Endocrinology (hyperthyroidism)

Question 1

What is causing feline hyperthyroidism

Answer 1

The vast majority of cases is due to benign adenomatous hyperplasia of one, or in around 70% of cases, both thyroid glands

Only 1-3% of cases are caused by a malignant thyroid adenocarcinoma

Question 2

Is there a specific cause for feline hyperthyroidism

Answer 2

Studies do not suggest a single unifying underlying etiology

Cellular regulation may be disrupted through different mechanisms, generally leading to the over-expression of cAMP

It seems likely that one or more cellular abnormalities may predispose to the development of adenomatous nodules, but dietary and possibly environmental influences may also have a role to play

Question 3

Can you give an example of possible risk to develop hyperthyroidism

Answer 3

A possible increased risk exists in cats that consume canned cat food because of the potential widely fluctuating levels of iodine in commercial cat foods

Question 4

Give some epidemiological points about feline hyperthyroidism (frequency, distribution, …)

Answer 4

Hyperthyroidism is by far the most common disorder diagnosed in cats

There is evidence for both increased incidence and geographical variation in the prevalence of the disease

Hyperthyroidism is primarily a disease of middle to old age cats

No sex predisposition

Question 5

List the most frequent clinical signs for hyperthyroidism

Answer 5

Palpable goiter that may represent a solid functional or non-functional mass or thyroid cyst

Weight loss despite polyphagia

Polyuria and polydipsia are common features

Although congestive heart failure is seen less commonly, cardiac changes are still prevalent (mild to moderate left ventricular hypertrophy affecting both the left ventricular free wall and the inter-ventricular septum). In uncontrolled disease, this will eventually lead to diastolic failure, left atrial enlargement and left-sided congestive heart failure

Vomiting and diarrhea may result from excessive and rapid ingestion of food. Hyperthyroidism also directly affects GI motility and results in a shorter oro-caecal transit time reducing the effective time for nutrient absorption

Cutaneous signs are usually manifested as a poor and unkempt coat

In more severely affected cats, panting, especially when stressed, can be quite a prominent sign. It is usually unrelated to cardiac disease and is another manifestation of the thyrotoxicosis

Clinical signs may be mild to severe, depending on the duration of the disease

Question 6

Could you explain what is apathetic hyperthyroidism

Answer 6

Apathetic hyperthyroidism occurs in a small proportion of cases where lethargy, weakness, and inappetence are dominant features

Congestive heart failure and other concomitant diseases are common in these cats and probably account for the different presentation

Weakness may also be a manifestation of hyperthyroid-induced myopathy also this appear to be rare in cats

Weight loss remains a prevalent clinical sign but with variable or reduced appetite rather than increased appetite, and with lethargy rather than increased activity or excitability

Question 7

What are frequent laboratory anomalies seen with hyperthyroidism

Answer 7

Leukocytosis, eosinopenia and mild erythrocytosis (the first two may be manifestations of increased sympathetic tone seen in hyperthyroidism)

The single most common change is a mild to moderate (occasionally severe) elevation in liver enzymes (ALT, ALP). These changes are in part due to direct thyrotoxic effects on the liver. This effect is rarely severe enough to cause significant alterations in bile acids

A significant proportion of the elevation in ALP arises from an increase in bone turnover that is associated with hyperthyroidism

Ionised calcium levels tend to be lower and phosphate levels tend to be higher and many hyperthyroid cats have concomitant hyperparathyroidism

Question 8

Which investigations can be done to reach a diagnosis of hyperthyroidism

Answer 8

Presence of palpably enlarged nodules on the neck doesn’t confirm the diagnosis (e.g, thyroid cyst, parathyroid adenoma)

Absence of palpable nodules doesn’t exclude the diagnosis as the adenomatous tissue may be at an unsual site or merely challenging to palpate

A diagnosis of hyperthyroidism must be confirmed by demonstrating elevated circulating thyroid hormone levels

Resting thyroxine levels are elevated in cats with hyperthyroidism and the elevation is proportional to the severity of the disease

Question 9

How can you explain normal thyroxine levels in a clinically hyperthyroidian cat

Answer 9

Presence of early/mild disease and inherent fluctuations in T4 levels

Presence of significant non-thyroidal illness which may result in a reduction of the circulating thyroid hormone concentrations to values within the reference range (usually at the upper end of the reference range)

Question 10

What are the options for suspected cases of hyperthyroidism without a definitive diagnosis

Answer 10

Repeat basal T4 measurement 2-6 weeks later

Measurement of free T4 by the method of equilibrium dialysis on the same sample as T4

Technetium scintigraphy is able to identify the site of hyper-functional tissue (bilateral versus unilateral cases, ectpoic thyroid tissue)

Question 11

What are the therapeutic options for hyperthyroidism

Answer 11

1/ Anti-thyroid drug therapy
2/ Dietary therapy
3/ Surgical thyroidectomy
4/ Radioiodine therapy

Question 12

Explain what are the drugs used for treating hyperthyroidism, what is their mechanism of action and dosing

