SA Endocrinology Flashcards
Is more T3 or T4 produced by the thyroid gland? Difference between them? How are T3 and T4 transported? What form is active?
80% T4, 20% T3
But most T4 converted to T3 in peripheral tissues
T3 has more rapid onset of action and more potent than T4
>99% are bound to plasma proteins (TBG)
Only unbound thyroid hormone is active
Functions of thyroid hormones?
Increase the metabolic rate and O2 consumption of most tissues
Positive inotropic and chronotropic effects on the heart
Increase number and affinity of β-adrenergic receptors and enhance the response to catecholamines
Catabolic effects of muscular and adipose tissue
Stimulate erythropoiesis and regulate cholesterol synthesis and degradation
Canine hypothyroidism - Which dogs affected? Types?
Middle age-older dogs (large/giant breeds also when younger)
Congenital, acquired primary (most common) and acquired secondary
Congenital canine hypothyroidism - Cause? Presentation? Breeds affected?
Result of thyroid hypoplasia, aplasia or dyshormonogenesis
Disproportionate dwarfism
Fox and rat terriers (autosomal recessive)
Isolated TSH?TRH deficiency reported in a family of Giant Schnauzer and in a young boxer
Feature of panhypopituitarism in GSD
Rare!
What causes acquired primary canine hypothyroidism?
Immune condition - lymphocytic thyroiditis
Or idiopathic atrophy
What causes acquired secondary canine hypothyroidism?
Defect in the pituitary or hypothalamus
E.g. Aggressive pituitary neoplasia, treatment with high doses of potentiated sulphonamides
Clinical signs of canine hypothyroidism?
Metabolic signs: - lethargy - obesity/weight gain - exercise intolerance - cold intolerance Dermatological abnormalities: - hair thinning or alopecia - dry/poor coat quality - skin hyperpigmentation - pyoderma - seborrhoea
Haematology and biochemistry findings with Canine Hypothyroidism?
Low total T4, high TSH
Mild normocytic normochromic non regenerative anaemia
Hypercholesterolaemia
Hypertriglyceridaemia
Mild CK elevation
Mild ALP and ALT elevation
Elevation of circulating fructosamine (so don’t automatically think also diabetic! unless other positive signs/tests)
Total T4 (tT4) for canine hypothyroidism - Advantages? Disadvantages?
Cheap and readily available
More accurate than tT3 as doesn’t fluctuate as much throughout day
Sensitive
Not specific (tT4 is reduced in many non thyroidal illnesses and by many drugs) = many false positives if used alone
Greyhounds, other sighthounds and sled dogs have low normal values - use tT3
Free T4 (fT4) for canine hypothyroidism - How measured? Advantages? Disadvantages?
Measured by equilibrium dialysis
Usually normal in animals with low tT4 due to non thyroidal illness
less affected by presence of T4 autoantibodies
Good specificity
Lower sensitivity than tT4 = false negatives - especially early cases, affected by drugs
Expensive and not always available
TSH for canine hypothyroidism - High or low? Any problems?
High (loss of negative feedback)
Sometimes normal
Can also be high in non thyroidal illness and normal dogs
So use in combo with tT4
TgAAs for canine hypothyroidism - What do they indicate? Any problems?
Evidence of active immune reaction/inflammation
Approx 20% of dogs with TgAAs progress to thyroid dysfunction within 12mo
Cause aberrant test results (falsely elevated values of tT4 and tT3)
Approx 15% of hypothyroid dogs have T4 TgAAs - use fT4
Not the best diagnostic test so not used very often
What are the primary tests carried out for suspected canine hypothyroidism? Outcomes?
tT4 and TSH - outcomes:
- tT4 low, TSH high with compatible clinical signs = hypothyroidism
- tT4 and TSH normal = euthyroidism so end testing
- tT4 low, TSH normal = non thyroidal illness, previous drug therapy, or hypothyroidsm so need to test fT4 and TgAA
- tT4 normal, TSH high = compensating hypothyroidism, recent withdrawal from thyroid suppressive medication, recovery from non thyroidal illness, or T4 antibody interference so should repeat after loner periodd of drug withdrawal/recovery or perform fT4 and TgAA
What do the outcomes of additional testing (fT4 and TgAA) for canine hypothyroidism mean?
Perform if tT4 low and TSH normal, or tT4 normal and TSH high
- fT4 normal and TgAA negative = hypothyroidism unlikely
- fT4 normal, TgAA positive = lymphocytic thyroiditis with solent or compensating hypothyroidism
- fT4 low and TgAA negative = hypothyroidism or severe non thyroidal illness
- fT4 low, TgAA positive = lymphocytic thyroiditis with hypothyroidism
Treatment for Canine hypothyroidism? Monitoring? When should signs improve?
