Hypothyroidism Flashcards
Review the HPA axis do it
do it
Which thyroid hormone is the most biologically active?
T3
T3
- Most biologically active
- Enters cell more rapidly
- 3-5x more potent than T4
How is T3 typically made?
- only 20% made in the thyroid
- Majority produced by peripheral deiodination of T4
How are thyroid hormones produced in the thyroid gland?
- Thyroid peroxidase binds together tyrosine on the thyroglobulins to oxidized iodide = iodinated tyrosine residues
- Iodinated tyrosine resudes are transformed into T3 and T4 and secreted bound to thyroglobulin
How common is primary hypothyroidism relative to secondary hypothyroidism?
- Most common
Definition of hypothyroidism
- Decrease in T3 and T4
Possible hypothyroidism etiologies
- Thyroiditis
- Idiopathic Atrophy
- Neoplasia
Thyroiditis
- Lymphocytic inflammatory infiltration
- Replacement with fibrous connective tissue
- Suspected to be immune mediated
Idiopathic atrophy
- Replacement by adipose and connective tissue
- End-stage thyroiditis?
Thyroid neoplasia
- Most thyroid tumors are non-functional
- Potentially destructive
- Uncommon overall
Breeds associated with hypothyroidism
- CAN BE ANY BREED
- Golden
- Dobie
- Beagle
- Great Dane
- English and Irish setters
- Shetland Sheepdog
- Borzoi
- Toy Fox Terrier
Typical age of Hypothyroid
- Middle-aged
- Mean of 7 years with a big range
- Breeds predisposed to thyroiditis tend to be younger at diagnosis
Sex of dogs with hypothyroid
- Spayed/neutered dogs of either gender
Common categories of clinical signs with hypothyroid
- Metabolic
- Dermatologic
- Neurologic
- Cardiovascular
- Other
Metabolic clinical signs underlying cause
- Decreased metabolic rate
- Insidious onset
Metabolic clinical signs
- Lethargy
- Weight gain
- Heat-seeking/cold intolerance
- Mental dullness
- Unwillingness to exercise
Dermatologic clinical signs
- Symmetric alopecia (failure of hair to grow back)
- Hyperpigmentation
- Dry, scaly skin
- Superficial pyoderma
- Otitis
- Rat-tail (hair loss in areas with more trauma, and the hair has a harder time re-growing)
- Seborrhea
- Change in hair quality (dry, brittle)
- Myxedema (thickening of skin, forehead, eyelids due to mucin deposits secondary to loss of thyroid hormone)
Tragic expression in hypothyroidism
- Myxedema (thickening of skin, forehead, eyelids due to mucin deposits secondary to loss of thyroid hormone)
Neurologic clinical signs in HypoTh affecting the Peripheral Nervous System
- Ranges from weakness and exercise intolerance to ataxia and quadriparesis
Neurologic clinical signs in HypoTh affecting the Central Nervous System
- Seizures, central vestibular disease, mentation changes
Neurologic clinical signs in HypoTh affecting the Cranial Nerves
- Facial nerve paralysis
- Vestibular disease
Cardiovascular Clinical signs with HypoTh
- Bradycardia
- Low QRS voltage
- Inverted T wave
- Reduced left ventricular pump function
- Rarely a primary cause of myocardial failure
- Leads to a weak heart
- NOT MAJOR
Concurrent DCM with Hypothyroidism
- They can occur, e.g. with a Great Dane
- Weak heart gets weaker
- Treatment for hypothyroidism might help DCM clinical signs
Reproductive signs associated with HypoTh
- Reproductive dysfunction
Other clinical signs associated with Hypothyroidism
- Megaesophagus (treatment can resolve)
- Laryngeal paralysis (treatment does not usually resolve)
- Ocular changes
- Not proven to be causal
- Treatment does not consistently reverse clinical signs
Other disease that can be confused with or dfdx’s for hypothyroidism?
- Cushing’s
- Atopic dermatitis
What is the most important question you should ask yourself before trying to diagnose hypothyroidism?
- IS THE DOG SICK?
- Base upon history, clinical signs, and physical exam
Other tests involved in diagnosing Hypothyroidism
- Minimum data base (CBC/Chem/UA)
- Thyroid-specific testing
Common signs on CBC with Hypothyroidism
- Normocytic, normochromic, nonregenerative anemia (30%)
- Based on chronic inflammation if disease and chronic disease in general
Hypothyroidism Common signs on Chemistry Panel
- Fasting hypertriglyceridemia
- Fasting hypercholesterolemia (>75%)
- Increased hepatic enzymes
Total T4 overview
- Good screening test
- Highly sensitive
- Moderately specific (~75%)
How will non-thyroidal illness impact tT4/fT4/TSH?
- Decreased tT4
- Normal to decreased fT4
- Normal TSH
- caused by concurrent illness and that effect on thyroid hormone levels
- Normal physiologic response
Should you supplement an animal with low total T4 if they have a concurrent illness?