Answer 12

Thioureylene drugs are the mainstay of medical therapy for hyperthyroidisim
- This group includes methimazole and carbimazole

Following administration, the drugs accumulate in the thyroid gland but are not cytotoxic
- They inhibit synthesis and release of thyroid hormones

Fixed dosing regimes can not be given as individual cats vary in their requirements (partly due to the variability in the severity of the disease)
- Starting dose of methimazole 2.5-5 mg PO BID
- Majority of cats requires 5-10 mg BID

Target of methimazole therapy is to achieve serum T4 levels in the lower half of the normal range
- This is usually achieved within 2-3 weeks of starting therapy

Question 13

Are there any side effects with methimazole therapy

Answer 13

Side effects of methimazole therapy are well characterised and relatively common with some form of reaction being seen in 10-20% of treated cats

Anorexia, vomiting and lethargy are the most commonly observed but these may only be mild and temporary, often resolving with continued therapy with dose reduction and administering therapy with food

Mild hematological side effects may also be transient

Development of clinically significant thrombocytopenia, agranulocytosis, hepatopathy is a reason to stop treatment
- Occur in less than 3% of treated cats and within the first 2 months of therapy

Iatrogenic hypothyroidism with anti-thyroid drug use occurs in approximately 20% of cases

Question 14

Is there any known resistance to methimazole therapy

Answer 14

Resistance to methimazole therapy is uncommon and if doses of greater than 15 mg daily are being used, assuming good owner compliance, this may suggest the possibility of underlying functional thyroid carcinoma

Question 15

Is there any alternative route to the oral route for methimazole administration

Answer 15

Transdermal methimazole therapy
- Interesting when owner can’t manage oral dosing
- For cats that develop intractable vomiting due to a local irritation of the drug given orally

Question 16

What can you say about carbimazole therapy

Answer 16

Carbimazole is actually a pro-drug

An oral dose of 5 mg carbimazole is equivalent to approximately 3 mg of methimazole

A starting dose of 15 mg once daily is usually recommended

Question 17

Could you cite any medical therapies other than methimazole or carbimazole

Answer 17

Stable iodine

B-blockers
- They are usually used in conjunction with other medications to provide additional control over some of the clinical signs of disease such as tachycardia, hyper-excitability, tachypnea and cardiac hypertrophy
- Atenolol (= selective B1 antagonist) is the preferred one because it cannot induce respiratory compromise via B2 antagonist bronchoconstriction
- Atenolol also has a longer duration of action and can be used at a dose of 6.25-12.5 mg/cat once daily

Ipodate

Question 18

What can you say about hyperthyroidism dietary therapy

Answer 18

Hill’s Y/D is the only diet designed for feline hyperthyroidism management
- It has approximately a 10 times lower iodine content than a regular cat food

The cat should be checked at 4 and 8 weeks after total transition onto the diet

Whilst there is some evidence that iodine-restricted diets can help normalise serum TT4 in cats with hyperthyroidism, this is not always effective and there is a lack of compelling evidence to suggest this is associated with a resolution of clinical signs in the long term

Question 19

What precaution should be taken before surgical thyroidectomy

Answer 19

Pre-operative medical stabilisation is advisable to reduce cardiac and metabolic risks associated with anesthesia

Only a short hospitalisation period is required (3-5 days)

Question 20

What are the main disadvantages with surgical thyroidectomy

Answer 20

The major disadvantage of surgery is the potential for induction of hypoparathyroidism through inadvertent removal/damage to the parathyroid glands

Another important problem is the recurrence of the disease because of lack of removal of all adenomatous tissue from the surgical site, lack of recognition of bilateral disease, lack of recognition of ectopic thyroid tissue, de novo recurrence of adenomatous change in previously normal tissue

If disease is genuinely unilateral, the negative feedback of excessive thyroid hormones has the effect of atrophying any normal thyroid tissue, thus the contralateral (unaffected) gland should be atrophied and would often be quite difficult to identify (bilateral disease is present in 75% of cases)

Question 21

What are the main post-operative complications following bilateral thyroidectomy

Answer 21

post-operative hypocalcemia

Horner’s syndrome (relatively uncommon)

Laryngeal paralysis (relatively uncommon)

Question 22

What can you say about post-operative hypoparathyroidism (do not develop clinical signs and hypocalcemia management)

Answer 22

Hypoparathyroidism is the most common serious potential complication of thyroidectomy

Disruption of the blood supply can be suffiecient to induce hypoparathyroidism

Hypoparathyroidism is much more common after bilateral thyroidectomy

A modified extra-capsular technique is commonly used for thyroidectomy

Even when all parathyroid tissue is removed, most cats recover parathyroid function, presumably as a result of hyperplasia of ectopic parathyroid tissue, which takes over normal function

Question 23

What are the clinical signs of hypocalcemia after bilateral thyroidectomy

Answer 23

Significant hypocalcemia will develop within seven days of surgery (usually within three days)

Monitoring of serum calcium (ideally ionised calcium) at least twice a day for a minimum of 3-5 days post-surgery is strongly recommended

