The clinical phenotype of Graves' disease occurring as an isolated condition or in association with other autoimmune diseases.

PURPOSE: Graves' disease (GD) can present as an isolated disease (iGD) or in association with other autoimmune diseases (aGD). The aim of this study, performed in two Endocrine referral centers settled in different geographical areas of Italy, was to compare the anthropometric, clinical, and biochemical phenotype of iGD patients with that of the aGD ones. METHODS: Clinical history, physical examination data, serum levels of TSH, FT4, FT3, thyroglobulin (TgAb), thyroid-peroxidase (TPOAb) and TSH-receptor (TRAb) antibody, presence of Graves' orbitopathy (GO), and thyroid ultrasound examination at disease diagnosis were recorded. RESULTS: 68 aGD and 136 iGD patients were consecutively recruited. At diagnosis, aGD and iGD patients did not differ for F/M ratio, age at presentation, thyroid function parameters, serum levels of TRAb, TgAb, TPOAb, presence of GO, and thyroid volume. The serum levels of TRAb were strongly correlated with the circulating concentrations of both FT3 (ρ = 0.667; p < 0.0001) and FT4 (ρ = 0.628; p < 0.001) in iGD patient, but not in the aGD ones (FT3: ρ = 0.231; p = 0.058; FT4: ρ = 0.096; p = 0.435). Compared with iGD patients, the aGD ones displayed a higher rate of transition from the previous hypothyroidism to hyperthyroidism (χ2 = 6.375; p = 0.012). CONCLUSION: Despite similar anthropometric, clinical, and biochemical features at diagnosis, aGD patients display a higher rate of transition from a thyroid functional status to the other as compared with iGD patients.

Hyperhomocysteinemia in acute iatrogenic hypothyroidism: the relevance of thyroid autoimmunity.

PURPOSE: Hyperhomocysteinemia is a known cardiovascular risk factor and a key player in the inflammatory activation of autoimmune diseases. Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism which, in itself, has been associated with a significant raise of homocysteine (Hcy) levels and increased cardiovascular risk. Our aim was to assess the impact of HT on Hcy levels in patients with acute hypothyroidism. METHODS: We prospectively enrolled 121 patients (mean age: 46 years, F/M = 102/19) with acute post-surgical hypothyroidism. Based on the presence of anti-thyroid antibodies and the histological description of an inflammatory infiltrate, 26 and 95 patients were classified as HT and non-HT, respectively. Several parameters including thyroid-stimulating hormone (TSH), levels of serum free T3 and free T4, weight, glucose levels, total cholesterol, creatinine, vitamin B12, ferritin and erythrocyte sedimentation rate were obtained from all patients and correlated with Hcy levels. RESULTS: Median Hcy level in the whole cohort was 16.8 µmol/L (normal values: < 12 µmol/l). Among all parameters analysed, only Hcy levels were significantly different between HT and non-HT patients (median Hcy = 19.7 vs 16.2 µmol/L, respectively; p = 0.018, Mann-Whitney U test). Analysis of covariance showed the presence of HT to be the strongest predictor of Hcy levels (coefficient = 0.25534, p = 0.001). Serum TSH was not significantly associated with Hcy levels (p = 0.943). CONCLUSION: In patients with iatrogenic hypothyroidism, those with HT have significantly higher Hcy levels than those without HT. The increase of Hcy levels appears to be mainly determined by the HT-related immune-inflammatory condition.

The relationship between thyroid disorders and vitamin A.: A narrative minireview.

