Small animal endocrinopathies 4 Flashcards
Hyperthyroidism, hypothyroidism, calcium disorders (100 cards)
1
Q
What are the severe side effects of hyperthyroidism medication?
A
- Facial pruritus
- Severe blood dyscrasia
- Neutropaenia, thrombocytopaenia, IMHA
- Hepatic necrosis
- Myasthenia gravis
2
Q
What are the consequences of severe side effects from hyperthryoidism medication?
A
Usually resolve within 5-7 days, but must withdraw treatment permanently - can occur at any stage of treatment
3
Q
What are the requirements for dietary management of feline hyperthyroidism?
A
- Can only eat iodine restricted diet and prevent other cats in household having same diet
- NO access to other food i.e. must be indoor cats
- May need to give bottled/filtered water
4
Q
What is the target response to dietary management of hyperthyroidism in cats?
A
Normal tT4 in 8 weeks
5
Q
What is a key concern regarding dietary management of feline hyperthyroidism?
A
Low protein diet not always ideal for older cats
6
Q
What are the 2 curative options for feline hyperthyroidism?
A
- Surgical thyroidectomy
- Radioactive iodine (I131)
7
Q
What are the main points take into account when considering a thyroidectomy in a case of feline hyperthyroidism?
A
- Will need to stabilise prior to surgery with medical management
- May not be appropriate for cats with pre-existing azotaemia
- Uni or bilateral? Commonly both
- High anaesthetic risk
- Potential for hypoparathyroidism or hypothyrodism following surgery
- Ectopic tissue easily missed
8
Q
What treatment is preferred in hyperthyroid cats with pre-existing azotaemia?
A
Reversible treatment preferred i.e. medical, dietary
9
Q
Explain the how radioactive iodine works as a treatment for feline hyperthyroidism
A
- Radioactive iodine injected SC
- Taken up and concentrated by active adenomatous thyroid tissue
- Emits radiation to local tissue causing necrosis
10
Q
What are the main advantages of radioactive treatment for feline hyperthyroidism?
A
- On off cost, curative
- Quiescete atrophied tissue spared and can recover after
- Low morbidity and mortality
- Is the only effective treatment for thyroid carcinomas
11
Q
What are the main disadvantages of radioactive therapy for feline hyperthyroidism?
A
- Irreversible
- High initial cost
- Prolonged hospitalisation (unsuitable if on other medication)
- May be advised to stop anti-thyroid medication
12
Q
What is the main complication of concern following any treatment for feline hyperthyroidism?
A
Iatrogenic hypoparathyroidism
13
Q
What are the signs of hypoparathyroidism?
A
- Hypocalcaemia usually within 72 hours, but can be up to 7d later
- Weakness, anorexia, muscle tremors, hyperaesthesia, twitching, seizures
- Can be mild, subclinical, self-limiting or life threatening
14
Q
What is the management for hypoparathyroidism?
A
- 10% calcium gluconate IV 0.5-1ml/kg to effect, best as part of IVFT
- vitD to promote calcium uptake, use with oral or injectable calcium -
- Reduce dose gradually over weeks to months if possible
15
Q
What elements are involved in the monitoring of cats with hyperthyroidism?
A
- Owner observations
- Examination of the cat
- Blood tests q2-3 weeks after start of treatment of change in dose
- Urinalysis if any suspicion of UTI
- Adverse effects common, as well as concurrent conditions e.g. facial pruritus, CKD, hypertension
16
Q
What aspects are addressed in the examinations of a feline hyperthyroid patient for monitoring?
A
- Weight (weight gain good)
- Concurrent disease
- Blood pressure
17
Q
What aspects are addressed in the monitoring blood tests for a feline hyperthyroid patient?
