Endocrine Flashcards
(257 cards)
1
Q
Percentage of lymphocytic thyroiditis?
A
> 50 %
2
Q
Percentage TGAA?
T4?
T3?
A
50 %
15 %
30 %
3
Q
What breeds predisposed TGAA?
A
Beagle, borzoi (inherited)
GRet, Gt Dane, Irish setter, Doberman, OES
4
Q
What ECG changes hypothyroidism?
A
Bradycardia, low QRS voltage, low P wave amplitude, inverted T waves
1st/2nd degree AV block
5
Q
How many TGAA pos dogs get decreased T4/signs hypothyroidism in a year?
A
20 % decreased T4, 5 % signs, 15 % TGAA negative
6
Q
What mutations cause congenital hypothyroidism? What breeds?
Genetic tests?
A
Nonsense TPO mutation, autosomal recessive, toy fox and rat terriers
Missense TPO mutation, autosomal recessive, Tenterfield terrier
Genetic tests available for both. Both goitre.
Also Spanish water dog/papillon
7
Q
Sensitivity and specificity of T4?
A
89 - 100/73 - 82
8
Q
T3?
A
10/poor
9
Q
Free T4?
A
80 - 98/93-94 most accurate
10
Q
TSH?
A
58-87/82-100
Normal up to 30 % hT4 dogs
11
Q
TGAA?
A
91-100/94-100
12
Q
T4 + TSH?
A
63 - 67/98-100
13
Q
FT4 + TSH
A
74/98
14
Q
What breeds have decreased T4?
A
Greyhound, Basenji, Sloughi, Saluki, Whippet
Small number Scottish deerhound, dogue de Bordeaux and giant schnauzer
15
Q
Decreased T3?
A
Saluki, Irish Wolfhound
NORMAL in greyhounds
16
Q
Decreased free t4?
A
Greyhound, Sloughi, Saluki, Irish wolfhound
NORMAL whippet
17
Q
What changes T4 to T3?
A
5’deiodinase
18
Q
What happens to TSH and GH after TRH stim in hT4 dogs?
A
Increase GH more and TSH less than healthy
19
Q
Why are human thyroid supplements inappropriate for dogs?
A
Too much T3
20
Q
When should thyroid supplementation starting dose be decreased?
A
Underlying heart disease, decrease 25 - 50 %
21
Q
What drugs decrease T4?
cTSH?
Free T4?
A
T4 - Prednisolone, phenobarbital, TMPS, aspirin, clomipramine
cTSH - prednisolone, phenobarbital (may also increase)
TMPS increases TSH
FT4 - prednisolone, phenobarbital, TMPS, aspirin, clomipramine
No effect on anything - NSAIDs (ketoprofen decrease T4?), propranolol, KBr
22
Q
What is Schmidt’s syndrome?
A
Polyglandular endocrinopathy type 2 - hypoadrenocorticism with hT4 and/or DM
23
Q
Skin histopathology hT4?
A
Telogen preedominance, dermal thickening, erector pili vacuolation
UNCOMMON - atrophic/dystrophic follicles
24
Q
Myopathy in hypothyroidism?
A
Increased T1 decreased T2 fibres, nemaline rod inclusion, myofiber degeneration
25
When will congenital hT4 be apparent by?
8w
26
Mechanism bradycardia hT4?
Decreased beta receptor number/function
Decreased sarcolemmal ATPase
Decreased Na K ATPase
27
Mechanism hyponatraemia hT4?
Aldosterone pumps require T4
28
Renal effects of hyperthyroidism?
Decreased TPR, decreased effective arterial filling volume, stimulation RAAS.
Sodium absorption, increased plasma volume, increased CO.
Increased chloride resorption PCT, increased tubuloglomerular feedback as decreased tubular chloride - inc GFR.
Impaired renal natriuretic peptide response.
Increased glomerular capillary hydrostatic pressure.
Increased plasma volume and decreased sodium excretion.
Increased tubular phosphate absorption.
Downregulate aquaporin, increase Na/K ATPase
29
Bilateral disease hyperthyroid cats?