The terms "vitamin A" and "retinoids" encompass a group of fat-soluble compounds essential for human nutrition. Some of them (retinol, retinal, 9-cis-retinoic acid, tretinoin, and 13-cis-retinoic acid) are fully natural, while others are synthetic compounds used mostly for therapeutic purposes. Some evidence indicates that the nutritional status of these retinoids (i.e., the presence or absence of deficiency) is able to modulate thyroid gland metabolism. Vitamin A deficiency is tightly correlated with structural and functional impairment of the thyroid gland and is often associated with iodine deficiency. Furthermore, retinoids are involved in different immune functions, as well as in the process of activation, proliferation, and differentiation of regulatory T cells (Treg). This is particularly significant given the high prevalence of thyroid autoimmune disorders, whose pathogenesis seems to be related to the altered homeostasis of regulatory T cells. Retinoids are also involved in the modulation of gene expression via their interaction with nuclear receptors, and they also act as cofactors in cell growth and differentiation. The ability of retinoic acid to increase iodine uptake and sodium-iodine symporter activity in human thyroid cancer cell lines suggests that some retinoids and their derivatives may be of use in the treatment of different thyroid tumors. This minireview summarizes the current knowledge on the link between nutritional intake of vitamin A and various thyroid disorders.

Early detection of biochemically occult autonomous thyroid nodules.

OBJECTIVE: Autonomously functioning thyroid areas may be associated with subclinical or overt hyperthyroidism, but may exist even in the presence of normal TSH. This study was aimed at comparing the rate of autonomously functioning areas and their cardiac sequelae in patients with nodular goitre studied with the usual and a novel approach. DESIGN AND METHODS: In total 490 adult outpatients with thyroid nodular goitre, living in a mild iodine-deficient area, were selected in our referral centre for thyroid diseases from 2009 to 2014 on the basis of a suspicion of thyroid functional autonomy. They were divided in three groups according to a non-conventional approach (excessive response to thyroxine treatment: group 1) or conventional approach (low/normal TSH with clinical suspicion or low TSH: groups 2 and 3). All patients of the study with the suspicion of thyroid functional autonomy underwent thyroid scan with radioactive iodine (I131) uptake (RAIU). RESULTS: The percentage of confirmed thyroid functional autonomy was 319/490, being significantly higher in group 3 than in groups 1 and 2 (81.5 vs 64.7 vs 52.6%; chi-square P < 0.0001). However, the diagnosis with non-conventional approach was made at a significant earlier age (P < 0.0001). Cardiac arrhythmias as well as atrial fibrillation were similarly detected by conventional and non-conventional approaches (chi-square test: P = 0.2537; P = 0.8425). CONCLUSIONS: The hyper-responsiveness to thyroxine treatment should induce the suspicion of thyroid functional autonomy at an early stage, allowing to detect autonomous functioning areas in apparently euthyroid patients.

Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study.

OBJECTIVE: Thyroxine (T4) requirement after total thyroidectomy for differentiated thyroid carcinoma (DTC) is a debated issue. As most of the studies in the area have been retrospective and/or performed with heterogeneous therapeutic approaches, we designed our study to determine T4 requirement in the same patients and treatment settings, before and after total thyroidectomy. DESIGN, PATIENTS AND METHODS: This was a longitudinal study including 23 goitrous patients treated with T4 in an individually tailored fashion. All patients exhibited a stable TSH (median TSH = 0.28 mU/l) at a stable T4 dose for at least 1 year before surgery (median T4 dose = 1.50 µg/kg per day). The patients underwent total thyroidectomy based on cancer suspicion or compressive symptoms. Eventually diagnosed as having DTC (pT1b-pT2N0) and following surgical and radiometabolic treatment, they were treated with the same pre-surgical doses of T4. RESULTS: Three months after surgery,using the same pre-surgical dose, median TSH increased up to 5.38 mU/l (P<0.0001) and so the T4 dose had to be increased (median T4 dose = 1.95 µg/kg per day; +30%; P < 0.0001). Once divided by patients' age, we observed that, after thyroidectomy and maintaining the same pre-surgical dose, serum TSH significantly increased both in younger and in older patients (median TSH = 4.57 and 6.11 mU/l respectively). Serum TSH was restored to the pre-surgical level by increasing the dose up to 1.95 and 1.77 µg/kg per day (+25 and +21%) respectively. CONCLUSIONS: Following the same treatment regimen, a thyroidectomized patient requires one-third higher therapeutic T4 dose than before surgery. Despite this increase, the dose of T4 needed in our patients remains significantly lower than that previously described in athyreotic patients.