A
- tT4, to avoid hypothyroid state (esp. if azotaemic) and assess if working
- +/- TSH
- Biochem: liver enzyme recovery, haematology (monitor side effects, assess kidney function in response to reduced GFR)
18
Q
Explain the relationship between CKD and hyperthyroidism at the time of diagnosis and how these complicate each other
A
- Hyperthyroidism can attenuate or resole mild/moderate azotaemia in CKD patients by increasing GFR, and hyperthryoidism also leads to lower creatinine due to lower muscle mass
- CKD can hide hyperthryoidism by causing euthyroid sick syndrome
19
Q
When interpreting endocrine results for T3 ro T4, what is the significance of thyroid hormone antibodies?
A
When thyroid inflamed by autoimmune process, thyroglobin antibodies released, some react with T3 or T4. Panel looks for these, if present then cannot trust the T3 and T4 results. Can only trust the “Free from antibody interference” result for T4 if antibodies present
20
Q
What are the potential causes of adult onset hypothyroidism in the dog?
A
- Lymphocytic thyroiditis
- Idiopathic thyroid atrophy
- thyroid carcinoma
- Iatrogenic
21
Q
Describe lymphocytic thyroiditis as a cause of adult hypothyroidism in the dog
A
- Most common
- Assumed autoimmune
- Infiltration of thyroid gland by lymphocytes, plasma cells and macrophages
- End stage leads to replacement of normal thyroid tissue by fibrous tissue
22
Q
Describe idiopathic thyroid atrophy as a cause of hypothyroidism in the dog
A
- Minimal inflammation or fibrosis
- End stage leads to replacement by adipose tissue i.e. fatty rather than fibrotic change
23
Q
Describe thyroid carcinoma as a cause of hypothyroidism in the dog
A
- Hypo if >75% of gland destroyed
- Rare, tumour cells usually functional and lead to hyperT
24
Q
Describe iatrogenic causes of hypothyroidism in the dog
A
- RARE
- Thyroidextomy, radioactive therapy
25
What are the potential causes of congenital 1yr old hypothyroidism in the dog?
- Dietary deficiency of iodine in bitch during pregnancy
- Dyshormoneogenesis (o.e. iodine organification defect)
- Thyroid a/hypoplasia or dysgenesis
26
What are common concurrent signs with congenital 1yr hypothyroidism?
- Mental retardation
- Stunted growth
- Disproportionate body size
- large broad heads
- Protruding tongue
- Square trunk
- Short limbs
- Dull, lethargic
- Persistence of puppy haircoat or alopecia
- Delayed dental eruption
- Can be primary or secondary
27
Describe the treatment of congenital hypothyroidism in dogs
Can be treated with supplementation but cannot be cured
28
What are the potential causes of secondary hypothyroidism?
- Disease at level of pituitary
- May be pituitary hypoplasia or cyst
- Or failure of piutuitary thyrotropic cells
- Or destruction of the pituitary gland
29
Describe pituitary hypoplasia or cysts as a cause of secondary hypothyroidism
- Rare
- Autosomal recessive inherited disorder in GSDs
- Leads to combined deficiency of GH, TSH, prolactin
30
Describe pituitary thryotropic cell failure as a cause of secondary hypothyroidism
- More common vs cyst/hypoplasia
- Decreased TSH results in thyroid atrophy
- Suppression by glucocorticoids
- Euthyroid sick syndrome may occur (low thyroid hormone in sick dogs with totally unrelated disease)
31
Describe destruction of the pituitary gland as a cause of secondary hypothyroidism
- Rare
- Neoplasia
- Pituitary tumour more likely to lead to Cushings than hypothyroidism
32
Describe the pathophysiology of tertiary hypothyroidism
- Decreased TRH
| - Normally would expect suppressed T4 due to excess glucocorticoid
33
Describe the typical signalment for canine hypothyroidism
- Middle ages to older dogs (mean age 7yrs)
- No sex/neuter predisposition
- Breed dispositions present but care not to over/mis diagnose based on breed
- Slow, progressive, gradual onset
34
What are the clinical signs of hypothyroidism related to the altered metabolic rate?
