An update in feline endocrine diseases (Proceedings)
Hyperthyroidism is the most common endocrine disorder in the cat. Since being first recognized in 1977, the incidence has increased steadily.
Hyperthyroidism is the most common endocrine disorder in the cat. Since being first recognized in 1977, the incidence has increased steadily. This is, no doubt partly due to greater awareness and early screening, but certainly also due to a real increase in occurrence of this disease. The etiology and pathogenesis are not certain, but epidemiological surveys have shown an increased incidence of this disease is seen in cats:
- fed a majority of tinned food in their diet,
- living strictly indoors, using litter,
- having a reported exposure to lawn herbicides, fertilizers and pesticides,
- having been regularly treated with flea sprays or powders, and
- who aren't Siamese (one study only, breed predilection has not confirmed in any other study).
- exposure to flame retardants
The disease has been reported in North America, Europe, Australia and New Zealand, but less frequently, or not at all, in other parts of the world. These risk factors implicate environmental, nutritional and genetic factors. It is also logical to assume, however, that cats who are well cared for and thus live longer, will be exposed to litter and canned foods.
Some of the goitrogens that are being studied include iodine and phyhalates (common in cat foods), resorcinol, polyphenols and PCBs, all of which may also be in diets, especially those containing fish, or in the environment. These hydrocarbons need to be metabolized in the liver, by glucuronidation, a process compromised in the cat, making this species more prone to toxicities. Goitrogen exposure may be sporadic, rather than ongoing, as sporadic exposure has been shown to induce thyroid hyperplasia in experimental models. Other theories consider that nodular goiter development may be a normal age-related condition.
Regardless of the cause(s), the condition of hyperthyroidism, is a multi-systemic disorder caused by excessive concentrations of circulating thyroglobulins, T4 and T3, produced most commonly by benign, hyperplastic adenomatous glands, but rarely by malignant, adenocarcinomatous glands. 97-99% of hyperplastic glands are benign and adenomatous. Approximately 70% of cases have bilateral disease, a fact that is critical when considering surgical therapy and favours pre-surgery technetium scanning.
Most recently, attention has been directed towards brominated-flame retardants. Dr. Janice Dye presented an abstract at ACVIM 2007 in which she states: “Coincident with global introduction of BFRs into household consumer products nearly 30 years ago, hyperthyroidism in cats has increased considerably. The etiopathogenesis of feline hyperthyroidism remains unknown. We hypothesized that increasing exposure of pet cats to BFRs such as the polybrominated diphenyl ethers (PBDEs) has, in some manner, contributed to the abrupt increase in and now common occurrence of feline hyperthyroidism…Our finding that pet cats in the U.S. have high PBDE serum levels is in good accord with the most consistently identified risk factor for development of FH, namely indoor living. We further propose that house cats--because of their meticulous grooming behavior--not only come in direct contact with these consumer products, they readily ingest any volatilized PBDE-like material or PBDE-laden dust that deposits on their fur. Future studies are needed to elucidate if and how PBDE bioaccumulation of this magnitude in cats can disrupt maintenance of their thyroid-endocrine-axis.” (Dye JA, Venier M, Ward CR, et al. Brominated-Flame Retardants (BFRs) in Cats--Possible Linkage to Feline Hyperthyroidism?)
While hyperthyroidism is a disease of middle aged to old cats (4-22 years old), it has been reported in cats aging from 8 months - 22 years of age. There is no breed or sex predilection.
The frequency and severity of clinical signs has decreased since the condition was originally reported. This is likely due to screening, as clients often aren't aware that their cat is ill early in this disease. In fact, because the thyroid hormones are generally anabolic and stimulatory, the client usually feels that their cat is in good health, with a good to excellent appetite and is lively (in fact hyperactive) relative to his/her age. The only sign may be defecating outside of their litter box and/or large, voluminous stools.
