Preliminary Investigation of Atypical Congenital Hypothyroidism in a Feline Colony
Phenotypic characteristics consistent with congenital hypothyroidism were identified in a feline colony used to study an inherited congenital form of glaucoma. The characteristics included: short stature, decreased growth rate, delayed dental eruption, and thyroid enlargement.
Dysmorphia and stunted growth were noted in a 5 week old kitten from a mixed breed colony (Siamese and DSH). Total cholesterol was elevated at 6 weeks of age. Total T4 (TT4) at 7 weeks was below the limit of detection but by 10 weeks was within the normal adult range (<0.5 µg/dl and 2.3 µg/dl respectively, normal 4-8 µg/dl). At 10 weeks, TSH was ~ 5 x normal at 1.37 ng/ml. Thyroid ultrasound was performed at 15 weeks, and thyroid scintigraphy was performed at 16 weeks. Sonographically, both lobes of the thyroid gland showed normal, homogeneous echogenicity and echotexture; however, overall thickness (0.41 cm) was increased compared to a phenotypically normal littermate (0.27 cm). Scintigraphic evaluation of the thyroid lobes showed bilaterally symmetric, uniformly increased activity, with T:S markedly greater than 1.0. Levothyroxine supplementation was initiated at this time.
Dysmorphia was noted in a closely related 3 week old female DSH. At 5 weeks TT4 was <0.5 µg/dl and TSH was >12 ng/ml (~250 times that of a clinically normal littermate). Levothyroxine supplementation was initiated at 7 weeks of age.
A mating of the affected cats produced 3 kittens. Kitten 1 died at 10 days of age of unknown causes. Of the 2 remaining kittens, dysmorphia was noted at 4 weeks and both kittens had low TT4 measured at 6 weeks (Kitten 2 = 0.52 µg/dl, Kitten 3 = 0.7 µg/dl). Kitten 3 was euthanized at 10 weeks due to complications of glaucoma. Kitten 2 remains alive and is currently not on levothyroxine supplementation so as to fully document the un-supplemented clinical condition.
Histopathology on Kitten 1 showed bilateral, severe, thyroid hypoplasia and edema. Thyroid histopathology on Kitten 3 showed severe, diffuse, bilateral adenomatous hyperplasia. No lesions were noted in pituitary or hypothalamic tissues.
Pedigree analysis suggests autosomal recessive inheritance. Breeding trials continue. To date, all affected cats have congenital glaucoma but not vice versa. It is unclear if these conditions are independent or co-segregating, or if the hypothyroid trait is dependent on expression of the glaucoma trait. Syndromic genetic diseases comprising hypothyroidism and glaucoma have been described in species other than the cat. The described hypothyroid cats are unlike reports of hypothyroidism due to dyshormonogenesis. This model could prove important in the implicated breed (Siamese), and as a useful model for understanding thyroid gland development and function.