Signalment
Hypothyroidism is common endocrine disease of dogs that can affect both males and females of nearly any age although it is rare in dogs less than two years old.

Pathophysiology
Hypothyroidism is invariably primary (i.e. disease of the thyroid gland itself) and is usually caused by either lymphocytic thyroiditis or idiopathic atrophy. As the disease progresses the ability of the thyroid gland to secrete the principal thyroid hormone T4 decreases and clinical signs develop. T4 normally inhibits the secretion of cTSH from the pituitary gland by a negative feedback mechanism. In primary hypothyroidism this feedback is lost and cTSH concentrations increase.

 

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Signalment
Hyperadrenocorticism (HAC) usually occurs in middle aged or old dogs. Predisposed breeds include poodles, small terriers (e.g. Border and Yorkshire terriers) and daschunds. Both males and females can be affected.

Pathophysiology
HAC results from excess production of glucocorticoids by the adrenal cortices. This is usually caused by excessive ACTH secretion from the pituitary gland pituitary dependant hyperadrenocorticism (PDH). PDH is most commonly caused by an adenoma the pars intermedia of the pituitary gland and accounts for approximately 80 % of all cases of HAC. The remaining 20 % of HAC cases result from excessive glucocorticoid secretion by a functioning adrenal tumour (AT) (either an adenoma or a carcinoma, both of which occur with approximately equal frequency).

 

Diagnostic Tests
It is important to recognise that there is no “perfect” test for HAC. Consequently, it is particularly important that tests of adrenal status are interpreted with a strong bearing ultimately being placed on your own clinical judgement. For this reason please provide as much clinical information as possible when submitting samples for the confirmation of HAC.

In the dexamethasone suppression test, cortisol is estimated before and after exogenous dexamethasone administration. In healthy dogs, the dexamethasone has a negative feedback effect on the pituitary gland and inhibits ACTH secretion. This reduces endogenous cortisol production by the adrenal cortices and consequently post dexamethasone cortisol concentrations are suppressed. However, in dogs with PDH, the pituitary gland is secreting large quantities of ACTH autonomously and is not responsive to the negative feedback effect of dexamethasone. Similarly, in dogs with AT, the secretion of cortisol by the neoplastic adrenocortical cells is independent of ACTH. Thus, in dogs with HAC caused by either PDH or AT, the cortisol concentration does not decrease significantly after dexamethasone administration. The dexamethasone suppression test is a good screening test for HAC, but can give false positive results. The most reliable method of minimising these false positive results, is to (as far as possible) avoid stressing patients during the test, and to judiciously select patients to test based on their clinical signs, routine biochemical and haematological changes, and the prior exclusion of other possible diseases.

In the ACTH stimulation test blood samples are collected for cortisol estimation before and after exogenous ACTH administration. The dose of ACTH given is supraphysiological and consequently the cortisol response to ACTH is essentially dependant upon the number of functioning adrenocortical cells. The test can therefore be considered to be an assessment of “adrenal size”. Since there is an increase in adrenal tissue in both PDH (which causes bilateral adrenal hyperplasia) and AT, an exaggerated cortisol response to ACTH usually occurs in dogs with HAC irrespective of the cause. Post-ACTH cortisol values greater than 600 nmol/L support a clinical diagnosis of HAC. The ACTH stimulation test can give false negative results and so don’t completely rule out the possibility of HAC because of a normal ACTH stimulation test, if you remain strongly clinically suspicious of the disease.

Monitoring Tests
When monitoring therapy for HAC, the ACTH stimulation test is the test of choice. A well controlled dog should have pre and post-ACTH cortisol concentrations in the region of 50 nmol/L.

The determination of the Urinary Cortisol to Creatinine Ratio (UCCR) can be used as a screening test for HAC. The UCCR is unable to definitively confirm HAC since non-adrenal disease can also give positive results, but the test can quite confidently rule out HAC as a possible diagnosis, helping in the overall final patient assessment. Since the secretion of cortisol (even in dogs with HAC) tends to be quite episodic, the estimation of “average” blood cortisol secretion would be a useful marker of adrenal status. Since cortisol is excreted in the urine, this can be achieved by measurement of urine cortisol concentration. Compensation for variable rates of glomerular filtration is achieved by determination of the UCCR. A UCCR less than 10 rules out the possibility of HAC. A UCCR more than 70 is consistent with HAC and warrants more specific testing such as the dexamethasone suppression or ACTH stimulation tests.

Differentiating PDH from AT
Endogenous ACTH measurement can be used to differentiate PDH (in which the ACTH concentration is usually elevated) from AT (in which the ACTH concentration is usually depressed). Samples must be collected using a strict protocol outlined below.

