Thyroid gland 1 + 2 Flashcards
Where are the thyroid glands located?
Compromised of two distinct lobes on either side of
the trachea
Describe the endocrine cells in the thyroid glands
Follicular cells produce thyroid hormones
Parafollicular, medullary or C cells produce calcitonin
Thyroid hormone secretion is regulated by?
The hypothalamic-pituitary-thyroid axis
The thyroid gland secretes two major hormones, what are they?
Thyroxine and triiodothyronine, commonly called T4 and T3
What is required in the diet for thyroid hormone synthesis?
Iodine
Describe the hypothalamic pituitary thyroid axis and the production of hormones
- TSH secretion by the pituitary is modulated by thyroid hormone in a negative feedback regulatory mechanism
- TSH increases synthesis and secretion of T4 and T3 from the thyroid gland
- In the peripheral tissues T4 is converted into T3
- T4 and T3 have a negative feedback mechanism on the hypothalamus and pituitary gland
Name the major modulator of thyroid hormone concentration
Thyroid stimulating hormone
Describe the overall production of T3 and T4
The thyroid glands produce all circulating T4 but only up to 40% of circulating T3
Describe unbound and bound T3 and T4
> 99% of T4 and T3 are bound to plasma proteins (TBG)
Only unbound thyroid hormone is active (reservoir of bound thyroid hormone)
Is T3 or T4 being described:
rapid onset of action and more potent
T3
What are the functions of the thyroid hormones in the body
- Increase the metabolic rate and O2 consumption of most tissues
- Positive inotropic and chronotropic effects on the heart (Contractility and rate)
- Increase the number and affinity of β-adrenergic receptors and enhance the response to catecholamines
- Have catabolic effects on muscle and adipose tissue – i.e. will get rid of these tissues when the hormones are in excess
- Stimulate erythropoiesis and regulate cholesterol synthesis and degradation
Hypothyroidism is seen in which spp?
Dogs
What is hypothyroidism?
Clinical syndrome resulting from a deficiency of T3 and T4
Which dogs are predisposed to hypothyroidism
- Middle age to older dogs (tends to develop at an earlier age in breeds predisposed to lymphocytic thyroiditis)
- Predisposed breeds include English Cocker spaniels, golden retrievers and Doberman pinchshers – but any dog can get this condition
How is hypothyroidism categorised?
Depends on whether the underlying lesion lies within the thyroid gland (primary), pituitary gland (secondary) or hypothalamus (tertiary)
Also described as congenital or acquired, depending on the age at which it develops
Is congenital or acquired hypothyroidism most common?
Acquired
What are the causes of congenital hypothyroidism
- Caused by thyroid hypoplasia, aplasia or dyshormonogenesis
-> Disproportionate dwarfism in GSD - Fox and rat terriers
- Also may develop in pups born to dams fed an iodine-deficient diet, dams given various drugs, or puppies exposed to iodine deficiency or excesses when young
Name the 3 types of primary acquired hypothyroidism
Lymphocytic thyroiditis
Idiopathic atrophy
(Aggressive/extensive thyroid neoplasia)
Describe Lymphocytic thyroiditis?
Destructive autoimmune process characterized by multifocal or diffuse infiltration of the thyroid gland by lymphocytes, macrophages and plasma cells and progressive replacement by fibrous connective tissue
Describe idiopathic atrophy
Degenerative process with minimal inflammatory change and gradual replacement of thyroid tissue by adipose and connective tissue
Describe secondary/tertiary acquired hypothyroidism
Defect in the pituitary or hypothalamus (<5% of hypothyroid dogs) - E.g. head trauma
Describe the main clinical signs of hypothyroidism
- Metabolic and dermatological signs are seen most commonly
- Lethargy
- Weight gain
- Thinning/sparse hair coat. Loss of hair - On dorsal muzzle common or tail
- Exercise intollerence
List some other, less common signs of hypothyroidism
Cardiovascular, neuromuscular, reproductive, ophthalmic, and/or gastrointestinal signs
Hypothyroidism can present in a similar way to Cushings, how can they be differentiated?
