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Endocrine system
Babetta Breuhaus

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Endocrine system
The endocrine system is comprised of glands that
secrete hormones into the bloodstream. These
hormones act as chemical signals at distant tissues,
usually to regulate their function. Proper function of
endocrine systems involves a number of steps that
can be regulated or controlled. Each hormone
must be synthesized by the gland, stored, and
secreted in response to an appropriate stimulus.
Transportation in the bloodstream usually involves
protein-binding, with only free fractions of
hormones being metabolically active. In order to
regulate target tissues, hormones must be able to
diffuse into the tissues and bind to receptors.
Excess hormone must be metabolized to an inactive
form and either be taken back up by the gland for
reprocessing and storage or be eliminated, usually
through the kidneys or liver. Most endocrine
systems are controlled by negative feedback,
whereby products produced by the target organs
inhibit further release of stimulatory or releasing
hormones. Endocrine diseases usually involve
problems with overproduction or underproduction
of hormones, or altered tissue responses
to them.

Diagnostic work-up _____________________

Physical examination
A complete physical examination is an essential part of the
diagnostic work-up for all diseases. For problems that are
likely to have an endocrine cause, particular attention
should be paid to body weight (e.g. underweight or
overweight, distribution of fat stores), haircoat (length,
condition, areas of alopecia), and mental alertness and
activity level (e.g. depression, lethargy, apprehension,
exercise intolerance).

Hematology

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A CBC and serum biochemical profile should be submitted

to rule out infectious or organ system diseases that could
be responsible for clinical signs. Specific or subtle changes
in a CBC or chemistry panel may be typical for some
endocrine diseases, as detailed in subsequent sections on
those specific diseases.

Endocrine system

Urinalysis
Endocrine-specific urinalysis is not routinely performed in
horses believed to be suffering from endocrine disease.
Measurement of urine concentrations of neurotransmitters
or hormones may be useful in certain cases (e.g. measurement of urinary catecholamines may be useful in the
diagnosis of pheochromocytoma), but these tests are not
commonly performed or readily available.

Hormone analysis
Measurement of serum concentrations of hormones and
response of these hormones to normal stimulants plays an
important role in the diagnosis of endocrine diseases.
Values of various hormones in normal healthy horses have
been published, but it is important to realize that normal
values will vary slightly among different laboratories using
different assay techniques. Therefore, it is important for clinicians to make certain that the laboratories that they are
sending samples to for analysis have validated their assay
techniques for horses and include a reference range of
values with the results that they report.

Diseases of the thyroid and

parathyroid gland ________________________
Hypothyroidism
Overview/Definition
Thyroid function plays an important role in organ growth
and maturation, as well as in metabolism. Both hypothyroidism and hyperthyroidism have been described in the
horse, but true thyroid gland dysfunction is probably much
less common in horses than in some other species, including humans, dogs, and cats. A large number of adult horses
that are administered thyroid hormones probably have
normal thyroid gland function.
Etiology/pathophysiology
Two syndromes of hypothyroidism have been described in
foals, but true hypothyroidism in adult horses has not been
well documented. A syndrome of hypothyroidism and
goiter has been observed in foals exposed to an excess or
deficiency of iodine in utero. Another syndrome of hypothyroidism associated with thyroid gland hyperplasia and
various skeletal abnormalities has been described mainly
in foals born in Western Canada and the US. The etiology
of this second syndrome is not known at this time, but
factors such as nitrate, low iodine, low selenium, or goitrogenic plant ingestion by the mare have been suggested.

