Hormonal Therapy - The Merck Veterinary Manual

Hormonal Therapy

Glucocorticoids

Thyroid Hormone

Glucocorticoids:

Glucocorticoids have profound effects on nearly all cell types and organ systems, particularly immunologic and inflammatory activity. They may be used in either an anti-inflammatory or immunosuppressive capacity, depending on the dosage selected. Glucocorticoids are used for hypersensitivity dermatoses, contact dermatitis, immune-mediated diseases (eg, pemphigus, pemphigoid, lupus erythematosus), and neoplasia (eg, mast cell tumor, lymphoma). Glucocorticoids may be classified according to their duration of effect and relative potency (Table: Glucocorticoids). They may be administered PO, IV, IM, or SC. The anti-inflammatory dosage of prednisolone is 0.5-1.0 mg/kg, sid in dogs (severe cases may require 2 mg/kg, sid) and 1-2 mg/kg, sid in cats.

This dosage is given for an induction period of 5-7 days and then reduced to the lowest possible maintenance dose (ideally 0.25 mg/kg, every 48-72 hr or lower in dogs). Maintenance doses must be given 48 hr apart to minimize adrenal suppression and chronic side effects. The immunosuppressive dosage of prednisolone is 2.2 mg/kg, sid in dogs (up to 6.6 mg/kg, sid, may be required in severe disease) and 4.4 mg/kg, sid in cats.

The induction period is generally longer (10-20 days) than with anti-inflammatory dosing, but is then gradually tapered in a stepwise fashion to an alternate-day dosing regimen once there is evidence of disease remission. Treatment should never be stopped abruptly, as there is a risk of inducing signs of hypoadrenocorticism. If relapse occurs during the tapering process, the dose is increased to at least 1 step above the point at which the relapse occurred and tapered again if possible. In many cases, therapy may be withdrawn entirely without relapse, while others require lifelong treatment.

Administration PO is preferred because dosing can be more closely regulated and physiologic processes are disrupted less than with repositol forms. In some cases, difficulties with animal handling or owner adherence may require injectable therapy. This is normally satisfactory for acute, short-term disease that does not require repeated administration (eg, a single injection of methylprednisolone acetate alters adrenocortical function in dogs for up to 10 wk).

Side effects include polyuria, polydipsia, polyphagia, weight gain, increased susceptibility to infection, GI ulceration, pancreatitis, osteoporosis, hyperglycemia, steroid myopathy, and calcinosis cutis. The extent and severity of side effects are related to the dose, duration, and type of glucocorticorticoid used, along with individual animal sensitivity. The most commonly encountered infections are urinary tract infections, pyoderma, and pulmonary infections. Urinary tract infections may develop in many animals on longterm glucocorticoid therapy (68% in one study), and these animals may show no clinical signs of the infection. Urine should be cultured for bacterial growth every 3-6 mo in all animals on longterm therapy.

Progressive hepatocellular swelling due to glycogen accumulation may develop during glucocorticoid therapy. Alkaline phosphatase (ALP), ALT, and γ-glutamyl transferase all show progressive increases. In dogs, the initial ALP increase is due to hepatic ALP but later is due to a cortisone isoenzyme.

Most injectable forms are labeled for IM use; however, they are commonly given SC. Local areas of alopecia, pigmentation, and epidermal and dermal atrophy may be seen with SC injection.

Thyroid Hormone:

Thyroid hormones are indicated as replacement therapy for primary, secondary, and tertiary hypothyroidism. Most cases of canine hypothyroidism are primary in nature and are due to autoimmune destruction of the thyroid gland. Drug-induced low hormone levels or “euthyroid sick syndrome” are not indications for supplementation with thyroid hormones.

Synthetic levothyroxine (T₄) is the drug of choice for canine hypothyroidism. Most dogs respond clinically to a dosage of 0.02 mg/kg, bid. Insufficient serum levels after 4-6 wk of treatment or lack of a clinical response after 12 wk are indications for increasing the dose. Synthetic liothyronine (T₃) may be used for those rare animals that cannot convert T₄ to T₃. It should not be used for routine treatment of hypothyroidism because it bypasses the normal cellular regulatory pathways and has a short half-life. Dosage is 4-6 µg/kg, PO, bid-tid. Crude preparations from thyroid tissue and synthetic thyroid hormone combinations that mimic the T₄:T₃ ratio in humans should not be used in animals.

