Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.

AIM: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up. METHODS: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months. RESULTS: The Kaplan-Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan-Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan-Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan-Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. CONCLUSIONS: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.

An acromegaly case treated with clomiphene citrate: add-on treatment in primary medical therapy.

INTRODUCTION: Acromegaly is a disease with various comorbidities and hypogonadism is a common comorbidity in patients with acromegaly. Herein, we aim to present our experience with clomiphene citrate in a patient with acromegaly accompanied by hypogonadism, who declined surgery. CASE REPORT: A 40-year-old male patient with impaired fasting glucose, hyperlipidemia, and psychosis and who complained of increasing tongue growth, snoring, enlargement of the hands, spacing between the teeth, and loss of libido for the last 6 years was followed up. Acromegaly was diagnosed, with high levels of insulin-like growth factor-1 (IGF-1) and a pituitary neuroendocrine tumor measuring 11 mm; the patient had concomitant hypogonadism. Lanreotide was started as the initial primary medical treatment. Clomiphene citrate was added to the patient's treatment. The patient, whose IGF-1 level was high during follow-up, did not want to use the intramuscular testosterone esters for hypogonadism. In the third month of clomiphene citrate treatment, IGF-1 normalization was achieved and the patient's total testosterone level increased. DISCUSSION: Biochemical control is not always achieved with somatostatin receptor ligands and dopamine agonists in the treatment of acromegaly. Therefore, we support the use of clomiphene citrate (CC) as a cost-effective oral add-on treatment option in selected hypogonadal acromegaly cases.

Homozygous LMNA p.R582H pathogenic variant reveals increasing effect on the severity of fat loss in lipodystrophy.

BACKGROUND: Classical heterozygous pathogenic variants of the lamin A/C (LMNA) gene cause autosomal dominant familial partial lipodystrophy type 2 (FPLD2). However, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants, and a few patients have been associated with generalized fat loss. CASE PRESENTATION: Here, we report a patient with a lamin A specific pathogenic variant in exon 11, denoted LMNA (c.1745G > A; p.R582H), present in the homozygous state. Fat distribution was compared radiographically to an unrelated heterozygote LMNA p.R582H patient from another pedigree, a healthy female control, a series of adult female subjects with congenital generalized lipodystrophy type 1 (CGL1, n = 9), and typical FPLD2 (n = 8). The whole-body MRI of the index case confirmed near-total loss of subcutaneous adipose tissue with well-preserved fat in the retroorbital area, palms and soles, mons pubis, and external genital region. This pattern resembled the fat loss pattern observed in CGL1 with only one difference: strikingly more fat was observed around mons pubis and the genital region. Also, the p.R582H LMNA variant in homozygous fashion was associated with lower leptin level and earlier onset of metabolic abnormalities compared to heterozygous p.R582H variant and typical FPLD2 cases. On the other hand, the heterozygous LMNA p.R582H variant was associated with partial fat loss which was similar to typical FPLD2 but less severe than the patients with the hot-spot variants at position 482. CONCLUSIONS: Our observations and radiological comparisons demonstrate an additive effect of LMNA pathogenic variants on the severity of fat loss and add to the body of evidence that there may be complex genotype-phenotype relationships in this interesting disease known as FPLD2. Although the pathological basis for fat loss is not well understood in patients harboring pathogenic variants in the LMNA gene, our observation suggests that genetic factors modulate the extent of fat loss in LMNA associated lipodystrophy.

