Presence or severity of Hashimoto's thyroiditis does not influence basal calcitonin levels: observations from CROHT biobank.

PURPOSE: The influence of Hashimoto's thyroiditis (HT) on calcitonin (Ct) production is unresolved question. The aim of this study was to explore if basal Ct levels are influenced by the presence/severity of HT or correlated with clinical phenotypes of HT patients. METHODS: We included 467 HT patients and 184 control participants, from Croatian Biobank of HT patients (CROHT), in this retrospective study. Calcitonin levels between HT patients and controls were compared using Mann-Whitney test. Ct levels between two subgroups of HT patients, divided by intake of levothyroxine (LT4) therapy, were additionally tested to take into account the illness severity. Spearman rank correlation test was used to analyze correlations between Ct levels and 14 relevant phenotypes. RESULTS: We have not detected significant differences in median Ct levels between HT patients and controls (2.2 vs 2.35 pg/mL, respectively, P = 0.717) nor in-between two subgroups of HT patients (P = 0.347). We have not detected statistically significant correlations between Ct levels and clinical phenotypes, although we identified three weak nominal correlations: negative correlation of Ct with TgAb in all HT patients (r = - 0.1, P = 0.04); negative correlation of Ct with age in subgroup of HT patients without LT4 therapy (r = - 0.13, P = 0.04); positive correlation of Ct with BSA in subgroup of HT patients on LT4 therapy (r = 0.16, P = 0.042). CONCLUSION: Our results suggest that HT patients of all disease stages preserve Ct production as healthy individuals and there is no need for Ct measurements in the absence of a nodule. Additional confirmation and clarification of observed nominal correlations are needed due to potential clinical relevance of TgAb and age-dependent Ct decrease in HT women.

Genome-wide association analysis suggests novel loci for Hashimoto's thyroiditis.

PURPOSE: Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid diseases. Current knowledge of HT genetics is limited, and not a single genome-wide association study (GWAS) focusing exclusively on HT has been performed to date. In order to decipher genetic determinants of HT, we performed the first GWAS followed by replication in a total of 1443 individuals from Croatia. METHODS: We performed association analysis in a discovery cohort comprising 405 cases and 433 controls. We followed up 13 independent signals (P < 10-5) in 303 cases and 302 controls from two replication cohorts and then meta-analyzed results across discovery and replication datasets. RESULTS: We identified three variants suggestively associated with HT: rs12944194 located 206 kb from SDK2 (P = 1.8 × 10-6), rs75201096 inside GNA14 (P = 2.41 × 10-5) and rs791903 inside IP6K3 (P = 3.16 × 10-5). Genetic risk score (GRS), calculated using risk alleles of these loci, accounted for 4.82% of the total HT variance, and individuals from the top GRS quartile had 2.76 times higher odds for HT than individuals from the lowest GRS quartile. CONCLUSIONS: Although discovered loci are implicated with susceptibility to HT for the first time, genomic regions harboring these loci exhibit good biological candidacy due to involvement in the regulation of the thyroid function and autoimmunity. Additionally, we observe genetic overlap between HT and several related traits, such as hypothyroidism, Graves' disease and TPOAb. Our study adds a new knowledge of underlying HT genetics and sets a firm basis for further research.

[Anaplastic Thyroid Carcinoma in a 17-Year-Old Female Patient].

Anaplastic carcinoma of thyroid gland is one of the four most malignant tumors in humans. It appears in one or two patients per million per year. It is very rare in children. A 17-year-old female patient was admitted to the Clinical Department of ENT and Head and Neck Surgery, Split University Hospital Center, for thyroid gland surgery due to rapid growth of a node in the thyroid gland left lobe. Preoperative examination indicated benign nature of changes. Total thyroidectomy with levels VI and VII neck dissection was done. Intraoperative slide of the left lobe was malignant. Positron emission tomography and computed tomography were also done. The finding was negative. The patient was examined by an ENT-oncology team and juvenile radiotherapy was administered. It was found to be carcinoma stage IVa according to TNM classification. One year after the operation, the patient was well and had no signs of illness. This case report is a contribution to the existing but scarce knowledge of anaplastic carcinoma of thyroid gland in young patients in the world.

Incidence and trends of childhood Type 1 diabetes in Croatia from 1995 to 2003.

AIMS/HYPOTHESIS: The aim of this study was to examine incidence and trends of Type 1 diabetes in children aged 0-14 years in Croatia from 1995 to 2003. METHODS: The incidence data were obtained from two sources. The incidence was calculated as the number of newly diagnosed Type 1 diabetes patients per 100,000 person-years for the age group 0-14 years, and subgroups 0-4, 5-9, and 10-14 years. Standardized incidence was calculated using the method of direct standardization to the world standard population for the age group 0-14 years. The ascertainment was estimated with capture-recapture method. Trends in the incidence of Type 1 diabetes for period from 1995 to 2003 in Croatia were analyzed using Poisson regression model. RESULTS: The standardized incidence of Type 1 diabetes for the whole age group was 8.87 per 100,000 person-years (95% CI: 5.07-12.68), for girls 8.47 (95% CI: 7.54-9.41) and for boys 9.26 (95% CI: 8.30-10.21). During the studied period, the trend in incidence raised significantly for the whole age group (chi(2)=32.6, p<0.001). The average annual increase in incidence was 9% (95% CI: 5.8-12.2). CONCLUSIONS/INTERPRETATION: This rate of incidence places Croatia in a group of countries with moderate risk for development of Type 1 diabetes. The average annual increase in incidence of 9% is markedly higher than in most European countries, and probably reflects lifestyle changes upon economic recovery of the country.

Congenital adrenal hyperplasia (21-hydroxylase deficiency) without demonstrable genetic mutations.

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is the most common inherited defect of adrenal steroid biosynthesis. At least 36 mutations in the CYP21 gene, which is mapped to chromosome 6p21.3, have been described. We performed genetic analysis of the CYP21 gene in a patient with classic 21-OHD CAH and her family. The entire exonic coding regions and intronic regions, as well as the -1 kb 5' upstream promoter region, were thoroughly sequenced and analyzed. Despite extensive sequencing, no mutation was found in this 3.7 kb area. The 11beta-hydroxylase defect, closely mimicking the clinical and biochemical phenotype of classic 21-OHD, was excluded by directly sequencing 2.6 kb covering the entire coding of the CYP11B1 gene. Herein we describe a phenotypically and hormonally affected patient with classic simple virilizing 21-OHD CAH who lacks a mutation in the entire CYP21 gene and coding region of the CYP11B1 gene.

Congenital syphilis associated with hyperlipoproteinemia.

An infant with congenital syphilis associated with transient disturbances of lipoprotein metabolism is reported. The dominant clinical sign was hepatosplenomegaly. Laboratory investigation upon admission revealed hyperimmunoglobulinemia and hyperchylomicronemia. After the administration of penicillin, the chylomicronemia ceased, but an increase of very low density lipoprotein fraction was observed. As the infant recovered, all the laboratory findings returned to normal. Hyperchylomicronemia was attributed to hyperimmunoglobulinemia. Absorption of immunoglobulins to lipoproteins can inhibit lipoprotein lipase activity. The increase in the very low density lipoprotein fraction was probably caused by the increase in serum lipoprotein production and the decrease in lipoprotein clearance that are frequently seen in patients with infectious diseases.