A dog with hypothyroidism wont have PU/PD
Describe haematology and biochemistry in hypothyroid diagnosis
Haematology and biochemistry will not diagnose hypothyroidism
- Can remove other differentials and help support a hypothyroid diagnosis
Describe the haematology results seen in hypothyroid dogs
Mild normocytic normochromic non-regenerative anaemia
Describe the biochemistry results seen in hypothyroid dogs
- Hypercholesterolaemia (75% of dogs – the higher the cholesterol, the more likely the dog is to have hypothyroidism)
- Hypertriglyceridaemia
- Mild increase in CK (usually <2x the upper limits of the reference interval)
- Mild increase in ALP and ALT (because of lipid deposition in the liver)
- Increased fructosamine (because of decreased protein turnover)
Which tests are used to diagnose hypothyroidism?
Thyroid hormone tests
- Total T4 (tT4)
- Free T4 (fT4) – active portion
- Total T3 (tT3)
- TSH
Cannot just use one of these test i.e. would need to do a T4 and TSH test to confirm a diagnosis
Describe the total thyroxine (tT4) test for hypothyroidism diagnosis
- Cheap and readily available
- Sensitive (low number of false negative results): circulating TT4 concentrations are decreased in most hypothyroid dogs.
- Not specific (high number of false positive results, if used alone): decreased in many non-thyroid illnesses, decreased by drugs
Describe the free thyroxine (fT4) test for hypothyroidism diagnosis
- Usually normal in animals with low tT4 due to non-thyroidal illness
- Less affected by the presence of T4 autoantibodies
- Good specificity (low number of false positive results)
- Measurement of FT4 is considered the single most accurate test for diagnosing hypothyroidism
- Low sensitivity (risk of false negative results)
- Need to spin down in good time and store correctly
How can you use the levels of TSH to help diagnose hypothyroidism?
- High in hypothyroid dogs (loss of negative feedback) – pituitary doesn’t receive the signals to stop producing it
- Sometimes normal in hypothyroid dogs (up to 30%)
- High values are a feature of sub-clinical hypothyroidism
- Always measure in combination with tT4
How can you use the levels of autoantibodies to help diagnose hypothyroidism?
- Provide evidence of active immune reaction/inflammation
- Approx. 20% of TgAA-positive euthyroidal dogs develop hormonal evidence of thyroid dysfunction within 12mth of testing, but only 5% become clinically hypothyroid
- Cause aberrant test results (falsely increased tT4 and tT3 concentrations)
If hypothyroidism is suspected which test/s are performed first?
Total T4 and TSH
Which result from a Total T4 and TSH test would allow immediate diagnosis of hypothyroidism?
Low total T4
High TSH
If total T4 is low but TSH is normal what should be done next?
- Consider non-thyroidal illness or previous dry therpay
- Perform Free T4 test and antibody test
If the total T4 is normal and the TSH test is increased, what should you do next?
- Consider compensating hypothyroidism
- Recent withdrawal from thyroid suppressive medication?
- Recovery from a non-thyroidal illness?
- Repeat total T4 and TSH tests, if still abnormal, perform free T4 and antibody test
Give the diagnosis for the following test result:
- Free T4 normal
- Antibody negative
Hypothyroidism highly unlikely
Give the diagnosis for the following test result:
- Free T4 normal
- Antibody positive
Lymphocytic thyroiditis with silent or compensating hypothyroidism
Give the diagnosis for the following test result:
- Free T4 decreased
- Antibody negative
Hypothyroidism
Give the diagnosis for the following test result:
- Free T4 decreased
- Antibody positive
Lymphocytic thyroiditis with hypothyroidism
Which drugs can give test results the same as hypothyroidism?
Phenobarbital
Sulphonamides
Which drug is used to treat hypothyroidism?
