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Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • Once T3 and T4 are excreted into the circulation, >99% is bound to circulating proteins (primarily albumin)
  • Protein-bound T4 acts as a reservoir to maintain a steady supply of free T4, which diffuses into cells, where it is deiodinated to form T3. Similarly, the majority of circulating T3 is protein bound, and the free T3 is the biologically active form
  • Increased amounts of T3 and T4 in the circulation lead to hyperthyroidism, whereas decreased amounts result in hypothyroidism. Both are pathologic conditions
  • The third form of thyroid hormone in the blood is reverse T3, which is formed from T4 in the peripheral tissues. Concentrations of reverse T3 decrease when there is increased production of T3
  • Goiter is an increase in thyroid size to twice its normal volume

Pathophysiology!!navigator!!

  • The thyroid gland is responsible for the synthesis of the thyroid hormones T4 and T3. These hormones enter cells, resulting in regulation of resting metabolic rate in adult animals. In utero and in growing animals, thyroid hormones are necessary for proper bone, pulmonary, and nervous system development
  • The net effect of hypothyroidism is decreased basal metabolic rate and decreased ability to respond to metabolic demands
  • Horses with systemic disease can exhibit the “euthyroid sick” syndrome—circulating thyroid hormone concentrations are reduced despite the presence of a normal thyroid axis. In these instances, the decreased thyroid concentrations are a response by the diseased animal that decreases the resting metabolic rate and thus conserves energy
  • Hyperthyroidism caused by either an overdose of exogenous hormone or a secreting thyroid tumor; produces an increased metabolic rate that manifests as weight loss and behavioral changes
  • A wide number of factors, including, diet, fitness, disease, and drug administration, result in concentrations of thyroid hormones below the normal reference ranges. In most instances, thyroid function as measured by either the TSH or TRH response test is normal, and the horses cannot be considered hypothyroid

Systems Affected!!navigator!!

Endocrine/Metabolic

  • The endocrine system is primarily affected by abnormal T3 and T4
  • Energy metabolism is altered by hypothyroidism, and affected horses have increased serum cholesterol and metabolize lipid poorly

Musculoskeletal

  • Foals affected with congenital hypothyroidism are born with underdeveloped tarsal and carpal bones, prognathism, ruptured common digital extensor tendons, and forelimb contracture
  • They are often weak and need assistance to stand

Behavioral

Horses with abnormal thyroid levels may have altered behavior such as increased aggression and lethargy with hypothyroidism or nervousness and pacing with hyperthyroidism.

Cardiovascular

  • Thyroidectomized horses have bradycardia, decreased cardiac output, and exercise intolerance
  • Immature respiratory tract and respiratory insufficiency have been reported in hypothyroid foals

Signalment!!navigator!!

  • No sex or breed predilections for abnormal T3/T4 levels
  • Hypothyroidism can occur at any age and exist in utero, with the foal showing characteristic signs at birth
  • Iatrogenic hyperthyroidism generally occurs in adults. Thyroid tumors occur in older horses (>10 years)

Signs!!navigator!!

  • Hypothyroidism foals—prognathism, ruptured common digital extensor tendon, forelimb contracture, retarded ossification and crushing of the carpal and tarsal bones, weakness, and poor suckle reflex. Less common signs—goiter, angular limb deformities, respiratory distress, abdominal hernia, poor muscle development, and osteoporosis
  • Hypothyroidism adults—hypothermia and bradycardia. Less common—cold intolerance, poor hair coat, and poor growth. Horses with experimentally induced hypothyroidism develop edema of the distal limbs and coarsened features
  • Horses with hyperthyroidism due to a functioning tumor exhibit weight loss, pacing, and nervousness

Causes!!navigator!!

  • Drugs, including phenylbutazone, iodine-containing compounds, corticosteroids, and sulfa drugs, may cause low serum levels
  • Ingestion of endophyte-containing fescue, high or low iodine levels, or high carbohydrate diets can decrease circulating hormone levels
  • Hypothyroidism in adults is often idiopathic
  • Iodine deficiency can cause hypothyroidism in horses, but this is extremely rare
  • Iodine deficiency or excess in the diets of broodmares can cause hypothyroidism in their foals; ingestion of endophyte-infected fescue also can result in congenital hypothyroidism
  • Training can decrease thyroid hormone levels
  • In most instances, thyroid tumors are clinically silent
  • Foals have increased thyroid hormone levels compared with older horses
  • Very cold weather also can lead to higher thyroid hormone levels

Risk Factors!!navigator!!

  • Primarily dietary
  • Excess or inadequate iodine or ingestion of other goitrogens can lead to hypothyroidism

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • The primary differential diagnoses for an adult horse suspected of hypothyroidism are a pituitary tumor or insulin resistance (equine metabolic syndrome, insulin dysregulation); these horses, however, suffer from euthyroid sick syndrome. The “classic” presentation of hypothyroidism in adult horses—weight gain, laminitis, “cresty neck,” and abnormal fat deposits—is now recognized as manifestations of insulin dysregulation
  • Hypothyroidism can be ruled out by provocative testing with either TSH or TRH. A history of administration of a drug that decreases thyroid hormone values can explain abnormally low T3 and T4 levels not caused by true disease. A history of overadministration of an exogenous thyroid supplement can explain abnormally high T3 and T4 levels
  • Differentials for foals with congenital hypothyroidism include fescue toxicosis, prematurity, angular limb deformities, and sepsis. Dietary history rules out abnormal iodine in the dam's diet. Physical examination and CBC should rule in sepsis or prematurity/dysmaturity

Laboratory Findings!!navigator!!

