DISEASES OF THE ENDOCRINE SYSTEM

1) DIABETES MELLITUS

Diabetes mellitus is a disorder affecting the beta cells in the Islets of Langerhans in the pancreas. These cells normally produce insulin. Damage to these cells can occur due to pancreatitis and auto-immune disease. Occasionally the pancreas fails to develop properly (congenital diabetes).

Other conditions may affect the body's response to insulin, causing the signs of diabetes :-

- Other disease (Hyperadrenocorticism, excessive growth hormone production).

- Drugs (Corticosteroids, Progestagens.)

- Dioestrus in the bitch (Increased progesterone levels).

There are, therefore two types of diabetes recognised :-

- Type 1- insulin dependent, in which there is little or no secretion from the pancreas. This is the type found in dogs, and many cats. (and young humans).

- Type 2- non insulin dependent, delayed secretion or poor secretion. This type responds to oral drugs and diet manipulation and is found in some cats. (and older humans).

Insulin is necessary for intracellular use of glucose, and the body's glucose monitoring area in the brain is also dependent on insulin to "see" blood glucose. When insulin levels fall, therefore, the brain thinks that there is less glucose in the blood stream, and gluconeogenesis starts in the liver. The body continues to make more and more glucose as the lack of insulin prevents the brain from detecting the rising blood levels. Eventually, the body thinks it is starving,biochemical panic occurs, and fats and proteins are broken down to manufacture emergency fuel. In particular fats are turned into ketones, and these give rise to ketoacidosis, which causes the more severe signs of diabetes such as coma.

Signs

-Polyuria

-Polydipsia (>60ml/kg/day due to the osmotic effect of the glucose in urine or glycosuria)

-Weight loss, often after obesity

-cataracts

-urinary and skin infections -

-occasionally weakness due to nerve damage.

In dogs Terrier breeds are most at risk, females more than males, and middle aged. In cats males are seen more often than females, and usually older animals.

Presentation at the surgery is usually:

a) Simple diabetics:- Polyuria (PU), Polydipsia (PD) and weight loss

b) Ketacidotics:- ketones present in the urine, and these animals may be quite ill - depression, anorexia, vomiting, halitosis, oliguria due to dehydration. This stage leads on to:

c)Diabetic coma

Treatment

a) Simple diabetics - can go straight on to stabilisation.

In-patient initial stabilisation is usually necessary using insulin therapy. There are two types of insulin for long term use, Protamine Zinc Insulin (PZI) which is long acting (12-36 hours duration) and Lente which is intermediate acting (6-12 hours). The insulin is given in the morning by subcutaneous injection then blood glucose levels are measured every 1-2 hours . The animal is fed at lowest blood glucose (=maximum insulin activity). Establishing a blood glucose curve is necessary because there is considerable individual animal variation both in timing of maximum activity and in dose of insulin. Ideally the blood glucose minimum at feeding time should be in the lower 1/3 of the normal range (i.e. around 4-4.5 mM/l)

When the patient is sent home, then either blood testing or urine monitoring or both can be used to check progress.

Some cats, particularly those which are obese, can be treated with oral medication (usually glibenclamide) and dieting. Cats metabolise insulin quickly so usually need PZI

It is also possible to use other strategies to control diabetes, such as twice daily feeding and twice daily injecting, or feeding little and often in conjunction with once or twice daily injections. These are usually reserved for more difficult to manage diabetics

b)Ketoacidosis - Attend to first aid measures if comatose (A.B.C.). These animals are very dehydrated and are acidotic. Assume a 10-15% level of dehydration, although lab tests of packed cell volume and plasma protein levels can be used as indicators.

Infuse Hartmann's at 20-40 ml for 2 hours then reduce the rate. Aim for 50% of the hydration deficit to be restored at 12 hours and 100% restored by 36 hours. Remember to also allow for normal daily loss (40ml/kg/day).

The veterinary surgeon may well use soluble insulin infusion to reduce blood glucose levels in emergency cases. This has a duration of action of only an hour or two.

Management of diabetics before surgery

1/No food after midnight the previous day

2/ Give 1/2 the usual insulin dose at the usual time

3/ 5% glucose drip during surgery, and monitor glucose every 1-2 hours post op until the animal eats again.

2/ DIABETES INSIPIDUS

Is unrelated to diabetes mellitus, except for the display of thirst, which is huge.

Diabetes insipidus arises due to either failure of production of Antidiuretic Hormone or ADH (from the pituitary), or insensitivity to it (at the kidney).

The sign of this disease is ENORMOUS thirst. This can lead to bizarre behaviour as the animal attempts to satisfy its craving for water. Intake usually exceeds 100ml/kg/day, and the urine specific gravity (SG) may be as low as 1.000 (=water).

These animals are unable to concentrate urine, so diagnosis is by Water Deprivation Test. Preliminary blood and urine testing is usual to check that there is no other concurrent disease which might put the animal at risk if it becomes dehydrated (e.g. renal failure).

In a simple deprivation test, the body weight and starting urine SG is recorded, then water is witheld. Urine is tested every 2 hours, by catheterisation if necessary, and the animal is weighed.The test is stopped when the animal has lost 5% body weight (Positive diagnosis) or when urine SG is >1.025 (negative diagnosis).

