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Clinical, pathological, and molecular studies of two families with lodide organification defect

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Abstract

Two unrelated families (CA and NA) in which an iodide organification defect (IOD) was present in two siblings of each family were studied. These patients had congenital goiters with hypothyroidism and a positive perchlorate discharge test. Examination of the thyroid tissue revealed no thyroid peroxidase (TPO) activity. Histologic findings were consistent with a microfollicular pattern of hyperplasia. Moderate cellular atypia was present, characterized by nuclear pleomorphism and hyperchromatism. Full length thyroglobulin was purified by gel filtration, but was not iodinated. Immunohistochemical studies using a polyclonal anti-human thyroid peroxidase (hTPO) antibody confirmed the presence of immunoreactive TPO protein in the thyroid tissues. Samples of normal and affected individuals were studied with respect to the presence of various fragments using TPO probes of varying sizes. The two affected siblings from family CA were homozygous for fragments 3.9, 4.6, and 7.0 kb (Bg/II) and 2.3 and 2.9 kb (Taql), whereas the parents were heterozygous. In the other family (NA), theBg/II digestion and TPO-31 hybridization revealed an interesting and informative polymorphism. The parents showed two different polymorphic patterns: the father had a 5.0/4.6 kb pattern and the mother a 4.7/4.5 kb pattern. However, the two affected siblings showed the same heterozygotic allelic pattern at 4.5/4.6 kb. The restriction fragment length polymorphism detected in these two families suggests an association between the TPO gene and an IOD. Results suggest that in these dyshormonogenetic tissues an altered TPO protein molecule is being synthesized, without detectable in vitro activity, but visible by immunostaining techniques in the goitrous tissue. Mutations in the TPO gene sequence are most likely associated with these changes.

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Authors and Affiliations

  1. Thyroid Laboratory, Hospital das Clínicas, Division of Endocrinology, University of São Paulo Medical School, São Paulo, Brazil

    Katia G. M. Rego MD, Ana Elisa C. Billerbeck PhD, Hector M. Targovnik MD, PhD, Cecília L. S. Santos PhD, Maria G. Alkmin PhD, Sonia Barbosa PhD, Rosalinda Camargo MD & Geraldo Medeiros-Neto MD

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  1. Katia G. M. Rego MD
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  2. Ana Elisa C. Billerbeck PhD
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  3. Hector M. Targovnik MD, PhD
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  4. Cecília L. S. Santos PhD
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  5. Maria G. Alkmin PhD
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  6. Sonia Barbosa PhD
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  7. Rosalinda Camargo MD
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  8. Geraldo Medeiros-Neto MD
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Correspondence to Geraldo Medeiros-Neto MD.

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Rego, K.G.M., Billerbeck, A.E.C., Targovnik, H.M. et al. Clinical, pathological, and molecular studies of two families with lodide organification defect. Endocr Pathol 8, 37–47 (1997). https://doi.org/10.1007/BF02739706

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