Congenital Hypothyroidism with Goiter in Toy Fox Terriers

Abstract

Congenital hypothyroidism with goiter was observed to segregate as a simple autosomal recessive trait in Toy Fox Terriers (TFTs). Neonatal affected pups exhibited inactivity, abnormal hair coat, stenotic ear canals, and delayed eye opening. Palpable ventrolateral cervical swellings were evident by 1 week of age. Serum thyroid hormone and thyroid-stimulating hormone concentrations were low and high, respectively. Histologic examination of the cervical masses disclosed cuboidal to columnar follicular epithelial cell hyperplasia with widely varying follicular size, shape, and amount of colloid. Oral thyroid hormone replacement therapy restored near-normal growth and development. At 8 weeks of age, radioiodine uptake and perchlorate discharge testing indicated an iodine organification defect. Biochemical analysis of thyroid tissue from affected dogs demonstrated enzymatic iodine oxidation deficiency and lack of sodium dodecyl sulfate-resistant thyroglobulin dimers, suggesting thyroid peroxidase deficiency. A nonsense mutation in the thyroid peroxidase gene of affected dogs was discovered and demonstrated to segregate with the disease. A DNA-based carrier test was developed and currently is used by TFT breeders to prevent this disorder.

Goiter with Vascular Anomalies in a Litter of Polish Lowland Sheepdogs

“…CGH has been reported with thyroid organification defects in toy fox terriers and rat terriers, Abyssinians, and domestic shorthairs as a result of a thyroid peroxidase deficiency. 1,2,5,6,13,14 Although the puppies in this report had serum thyroid concentrations below the reference ranges and one puppy also had a serum TSH concentration mildly above the reference range, those three puppies did not show the classic clinical features of CH (known as cretinism), such as dwarfism, dullness, and skeletal deformities.…”

“…It is not likely that the same type of organification defect (i.e., thyroid peroxidase deficiency) exists in this family because the dogs would have been expected to show clinical signs of hypothyroidism. 1,2 The mechanism for why goiters developed, but other clinical signs did not, remains unclear based on the evaluation of those three puppies. Specific testing for defects in thyroid organification, such as a perchlorate discharge test or thyroid peroxidase enzyme assay, was not performed in the puppies due to high costs, unavailability, and/or radioactivity concerns.…”

“…Congenital goitrous hypothyroidism (CGH) has been described in humans, dogs, cats, and other species. 1–7 In humans, congenital hypothyroidism (CH) occurs at a frequency of 1 in 3,000 live births. 7 Approximately 10–15% of human cases of CH are attributed to mutations in genes that encode enzymes required for normal thyroid hormone synthesis, resulting in CGH.…”

Thyroid Ultrasound in Dogs: a Review

“…4). 44,[52][53][54][55][56] Acquired secondary hypothyroidism [thyroid stimulating hormone (TSH) deficiency] is rarely reported and is related to pituitary tumours or pituitary malformations. 1,44 Tertiary hypothyroidism [thyroid releasing hormone (TRH) deficiency] has not been described in dogs.…”

“…An isolated TSH or TRH deficiency in young dogs has only been described in two case reports. 53,57 Ultrasonography of the Normal Gland…”