> 66 %
30
Possible mechanisms for hyperthyroid renal injury?
Hyperphosphataemia, glomerular hyperfiltration, proteinuria
31
Ectopic thyroid tissue in hyperthyroidism?
4 - 20 %
32
Risk factors for hyperthyroidism
Non pure breed, canned food, cat litter, flea control, long hair, female
33
Tachycardia in hyperthyroidism?
Thyroid hormone positive chronotrope, increase myocardial beta receptors, decrease AV conduction time, positive inotrope
34
Predictors of azotaemia post-I131?
GFR, SDMA
NOT proteinuria, creatinine, USG, cystatin C
35
T/F: Cats with hyperthyroidism have a higher prevalence of subclinical bacteriuria
False
36
Cystatin C in HT4?
Increased in serum versus FIV cats and increased in urine versus healthy cats
No difference azotaemic and didn't change with treatment
37
T4/TSH association with mortality in cats?
Decreased predicts 30 d mortality
38
How much feline TSH does canine assay detect?
40 %
39
Sensitivity T4/free T4 for HT4?
91/98
fT4 low specificity - increased 12 % NTI
40
Side effects thyroperoxidase inhibitors?
GI upset (less transdermal methimazole), hepatopathy (necrosis/degeneration/glutathione depletion), bleeding diathesis (inh vit K epoxide reductase?), cytopenia, facial excoriation, myasthenia graves
41
Negative prognostic indictors HT4 cat?
```
Azotaemic pre-treatment (NOT POST)
Hypothyroid and azotaemic after therapy
Older
Hypertensive
Proteinuric
Male
Methimazole vs I131 tx
```
42
Post-I131 hypothyroidism?
Usually return to normal 3 months.
Increased risk hypothyroidism if bilateral/previous medical management/medical management close to I131
5 - 83 % depending on classification
57 % azotaemic (more than euthyroid) - will resolve azotaemia in 50 % if supplement
TSH most specific and sens.
43
Efficacy methimazole?
90 % if use BID, 54 % SID
44
Post-treatment azotaemia prevalence?
15 - 20 %
45
Methimazole effect on technetium scanning?
None - no effect iodine uptake
46
Association between methimazole and I131 efficacy?
None
47
Beta blockers in HT4?
Decrease T4 - T3 conversion
Propanolol non-selective (bronchospasm)
Atenolol B1 selective
48
Half life of radio iodine?
8 days
49
Can you use Y/D in cats with renal disease?
Might be ok - controlled phosphorous and sodium, high quality protein, supplemented with omega 3
50
Response to diet HT4?
90 % euthyroid
51
Mechanism of action of I131?
Beta particles damage hyper functional thyroid tissue (80 %) - gamma other 20 %
52
Most sensitive diagnostic for hyperthyroidism?
Pertechnate scan
53
Levothyroxine dosing hypothyroid cats?
Twice daily, short T4 half life
54
Lipid changes in canine hypothyroidism?
Increased cholesterol/triglyceride (75 %), decreased LDL receptors, decreased cholesterol-rich LDL entry into liver for clearance
55
Altered initial management of concurrent hypothyroidism and DM?
Slow intro levothyroxine 25 % dose at first as insulin requirements will decrease (improvement of receptor and post receptor factors)
56
Insulin action on adipocytes?
Inhibit hormone sensitive lipase and stimulates lipoprotein lipase
57
Glargine insulin characteristics?
Asparagine replaced with glycine, two arginine additions.
| Microprecipitates at neutral pH, soluble pH 4
58
Detemir characteristics?
Myristic acid replaces threonine
Binds to albumin to prolong metabolism
59
Factors increasing/decreasing fructosamine?
Increase: hyperproteinaemia, hypothyroidism.
Decrease: azotaemia, haemolysis, hyperlipidemia, hyperthyroidism
60
DoA insulin dog?
```
Lente 8 - 14
NPH 4 - 10
PZI 10 - 16
Glargine 8 - 16
Detemir 8 - 16 - much more potent
```
61
Number of HAC dogs with DM?
8 %, 40 % increase glucose
62
UTI prevalence in canine DM?
