Thyroid hyperplasia and musculoskeletal deformity in a standardbred filly in Ontario

Abstract

Thyroid hyperplasia and musculoskeletal deformity, described in foals in western Canada, has not been recognized as a common cause of neonatal foal mortality in Ontario. A case is reported from Ontario, with clinical and histopathological findings consistent with the syndrome described in western Canada.

Thyroid hyperplasia and musculoskeletal deformity (TH-MSD), a syndrome of neonatal foals well recognized in western Canada (1–4), where it is considered an important cause of foal mortality and reproductive loss (5), has not been commonly reported in eastern Canada. The musculoskeletal deformities observed include flexural deformities of the limbs, muscular weakness, mandibular prognathism, and doming of the head.

A standardbred filly in southwestern Ontario was born June 6, 2002, after a gestation of 360 d (reference range, 342 ± 10 d). Despite the prolonged gestation, parturition proceeded unassisted, and the owner was present soon after delivery. Three hours after the birth, the veterinarian was called because the foal had not stood up. On physical examination, the foal appeared somewhat maladjusted.

When reexamined at 11 h old, the foal still had not stood up and several abnormalities were observed, including congenital deviation in the sagittal plane of both carpal joints, and severe, non-reducible, bilateral flexural deformities of the forelimbs. The tendons of the common digital extensor muscle, evaluated by palpation, appeared to be intact. Bilateral hind limb weakness was observed when the filly was assisted in standing up, and flexural deformity of the hocks was also noted. The foal was unable to bear weight when placed in an erect position. There was pronounced mandibular prognathism, with a 1.5-cm deviation from normal jaw alignment, and exposure of the mucous membranes of the lower jaw. Mild ulceration was present on the buccal mucosa of the lower jaw. The head was slightly domed and the haircoat was short and silky, indicative of dysmaturity. The thyroid gland was not palpably enlarged.

A grade III/IV continuous heart murmur was auscultated on the left and right sides of the thorax, with the point of maximal intensity at the mid-ventral 3rd inter-costal space on the left side. This was considered to be indicative of a patent ductus arteriosus, a common finding in neonatal foals. A 6-cm, nonreducible umbilical hernia was also palpated. Dehydration was estimated at 5% on the basis of a prolonged skin tent and tacky mucous membranes. The filly had a normal rectal temperature (37.7°C; reference range, 37°C to 38°C), heart rate (88 beats/min (bpm); reference range, 80 to 120 bpm), and respiratory rate (36 breaths/min; reference range, 30 to 40 breaths/min). Oral mucous membranes were dark pink and capillary refill time was prolonged (3 s; reference range, 1 to 2 s). The foal appeared bright and responsive and exhibited a normal suckle reflex. Lateral and dorsopalmar plain radiographs of both carpi and both tarsi were taken. All bones appeared radiolucent for the age of the foal, and a radiographic diagnosis of incomplete ossification of the cuboidal bones was made (Figure 1). The differential diagnoses at initial presentation were neonatal maladjustment syndrome and TH-MSD.

Figure 1.

Dorsopalmar plain radiographs of both carpi of a 1 day-old standardbred foal with thyroid hyperplasia and musculoskeletal deformity showing incomplete ossification of the cuboidal bones.

The owner was aware of the poor prognosis for nonreducible flexural deformities, but was willing to provide nursing and supportive care for the recumbent foal and to perform physical therapy to attempt to correct these deformities. Repeated flexion and extension of the carpal and tarsal joints and support to assist the filly to stand 1 to 3 times daily was recommended. On day 2, with bodyweight (BW) estimated at 50 kg, the filly was treated with a single infusion of oxytetracycline (Liquamycin LP; Pfizer Animal Health, London, Ontario), 66 mg/kg BW, IV, diluted in 1 L of physiologic saline. The owner was instructed to bottle-feed 400 mL of mare’s milk 4 to 5 times per day.

Despite continued physical and supportive therapy, the filly became dull and depressed on day 8. Physical examination on day 9 revealed no improvement in the flexural deformities of either the fore or the hind limbs. Dehydration was estimated at 7%, and the filly appeared emaciated, as evidenced by marked generalized muscle wasting. Abrasions were noted on the dorsal aspect of the fetlocks of both fore and hind limbs, attributed to repeated unsuccessful attempts to stand. A 2-mm thick, white, caseous coating was present on the tongue and oral mucous membranes, consistent with oral yeast infection. The mandibular prognathism was unchanged, the oral mucous membrane ulceration was pronounced and, in addition, there was petechiation of the oral mucous membranes. The filly was hypothermic (35.5°C) and bradycardic (48 bpm); however, there was no audible heart murmur. A white ocular discharge was present bilaterally. The filly was listless, recumbent, and unresponsive to stimulation.