- Lethargy/weakness
- Mental dullness
- Exercise intolerance
- Weight gain or obesity
- Cold intolerance/heat seeking behaviour
- Bradycardia
35
What are the dermatological clinical signs of hypothyroidism?
- Alopecia/no regrowth
- Dorsal nose alopecia
- Seborrhoea
- Pyoderma
- Ceruminous otitis
- Secondary Malassezia +/- demodex
- Hyperkeratotis
- Hyperpigmentation
- Comedoes
- Bruising, poor wound healing
- Dry, brittle hair, dull colour, loss of undercoat and primary guard hairs, sometimes hair retention (variable)
36
Compare the dermatological signs in hypothyroidism and Cushing's
Cushing's usually thinning of skin, hypothyroidism usually thickening
37
Explain the cause of the alopecia seen in hypothyroidism
- Failure to initiate anagen phase of hair growth if t4 deficient
- Bilaterally symmetrical and areas of wear and tear particularly affected, head and extremities often spared
38
Explain the pyoderma that may be seen in hypothyroidism
- Decreased thyroid hormones = suppression of immune response
- impaired T cell function and reduced circulating lymphocytes
- Can be focal, multifocal, generalised and cause marked pruritus
39
Explain the tragic facial expression that may be seen in hypothyroidism
- Occurs with severe thyroid deficiency
- Mucopolysaccharide (hyaluronic acid) deposits in the dermis bind water
- Leads to thickened and puffy skin, face and forehead, facial skin folds, upper eyelids drop
- Rare cases may develop myxoedema coma
40
What are the potential neurological signs that may be seen in hypothyroidism? (List)
- Peripheral neuropathy (e.g. facial nerve paralysis, laryngeal paralysis, ataxia, paraparesis)
- Seizures
- Vestibular disease
- Behavioural changes
41
Describe the mechanism of neurological signs in hypothyroidism
- Poorly understood
- Segmental demyelination and/or axonopathy
- Mucopolysaccharide deposition in the perineum
- Cerebral atherosclerosis leading to infarction
42
Evaluate the relevance of neurological signs in the diagnosis of hypothyroidism
- Rare, poorly understood, unlikely to be hypoT if only see neurological signs
- Variable evidence
43
Evaluate the relevance of cardiovascular signs in the diagnosis of hypothyroidism
- Variable evidence
| - Unlikely that hypoT will be the only cause of cardiovascular signs
44
What are potential cardiovascular signs in hypothyroidism?
- Sinus bradycardia, weak apex beat
- Mild asymptomatic decrease in contractility (echo finding)
- Rare event: atherosclerosis associated with hypercholesterolaemia (common, deposition of cholesterol plaques in blood vessels)
45
Outline ophthalmological signs in hypothyroidism
- Corneal lipidosis, but clinically insignificant
| - Variable evidence associated with other signs incl: corneal ulceration, dry eye, lipaemia retinalis
46
What are potential reproductive signs associated with hypothyroidism?
- Males: male loss of libido and testicular atrophy
| - Females: prolonged inter oestrus interval, weak or silent oestrus, inappropriate lactation
47
At what degree of destruction of the thyroid gland do clinical signs of hypothyroidism occur?
>75-80% destruction
48
Describe the progression of hypothyroidism and how this relates to diagnosis
- Chronic and slowly progressive (can be 1-3 years)
- Initially subtle clinical signs, diagnosis challenging, sub clinical disease
- Intermediate: need to ensure clinical signs are present before interpreting diagnostic tests
- Severe: clinical signs obvious and diagnosis easy
- Need to wait until clinical signs are visible, early diagnosis no better as is unlikely to be life threatening and likely to get false negatives
49
Describe the diagnostic approach to a case of hypothyroidism
- Presenting complaint (derm, metabolic signs?)