50 %
63
Histopath diabetic neuropathy?
Segmental demyelination, axonal degeneration
64
Diabetic renal changes in dogs?
Membranous glomerulonephropathy
| Increased UPCR/albuminuria in 50 %
65
Factors impacting PBGM
Haematocrit, hypotension, hypoxia, triglycerides
66
Factors increasing the probability of DM remission in cats?
Protocol, shorter time since diagnosis, steroid administration, high protein low carb diet, longer acting insulins, tight control, older animal.
Less likely - plantigrade stance, increased insulin dose for glycemic control, increased cholesterol
67
GH and IGF1 effects?
GH catabolic - insulin resistance, carbohydrate intolerance, hyperglycaemia, DM
IGF-1 - anabolic
68
Risk factors feline DM?
Male, Burmese (incomplete penetrant autosomal dominant), obesity, diabetogenic drugs, high fat/high carb diet, Maine Coone, Russian blue, Siamese
69
What polymorphism do obese cats with DM have?
Melanocortin 4 receptor
70
Mechanisms of beta cell toxicity feline DM?
Misfolded amyloid deposition and cytokine infiltration.
ROS generation and apoptosis.
ER stress, misfolded protein, apoptosis.
Hexosamine biosynthetic pathway and glucose flux
Overabundant nutrient supply (glucolipotoxicity)
Advanced glucosylation end products
Inflammation
Dedifferentiation and death
71
How many cats are in DKA at DM diagnosis?
12 - 37 %
72
How many DM cats have hypersomatotropism?
25 - 30 %
73
SDMA in feline DM?
Decreased cf healthy cats
74
Risk factors for relapse after DM remission in cats?
30 - 80 % remission, 25 - 30 % relapse, < 25 % second remission
Impaired fasting glucose/impaired glucose tolerance, obesity, use of steroids.
75
Why might lente insulin have a very short duration of action in cats?
Shorter duration of action anyway, glucose very high, rapid drop, counter-reg hormones (glucagon cortisol epinephrine)
76
When should insulin be stopped in a cat with DM?
Preinsulin blood glucose consistently < 10, nadir 4 - 7 and 0.5 IU once daily for two weeks
77
Mechanism of action of glipizide? Drug class? DM cat response?
Stimulates potassium channel on beta cell therefore increases insulin secretion
Sulfonylurea
< 20 % remission, improvement 30 %
78
Acarbose DM?
Inhibit brush border disacharidase
Alpha glucosidase inhibitor
Similar to low carb diet for glucose lowering post prandial but only if 1/2 meals per day
79
Risk of CKD in DM cats?
44 % (versus 11 % without DM)
80
UTI in DM cats?
12 - 13%
81
Renal changes DM cats?
50 % glomerular changes, 33 % tubulointerstitial, 70 % increase UPCR/albuminuria
82
Negative prognostic indicators for feline DKA?
Azotaemia, hyperbilirubinemia
83
Changes in IGF1 in DM cats?
IGF1 predicts remission (increased) at 2w. Ternary complex (acid labile complex) and IGFB3 increased in cats achieving remission.
84
Lispro versus soluble insulin for feline DKA?
One study found quicker time to BG <13, other no diff.
85
Carbohydrate content for DM cats?
< 12 %
86
Mechanism/drug class/response nateglinide?
Stim potassium channel beta cells (different site cf sulfonylureas)
Meglitinide
Faster action/shorter duration cf sulfonylurea, renal excretion
87
Metformin?
Insulin sensitiser
Biguanide
One case report good glycemic control
88
Chromium/vandium
Chromium = insulin function cofactor
Vandium glycemic control, bypass insulin receptor to activate glucose metabolism in the cell - can help with receptor problems
Trace elements
Chromium increase glucose tolerance, vandium improved clin signs, PZI req, BG and fructosamine
89
Frequency of hypoglycaemia/rebound hyperglycaemia?
Common hypoglycaemia with 25 % rebound hyperglycaemia, however insulin resistance rare. No diff PZI/glargine
90
DoA insulin cat?
