An outbreak of congenital goiter and chondrodystrophy among calves born to spring-calving beef cows

Abstract

An outbreak of congenital diffuse hyperplastic goiter and chondrodystrophy occurred among springborn calves at an Angus-based cow-calf operation in southern Alberta. Although these diseases are observed globally in multiple species, reports of their occurrence concurrently are exceptionally rare. A nutritional cause is highly suspected as previous matings between the same sires and dams resulted in apparently normal calves. However, it is unclear if multiple mineral deficiencies manifested as goiter and chondrodystrophy independently or if a primary hypothyroidism inhibited normal fetal growth and skeletal development. This is apparently the first large-scale outbreak of concurrent congenital goiter and chondrodystrophy reported in calves.

Case description

An outbreak of congenital diffuse hyperplastic goiter and chondrodystrophy occurred at an Angus-based commercial cow-calf operation in southern Alberta during Spring 2018. The herd was comprised of 34 Angus-based mature cows (~8 y of age) and 2 half-sibling Red Angus bulls. Matings between these sires and cows during the previous 4 breeding seasons resulted in apparently normal calves. The first calf of 2018, born April 5, was weak, smaller than normal, and died within hours of birth. The second calf, born April 9, was weak and initially required assistance to nurse. The third calf, born April 12, exhibited multiple abnormalities. This singleton Red Angus bull calf was abnormally small and had a large swelling in the laryngeal area. The producer noted the calf was also weak since birth and failed to stand, necessitating feeding of colostrum by an esophageal feeder. The producer subsequently requested examination of the calves by a veterinarian.

Upon physical examination, the 1-day old Red Angus bull calf was dull, severely hypothermic and bradycardic, exhibited shallow breathing, and failed to respond to the suckle reflex test. Notable congenital abnormalities included a dwarf-like appearance with superior brachygnathia, suspected diffuse hyperplastic goiter, and unerupted incisors. Due to diminished welfare and poor prognosis for recovery, the calf was euthanized via barbiturate overdose. The entire calf was immediately submitted to a regional diagnostic laboratory for postmortem examination by a Board-certified pathologist. On April 17, 2018, a set of stillborn Angus twins (1 heifer calf and 1 bull calf ) both exhibiting similar congenital abnormalities were also submitted to the same regional diagnostic laboratory. A summary of gross pathologic and histopathologic findings for all 3 calves is reported in Table 1.

Table 1.

Summary of gross pathology and histopathology results for 3 affected calves.

Results for gross pathology and histopathology	Red single bull calf	Twin heifer calf	Twin bull calf
Diffuse hyperplastic goiter (diffusely collapsed follicles with scant globules of colloid; hyperplastic follicular epithelium; vacuolated cytoplasm) with secondary tracheal compression	✓	✓	✓
Chondrodystrophy	✓	✓	✓
Pulmonary atelectasis	✓	✓	✓
Meconium aspiration		✓	✓
Cardiac hypertrophy, liver congestion, and ascites		✓
Diaphragmatic myodegeneration		✓

Sections of liver, lung, kidney, heart, brain, thymus, and spleen from all 3 calves were submitted to a different regional diagnostic laboratory to test for diseases commonly associated with bovine abortion. All 3 calves tested negative for bovine herpesvirus 1, Leptospira spp., Neospora caninum, and bovine viral diarrhea virus via polymerase chain reaction (PCR). Liver samples from these calves were submitted to various diagnostic laboratories for determination of mineral and vitamin concentrations (Table 2).

Table 2.

Liver mineral and vitamin analysis results and interpretations for 3 affected calves.