Sometimes a more gradual version of the test is used with reduction in allowed water over 3 days preceding the complete withdrawal test.

Treatment is with an ADH replacer drug - DDAVP which comes as nasal drops. If the problem is at the kidney DDAVP may be ineffective, and a type of diuretics known as thiazides can be used which have a paradoxical effect to reduce urine output.

3)HYPERADRENOCORTICISM (Cushing's Disease)

This disease occurs when there is an excess of cortisol in the body. This can be due to a pituitary tumour or an adrenal tumour . In 80% of cases the problem is in the pituitary, producing too much adrenocorticotrophic hormone (ACTH) which overstimulates the adrenal cortex. In the 20% of cases which are adrenal, overproduction of cortisol will suppress ACTH production by feedback.

Signs:

There are a considerable number of signs related to excessive steroids in circulation, but some occur frequently, and others more rarely. Commonly seen in association with Cushing's disease are polyuria and polydipsia; polyphagia; abdominal enlargement; coat change- colour, character, alopecia; muscle wasting; and weakness; anoestrus, infertility and testicular atrophy.

Laboratory testing of blood samples shows reduced numbers of lymphocytes and eosinophils, and gross increases in serum Alkaline Phosphatase.

This disease is rarer in cats; they are much less likely to show characteristic signs, but much more likely to present as diabetics.

Certain breeds seem predisposed. Terriers, Dachshunds and miniature poodles are more likely to suffer from pituitary tumours, If larger breeds are affected then they are more likely to be female and to have the adrenal variety.

Testing

Because the blood level of cortisol fluctuates markedly throughout the day, it is necessary to perform dynamic testing of the pituitary / adrenal gland system. Two tests are in common use.

i)-Low Dose Dexamethasone Suppression looks for the suppressing effect on circulating cortisol of an injected dose of dexamethasone. Suppression is either not found or is short lived due to the overactive adrenal.

ii)-ACTH stimulation test looks for an exaggerated response to an injection of ACTH, again due to the enlarged adrenal gland.

A high dose dexamethasone test is sometimes used to try to decide whether the problem lies with the adrenals or the pituitary.

Treatment

Uses a drug called trilostane which interferes with steroid synthesis. Treatment is monitored by watching for reduction in water intake to 60ml/kg/day or less and by performing repeat ACTH stimulation tests.

Improvement of overall signs may take 6-8 weeks and coat signs may take 3 months.

The older treatment Mitotane is difficult to obtain and heavily regulated by the medicines authorities. It is quickly passing out of use.

4)HYPOTHYROIDISM

The commonest endocrine disease in the dog, and extremely rare in the cat. Most cases are due to auto-immune destruction of the thyroid. Occasional congenital cases are seen.

Seen in all breeds at 4-10 years and more likely in spayed females.

Lots of signs, but often a different selection for each case and may mimic other disease.

-Alopecia and coat change, non pruritic and symmetrical.

-Lethargy, depression, gain (occasionally loss) in weight.

-Coat colour change and skin problems such as infections

-Bradycardia

-Anoestrus and infertility

-Neurological problems (laryngeal paralysis, megaoesophagus).

Testing

Blood levels of thyroid hormone vary and may not be diagnostic. Other disease can markedly affect baseline levels. Usually a "panel" of tests is run to try to diagnose the disease - TSH / T4 / Free T4 may all be tested.

Treatment: Thyroxine (specifically Soloxine)tablets, given once or twice daily. Assessment of blood thyroxine levels is used to monitor, but it can take 4 weeks for these to stabilise after start of treatment. Many other drugs can interfere with blood levels. In some animals, coat signs never reverse adequately.

5)HYPERTHYROIDISM

Extremely rare in the dog, but seen in older cats (12/13 yrs ).

Benign thyroid adenomas (very rarely malignant adenocarcinomas) secrete increasing levels of thyroid hormone. The nodules (goitres) are usually palpable in the thyroid gland, located to either side of the trachea in the neck.

Signs:

Weight loss, polyphagia, vomiting, hyperactivity and palpable tachycardia, temperament change. Occasionally cats become sluggish and dull.

Tests:

Diagnosis is by simple blood measurement of thyroid hormone as this is usually considerably elevated at the time of examination. It is important to perform basic profiling before treatment as older cats often have compromised renal function, and the increased blood pressure caused by hyperthyroidism may be keeping the kidneys working. In these cases it may not be possible to treat the thyroids.

Treatment:

1/ Surgical removal of the affected gland(s). May affect the parathyroid glands which are necessary for calcium regulation.

2/ Anti thyroid drugs (methimazole is usually used).

3/ Treatment of the side effects- usually beta blockers to slow the heart.

4/ Radio active iodine treatment to destroy the thyroid, followed by supplementation.

Damage to the parathyroids at surgery is potentially very serious. Owners who ring in a day or two after their cat has had thyroid surgery, saying their cat is off colour or trembling or "not itself" MUST BE SEEN IMMEDIATELY. The cat may be hypocalcaemic and need emergency treatment.

Click HERE to return to the list of topics