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Background: Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids., Case Presentation: Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient's symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality., Conclusions: Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis., (© 2023. The Author(s).)

Although prolonged hypercortisolism is associated with increased mortality and substantial morbidity, the clinical signs and symptoms are wide ranging and often nonspecific, contributing to challenges in diagnosis, as well as treatment delays. Greater awareness is needed among clinicians to help identify which patients should undergo biochemical screening for excess cortisol. Several biochemical tests are available, each with important caveats that should be considered in the context of the individual patient. Cortisol secretion varies widely, further complicating the biochemical diagnosis of hypercortisolism, which relies on the use of definitive cutoff values. Patients with hypercortisolism resulting from adrenal adenomas, including those discovered incidentally, often do not present with overt Cushingoid features (plethora, striae, muscle weakness, moon facies, etc. ). However, the consequences of prolonged exposure to even slight elevations in cortisol levels are profound, including increased risk of diabetes, hypertension, fractures, cardiovascular events, and mortality. Because most cases of hypercortisolism resulting from an adrenal adenoma can be managed, it is imperative to identify patients at risk and initiate testing early for the best outcomes. The aim of this report is to increase awareness of the indications for screening for hypercortisolism and to review the biochemical screening tests and diagnosis for hypercortisolism associated with adrenal adenomas.

Background: The purpose of this study was to compare treatment satisfaction among people with type 1 and type 2 diabetes after switching from insulin lispro to insulin aspart in continuous subcutaneous insulin infusion (CSII). Efficacy of glycemic control between treatments was also investigated., Methods: Subjects using CSII with insulin lispro for 6 months or longer continued this therapy over a 4-week period and then switched to insulin aspart in CSII for 12 weeks. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Insulin Treatment Satisfaction Questionnaire (ITSQ) were administered immediately prior to the switch and again at the end of 12 weeks of therapy with insulin aspart. Hemoglobin A(1c)(A1C) and fasting blood glucose (FBG) levels, insulin dose, and body weight were recorded at the same time points., Results: Although average overall DTSQ score did not change significantly, average overall ITSQ score was significantly improved following the insulin aspart treatment. There was a small but statistically significant reduction in mean A1C and FBG following 12 weeks of CSII using insulin aspart., Conclusions: Both insulin aspart and insulin lispro are appropriate for CSII. ITSQ improvements suggest that aspects of CSII therapy with insulin aspart positively impact treatment satisfaction.

Because patients with type 2 diabetes are at high risk for cardiovascular events, lipid abnormalities in these patients should be aggressively and efficiently treated. What is the rationale behind such an approach, and what are the goals of therapy? Dr Marcus addresses these questions and provides up-to-date recommendations for lipid-lowering treatment.

Purpose: Our purpose was to determine if complete revascularization could be successfully performed off bypass in the majority of coronary artery bypass graft (CABG) patients., Methods: Using a metabolic protocol and the Medtronic Octopus stabilizer device (Medtronic, Inc., Minneapolis, MN), 285 consecutive patients between July 1, 1997 and July 31, 1999 were successfully revascularized off pump via median sternotomy. A relative contraindication for off bypass CABG was cardiogenic shock. The metabolic protocol was designed to enhance systolic and diastolic cardiac function during surgery., Results: Of 298 patients on whom we attempted off-pump revascularizations, 96% (285/298) were successful. The mean number of grafts per case was 3.3. The mean age of patients was 69.5 years, and 38% (109/285) were 75 years of age or older. Perioperative myocardial infarction (MI) occurred in two patients (0.7%) and operative mortality was 2.8% (8/285). Average Parsonnet score was 4.8. Cost savings were realized through minimal blood product utilization (average 1.5 units per case) and decreased cardiopulmonary bypass supplies., Conclusion: Complete revascularization can be performed off bypass in the majority of CABG patients. The concomitant use of the Octopus off-bypass technique with aggressive metabolic support ensures manual manipulation of a beating heart and results in a low incidence of postoperative complications and significant cost savings.

It is becoming increasingly acknowledged that people with Type 2 Diabetes represent what can be termed "an enriched population": a group that has the greatest risk of morbidity and mortality from cardiovascular diseases such as myocardial infarcts and strokes. Due to the tremendous toll, both human and financial, that these cardiovascular diseases result in, major efforts are being put forth to decrease their occurrence. It is clear that success in this endeavor is optimized by achieving target levels of glucose, blood pressure, and cholesterol. Analysis of the individual drugs used to treat these comorbidities of the cardiovascular dysmetabolic syndrome has brought an understanding that frequently monotherapy is ineffective, and a clear appraisal of the benefits of available pharmaceuticals can result in a successful decision about which agents to include in regimens of combination therapy. This success translates into ultimately reducing the untimely death and disability that is unfortunately all too common among the people with these illnesses. As diabetes continues to be increasing alarmingly among all segments of the population, there is an urgency for this need. The knowledge is present; only the application is not.

