Diagnosis and Long-term Treatment of Suspected Congenital Hypothyroidism in a Pigeon (Columba livia domestica).

An approximately 6-month-old domestic pigeon (Columba livia domestica) was presented for lethargy and an inability to perform its first molt. The pigeon was obese, had anatomical characteristics of a chick, including cere and plumage, and had a ventral coelomic soft tissue mass. Initial blood work was unremarkable. A computed tomographic scan confirmed excessive fat deposition in the coelom and a mass adherent to the liver. A fine-needle aspirate of the mass indicated fat accumulation. A thyroid-stimulating hormone (TSH) test was planned for this pigeon and 3 presumed euthyroid pigeons. Each pigeon was administered 80 µg (∼230 µg/kg) of recombinant human TSH. Blood was drawn at time 0 and 3 and 6 hours after administration of recombinant human TSH. Plasma total thyroxine (TT4) was measured in duplicate with an in-house analyzer and a reference laboratory. After recombinant human TSH administration, healthy pigeons showed a 4- to 21-fold increase in TT4, whereas the hypothyroid pigeon had all values <0.12 µg/dL. The pigeon was prescribed 20 µg of compounded levothyroxine twice daily. In the following months, the pigeon molted and developed adult features. The ventral coelomic soft tissue mass disappeared and repeated computed tomography scans showed a decreased amount of body fat and a reduction in the size of the coelomic mass. Levothyroxine was further adjusted multiple times according to additional TT4 testing to a dose of 2.5 µg once daily. The pigeon has been under treatment with levothyroxine for more than 2 years. Here we present the first reported case of confirmed hypothyroidism in a pigeon. Diagnosis with a TSH stimulation test was unequivocal, even when only considering the results of the in-house analyzer. Levothyroxine treatment resolved clinical signs and could be titrated to an appropriate dose.

Medical Management of Dental Abnormalities Related to Congenital Hypothyroidism in a Cat.

A 5-month-old intact male domestic shorthair cat presenting for routine vaccinations was diagnosed with congenital hypothyroidism. His primary presenting symptom was incomplete dentition with delayed dental eruption. Congenital hypothyroidism was confirmed by baseline thyroxine (T4), free T4, and thyroid-stimulating hormone testing. The cat was treated with oral thyroid hormone supplementation and 16 weeks after initiation of therapy the cat was clinically normal with age-appropriate dentition. No surgical intervention was necessary to achieve normal dental eruption.

Association of recessive c.430G>A (p.(Gly144Arg)) thyroid peroxidase variant with primary congenital hypothyroidism in cats.

BACKGROUND: Primary congenital hypothyroidism (CH) is a rare endocrine disorder in cats with a largely unknown genetic cause. OBJECTIVES: Describe the clinical presentation of CH in 11 affected cats and identify the causal genetic variant. ANIMALS: Eleven CH-cats from 10 unrelated families, 11 CH-free family members, 21 unrelated CH-free cats, and 155 unrelated nondiagnosed cats from different breeds. METHODS: Case control study of CH-cats and their siblings (2019-2021). Diagnosis was based on low to low-normal serum thyroxine (T4) concentrations, high thyroid-stimulating hormone (TSH) concentrations and clinical signs compatible with CH. We identified the causal variant using Sanger sequencing, genotyping via PCR-RFLP and variant interpretation using ACMG/AMP guidelines. RESULTS: All CH-cats (5 weeks-8 years) had disproportionate dwarfism. A goiter was not palpable in all. Thyroid scintigraphy with radiopertechnetate showed abnormally high uptake by thyroid glands, whereas scintigraphy with radioiodine showed abnormally low uptake, compatible with a defect in iodine organification by thyroid peroxidase (TPO). All cases were homozygous for TPO variant XM_006930524.4:c.430G>A(p.(Gly144Arg)), while none of the CH-free cats were. All sampled parents were heterozygous for this recessive variant. This variant was found in 15 cat breeds with an estimated allele frequency of 9%. CONCLUSIONS AND CLINICAL IMPORTANCE: Disproportionate dwarfism, abnormally high TSH and abnormally low to low-normal T4 concentrations are diagnostic for CH in cats. All cases had dyshormonogenesis demonstrated by thyroid scintigraphy. This novel TPO missense variant (not described in humans) causes CH in cats and awareness of it can assist in diagnosis and breeding.