Liver analysis		Red single bull calf		Twin bull calf		Twin heifer calf
	Reference rangea (mg/kg)	Result		Result		Result
Mineral
Manganese	2.5 to 6.0	1.08	Marginal	1.1	Marginal	< 0.05	Deficient
Iron	45 to 300	521.1	High	590	High	270	Normal
Cobalt	0.02 to 0.09	0.008	Deficient	< 0.01	Deficient	< 0.01	Deficient
Copper	25 to 100	81.9	Normal	150	High	14	Marginal
Zinc	25 to 100	258.9	High normal	340	High	84	Normal
Selenium	0.25 to 1.0	0.7	Normal	0.47	Normal	0.28	Normal
Molybdenum	0.14 to 1.4	0.3	Normal	0.23	Normal	0.13	Marginal
Vitamin
A	14.2 to 36	2.45	Deficient	1.59	Deficient	0.09	Deficient
E	3.4 to 5.6	3.53	Normal	3.32	Marginal	4.55	Normal

^aPuls R. Mineral Levels in Animal Health, Diagnostic Data. 2nd ed. Clearbrook, British Columbia: Sherpa International, 1994.

On April 18, 2018, a follow-up site visit was conducted to examine the dams and calves. Dams of affected and unaffected calves appeared clinically normal and were in adequate body condition (range: 3 to 4/5). A total of 6 live calves were briefly examined. Various clinical signs with varying degrees of severity were noted. The most common abnormality was apparent diffuse hyperplastic goiter, affecting all 6 calves (Figure 1). Abnormalities associated with chondrodystrophy affected 5/6 calves and included shortened appendicular skeletons and superior brachygnathia. A single calf also exhibited widened epiphyses affecting the carpal and proximal interphalangeal joints (Figure 2). Unerupted incisors were noted in the 2 newborn calves; however, a full hair coat and expected calving date indicated that these calves were likely term births. The producer noted that all but 1 live calf born to date were weak at birth and required assistance to either stand or nurse for 1 to 2 d following birth.

Figure 1.

Live Black Angus calf affected with congenital diffuse hyperplastic goiter and mild chondrodystrophy.

Figure 2.

Live Red Angus calf affected with congenital diffuse hyperplastic goiter, moderate chondrodystrophy, superior brachygnathia, and widened epiphyses.

The calving season concluded on June 5, 2018 and, of 35 total calves that were born, an estimated 20 were diagnosed with congenital abnormalities. Of these 20 affected calves, 7 were either stillborn, found dead shortly after birth, or euthanized. The 13 surviving affected calves were diagnosed with congenital diffuse hyperplastic goiter accompanied by varying degrees of chondrodystrophy and generalized weakness. Most of the dead affected calves were born early in the calving season. Severity of congenital abnormalities among both dead and live affected calves tended to decrease as the calving season progressed. Incomplete producer records precluded a more accurate quantification of the affected and unaffected calves and description of temporal events.

A feeding history was obtained from the producer. The herd grazed mixed pasture from the last week of June until the first week of November during 2017. During this time, free-choice loose mineral was offered; however, consumption was noted to be “low.” The herd was transitioned to a home-grown ration consisting of 2/3 wrapped high-moisture barley greenfeed round bales and 1/3 mixed grass hay round bales throughout the winter feeding period and 2018 calving season, similar to previous years. It is noteworthy that the herd was not supplemented with trace mineral or vitamins throughout the winter-feeding period. This is in contrast to previous years, where free-choice loose mineral with added selenium, and vitamins A and E was offered. The high-moisture barley greenfeed was not tested for nutrient analysis. Water was sourced from 2 wells and had not been tested in recent years.

The whole herd was ultimately treated by mixing approximately 14 g ethylenediamine dihydroiodide with every 25 kg bag of loose free-choice trace mineral. Difficulty associated with repeatedly restraining and treating calves greater than several days of age precluded prolonged treatment of individual calves; however, both ethylenediamine dihydroiodide and levothyroxine sodium were prescribed for individual treatment.

Discussion

This is apparently the first reported large outbreak of congenital goiter and chondrodystrophy occurring concurrently in calves. There is 1 other known incidence of this phenomenon affecting 2 beef calves from a Simmental operation in Ontario; however, that case was not reported in a peer-reviewed journal (2). Incidences of concurrent congenital goiter and chondrodystrophy have been reported in other species such as humans (Ellis-van Creveld syndrome), rats, and mice; however, all have been linked to a genetic etiology (3–5). Independent occurrences of goiter and chondrodystrophy in calves can be inherited (6,7); however, the possibility for a genetic etiology in the current case is unlikely, as 4 previous seasonal matings between these sires and dams had resulted in all apparently normal calves.