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In adult horses a few cases of hypothyroidism resulting
from thyroid neoplasia have been described, but most
thyroid gland tumors are benign, nonfunctional adenomas.
C-cell tumors and carcinomas have also been reported.
Serum thyroid hormone concentrations in most horses
with thyroid gland tumors are within reference ranges.
The irreversible thyroid pathology that occurs with autoimmune thyroid disease in humans and dogs has not been
described in the horse.
The thyroid traps and concentrates iodide, which is
oxidized and bound to tyrosine, either as monoiodotyrosine or as di-iodotyrosine. Two molecules of di-iodotyrosine are combined to form thyroxine (T4), whereas
tri-iodothyronine (T3) is formed from one molecule of
monoiodotyrosine and one molecule of di-iodotyrosine.
Thyroid hormones, primarily T4, are stored within the
gland bound to thyroglobulin. Control of hormone secretion occurs at three sites. Thyrotropin- releasing hormone
(TRH) from the hypothalamus stimulates release of thyrotropin or thyroid-stimulating hormone (TSH) from the
anterior pituitary. At the thyroid gland, TSH increases the
size and activity of the epithelial cells, stimulates proteolysis of thyroglobulin, increases iodide trapping, and increases coupling of monoiodotyrosine and di-iodotyrosine. T4
and T3 are released into the circulation, where they bind to
plasma-binding proteins. Only free (unbound) thyroid
hormones are metabolically active. While the thyroid gland
secretes primarily T4, T4 is deiodinated to T3 (or reverse T3)
in blood and tissues. T3 is much more active than T4, while
reverse T3 has very little activity.
Alterations in circulating concentrations of thyroid
hormones can be mediated centrally by alterations in
TRH (tertiary hypothyroidism) or TSH (secondary hypothyroidism), by alterations in thyroid gland function itself

(primary hypothyroidism), or by alterations in peripheral

thyroid hormone metabolism or binding. Primary hypothyroidism can be caused by interference with iodine
uptake by the thyroid gland or by interference with
thyroid-hormone synthesis or release. Iodine deficiency
or ingestion of goitrogens (e.g. sulfurated organic compounds, thiocyanates, and isothiocyanates) causes goiter
in humans. Iodine deficiency also causes goiter in horses.
Selenium deficiency and mustard have been suggested as
potential dietary goitrogens in the horse. Excessive iodine
ingestion by the mare (e.g. kelp supplements) can cause
goiter and hypothyroidism in neonatal foals.
Certain drugs and various physiologic or pathologic
states can alter thyroid-hormone synthesis, metabolism, or
binding, resulting in altered serum concentrations of
thyroid hormone. In the horse, these include phenylbutazone administration, fasting, and strenuous exercise. Diets
high in energy, protein, zinc, and copper have also affected circulating concentrations of thyroid hormones. Nonthyroidal illness syndrome has not been characterized in
the horse, but unpublished data of the author suggest that
it is similar to the syndrome in other species.

Clinical presentation
Foals
Clinical signs in neonatal foals born to mares ingesting
excessive iodine during gestation (e.g. kelp) include
goiter, incoordination, hypothermia, and poor suckle and
righting reflexes. Clinical signs of a syndrome of hypothyroidism described in foals in Western Canada and the US
primarily involve congenital musculoskeletal abnormalities, including mandibular prognathia (870, 871), flexural
deformities of the forelimbs, ruptured digital extensor
tendons, and incomplete ossification of the carpal and

870, 871 Photograph (870) and lateral skull radiograph

(871) of a foal with congenital hypothyroidism. Note the
mandibular prognathia.

870

871

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872

873

tarsal bones (872, 873). At birth, serum concentrations of

thyroid hormones may be normal in these foals. It is
thought that the musculoskeletal problems are caused by
hypothyroidism during key developmental stages in utero.

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Adults
Clinical signs of hypothyroidism in adult horses are not
well defined. Overweight horses that are easy keepers,
with cresty necks, abnormal fat pads, and a predisposition
to recurrent laminitis have traditionally been described
as hypothyroid. However, thyroid function tests in these
horses are usually normal. Instead of hypothyroidism,
some of these horses have pituitary pars intermedia dysfunction (equine Cushings disease) or equine metabolic
syndrome. Clinical signs in horses properly documented to
be hypothyroid in published case reports include lethargy
or work intolerance and alterations in haircoat. Horses
with experimentally-induced hypothyroidism (either
through surgical removal of the thyroid glands or by
administration of anti-thyroid drugs) demonstrate vague
clinical signs. Surgical removal of the thyroid glands of
adult horses results in decreased basal heart rate, cardiac
output, respiratory rate, and rectal temperature, and
increased serum concentrations of triglycerides, cholesterol, and VLDLs. However, these changes are mild and do
not result in resting values clearly outside reference ranges.
Hypothyroidism has been suggested as a contributing
cause to several other problems in horses (in addition to
laminitis) including chronic myositis, reduced fertility in
broodmares, and anhidrosis, but documentation for these
claims is currently lacking or incomplete. A recent study of
thyroid function in anhidrotic horses demonstrated that

Endocrine system

872, 873 Hypothyroidism.

