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Feline
Thyroid Storm:
Rapid Recognition
to Improve Patient
Survival
Mary Katherine Tolbert, DVM, DACVIM
North Carolina State University
Cynthia R. Ward, VMD, PhD, DACVIMa
University of Georgia
Abstract: In human medicine, thyroid storm is a well-recognized
condition of acute thyrotoxicosis in which the patient’s metabolic,
thermoregulatory, and cardiovascular mechanisms are overwhelmed by excessive circulating levels of thyroid hormone. The
etiology is unknown, but multiple precipitating factors have been
proposed. Hyperthyroid cats presenting in thyrotoxic crisis have
clinical signs similar to those of human thyroid storm patients; however, thyroid storm has not yet been fully characterized in veterinary
medicine. Early recognition and prompt, appropriate treatment of
this life-threatening condition are essential to obtaining a favorable
outcome.
H
yperthyroidism is defined as an endocrine disorder characterized by thyroid hyperfunction.
Thyrotoxicosis, although often used interchangeably
with hyperthyroidism, refers to a clinical spectrum of disease
ranging from an uncomplicated syndrome characterized by
mild clinical signs to an acute, life-threatening form known
as thyroid storm.1–4 Human patients with hyperthyroidism secondary to Graves disease or toxic multinodular goiter may
infrequently experience thyroid storm or thyrotoxic crisis.4,5
Rarely, thyroid storm occurs in patients without hyperthyroidism. In veterinary medicine, the syndrome of thyroid storm
has yet to be fully described. As hyperthyroidism is a commonly recognized endocrine disorder in cats, hyperthyroid
cats are the veterinary patients most likely to present with
clinical signs of thyrotoxic crisis or thyroid storm.6
In humans, thyroid storm is defined as organ dysfunction
and decompensation secondary to exposure to high concentrations of serum thyroid hormone.3,7 Its exact incidence
in human and veterinary medicine is difficult to estimate
because no definitive and universally accepted criteria exist
for establishing a diagnosis.5,7 The mortality rate among human
thyroid storm patients is approximately 30%.3 The mortality
rate among feline thyroid storm patients is unknown but may
approach similar, if not higher, levels. Recognition of thyroid
storm through observation of compatible clinical signs and
identification of predisposing factors is critical to reversing
this potentially life-threatening syndrome.
Physiology
a
Dr. Ward discloses that she has received financial benefits
from Banfield, The Pet Hospital; Morris Animal Foundation;
Pfizer Animal Health; and Intervet/Schering-Plough Animal
Health.
The thyroid hormones, thyroxine (T4, a prohormone) and triiodothyronine (T3), have a wide variety of physiologic effects,
including increasing the metabolic rate of most tissues, enhancing the catecholamine response, acting as positive inotropes
and chronotropes, exerting catabolic effects on muscle and
adipose tissue, and aiding in normal growth and development.
The synthesis and secretion of these hormones are controlled
by thyroid-stimulating hormone, which is secreted by the ante-
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rior pituitary gland in response to thyrotropin-releasing hormone, which is produced and secreted by the hypothalamus.
Although T3 is more potent than T4, most thyroid hormone is
secreted in the form of T4. Peripheral monodeiodination controls thyroid hormone effects by converting T4 to T3. Most thyroid hormone (~99%) in the bloodstream is bound to specific
T4-binding proteins and is, therefore, metabolically inactive;
it becomes unbound before entering cells, where it exerts its
effects through nuclear receptor binding. Unbound T3 and T4
suppress the release of thyroid-stimulating and thyrotropinreleasing hormone through negative feedback.3,8
Pathophysiology
Although the exact causes of thyroid storm are not yet elucidated, five pathophysiologic mechanisms have been proposed: (1) high circulating levels of thyroid hormones, (2)
dramatic changes in thyroid hormone levels, (3) increased
cellular sensitivity to thyroid hormones, (4) increased tissue
sensitivity to sympathetic activation, and (5) a precipitating
event.5,7 Intuitively, high circulating thyroid hormone levels would seem to be an important cause of thyroid storm;
however, studies in humans have shown no difference in
mean serum T4 concentrations between patients with thyroid storm and those with uncomplicated thyrotoxicosis.1,9
A rapid increase in free thyroid hormone availability, leading to an acute rise in serum thyroid hormone, may prove
to play a more important role.1,7,10 Impaired binding affinity
and/or decreased binding protein concentration have both
been implicated as causes of increased serum levels of free
T4 and free T3.9
FELINE
PRACTITIONERS
AMERICAN
ASSOCIATION OF
About AAFP
The American Association of Feline Practitioners improves the health and
well-being of cats by supporting high standards of practice, continuing
education, and scientific investigation. Feline practitioners are veterinary
professionals who belong to this association because they are “passionate
about the care of cats”!
