ACTA ENDOCRINOLOGICA (BUC)

Background and aims. Increased fat accumulation associated to increased cardiometabolic risk factors is a prominent feature of type 2 diabetes. In type 1 diabetes, increased fat accumulation is not prevalent and its metabolic impact has not been fully evaluated. We aimed to evaluate differences in body composition, clinical and metabolic\r\nprofile in type 1 and type 2 diabetes patients with varying degrees of adiposity.\r\nMaterials and methods. Clinical, biochemical and body composition data (using a bioelectric impedance analyzer) from 96 type 1 and 253 type 2 adult diabetes patients have\r\nbeen collected.\r\nResults. In type 1 patients estimated visceral fat area (eVFA) increased significantly (84.3?27.9 vs. 103.0?27.9 vs. 128.1?29.1 cm2, p=0.006, 0.003, and <0.001) while BMI, body fat mass (BFM) did not differ across age tertiles. Between normal weight (BMI<25 kg/m2) and overweight (BMI>25 kg/m2) type 1 patients there were no significant differences either in triglycerides (128.7?135.6 vs. 92.8?50.6 mg/dl, p=0.1), HDL-cholesterol (53.6?15.9 vs.\r\n52.3?13.7 mg/dl, p=0.6) and uric acid levels (3.4?2.0 vs. 2.9?1.2 mg/dl, p=0.2), or in hypertension (39.5% vs. 40.0%, p=0.7) and nonalcoholic hepatosteatosis (NASH) (10.0% vs.\r\n10.5%, p=0.6) prevalences. In type 2 patients, BMI (32.3?5.9 vs. 29.5?5.1 vs. 27.9?5.0 kg/m2, p=0.001, p=0.04, p<0.001) and BFM (34.5?12.7 vs. 29.6?10.2 vs. 27.1?10.8 kg, p=0.007, p=0.11, p <0.001) decreased, while eVFA did not differ across age tertiles, suggesting that older age increases central fat distribution. Compared to normal weight, overweight type 2 diabetes patients had greater triglycerides (218.8?303.4 vs. 110.9?44.9 mg/dl, p=0.01), uric acid (4.5?2.4 vs. 3.3?1.4 mg/dl, p=0.01), and lower HDL-cholesterol (43.9?12.9 vs. 54.1?15.4 mg/dl, p<0.001) serum levels, and higher prevalences of hypertension (71.8% vs. 39.4%, p=0.005) and NASH (59.1% vs. 25.0%, p=0.005).\r\nConclusion. Visceral fat accumulation is associated with older age in both types of diabetes, but only in type 2 diabetes is associated with cardiometabolic anomalies.

Context. The metabolic syndrome is a profound, systemic impairment of the metabolism of lipids, carbohydrates and branched amino-acids, affecting specially obese people. Recently, many studies outlined the presence of the metabolic syndrome, also in non obese persons. Objective and design. To assess the relationship between insulin resistance and the cardiovascular component of the metabolic syndrome in a group of young, non obese subjects using a cross sectional study. Subjects and methods. We enrolled 103 subjects with body mass index < 30 Kg/m2, without metabolic syndrome to whom fasting glucose, triglycerides, high density lipoprotein cholesterol, insulinemia, waist circumference and arterial pressure were recorded in a crosssectional approach. Insulin resistance was evaluated using the homeostasis model assessment for insulin (HOMA-IR) index. Statistic data processing included Pearson relation and multiple regression (backward method), using the SPSS version 21 software. Results. A significant relationship between waist circumference, diastolic blood pressure and HOMA-IR is found. High value of HOMA-IR (>2.6) was more frequently in men (p=0.011). The incidence of the 2 metabolic components mentioned above was higher in the high value HOMA-IR group: 33% vs. 7% in women and 50% vs. 4% in men. Multiple regression showed a strong correlation between HOMA-IR and waist circumference (p<0.001) and diastolic blood pressure (p=0.008) that was maintained inside the women group (p=0.016 and p=0.032, respectively). In men, HOMA-IR correlated with waist circumference (p=0.031). Conclusion. We found a significant interdependence between waist circumference, diastolic blood pressure and HOMA-IR. Based on our results, we consider that lifestyle intervention should start as soon as abnormal waist circumference is recorded.

