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 meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone.

PURPOSE: Thyroid hormones are essential for the normal function of almost all human tissues, and have critical roles in metabolism, differentiation and growth. Free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels are under strong genetic influence; however, most of the heritability is yet unexplained. METHODS: In order to identify novel loci associated with fT3, fT4 and TSH serum levels we performed a genome-wide meta-analysis of 7 411 206 polymorphisms in up to 1731 euthyroid individuals from three Croatian cohorts from Dalmatia region: two genetically isolated island populations and one mainland population. Additionally, we also performed a bivariate analysis of fT3 and fT4 levels. RESULTS: The EPHB2 gene variant rs67142165 reached genome-wide significance for association with fT3 plasma levels (P = 9.27 × 10-9) and its significance was confirmed in bivariate analysis (P = 9.72 × 10-9). We also found a genome-wide significant association for variant rs13037502 upstream of the PTPN1 gene and TSH plasma levels (P = 1.67 × 10-8). CONCLUSION: We identified a first genome-wide significant variant associated with fT3 plasma levels, as well as a novel locus associated with TSH plasma levels. These findings are biologically relevant and enrich our knowledge about the genetic basis of pituitary-thyroid axis function.

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.

Association of established hypothyroidism-associated genetic variants with Hashimoto's thyroiditis.

PURPOSE: Hashimoto's thyroiditis (HT) as a chronic autoimmune disease of the thyroid gland is the most common cause of hypothyroidism. Since HT and hypothyroidism are closely related, the main aim of this study was to explore the association of established hypothyroidism single-nucleotide polymorphisms (SNPs) with HT. METHODS: The case-control dataset included 200 HT cases and 304 controls. Diagnosis of HT cases was based on clinical examination, measurement of thyroid antibodies (TgAb, TPOAb), hormones (TSH and FT4) and ultrasound examination. We genotyped and analysed 11 known hypothyroidism-associated genetic variants. Case-control association analysis was performed in order to test each SNP for the association with HT using logistic regression model. Additionally, each SNP was tested for the association with thyroid-related quantitative traits (TPOAb levels, TgAb levels and thyroid volume) in HT cases only using linear regression. RESULTS: We identified two genetic variants nominally associated with HT rs3184504 in SH2B3 gene (P = 0.0135, OR = 0.74, 95% CI = 0.57-0.95) and rs4704397 in PDE8B gene (P = 0.0383, OR = 1.32, 95% CI = 1.01-1.74). The SH2B3 genetic variant also showed nominal association with TPOAb levels (P = 0.0163, ß = -0.46) and rs4979402 inside DFNB31 gene was nominally associated with TgAb levels (P = 0.0443, ß = 0.41). CONCLUSIONS: SH2B3 gene has previously been associated with susceptibility to several autoimmune diseases, whereas PDE8B has been associated with TSH levels and suggested to modulate thyroid physiology that may influence the manifestation of thyroid disease. Identified loci are novel and biologically plausible candidates for HT development and represent good basis for further exploration of HT susceptibility.

Clinical manifestations of neurosarcoidosis.

Sarcoidosis is a chronic disease of unknown aetiology. Neurosarcoidosis is registered in 5% of patients with sarcoidosis. Clinical manifestations of sarcoidosis are numerous and diverse. Manifestation of Neurosarcoidosis includes partial- and grand-mal seizures, low-grade fever, headache, increased intracranial pressure, visual disturbances, diabetes insipidus, amenorrhea- galacterorrhea syndrome and pituitary failure, hypogonadotropic hypogonadism, hyperprolactinemia, unilateral and bilateral facial palsy, infiltration of meninges (aseptic meningitis) and nerve roots, leptominingitis, pachymeningitis with cranial neuropathies, pseudotumor, mild cognitive disorder, psychosis, delirium, dementia, disorientation, amnesia, progressive visual deterioration and proptosis, axonal polyneuropathies, mononeuropathies, chronic polyradiculoneuritis, peripheral neuropathy, cranial nerve abnormalities, radiculopathies, peripheral neuropathy, mononeuritis multiplex, progressive numbness and deep sensation disturbance in bilateral lower extremities, hemiplegia, hyperreflexia with pathological reflexes and hypesthesia, upward gaze palsy, spinal cord compression, dysarthria, dysphagia, weakness, episodes of blurred vision, diplopia, intracerebral hemorrhage, neuro-ophthalmic manifestations, intranuclear ophthalmoplegia, dysorientation, vasculitis presenting with strokes, intracranial hypothalamic lesion, paresthesis, hemiparesis, myelopathy in the cervico-thoracic region, lumbar pain, sensory level and inability of lateral gaze (Tab. 2, Ref. 60).

Lamotrigine in the treatment of pain syndromes and neuropathic pain.

