Canine Hypothyroidism Flashcards
What specific metabolic processes do thyroid hormones affect?
Concentration/activity of various enzymes.
Metabolism of proteins, carbohydrates, lipids, minerals, vitamins.
Secretion/degradation of and regulate response to many other hormones.
The heart - positive chronotopy / positive inotropy.
Enhance responsiveness to catecholamines.
Foetal development.
Stimulate erythropoiesis.
- What are thyroid hormones?
- Where is the thyroid gland located?
- How does the iodide enter thyroid gland?
- Iodine containing amino acids (tyrosine residues), produced by the thyroid gland (production requires adequate dietary iodide).
- Trachea - 2 lobes = 1 lobe either side of the trachea.
- follicular structure containing large reservoir of thyroglobulin which thyroid hormone is bound to.
- should not be palpable in healthy dogs and cats. - Actively transported from extracellular fluid into thyroid gland.
Thyroid hormone fractions.
Protein-bound vs free.
- primarily circulate in protein-bound – reservoir.
- only the ‘free’ portion is metabolically active (<1%).
Active thyroid hormones.
- total thyroxine (T4) – major secretory product of thyroid gland.
–> 4 indicates has been iodinated 4 times.
- triiodothyronine (T3) – much less produced by thyroid gland and primarily produced peripherally.
–> much more potent than T4.
How are thyroid hormones regulated by the body?
Via hypothalamic-pituitary-thyroid axis, with negative feedback loops.
- HT produces Thyrotropin Releasing hormone (TRH).
– which stimulates pituitary gland to produce Thyroid Stimulating Hormone (TSH) = Thyrotropin.
–> TSH stimulate thyroid to synthesis and release more hormones.
- Negative feedback loops arise from the peripheral thyroid hormone which feed back at the level of the pituitary to inhibit TSH production.
- Also inhibit TRH production at the level of the hypothalamus – identified in brain by conversion of T4 to T3 in the brain.
‘Non-thyroidal illness’ / euthyroid sick syndrome.
- suppresses production of T4.
- many sick patients will have measurably low T4 levels.
- conserve energy to fight disease.
- need other diagnostic tests to diagnose hypothyroidism.
Canine hypothyroidism is most commonly an acquired disease of adult dogs.
Primary (thyroid level), secondary (pituitary level - rare), tertiary (HT level - rare).
Most commonly:
- immune-mediated lymphocytic thyroiditis (clinically silent until 70% destruction).
- progressing to idiopathic atrophy.
Typically middle aged to older dogs.
- rare in young (<2yrs) adults.
Any breed, although predispositions reported:
- Doberman Pinscher.
- Golden Retriever.
What is the most common clinical sign?
Dermatological changes.
- Alopecia.
– trunk.
– sites of wear.
– spares head and limbs.
- Secondary bacterial or yeast skin infections.
- Myxoedema coma.
– increased hyaluronic acid deposited in skin.
– thick and mucinous substance.
– makes skin very thick.
–> esp. on head.
–> non-pitting.
Other clinical manifestations.
Lethargy/weight gain.
- NB. most overweight/lethargic dos are just fed too much.
Cardiovascular (bradycardia).
Neuromuscular (primarily weakness).
Heat-seeking.
Others - rare.
– reproductive failures, ocular (corneal lipid deposition), megaoesophagus.
Dx of hypothyroidism.
Test for hypothyroidism in presence of a clinical suspicion.
Non-thyroidal illness (euthyroid sick syndrome) - concurrent illness suppresses serum thyroid hormone concentrations.
– incorrect diagnosis of hypothyroidism.
– failure to diagnose the actual underlying disease.
– patient morbidity/mortality/ client expense.
Haematology and biochemistry to support clinical suspicion.
Haematology:
- mild, non-regenerative (normocytic, normochromic) anaemia (of chronic disease).
– approx. 30% dogs.
Serum biochemistry:
- hyperlipidaemia common.
– >75% have hypercholesterolaemia +/or hypertriglyceridaemia.
– ideally evaluate on fasted sample (16-20hr fast).
- other changes uncommon.
Evaluating a thyroid panel when bloods support clinical suspicion
Measure T4 AND TSH together.
Primary hypothyroidism:
- expect low T4 and high TSH as pituitary recognises not enough T4 so makes more TSH to try and stimulate thyroid gland to produce T4.
NOT hypothyroid:
- expect both T4 and TSH to be normal – consider another cause of the signs.
Most likely non-thyroidal illness/normal daily variation, POSSIBLY hypothyroid:
- expect low T4, normal TSH.
– evaluate for non-thyroidal illness +/- further diagnostic testing for hypothyroidism.
– if remain clinically suspicious, could either re-test in 1-3m OR tx trial.