Early clinical signs of hypocalcemia will be lethargy, inappetence, and muscle twitching/fasciculation

These signs become progressively more severe with tetanic muscle spasms that may be induced or exacerbated by stimuli (sound, touch, light)

Question 24

Could you explain your decision making process for post-operative hypoparathyroidism management

Answer 24

Mild hypocalcemia (1.8-2 mmol/l)
- In a clinically normal cat only close monitoring of calcium twice a day is necesssary

Mild-moderate hypoacalcemia (1.5-1.8 mmol/l) but no clinical signs
- These cats may either be treated prophylactically (SQ and oral calcium, oral vitamin D) or blood calcium levels may be checked every 1-3 hours

Moderate-severe hypocalcemia (<1.5 mmol/l) and showing clinical signs (muscle fasciculations, seizures)
- IV calcium therapy is required
- Cats should also receive oral calcium and vitamin D

Question 25

How would you treat hypocalcemia

Answer 25

Acute therapy
- 10 % calcium gluconate diluted at least 1:1 with normal saline is used for acute/severe hypocalcemia
- Administer 1-3 ml/kg of diluted solution
- Give IV for acute clinical hypocalcemia, slowly over 20 minutes and monitor for bradycardia
- Give SQ for sub-clinical or mild clinical hypocalcemia. Repeat as required for the first few days

Maintenance therapy
- Oral calcium supplementation is prudent during initial stabilisation
- When the cat is eating well, this should no longer be necessary (only vitamin D) so long as the cat is on a good quality commercial diet
- CaCO3: approx 200 mg/kg/day PO divided with food

- Vitamin D therapy is crucial for maintenance therapy
- An active form of D3 (calcitriol) should be used
- The initial dose of calcitriol is 0.03-0.06 mg/kg/day and needs to be adjusted on the basis of daily calcium monitoring
- Most cats regain parathyroid function over weeks or months
- The aim of calcitriol therapy is to maintain blood calcium concentrations around 1.8-2 mmol/l to provide a stimulus for the parathyroid function to recover

Question 26

Explain radioiodine therapy as a treatment for hyperthyroidism

Answer 26

Radioiodine therapy uses I 131 and has proven to be an extremely effective therapy for hyperthyroid cats (it is the treatment of choice if available)

Administered radioiodine is taken up by the thyroid gland, and selectively by the active (hyperfunctioning, adenomatous) thyroid tissue while the unaffected thyroid tissue is atrophied and takes up the iodine poorly

It is the local effect of the beta radiation (average penetration < 0.5 mm) that results in rapid destruction of the thyroid tissue that takes up the radioidine but adjacent non-functional thyroid tissue and structures are usually left unaffected

The efficacy of radioidine is reported to be 95-97% following a single dose and is remarkably free of side effects

Cats need to be hospitalised for 1-3 weeks according to health regulations

Radioiodine is usually administered at a dose of 110-185 MBQ

Question 27

What is the most significant potential complication with radioidine therapy

Answer 27

Short or long term induction of hypothyroidism
- low total T4
- obesity, lethargy
- seborrhea sicca and sometimes alopecia (especially of the caudal pinnae)

Cats require regular ongoing monitoring of their thyroid and renal status post-radioiodine treatment to allow early detection and treatment of hypothyroidisim
- 1, 3, 6 and 12 months post-treatment
- then every 6 months ongoing

Question 28

How would you manage concomitant chronic kidney disease and hyperthyroidism

Answer 28

Hyperthyroidism is known to result in increased cardiac output, increased renal blood flow and a tendency for an increased glomerular filtration rate

Successful treatment of hyperthyroidism commonly results in a reduction of renal blood flow and thus a reduced GFR

Renal function should be carefully assessed prior to starting any therapy
- In cats that experience a significant deterioration in renal function, it may be prudent to avoid surgery or radioiodine therapy and manage the balance between hyperthyroidism and renal function by carefully adjusting the dose of methimazole

The finding of high serum TSH concentrations best identifies feline iatrogenic hypothyroidism and differentiates it from non-thyroidal illness syndrome in cats that develop azotemia after treatment

Question 29

How would you manage thyroid adenocarcinoma

Answer 29

Feline thyroid carcinoma has a metastatic rate up to 71 % with regional lymph nodes and lungs most commonly affected

There are no definitive scintigraphic features

Pre-mortem diagnosis of malignancy relies principally upon histopathological evaluation

Higher doses of radioiodine are required than for benign disease as malignant tumor cells concentrate and retain I131 less efficiently than thyroid adenomas and the tumor size is usually much larger

Transient bone marrow suppression is a well-recognised potential adverse effect of high dose systemic radioiodine therapy in humans and potentially in cats

I131 distribution is limited to functional cells and treatment failure may be explained by tumor heterogeneity, meaining that areas of the tumor were not exposed to adequate levels of radiation to ensure uniform cell death

Prognosis for cats with thyroid carcinoma and treated with high-dose radioiodine is good, with extended survival times commonly achieved