Sample Requirements
In the ACTH stimulation test clotted blood samples are collected for cortisol estimation immediately before and one hour after intramuscular administration of 250 pg soluble exogenous ACTH. In the dexamethasone suppression test clotted blood samples are collected for cortisol estimation immediately before, and three and eight hours after the intravenous administration of 0.015 mg/kg dexamethasone. For both tests 1 ml serum is required per sample. For the urinary cortisol:creatinine ratio, an overnight urine sample should be collected at approximately gam at home.

In cats the ACTH should be given intravenously. Basal samples together with samples at 60 minutes and 90 or 120 minutes should be collected. This is not a reliable test in the cat and the HDDST is recommended. 0.1mg/kg dexamethasone is given i/v and samples collected at time 0 4 and 8 hrs.

Endogenous ACTH is very labile and consequently strict sample handling procedures must be followed. Collect blood into a chilled plastic (not glass) tube containing EDTA as the anticoagulant. Gently mix and then immediately centrifuge for 3-5 minutes. Immediately decant the plasma into a chilled plain plastic (not glass) tube and freeze. Transport the sample frozen on ice for ACTH estimation.

Points to Note:
Try and avoid patient stress as much as possible during these tests. In particular, do not collect urine for the UCCR in a hospital environment as the stress of hospitalisation can in itself lead to false positive results. Instead, have the sample collected from the dog by the owner in the home environment.

Steroid therapy will interfere with both normal adrenal physiology and assays for cortisol estimation. If in doubt about which test to use in this situation, please contact the laboratory for specific advice.

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Signalment
Hyperthyroidism is a very common disease of older cats. It is rare in cats less than seven years. All breeds and types of cats may be affected but Siamese are under?represented. Hyperthyroidism has been increasingly recognised in dogs over the past five years, but it remains a rare disease in this species.

Pathophysiology Feline hyperthyroidism almost always results from excessive secretion of T4 caused by benign adenomatous hyperplasia usually affecting both thyroid lobes. Canine hyperthyroidism is usually caused by a functional thyroid carcinoma. 

Diagnostic Tests
Confirmation of hyperthyroidism is usually achieved by measurement of total T4 in a serum sample. In equivocal cases, with borderline total T4 values, dynamic tests such as the T3 suppression test can be used. However, the recommended approach in such cases is usually to wait and re-test total T4 about four weeks later. This usually clarifies thyroid status.

Monitoring Tests
Monitoring therapy for hyperthyroidism relies upon demonstration of a normalisation of thyroid hormone concentrations. It is generally desirable to decrease total T4 values to approximately 15-30 nmol/L to maintain optimal clinical control. latrogenic hypothyroidism very rarely occurs as a complication of therapy, and certainly it is much more common for cats to be inadequately treated than to be over-treated.

Sample Requirements
Serum (clotted blood) is required for total T4 estimation and this is the test of choice for both confirming the diagnosis, and monitoring therapy.

Signalment
There are multiple underlying factors that may contribute to the development of diabetes mellitus (DM) in dogs and cats. Consequently, nearly any age or breed may be affected. However, DM occurs most commonly in middle aged dogs, and crossbreeds, cairn terriers, English setters, poodles and rottweilers have been reported to be over-represented.

Pathophysiology
The causes and contributors to a state of DM are numerous and a detailed review is beyond the scope of this manual. As a generalisation, the most common causes of DM produce a relative or absolute deficiency of insulin through combinations of reduced insulin production and/or decreased peripheral insulin sensitivity. Common specific causes include autoimmune pancreatic islet cell destruction, increased concentrations of endogenous or exogenous glucocorticoids, and increased circulating progesterone and growth hormone concentrations associated with metoestrus. 

Diagnostic Tests
Demonstration of concurrent glucosuria and persistent fasting hyperglycaemia is confirmatory of DM. Transient hyperglycaemia caused by stress and other illnesses can complicate the diagnosis of DM, particularly in cats. Broadly speaking demonstration of a fasting blood glucose concentration greater than 14 nmol/L (dogs) or 20 nmol/L (cats) is highly suspicious of DM, but if confirmation of glycaemic control is required, fructosamine estimation can be performed. Fructosamine is a glycated protein the concentration of which reflects the “average” blood glucose concentration over the previous 2-3 weeks. Markedly increased fructosamine concentrations are confirmatory of DM.