In a study comparing findings in hyperthyroid cats in 1983 and 1993, weight loss was the most common historical finding in both studies, but its prevalence was much higher in 1983 (98 vs. 87% in 1993). Other clinical signs also have significantly decreased prevalence in 1993 (all following statistics given as 1983 vs. 1993): polyphagia (81 vs. 49%), hyperactivity (76 vs. 31%), polyuria/polydipsia 60 vs. 36%), diarrhea (33 vs. 15%), muscle weakness (25 vs. 12%), panting (25 vs. 9%), large fecal volume (31 vs. 8%) and anorexia (25 vs. 7%). Vomiting is still prevalent in approximately 50%2.
generally thin, active, bounding, rapid heart with a cardiac murmur (b-lub-dub), palpably enlarged thyroid gland, +/- agitated, unkempt coat. Apathetic hyperthyroidism is a less common presentation (~5%) in which the cats are depressed, weak and may be anorectic. Be aware that obesity may also be present in some hyperthyroid cats.
Physical examination findings in the 1993 paper: Number of cats (% of 202 cats): Large thyroid gland: 167 (83%), Thin: 132 (65%), Heart murmur: 109 (54%), Tachycardia: 85 (42%), Gallop rhythm: 30 (15%), Hyperkinesis: 30 (15%), Aggressiveness: 20 (10%), Unkempt hair coat: 19 (9%), Increased nail growth: 13 (6%), Alopecia: 6 (3%), Congestive heart failure: 4 (2%), Ventral neck flexion: 2 (1%)2.
Thyroid hormones regulate metabolic processes in virtually every tissue. Thus, increased appetite, weight loss, polydypsia, polyuria, vomiting, diarrhea, tachycardia, heat intolerance, hyperexcitability/nervousness, behavioural changes, tremour and tachycardia are classic findings in the hyperthyroid cat. However, as the signs are gradual in onset and range from mild to severe, a client may not be aware of any abnormalities.
Baseline CBC, chemistry screen, urinalysis, total T4
Elevations of the liver enzymes alanine aminotransferase (alt) and serum alkaline phosphatase (sap) are common findings in > 90% of hyperthyroid cats, although the cause for this is not clear. Histologic evaluation of the liver of these cats shows mild, non-specific changes. SAP has been hypothesized to increase due to increased metabolism of bone. Increases in alt are harder to explain, as alt is an intra hepatocellular enzyme, yet there is no increased hepatocellular membrane damage. Thyroid hormones may have direct toxic effects on the liver, hypoxia, CHF, infection, malnutrition may all play a role, but the exact cause for increases in alt and sap are not known. These enzyme values return to normal when euthyroidism is achieved.
Concurrent renal dysfunction is also fairly common in untreated hyperthyroid cats, allowing for low urine specific gravity (usg), +/- elevations of blood urea nitrogen (BUN) and serum creatinine (SC). However, the beneficial effect of the excessive thyroid hormone on cardiac output, causing an increase in renal blood flow, can also act to mask underlying renal disease. Therefore, it is essential to continue to monitor these renal parameters during therapy. Numerous studies have shown that amelioration of the hyperthyroid state by any method (i.e. medical therapy, 131I treatment or surgery) can lead to decreased GFR, elevations in BUN and creatinine, and, in some cases, overt azotemia3.
The question that remains is how to assess cats prior to definitive therapy (131I or surgery) and which cats need to be evaluated. One study found that none of the cats with a GFR above 2.25 ml/kg/min prior to 131I administration developed renal failure as the hyperthyroidism resolved. While this GFR value may represent a cut-off for deciding if renal failure/insufficiency is a possibility, measurement of GFR is not easily obtained and another study could not substantiate this finding. Another option is to treat cats transiently with methimazole until the serum T4 is adequately controlled. When the serum T4 is maintained within the normal range, the effect of definitive therapy can be assessed. If renal failure does become overt after definitive correction of hyperthyroidism, exogenous thyroid hormone can be supplemented to support the kidneys. A balance must then be struck between creating iatrogenic hyperthyroidism and maintaining renal function.