Accordingly, the filly was euthanized on day 9. Serum was submitted to the Michigan State University Laboratory, East Lansing, Michigan, for evaluation of thyroid function. Total serum triiodothyronine (T₃) was 1.0 nmol/L (reference range, 7.3 to 12.1 nmol/L) and thyroxine (T₄) was 63 nmol/L (reference range, 71.9 to 119.8 nmol/L); free T₄ by dialysis was 17 pmol/L (reference range, 8 to 39 pmol/L) and free (unbound) T₃ was 1.0 pmol/L (reference range, 1.7 to 5.2 pmol/L) (6). These results, which were considered subnormal for a 9-day-old foal, suggested thyroid hypoplasia.

A postmortem examination was conducted within 4 h of euthanasia. In addition to the previously described external findings, several other abnormalities were noted. On dissection, the cuboidal bones of the carpi were noticeably soft and immature, and appeared incompletely ossified. The extensor tendons of both forelimbs were intact. There was no visible pericardial fat, but otherwise the heart appeared normal. The lungs showed areas of consolidation, consistent with a history of recumbency, but no other abnormalities. Seven gastric ulcers were present near the margo plicatus, ranging in diameter from 3 to 5 mm. Although 3 individual areas of intestinal intussusception were present at various levels of the jejunum, the tissue did not appear to be devitalized. A 6-cm umbilical defect was dissected. Internally, the umbilical stalk was 2 cm in diameter by 8 cm long, extending to the urinary bladder, and was filled with caseous, granular material containing several small hemorrhagic areas. There was a 4-mm circular tear in the bladder wall and urine was present in the abdominal cavity. There was no perirenal fat, but the kidneys appeared relatively normal. The thyroid gland appeared to be of normal size (2.5 × 4 cm each side) and was collected into 10% buffered formalin for histopathologic examination.

Histologically, there were very few thyroid follicles, which contained a small amount of colloid. Most follicles were lined with hypertrophic vacuolated epithelial cells, a finding consistent with the diagnosis of TH-MSD. Necropsy revealed several secondary problems attributable to recumbency, physical manipulation, malnutrition, and opportunistic infection.

Congenital thyroid hypoplasia was not reported in association with congenital musculoskeletal deformities in the foal until the early 1980s (7); however, critical evaluation of the literature indicates that cases may have been investigated as early as the 1940s (8). Many history and physical examination findings are common to most cases of TH-MSD. Gestation is often prolonged and the affected foals tend to be born in the latter part of the foaling season. Affected foals exhibit signs of prematurity, despite prolonged gestation. Marked flexural deformities are present in most cases, as well as mandibular prognathism, domed head, and incomplete skeletal ossification (3), all of which were noted in this case.

Other cases of TH-MSD were reported in Ontario in the spring and summer of 2002. A large standardbred breeding farm in southwestern Ontario, located approximately 10 km from the farm where this foal was born, reported 7 cases in May 2002. At least 1 other case was reported in north-central Ontario, involving a Friesian filly. To the author’s knowledge, there are no previous reports in the literature of TH-MSD in eastern Canada.

The etiology of this disease is highly debated. Poor nutritional management of the mare appears to be the most likely cause in most cases. Pregnant mares fed diets that contain high levels of nitrate or that are iodine deficient have been associated with an increased risk of producing an affected foal (4). Also, the presence of fungal toxins in the diet of pregnant mares has been associated with congenital thyroid hypoplasia (9).

In this case, the mare was fed a diet of moderate quality hay and oats throughout gestation, with no mineral supplementation or access to pasture. The mare may have been iodine deficient due to the lack of mineral supplementation, the hay may have contained nitrate, or both. Nitrate is more likely to be present in greenfeed (immature cereal crops). Forage grown under stressed conditions, such as dry weather, has an increased probability of containing nitrate (10). The summer of 2001 was very dry in southwestern Ontario, which may have resulted in an increased nitrate level in some Ontario forages. The forage grown during the summer of 2001 would have been fed during the latter two-thirds of gestation to mares that were bred late in the season (May and June 2001). The equine fetal thyroid gland becomes active by the 4th or 5th mo of gestation (2) and may be most susceptible to insult from poor nutritional conditions in the early to middle part of gestation.

The dry summer of 2001, combined with lack of mineral supplementation, may have predisposed some late-bred mares in Ontario to produce hypothyroid offspring in the spring and summer of 2002. However, it is important to note that there are other potential sources of nitrate, including contaminated drinking water and irrigated pastures. Further investigations should be conducted regarding the prevalence and etiology of TH-MSD in foals in Ontario to increase awareness of this disease.