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Liothyronine

The thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃), are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis is iodine. The major form of thyroid hormone in the blood is thyroxine (T₄). This is converted to the active T₃ within cells by deiodinases. These are further processed by decarboxylation and deiodination to produce iodothyronamine (T₁a) and thyronamine (T₀a). more...

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Circulation

Most of the thyroid hormone circulating in the blood is bound to transport proteins :

Thyroxine-binding globulin (TBG)
Thyroid-binding prealbumin (TBPA) - this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR)
albumin.

Only a very small fraction of the circulating hormone is free (unbound) - T₄ 0.03% and T₃ 0.3%. This free fraction is biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. These values are referred to as fT₄ and fT₃. Another critical diagnostic tool is the amount of thyroid-stimulating hormone that is present. When thyroid hormone is bound, it is not active, so the amount of free T₃/T₄ is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

Function

The thyronines act on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline).The thyroid hormones are essential to proper development and differentiation of all cells of the human body. To various extents, they regulate protein, fat and carbohydrate metabolism. But they have their most pronounced effects on how human cells use energetic compounds. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

The thyronamines function via some unknown mechanism to inhbit neuronal activity; this plays an important role in the hibernation cycles of mammals. One effect of administering the thyronamines is a severe drop in body temperature.

Related diseases

Both excess and deficiency of thyroxine can cause disorders.

Thyrotoxicosis or hyperthyroidism is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.
Hypothyroidism is the case where there is a deficiency of thyroxine.

Medical use of thyroid hormones

Both T₃ and T₄ are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally. Levothyroxine, the most commonly used form, is a stereoisomer of physiological thyroxine, which is metabolised more slowly and hence usually only needs once-daily administration.

Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia which causes the brain to enter a protective cycle, useful in preventing damage during ischemic shock.

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Understanding feline hyperthyroidism
From International Journal of Pharmaceutical Compounding, 9/1/03 by Davidson, Gigi

Hyperthyroidism is one of the most common endocrine disorders found in middle-aged to older cats. Insidious in onset, it is thought to affect one in every 300 felines. Cats aged 4 to 22 years have been diagnosed with hyperthyroidism, but only about 5% of cats develop hyperthyroidism before the age of 10; the average age of onset is 13.1 Although there are multiple treatment options, including radiation and surgical excision of the thyroid gland, medical treatment with methimazole remains the most common therapy. Novel compounded dosage forms of methimazole (flavored suspensions, chewable treats and transdermal gels) are more readily accepted by feline patients than the commercially available, human-approved tablets. As a result, compounding pharmacists have greatly contributed to im proved compliance in the treatment of this disease.

Pathophysiology

Located in the neck proximal to the trachea and carotid arteries, thyroid glands produce hormones that regulate cellular metabolism. Once circulating thyroid hormones have elicited the necessary physiologic responses, the pituitary gland exerts a negative feedback that stops the production of thyroid hormones. Approximately 70% of hyperthyroid cats develop a benign tumor of the thyroid gland, which causes the thyroid to become overactive.1 Once the thyroid glands become overactive, the usual negative feedback that is provided by the pituitary gland is no longer effective. Overproduction of thyroid hormones results in a multitude of systemic adverse effects and clinical signs.

Clinical Signs

Typically, cats with feline hyperthyroidism begin to show signs of hyperactivity, dementia and increased nocturnal vocalization. They soon progress to symptoms of weight loss, increased appetite, increased thirst and increased volumes of fecal and urinary elimination. Almost all hyperthyroid cats exhibit vomiting and panting, and they become tachycardic. Approximately one half of cats with feline hyperthyroidism develop arrhythmias and murmurs. Many owners complain that their cats shed excessively and that the cats now have a very poor hair coat. A common symptom of hyperthyroidism in a cat is hypertrophied claws, which become unretractable to the point that the cat's approach can be heard when it walks on hard surfaces. It is important to note that the increased organ blood flow caused by hyperthyroidism can mask the onset of other diseases. Once hyperthyroidism is corrected, kidney disease, diabetes mellitus and cardiovascular disease may emerge post-treatment. It is important to emphasize to clients that these diseases were already present in the cat and are not a result of medical or surgical therapy.