Thyroid function tests
The total T4 is the first test used to assess thyroid function. Total T4 values may fall within normal reference range in a) early in the course of disease, b) because of normal fluctuations of this hormone and c) when there is concurrent, non-thyroidal illness present (“euthyroid sick syndrome”). When one is suspicious of hyperthyroidism but T4 values are normal, one can use one of the alternative testing methods or repeat the T4 measurement at a later date4. In-house testing has been shown to be inaccurate for measurement of T4 in cats (and dogs)5.
Free T4 can be helpful in confirming a diagnosis of hyperthyroidism in a patient with high normal total T4 along with clinical signs suggestive of hyperthyroidism. It must be noted that nonthyroidal illness can, in <1-% of cats, cause artificial elevations resulting in an incorrect diagnosis. Thus, its use should be restricted to use in cases where confirmation is needed rather than as a screening test. Equilibrium dialysis is the methodology that has been shown to be the most reliable for measurement of this hormone2.
Thyrotropin Releasing Hormone (TRH) Stimulation Test:
This test is easily performed. Collect a serum sample prior to administration of Relefact TRH (0.1 mg/kg IV), then collect a second serum sample 4 hours later requesting a T4 measurement. A fresh baseline value must be taken at time zero. Common side effects include panting, vomition, salivation and defecation.
Hypothalamus (TRH) -> Pituitary (TSH)-> Thyroid (T4 --> T3) -> negative feedback loop. Hyperthyroid cats, because of the autonimity of their thyroid gland function, experience less, if any elevation in their post TRH serum T4 values.
Triiodothyronine (T3) Suppression Test
The protocol for this test is slightly more involved, but still very simple. Draw a serum sample to determine baseline T3 and T4, separate the serum by centrifugation, then refrigerate or freeze the serum. Clients are instructed to administer T3 (Cytomel: 25 mcg) PO q8h for two days; on the morning of the third day, a 7th dose of T3 is administered, and serum is collected within 2-4 hours for T3 and T4 determinations. Both the basal (day 1) and post T3 serum samples should be submitted to the laboratory together to eliminate inter-assay variation. Again, as a hyperthyroid gland is autonomous from superior control, we expect to see no suppression of the T4 value. The T3 assays must be run to ascertain that the client was successful in administering the Cytomel to the cat. While Cytomel is much less expensive than Relefact, this test is prone to inconclusive results.
Thyroid imaging is a safe, easy and reliable adjunct in diagnosing hyperthyroidism in cats. It has the advantage of determining the extent of involvement, namely whether both lobes are involved and whether metastasis is present as well as being a good predictor of thyroid metabolic status6.
Thyroid Stimulating Hormone (TSH) Response Test
This test is currently unavailable and not validated in cats.
- Methimazole (Tapazole) acts by inhibiting synthesis of thyroid hormones. Initially dose at 2.5 mg/cat PO BID, recheck T4 after 10-14 days and adjust dose accordingly. Side-effects to be aware of include an acute facial pruritis, with red wheals on the ears (uncommon). Gastrointestinal upset (anorexia, vomiting) and lethargy are more common (up to15%), but these are transient and resolve when the drug is stopped and then started again at a lower dose. Hepatotoxicity may arise and is a serious side effect if it occurs. Severe thrombocytopenia and leukopenia (agranulocytosis) or development of ANA titers may occur and will require cessation of the drug. Because of these potential effects, as well as the renal precautions discussed above, and the possible growth of the tumour, regular monitoring of CBC, T4, BUN, SC and a urine specific gravity should be done at 3-4 month intervals. Transdermal methimazole has been shown to be absorbed but that it may take four weeks of use to get therapeutic serum levels7,8.
- Ipodate (Orograffin) or iopanoic acid (Telepaque)
- The major disadvantage of medical therapy is that it must be continued (along with monitoring) lifelong.