Congenital goiter in cattle is characterized by enlargement of the thyroid gland often resulting in tracheal compression and dyspnea (8). As observed in the current case, calves are commonly weak, necessitating assistance to stand and nurse for several days after birth, or are stillborn (8–10). Rarely, calves may exhibit partial alopecia (8). An iodine-deficient diet resulting in decreased thyroxine and subsequent secretion of excess thyroid-stimulating hormone (TSH) from the pituitary is the most common cause of congenital diffuse hyperplastic goiter in calves (8,9). It is recommended that gestating dams consume 1 mg/kg DM of iodine in the diet to prevent goiter (8). In the absence of a feed nutrient analysis, a dietary iodine deficiency is suspected in the current case due to the lack of mineral supplementation throughout mid to late gestation.

Congenital abnormalities indicative of chondrodystrophy include a shortened appendicular skeleton, domed cranium, superior brachygnathia, and irregular cartilage and growth plates resulting in angular limb deformities and other structural issues (11). All of these abnormalities were observed in the current outbreak. Outbreaks occurring since the early 1900’s have been reported under various names; however, congenital chondrodystrophy of unknown origin has recently been formally adopted to describe non-genetic associated cases (12). Outbreaks of this nature can be confirmed histologically by the presence of disorganized chondrocytes and cystic spaces within cartilaginous zones of hypertrophy (11). Unlike calves affected with only congenital goiter, chondrodystrophic calves are typically vigorous. Difficulty ambulating and nursing is largely due to structural abnormalities including joint laxity (11,13).

Reduced quantity or quality of feed or other nutritional insult occurring during mid gestation, specifically 3 to 7.5 mo, is the primary risk factor associated with outbreaks of chondrodystrophic calves (13,14). In Canada, feeding silage is often a common denominator (12,13). Although the herd in the current case was not fed silage, they did receive wrapped high-moisture barley greenfeed round bales that undergo a similar ensiling process.

It is theorized the ensiling process results in a leaching of minerals critical for skeletal development or in mycotoxin overgrowth (13,15). A primary or secondary manganese deficiency is the most common underlying nutrient deficiency implicated in outbreaks of chondrodystrophic calves, due to its pivotal role in normal growth plate development and cartilage formation (12,15,16). Gestating beef cattle should consume a minimum of 40 mg/kg DM manganese in the diet (17). However, antagonist minerals such as calcium, iron, phosphorus, and sulfur may reduce manganese bioavailability (18–21).

In the current case, concentrations of multiple minerals were outside normal reference ranges. Liver iron concentration was high in 2 deceased calves and liver manganese concentration was marginal or deficient in 3 deceased calves, suggesting a possible antagonistic interaction. Incidentally, all 3 deceased calves were also deficient in cobalt. As Alberta prairies are deficient in both cobalt and iodine, these trace minerals must be continuously supplemented (22). This is typically achieved via the provision of cobalt-iodized salt or trace mineralized salt (23). As such, the deficient levels of cobalt may serve as a proxy for deficient levels of iodine. These results collectively suggest a primary mineral deficiency, secondary mineral deficiency, or combination thereof as cause of the congenital abnormalities.

In conclusion, it can be inferred from the calf liver analyses that the cows giving birth to affected calves likely experienced multiple mineral deficiencies as a result of inadequate mineral supplementation. However, it remains unclear if these multiple mineral deficiencies manifested as congenital goiter and chondrodystrophy independently or if a primary hypothyroidism had the potential to inhibit normal fetal growth and skeletal development. Adequate maternal and fetal thyroid function is critical for both normal skeletal system development, as well as nervous system development and function (24–27). Reduced long bone growth has long been associated with hypothyroidism in children (25). Additionally, clinical trials conducted with mice demonstrate that high TSH levels are associated with epiphyseal dysgenesis (24). Thus, the hypothesis that a primary fetal hypothyroidism caused signs of chondrodystrophy in the current case is plausible. Further research to adequately test this hypothesis in calves is warranted.

Regardless of the pathogenesis, this case is the first large-scale outbreak of congenital diffuse hyperplastic goiter and chondrodystrophy occurring concurrently in calves.