- Clinical history (owner may not be aware of normal), absence of PUPD to diff. from HAC
- Physical exam (derm)
- Haematology and biochemistry samples
- Urinalysis
- Thyroid function tests
50
Describe the haematology findings in a patient with hypothyroidism
Mild non-regenerative anaemia
51
Describe the biochemistry findings in a patient with hypothyroidism
- MUST be fasted sample as are looking at cholesterol
- Hypercholesterolaemia (70% of cases)
- Hypertriglyceridaemia (88% of cases)
- Mild increase in ALP, ALT, CK less common but possible
52
Describe the urinalysis findings in a patient with hypothyroidism
Should be unremarkable, only performed to back up biochem (good practice)
53
Explain why the interpretation of thyroid function tests can be problematic in a hypothyroid animal
- Overlap between reference values and values found in sick animals
- Non-thyroidal illness can occur (sick euthyroid)
- Suppression of thyroid hormones by drugs incl. glucocorticoids, phenobarbitone
- Sulphonamide antibiotics can affect tests
- Breed variations (sight hounds low T4)
54
What should be done prior to carrying out thyroid function tests in a suspected hypothryoid animal?
Take off treatment (e.g. glucocorticoids, phenobarbitone) for 2-6 weeks before test to try and make an accurate diagnosis
55
What thyroid function tests are used in the diagnosis of hypothyroidism?
- tT4
- Serum TSH
- Free T4 equilibrium dialysis technique
- Serum thyroglobulin autoantibody
56
Explain the interpretation of a tT4 test in the diagnosis of hypothyroidism
- Sensitive, good for ruling OUT
- Normal useful
- Low: non-specific (25% normal dogs have low tT4 due to non-thyroidal illness, concurrent medication, breed)
- Must have high clinical index of suspicion to use effectively
57
Explain the interpretation of a serum TSH in the diagnosis of hypothyroidism
- Good specificity, good for ruling IN in combination with appropriate history, signs, clin path results and low tT4
- MUST be performed with tT4
- 15-20% of hypothyroid dogs have normal TSH
58
How does the serum TSH test work for the diagnosis of hypothyroidism?
Serum TSH increased in primary hypothyroidism (most dogs) due to loss of negative feedback on pituitary gland
59
Explain the interpretation and use of a free T4 equilobrium dialysis technique in the diagnosis of hypothyroidism
- May be helpful in dogs with non-diagnostic tT4/TSh but strong suspicion (e.g. non-thyroidal illness)
- Can improve confidence of diagnosis
- Always need to start with tT4
60
Explain the interpretation and use of serum thyroidglobulin autoantibody in the diagnosis of hypothyroidism
- Good for early diagnosis in subclinical cases, screening of breeding lines
- Does not indicate need to supplement thyroxine
- TgAA levels fall in end stage disease
- TgAA can cross react and give false results in T4 assays - need to consider if expect low T4 and get high
61
What is the serum thyroglubulin autoantibody test?
TgAA is a marker for immune mediated lymphocytic thyroiditis i.e. a marker of pathology not function
62
What actions should be taken where there is a high index of suspicion for hypothyroidism but this is not reflected in the test results?
- Re-evaluate patient: what else? Medications?
- Wait and repeat in 2-3 months
- Skin biopsy: may increase suspicion or find another disease
- Consider dynamic hormone assays (TSH or TRH stimulation tests)
- Thyroid ultrasound and scintigraphy if suspect neoplasia
63
In what scenarios would treatment trials for hypothyroidism be acceptable?
- Strong suspicion and feel dog needs treatment
- If sure that supplementation poses no risk
- If you and owner understand: response does not confirm hypoT, and that further tests will be compromised by treatment
64
Outline a treatment plan for hypothyroidism
- Discuss with owner why treatment is appropriate
- Set clinical goals to help owner assess response to treatment
- Levothyroxine: give with food, SID/BID, titrate dose
- Life-long and expensive monitoring, correct diagnosis important
65
Describe a monitoring plan for hypothyroidism
- Check ups every 2 weeks initially
| - Review history: owner perception, brighter, more active- - Review physical exam: bodyweight, dermatological lesions
66
When can improvement be expected following starting treatment for hypothyroidism in a dog?