While thyroidectomy is an easy procedure. Ideally, a technicium scan should be preformed ahead of time to determine whether unilateral or bilateral disease is present as well as to detect extrathyroidal tumour is present. Thoracic radiographs and an echocardiographic evaluation of cardiac function are recommended precautions prior to anaesthesia. It is important to achieve pre-operative euthyroidism and cardiac stability by treating with methimazole and atenolol for 4-6 weeks prior to surgery. These cats are major anaesthetic risks and the choice of anaesthetic regimes needs to be considered carefully. Avoid xylazine and atropine; be aware of the hyperthyroid predisposition to catecholamine-induced arrhythmias and choose agents accordingly. Ketamine may be contraindicated because of its propensity towards creating hypertension.
Post-operative measurement f serum calcium at 48 and 72 hours post- op if bilateral surgery is done. A cat who is hypocalcemic will present with facial twitching (early), muscle weakness and spasms, to full-blown seizures and death.
Therapy for hypocalcemia
- 1.DHT (Dihydrotachysterol) 0.03 mg/kg daily
- Ca gluconate tablets (1-3/day)
- For acute hypocalcemic tetany
- 2-5 cc calcium gluconate (10%) IV SLOWLY!
- EKG monitoring advisable
- Do not use calcium chloride
Other possible post-op complications include paralysis of the laryngeal nerve, or Horner's Syndrome. Levothyroxine supplementation is advised in cats who have had bilateral thyroidectomy performed, starting (0.1-0.2 mg/day PO) 24-48 hours post-op for several weeks or months. Monitor T4 levels, to determine when this supplementation can be ceased.
Radioiodine therapy is “the gold standard”
Other treatments that have recently been evaluated are ethanol injection of the thyroid and percutaneous heat ablation of the thyroid. The former cannot be recommended because of serious adverse effects and the latter is not a permanent solution.
Regardless of form of therapy the T4 should be checked every 4-6 months, as the condition may recur either due to incomplete surgical removal, an inadequate 131I dose, or growth of the tumour necessitating a higher dose of methimazole. Following 131I, a one month and 3 month evaluation of BUN and SC are advisable.
Adrenal disorders in cats
Hyperadrenocorticism (HAC, Cushings Disease)
Cushings is a disease of middle-aged to older cats (7-12 years), and may be caused by a pituitary tumor (90% are adenomas), pituitary hyperplasia, adrenal tumors, adrenal hyperplasia, by non-endocrine tumors (usually lung) or it may be iatrogenic. Clinical signs in cats include uncontrolled diabetes: (PU/PD, polyphagia, weight loss), pendulous abdomen, lethargy, thin skin, recurrent infections and poor muscle mass are common. Thin skin is the hallmark of feline hyperadrenocorticism and these cats may develop open wounds just by grooming themselves. Often we see severe insulin resistance and this often predates the diagnosis of Cushings by several months. Cushings should always be on the differential with cats that need very high doses of insulin. The thin skin is another feature of the disease. This also occurs in the dog but it seems to be more pronounced in the cat perhaps due to later recognition.
Changes expected in the bloodwork are non-specific but include hypercholesterolemia, hyperglycemia, mild leukocytosis and erythroid regeneration (nrbcs). The serum alkaline phosphatase and alt will be elevated. In cats this is not a steroid effect; it is due to concurrent lipidosis or possibly pancreatitis. Decreased T4 and T3 caused by "euthyroid sick syndrome" and attenuated response to TSH stimulation caused by overcrowding of pituitary thyrotrophs by adrenocorticotrophs. Overt diabetes mellitus may result from the insulin antagonism caused by hypercortisolemia in about 85% of cats with hyperadrenocorticism. Urinalysis changes include glucosuria, possibly a low urine specific gravity and a secondary bacteruria.