(872) Dorsopalmar radiograph of
incomplete ossification of cuboidal
bones of the carpus in a foal with congenital hypothyroidism.
(873) Lateral radiograph of incomplete
ossification of cuboidal bones of the
tarsus in a foal with congenital hypothyroidism.

anhidrotic horses had normal serum thyroid hormone concentrations and responses to TRH. However, serum TSH
response to TRH was mildly enhanced, suggesting that
there may be some degree of subclinical hypothyroidism,
or at least an altered sensitivity of the thyroid gland to TSH.

Differential diagnosis
Differential diagnoses for hypothyroidism in adult horses
include pituitary pars intermedia dysfunction, equine
metabolic syndrome, nonthyroidal illness syndrome, or,
perhaps, overfeeding. Additional differential diagnoses for
exercise intolerance could include abnormalities of the
cardiovascular, respiratory, or musculoskeletal systems.
Diagnosis
Because certain drugs and pathophysiologic states can
lower serum concentrations of thyroid hormones in otherwise euthyroid horses, it is important that thyroid-function
tests are not performed while horses are ill, are receiving
certain drugs (e.g. phenylbutazone), or are on thyroidhormone supplementation. The author recommends that
thyroid-hormone testing be performed in horses that have
not received any medications for at least 2 and preferably
4 weeks prior to testing. If a horse has been receiving
thyroid-hormone supplementation without prior documentation of hypothyroidism, the author recommends
weaning the horse off supplementation and then testing
thyroid function once the horse has not received any supplementation for at least 4 weeks.
Tests that are currently available for the assessment of
thyroid function in the horse include measurement of total
and free fractions of T4 and T3 and response of these

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hormones to administration of either TRH or TSH. TRH or
TSH stimulation tests are considered to be superior to
measurement of baseline thyroid hormone concentrations
for the evaluation of thyroid function. However, these tests
are not routinely performed because of the impracticality
of having to take multiple blood samples over time and
because TRH and TSH have not been readily available
commercially or have been prohibitively expensive.
Guidelines for performing a TRH stimulation test in adult
horses are shown in Table 31.
If single point-in-time measurement of thyroid hormones is the only option available for the evaluation of
thyroid status, measurement of free fractions of thyroid
hormones (alone or in conjunction with measurement of
total amounts) provides more useful information than does
measurement of total amounts of thyroid hormones alone.
Serum concentrations of free T4 measured by equilibrium
dialysis are more likely to reflect true thyroid status in ill
horses, compared with other methods. Measurement of
serum TSH concentrations in single samples will also aid in
the diagnosis of thyroid status, once a TSH assay for the
horse becomes available. Ranges for baseline serum concentrations of thyroid hormones from normal, healthy
horses are shown in Table 32 and can be used as a guideline. However, normal values for serum concentrations of
thyroid hormones vary from laboratory to laboratory due
to differences in assay procedures, units of measurement,
and populations of horses used to establish the
laboratorys normal values. Therefore, when choosing a
diagnostic laboratory, it is important to verify that the
laboratory has validated its assays and established reference ranges in a population of normal horses.

TA B L E 3 1 Protocol for thyrotropinreleasing hormone stimulation testing

1 Take a control serum sample.
2 Administer 1mg TRH/400600 kg horse i/v.
Administer 0.5 mg to ponies and foals. TRH (obtained
from a chemical supply house) is put into solution in
sterile water, and frozen in 0.5 and 1 mg aliquots for
individual use.
3 Take additional serum samples 1, 2, and 4 hours
following administration.
4 Submit samples for measurement of free T3, total T3,
free T4, and total T4 analysis. If a TSH assay becomes
available, samples can also be submitted for TSH
measurement.
5 TSH should peak after 1 hour and should increase to
2.53 times the baseline level after TRH administration.
6 Free and total T3 should double approximately 2 hours
following TRH administration.
7 Free and total T4 should increase by at least 1.7 times
the baseline levels at 46 hours following TRH
administration.
8 The time frame for increases in thyroid hormones in
response to TRH is similar in foals to that in adults, but
the amount of increase is less. In foals less than 3 days
of age, total and free T4 should increase approximately
10% 4 hours after administration of 0.5 mg TRH.
Free T4 after equilibrium dialysis should increase by
approximately 30%. Total and free T3 should increase
by 40% and 60%, respectively, 2 hours after TRH
administration.

