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Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • TRH and TSH stimulation tests are performed to evaluate the ability of the thyroid gland to secrete T3 and T4. TRH may also be used to test horses with suspected PPID
  • TRH test to evaluate thyroid function—give TRH (1 mg IV) and measure T3 and T4 levels at 0, 2, and 4 h. In normal horses baseline T3 and T4 are in the reference range. T3 concentration doubles at 2 h, and T4 concentration doubles at 4 h after TRH or TSH administration
  • TSH test (5 IU IV) is performed in the same manner, with the same expected endpoints
  • TRH test to evaluate pituitary function—give TRH (1 mg IV), and measure blood ACTH at 0 and at 10 min. In normal horses, ACTH concentrations do not change; however, an ACTH concentration >1.5 times baseline 10 minutes after TRH administration suggests that PPID is present

Pathophysiology!!navigator!!

  • Thyroid hormone levels in blood are regulated by the thyroid–pituitary–hypothalamic axis. Endogenous TRH is released from the hypothalamus and travels to the pituitary gland. The pituitary gland then secretes TSH, which stimulates release of T4 and T3 from the thyroid gland
  • When exogenous TSH is given, the thyroid gland's ability to secrete hormone is tested
  • When TRH is given, the pituitary gland's ability to respond to this by secreting TSH and then the thyroid gland's ability to respond to the endogenous TSH are tested
  • In equine medicine, test selection is based primarily on availability of the reagents. Presently, TSH is not available for clinical use but TRH can be obtained from compounding pharmacies at reasonable cost
  • The inappropriate response of pituitary tumor cells to TRH is not completely understood. Tumor cells are hypothesized to have an alteration in the receptor/adenylate cyclase system that allows for a paradoxical response to specific and nonspecific challenges

Systems Affected!!navigator!!

The endocrine system is affected by abnormal results of the TSH or TRH stimulation tests—decreased thyroid hormone response to the stimulation test is diagnostic of hypothyroidism while increased ACTH in response to TRH suggests, but is not diagnostic, of PPID. The TRH stimulation to diagnose PPID should not be performed in the fall as the seasonally adjusted normal ranges have not been established.

Signalment!!navigator!!

  • No sex or breed predilections
  • Hypothyroidism can occur at any age
  • PPID occurs in older horses (>15 years)

Signs!!navigator!!

  • Signs associated with an abnormal TRH/TSH stimulation test are those of hypothyroidism or PPID
  • Clinical signs of congenital hypothyroidism in foals—prognathism, ruptured common digital extensor tendon, forelimb contracture, retarded ossification, crushing of the carpal and tarsal bones, weakness, and poor suckle reflex
  • Less common signs of congenital hypothyroidism in foals—goiter, angular limb deformities, respiratory distress, abdominal hernia, poor muscle development, and osteoporosis
  • Hypothermia and bradycardia are consistent findings in adults with hypothyroidism. Other signs include poor hair coat and poor growth
  • Clinical signs of PPID include hypertrichosis (previously termed hirsutism) and failure to shed. Also common are abnormal fat distribution, pendulous abdomen, weight loss, polyuria and polydipsia, laminitis, and chronic infections

Causes!!navigator!!

  • The primary cause for lack of response in a TSH/TRH stimulation test is primary hypothyroidism. Many factors can cause low T3 and T4 concentrations in blood; however, the horse cannot be diagnosed as truly hypothyroid unless it fails to respond to TSH/TRH stimulation testing
  • The primary cause for increased ACTH after TRH administration is inappropriate response of a pituitary tumor to TRH

Risk Factors!!navigator!!

  • Known risk factors for thyroid abnormalities are dietary. Intake of excess or inadequate iodine or ingestion of goitrogens can lead to hypothyroidism
  • In old populations, thyroid tumor is a risk factor for development of thyroid abnormalities
  • PPID is a risk factor for development of abnormal ACTH secretion in response to TRH

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

The primary differential diagnosis for increased ACTH after TRH administration is stress response. Psychic stress from handling, receiving injections, and blood sample collections may result in increased blood ACTH.

Laboratory Findings!!navigator!!

Drugs That May Alter Laboratory Results

N/A

Disorders That May Alter Laboratory Results

N/A

Valid if Run in a Human Laboratory?

Laboratory determination of ACTH, T3, free T3, T4, and free T4 is valid if run in a human laboratory. Use equine reference ranges to interpret results. Free T3 and T4 should be determined by equilibrium dialysis method.

CBC/Biochemistry/Urinalysis!!navigator!!

  • Hypothyroidism—anemia, leukopenia, and hypercholesterolemia
  • PPID—stress response with a mature neutrophilia, lymphopenia, and eosinopenia; possibly increased blood glucose and glucosuria

Other Laboratory Tests!!navigator!!

Pituitary function—endogenous ACTH determination, dexamethasone suppression testing, and domperidone response test; if results are consistent with PPID, this would support a positive TRH test.

Imaging!!navigator!!