Either recovery from non-thyroidal illness or early hypothyroidism.
- expect normal T4 and high TSH.
– depending on suspicion, further testing for hypothyroidism OR re-test in 1-3m.
Other diagnostic testing - utility of free T4.
More accurately reflects thyroid function (biologically active fraction).
Need to use validated (equilibrium dialysis) methodology.
May be less affected by non-thyroidal illness.
- however, severe illness may also suppress free T4.
More expensive and more difficult to measure than total T4.
Other diagnostic testing - utility of thyroglobulin antibody (TgAb) assays.
Lymphocytic thyroiditis is gradually progressive.
- clinically significant hypofunction does not occur until 80% of the gland is destroyed.
Antibodies:
- present during the destructive phase.
- NOT when destruction is complete (i.e. end-stage atrophy).
- Antibodies = thyroiditis (NOT hypothyroidism).
Pitfalls in measurement of thyroid profiles?
Non-thyroidal illness (NTI)
- extremely common cause of suppression of TT4 – identify / treat NTI first.
Greyhounds (and related breeds).
- T4 is lower than other breeds.
Drugs:
- TMPS and phenobarbitone mimic hypothyroidism – cause low free T4, low total T4 and high TSH.
– reversed when drugs stopped.
– never test for hypothyroidism when dogs are on these drugs.
- Many other drugs, esp. glucocorticoids, NSAIDs, that cause decreased free T4 and decreased total T4.
Anti-thyroid hormone antibodies (rare).
- can incorrectly increase or reduce blood test for thyroid testing.
Treatment of hypothyroidism.
Lifelong daily supplementation with synthetic levothyroxine sodium.
Available as tablets or liquid.
Dose/frequency depends on formulation.
Doses given to dogs higher than doses given to people as dogs do not absorb the drugs as well as people do.
Ideally given without food.
- food decreases bioavailability.
- at the very least, be consistent.
Monitoring levothyroxine replacement.
2-4w after starting (or dose change).
- 6-8w after starting.
- 6-12 monthly longer term.
- at any time point there is a clinical concern for hypo/hyperthyroidism.
Lab testing:
- peak T4/TSH – timing and target T4 value varies depending on formulation, TSH should be normal (too high - need to give more, too low - need to give less).
- if giving SID (rare), trough T4/TSH (T4 should be low normal, TSH should be normal).
- any noted haematological / biochemical abnormalities.
– should see normalisation of anaemia, normalisation of fat levels.
- want normalisation of clinical signs too.
With correct treatment, time to normalisation of…
1. Demeanour, mentation.
2. Lab tests (anaemia, hyperlipidaemia).
3. Cardiac, neurological.
4. Dermatological.
5. Reproductive.
- 1w.
- 1m.
- 2-3m.
- 4m.
- 10m.
Considerations when the treatment fails.
Incorrect diagnosis?
Insufficient time?
Expired drug?
Inadequate dose/frequency?
Owner/dog compliance.
Poor absorption (with food, concurrent GI disease)?
Concurrent disease (i.e. causing the signs)?
Prognosis of hypothyroid dogs on treatment?
Standard primary hypothyroidism.
- excellent/normal life span.
– assuming appropriate levothyroxine replacement / monitoring.
Myxoedema coma - guarded.
– many die of the concurrent disease.
Congenital hypothyroidism
- guarded.
– partly depends on age of dx / treatment.
Congenital hypothyroidism (cretinism).
Rare.
Disproportionate dwarfism and impaired mental development.
- compared to GH deficiency which causes proportionate dwarfism.
Thyroid hormone essential for:
- neuro development.
- bone growth.
- kidney development and maturation.
Canine thyroid neoplasia - Dx.
Older dogs - 9-11yrs.
Usually non-secretory (i.e. NOT associated with hyperthyroidism) and unilateral.
- most commonly present due to owner palpation of ventral neck mass.
Typically malignant - carcinomas.
– thorough palpation
–> adherence and local LNs.
Diagnose with:
- imaging – CT –> locally, thoracic staging (pulmonary mets).
- thyroid panel.
- cytology usually avoided (US guided if so, due to highly vascular nature).
- histology – usually as part of curative intent surgery.
Treatment of canine thyroid neoplasia?
Surgical resection +/- adjunctive radiation therapy.
- histology – incisional/excisional biopsy may be appropriate depending on findings on initial bloods/imaging.
- post-op survival (unilateral).
– approx. 3yrs.
- post-radiation survival (non-resectable).
– 2-4yrs (absent visible mets).
– 8m (in presence of mets).
Naturally occurring feline hypothyroidism.
Very rare.
Most commonly iatrogenic.
- secondary to treatment of hyperthyroidism.