PRESUMPTIVE CONGENITAL HYPOTHYROIDISM IN RED PANDAS (AILURUS FULGENS FULGENS) FROM FOUR SUCCESSIVE LITTERS.

High neonatal mortality among red pandas (Ailurus fulgens) challenges the long-term sustainability of the Species Survival Plan population. Congenital hypothyroidism (CH) is a rare condition in domestic animals, typically due to an inherited genetic defect. Nongoitrous CH was presumptively diagnosed in 75% (n = 6/8) of red panda neonates from four successive litters, with a common sire and two closely related dams. Antemortem diagnosis of CH was made in three cubs (n = 3/6) based on elevated thyroid stimulating hormone and decreased free thyroxine and total thyroxine levels. Affected cubs also had suggestive clinical signs, which included delayed growth with cretinous dwarf appearance, atonic bladder, delayed gastrointestinal motility, hypercholesterolemia, and hypocalcemia. With sodium levothyroxine therapy, two of the three cubs developed into normal adult red pandas in terms of body size, appearance, and behavior. On necropsy cubs (n = 4) were small with varying degrees of cretin dwarf appearance and hypoplastic thyroids with reduced to no colloid in follicles. These cases demonstrate the importance of collecting thyroid tissue, (or proximal trachea/larynx if gross visualization not possible), in neonates for histopathology. Further investigation into the role of thyroid disease in neonatal red panda mortality is warranted.

Cluster of cases of congenital feline goitrous hypothyroidism in a single hospital.

OBJECTIVES: To describe the clinicopathological findings and outcomes of cases of feline congenital hypothyroidism diagnosed in a single veterinary hospital in Santiago, Chile. MATERIALS AND METHODS: Medical records were searched for cases of congenital hypothyroidism over an 18-month period. Inclusion criteria were a diagnosis of congenital hypothyroidism based on consistent historical and clinical findings, a low or low-normal serum total T4 and elevated serum canine TSH (cTSH). RESULTS: Six unrelated cats ranging in age from 4 to 19 months met the inclusion criteria. The most common historical signs were small stature and lethargy. All cats had disproportionate dwarfism, delayed tooth eruption, retained deciduous teeth, bilateral palpable goitres and low rectal temperatures. Other findings were bradycardia, obesity, poor hair coat and focal alopecia on the ventral aspects of the elbows and hocks. In all cases, cTSH was markedly elevated. Sequential changes noted after the initiation of therapy included normal T4 after 6 weeks, improved hair coat and increased physical activity by 8 weeks, normal cTSH by 10 weeks and normal physical appearance and dentition after 4 months. Goitres shrank markedly but remained palpable. Hypothyroidism was well managed clinically in all cases 2 years after diagnosis except for one cat that died of unrelated causes. CLINICAL SIGNIFICANCE: This is the first report to describe a cluster of congenital hypothyroidism cases in non-related cats that were presented over a short period of time. Growth defects resolve with treatment, even in cats diagnosed after puberty. Larger, prospective multi-centre studies are warranted to determine the incidence of congenital hypothyroidism in cats.

Severe calcification of systemic blood vessel walls caused by continuous hypercalcemia in a cat with congenital hypothyroidism.

A 97-day-old male Japanese domestic cat was diagnosed as congenital hypothyroidism. During the treatment, continuous hypercalcemia was detected. Although fluid therapy was performed, the cat died at the age of 1785 days. At autopsy, both parathyroid glands were enlarged, and elastic arterial walls were increased in thickness and hardness. Histopathological examination revealed hyperplasia of both parathyroid glands and interstitial fibrosis of bilateral kidneys. Severe calcification of the tunica media and tunica externa in systemic elastic and muscular arteries were also observed. These calcifications were considered to be due to renal secondary hyperparathyroidism. In the present case, hypothyroidism might have caused hyperparathyroidism through renal failure. In veterinary medicine, this is the first reported case of hypothyroidism accompanied with hyperparathyroidism.

CONGENITAL HYPOTHYROIDISM IN A BORNEAN ORANGUTAN (PONGO PYGMAEUS) AND A SUMATRAN ORANGUTAN (PONGO ABELII).