In order to get the adrenals to suppress in the cat, the “Low-dose dexamethasone test” requires 0.1mg/kg dexamethasone sodium phosphate IV and sample plasma at times 0,2,4,6 and 8 hours after injection. Because cats may escape suppression earlier than 8 hours, so the plasma should be sampled at more frequent intervals than in dogs. Normal cats and cats with non-adrenal illnesses will consistently show cortisol suppression at this dose. However, unlike dogs, it may not suppress cats with pituitary dependent HA. Thus, we can't use it to discriminate between adrenal tumours and PDHA in cats. Rather, the feline “High-dose dexamethasone test”, i.e. administering 1.0mg/kg dexamethasone IV and sampling at times 0,2, 4, 6 and 8 hours will differentiate PDHA from adrenal tumours in most cases. In the rare cat who doesn't suppress even at this dose, endogenous ACTH levels, abdominal ultrasound, CT or MRI are required to confirm the location of the tumour. There is controversy about the definitive test with some endocrinologists saying that ACTH stimulation test is the test of choice in cats. The majority of cats have pituitary dependent HA.
Ultrasound is very helpful. It can be used together with endocrine tests to provide a diagnosis of PDHA. With PDHA, one will see 2 normal or enlarged adrenal glands. With adrenal tumors there will be atrophy of the contralateral gland. In cats, adrenal calcification is a normal aging change unlike in the dog where calcified adrenals on radiography are cause for concern.
- Control the diabetes with as much insulin as is required. This is important, not only from the perspective of glycemic control, but also because the immunosuppressive effects of glucocorticoids predispose an already prone individual to infections.
- op-DDD (Lysodren): 25 mg/kg BID for 10 days. Check an ACTH stimulation test and if the values are below 5mcg/dl, then reduce the frequency of administration to once weekly. Retest ACTH stimulation after 4 weeks.
Note: when performing an ACTH stimulation test in cats, collect plasma at time 0, administer 2.2 units of porcine ACTH gel/kg IM (Repository Corticotropin injection USP) and collect plasma again at 1 and 2 hours post injection or administer 0.25 mg synthetic ACTH/cat IM (Cortrosyn) and collect plasma again at 30 minutes and 1 hour after injection. It is important that the reference laboratory being used has established feline reference ranges.
- Metyrapone, which blocks adrenal conversion of 11-deoxycortisol to cortisol may be used at 65mg/kg PO q12h. Clinical improvement is expected within 5 days of initiation of therapy. Monitor blood glucose closely as diabetic cats will be prone to becoming hypoglycemic rapidly.
- Recently, trilostane, a steroid synthesis inhibitor, has been reported for the treatment of PDHA.
Op-DDD, metyrapone or aminoglutasamine may be used to stabilize the patient prior to adrenalectomy. While the challenge is very real to stabilize these patients prior to surgery, adrenalectomy (unilateral for adrenal tumour or bilateral for PDHA) offers the best success.
Post-operatively, cats may develop sepsis, pancreatitis, thromboembolism, wound dehiscence, adrenal insufficiency and hypoglycemia. For patients who had a unilateral adrenalectomy, prednisolone 2.5mgPO q12h should be started in the evening after surgery, continued for several weeks before tapering. For bilaterally adrenalectized cats, lifelong mineralocorticoids will be required. Pituitary tumour enlargement may be treated safely and effectively with external beam radiation therapy.
There are several reports of cats with progesterone secreting adrenal gland tumours. Progestins have a similar structure to cortisol and can mimic the effects of glucocorticoids in cats resulting in the signs of hyperadrenocorticism by suppressing the hypothalamic-pituitary-adrenal axis. When insulin resistance is being evaluated in a cat, HAC, acromegaly and progesterone excess should be considered. If a diagnosis of HAC cannot be confirmed by measurement of cortisol during an ACTH response test or dexamethasone suppression test, adrenal sex hormone assays should be considered. Medical treatment using aminoglutethimide, a drug capable of inhibiting steroid hormone synthesis may be effective short-term; adrenalectomy is the recommended long-term therapy.
Hypoadrenocorticism (addison's disease)
This condition may be more common than Cushings in the cat and may readily be misdiagnosed as renal insufficiency. The clinical signs are similar to those in the dog and include lethargy, weakness, inappetance/anorexia, vomiting, diarrhea, PU/PD. On physical examination, the patient is depressed, dehydrated, has a slow capillary refill time, weak pulses (signs of dehydration and electrolyte imbalance), hypothermic and bradycardic. The major differentials are renal insufficiency, shock and urethral obstruction.
