Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

Fixed 30 mCi (1110 MBq) 131I-iodine therapy in autonomously functioning nodules: Single toxic nodule as a predictive factor of success.

AIMS: The aim of this study is to evaluate the efficacy of a fixed 30 mCi (1110 MBq) 131I-iodine dose for the treatment of hyperthyroidism due to uninodular or multinodular toxic goiter and identify predictors of success. MATERIALS AND METHODS: Fifty-nine patients diagnosed with nonautoimmune toxic goiter were treated with a fixed 30 mCi dose of 131I-iodine and were followed at a tertiary service between 2000 and 2016. The therapy was considered successful if the patient reached euthyroidism or hypothyroidism without needing an extra 131I-iodine dose or antithyroid drugs for at least 1 year after the radioiodine therapy (RIT). RESULTS: Patients with a single toxic nodule were younger at diagnosis (52 vs. 63 years; P = 0.007), presented a shorter disease duration until RIT (2 vs. 3.5 years; P = 0.007), smaller total thyroid volume (20 vs. 82 cm3; P = 0.044), and lower pre-RIT thyroid uptake (P = 0.043) than patients with multinodular goiter. No significant difference was seen with antithyroid drug use, thyroid-stimulating hormone and free thyroxine level, and follow-up after RIT. After RIT, 47 patients (79.66%) met the success criteria, and 12 (20.33%) remained hyperthyroid. Among the success group, 32 (68.08%) reached euthyroidism, while 31.92% developed hypothyroidism after 1 year. Patients with single toxic nodules who achieved success after RIT presented smaller nodules (2.8 vs. 5.75 cm; P = 0.043), while the pre-RIT thyroid uptake was higher among patients with multinodular toxic goiter who achieved success after RIT (5.5% vs. 1.5%; P = 0.007). A higher success rate was observed among patients with a single toxic nodule than those with a toxic multinodular goiter (92.3% vs. 55%; P = 0.001), and a single toxic nodule presentation was found to be an independent predictor of success (P = 0.009). CONCLUSIONS: The fixed 30 mCi 131I-iodine dose was particularly effective in the group of patients with single autonomously functioning nodule rather than the group with multiple nodules. A single toxic nodule was an independent predictor of treatment success.

The relationship between quality of life, cognition, and thyroid status in Graves' disease.

PURPOSE: To assess quality of life (QoL) and cognitive function among Graves' disease (GD) patients with different thyroid status, with and without ophthalmopathy. METHODS: This is a cross-sectional clinic-based study involving 154 patients with GD (81.27% were female, mean age 45.6 ± SD 11.2 years) and 54 (35.06%) had ophthalmopathy. Data were collected after an informed consent from all patients was obtained. All patients completed the 36-Item Short Form Health Survey and Mini-Mental State Examination. Patients with ophthalmopathy also completed the Graves' Orbitopathy Quality of Life Questionnaire. RESULTS: Patients with hyperthyroidism presented a greater impairment in QoL when compared to euthyroidism group. A lower score in physical role functioning was found in both subgroups with active disease (hyperthyroidism and euthyroidism using thionamides). A lower score was also seen in visual function, only in patients with hyperthyroidism, without difference in appearance. No difference was found in cognition between patients. Younger ages at diagnosis, male sex, euthyroidism and absence of ophthalmopathy were factors associated with better QoL, as well as a shorter disease duration was associated with better recall, attention and calculation. CONCLUSIONS: An impairment in QoL among patients with active GD was evidenced, even in those receiving thionamides and in euthyroidism. Ophthalmopathy was a factor associated with a poor QoL and no clear evidence of cognitive impairment was demonstrated.

Panhypopituitarism Without GH Replacement: About Insulin Sensitivity, CRP Levels, and Metabolic Syndrome.