Diagnosis

Diagnosis of feline hyperthyroidism is relatively simple and is usually made with a single blood test. The normal blood levels of levothyroxine (T4) are from 1.0 ng/dL to 4 ng/dL. Although both liothyronine (T3) and T4 can be elevated in hyperthyroidism, serum T4 levels are primarily used in diagnosis. Serum T4 values that exceed 4.0 ng/dL are diagnostic. However, occasionally serum T4 levels are not elevated above normal, even though the cat is "clinically" hyperthyroid. Veterinarians then employ other diagnostic methods such as the T3 suppression test, the thyrotropinreleasing hormone stimulation test, and thyroid radionucleotide uptake and imaging. It is extremely important to note that doses of diagnostic agents are designed to evoke a very specific physiological response from the thyroid. The use of novel compounded dosage forms of diagnostic agents is not warranted and may cause equivocal results in diagnostic tests.

Treatment

Three treatment options for feline hyperthyroidism are currently available, as follows:

Surgery-surgical excision of the affected glands (curative),

Radioactive iodine-a single treatment of radioactive iodine that destroys the affected glands (curative), and

Antithyroid medication-chronic treatment (supportive, not curative).

Surgery

Surgery is curative but not without risks. Older cats are already poor candidates for anesthesia, and thyrotoxic cardiomyopathy may make hyperthyroid cats poor candidates for surgery. Another potential risk of surgery is that the thyroid glands reside in extremely close proximity to the parathyroid gland. Accidental removal of the parathyroid can result in hypoparathyroidism, which severely disturbs calcium regulation. Hypoparathyroidism results in hypocalcemia, weak and fragile bones, muscle cramps and weakness, and potentially tetanic seizures. Also, removal of both glands may result in permanent hypothyroidism, for which the only therapy is lifelong levothyroxine replacement. Many veterinarians do not perform this surgery, and referral to a specialist may be necessary. The average cost of surgery is from $600 to $1000 (phone survey of veterinary practices that perform this surgery in the Piedmont region of North Carolina, unpublished data, March 2002).

Radioactive Iodine

Currently, the safest and most effective treatment for hyperthyroidism in cats is radioactive iodine therapy-the optimal treatment. There was a rapid return-to-normal thyroid function in approximately 95% of cats treated with a single dose of radioactive ^sup 131^I.2 However, there are disadvantages to radioactive iodine therapy:

Only specially trained veterinarians are licensed to offer it. In some cases, owners have to drive long distances to a specialty referral center.

Cats must remain isolated for a period of 5 to 7 days (occasionally as long as 2 weeks) in the facility until their radiation levels no longer pose a threat to human health.

The average cost of ^sup 131^I therapy is $850 to $1200.2

Antithyroid Medication

Medical management does not cure the disease. To properly regulate the overactive thyroid, medications such as methimazole (Tapazole) must be given once or twice daily for the remainder of the cat's life. Because of the risk of removal of the parathyroid gland during surgery, daily medication, although inconvenient, is less risky than surgery. Although some adverse drug reactions may occur with methimazole, eg, vomiting, hair loss, decreased white blood cell count, these reactions are usually resolved once the medication is discontinued. Methimazole is a human-labeled tablet for oral administration. Cats that resist administration of the commercially available tablets can receive methimazole compounded into flavored suspensions, chewable treats or a transdermally penetrating gel.3,4 Voluntary and noninvasive acceptance of medication is critical for cats that have cardiovascular compromise from thyrotoxicosis. For cats that do not respond to methimazole, calcium ipodate has been effective (in a few cats). T4 levels have returned to the normal range in cats that have been given calcium ipodate in daily doses of 50 mg to 150 mg per cat.5 Calcium ipodate is not commercially available and can only be obtained from compounding pharmacists. Propylthiouracil is not used for treatment, as it is associated with a high incidence of inducement of autoimmune disease in cats. In rare circumstances, some veterinarians have also imported carbimazole for therapy. Medical management is not curative; therefore, thyroid levels and other blood work must be monitored on a quarterly basis. The estimated cost for medical management and follow-up laboratory work is approximately $600 per year.6

Prognosis

Once feline hyperthyroidism is corrected by surgery or radiation or it is controlled medically, the cat's prognosis for leading a normal, healthy, happy life is excellent.