Therapeutic plasma exchange in hypertriglyceridemic patients

Background/aim: High triglyceride (TG) levels are associated with increases in atherosclerotic cardiovascular disease (CVD), hepatic steatosis, and pancreatitis. Acute pancreatitis is a condition with high mortality. Therapeutic plasma exchange (TPE) in the treatment of hypertriglyceridemic pancreatitis (HTGP) is a rapid and effective treatment modality. In this study, the results of TPE were evaluated and the frequency of lipoprotein lipase (LPL) mutation in these patients was determined. Materials and methods: TPE was performed in 31 patients with HTGP at the Adult Therapeutic Apheresis Center. Results: A TG level under 500 mg/dL was achieved by applying apheresis at a median of 2 times (IQR 2­2, min 1, max 6) in the 31 cases. LPL mutation was detected in 8 (25.8%) of the 31 hypertriglyceridemia cases. When TG levels before and after TPE were evaluated, the mean TG level before TPE was significantly higher (3132 ± 1472 mg/dL) than the mean TG level afterwards (948 ± 465 mg/dL, P < 0.001). This result represented a decrease of 69.7% TG after TPE. Conclusion: TPE is a safe, fast, and effective treatment modality in experienced centers.

Levothyroxine absorption test results in patients with TSH elevation resistant to treatment.

INTRODUCTION: Persistent elevation of thyroid-stimulating hormone (TSH) is common in endocrinology practice in patients undergoing replacement or suppression therapy with levothyroxine sodium (LT4). After examining the causes of this condition, LT4 absorption test is recommended. In this report, we wanted to share our results of LT4 absorption test in patients with elevated TSH levels. MATERIALS-METHODS: The files of patients who presented to our clinic between 2015 and 2018, whose TSH elevation continued despite high-dose LT4 therapy, and who underwent absorption test were reviewed retrospectively. RESULTS: Levothyroxine sodium absorption test was applied to five patients. Absorption test revealed LT4 malabsorption in two patients and pseudomalabsorption in the other three patients. DISCUSSION: When all published pseudomalabsorption cases were considered, it has been stated that at least 2.5 times increase in basal fT4 level may exclude malabsorption. The formula we used has been implemented by Cleveland Clinic since 2014. CONCLUSION: In cases where TSH normalization is not achieved despite high doses of LT4 therapy, LT4 absorption test is an easy test for administration and interpretation and prevents unnecessary medical treatments and examinations.

Glucagon like peptide-1 (GLP-1) likes Alzheimer's disease.

Glucagon-like peptide-1 (GLP-1) is a 30 amino acid long peptide hormone derived from the proglucagon gene and secreted in the distal small intestine when food enters the duodenum. GLP-1 is also produced in the central nervous system (CNS), predominantly in the brainstem, and subsequently transported to a large number of regions in the CNS. Neuronal cells in nucleus tractus solitarius (NTS) can synthesize GLP-1 and extends to hypothalamus, some thalamic and cortical areas. A G protein coupled receptor (GPCR) provides the majority of GLP-1 actions. GLP-1 receptor activation triggers some in vivo signaling pathways. GLP-1 receptor agonists (GLP-1 RA) are used in the treatment diabetes and obesity. GLP-1 stimulates insulin secretion, inhibits glucagon secretion, decreases food intake, reduces appetite, delays gastric emptying, provides weight reduction, and protects ß cells from apoptosis. Alzheimer's disease (AD) is the most prevalent form of dementia. It is characterized by cognitive insufficiencies and behavioral changes that impact memory and learning abilities, daily functioning and quality of life. Hyperinsulinemia and insulin resistance, which are known as pathophysiological features of the T2DM, have also been demonstrated to have significant impact on cognitive impairment. It is thought that GLP-1 affects neurological and cognitive functions, as well as its regulatory effect on glucose metabolism. The pathophysiological relationship between GLP-1 and AD is discussed in this review.

Fludarabine Treatment of Patient with Chronic Lymphocytic Leukemia Induces a Digital Ischemia.

We report a 63-year-old man with a history of chronic lymphocytic leukemia (CLL) who presented with asymmetrical Raynaud's phenomenon of sudden onset which progressed to acral gangrene rapidly in a week. These symptoms began approximately one week after the fourth cycle of fludarabine and cyclophosphamide chemotherapy and were accompanied by pain, numbness, and cyanosis in the fingers of his right hand except the first finger. Fludarabine may play a role in acral vascular syndrome. The treatment with fludarabine in patients with evolving digital ischemia should be carried out with caution.