title: Goiter and hypothyroidism in two siblings due to impaired Ca(+2)/NAD(P)H-dependent H(2)O(2)-generating activity.
abstract: We report herein the study of two siblings (DESM and DSM) with hypothyroidism, goiter, and positive perchlorate discharge tests (50% and 70%) in a family (M) with no history of consanguinity. Thyroid gland histology showed a predominance of hyperactive follicles, with high epithelial cells and variable colloid content. Thyroid peroxidase iodide oxidation (DESM, 1034; DSM, 1064 U/g protein) and albumin iodination (DESM, 16; DSM, 8 nmol I/mg protein) activities were within the normal range. Tg content was normal in both glands compared with that in diffuse toxic goiter (DESM, 28; DSM, 17; diffuse toxic goiter, 19 mg/g tissue), and Tg could be normally iodinated by thyroid peroxidase in vitro (DESM, 3.4; DSM, 4.3; diffuse toxic goiter, 6.3 nmol I/mg Tg). Thyroid cytochrome c reductase activities in these goiters were higher than that in paranodular tissues (DESM, 473; DSM, 567; paranodular tissues, 78 nmol NADP(+)/h/mg protein). However, thyroid NADPH oxidase activities were very low both in the particulate 3,000 x g (DESM, 4.8; DSM, 44; paranodular tissues, 224 nmol H(2)O(2)/h/mg protein) and in the particulate 100,000 x g fractions (DESM, 40; DSM, 47; paranodular tissues, 200 nmol H(2)O(2)/h/mg protein). Thus, a decreased Ca(2+)/NAD(P)H-dependent H(2)O(2) generation is the probable cause of the organification defect in these goiters.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Departamento de Histologia e Embriologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil.
authors.forename: M D
authors.initials: MD
authors.lastname: Figueiredo
authors.forename: L C
authors.initials: LC
authors.lastname: Cardoso
authors.forename: A C
authors.initials: AC
authors.lastname: Ferreira
authors.forename: D V
authors.initials: DV
authors.lastname: Campos
authors.forename: M
authors.initials: M
authors.lastname: da Cruz Domingos
authors.forename: R
authors.initials: R
authors.lastname: Corbo
authors.forename: L E
authors.initials: LE
authors.lastname: Nasciutti
authors.forename: M
authors.initials: M
authors.lastname: Vaisman
authors.forename: D P
authors.initials: DP
authors.lastname: Carvalho
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000502:physiology*; D005260:Female; D006042:Goiter / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D009245:NADH Dehydrogenase / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D013954:Thyroglobulin / Q000378:metabolism
chemical_list: D013954:Thyroglobulin; D006861:Hydrogen Peroxide; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; D009245:NADH Dehydrogenase; D002118:Calcium