Laboratory findings show hyperkalemia, hyponatremia, hypochloremia, hyperphosphatemia (rarely hypercalcemia), and prerenal azotemia with a concurrent low urine specific gravity (caused by medullary washout). The CBC may show a lymphocytosis and eosinophilia with a mild, non-regenerative anemia. The diagnosis is made, after initiating treatment, using the ACTH stimulation; a lack of response is diagnostic for hypoadrenocorticism.
Treatment consists of fluid therapy, glucocorticoids and mineralocorticoids. Florinef is administered at 0.1 to 0.2 mg PO q12h or DOCP at 1 mg/lb. IM or SQ every 21-28 days. Cats seem to due better on supplemental prednisolone especially in terms of eliminating GI side effects. Prednisolone also seems to be needed more in cats receiving DOCP, as DOCP has no glucocorticoid activity. Prednisolone doses are low: 1.25 to 2.5 mg once a day or q48h.
There is also an atypical form of hypoadrenocorticism that cats get probably more frequently than the form described above. This is a glucocorticoid-deficiency state in which electrolyte disturbances are not present at the time of initial presentation. Hence, the cats appear in a similar state and may be thought to have renal or gastrointestinal disease but on evaluation of the minimum database, the characteristic hyperkalemia and hyponatremia are absent. Iatrogenic secondary hypoadrenocorticism is similar but has low endogenous ACTH. Atypical Addison's responds to oral prednisolone therapy.
Hyperaldosteronism (conn's syndrome)
Conn's syndrome is a rare but recently reported condition in the cat and is caused by a unilateral neoplasm of the adrenal cortex producing excess mineralocorticoids. Cats present with systemic hypertension, muscle weakness from hypokalemia, and polyuria. This is a condition usually seen in geriatric cats and can be mistaken for renal insufficiency. Treatment consists of potassium supplementation and control of hypertension. Some require very high doses of IV and oral K supplementation to resolve the hypokalemia. Doses as high as 60-80 mEq of KCl/liter of fluids may be required in some cats. The first clinical clue to the hypertension may be retinal detachment. Blood pressures are in 200-280 systolic range. Amlodipine is indicated to reduce the hypertension and doses are titrated to effect. The diagnosis is made by documenting elevated serum aldosterone levels. Urinary fractional excretion of potassium may be very elevated. On ultrasound, a unilateral adrenal mass is found. These tumours are usually benign and surgery can be curative. If surgery is declined, then amlodipine and potassium supplementation will help to control the clinical signs. Spironolactone, a potassium-sparing diuretic works by antagonizing aldosterone receptors (2-4 mg/kg/d). Interestingly, almost all of the cats have had other endocrine disorders (esp. hyperthyroidism). It has also been seen with insulinoma, so this may be a feline example of multiple endocrine neoplasia (MEN). Given the recent number of case studies in the literature, It is recommended that primary hyperaldosteronism should be considered as a differential diagnosis in middle-aged and older cats with hypokalaemic polymyopathy and/or systemic hypertension and should no longer be considered a rare condition.
Acromegaly has been studied in the last several years with an increased level of interest as it has been discovered that ¼ to 13 of cats with diabetes may have unrecognized acromegaly. This condition is usually caused by an adenoma in the pars distalis of the anterior pituitary gland that secretes excessive growth hormone (GH). Less commonly, pituitary hyperplasia is suspected to result in acromegaly. Insulin-like growth factor 1 (IGF-1) is produced in the liver in response to the GH. GH has catabolic and diabetogenic effects, while IGF-1 has anabolic effects.