Levothyroxine
Care in cardiac patients - start at lower dose
Monitor tT4 4-6h post-pill (want to be in middle/top end of reference range)
Metabolic signs should resolve within first few weeks
Dermatological changes may take months
Feline hyperthyroidism - Cause?
98% due to nodular adenomatous hyperplasia (benign)
Usually bilateral
2% due to functional malignant tumours
Underlying causes - nutrition (canned food, liver, fish, giblet), environmental (indoor cats, using cat litter), genetic predisposition
Typical clinical signs of feline hyperthyroidism?
Weight loss despite polyphagia
PUPD
Hyperactivity
GI signs - V+D
Tachycardia, systolic heart murmur, gallop rhythm, arrhythmia, cardiac failure
Systemic hypertesnion
Skin and hair coat changes
<10% are ‘apathetic form’ - anorexia, depression, lethargy
In 80% of cases, enlargement of one or both thyroid lobes can be detected on palpation
Haematology and biochemistry findings for feline hyperthyroidism?
Mild to moderate erythrocytosis and macrocytosis Increased Heinz bodies Increased mean lately size Leucocytosis Increased ALP, ALT, AST, LDH Azotaemia Hypokalaemia, hyperphosphataemia Reduced fructosamine
Total T4 (tT4) for feline hyperthyroidism? Advs and disadvs?
Most commonly used diagnostic test
Detects >90% of hyperthyroid cats
Used to monitor thyroid status in response to therapy
May not be elevated in early cases and when concurrent illness
Free T4 (fT4) for feline hyperthyroidism? Advs and disadvs? How measured?
Measured by equilibrium dialysis
More sensitive in early cases
False positives in cats with other illness
False positives are more common than with tT4
T3 suppression test for feline hyperthyroidism - How to do? Interpretation?
Collect basal bood sample for tT4 and tT3
Administer T3 orally every 8h for 7 doses (20ug if <5kg, 30ug if >5kg)
Collect second blood sample 2-6h after final dose 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
How does radionucelotide uptake and imaging (scintigraphy) work for feline hyperthyroidism?
Technetium-99m
Amount of fluorescing shown = allows identification of all hyper functional tissue
So if fluorescing more than salivary glands then is more active (abnormal)
Useful to show if ectopic thyroid tissue - thoracic inlet at base of heart (useful to know what to remove when planning surgery)
Medical management options for feline hyperthyroidism? Disadvantages? Adverse reactions?
Thiamazole/methamizole
- check tT4 after 2 weeks, then every 3 months
- now also available as a cream for trans-dermal absorption
Carbimazole
- slow release form in licensed
Both inhibit synthesis of thyroid hormone (blocks oxidation of iodine and coupling of iodothyronines to form T3 and T4)
Need owner and cat compliance
Rapid recurrence if medication missed
Adverse reactions
- anorexia
- lethargy
- vomiting
- pruritus
- haematological changes e.g. eosinophilia, lymphocytosis, leucopenia, agranulocytosis, thrombocytopenia
- hepatopathy
- acquired myasthenia gravis etc
B-adrenergic blockers and stable iodine to counteract the effects of thyroid hormone
Why may cats with hyperthyroidism and CKD have normal creatinine?
Muscle loss
Glomerular hyper filtration of creatinine
Surgery for feline hyperthyroidism? Options? Pre-op management? Complications?
Thyroidectomy
- unilateral or bilateral
- staged or single
- intracapsular or extracapsular
Pre-op management
- must manage medically for first 3-4 weeks
- monitor biochemistry
- hyperthyroidism increases GFR and can mask underlying CRF so consider reversible treatment if this is the case
- thoracic radiographs to assess for evidence of CHF/pleural effusions
- echocardiogram to assess systolic function
Complications:
- iatrogenic hypoparathyroidism -> hypocalcaemia
- laryngeal paralysis
- Horner’s syndrome
- recurrent laryngeal nerve damage resulting in voice change
- hypothyroidism
- recurrence of hyperthyroidism
Radioiodine for feline hyperthyroidism - how does it work? Advantages? Disadvantages?
Treatment of choice for permanent resolution
Brachytherapy technique
131I preferentially concentrates in cells where there is upregulation of thyroid hormone production
Concentrated very effectively in hyperplastic and adenomatous tissue
131I emits 80% β particles and γ rays
β particles travel about 2mm in tissue (destroy the cells?)