Levothyroxine - supplement for thyroid hormone
Describe the considerations of using levothyroxine
- Care in cardiac patients - start at a lower dose
- Monitoring: measure tT4 4-6 h post-treatment
- Metabolic signs should resolve within the first few weeks
- Dermatological changes may take 2-3mth to resolve and neurological signs may take up to 6mth
- Need lifelong therapy
- Poorly absorbed orally: availability is affected by food
Describe/list the neurological complications of hypothyroidism
- Peripheral neuropathy (localised [vestibular or facial] or generalised) E.g. facial nerve paralysis - Dry nose, head tilt, ataxia (if vestibular)
- Generalised myopathy - Muscular weakness
- Megaoesophagus
- Laryngeal paralysis
- CNS e.g. strokes
Describe a myxoedema coma as a complication of hypothyroidism
- Most serious complication, with a high mortality rate
- Clinical signs include an obtunded or comatose mental condition, hypothermia without shivering, bradycardia, hypotension, hypoventilation and focal CNS deficits
- Thyroid hormone replacement should be given IV to avoid any delay in absorption from the GIT
Describe the most common cause of hypothyroidism in cats
Iatrogenic
- Overdose of anti-thyroid drug administration
- Bilateral thyroidectomy
- Radioactive iodine
Which test is most sensitive for diagnosing hypothyroidism in cats?
TSH
Describe the predispositions for hyperthyroidism
- Older cats (mean age of onset 13-14 years, with a range of 5 to 21)
- No breed or sex predisposition
- Decreased risk in Persian, Siamese, Burmese, Tonkinese, Abyssinian and British short hair
What is the most common aetiological cause of hyperthryoidism?
97-99% of cases are due to nodular adenomatous hyperplasia of the thyroid gland (benign enlargement) – hyperplasic tissue becomes overactive
Is hyperthyroidism most commonly uni or bilateral?
Both lobes are generally involved (>70% of cases)
Not necessarily symmetrically – one may be larger than the other
1-2% of hyperthyroid cases are due to?
Functional malignant tumours
List and describe the underlying causes of hyperthyroidism
- Nutrition (canned food, liver, fish, giblet)
- Environmental (indoor cats, use of cat litter)
- Genetic predisposition (Plummer’s disease in humans)
List the clinical signs of hyperthyroidism
Progressive disease
- Weight loss (despite polyphagia) – most common sign
- PU/PD
- Hyperactivity (change in behaviour and tetchiness)
- GI signs (vomiting, diarrhoea)
- Tachycardia, heart murmur, cardiac failure
- Systemic hypertension
- Skin and hair coat changes: stop grooming -> greasy coat
- In 80% of cases enlargement of one of both thyroid lobes can be detected on palpation
What happens if hyperthyroidism is untreated?
Likely that animals will die of cardiac failure
Describe the apathetic form of hyperthyroidism
Less than 10% of cases
- Anorexia, depression, lethargy
Describe the findings on haematology which indicate hyperthyroidism
- Mild-to-moderate erythrocytosis and macrocytosis (increased oxygen demand)
- Increased Heinz bodies = Oxidative damage to RBCs
- Increased mean platelet size
- Leukocytosis
Describe the findings on serum biochemistry which indicate hyperthyroidism
- Increased ALP, ALT, AST, LDH
- Hypokalaemia, hyperphosphataemia
- Decreased fructosamine – protein catabolism is increased so there are lower levels in the blood
Name the 3 specific thyroid tests used to diagnose hyperthyroidism
Free T4
Total T4
T3 suppression test
Describe the Total T4 test for hyperthyroidism
Most commonly used diagnostic test
Detects >90% of hyperthyroid cats
Used to monitor thyroid status in response to therapy
May not be increased in early cases or when there is concurrent illness
Describe the free T4 test for hyperthyroidism
- Measured by equilibrium dialysis
- More sensitive in early cases
- False positives in cats with other illness
- False positives are more common than with tT4
Describe the T3 suppression test for hyperthyroidism
- Collect basal blood sample for tT4 and tT3
- Administer T3 (Tertroxin) orally every 8 hours for a total of 7 doses
- Collect second blood sample 2 - 6 hours after final dose of Tertroxin for both tT4 (for diagnosis) and tT3 (to confirm tablets successfully given/absorbed)
- Normal cats usually show at least 50% reduction in tT4 levels following suppression. Hyperthyroid cats generally show limited suppression
Describe the use of scintigraphy for hyperthyroid diagnosis
- Thyroid gland uptake of pertechnetate or radioactive iodine is extremely sensitive for diagnosing FHT.