American Association of Feline Practitioners
203 Towne Centre Drive
Hillsborough, NJ 08844-4693
Telephone: 800-874-0498 or 908-359-9351 | Fax: 908-292-1188
E-mail: [email protected]
Media contact: Valerie Creighton, DVM, DABVP
E2
Increased sensitivity to thyroid hormone at the cellular
level is another factor thought to precipitate thyroid storm.7
Nonthyroidal illnesses characterized by sepsis, hypoxemia,
lactic acidosis and ketoacidosis, and hypovolemia have
been associated with increased cellular sensitivity to thyroid
hormone.5 The pathophysiologic mechanisms are poorly
understood but may be associated with decreased thyroid
hormone clearance and/or abnormalities associated with
nucleic acid receptor binding.1
Additionally, because thyroid storm is similar to a hyperadrenergic state, increased sympathetic activation through
interaction between the adrenergic system and excessive
circulating thyroid hormone has been suggested as a precipitating event.1,5,7 This theory is supported by the marked
improvement often seen in thyroid storm patients after therapeutic blockade of the β-adrenergic system.1,5 Serum and
urine catecholamine levels in human patients with thyrotoxicosis have been shown to be within normal limits or
even below the reference interval.1,5,7 Although the mechanism is not completely understood, it may be that the excess
circulating thyroid hormone does not cause an increase
in catecholamine release but rather increases adrenergic
receptor expression or intensifies its effects via postreceptor
pathways.7 This could result in the signs of adrenergic overstimulation despite normal catecholamine levels.
In human medicine, precipitating events have been
documented in approximately 98% of cases.5 Known precipitants of thyroid storm include thyroidal and nonthyroidal surgery, infection and other nonthyroidal illness (e.g.,
diabetic ketoacidosis, trauma, vascular accidents, emotional
stress), administration of iodine-containing agents, vigorous
palpation of the thyroid, and sudden withdrawal of antithyroid medication.1,5,11 Trauma has been found to predispose
patients to thyroid storm through the release of cytokines,
leading to activation of the sympathetic nervous system as
well as increased free thyroid hormone fractions due to
reduced protein binding.12
Clinical Presentation
The clinical signs of thyroid storm reflect severe hypermetabolism. In humans, the diagnosis of thyroid storm is based
largely on observation of four major categories of clinical
signs: (1) central nervous system dysfunction, including agitation, seizures, and coma; (2) fever; (3) gastrointestinal and/
or liver dysfunction; and (4) cardiovascular abnormalities
ranging from sinus tachycardia to atrial fibrillation and congestive heart failure.7 Most of the clinical signs associated
with thyroid storm resemble those of a hyperadrenergic state.
The same clinical signs are observed in human patients with
uncomplicated thyrotoxicosis but to a much milder degree.4
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Feline patients with thyroid storm may have clinical signs
similar to those of human thyroid storm patients, including
heart disease secondary to increased cardiac output due to
increased metabolic demand. Heart disease in these patients
is characterized by arrhythmias, murmurs, gallop sounds,
vascular accidents, pulmonary edema, or pleural effusion.
Additional clinical signs may include neurologic dysfunction, hypertension, acute respiratory distress, dehydration
and hypovolemia, gastrointestinal signs, and hypokalemic
myopathy, predominantly characterized by extreme weakness and neck ventroflexion.2,13,14 As this syndrome is more
frequently recognized in feline patients, the clinical picture
will become more defined.
Diagnosis
The diagnosis of thyroid storm in human patients is often
based on a history of hyperthyroidism and compatible clinical signs and/or resolution of clinical signs with appropriate
treatment.12 Burch and Wartofsky’s scoring system,1 developed in 1993 as an ancillary diagnostic tool, is used to distinguish human patients with uncomplicated thyrotoxicosis
from those with thyroid storm.7 Points are assigned based
on the severity of clinical signs. A score of 45 or greater is
considered highly suggestive of impending or current thyroid storm. We have created a scoring system based on the
Burch and Wartofsky system that may be used to aid in the
diagnosis of feline thyroid storm or to anticipate impending
storm in at-risk patients (BOX 1). Often, response to treatment may be the only means of obtaining a diagnosis.1,10
Laboratory test results, including routine blood work
and measurement of total and free T4, are consistent with
hyperthyroidism and cannot be used to distinguish a cat
with uncomplicated hyperthyroidism from a cat with thyroid storm. In addition, thyroid function tests are of no
value in the veterinary emergency room setting because
rapid results are not available. Nonspecific clinicopathologic
changes consistent with hyperthyroidism and thyroid storm
may include mild erythrocytosis, macrocytosis secondary to
increased oxygen-carrying capacity demand, mild hyperglycemia secondary to catecholamine-mediated insulin antagonism, a stress leukogram secondary to increased circulating
catecholamines, and mildly elevated liver enzymes, including alanine aminotransferase, alkaline phosphatase, lactate
dehydrogenase, and aspartate aminotransferase.13,14 Mild to
severe hypokalemia may also be noted.