Treats any hyperfunctioning tissues
Advs - permanent, no further treatment needed, no requirement for GA/surgery, up to 95% success rate
Disadvs - expensive upfront cost, but poss cheaper than cumulative tablet cost, need cat isolation and facilities for disposal of radioactive litter etc, not widely available in UK
Non medical non surgical treatments of feline hyperthyroidism?
Percutaneous ethanol injection - only solitary nodules, side effects due to leakage of ethanol
Hyperthermia - ultrasound guided heat ablation, transient responses, all cases recurred within 18mo
Iodine restricted diet - difficult in multicat households (must be strict), not v palatable
Which part of the adrenal cortex secretes mineralocorticoids, glucocorticoids and androgens?
Zona reticularis: androgens
Zona fasciculata: glucocorticoids
Zona glomerulosa: mineralocorticoids?
RFG
AGM?
What are the effects of cortisol?
Facilitates: - gluconeogenesis - catabolism of fats to fatty acids and protein to amino acids - Na retention and H20 excretion - catecholamines -> vasoconstriction Inhibits: - uptake of glucose by muscle - ADH - bone resorption - calcium absorption in the intestine - collagen formation - protein synthesis - wund healing
Which animals get HAC?
Medium to older age dogs
Very rare in cats (usually become diabetic first)
PDH: more common in small breeds
ADH: more common in large breeds
Common signs of cushings? And less common?
PUPD Polyphagia Panting Abdominal distension Endocrine alopecia Hepatomegaly Muscle weakness Systemic hypertension Less common: lethargy, hyper pigmentation, comedones, thin skin, poor hair regrowth, urine leakage, insulin resistant DM
Haematology, biochemistry and urinalysis findings of Cushings? Other general tests?
Haematology: - neutrophilic leucocytosis - lymphopenia - eusinopenia - thrombocytosis - mild erythrocytosis Serum biochemistry: - increased ALKP - increased ALT - hypercholesterolaemia - hypertriglyceridaemia - hyperglycaemia Urinalysis: - SG = 1.018-1.020 - proteinuria - UTI Reduced T4, normal TSH May see increased cPLI and snap PLI with no evidence of pancreatitis
Best screening test for Cushings? How does it work?
Low dose dexamethasone suppression test:
- give dex
- blood sample at 3 and 8h
- avoid feeding during test
- 85-100% se
- 45-75% sp
ACTH stimulation test for cushings - how does it work?
Give ACTH Blood sample at 0 and 1h Avoid feeding during test Se 60% for AT, 80% for PDH Sp 60-90% Less effective screening test than low dose dex suppression test
Urine cortisol creatinine ratio for Cushings?
Random sample:
- Se 75-100%
- Sp 20-25%
Sampling 2d after a clinic visit ie away from time of stress (2 samples both above cut off):
- Se 94-100%
- Sp 65-85%
Used to rule out cushings (ie if negative, v unlikely to be cushings)
What does an adrenal panel test?
Baseline and post-ACTH Cortisol Progesterone 17-hydroxyprogesterone Oestradiol Androstenedione Testosterone
How to differentiate between PDA and FAT?
ACTH assay - normal reference range 20-100 - PDA >45 in 90% cases - FAT <20 in 70% cases Imaging High dose dexamethasone suppression test (not often used)
Treatment for cushings? Monitoring?
Trilostane
- inhibits production of cortisol
- other effects: adrenal necrosis, hypoadrenocorticism, lack of efficacy, V+D
Monitor:
- clinical signs
- ACTH stimulation at 10-14d, or if dog well 3 months and repeat every 3 months for first year then every 6 months
- single measure: pre-pill cortisol- if get hypertension (frequently occurs), treat with benazepril initially, amlodipine if refractory
Surgery for cushings?
Adrenal tumours - if not invading renal vein or vena cava, high morbidity at surgery but potentially curative
Pituitary tumours - survival improving
Macroadenoma - What is it? Treatment?
Patient gets duller when treated but ACTH stimulation and metabolic screens are good
Treat with hypophysectomy, radiotherapy
Which breed can look like they have cushings but actually have hepatopathy?
Scottish Terrier hepatopathy
Don’t need trilostane!
Aetiology of hypoadrenocorticism?
Primary (Addison’s): destruction of >90% of adrenal cortices - multiple autoimmune-associated genes may be involved
Secondary: deficient ACTH (trauma, tumour) leading to atrophy go the adrenal cortex (primarily cortisol deficiency)