Monitoring Tests
If monitoring is being performed with blood glucose estimation, blood samples should be collected six hours after insulin jadministration to determine the nadir (lowest) blood glucose concentration. However, monitoring therapy of diabetic patients can be complicated, particularly in cats in which stress hyperglycaemia makes routine blood glucose measurement problematic. The clinical assessment of diabetic stability is therefore of paramount importance. In addition to blood and urine glucose measurement, routine estimation of blood fructosamine concentration can be used to improve evaluation of glycaemic control.
A decrease in fructosamine values towards normal is generally consistent with an improvement in glycaemic control, whilst an increase suggests a worsening of diabetic control.

Sample Requirments
Blood glucose can be performed on whole blood collected into fluoride anticoagulant tubes. Fructosamine measurement can be performed on a heparinised blood sample.

Points to Note:
Note that falsely decreased urine glucose results can be obtained if standard dip-stick methods for glucose estimation are used in patients receiving vitamin C supplements.
Blood glucose cannot be measured on heparinised or EDTA samples sent through the post. If blood is taken into these tubes by mistake, immediately centrifuge the samples and separate the plasma before sending off for analysis. Wait 2-3 weeks after instituting or changing therapy before evaluating control with fructosamine measurements.

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Signalment
Hypoadrenocorticism occurs in most large breed dogs, but a particular predisposition has been reported in bearded collies, spaniels and standard poodles. It is most commonly a disease of young animals, typically aged around 3-4 years. However, it has been reported in dogs as young as three months and as old as 14 years.

Pathophysiology
The normal adrenal cortex consists of three layers, the zona glomerulosa, zona fasiculata, and zona reticularis. The first of these secretes mainly mineralocoricoids, the most important of which is aldosterone, whilst the latter two layers synthesise and secrete mainly glucocorticoids, the most important of which is cortisol. Spontaneous hypoadrenocorticism is usually caused by immune mediated destruction of the adrenal cortex. This usually affects all three cortical zones and consequently there is failure of both glucocorticoid and mineralocorticoid secretion. Failure to synthesis mineralocorticoids and glucocorticoids can have profound, frequently fatal consequences, reducing the ability to maintain electrolyte homeostasis and respond to stressful stimuli.

Clirllcal Signs
Because the adrenal cortices are destroyed progressively over a period of months or years, the clinical signs of hypoadrenocorticism can be vague and often intermittent. However, dogs can also present acutely in an “Addisonian crisis”.

Diagnostic Tests
The identification of hyperkalaemia and hyponatraemia is useful in supporting a diagnosis of hypoadrenocorticism. These are routinely measured on heparinised samples. Other routine abnormalities that may be encountered in dogs with Addisons disease include hypercalcaemia, mild normochromic normocytic non-regenerative anaemia, lymphocytosis and eosinophilia. Particularly in dogs with an acute crisis, increased urea and creatinine are common due to profound hypovolaemic pre-renal azotaemia. Confirmation of hypoadrenocorticism is readily achieved with an ACTH stimulation test. Failure of cortisol to significantly increase confirms a lack of functioning adrenocortical cells and supports a diagnosis of hypoadrenocorticism.

Monitoring Tests
Biochemical therapeutic monitoring of hypoadrenocorticism relies largely on electrolyte (Na & K) estimation.

Sample Requirements
Heparinised blood is suitable for the routine electrolytes. Note that separation of the plasma prior to sending to the laboratory is recommended to help accurately determine electrolyte concentrations. For the ACTH stimulation test, whole blood (clotted) should be collected immediately before and one hour after the intramuscular administration of 250 pg synthetic ACTH.

Points to Note:
Most steroids used in veterinary practice cross?react with cortisol assays and if administered prior to or during an ACTH stimulation test, will give inaccurate cortisol results. Dexamethasone does not cross react in this way and can be used in the emergency situation for patients who needs urgent glucocorticoid replacement whilst the ACTH stimulation test is being performed.

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In equine serum PMSG levels can be measured for pregnancy between days 45-90. The production of PMSG is biologically variable and it is better to sample between these dates e.g. around 60 days, rather than at either end of the range.

Oestrone sulphate will be present at approximately day 70 and in significant amounts between days 110 & 240. It is present until the end of pregnancy but values fall in the last 4-6 weeks and interpretation can be difficult in this period. The cow and pig have raised oestrone sulphate levels at certain periods through pregnancy. It is advisable to therefore contact the lab first to discuss.

Recently a test for serum Relaxin concentration has been validated for confirming pregnancy in bitches. This test is available at Axiom Veterinary Laboratories. Pregnancy can be confirmed from day 21 using this method. Single progesterone values have been used in the horse and cow, at the predicted return to oestrus dates, to indicate possible early pregnancy. They are not specific indicators of pregnancy, just indicators of luteal activity, from which assumptions are made.  

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