure that causes weight loss via volume restriction and malabsorption. It is now rarely performed due to the risk of severe nutritional deficiencies including vitamin A. We report a case of severe vitamin A deficiency due to malabsorption from a biliopancreatic diversion procedure for weight loss. By the time the patient presented to our department, she had developed blindness refractory to parenteral vitamin A treatment. A unique feature of her case is the development of a rash with vitamin A injections. This reaction has only been reported in one case series of 3 patients in the published literature. Her case highlights the importance of vitamin deficiency screening in patients after bariatric surgery, and her skin reaction to the injections is a unique side effect that is not frequently observed.

Effects of 28 Days of Oral Dimethandrolone Undecanoate in Healthy Men: A Prototype Male Pill.

Context: Dimethandrolone (DMA) has androgenic and progestational activity. Single oral doses of DMA undecanoate (DMAU) were well tolerated and reversibly suppressed serum LH and testosterone (T) in men. Objective: Assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral DMAU. Design: Double-blind, randomized, placebo-controlled study. Setting: Two academic medical centers. Participants: Healthy men (18 to 50 years). Interventions: One hundred men received DMAU [0, 100, 200, or 400 mg, formulated in castor oil/benzyl benzoate (C) or powder (P)] for 28 days. Subjects underwent 24-hour PK sampling on days 1 and 28 and twice weekly ambulatory visits throughout treatment. Main Outcome Measures: Primary outcomes were safety and tolerability parameters (vitals, laboratory data, mood, and sexual function scores) and adverse events. Secondary outcomes were drug PK profiles and PD effects (serum LH, FSH, and sex hormones). Results: Eighty-two subjects completed the study and were included in the analysis. There were no serious adverse events. No clinically significant changes developed in safety laboratory parameters. A significant dose effect was seen for weight, hematocrit, high-density lipoprotein cholesterol, corrected QT interval, and sexual desire. Serum 24-hour average concentrations of DMAU and DMA showed dose-related increases (P < 0.001). All six subjects in the P400 group and 12 of 13 subjects in the C400 group achieved marked suppression of LH and FSH (<1.0 IU/L) and serum T (<50 ng/dL). Conclusions: Daily oral administration of DMAU for 28 days in healthy men is well tolerated. Doses of ≥200 mg markedly suppress serum T, LH, and FSH. These results support further testing of DMAU as a male contraceptive.

Blood glucose levels before and after cognitive testing in diabetes mellitus.

The primary indices of diabetes mellitus (DM), including hemoglobin A1c (HbA1c) and fasting glucose, appear to be only moderately predictive of the cognitive impairments exhibited by patients with DM. There is evidence that in DM the ability to utilize glucose is compromised and the authors hypothesized that this difficulty might be relevant to the study of cognitive function in DM. Thus, the authors examined the relationship between cognitive performance and changes in peripheral glucose from the start to the conclusion of cognitive testing. Individuals who showed decreased glucose levels from the start to the conclusion of cognitive testing performed significantly better than those exhibiting moderate to slight increases in glucose levels from the start to the conclusion of testing. Apparently, the putative utilization of blood glucose rather than the glucose levels prior to or following a cognitive challenge is associated with better cognitive performance primarily on more complex cognitive tests. This brief and inexpensive test of changes in glucose levels has potential clinical implications for assessing cognitive status in DM.

Rate of peripheral glucose change during cognitive testing predicts performance in diabetes mellitus.

BACKGROUND: The reason for cognitive deterioration in diabetes mellitus (DM) remains unknown. One suggestion is that despite elevated glucose levels, patients with DM generally have difficulty utilizing glucose during cognitive tasks. This assumption was tested in the present study. METHODS: Male outpatients with DM (n = 46; age 52-85 years) were administered a series of standard neuropsychological and cognitive tests. In addition to assessing the time to complete the series of tests, peripheral blood glucose levels were measured prior to and following testing. RESULTS: The rate at which peripheral blood glucose levels changed was examined in relation to cognitive performance. Multiple linear regression analyses revealed significant relationships between the rate of glucose change and performance on tests measuring psychomotor skills, attention, visuoperceptual abilities, sequencing skills, mental flexibility, and planning. Higher rates of decline in peripheral blood glucose levels were associated with better performance on all cognitive measures, except verbal fluency. CONCLUSIONS: During cognitive testing, higher rates of decline in peripheral blood glucose levels may reflect stronger glucose utilization by the brain, thereby facilitating higher levels of cognitive performance. This non-invasive measure may be useful in primary care settings to provide a link between blood glucose changes and cognitive status.