Several mechanisms have been proposed for hyperthyroid-induced hypokalemia. Hyperthyroidism can promote
potassium losses through the kidneys via decreased proximal tubule reabsorption due to increased renal blood flow
and glomerular filtration.13,14 Polyuria associated with hyper-
Box 1
Diagnostic Criteria for Thyroid Storm
in Catsa
Impending or current thyroid storm should be
considered if the clinical signs/criteria listed are
present for three or more organ systems.
Thermoregulatory dysfunction
• Temperature >104°F (40°C)
Central nervous system effects
• Seizure
• Coma
• Hyperesthesia
• Extreme agitation
• Ataxia/paresis
• Altered mentation
Neuromuscular effects
• Neck ventroflexion
• Lower motor neuron weakness
Gastrointestinal-hepatic dysfunction
• Diarrhea
• Vomiting
• Unexplained hyperbilirubinemia
Cardiovascular dysfunction
• Severe tachycardia
• Cardiac arrhythmias
• Congestive heart failure
• Thromboembolic disease
Precipitating cause
a
Based on the Burch and Wartofsky algorithm for diagnosing human thyroid
storm.5
thyroidism also results in renal potassium wasting via losses
into the urinary filtrate from the distal nephron.15 Polyuria
due to concurrent chronic kidney disease can further exacerbate renal potassium losses in hyperthyroid cats.13,14
Treatment
Rapid, aggressive therapeutic intervention (TABLE 1) should
be directed toward four main treatment goals: inhibition of
the deleterious peripheral effects of thyroid hormones, inhibition of hyperactive thyroid tissue, provision of supportive care, and identification and treatment of precipitating
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table 1
Medications for Treating Cats With Thyroid Storm2,13,14,22,23
Drug
Dosage/Route
Mechanism of Action
Antithyroid drugs
Methimazole
2.5–5 mg PO, per rectum, or transdermally q12ha
Inhibits thyroid hormone synthesis
Potassium iodate
25 mg PO q8h
Inhibits preformed thyroid hormone release
Iopanoic acid
100–200 mg PO q24h
Inhibits preformed thyroid hormone synthesis;
blocks peripheral conversion of T4 to T3
Inhibition of peripheral effects
Propanolol
0.02 mg/kg IV slowly (may repeat up to four times);
2.5–5 mg PO q8–12h
Antagonizes hyperadrenergic effects with or
without inhibiting peripheral conversion of T4
to T3
Atenolol
1–3 mg/kg PO q12–24h
Antagonizes hyperadrenergic effects
Esmolol
Loading dose: 200–500 μg/kg IV over 1 min;
IV CRI: 25–200 μg/kg/min
Antagonizes hyperadrenergic effects
Dexamethasone sodium phosphate
0.1 mg/kg IV q12–24h
Inhibits peripheral conversion of T4 to T3
Potassium gluconate
¼ tsp (2 mEq) per 4.5 kg in food q12h
Potassium supplementation
Vitamin B­12 (B complex)
1 mL IV (in fluids), IM, or SC
Vitamin B12 supplementation
Low-dose aspirin
5 mg/cat PO q72h
Anticoagulation
Unfractionated heparin
200–400 U/kg SC q8h until aPTT = 1.5–2 × baseline
Anticoagulation
Supportive care
In patients with normal renal function.
aPTT = activated partial thromboplastin time.
a
causes.1,7 Precipitating causes should be ruled out through a
thorough diagnostic evaluation, including a complete blood
count, serum chemistry, urinalysis, FeLV/FIV testing, blood
pressure measurement, fundic examination, and imaging;
other diagnostic tests may also be indicated.
in cats is poorly understood and requires further investigation. Propranolol is a nonselective β blocker and, therefore,
is contraindicated in cats with asthma or congestive heart
failure.13 It has poor bioavailability and requires frequent
dosing because of its rapid hepatic metabolism, but it may
be beneficial in cases of thyroid storm because it can be
Inhibition of Peripheral Effects of Thyroid Hormone
administered intravenously.2,18
The mainstay of treatment directed toward the inhibition of Atenolol, a selective β1 blocker, requires only once-daily
the peripheral effects of thyroid hormones is β-adrenergic dosing because of enhanced oral bioavailablity,2,13,14 making
blockade, unless contraindicated (i.e., in patients with pul- it a more appropriate choice to treat feline thyroid storm.