Signs of thyrotoxicosis in cats and dogs are rare. They include polyuria, polydipsia, nervousness, aggressiveness, panting, diarrhea, tachycardia, pyrexia, and pruritus. Complications in dogs are usually related to concurrent cardiac or adrenal insufficiencies. In animals with a marginal cardiac reserve, T₄ medication should be initiated at one-fourth the recommended dosage and gradually increased to full dosage over a 1-mo period.

Progesterones:

The 2 most commonly used forms of progesterone are megestrol acetate and medroxyprogesterone acetate. Megestrol acetate has a quick onset of action, potent glucocorticoid and slight mineralocorticoid activity, and may be given PO. Medroxyprogesterone acetate is antiestrogenic and has significant glucocorticoid activity. Neutered male and female cats with bilateral alopecia suspected to be caused by sex hormone imbalances may respond to treatment. The dosage of megestrol acetate is 2.5-5.0 mg/cat, PO, every 48 hr, decreasing to every 1-2 wk for maintenance. Medroxyprogesterone acetate is given at a dosage of 50-100 mg/cat, IM, and may be repeated in 3-6 mo.

Progestagens should be avoided whenever possible because of side effects; severe, prolonged adrenocortical suppression is seen even with low doses. Diabetes mellitus has been reported in cats treated with megestrol acetate. Decreased spermatogenesis, pyometra, increased levels of growth hormone with acromegaly, mammary gland hyperplasia and tumors, and behavioral changes may be seen.

Growth Hormone:

Growth hormone (somatotropin) is a polypeptide produced by the anterior pituitary that acts either directly on target tissues or indirectly through insulin-like growth factors (somatomedins) produced by the liver (see also the pituitary gland, The Pituitary Gland: Introduction). It is necessary for hair growth and for development of elastin fibers in the skin. It is used to treat growth hormone-responsive alopecia in dogs. Either bovine, porcine, or human growth hormone (0.1 IU/kg, 3 times/wk for 4-6 wk) is effective. Hair usually regrows in 2-3 mo, and remission may last from 6 mo to 3 yr. Growth hormone is diabetogenic, and dogs can develop transient or permanent diabetes mellitus during therapy. Weekly monitoring of blood glucose before and during therapy is recommended.

Sex Hormones:

Several clinical syndromes in dogs and cats have been attributed to imbalances of sex hormones; however, the etiopathogenesis of these disorders is generally poorly documented. Hypoestrogenism in spayed female dogs, hypoandrogenism in male dogs, and feline acquired symmetric alopecia may respond to sex-hormone therapy. Dosages for sex-hormone replacement therapy are empirical. Hypoestrogenism in spayed female dogs may be treated with diethylstilbestrol (0.02 mg/kg, sid for 3 wk of every month until hair regrows or for a maximum total dose of 1.0 mg/dog). After hair regrows, the maintenance dosage should be given 1-2 times /wk. An alternative protocol is to treat every other day or twice weekly until a clinical response is seen. Hair regrowth should be evident in 3-4 wk, with a complete response within 4 mo. Exogenous estrogen can cause bone marrow hypoplasia, so a CBC and platelet count should be performed weekly during therapy. Other potential side effects include induction of estrus, hepatotoxicity, nymphomania, abortion, pyometra, or prostatic hyperplasia. Cats are highly sensitive to estrogens, and a total dose of 10 mg of diethylstilbestrol can be lethal.

Hypoandrogenism of male dogs may be treated with methyltestosterone, 0.5-1.0 mg/kg, PO, up to a total maximal dose of 30 mg every 48 hr. Alternatively, testosterone proprionate can be given IM once weekly at dosages of 0.5-1.0 mg/kg, or every 4-16 wk at 2 mg/kg. Complications include aggressive behavior, greasy hair coat, prostatic hypertrophy, and hepatotoxicity. Liver function should be evaluated before treatment and monthly during therapy.

Repositol testosterone, 12 mg/cat, IM, may be given once for treatment of feline acquired symmetric alopecia or may be combined with a low dose of diethylstilbestrol, 0.625 mg/cat, IM, or with a low dose of estradiol, 0.5 mg/cat, IM. Hepatobiliary disease has also been reported in cats given testosterone.

Melatonin:

Melatonin is produced in the pineal gland and is involved in the control of photoperiod-dependent molting of some mammals. Secretion is inversely related to daylight length and is highest during the winter. Various canine hair-growth disorders including recurrent flank alopecia, pattern baldness, and excessive tricholemmal keratinization have improved with melatonin supplementation. Recurrent flank alopecia may be treated with 36 mg SC implants. Oral melatonin is also available; an empirical dosage of 3-6 mg/dog, tid-qid, has been used successfully.