Dyshormonogenetic Goiter

Dyshormonogenetic Goiter

Lester D. R. Thompson, MD

The thyroid gland is asymmetric and nodular, with the nodules resembling adenomatoid nodules. There is colloid present, although it is not prominent. The nodules are cellular.

Within the septal regions of the gland, there are a number of isolated, highly atypical cells image. Note the variability in the colloid in this high-power field. There is also a background of fibrosis.



  • Inherited goiter


  • Thyroid enlargement due to hereditary defect in thyroid hormone synthesis


Developmental Anomaly

  • Genetic defect in one of the biochemical steps of thyroid hormone synthesis

    • Usually autosomal recessive

    • Several major enzyme defects are known

      • Loss of any of genes involved in thyroglobulin synthesis, iodine transport, iodide oxidation and organification, coupling of MIT and DIT, proteolytic breakdown of thyroglobulin, and iodide recycling

      • Deficiency in thyroperoxidase (TPO) activity is most frequent cause of dyshormonogenetic goiter



  • Incidence

    • Very rare cause of permanent congenital hypothyroidism

      • 2nd most frequent cause of permanent congenital hypothyroidism

    • Congenital hypothyroidism (thyroid dysgenesis): 1 in 3,000-4,000 births

      • About 15% due to dyshormonogenetic goiter

    • Prevalence of dyshormonogenetic goiter: 1 in 30,000-50,000 population

  • Age

    • Average age at presentation: 16 years

      • Majority manifest before age 25 years

    • Ranges from neonates to adults

  • Gender

    • Female slightly > Male


  • Entire thyroid gland affected

    • Whenever “whole thyroid” is affected, must consider genetic or autoimmune etiologies


  • Absent or severely decreased thyroid hormone synthesis

    • Results in increased secretion of TSH due to functional hypothyroidism

      • Insufficient hormone production for feedback loop

    • Insufficient hormone production results in continuous TSH stimulation

    • Yields thyroid hyperplasia without thyroid function improvement

  • Only patients with most severe impairment in thyroid hormone production present in infancy with cretinism

  • Most patients (2/3) have known hypothyroidism prior to recognition of goiter

    • Thyroid enlargement (goiter) tends to develop later in life

  • Family history of hypothyroidism &/or goiter is elicited in 20% of patients

  • Pendred syndrome very rare (SLC26A4 at 7q31)

    • Association of dyshormonogenetic goiter (impaired iodide organification) with familial deaf-mutism due to sensorineural deafness

    • Biallelic mutations in SLC26A4 gene

      • SLC26A4 gene encompasses 21 exons and contains open-reading frame of 2343 bp

Laboratory Tests

  • Low to absent T4 and T3

  • High TSH

Natural History

  • If severe or complete, cretinism at birth

  • Death without replacement therapy

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Dyshormonogenetic Goiter
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