An uncommon association of familial partial lipodystrophy, dilated cardiomyopathy, and conduction system disease

A 46-year-old African American woman presented with severe respiratory distress requiring intubation and was diagnosed with nonischemic cardiomyopathy. She had the typical phenotype of familial partial lipodystrophy 2 (FPLD2). Sequence analysis of LMNA gene showed a heterozygous missense mutation at exon 8 (c.1444C>T) causing amino acid change, p.R482W. She later developed severe coronary artery disease requiring multiple percutaneous coronary interventions and coronary artery bypass surgery. She was later diagnosed with diabetes, primary hyperparathyroidism, and euthyroid multinodular goiter. She had sinus nodal and atrioventricular nodal disease and had an implantable cardioverter defibrillator implantation due to persistent left ventricular dysfunction. The device eroded through the skin few months after implantation and needed a reimplant on the contralateral side. She had atrial flutter requiring ablation. This patient with FPLD2 had most of the reported cardiac complications of FPLD2. This case is presented to improve the awareness of the presentation of this disease among cardiologists and internists.The author(s) received no financial support for the research, authorship, and/or publication of this article.S

Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature

<p>Abstract</p> <p>Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries.</p> <p>In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings.</p> <p>An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.</p

PCOS remains a diagnosis of exclusion:a concise review of key endocrinopathies to exclude

Polycystic ovarian syndrome (PCOS) is a heterogenous disorder associated with clinical, endocrine and ultrasonographic features that can also be encountered in a number of other diseases. It has traditionally been suggested that prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made. However, there is paucity of data regarding the prevalence of PCOS phenotype in some of these disorders, whereas other endocrine diseases that exhibit PCOS-like features may elude diagnosis and proper management if not considered. This article reviews the data of currently included entities that exhibit a PCOS phenotype and those that potentially need to be looked for, and attempts to identify specific features that distinguish them from idiopathic PCOS

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3) : a multicentre phase III study with a doubleblind, randomised withdrawal phase

Background Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11β-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease. Methods LINC 3 was a prospective, multicentre, open-label, phase III study with a double-blind randomised withdrawal period, that comprised four periods. Patients aged 18–75 years, with confirmed persistent or recurrent Cushing's disease (defined as mean 24-h urinary free cortisol [UFC] concentration >1·5 times the upper limit of normal [ULN] and morning plasma adrenocorticotropic hormone above the lower limit of normal) who had previously had pituitary surgery or irradiation, or were newly diagnosed and who refused surgery or were not surgical candidates, were recruited from 66 hospital sites and private clinical practices in 19 countries. In period 1, open-label osilodrostat was initiated in all participants and adjusted every 2 weeks (1–30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h UFC concentration and safety until week 12. In period 2, weeks 13–24, osilodrostat was continued at the therapeutic dose determined during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomly assigned (1:1), via an interactive-response technology, stratified by osilodrostat dose at week 24 and history of pituitary irradiation, to continue osilodrostat or switch to placebo for 8 weeks. Participants and investigators were masked to treatment assignment. Ineligible participants continued open-label osilodrostat. In period 4, weeks 35–48, all participants were given open-label osilodrostat until core-study end. The primary objective was to compare the efficacy of osilodrostat versus placebo at the end of period 3. The primary endpoint was the proportion of participants who had been randomly assigned to treatment or placebo with a complete response (ie, mean 24-h UFC concentration of ≤ULN) at the end of the randomised withdrawal period (week 34), without up-titration during this period. The key secondary endpoint was the proportion of participants with a complete response at the end of the single-arm, open-label period (ie, period 2, week 24) without up-titration during weeks 13–24. Analysis was by intention-to-treat for all patients who received at least one dose of osilodrostat (full analysis set; key secondary endpoint) or randomised treatment (randomised analysis set; primary endpoint) and safety was assessed in all enrolled patients who received at least one dose of osilodrostat and had at least one post-baseline safety assessment. LINC 3 is registered with ClinicalTrials.gov, NCT02180217, and is now complete. Findings Between Nov 12, 2014, and March 22, 2017, 202 patients were screened and 137 were enrolled. The median age was 40·0 years (31·0–49·0) and 106 (77%) participants were female. 72 (53%) participants were eligible for randomisation during the withdrawal phase, of whom 36 were assigned to continue osilodrostat and 35 were assigned to placebo; one patient was not randomly assigned due to investigator decision and continued open-label osilodrostat. More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7–53·4]; p25% of participants) were nausea (57 [42%]), headache (46 [34%]), fatigue (39 [28%]), and adrenal insufficiency (38 [28%]). Hypocortisolism occurred in 70 (51%) patients and adverse events related to adrenal hormone precursors occurred in 58 (42%) patients. One patient died, unrelated to study drug, after the core study phase. Interpretation Twice-daily osilodrostat rapidly reduced mean 24-h UFC and sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. Osilodrostat is an effective new treatment option that is approved in Europe for the treatment of endogenous Cushing's syndrome and in the USA for Cushing's disease