Lente 8 - 10 (nadir 3 - 6)
PZI 9 - 24 (nadir biphasic 1st 5 - 7)
Glargine 6 - 24 (nadir 10 - 24)
Detemir 9 - 14, more potent
91
Mechanism exenatide?
GLP1 agonist - remission 40 % good control 89 % cats DM versus placebo, no weight gain, decreased glycemic variability
92
PZI versus lente cat?
Longer duration of action, transition from lente better QoL and control
93
When is IGF-1 produced?
GH stimulation, in the liver, with sufficient portal insulin concentrations
94
Cause of feline hypersomatoptropism?
Pituitary acidophil adenoma or acidophil hyperplasia (latter = minority). Anterior pituitary.
Some produce other pituitary hormones.
Cause - organohalogenated contaminants eg polybrominated diphenyl ethers. AIP protein mutation.
95
Sex bias feline hypersomatoropism?
Male
96
Breed bias?
DSH
97
Phosphate in hypersomatotropism?
Increased - increased tubular absorption
98
T/F - hypersomatotopism and DM cats have increased prevalence azotaemia
False
99
GH sens/spec for hypersomatotropism?
> 10 84/95 - feline assay
| Above RI 100 %
100
Prevalence CNS signs hypersomatotropism?
10 - 15 %
101
What does IGF1 do to somatostatin?
Increases - which inhibits insulin release
102
IGF-1 performance for feline hypersomatotropism?
84 - 100 % sens, 88 - 92 % spec. PPV 95 %.
False neg untreated DM, malnutrition, hepatic/renal failure, hypothyroidism
Decreases after hypophysectomy and pasireotide, not XRT
103
What does ghrelin do to GH? What happens in hypersomatotropism?
Stimulates secretion. Is decreased in hypersomatotropism.
104
N-terminal type 3 procollagen polypeptide (PIIIP) in hypersomatotropism?
Increased versus DM cats alone, > 10 87/100 sens/spec. Decreases with hypophysectomy not XRT.
105
Pasireotide mechanism of action? Response in hypersomatotropism cats?
```
Somatostain analogue (1/2/3/5)
Decrease IGF1, insulin requirement, no change fructosamine. 21 % remission. Hypoglycaemia/polyphagia
```
106
Hypophysectomy response hypersomatotropism?
Decrease (normalise) IGF1, P3P, fructosamine and insulin dose. Remission 85 %. 10 % period mort.
Contraindication large tumour/concurrent disease.
Transient CD permanent hAC.
107
XRT for hypersomatotropism?
Reduce size and secretory capacity of tumour. Ghrelin increases, no normalisation P3P/IGF1. Sig decrease fructosamine/insulin req. 95 % decrease insulin dose. 32 % remission (permanent 62 %). 9m to lowest dose insulin. 15 % hT4. MST 1000d.
HS might progress despite DM improvement.
108
Does perivascular administration of ACTH on ACTH stim for healthy dogs or those receiving trilostane for PDH?
No sig diff versus IV
109
Possible aetiologies for 'occult/atypical' HAC?
Increased adrenal production of 17OHP due to partial 21 hydroxylase deficiency.
For - some studies all dogs with HAC inc 17OHP
Against - only female poms have inc 17OHP. Sex hormones (many) only increased 73 % alopecia X, progesterone most common 37 %. No 21 hydroxylase gene mutation identified. No HAC in oestrus/diestrus (60 - 90d). Only hair changes not other signs. 17OHP low spec (neoplasia, phaeo, nonfunc AT)
Progesterone binds cortisol receptor and increases free cortisol?
Against - ACTH not suppressed, higher in the poms
Alopecia X - some animals respond to trilostane/mitotane however inconsistent, also respond melatonin, sex hormones remain increased in many
110
Mitotane mechanism of action? Response canine ADH/PDH?
Adrenocorticolytic, fasciculate/reticularis with selective, gomerulosa with non-selective. Inhibit CYPIIA1 (cP460 side chain cholesterol cleavage), inhibit sterol-o-transferase I (SOAT-1 - inhibit cholesterol - cholesterol Esthers), inhibit CYPIIB1 (11beta hydroxylase). Increase CYP3A4 (cortisol clearance).