monary disease and/or severe congestive heart failure not A rapid-onset, short-acting β blocker like esmolol may be
associated with thyrotoxicosis), because β blockers have a used initially in the emergency setting while monitoring the
rapid onset of action and the potential to reverse clinical patient for improvement or deterioration.
signs of thyroid storm.16 The actions of β blockers in the
treatment of thyroid hyperactivity are poorly understood. Inhibition of Thyroid Hyperactivity
Although the thyroid is innervated by sympathetic fibers, β The preferred antithyroid drug, methimazole, is a thionamide
blockers do not act directly to inhibit thyroid hormone syn- used to decrease circulating thyroid hormone concentrations by blocking T4 synthesis through inhibition of tyrosine
thesis or secretion.17
In humans, propranol is thought to act as a weak inhibitor residue organification.19 Methimazole may be administered
of the peripheral conversion of T4 to T3.10 This mechanism orally, rectally, or transdermally. However, it has no effect on
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the amount of preformed thyroid hormone in active thyroid
cells.19 Medications that can be used to block the release of
preformed thyroid hormone from the thyroid include iodine
preparations such as iopanoic acid and potassium iodate.1
Iopanoic acid also inhibits the peripheral conversion of T4 to
T3.20 Methimazole should be given 1 hour before administration of iodine preparations because iodine therapy can transiently increase the release of thyroid hormone, resulting in
a worsening of the thyrotoxic state.1,5
Supportive Care
Supportive care should begin with correction of dehydration
along with aggressive potassium and glucose supplementation for hypokalemic and hypoglycemic patients. Cooling
fluids should be administered to hyperthermic patients.
Blood exchange methods (peritoneal dialysis, plasmapheresis, hemodialysis) have been used in human patients with
severe thyroid storm; however, the expense associated
with these treatment modalities may make them impractical in veterinary medicine.2 Glucocorticoids are used in
human medicine to decrease thyroid hormone release and
to inhibit peripheral conversion of T4 to T321; these agents
are controversial in veterinary medicine and require further
investigation.
Identification and Treatment of Precipitating Causes
Preventive measures to guard against thyroid storm are
important. Because surgery has been reported to be one of
the most common precipitating causes of thyroid storm in
human patients, pre- and perioperative treatment may be
indicated for known hyperthyroid feline patients undergoing surgery.11 A euthyroid state should be ensured before
surgery, and the administration of β blockers may prevent
the development of thyroid storm postoperatively. Another
known precipitant of thyroid storm, abrupt withdrawal of
antithyroid medication, may be addressed by the use of
a β blocker if methimazole is to be discontinued before
iodine 131 (131I ) therapy. After resolution of thyroid storm
(if one occurs) and clinical stabilization, 131I therapy may be
considered.
Conclusion
Thyroid storm is a severe, potentially fatal syndrome
described in human medicine that is characterized by multiorgan decompensation after exposure to excessive circulating levels of thyroid hormones. While further investigation
regarding the prevalence of thyroid storm in hyperthyroid
cats presenting on an emergency basis is warranted, hyperthyroid cats may present with signs compatible with thyroid
storm. The clinical manifestations of thyroid storm are more
Key Points
• Thyroid storm is a life-threatening multisystemic
disease that may occur in cats with hyperthyroidism.
Early recognition and immediate intervention are
critical to achieve a successful outcome.
• Treatment of thyroid storm is directed toward
inhibition of peripheral effects of thyroid hormone,
inhibition of hyperactive thyroid tissue, provision of
supportive care, and identification and treatment of
precipitating causes.
readily treatable when recognized early; therefore, rapid recognition and appropriate treatment are mandatory to ensure
patient survival.
References
1. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol
Metab Clin North Am 1993;22(2):263-277.
2. Ward CR. Feline thyroid storm. Vet Clin North Am Small Anim Pract 2007;37(4):
745-754.
3. Pimentel L, Hansen KN. Thyroid disease in the emergency department: a clinical
and laboratory review. J Emerg Med 2005;28(2):201-209.
4. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocr Metab Clin North
Am 2006;35:663-686.
5. Sarlis NJ, Gourgiotis L. Thyroid emergencies. Rev Endocr Metab Disord 2003;4(2):
129-136.