Context. Metabolic surgery is currently the most efficient treatment for obesity, but concern is raised about the possible long-term nutritional side effects. Bone metabolism is often adversely affected after surgery, but literature data are contradictory. Objective. The aim of this study was to evaluate the evolution of bone mass parameters in the first year after laparoscopic sleeve gastrectomy in relation to anthropometric and body composition parameters and specific hormones of obesity. Design. We conducted a prospective study on 75 patients with obesity that underwent metabolic surgery over a course of 18 months at our center, with a follow-up period of 12 months. Subjects and Methods. All patients underwent a complex preoperative assessment and were required to return for medical follow-up at 6 and 12 months after surgery. Each visit included anthropometric parameters, DEXA and determination of specific hormonal parameters. Results. We noticed a significant improvement in anthropometric and body composition parameters after surgery. The value of adiponectin presented a significant increase after surgery and leptin showed a significant decrease at 6 and 12 months postoperative; ghrelin level decreased postoperative compared to preoperative, but without statistical significance. We observed no reduction in BMD after surgery, but a significant improvement in BMC at 12 months after surgery compared to preoperative. Ghrelin negatively correlated to BMD preoperative. Conclusions. Despite the significant alterations in anthropometric, body composition and hormonal parameters, we found no negative effect on BMD and BMC in our study population.

Resistance to thyroid hormone (RTH) is an inherited disease transmitted in an autosomal dominant manner. The diagnosis is suspected when peripheral thyroid hormones are increased contrasting with normal or increased levels of thyroid stimulating hormone. Usually, people harboring the rare syndrome have few or no symptoms. However, in some patients signs of hyperthyroidism may be the revealing anomalies as in the following case: A 75 year-old woman was referred to our department for a benign adrenal incidentaloma. In her medical history she was treated for systemic hypertension and diabetes mellitus for 15 years. Clinical examination did not show any sign of adrenal secretion, but discovered rapid irregular cardiac rhythm with some hyperthyroidism features such as increased sweating and upper limbs and jaw tremor. Electrocardiogram showed atrial fibrillation. Hormonal assessment confirmed hyperthyroidism as FT4 levels were high (mean value: 30.2pmol/L (n= 9–23)), contrasting with non-suppressed TSH levels (13.8μU/mL (n = 0.2 – 4)). Cerebral magnetic resonance imaging was normal. Genetic testing revealed a new heterozygous mutation on exon 10 in the THRβ gene (c.1366T>G) compatible with RTH syndrome. Screening of her children showed the same hormonal profile in five out of ten. These results confirmed RTH and the familial character.

Background. Hip fractures are a major issue of public health as they are responsible for high morbidity, excess mortality and costs. There are differences in Europe and worldwide in the incidence rates of hip fractures and time trends, in the context of the population aging. Ten years ago, we characterized the incidence of hip fracture in Romania using data from the national hospital discharge register. Objective. This is the first Romanian study to assess the hip fracture incidence rates over a period of 11 years, between 2008 and 2018. Subjects and Methods. This analysis is a nationwide retrospective study on hospitals reporting primary DRG data on hip fracture, using a rigorous definition with both diagnostic and surgical procedure codes. The population aged 40+ was stratified in 5-year intervals and both the crude incidence rates and the adjusted incidence rates of hip fracture using standardization on age for the 2018 reference population were calculated in women and men. Results. From 2008 to 2018, the number of hip fractures rose by 53 % in women (from 7513 to 11512) and 22.4 % in men (from 4266 to 5220). Meanwhile, the Romanian population over 40 years increased by 12.5% in women and 14.2% in men. The crude incidence rate rose by 36.2% in women and 7.2% in men and the age-standardized incidence rates by 27.4% in women and 6% in men. These increases are mostly based on 85+ age populations’ changes. Conclusions. In Romania, the hip fractures incidence continues to grow throughout an 11-year-period, especially in women, representing an increasing burden for our society.