The characteristic signs of acromegaly are insulin resistance, believed to be caused by a GH-induced post-receptor defect in the tissues; most are middle-aged to older, neutered male mixed breed cats. Physical changes consisting of prognathism and a broad face, large thickened limbs with clubbed paws and organomegaly may be present but subtle. Upper respiratory stridor associated with structural changes may be seen. Organomegaly refers to hypertrophy of the heart and enlargement of the kidneys in particular. In addition, arthropathies occur and, in some cases, there may be neurological signs from intracranial tumour expansion.
Classic signs of diabetes: PU/PD with polyphagia are present despite increasing doses of insulin. Uncharacteristic of diabetes, however, is concurrent weight gain. There are two populations of acromegalic cats: those who have been diabetic for some time and then deteriorate while the second group consists of those cats who appear to be acromegalic from the beginning of their diabetes.
Differentials that need to be considered when dealing with an insulin resistant or uncontrolled diabetic cat include treatment compliance or comprehension failure, inappropriate insulin handling, resistance associated with concurrent, uncontrolled inflammatory or infectious conditions, neoplasia or hyperadrenocorticism.
Diagnosis is suggested by measurement of increased IGF1 levels or imaging studies of the pituitary gland. If possible, GH measurements should be included. It must be noted, however, that no single antemortem test is 100% reliable as there may be false positives and negatives in any of them. GH is secreted in a pulsatile fashion. This may result in false negatives, i.e., normal GH values in an acroegalic cat and, important from a therapeutic perspective, may intermittently allow marked hypoglycemia to occur as a result of large insulin doses. IGF-1 is secreted continuously and is, therefore, theoretically more reliable. Contrast enhanced CT or MRI studies are very useful for diagnosis as well as for treatment planning, should radiation or stereotactic radiosurgery be a consideration.
There are several therapeutic options. Conservative treatment with high doses of insulin as needed may be used, however the risk is that iatrogenic hypoglycemia may occur if the insulin dose is too high for the GH surge at the time. Thus, should this form of treatment be the one chosen, the client and veterinary team needs to work closely together to ensure that the client is able to assess blood glucose levels and trends.
Medical therapeutic options are of three kinds in humans.
- Somatotropin analogues (octreotide, followed by longer-acting lanreotide) or more recent, long acting, once a month agents have been developed. In about 50% of humans, GH and IGF-1 secretion is controlled. Octreotride has not been effective in cats.
- Pegvisomant is a GH-receptor antagonist that is used in humans but also has not been effective in cats. It isn't known whether it binds to cat GH receptors.
- The third type of drug are dopamine antagonists such as bromocriptine and L-deprenyl (Selegiline). 70% of humans respond well to them but neither have been properly evaluated in cats.
Currently the best treatment option is radiation therapy with either 39 to 54 Gray (Gy) administered either once weekly for 4-5 weeks; Monday through Friday in 2.7 or 3.0 Gy fractions or twice or three times weekly. By reducing the bulk and function f the pituitary mass, neurological signs associated with mass as well as insulin resistance improve. Adjustment of insulin doses is not straightforward as resolution of insulin resistance can occur immediately or months after radiotherapy.
Hepatic IGF-1 hyperproduction does not always resolve, so while diabetic management may become significantly easier or diabetes may resolve, the anabolic effects (polyphagia, bone growth, organomegaly, etc.) may still cause problems.
Stereotactic radiosurgery is being evaluated at Colorado State University. This ivolves use of a gamma knife to reduce the tumour mass. Cryotherapy is another technique that has been attempted in a small number of cats.
In cats with pituitary-dependent hyperadrenocorticism, microsurgical transphenoidal hypophysectomy has been described in 7 cats; in five cats the hyperadrenocorticism disappeared. This may be another possible technique for acromegaly.
Because there are chronic, ongoing changes associated with the effects of the IGF-1, namely possible arthropathy, HCM, renal insufficiency and hypertension, these, along with quality of life must be addressed regardless of form of therapy.
Without treatment, acromegalic cats may suffer neurological damage from the mass effect, iatrogenic hypoglycemia, congestive heart failure, respiratory distress, renal failure or pain from arthropathies.
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