- Most valuable for pre-surgical evaluation of cats undergoing thyroidectomy because it can be used to identify unilateral versus bilateral disease, ectopic disease, intrathoracic disease, and can raise the index of suspicion of thyroid carcinoma.
List the 4 overall treatment options for hyperthyroidism
Medical management
Surgery
Radioiodine (curative)
Other therapies
Name two anti-thyroid drugs
Thiamazole - methimazole
Carbimazole
Describe Thiamazole as an anti-thyroid drug
- Inhibits synthesis of thyroid hormone at several levels – acts directly on the thyroid gland
- Check tT4 after 2 weeks then every 3 months (once in lower half of the reference range)
- Also available as a cream for transdermal absorption
- Also, owners should be warned to use gloves when administering transdermal methimazole to avoid all dermal contact. Methimazole is much more potent in people than in cats.
Describe Carbimazole as an anti-thyroid drug
Inhibits synthesis of thyroid hormone at several levels
Pro-drug (converted to methimazole in situ)
Slow release form is licensed
What are the considerations of using anti-thyroid drugs?
- Do not cure the condition
- Owner and cat compliance
- May seem like the ‘cheaper’ option but is required to be used life long
- Rapid recurrence if medication missed
- Adverse reactions (often with the first 3mth): if any of these reactions occurs, the anti-thyroid drug must be stopped immediately
Describe surgical treatment for hyperthyroidism
- Thyroidectomy (uni- or bilateral) – removal of the thyroid glands
- CARE with anaesthesia: want them to have normal thyroid hormone levels when undergoing surgery
What are some complications of surgery for hyperthyroidism?
- Iatrogenic hypoparathyroidism (life-threatening hypocalcaemia): need to make sure at least one (of the four) parathyroid glands is maintained
- Laryngeal paralysis
- Horner’s syndrome: Nerve damage in the area
- Recurrent laryngeal nerve damage resulting in voice change
Describe radioiodine as a treatment for hyperthyroidism
- Bachytherapy technique
- Administered subcutaneously
- Treats all hyperfunctioning tissue
- Curative in >95%, low prevalence of complications
- Treatment of choice – but not widely available. Cats are required to stay hospitalised for 4 days due to radiation that comes from excretions
Name the grading system used to characterise cats with hyperthyroidism
SHIM-RAD
Describe SHIM-RAD
Severe hyperthyroidism (T4>300nmol/L)
Huge thyroid tumour size
Intrathoracic tumour
Multifocal disease pattern (3 or more nodules)
Resistance to Antithyroidal Drug treatment
Describe the effects of severe hyperthyroidism
It is suspected that over time some benign adenoma cells can transform to malignant carcinoma cells. Most cats with thyroid carcinoma have been being treated for hyperthyroidism for years
Become non-responsive to treatment and clinical signs worsen
How is hyperthyroidism linked to chronic kidney disease?
Treatment of hyperthyroidism can have deleterious effects on renal function in cats, likely because hyperthyroidism increases GFR and decreases muscle mass, which could mask pre-existing underlying CKD.
Treatment of hyperthyroidism -> Decreased GFR -> development of CKD
What is ‘thyroid storm’
A condition of acute thyrotoxicosis in which the patient’s metabolic, thermoregulatory, and cardiovascular mechanisms are overwhelmed by excessive circulating levels of thyroid hormone
- Unknown aetiology
- Open mouth breathing
- Life threatening state
Describe hyperthyroidism in dogs
- Functional, malignant thyroid tumour autonomously excreting thyroid hormone (10% to 29% of thyroid carcinomas)
- Iatrogenic thyroxtoxicosis secondary to over supplementation (most common) or accidental ingestion (including in the faeces!)
- Seen in dogs receiving a raw food diet containing thyroid tissue