Anti-epileptic drugs are increasingly used in the treatment of pain syndromes and neuropathic pain. Sodium channel blockers can be effective in the treatment of pain. The object of our interest is the efficiency of lamotrigine in treating the pain. A MEDLINE search was conducted to identify pertinent studies, case reports, letters, and reviews in English published from 1986 to May 2007. The search has indicated efficiency in treating a number of painful syndromes and neuropathic pain; central pain, trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis, pain in multiple sclerosis, SUNCT syndrome, cluster headache, glossopharyngeal neuralgia, neuropathic pain, allodynia, neuralgia after nerve section, postherpetic neuralgia, HIV-associated neuropathy. Further researches are required on the role of lamotrigine in treating the spinal cord injury pain, neuralgia after nerve section, postoperative analgesic requirement, and in migraine (Tab. 1, Ref. 46). Full Text (Free, PDF) www.bmj.sk.

Is it possible to determine the origin of cyst in empty thyroid bed in patient with lingual thyroid?

Some patients with ectopic thyroid gland or athyreotic patients have one or more cysts in empty thyroid bed. The origin of these cysts is uncertain. We present the patient with lingual thyroid gland and small cyst in empty thyroid bed featuring the diagnostic algorithm used and discussing the possible etiologic scenarios.

Thyroid echogenicity: A clue to precise individual dosimetry in radioiodine therapy of hyperthyroidism.

BACKGROUND: Radioiodine therapy is a frequent option in treatment of patients with hyperthyroidism. Despite efforts to plan the thyroid absorbed dose by accounting for the gland size and radioiodine kinetics, the success of radioiodine therapy remains largely unpredictable. The current methods plan the mean thyroid radiation absorbed dose, assuming that it applies to target tissue - the thyroid follicular cells. However, the unique thyroid follicular structure and iodine kinetics may violate this assumption. Upon oral administration and capture by thyroid, the vast majority of time radioiodine spends in organified form in follicular colloidal lumen: the greater the follicle the more radiation is wasted before reaching the target cells. HYPOTHESIS: The (131)I radiation absorbed dose to thyroid follicular cells is less than the average thyroid dose, the more the greater the follicles. Thyroid echogenicity can be used to assess the amount of colloid in thyroid tissue, which in turn can be used to assess the follicle size and adjust the planned absorbed dose to patient-specific thyroid micro-architecture. EVALUATION: Animal data on intrathyroidal iodine kinetics were considered in conjunction with model predictions that relate the size of thyroid follicles with (131)I irradiation of follicular cells. It turned out that the correction factors in the range 5-40% should be applied to oral activities of radioiodine calculated by the standard method. Next, several histology studies documented that normoechogenic thyroids have relatively large follicles, while hypoechogenic thyroids are mostly cellular, with almost empty, small follicles. All these concur with clinical data that Graves' disease patients with normoechogenic thyroids that received 200Gy in thyroid had comparable outcome to Graves' disease patients with hypoechogenic thyroid that received 100-120Gy in thyroid. CONCLUSION: Thyroid echogenicity is a probable clue to a better patient-specific dosimetry in radioiodine therapy of hyperthyroidism; direct evidences and precise estimates of benefits over current practices would be provided by controlled clinical trials.

Early cardiac rupture following streptokinase in patients with acute myocardial infarction: retrospective cohort study.

AIM: To assess the incidence and timing of cardiac rupture following streptokinase (SK) administration in acute myocardial infarction (AMI). METHODS: We analyzed retrospectively the clinical sheets of AMI patients treated at the Coronary Care Unit in University Hospital Split, Croatia, between January 1, 1996, and December 31, 1998. We selected the patients who died after SK administration (1.5 million U in a 30 min iv. infusion), with a discharge diagnosis of "AMI" and "cardiac tamponade - ventricular rupture". AMI was defined by typical chest pain, ECG, and/or enzymatic changes. Echo or autopsy verified diagnosis of cardiac tamponade and/or rupture, as well as pericardial effusion and/or free-wall rupture. RESULTS: Out of 726 AMI patients, 136 (18.7%) were treated with SK, and 6 had cardiac rupture (4 men and 2 women; 4.4%). Autopsy revealed that 1 patient had ischemic and 2 had transmural hemorrhagic AMI. Three out of 6 patients died 2-4, and 3 died 5-7 hours after SK administration. Six patients who died from cardiac rupture (mean age 72.3+/-9.0) were significantly older than AMI survivors treated with SK (121 patients, mean age 60.5+/-12.0 years, p<0.001). CONCLUSION: In case of unexplained clinical deterioration in AMI patients over 70 during the first hours after SK administration, cardiac tamponade due to a free-wall rupture should be suspected. SK administration in patients with AMI over 70 years should be a selective and not a routine treatment.