Evolution of hypothyroidism in familial goitre due to deiodinase deficiency: report of a family and review of the literature (original) (raw)
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Molecular and Cellular Endocrinology, 2010
Iodotyrosine deiodinase is a thyroidal enzyme that deiodinates mono-and di-iodotyrosines (MIT, DIT) and recycles iodine, a scarce element in the environment, for the efficient synthesis of thyroid hormone. Failure of this enzyme leads to hypothyroidism, goiter and mental retardation, a clinical phenotype yet described in the 1950s, whose diagnostic hallmark is the elevation of iodotyrosines in serum and urine.
Increased incidence of congenital hypothyroidism due to iodine deficiency
Pediatrics international : official journal of the Japan Pediatric Society, 2007
The incidence of congenital hypothyroidism (CH) is expected to be elevated in iodine-deficient areas. In this study, the authors aimed to determine the incidence of transient and permanent CH in a large city which is known to be in the zone of moderate iodine deficiency. Newborn babies in Bursa, Turkey, were screened by measurement of serum thyroid-stimulating hormone (TSH) obtained by heel prick. The babies who had a serum TSH >20 mIU/L were recalled for measurement of T4 and TSH in venous serum. A total of 11 770 newborns were screened over a period of 9 years. The incidence of CH was found to be 1/840. However, after excluding the transient cases, permanent CH was diagnosed in 1/2354. It was impossible to distinguish transient patients from permanent CH by initial laboratory tests (P > 0.05). The estimated power of the study in determining the incidence of CH in the population was 90% (P < 0.05). The authors conclude that the incidence of CH is very high in their populat...
Molecular Characterization of Iodotyrosine Dehalogenase Deficiency in Patients with Hypothyroidism
The Journal of Clinical Endocrinology & Metabolism, 2008
Context: The recent cloning of the human iodotyrosine deiodinase (IYD) gene enables the investigation of iodotyrosine dehalogenase deficiency, a form a primary hypothyroidism resulting from iodine wasting, at the molecular level. Objective: In the current study, we identify the genetic basis of dehalogenase deficiency in a consanguineous family. Results: Using HPLC tandem mass spectrometry, we developed a rapid, selective, and sensitive assay to detect 3-monoiodo-L-tyrosine and 3,5-diodo-L-tyrosine in urine and cell culture medium. Two subjects from a presumed dehalogenase-deficient family showed elevated urinary 3-monoiodo-L-tyrosine and 3,5-diodo-L-tyrosine levels compared with 57 normal subjects without thyroid disease. Subsequent analysis of IYD revealed a homozygous missense mutation in exon 4 (c.658GϾA p.Ala220Thr) that co-segregates with the clinical phenotype in the family. Functional characterization of the mutant iodotyrosine dehalogenase protein showed that the mutation completely abolishes dehalogenase enzymatic activity. One of the heterozygous carriers for the inactivating mutation recently presented with overt hypothyroidism indicating dominant inheritance with incomplete penetration. Screening of 100 control alleles identified one allele positive for this mutation, suggesting that the c.658GϾA nucleotide substitution might be a functional single nucleotide polymorphism. Conclusions: This study describes a functional mutation within IYD, demonstrating the molecular basis of the iodine wasting form of congenital hypothyroidism. This familial genetic defect shows a dominant pattern of inheritance with incomplete penetration.
Iodine Deficiency Among Hypothyroid Patients Living in Jeddah
Biological Trace Element Research, 2009
The objective was to determine the prevalence of iodine deficiency among hypothyroid patients and the effect of dietary goitrogens on indices of iodine and thyroid status. This is a case-control study of 106 subjects who were recruited from King Abdulaziz University Hospital, Jeddah. Blood and urine were collected for serum thyroid hormones, thyroid autoantibodies, thyroglobulin (Tg) and urinary iodine concentration (UIC). Dietary iodine and goitrogenic food intake were assessed by questionnaire. Using World Health Organization (WHO) cutoff values for UIC, both controls and cases were iodine deficient (85% and 83%, respectively). Furthermore, dietary iodine was deficient in 23% of controls and 36% of cases. In cases, there was a positive association between UIC levels and serum thyroid stimulating hormone (r = 0.405, p < 0.01) and a negative association with serum fT4 (r = −0.358, p < 0.01). Serum Tg antibody titers were also positively associated with dietary iodine (r = 0.328, p < 0.05). Patients with elevated serum autoantibodies had lower UIC and dietary iodine than those with normal serum autoantibodies. UIC was associated with dietary goitrogens including turnip (r = 0.280, p < 0.05) and pine (r = 0.289, p < 0.05) among cases. Iodine deficiency is common and the consumption of dietary goitrogens is high among euthyroid and hypothyroid subjects living in Jeddah.
