The Mount Sinai Clinical Pathway for the Diagnosis and Management of Hypercortisolism due to Ectopic ACTH Syndrome.

Neoplasms that secrete ectopic adrenocorticotropin (ACTH) may cause severe, life-threatening hypercortisolism. These tumors are often difficult to localize and treat, requiring a comprehensive and systematic management plan orchestrated by a multidisciplinary team. The Mount Sinai Adrenal Center hosted an interdisciplinary retreat of experts in adrenal disorders and neuroendocrine tumors (NETs) with the aim of developing a clinical pathway for the management of Cushing syndrome due to ectopic ACTH production. The result was institutional recommendations for the diagnosis, localization, surgical approaches to intrathoracic tumors and bilateral adrenalectomy, and perioperative and postoperative medical management of hypercortisolism and its sequelae. Specific recommendations were made regarding the timing and selection of therapies based on the considerations of our team as well as a review of the current literature. Our clinical pathway can be applied by other institutions directly or serve as a guide for institution-specific management.

Increased Thyroid-Hormone Requirements Consistent With Type 3 Deiodinase Induction Related to Ibrutinib in a Thyroidectomized Woman.

OBJECTIVE: Tyrosine-kinase inhibitors (TKIs) are chemotherapeutic agents associated with increased thyroid-hormone requirements and altered deiodinase activity. We present the first case to link these findings to the TKI ibrutinib. METHODS: Serial thyroid-stimulating hormone (TSH), free-thyroxine (FT4), free-triiodothyronine (FT3), and reverse-triiodothyronine (rT3) levels were assessed. RESULTS: An 80-year-old, 62-kg woman with hypothyroidism secondary to total thyroidectomy for stage I papillary thyroid cancer, on maintenance levothyroxine (LT4) 137 µg daily, presented for follow-up. Compared to one year prior, the patient's weight had increased by 2 kg and TSH from 2.58 to 27.60 µIU/mL (normal: 0.45-4.50 µIU/mL) while on pantoprazole. Ibrutinib, her other medication, had been started seven months prior for chronic lymphocytic leukemia. Despite sequential confirmation of proper LT4 adherence and self-administration, adjustment of LT4 to 150 µg, and discontinuation of pantoprazole, the patient's hypothyroid symptoms worsened, and the TSH was 73.90 µIU/mL six months later. LT4 was increased to 175 µg six days a week and 262.5 µg once weekly. Two months later, the TSH was 3.92 µIU/mL (steady-state condition), FT4 2.32 ng/dL (normal: 0.82-1.77 ng/dL), FT3 1.6 pg/mL (normal: 2.0-4.4 pg/mL), and rT3 69.6 ng/dL (normal: 9.2-24.1 ng/dL). Ibrutinib was discontinued the next month due to gastrointestinal side effects and elevated blood pressure. Four months later, LT4 had been reduced to 150 µg, and the FT4 reached 1.92 ng/dL, FT3 2.0 pg/mL, and rT3 26.6 ng/dL. CONCLUSION: This report links ibrutinib to increased thyroid-hormone requirements in a thyroidectomized woman whose decreased T3:T4, T3:rT3, and T4:rT3 ratios suggested type 3 deiodinase induction and type 2 deiodinase inhibition.

Durability of the effect of online diabetes training for medical residents on knowledge, confidence, and inpatient glycemia.

BACKGROUND: Inpatient dysglycemia is associated with increased morbidity, mortality and cost. Medical education must not only address knowledge gaps, but also improve clinical care. METHODS: All 129 medicine residents at a large academic medical center were offered a case-based online curriculum on the management of inpatient dysglycemia in the fall of 2009. First-year residents took a 3-h course with 10 modules. Second and third-year residents, who had been educated the prior year, underwent abbreviated training. All residents were offered a 20-min refresher course in the spring of 2009. We assessed resident knowledge, resident confidence, and patient glycemia on two teaching wards before and after the initial intervention, as well as after the refresher course. RESULTS: A total of 117 residents (91%) completed the initial training; 299 analyzed admissions generated 11, 089 blood glucose values and 4799 event blood glucose values. Admissions with target glycemia increased from 19.4% to 33.0% (P = 0.035) by the end of the curriculum. There was a strong downward trend in hyperglycemia from 22.4% to 11.3% (P = 0.055) without increased hypoglycemia. Confidence and knowledge increased significantly among first-time and repeat participants. Residents rated the intervention as highly relevant to their practice and technologically well implemented. CONCLUSION: Optimization of an online curriculum covering the management of inpatient glycemia over the course of 2 years led to significantly more admissions in the target glycemia range. Given its scalability, modularity and applicability, this web-based educational intervention may become the standard curriculum for the management of inpatient glycemia.

Effect of case-based training for medical residents on inpatient glycemia.