A complete deficiency of anterior pituitary hormones from several etiologies characterizes Panhypopituitarism (PH). Despite advances in treatment, patients with PH maintain high rates of morbidity and mortality, a reason to investigate some insulin sensitivity, metabolic and inflammatory parameters that could be related to the increase of these indicators. This was a cross-sectional study comprising 41 PH patients under hormonal replacement, except for growth hormone, and 37 individuals in a control group (CG) with similar age, gender and body mass index (BMI). We assessed clinical data as age, sex, BMI, waist circumference, waist/hip ratio (WHR), history of hypertension, diabetes mellitus and dyslipidemia as well as fasting glycaemia, insulin, HOMA-IR, HbA1c, high-sensitivity CRP (hs-CRP), and lipid profile. PH patients presents lower values of glycaemia, insulin, HOMA-IR (0.88 vs 2.1) and WHR, but higher levels of hs-CRP (0.38 vs 0.16mg/dl) when compared with the CG. Although the occurrence of dyslipidemia was higher in patients with PH, the frequency of metabolic syndrome was similar between the groups. In multivariate linear regression analysis, the PH group independently predicted lower HOMA-IR and WHR values. In conclusion, this study demonstrated that patients with PH without GH replacement have lower HOMA-IR and WHR values and higher levels of hs-CRP than a CG paired by age, gender and BMI. The diagnosis of dyslipidemia was more frequent in patients with PH, but the occurrence of MS was similar to CG. Further studies are needed to confirm our findings and to better understand the metabolic characteristics of patients with PH.

Extremely high doses of radioiodine required for treatment of Graves' hyperthyroidism: a case report.

INTRODUCTION: Radioactive iodine ((131)I) is widely prescribed for treatment of Graves' disease. A dose of 370 to 555 MBq (10 to 15 mCi) is usually enough, but reports of improved remission rates with single doses up to 20-30 mCi, and 38.5 mCi at most, exist. CASE PRESENTATION: A 53-year-old male patient was evaluated in September 2005, with symptoms of thyrotoxicosis for 2 years. He presented with tachycardia (130 bpm) and a large goiter. Thyrotropin was <0.01 uIU/ml (0,41-4,5), free thyroxin >7.77 ng/dl (0.9-1.8), anti-thyreoperoxidase antibody: 374 IU/ml (<35) and anti-thyroglobulin antibody: 749 IU/ml (<115). Ultrasound: diffuse goiter, no nodules; right lobe: 7.9 x 3.8 x 3.8 cm; left: 7.7 x 3.5 x 3.8 cm; isthmus: 1.6 cm. Propylthiouracil 300 mg t.i.d. and propranolol were prescribed. Thyroid (99m)Tc-pertechnetate uptake: 52% (0.35-1.7%) and estimated thyroid volume: 149 mL. After 30 days, he received 555 MBq (15 mCi) of (131)I-iodide. Six months after radioiodine therapy, under methimazole 40 mg, thyroid stimulating hormone was 1.5 uIU/ml; free thyroxine 0.54 ng/dl. Methimazole was suspended. In 21 days, thyroid stimulating hormone was 0.03 uIU/ml; free thyroxine 0.96 ng/dl. Methimazole was reintroduced. One year later, thyroid stimulating hormone was <0.01 uIU/ml and free thyroxine >7.77 ng/dl. Thyroid (99m)Tc-pertechnetate uptake was 45% and estimated thyroid volume 144 mL. A 1110 MBq (30 mCi) radioiodine therpy was administered. He used Methimazole for 8 months, when overt hypothyroidism appeared (TSH: 25.30 uIU/ml; free thyroxine: 0.64 ng/dl). Methimazole was interrupted. Hyperthyroidism returned 6 weeks later (thyroid stimulating hormone <0.01 uIU/ml; free thyroxine >7.77 ng/dl). Thyroid (99m)Tc-pertechnetate uptake was 25% and estimated thyroid volume 111 mL. Methimazole was prescribed again. In March 2008 he received a 2590 MBq (70 mCi) radioiodine therapy. By may/2008, under methimazole 20 mg, his TSH was 0.07 uIU/ml; free thyroxine 1.31 ng/dl. In October 2008 he presented overt hypothyroidism (TSH 91.6 uIU/ml; free thyroxine 0.34) and was given levothyroxine 75 mcg/day. He remains euthyroid under hormone replacement. CONCLUSION: Our presented case of Graves' disease received a cumulative dose of 4255 MBq (115 mCi). The high uptake could indicate accelerated iodine turnover with (131)I short time of action. Impaired hormone synthesis could also be present. We believe the extremely high dose required was due to the initial very high iodine uptake and large thyroid volume.