TA B L E 3 2 Examples of reference ranges for thyroid hormone and TSH concentrations

in adult and neonatal horses
TT4
nmol/l

fT4
pmol/l

fT4 D
pmol/l

TT3
nmol/l

fT3
pmol/l

TSH
ng/ml

Normal adults

n = 71

n = 71

n = 71

n = 71

n = 71

n =71

Mean

20

11

23

1.0

2.1

0.36

95% CI

1822

1012

2125

0.91.1

1.82.4

0.310.41

Range

646

621

747

0.32.9

0.15.9

0.020.97

Normal foals,
2436 hours old

n = 18

n = 18

n = 18

n = 18

n =1 8

n=18

Mean

249

62

92

8.4

11.3

0.28

Range

191318

4482

49144

6.011.8

5.624.2

0.100.68

95% CI

231268

5668

76107

7.59.3

9.013.5

0.210.36

TT3/TT4 = total T3/T4; fT3/fT4 = free T3/T4; fT4D = free T4 by equilibrium dialysis

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Serum concentrations of thyroid hormones are much
higher in neonates than they are in adults. It is thought that
these high concentrations are important for perinatal organ
system growth and maturation. Serum concentrations
decrease gradually after birth, with free concentrations
entering the adult reference range within the first few
weeks of life, and total concentrations reaching adult reference ranges when foals are around 1 month old.

Management
Foals
Ensuring proper iodine concentrations in diets fed to pregnant mares can prevent neonatal goiter. Thyroid hormone
supplementation may be helpful in the treatment of hypothyroid foals in terms of body-temperature regulation, suck
reflex, and mental alertness. Since T4 must be converted to
T3 for biological activity, there is a greater lag period
between administration and metabolic effect for T4 compared with T3. Therefore, a combination of T3 and T4 supplementation would theoretically be more beneficial to a
neonate, but appropriate dosing is unclear. Current dosing
recommendations are listed in Table 33. Since the cause of
the Western syndrome of thyroid dysfunction in foals is
unknown at this time, preventive measures are also
unknown.
Exercise should be restricted in foals born with incompletely ossified cuboidal bones and/or ruptured extensor
tendons. Lightweight splints may be necessary to prevent
foals from knuckling or to prevent collapse of the cuboidal
bones on the medial sides of the joints. If used, splints
must be applied carefully and monitored closely. Foals
wearing splints may require help getting up to nurse and
are at risk for developing decubital ulcers.

Adults
Options for thyroid-hormone supplementation in adult
hypothyroid horses primarily include thyroxine and iodinated casein (Table 33). While 10 mg thyroxine per adult
horse per day is the usual recommended dose, doses of
2040 mg thyroxine per horse per day have been given
short term to euthyroid horses without causing detectable
adverse clinical effects. However, higher doses may
produce agitation and hyperexcitability. Monitoring serum
thyroid-hormone concentrations and maintaining them in
the normal adult range can assure proper dosing.

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TA B L E 3 3 Recommended doses of T4 and

T3 for neonatal and adult horses
Foals
L-thyroxine: 2050 g/kg p/o q24h. Monitor blood T4
to avoid overdosing.
Tri-iodothyronine: 1 g/kg p/o q24h.
Adults
L-thyroxine: 20 g/kg p/o q24h (approximately 10
mg/adult horse q24h).
Iodinated casein: contains approximately 1% T4
(50 mg T4/5 g iodinated casein).
Dose rate: 515 g/horse p/o q24h.
Tri-iodothyronine: 1 mg/horse p/o q24h.

Prognosis
The prognosis for hypothyroid neonates is guarded.
For foals born with goiter, the prognosis improves if the
foal can survive the first week of life. The prognosis for
foals with musculoskeletal abnormalities depends on the
severity of the abnormalities. Certain problems, such as
mandibular prognathia, are unlikely to correct. Incompletely ossified cuboidal bones will ossify in time, but
long-term prognosis depends on whether or not the bones
collapse before ossification occurs. The prognosis for adult
horses with hypothyroidism is good if they are properly
diagnosed and treated.