- DO NOT NEED SUPPLEMENTATION
- Normal physiologic response
- Treat by correcting underlying illness
Total T4 in a healthy animal with no clinical signs of Hypothyroidism
- Don’t run it
Total T4 in a dog with clinical signs attributable to another disease process and not hypothyroidism?
- Be wary of running or interpreting tT4 test in dogs with clinical signs like this
Interpretation of tT4 within middle to upper half of reference range
- Normal dog
Interpretation of tT4 with low-normal or low range
- Normal fluctuation in euthyroid dog?
- Non-thyroidal illness (sick euthyroid syndrome)?
- Hypothyroid?
What should you do after you see a low tT4?
- fT4 and/or TSH
Free T4
- should be by equilibrium dialysis
- ACTIVE form of T4
- Less affected by non-thyroidal illness
What is the advantage of free T4 over total T4?
- Separate out the T4 from the forms that are bound to the antibodies or are structurally larger
- More SPECIFIC than tT4
Cost of TT4 vs FT4
- FT4 is more expensive
Primary purpose of TT4 vs FT4
- TT4 is a good screening test
- FT4 is used to help confirmation
TT4 vs FT4 in terms of being affected by other illness
- TT4 is more affected by euthyroid sick syndrome
- FT4 is less affected by illness but STILL CAN BE
TT4 vs FT4 in terms of sensitivity
- TT4 is more sensitive than FT4 (95% compared to 90%)
TT4 vs FT4 in terms of specificity
- FT4 is more specific than TT4 (93% compared to 75%)
TSH overview
- Screening test in people
- Due to a lack of negative feedback TSH should be high, but dogs don’t like to follow the rules
TSH elevation in what % of dogs?
- Only high in ~70% of hypothyroid dogs
TSH and tT4 or tT4 results for a dog with hypothyroidism
- High TSH combined with low TT4 or free TT4
- Diagnostic for hypothyroidism (99% specific)
If you have a normal TSH can you rule out hypothyroidism?
- NO
- Because 30% of hypothyroid dogs have normal TSH
If a patient is on ____ or _____, avoid testing thyroid function (if possible).
- Steroids
- Phenobarbital
- e.g. derm patients
Effects of glucocorticoids on:
Total T4
Free T4
TSH
Treat or not?
- TT4: D to N
- FT4: D to N
- TSH: N to D
- No tx
Effects of phenobarbital on:
TT4
FT4
TSH
Treat or not?
- TT4: D
- FT4: D
- TSH: Slight elevation
- No tx
Effect of TMS on:
TT4
FT4
TSH
Treat or not?
- TT4: D
- FT4: D
- TSH: I
- May tx if clinical
Thyroglobulin antibody testing
- Found in up to 50% of hypothyroid dogs
- Can increase tT4 measurement
- Increase suspicion of hypothyroidism
- Presence can indicate progression into hypothyroidism in the future
Are thyroglobulin antibodies diagnostic of hypothyroidism if elevated?
- No, just supportive
T3 and fT3
- Significant fluctuation during the day (even more than fT4)
- Not useful
- DO NOT LOOK AT THEM
- IGNORE THEM
TSH stimulation testing
- GOLD STANDARD
- Very expensive
- If you have an animal with clinical signs (lab changes, total T4 low, TSH normal) and want to make a slam dunk
TRH stimulation test
- Equivocal results
Ultrasound
- Insensitive
- Operator-dependent
Therapeutic trial for hypothyroidism
- Treat with levothyroxine
- Wait 4-8 weeks
- Assess for any (even subtle0 improvements in clinical signs
- If response seen, stop supplementation to prove diagnosis (wait 2-3 weeks)
- If see signs return, then hypothyroidism likely
- Don’t do this in a healthy animal!
Levothyroxine overview
- Synthetic thyroxine (T4)
Route and Frequency of Levothyroxine
- q12hr PO initially
- It’s a big dose
- Even in big dogs they do not like to exceed this
Monitoring Levothyroxine
- Recheck TT4 after 4-8 weeks of therapy
- Most dogs show good control at this dose, but treatment needs to be individualized to each patient
- Recheck total T4 4 weeks after a dose change then every 6 months if doing well
Side effects of levothyroxine
- Hyperthyroidism (PU/PD, Polyphagia, Tachycardia, nervousness)
- Lack of response/treatment failure (inaccurate diagnosis, inadequate dose/compliance, poor absorption)
When should you start to see improvement after starting levothyroxine?
- 1-2 weeks
When should you start to see improvement in terms of activity levels after starting levothyroxine?
- First 1-2 weeks
When should you start to see improvement in terms of weight loss after starting levothyroxine?
- seen in 8 weeks
When should you start to see improvement in terms of hair coat after starting levothyroxine?
- Normal hair coat may take several months and may appear worse before it gets better
When should you start to see improvement in terms of Neuro signs after starting levothyroxine?
- Improve rapidly, may take 8-12 weeks for complete resolution