Hypothyroidism is a common endocrine disease with characteristic symptoms and signs such as fatigue, weight gain, intolerance of cold, constipation, depression, mental slowdown and muscle cramps. Myopathic changes are observed in 30-80% of patients with hypothyroidism, but muscular hypertrophy with muscle stiffness has been reported in less than 10% of patients. Hoffmann’s syndrome is a specific form of the hypothyroid-associated myopathy, rarely seen. Symptoms of this syndrome include proximal muscle weakness, hypertrophies in extremities, stiffness, muscle cramps, spontaneous muscle pain; and are associated with increased muscle enzymes. These findings can be seen at any time during hypothyroidism. Hofmann’s syndrome has a very good prognosis. Its response to hormone replacement therapy is very good. Therefore, in patients with myopathylike symptoms, considering in the differential diagnosis that the myopathy may be a reflection of hypothyroidism will facilitate the diagnosis and treatment. In this case, we aimed to present together Hashimoto thyroiditis and muscular hypertrophy, which is an atypical presentation of hypothyroidism and rarely seen in the literature, namely Hoffmann’s syndrome.

Context. Amiodarone use has been associated with Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH) with only 12 cases reported from its first description in 1996. Objective. The clinical use of the antiarrhythmogenic drug amiodarone is frequently complicated by a very broad spectrum of side effects: cardiac toxicity, hypo- and hyper-thyroidism, pulmonary fibrosis and liver function abnormalities. We report the case of a patient with amiodarone-induced SIADH with the particularity of a very late onset of these adverse effects. Case. A 78 years old man on amiodarone therapy for a history of complex ventricular arrhythmia after a myocardial infarction, comes to the Emergency Department of our Hospital for pre-syncopal symptoms. Laboratory test showed a hypo-osmotic hyponatremia (sodium 110 mEq/L, serum osmolality 233 mOsm/kg) associated with liver enzymes increases. A not suppressed urinary osmolality with high urinary sodium excretion associated with normal thyroid and adrenal functions led to the diagnosis of SIADH. Known associated disorders (neoplasms, lung diseases and central nervous system disorders) were suspected and excluded. A pharmacologic aetiology was suspected and, in the absence of diuretics and neurological drugs, amiodarone seemed the most probable cause of the SIADH. Hypertonic saline solution and fluid restriction were initiated and amiodarone discontinued with a gradual normalization of plasma sodium levels and liver enzymes. Conclusion. The clinical case underlines the importance of monitoring amiodarone-related SIADH with frequent electrolytes biochemical assessment not only in relation to an early but also to a late clinical onset.

Context. Subacute thyroiditis (SAT) is an inflammatory disease of the thyroid gland and commonly affects females. Despite adequate treatment, the recurrence of SAT can be seen in some patients. Although there is insufficient data about the reasons for recurrences, HLA predisposition is one of the reasons thought to be responsible and is a current issue for clinicians. Objective. This case report presented the management of 7 SAT attacks of a patient who had HLA-B35:01 and B41:02 alleles in the genotype analysis. Case Report. A 37-year-old male patient who had consecutive 7 SAT attacks was presented in this report. Corticosteroid or non-steroidal anti-inflammatory drugs were initiated at each recurrence depending on the severity of clinical symptoms and laboratory findings. The genotype analysis showed the positivity for HLA-B35:01 and B41:02 alleles. The anti-thyroglobulin antibody was detected positive after the last attack. The patient was followed up as asymptomatic and euthyroid in the third month after the last attack. Results. The management of some SAT cases may be challenging for clinicians. Although recurrence can be seen despite adequate treatment, repetitive seven attacks are extraordinary in SAT. HLA genotyping showed cooccurrence of HLA-B35:01 and B41:02 alleles in our patient. The co-occurrence of these alleles has been described firstly in this case. Explaining high recurrence rates of SAT with these HLA alleles is difficult, though the present case may shed light on further studies.

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Background. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. Antibodies directed against programmed cell death receptor 1 (PD-1) interrupt the ability of the cancerous cell to depress the immune system. Methods and results. We report three patients who developed different endocrine abnormalities after treatment with nivolumab, a monoclonal antibody directed against PD-1. First, we report a 76-year-old male presenting with generalized fat loss after treatment with nivolumab which predominantly affected his face and trunk. Second, we described the development of thyroiditis that presented with thyrotoxicosis and the expression of thyroid-stimulating hormone receptor antibodies (TRAb). Finally, we observed the emergence of adrenal insufficiency due to hypophysitis in another case. Conclusion. Although immune checkpoint inhibitors are an effective anticancer treatment modality, adverse effects are evident that can affect the endocrine system. These adverse events may relate to different endocrine systems that include the thyroid and pituitary glands. Also, acquired generalized lipodystrophy should be suspected in patients developing unusual fat loss after treatment with ICIs.