Hyperthyroidism
Hyperthyroidism is extremely rare in horses. There have
only been a few cases of hyperthyroidism in adult horses
properly documented in the literature, and these have
been in association with thyroid hormone-producing
tumors. Reported clinical signs in these horses include
weight loss, tachycardia, tachypnea, hyperactive behavior,
ravenous appetite, and cachexia. Circulating thyroidhormone concentrations are also sometimes temporarily
increased in horses exposed to excess iodine, such as in a
topical blister.
Horses with hyperthyroidism secondary to thyroid
gland neoplasia have been successfully treated with
thyroidectomy or hemithyroidectomy, followed by
replacement hormone therapy.

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Nutritional secondary hyperparathyroidism
(big head disease, bran disease)

874

Definition/overview
Nutritional secondary hyperparathyroidism is characterized by bone demineralization caused by an imbalance of
calcium and phosphorus in the diet. Young, growing
horses and lactating mares are more susceptible. Primary
hyperparathyroidism has also been reported in scattered
case reports of parathyroid gland adenoma. Clinical signs
and results of diagnostic tests in cases of primary
hyperparathyroidism are similar to those of secondary
hyperparathyroidism.
Etiology/pathophysiology
As the name implies, nutritional secondary hyperparathyroidism is caused by an improper diet (deficient in calcium
or excessive in phosphorus). Ingestion of oxalatecontaining plants that bind calcium in the GI tract can also
cause this disease by decreasing calcium absorption.
Specific diets that can cause nutritional secondary hyperparathyroidism are listed in Table 34.
Low dietary calcium or high phosphorus leads to
increased parathyroid hormone release from the parathyroid gland and increased active vitamin D. The combination of increased parathyroid hormone and vitamin D
promotes calcium and phosphorus resorption from the GI
tract and bone, keeping serum calcium in the normal
range. Serum phosphorus is unchanged (i.e. not
increased), because parathyroid hormone also promotes
renal tubular excretion of phosphate (although vitamin D
inhibits it). Chronic stimulation of the parathyroid gland
results in parathyroid gland hypertrophy and hyperplasia.
The net result is maintenance of a normal serum calcium
level at the expense of bone resorption.

TA B L E 3 4 Diets associated with increased

risk of nutritional secondary hyperparathyroidism
Grain with high phosphorus content and poor to average
hay (i.e. oats [Ca 0.07%, P 0.37%] and grass hay [Ca
0.3%, P 0.3%]).
Increased grain to roughage ratio.

874 Young horse with nutritional secondary hyperparathyroidism. Note the thin, unthrifty appearance and the
enlarged head.

Clinical presentation
Affected horses usually look unthrifty (874). Clinical signs
mainly involve the appendicular skeleton, the teeth, and
the skull. Bone demineralization results in a stiff gait, lameness, painful joints, loose teeth, and painful mastication.
Pathologic fractures can occur. Demineralization and
fibrous proliferation (hyperostotic fibrous osteodystrophy)
in the skull result in firm enlargements of the facial
bones dorsocaudal to the facial crest, thickening of the
mandibles, and thickening of the nasal bones, eventually
resulting in nasal obstruction.
Differential diagnosis
Differential diagnoses for hypercalcemia include renal
failure, primary hyperparathyroidism, nutritional secondary hyperparathyroidism, vitamin D toxicosis, and malignancy (pseudohyperparathyroidism). Intestinal parasitism
should be considered in a thin, young horse that is
primarily unthrifty. Physitis should also be considered in a
young horse with stiffness or pain in multiple limbs.
However, if coarse facial features are present, nutritional
secondary hyperparathyroidism should be strongly
suspected.

Supplemenation with rice or wheat bran (i.e. rice bran

[Ca 0.04%, P 1.8%] and wheat bran [Ca 0.12%, P
1.43%]).
Pasture or hay with oxalate:calcium ratios >0.5%
(i.e. Setaria, Argentine or dallas grass, and buffel grass).

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