OBJECTIVE: To determine whether an educational intervention for medical house staff improves blood glucose (BG) in hospitalized patients. RESEARCH DESIGN AND METHODS: All 116 medicine residents at an academic medical center were assigned to online or classroom training on inpatient dysglycemia in fall 2008. Both groups were offered an online refresher course in spring 2009 addressing gaps in clinical practice identified on chart review. We assessed event BG, the first BG of any 3-h period, on two teaching wards. RESULTS: A total of 108 residents (93.1%) completed the initial training. The primary outcome, median event BG, decreased from 152 mg/dL in August 2008 to 139 mg/dL in December 2008 (P < 0.0001). Prevalence of event BG >200 mg/dL decreased from 25.5 to 22.7% (P = 0.0207), at the expense of more event BGs <70 mg/dL (2.0-3.9%, P = 0.0124). CONCLUSIONS: A curriculum for medicine residents on inpatient glycemia led to lower inpatient BG.

Effect of case-based training for medical residents on confidence, knowledge, and management of inpatient glycemia.

OBJECTIVE: To determine whether a brief, case-based educational intervention improves resident confidence, knowledge, and management of glycemia in hospitalized patients. RESEARCH DESIGN AND METHODS: All 116 medical residents at a large academic medical center were offered a case-based curriculum on the management of inpatient glycemia in fall 2008. Residents on ambulatory and elective rotations were taught in small groups, whereas all others underwent online training. All participants were offered a brief online refresher course in spring 2009. We assessed resident confidence across 9 domains of treating inpatient dysglycemia, knowledge based on 4 questions before the course, a 23-part questionnaire after the intervention, and changes in resident behavior as documented in chart abstractions. RESULTS: One hundred eight (93.1%) residents completed initial training, and 102 (87.9%) completed the refresher course. The share of scores indicating that residents felt "somewhat comfortable" or "completely comfortable" treating inpatient dysglycemia increased from 62.5% before the course to 94.3% (P<0.001) after the initial intervention and 92.8% (P<0.001) after the refresher. Knowledge scores improved from 72.2% correct answers to 88.9% (P<0.001) for the 4 questions asked before and after the course. Across all 23 questions posed after the initial course, residents answered 86.1% correctly and maintained a score of 85.5% after the refresher course. Online-trained residents, at 89.7%, outscored their classroom-trained peers (82.3%; P<0.001) after the initial course. Chart abstractions did not show any significant changes in managing glycemia. CONCLUSION: A curriculum on the management of inpatient glycemia was broadly adopted by medical residents at a large academic medical center and led to greater confidence and knowledge among residents. Further expansion to other health care providers and hospitals using a Web-based format and incorporation of updated guidelines is needed to confirm and build on these encouraging results.

Autoimmune hyperthyroidism due to secondary adrenal insufficiency: resolution with glucocorticoids.

OBJECTIVE: To describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids. METHODS: We report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis. RESULTS: Autoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient's symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency. CONCLUSIONS: The hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis.

Weight management in type 2 diabetes mellitus.

Obesity is a well known risk factor for type 2 diabetes mellitus. Individuals with type 2 diabetes mellitus are at risk for weight gain as a result of multiple influences, including sedentary lifestyle, high-calorie diet, diabetes medications, sociocultural factors, chronic medical and psychiatric illnesses, and a dysregulated enteroendocrine axis. Because both diabetes mellitus and obesity predispose patients to abnormal cardiometabolic profiles and increased cardiovascular disease, management of diabetes mellitus should focus on weight management and optimizing cardiometabolic parameters, concomitant with glycemic control. Lifestyle modification incorporating healthy, calorie-appropriate diets and increased physical activity, in addition to metformin, are central components to diabetes management and weight management. These interventions have been shown to improve body weight, glycemic control, and overall cardiometabolic profile. The weight-neutral and weight-losing diabetes medications include metformin, alpha-glucosidase inhibitors, glucagon-like peptide-1 analogs, dipeptidyl peptidase-4 inhibitors, and amylin analogs. It is essential that providers understand the metabolic and weight effects of diabetes medications in order to develop strategies for managing diabetes mellitus while helping patients maintain or lose weight in order to improve their overall health outcomes.

Bromocriptine approved as the first medication to target dopamine activity to improve glycemic control in patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) continues to rise in prevalence in the United States and worldwide. Despite advances in medical treatments for T2DM, many patients remain uncontrolled. By targeting centrally mediated pathways of glucose metabolism, bromocriptine represents a novel therapeutic option in T2DM. Several small clinical trials demonstrate improvements in insulin resistance and glycemic control. After the submission of data from four recent, large clinical trials, the US Food and Drug Administration has approved the use of bromocriptine in T2DM. We review the available data from these four trials and other published studies. Bromocriptine is a promising therapy for diabetes patients and demonstrates modest improvements in glycemic control.