6. Greco DS. Endocrine emergencies, part II. Compend Contin Educ Pract Vet 1997;
19(2):23-44.
7. Migneco A, Ojetti V, Testa A, et al. Management of thyrotoxic crisis. Eur Rev Med
Pharmacol Sci 2005;9(1):69-74.
8. Boelaert K, Franklyn JA. Thyroid hormone in health and disease. J Endocr 2005;
187(1):1-15.
9. Brooks MH, Waldstein SS, Bronsky D, Sterling K. Serum triiodothyronine concentration in thyroid storm. J Clin Endocrinol Metab 1975;40:339-341.
10.Jao T, Chen Y, Lee H, Tai T. Thyroid storm and ventricular tachycardia. South Med
Assoc 2004;97(6):604-607.
11.Hirvonen EA, Niskanen LK, Niskanen MM. Thyroid storm prior to induction of anaesthesia. Anaesthesia 2004;59:1020-1022.
12.Kanbay M, Sengul A, Güvener N. Trauma induced thyroid storm complicated by
multiple organ failure. Chin Med J 2005;118(11):963-965.
13.Mooney CT, Thoday KL. CVT update: medical treatment of hyperthyroidism in
cats. In: Bonagura JD, ed. Current Veterinary Therapy XIII. Philadelphia: Saunders;
2000:333-337.
14.Mooney CT. Hyperthyroidism. In: Ettinger SJ, Feldman EC, ed. Textbook of Veterinary Internal Medicine. 6th ed. St. Louis: Elsevier Saunders; 2005:1544-1560.
15.Willard MD. Disorders of potassium homeostasis. Vet Clin North Am Small Anim
Pract 1989;19(2):241-263.
16.Langley RW, Burch HB. Perioperative management of the thyrotoxic patient. Endocrinol Metab Clin North Am 2003;32(2):519-534.
17.Geffner DL, Hershman JM. Beta-adrenergic blockade for the treatment of hyperthyroidism. Am J Med 1992;93(1):61-68.
18.Jacobs G, Whittem T, Sams R, et al. Pharmacokinetics of propanolol in healthy
cats during euthyroid and hyperthyroid states. Am J Vet Res 1997;58(4):398-403.
19.McKeown N, Tews M, Gossain V, Shah S. Hyperthyroidism. Emerg Med Clin North
Am 2005;23(3):669-685.
20.Chopra IJ, van Herle AJ, Korenman SG, et al. Use of sodium ipodate in management of hyperthyroidism in subacute thyroiditis. J Clin Endocrinol Metab 1995;80(7):
2178-2180.
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Nat Clin Pract Endocrinol Metab 2007;3(9):662-666.
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1. Which statement regarding thyroid
storm in human patients is true?
a. It is always associated with
hyperthyroidism.
b. A precipitating event is generally not
identified.
c. Clinical signs are associated with
hypometabolism.
d. The clinical signs are the same as for
uncomplicated thyrotoxicosis but more
severe.
2. ________ is not a treatment option for
asthmatic cats with thyroid storm.
a. Propanolol
b. Methimazole
c. Potassium supplementation
d. Atenolol
3. Which is not thought to be an underlying
mechanism of thyroid storm?
a. increased sympathetic activation
b. increased sensitivity to thyroid
hormone
c. rapid increases in free T4
d. decreased conversion of T4 to T3
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4. The clinical signs associated with thyroid storm do not include
a. gastrointestinal signs.
b. fever.
c. central nervous system signs.
d. upper respiratory signs.
8. Appropriate therapy for thyroid storm
does not include
a. β blockade.
b. β agonists.
c. methimazole.
d. potassium iodate.
5. Most thyroid hormone in the blood is in
the form of
a. free T3.
b. free T4.
c. protein-bound T4.
d. protein-bound T3.
9. Measures to prevent thyroid storm might
include
a. vigorous palpation of the thyroid before
131
I therapy.
b. discontinuation of methimazole immediately before surgery.
c. administration of atenolol before discontinuing methimazole in preparation
for 131I therapy.
d. treatment with a β agonist immediately
before surgery.
6. Possible precipitating factors for thyroid
storm include
a. methimazole treatment.
b. intravenous fluid therapy.
c. trauma.
d. β blockade.
7. Diagnostic criteria for thyroid storm
include
a. appropriate clinical signs.
b. hyperthyroidism.
c. resolution with appropriate treatment.
d. all of the above
10.Impending or current thyroid storm may
be diagnosed based on
a. the presence of clinical signs in three or
more organ systems.
b. a history of hyperthyroidism.
c. the presence of mild clinical signs.
d. a history of recent thyroid surgery.
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