Endocrinology (hyperthyroidism) Flashcards
Hyperthyroidism
What is causing feline hyperthyroidism
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
Is there a specific cause for feline hyperthyroidism
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
Can you give an example of possible risk to develop hyperthyroidism
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
Give some epidemiological points about feline hyperthyroidism (frequency, distribution, …)
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
List the most frequent clinical signs for hyperthyroidism
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
Could you explain what is apathetic hyperthyroidism
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
What are frequent laboratory anomalies seen with hyperthyroidism
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
Which investigations can be done to reach a diagnosis of hyperthyroidism
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
How can you explain normal thyroxine levels in a clinically hyperthyroidian cat
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)
What are the options for suspected cases of hyperthyroidism without a definitive diagnosis
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)
What are the therapeutic options for hyperthyroidism
1/ Anti-thyroid drug therapy
2/ Dietary therapy
3/ Surgical thyroidectomy
4/ Radioiodine therapy
Explain what are the drugs used for treating hyperthyroidism, what is their mechanism of action and dosing
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
Are there any side effects with methimazole therapy
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
Is there any known resistance to methimazole therapy
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
Is there any alternative route to the oral route for methimazole administration
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
What can you say about carbimazole therapy
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
Could you cite any medical therapies other than methimazole or carbimazole
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
What can you say about hyperthyroidism dietary therapy
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
What precaution should be taken before surgical thyroidectomy
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)
What are the main disadvantages with surgical thyroidectomy
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)
What are the main post-operative complications following bilateral thyroidectomy
post-operative hypocalcemia
Horner’s syndrome (relatively uncommon)
Laryngeal paralysis (relatively uncommon)
What can you say about post-operative hypoparathyroidism (do not develop clinical signs and hypocalcemia management)
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
What are the clinical signs of hypocalcemia after bilateral thyroidectomy
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)
Could you explain your decision making process for post-operative hypoparathyroidism management
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
How would you treat hypocalcemia
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
Explain radioiodine therapy as a treatment for hyperthyroidism
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
What is the most significant potential complication with radioidine therapy
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
How would you manage concomitant chronic kidney disease and hyperthyroidism
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
How would you manage thyroid adenocarcinoma
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