Congenital hypothyroidism (CH) in humans is most commonly caused by disruption of thyroid gland development (dysgenesis) or an inherited defect in thyroid hormone biosynthesis (dyshormonogenesis). CH has not been previously documented in great apes. This report describes the clinical presentation, diagnosis, and treatment of CH in a 9-mo-old male Bornean orangutan (Pongo pygmaeus) and a 6-wk-old female Sumatran orangutan (Pongo abelii). Primary CH due to thyroid dysgenesis was confirmed in the Bornean orangutan using sonography and radioisotope scintigraphy. Although commercial thyroid immunoassays are not validated for use in orangutans, in comparison to age-matched controls, thyroid-stimulating hormone level was markedly elevated, and serum thyroxine (T4) and free T4 levels were markedly decreased in both cases. Oral supplementation with levothyroxine sodium resulted in noticeable clinical improvement in both orangutans within 30 days of initiating treatment.

Congenital Feline Hypothyroidism With Partially Erupted Adult Dentition in a 10-Month-Old Male Neutered Domestic Shorthair Cat: A Case Report.

Congenital feline hypothyroidism was diagnosed in a 10-month-old kitten. The kitten appeared to have disproportionate dwarfism, with the clinical signs of incompletely erupted permanent dentition covered by thickened gingival tissue, short stature, a broad, flattened face, short neck, pendulous abdomen, kitten-like hair coat, and goiter. Hypothyroidism was confirmed with baseline T4, freeT4, and thyroid-stimulating hormone testing. The kitten was treated with thyroid hormone supplementation and monitored. The kitten appeared clinically like a normal healthy cat at 22 months of age on thyroid supplementation.

Congenital dyshormonogenic hypothyroidism with goiter caused by a sodium/iodide symporter (SLC5A5) mutation in a family of Shih-Tzu dogs.

An iodide transport defect (ITD) in the thyroid gland was determined to cause congenital dyshormonogenic hypothyroidism with goiter (CDHG) in 2 members of a family of Shih-Tzu dogs. Strikingly, both dogs were also diagnosed with dilated cardiomyopathy at 24 and 1.5 mo of age. The only sign of hypothyroidism was a moderate growth delay in the adult dog. The ITD was recognized by the absence of uptake of technetium-99m in the salivary glands (sg) and goiter observed by scintigraphy. In the same scan, radiopharmaceutical uptake was found in the anterior mediastinum of both dogs and in the right axillary lymph node in the oldest dog. A follicular thyroid carcinoma was diagnosed by histopathology after thyroidectomy of the older dog. An adenomatous goiter with ectopic thyroid tissue, and degenerative changes in myocardium were the findings after necropsy in the youngest dog. A homozygous mutation of the intron 9 splice acceptor site of SLC5A5 gene, encoding the sodium/iodine symporter (NIS), was found in the DNA of one of the affected dogs. The mutation was a single base transition of guanine > adenine (G > A) at position 45,024,672 of dog chromosome 20 (CFA20). Five of eight healthy dogs, including both parents of one of the dogs exhibiting CDHG, were heterozygous A/G, and the other 3 were homozygous for the wild-type allele G/G. No sequence variant was found in thyroid peroxidase of the affected dog. Congenital dyshormonogenic hypothyroidism with goiter in this family is an autosomal recessive trait. Our findings are the first evidence of an SLC5A5 mutation in dogs and establish a new genetic cause of CDHG.

Transient Congenital Hypothyroidism Alters Gene Expression of Glucose Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring Rats.

BACKGROUND/AIMS: Transient congenital hypothyroidism (TCH) could disturb carbohydrate metabolism in adulthood. Aging is associated with increased risk of type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of glucose transporters (GLUTs) and glucokinase (GcK) in islets and insulin target tissues of aged offspring rats. METHODS: The TCH group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH groups (n=6 in each group) were followed until month 19. Gene expressions of GLUTs and GcK were measured at months 3 and 19. RESULTS: Compared to controls, aged TCH rats had higher GLUT4 expression in heart (4.88 fold) and soleus (6.91 fold), while expression was lower in epididymal fat (12%). In TCH rats, GLUT2 and GcK expressions in islets were lower in young (12% and 10%, respectively) and higher in aged (10.85 and 8.42 fold, respectively) rats. In addition, liver GLUT2 and GcK expressions were higher in young (13.11 and 21.15 fold, respectively) and lower in aged rats (44% and 5%, respectively). CONCLUSION: Thyroid hormone deficiency during fetal period impaired glucose sensing apparatus and changed glucose transporter expression in insulin-sensitive tissues of aged offspring rats. These changes may contribute to impaired carbohydrate metabolism.

Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog.

BACKGROUND: A case of congenital hypothyroidism with goiter (CHG) in a juvenile French bulldog was identified and hypothesized to be caused by dyshormonogenesis of genetic etiology. OBJECTIVES: To describe case management, unusual phenotypic aspects, and a CHG-causing mutation in a French bulldog. ANIMALS: Thyroid tissue and blood from a CHG-affected French bulldog and 4 normal control dogs and buccal brush samples of 125 French bulldogs were studied. METHODS: Standard clinical assessment and laboratory tests were applied. Thyroid peroxidase (TPO) iodide oxidation activity was measured in vitro, and TPO protein was assessed on Western blots. Thyroid peroxidase exons and flanking splice sites were amplified from genomic DNA and sequenced. Thyroid peroxidase cDNA was amplified from thyroid RNA and sequenced. RESULTS: At 9 months of age, the affected dog had signs of cretinism, but near-normal skeletal maturation. The enlarged thyroid glands exhibited noninflammatory fibrosis and aberrant follicular organization. Thyroid peroxidase activity and immunocrossreactive protein were undetectable. There was a T>C mutation of the intron 12 splice donor consensus that caused abnormally spliced mRNA, consistent with absent TPO function. The mutant allele was not observed in 125 clinically normal French bulldogs. CONCLUSIONS: Presumptive CHG in a French bulldog with unusual clinical presentation is described. Genetic etiology was confirmed by identifying the underlying TPO mutation.

Congenital hypothyroidism and concurrent renal insufficiency in a kitten.

A 3-month-old male domestic short-hair kitten was presented with chronic constipation and disproportionate dwarfism. Radiographs of the long bones and spine revealed delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of congenital primary hypothyroidism was confirmed by low serum total thyroxine and high thyroid stimulating hormone concentrations. Appropriate supplementation of levothyroxine was instituted. The kitten subsequently developed mild renal azotaemia and renal proteinuria, possibly as a consequence of treatment or an unmasked congenital renal developmental abnormality. Early recognition, diagnosis and treatment are vital as alleviation of clinical signs may depend on the cat's age at the time of diagnosis.

Congenital adenohypophyseal hypoplasia associated with secondary hypothyroidism in a 2-week-old Portuguese water dog.

This report describes the histomorphological changes of central hypothyroidism (pituitary dependent) in several target organs of thyroid hormones of a Portuguese water dog, and contrasts those with the reported features of central hypothyroidism in German shepherd dogs, in which central hypothyroidism is a part of a combined pituitary hormonal deficiency.

Congenital hypothyroidism with goiter in Tenterfield terriers.

BACKGROUND: A cluster of cases of congenital hypothyroidism with goiter (CHG) in Tenterfield Terriers was identified and hypothesized to be dyshormonogenesis of genetic etiology with autosomal recessive inheritance. OBJECTIVES: To describe the phenotype, thyroid histopathology, biochemistry, mode of inheritance, and causal mutation of CHG in Tenterfield Terriers. ANIMALS: Thyroid tissue from 1 CHG-affected Tenterfield Terriers, 2 affected Toy Fox Terriers, and 7 normal control dogs. Genomic DNA from blood or buccal brushings of 114 additional Tenterfield Terriers. METHODS: Biochemical and genetic segregation analysis of functional gene candidates in a Tenterfield Terrier kindred. Thyroid peroxidase (TPO) iodide oxidation activity was measured, and TPO protein and SDS-resistant thyroglobulin aggregation were assessed on western blots. TPO cDNA was amplified from thyroid RNA and sequenced. Exons and flanking splice sites were amplified from genomic DNA and sequenced. Variant TPO allele segregation was assessed by restriction enzyme digestion of PCR products. RESULTS: Thyroid from an affected pup had lesions consistent with dyshormonogenesis. TPO activity was absent, but normal sized immunocrossreactive TPO protein was present. Affected dog cDNA and genomic sequences revealed a homozygous TPO missense mutation in exon 9 (R593W) that was heterozygous in all obligate carriers and in 31% of other clinically normal Tenterfield Terriers. CONCLUSIONS: The mutation underlying CHG in Tenterfield Terriers was identified, and a convenient carrier test made available for screening Tenterfield Terriers used for breeding.