Often seen within a month but max benefit can take many months
67
What dermatological signs may be expected following starting hypothyroid treatment?
Telogen stage hairs may shed before new hairs grow, so can look worse before improvement of derm signs
68
What are potential complications of hypothyroid treatment?
- Signs of thyrotoxicosis rare, but incl: nervous/anxious behaviour, panting, tachycardia, PUPD, polyphagia, weight loss
69
If complications occur during hypothyroid treatment, what actions should be taken?
- Check dosing: correct dose? SID? BID?
- Consider reasons for impaired drug metabolism e.g. renal/hepatic insufficiency, idiosyncratic, rare
- tT4 high? TSH very low?
70
Describe the use of tT4 tests in the monitoring of hypothyroid treatment
- Timing with respect to last treatment must be known for interpretation
- Aim for top 1/3rd of reference range, lower ok if "pre-pill" sample
- Gives information on last dose only
71
Describe the use of a TSH test in the monitoring of hypothyroid treatment
- Should normalise
- Gives information about compliance over a few days as fluctuates less than tT4
- Fluctuations suggest poor owner complaince
- NOT commonly done for monitoring
72
Why might there be a poor response to hypothyroid treatment in a dog?
- Expectations too high?
- Correct diagnosis?
- Concurrent disease? e.g. atopy, FAD, superficial pyoderma
- Compliance issues? Correct dose and time, correct product
- Bioavailability issues? GI disease?
73
Describe the normal physiological response if calcium rises
- Thyroid releases calcitonin from follicular cells
- Leads to fast phase bone response (inhibition of osteoclast absorptive acitivity), slow phase bone response (reduce formation of new osteoclasts)
- Slight effects on kidney and GI tract (decrease uptake, increase renal excretion)
74
Describe the normal physiological response to low calcium
- Increased PTH secretion
- Leads to increased osteoclast activity
- Increase calcuim uptake from duodenum and reuptake in nephron
- Increase vitD activation (to calcitriol) and therefore increased bone resorption
75
Describe the distribution of calcium in the body
- Some in ICF and most in ECF
- In ECF: 45% protein bound, 55% diffusable ultrafiltrable
- Of protein bound: 90% albumin, 10% globulin
- Of diffusable: 45% ionised, 10% complexed
76
Explain the difficults related to measuring ionised calcium
- Must be correct pH, temp, and free of oxygen when collected
- CARE with heparin samples (bind calcium), serum sample better
- Calcium labile, run quickly
- Aim to mimic normal physiology
77
Explain the relationship between albumin and calcium concentration
- Bound calcium related to albumin (+ other proteins), so total Ca affected by albumin
- Does not affect total amount (if measure total, cannot say which has changed)
- Albumin concentration decrease, total calcium decreases as ionised calcium is in equilibrium with interstitial fluid, regulated by PTH
- More calcium ionised, lost from blood as moves into tissues and PTH down regulated
78
What are the formulae for calculating corrected calcium concentration relative to albumin/total protein?
Albumin: Total calcium (mmol/l) -(0.025xalbumin g/L) + 0.875 = mmol/L
Total protein: total calcium (mmol/L) - (0.01xtotal protein in g/L) +0.825= mmol/L
79
What factors can affect calcium concentrations?
- Lipaemia
- Haemolysis
- pH (affects ionised fraction)
- Albumin
80
What interpretation is most likely in a case where signs are not suggestive of hypercalcaemia but tests show hyperCa?