Thyroid nodules: diagnosis and therapy

Less than 1% of all cancers are present in the thyroid, yet thyroid nodules are found in 4 to 10% of the adult population. Because thyroid nodules are relatively common, the diagnostic dilemma is to distinguish between a more common benign nodule, which usually does not require specific treatment, and a malignant nodule, which requires thyroidectomy and further treatment. Thyroid nodules usually are an incidental finding on a routine examination by a primary care physician. When patients seek treatment for symptomatic nodules, a more serious problem may be indicated, and thyroid cancer is suggested. However, additional studies have demonstrated the use of genetic markers and immunohistochemistry in the diagnosis of thyroid nodules, which may lead to a more rational approach to the treatment. This article reviews literature published in the last 12 months pertaining to the pathogenesis, diagnosis, and treatment of thyroid nodules

Sweet Seizures – Epilepsia Partialis Continua

Epilepsia partialis continua (EPC) refers to focal and recurrent seizures that happenevery few seconds to minutes for extended periods of time. The most common causesof these seizures are stroke, Rasmussen’s encephalitis (in children), and viral encephalitis.Metabolic disorders, like hyperglycemic hyperosmolar state (HHS), infrequentlycause EPC. Correction of the HHS stops the EPC and eliminates the need for antiepilepticdrugs. Synaptic transmission in the central nervous system requires normal glucoseconcentrations. Hyperglycemia can lower the seizure threshold, and this possiblyexplains the development of seizures in patients with HHS

Regional decrease of subcutaneous adipose tissue in patients with type 2 familial partial lipodystrophy is associated with changes in thyroid hormone metabolism

6 páginas, 2 figuras.-- et al.[Background]: Familial partial lipodystrophy of the Dunnigan type (FPLD2) presents with a decrease of subcutaneous adipose tissue (SAT) in the limbs and trunk. As thyroid hormones (TH) play an important role in adipogenesis, we studied if SAT from subjects with FPLD2 have changes in the gene expression levels of monocarboxylate transporter 8 (MCT8), a TH transporter, and TH nuclear receptors and in iodothyronine deiodinases (DIOs) expression and activities that could affect TH bioavailability and action in white adipose tissue. [Methods]: Seven subjects with FPLD2 and 10 healthy controls were studied. Two biopsies of SAT were obtained from each subject, one near the umbilicus and the other from the thigh. Expression of MCT8, DIO2, DIO3, THRA1, THRB1, and RXRG mRNAs were quantified by real-time polymerase chain reaction. DIO1 and DIO2 activities in adipose tissue homogenates were determined. Serum thyroid-stimulating hormone and TH levels were measured by chemiluminescence. [Results]: Subjects with FPLD2 had lower levels of MCT8 mRNA expression in the thigh than in the abdomen SAT, and lower than in the abdomen and thigh SAT from control subjects. FPLD2 subjects also had higher DIO2 expression and activity in the thigh than in the abdomen SAT and higher than in controls. [Conclusions]: Thigh SAT from subjects with FPLD2 has lower expression of MCT8 and higher DIO2 expression and activity than abdominal SAT, suggesting that changes in local TH metabolism may occur in areas with lipoatrophy. DIO2 expression and activity in SAT suggest that DIO2 can regulate the metabolism and action of TH in human white adipose tissue.This work was supported by the Ministerio de Educación (grant SAF2006-02542 to J.L.-A., SAF2006-01319 to M.J.O., FMM2005-X0582 to R.M.C., and FMM2006-0835 to M.J.O.) and Xunta de Galicia (grant PGIDIT04PXIC20801PN to J.L.-A., PGIDIT06PXIB 208360PR to J.L.-A., and PGIDIT03PXIB20801PR to D.A.-V.). CIBEROBN is an initiative of Instituto de Salud Carlos III (ISCIII), Spain.Peer reviewe