Congenital hypothyroidism of dogs and cats: a review.

Congenital hypothyroidism is a rare and underdiagnosed congenital endocrine disorder in dogs and cats and the true incidence is unknown. The disorder may cause a range of clinical signs depending on the primary defect, which affect production of thyroid hormones; some cases present when adult. Hallmark clinical signs of congenital hypothyroidism are mental impairment and skeletal developmental abnormalities, resulting in disproportionate dwarfism; goitre may or may not be present. Documented causes of congenital hypothyroidism in dogs include deficiency of, or unresponsiveness to, thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH), thyroid dysgenesis, dyshormonogenesis and iodine deficiency. In cats, TSH unresponsiveness, thyroid dysgenesis, dyshormonogenesis and iodine deficiency have been confirmed. Adequate replacement therapy results in a successful outcome in the majority of cases, especially when started early in life, as permanent developmental abnormalities can be prevented. This review describes reported cases in dogs and cats, diagnostic investigation, and recommendations for treatment.

Congenital hypothyroidism in a kitten resulting in decreased IGF-I concentration and abnormal liver function tests.

A 7-month-old male kitten was presented with chronic constipation and retarded growth. Clinical examination revealed disproportional dwarfism with mild skeletal abnormalities and a palpable thyroid gland. The presumptive diagnosis of congenital hypothyroidism was confirmed by low serum total thyroxine (tT(4)) concentration prior to and after the administration of thyroid stimulation hormone (TSH), increased endogenous TSH concentration and abnormal thyroid scintigraphic scan. The kitten had abnormal liver function tests and decreased insulin-like growth factor 1 (IGF-1) concentration, both of which returned to normal in correspondence with an improvement of the clinical signs after 6 weeks of thyroxine therapy. Congenital hypothyroidism is a rare disease that may present with considerable variation in clinical manifestation. In cases in which clinical signs are ambiguous, disorders such as portosystemic shunt and hyposomatotropism have to be taken into account as differential diagnosis. As hypothyroidism may be associated with abnormal liver function tests and low IGF-1 concentrations, test results have to be interpreted carefully.

Testicular development in growth-retarded mice.

To assess delayed fertility in male growth-retarded (grt) mice with congenital primary hypothyroidism, their testes were chronologically examined. The testicular weight in grt mice was significantly lower than age-matched normal mice until 8 weeks but was comparable at 13 and 26 weeks. While normal mice had mature sperm cells in both testes and epididymides at 5 weeks, age-matched grt mice did not. The size of the seminiferous tubules in testes of grt mice was smaller than that of normal mice before 13 weeks but was comparable at 26 weeks. These findings suggest that male grt mice might need more than 13 weeks to develop mature testes.

CNS hypomyelination in Rat Terrier dogs with congenital goiter and a mutation in the thyroid peroxidase gene.

Arrested physical development and neurologic abnormalities were identified in 3 of 5 Rat Terrier puppies at 9 weeks of age. Bilaterally firm symmetrical masses were palpated in the region of the thyroid glands. Low serum total (T4) and free thyroxine (FT4, by equilibrium dialysis) and markedly elevated thyroid stimulating hormone (TSH) concentrations supported the diagnosis of hypothyroidism. At necropsy, the thyroid gland was grossly enlarged and histologically exhibited severe, diffuse hyperplasia of the follicular epithelium. Gross examination of the central nervous system revealed a myelin deficiency, most evident in the corpus callosum. Regional distribution of hypomyelination was confirmed histologically, affecting the corpus callosum and, to a lesser degree, the corona radiata, the longitudinal fibers of the pons, the pyramids, and the lateral funiculi of the spinal cord. Myelin reduction was paralleled by axon reduction, suggesting that hypomyelination was a consequence of reduced axonal formation. A homozygous nonsense mutation in the thyroid peroxidase gene was identified in the affected puppies. The dam and a clinically normal litter mate were heterozygous for this mutation, confirming simple autosomal recessive inheritance of the disease trait. The same mutation, causing congenital hypothyroidism with a goiter was previously described in the Toy Fox Terrier breed. Given the ongoing practice of introducing the Toy Fox Terrier genetic background into some Rat Terrier breeding programs to obtain a smaller stature and the apparent relative incidence of the disorder in the 2 breeds, it is likely that this mutation crossed into the Rat Terrier breed from Toy Fox Terriers fairly recently.