Lipaemia or haemolysis
81
Explain the impact of alkalosis on ionised calcium concentration
- Increases binding of calcium, therefore tends to cause ionised hypocalcaemia
(Rare in dogs, may occur with respiratory disease)
82
Explain the impact of acidosis on ionised calcium concentration
Reduces binding of calcium to albumin and therefore tends to caused ionised hypercalcaemia
83
Explain the physiological relevance of the effect pH on calcium concentration and neuron function
- Ionised calcium concentration affects threshold potential of cells
- i.e. hypocalcaemia = lowered threshold = more easily depolarised
- NO effect on resting potential
84
List the major differential diagnoses for hyperalcaemia in the dog and cat
HOGSINYARD
- Hyperparathyroidism
- Osteolytic lesions
- Granulomatous disease
- Spurious
- Idiopathic
- Neoplasia
- Young animal hypercalcaemia
- Addison's
- renal failure
- Vitamin D toxicity
- Lungworm (Angiostrongylus)
85
What are the potential mechanism that may lead to hypercalcaemia of malignancy and give their associated cancers where possible?
- PTHrP production (low PTH): lymphoma, carcinoma
- Vitamin D production (lymphoma)
- Ectopic PTH secretion (mainly human)
- IL-1 and TGFb stimulating bone resporption
86
If suspicious of hypercalcaemia of malignancy, how should this be tested?
- Need to sample and test for PTH
- Take sample into chilled EDTA tube ensure not clotted, spin immediately
- Separate plasma and freeze, keep frozen in transit to lab then analyse
- Can easily get false negatives
87
If all other causes of hypercalcaemia ruled out, but PTHrP is negative, how should this be interpreted?
- Not just PTHrP that can cause hypercalcaemia of malignancy
| - Can still be fairly certain that neoplasia is the cause
88
Describe the clinical signs of hypercalcaemia (NB: consider as systems)
- Renal: PUPD
- General: muscle weakness, lethargy, depression, tremores (neuromuscular)
- GI: anorexia, vomiting, constipation (esp. in cats)
- Cardiac (rare): arrhythmias secondary to myocardial calcification
89
Explain the renal presentation of hypercalcaemia
- Decreased sensitivity of renal tubules to ADH
| - Tubular changes secondary to mineralisation of basement membranes (degeneration and interstitial fibrosis)
90
What is an important point to check in an animal presenting with PUPD and why?
Always check anal sacs, in case of adenocarcinoma, which may be causing a hypercalcaemia of malignancy
91
What are the 4 most important differentials in a dog for hypercalcaemia?
- Hypercalcaemia of malignancy
- Hypoadrenocorticism
- Primary hyperparathyroidism
- Chronic kidney disease
- Also granulomatous disease
92
What are the most common causes of hypercalcaemia of malignancy in the dog?
- Lymphosarcoma
| - Anal sac adenocarcinoma
93
Explain how granulomatous disease can cause hypercalcaemia
- Autogenous production of active vitamin D (calcitriol) by macrophages
- Similar action to 1alpha-hydroxylase in the kidney
94
Explain how Addison's can cause hypercalcaemia
- Enhanced absorption of calcium in GIT
- Haemoconcentration
- decreased GFR from volume contraction
- Increased complexing and protein binding of calcium
- Lack of cortisol action on renal handling of calcium
95
What ionised calcium results would be expected in Addison's?
Normal ionised calcium concentrations
96
What condition would these blood values indicate? Hypercalcaemia, high BUN, creatinine, UA and high PTH
Chronic kidney disease
97
What findings would indicate hypercalcaemia due to primary hyperparathyroidism?
- High PTH
| - Enlarged parathyroid gland (CT or ultrasound rather than palpation)
98
How may hypervitaminosis D occur?
- Intoxication with Dovonex anti-psoriasis medication
- Excessive vit D supplementation e.g. salmon oil
- Intoxication with vit D rodenticide
99
What condition would these signs indicate?
| Hypercalcaemia, low PTH, "chalky" appearance of hard palate and spleen
Hypervitaminosis d
100
Explain why a hyperparathyroid state does not usually result in the patient becoming chalky
- In hyperparathyroid, phosphorous is low so calcification does not occur
- In hypervitaminosis D, phosphorous is normal so calcification can occur