The benefits of blood pressure lowering, lipid lowering, and glycemic control on morbidity and mortality have been established in major long-term clinical trials. The most extensive information is available for diuretics or beta-blockers in hypertension, hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in dyslipidemia, and insulin or sulfonylureas in diabetes. Other drug classes provide similar improvements in blood pressure, lipid profile, and glycemic control, and thereby might be expected to provide comparable long-term benefits. As a result, national guidelines advocate treating patients aggressively in order to achieve control of blood pressure low-density lipoprotein (LDL) cholesterol, and blood glucose. The risks associated with drug treatment are generally class-specific. Among antidiabetic agents, sulfonylureas and insulin are associated with risk for severe hypoglycemia, metformin with risk for lactic acidosis, and troglitazone with risk for idiosyncratic hepatocellular injury. Similarly, widely used antihypertensive and lipid-lowering agents are associated with risk for serious complications, such as angioedema with angiotensin-converting enzyme inhibitors, possible increased risk for myocardial infarction and cancer with calcium antagonists, and myositis and liver dysfunction with statins. Physicians must take an aggressive approach to patient management in order to achieve a level of disease control that optimally reduces risk for morbidity and mortality. Serious adverse events may occur rarely with most drug classes; these events can be minimized by appropriately monitoring or selecting patients for treatment.

The primary objective of treating hypercholesterolemia is to reduce the patient's risk of developing coronary artery disease (CAD). Reducing low-density lipoprotein (LDL) cholesterol levels to achieve National Cholesterol Education Program (NCEP) goal lipid levels greatly reduces this risk. Treatment of additional risk factors for CAD (high blood pressure, diabetes, smoking) should be addressed and modified as part of appropriate patient management, but a high LDL cholesterol level is a major risk factor. Therefore, to effectively modify morbidity and mortality, reaching and maintaining NCEP target lipid levels should be the goal of lipid-lowering therapy. Epidemiologic data indicate that most adults in the United States need <30% reduction in LDL cholesterol level to achieve their NCEP goal. Regardless of the intervention or therapeutic agent used, the results of numerous studies have demonstrated that reducing LDL cholesterol levels to NCEP goals will result in significant reduction of CAD risk.

Initiation of insulin therapy is an exhilarating although anxiety-provoking experience for diabetic patients. It is, in a metaphysical sense, a time of rebirth. Patients are no longer victims of their diabetes but truly masters of it. No statement better illustrates how basic this change is than that of a patient who says, "What a difference it has made in my life to eat a meal because I want to, not because I have to." This article examines a means of insulin delivery that is growing in acceptance--insulin pump therapy.

A new TSH immunoenzymometric assay was found to be capable of discriminating between the serum TSH values of normal subjects [2.28 +/- 1.02 (+/-SD); range, 0.6-6.5 microU/ml] and those of clinically euthyroid, antithyroid drug-treated (n = 22) or clinically thyrotoxic (n = 34) patients. While a wide spectrum of basal TSH values was found in the antithyroid drug group [ranging from undetectable (less than 0.05 microU/ml: 57%) to 17.9 microU/ml], all clinically thyrotoxic patients had undetectable values. In 33 patients receiving chronic oral T4 therapy for treatment of goiter (n = 15) or thyroid cancer (n = 18), 48% (6 of 33) had undetectable basal TSH levels and no TSH response to TRH stimulation. Detectable TSH levels were found in 42% (14 of 33), and TRH responsiveness was found in 52% (17 of 33). The TSH response to TRH stimulation was less than 2.0 microU/ml in 7 patients. Serum free T4 index, free T3 index, and free T4 levels and oral T4 dosage were inferior predictors of TRH responsiveness compared to the basal TSH value. No patient receiving more than 0.2 mg T4 daily or having a free T4 index above 18, a free T3 index above 205 or a free T4 level above 3.0 ng/dl had a TSH response to TRH. Seventy-six percent (16 of 21) of the patients, when reevaluated 1-6 weeks after increased oral T4 dosage, had a significant reduction in their serum thyroglobulin level. This was true of both patients with initially detectable (11 of 14) as well as undetectable (5 of 7) basal serum TSH levels. These findings support the concept that subnormal and, for that matter, as yet undetectable levels of circulating TSH may exert stimulatory effects on thyroid tissue.

A 24-year-old woman presented with progressive optochiasmatic arachnoiditis causing progressively worsening visual loss associated with headache and amenorrhea. Treatment with the standard initial therapy of dexamethasone, warfarin, and dipyridamole was unsuccessful at halting her disease process. Surgical lysis of adhesions led to a temporary improvement and then deterioration. A course of therapy with cyclophosphamide was initiated and her response to this therapy resulted in resolution of her headaches, return of her vision to normal, and resumption of her normal menstrual cycles.