Defective Organification of Iodide Causing Hereditary Goitrous Hypothyroidism
Thyroid, 1993
We present a survey of the current state of knowledge about the prevalence of the syndrome involved in defective organification of iodide, and the mechanism of iodination and coupling catalyzed by the thyroid peroxidase (TPO) enzyme. A brief summary of the recent developments in molecular cloning of TPO and regulation^T PO gene expression is also included. Methods for purification of the enzyme and details about the assessment of TPO activity in tissue are briefly explained. The classification of defective organification of iodide is primarily based on the site of the biochemical defect, being quantitative (TPO absent) or qualitative (TPO structure, localization or apoenzyme are defectives). The presence of TPO inhibitors is also briefly described. The rare possibility of an absent source of peroxide (H202) causing defective iodide organification is discussed. Analysis of the 118 reported cases shows that the biochemical classification covers a spectrum of abnormalities and it is likely that further molecular biology studies will increase this heterogeneity as well as refining it. Genetic studies have suggested linkage between the TPO gene polymorphisms and the iodide organification defect and can be of importance for carrier detection and prenatal diagnosis. Neonatal screening for hypothyroidism is likely to expand the number of cases available for DNA analysis and possibly the molecular diagnosis. The importance of the mutations that would affect the histidine (His) residues in the translated protein was recently documented by the finding of a deletion removing part of exon 9 and thus also deleting a proximal His residue. The resulting TPO enzyme was inactive for iodide organification and coupling reaction. It is hoped that in time we will be able to expand our knowledge of the molecular diagnosis of the inborn errors of iodide organification.
Revista Romana de Medicina de Laborator, 2019
The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92Ala polymorphism in children from West of Romania with congenital hypothyroidism (CH) and association with TSH levels in response to levothyroxine monotherapy. Genotyping in 50 children with CH and 52 healthy controls was done using real time PCR. The results showed that there was no statistical difference between the frequencies of genotypes in patients vs. controls. Patients were treated with L-thyroxine and most had normal values for fT3 and fT4. However, high TSH values were found in 21 patients (42%) after treatment. Among patients with high TSH values, AA genotypes were significantly more prevalent (p = 0.044) than TT and AT genotypes. Our results suggest that for the D2 gene Ala92Thr polymorphism, the AA genotype may be detrimental for achieving euthyroidism in patients with CH and levothyroxine monotherapy, therefore polytherapy could be considered as a better approach in these p...
European Journal of Clinical Investigation, 1987
Two cases of congenital defect in iodide trapping mechanism are related. The absence of thyroid and gastric concentration of 99mTc04 led to the diagnosis. The study of saliva and gastric: serum concentration ratios confirmed the complete defect. The kinetics of radioiodine studied by external detection showed an early simultaneous decay in the thyroid, the stomach and the left ventricle. Thyroid accumulation of I3'I, demonstrated by camera imaging, was estimated to be 0.1% at 48 h. It probably originated from simple diffusion. Iodide supplementation was progressively increased to 4.5 g and 10 g day-' respectively. It resulted in a normalization of all parameters. Huge doses of iodide did not result in any evidence of hyperthyroidism as TSH rose normally after TRH. Intermittent iodide supplementation in one case could not maintain euthyroidism longer than a few weeks. Daily treatment, therefore, seems necessary.
Iodine Deficiency Disorders in the Iodine-Replete Environment
The American Journal of the Medical Sciences, 2009
Background-Iodine deficiency disorders (IDD) constitute significant public health problems in parts of the world with poor iodine nutrition, but have been eradicated in North America and other regions. We herein report three cases of iodine deficiency disorders (IDD) which occurred in women living in iodine-replete environments. Methods-The clinical presentation, biochemical findings, and radiological features of the patients were analyzed and presented in three case reports. The radiological features are illustrated in sonographic and scintigraphic images. A literature review and discussion which highlight the risk factors, pathogenesis, ancillary investigations and rational treatment of iodine deficiency goiter and hypothyroidism are provided. Results-All of our three patients were young females, aged 24-38 years, who had goiter. Two of them presented with goitrous hypothyroidism. Radioactive iodine scintigraphy showed a characteristic finding of diffusely increased uptake (in the absence of clinical and biochemical evidence of hyperthyroidism). This scintigraphic pattern was found to be pathognomonic. Dietary iodine supplementation alone resulted in complete remission of IDD in the subjects, including the two patients with hypothyroidism. Conclusion-IDD can occur in iodine replete-environments. A high index of suspicion is needed to recognize these cases. It is pertinent that the correct diagnosis be made to avoid unwarranted lifelong thyroxine therapy in patients presenting with goiter and hypothyroidism, which is easily treatable with iodized salt. These cases underscore the need for considering iodine deficiency in the etiologic diagnosis of goiter and hypothyroidism, even in iodine sufficient regions.