  • Ultrasonography—rarely useful in hypothyroidism, but an enlarged thyroid gland caused by tumor or goiter could be visualized
  • Radiography—an enlarged thyroid gland caused by tumor or goiter might be seen as an increased soft tissue density in the throat-latch area
  • Increased pituitary gland size may be visualized with specialized modalities—CT or venous contrast

Other Diagnostic Procedures!!navigator!!

Fine needle aspiration or biopsy may assist in assessing the thyroid gland.

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Foals with congenital hypothyroidism may require inpatient medical management as they often suffer from severe musculoskeletal disease
  • All other horses with abnormal TRH/TSH tests can be treated as outpatients

Nursing Care!!navigator!!

  • Foals may need assistance standing and milk administered via nasogastric tube if they are too weak to suckle
  • Foals may need mechanical ventilation if they cannot breathe on their own
  • Animals with a poor haircoat may need blanketing
  • Horses with laminitis need corrective hoof trimming and shoeing. They may also require a low-carbohydrate diet if they evidence insulin dysregulation

Activity!!navigator!!

  • Limit activity of foals with musculoskeletal deformities—incomplete ossification of the carpal or tarsal bones
  • Limit activity of horses with laminitis

Diet!!navigator!!

  • Examine the diet of any horse with hypothyroidism and of dams with foals born with hypothyroidism to ensure that the proper amount of iodine is being fed
  • Pregnant mares should not receive endophyte-infected fescue hay or iodine supplementation, particularly during the last months of gestation
  • Horses with laminitis generally benefit from a low-carbohydrate diet

Client Education!!navigator!!

  • The prognosis is poor in most foals with congenital hypothyroidism and, thus, should be discussed with owners before expensive treatments begin
  • Adult horses with hypothyroidism respond well to exogenous replacement hormone. Their prognosis generally is good.
  • Mares in the northwestern portions of North America should not be fed green feed or irrigated pastures that are high in nitrates and should receive mineral supplementation including adequate amounts of iodine
  • Horses with PPID may be managed via medication (pergolide) and nursing care, but their prognosis is quite variable. Some do well for several years; others are refractory to treatment. Owners need to understand that treatment is palliative and required for life

Surgical Considerations!!navigator!!

If the abnormal TRH/TSH response test results from a tumor of the thyroid gland, surgical removal of the affected thyroid lobe should be curative.

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • For decreased T3 and T4 caused by hypothyroidism, replacement therapy with synthetic T4 is the drug of choice—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
  • The agent most commonly used to alter symptoms of PPID is pergolide (0.5–2 mg/day)

Contraindications!!navigator!!

If the horse has low resting T3 and T4 values because of some other severe disease (e.g. euthyroid sick syndrome), thyroid replacement therapies may cause further deterioration. Perform provocative testing before administering medication in any horse with suspected hypothyroidism that is debilitated or exhibits signs of any other disease.

Precautions!!navigator!!

  • Exogenous thyroid hormone causes downregulation and, potentially, atrophy of the thyroid gland. Discontinue the supplement gradually over the course of several weeks
  • Horses that receive overdoses of pergolide may exhibit anorexia, lethargy, and ataxia

Possible Interactions!!navigator!!

N/A

Alternative Drugs!!navigator!!

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

Follow-up ⬆ ⬇

FOLLOW-UP

Patient Monitoring

  • Monitor horses on thyroid supplement by retesting serum T4 and T3 levels every 30–60 days. If the serum level is low, increase the dosage until the normal range is achieved. If the serum level is too high or at the higher end of the normal range, decrease the dosage and retest the horse
  • Failure to respond clinically after 6 weeks of therapy should prompt reconsideration of the original diagnosis of thyroid disease
  • Retest horses with PPID every 12–20 weeks by endogenous ACTH determination. Abnormal results indicate the need for an increased dose of pergolide

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Angular limb deformities, hypognathism, weakness, and respiratory distress often are associated with congenital hypothyroidism
  • Skin problems and myositis have been associated with hypothyroidism in adults
  • Hypertrichosis (previously termed hirsutism), chronic infections, and laminitis are commonly associated with PPID

Age-Related Factors!!navigator!!

On the first day of life, foals have little T3 response to TRH/TSH administration. Only a T4 response should be evaluated in neonatal foals.

Zoonotic Potential!!navigator!!

N/A

Pregnancy/Fertility/Breeding!!navigator!!

N/A

Abbreviations!!navigator!!

  • ACTH = adrenocorticotropic hormone
  • CT = computed tomography
  • PPID = pituitary pars intermedia dysfunction
  • T3 = triiodothyronine
  • T4 = thyroxine
  • TRH = thyroid-releasing hormone
  • TSH = thyroid-stimulating hormone

Suggested Reading ⬆ ⬇

Beech J, Boston R, Lindborg S, Russell GE. Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia. J Am Vet Med Assoc 2007;231:417–426.

Durham AE, McGowan CM, Fey K, et al. Pituitary pars intermedia dysfunction: diagnosis and treatment. Equine Vet Educ 2014;26:216–223.

Frank N, Sojka J, Messer 4thNT. Equine thyroid dysfunction. Vet Clin North Am Equine Pract 2002;18:305–319.

Author(s) ⬆

Author: Janice Kritchevsky

Consulting Editors: Michel Levy and Heidi Banse