Valid if Run in a Human Laboratory?

Laboratory determination of T3, free T3, T4, and free T4 is valid. Use equine reference ranges to interpret results. Free T3 and T4 should be determined using the equilibrium dialysis method for most accurate results.

CBC/Biochemistry Urinalysis!!navigator!!

Hypothyroid horses may exhibit anemia, leukopenia, and hypercholesterolemia.

Other Laboratory Tests!!navigator!!

To confirm the diagnosis of hypothyroidism, consider a TRH or TSH response test. TSH is currently not readily available. For a TRH stimulation test, give 1 mg TRH IV. Collect blood for T3 and T4 determination 0, 2, and 4 h later. One expects to see baseline T3 and T4 in the reference range, the T3 to double at 2 h, and T4 to double at 4 h.

Imaging!!navigator!!

Ultrasonography

  • Rarely useful in diagnosing hypothyroidism
  • Thyroid tumor or goiter could be seen via ultrasonography

Radiography

A thyroid tumor or goiter might be seen as increased soft tissue density in the throat-latch area.

Other Diagnostic Procedures!!navigator!!

A fine needle aspiration or biopsy may assess the thyroid gland.

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Foals with congenital hypothyroidism may require inpatient medical management if the disease is severe
  • All other horses with abnormal T3 and T4 levels can be treated on an outpatient basis

Nursing Care!!navigator!!

  • Foals may need assistance if they are too weak to suckle or mechanical ventilation if they cannot ventilate on their own
  • Animals with poor hair coat may need blanketing, and cold temperatures should be avoided

Activity!!navigator!!

Limit activity in foals with musculoskeletal deformities.

Diet!!navigator!!

  • Examine the diet of any horse with hypothyroidism and the dams of foals born with hypothyroidism to ensure the proper amount of iodine is being fed
  • Pregnant mares should not receive endophyte-infected fescue hay, particularly during their last months of gestation or iodine supplementation. If fescue cannot be avoided, domperidone should be given daily to counter the anti-prolactin effects of the fescue endophytes

Client Education!!navigator!!

  • Prognosis for soundness is poor in most foals with congenital hypothyroidism and should be discussed with owners
  • Adult horses with hypothyroidism respond well to exogenous replacement hormone, and their prognosis is generally good
  • Horses with hyperthyroidism should have their dose of thyroid supplement decreased
  • Animals that are euthyroid despite low blood T3 and T4 levels should have their primary disease treated, but do not require hormone supplementation

Surgical Considerations!!navigator!!

If the cause of increased or decreased T3 and T4 concentrations is a tumor, surgical removal of the affected thyroid lobe should be curative.

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

For decreased T3 and T4 levels caused by hypothyroidism, replacement therapy with T4 20 µg/kg maintains T4 and T3 levels in the normal range for 24 h; this constitutes a dose of 10 mg in a 450 kg (1000 lb) horse.

Contraindications!!navigator!!

Thyroid replacement therapies of euthyroid sick horses may cause further deterioration of the horse's condition. Thus, perform provocative testing to establish the diagnosis of hypothyroidism before beginning to treat.

Precautions!!navigator!!

Exogenous thyroid hormones causes downregulation and, potentially, atrophy of the thyroid gland; gradually discontinue the hormone supplement over the course of several weeks.

Alternative Drugs!!navigator!!

Other sources of thyroid hormone replacement—iodinated casein (5.0 g/day) and concentrated bovine thyroid extract (10 g/day).

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Monitor by measuring serum T4 and T3 levels every 30–60 days. If the serum levels are low, increase the dose of supplement until serum levels reach normal range; if the serum levels are too high or in the higher end of the normal range, decrease the dosage and retest in 30–60 days
  • Reconsider the original diagnosis if the patient fails to respond after 6 weeks of therapy

Possible Complications!!navigator!!

N/A

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Angular limb deformities, hypognathism, weakness, and respiratory distress often are associated with congenital hypothyroidism
  • Infertility and poor hair coat have been associated with hypothyroidism in adults

Age-Related Factors!!navigator!!

  • Higher T3 and T4 levels are normal in neonatal foals. Levels are highest at birth (10 times adult levels), then decrease rapidly in the first weeks of life to adult levels
  • Resting T3 and T4 levels decline gradually with age, and levels in old horses may be lower than those in younger animals

Abbreviations!!navigator!!

Suggested Reading ⬆ ⬇

Allen AL, Townsend HG, Doige CE, Fretz PB. A case-control study of the congenital hypothyroidism and dysmaturity syndrome of foals. Can Vet J 1996;37:349–358.

Frank N, Sojka J, Messer NT. Equine thyroid dysfunction. Vet Clin North America Equine Pract 2002;18:305–319.

Hilderbran AC, Breuhaus BA, Refsal KR. Nonthryoidal illness syndrome in adult horses. J Vet Intern Med 2014;28:609–617.

Author(s) ⬆

Author: Janice Kritchevsky

Consulting Editors: Michel Lévy and Heidi Banse