Goiter and hypothyroidism in two siblings due to impaired Ca(+2)/NAD(P)H-dependent H(2)O(2)-generating activity.
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.
Figueiredo
M D
MD
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.
Cardoso
L C
LC
Ferreira
A C
AC
Campos
D V
DV
da Cruz Domingos
M
M
Corbo
R
R
Nasciutti
L E
LE
Vaisman
M
M
Carvalho
D P
DP
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
D013954:Thyroglobulin; D006861:Hydrogen Peroxide; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; D009245:NADH Dehydrogenase; D002118:Calcium