FAT MST 100 - 476, no sig diff trilostane
PDH - MST 700 d
50 - 60 % relapse, less with non selective protocol
111
Trilostane mechanism of action? Response canine ADH/PDH?
Competitive inhibitor 3betahydroxysteroid dehydrogenase (maybe 11 beta hydroxylase too) - decrease pregnenolone/17alphapregnenolone conversion to progesterone/17OHP, DHEA to androstenedione, 11deoxycorticosteroine to corticosterone, 18-hydroxycorticosterone and aldosterone, and 11deoxycortisol to cortisol.
Effective 75 % PDH, MST longer BID
MST FAT 300 - 500 d. Not sig diff mitotane.
112
Concurrent trilostane and spironolactone?
Potentiates spironolactone
113
What causes adrenal necrosis?
Oversecretion of ACTH
114
Ketoconazole mechanism of action? Canine response?
Inhibit CYPIIA1 (p450 cholesterol side chain cleavage), 17 alpha hydroxylase (CYP17 - pregnenolone to 17alphaOHpregnenolone and progesterone to 17OHP), 17,20lyase (CYP17 17OHpregnenolone to DHEA and 17OHprogesterone to androstenedione) and CYPIIBI (11deoxycorticosterone down to aldosterone and 11deoxycortisol to cortisol)
50 - 75% respond
115
Selegiline mechanism of action? Canine response?
Selective irreversible MAO B inhibitor - increase dopamine decrease ACTH.
80 % clin imp no ACTH stim change
116
Cabergoline mechanism? Response canine?
Dopamine 2 receptor agonist, decrease ACTH.
40-60% response with decrease in ACTH, cortisol, alphaMSH, pit size and imp clin signs. Most effective small tumour. Longer survival cf ketoconazole.
117
Retinoic acid?
Decreased transcription factor binding and POMC expression, decrease ACTH, decrease cell proliferation and induce apoptosis.
Clin imp 80 % with decreased pit size, ACTH and cortisol. Synergy with cabergoline.
118
Pasireotide?
Somatostatin analogue (1,2,3,5). Problem - SST 2 dominates canine pituitary.
119
Melanocortin 2 receptor antagonist?
MC2R - adrenal ACTH receptor
120
Abitaterone acetate?
Selective CYP17 (17alphahydroxylase) inhibitor
121
Steryl-o-acyl transferase inhibitors
Increase free cholesterol (no cleavage to cholesterol esters) - cytotoxic
122
Most common place for ACTH secreting tumour?
Pars distalis anterior pituitary
123
Hypothalamic and pituitary theories of PDH?
Increased CRH/vasopressin with glucocorticoid receptor defects and dopaminergic neurodegeneration, or somatic corticotroph mutation (latter more likely as CRH decreased in HAC and adenomas are monoclonal)
124
When to suspect malignant adrenal tumour?
> 2cm or invasion
125
Bilateral tumours in canine FAT HAC?
Up to 14 %
126
Prevalence hypertension in canine HAC?
40 - 90 %, one study all dogs with increased platelets had increased BP, no diff PDH/FAT, DM lowered and hypokalaemia increased risk of hypertension
127
Sensitivity and specificity of adrenal function tests for HAC in dogs?
ACTH stim: 0 - 95/59-95, less sens FAT
LDDST: NB increased dose polyethylene glycol vs sodium phosphate - 85-100/44 - 95, highest sensitivity for FAT
UCCR - 75 - 100, 21 - 100, 90 % chance PDH if > 100. Increased by hospitalisation
128
Differentiate PDH and FAT?
> 50 % suppression at 4 or 8 hours, complete suppression at 4h then loss of suppression,
Partial, escape, inverse. In order from highest to lowest PPV.
HDDST - 65 % PDH suppress, less likely if large tumour (only get extra info 10 %)
eACTH - not perfect, overlap and misclassification
129
Abdominal ultrasonography in canine HAC?
25 % PDH normal adrenals, highly sens/spec for identify adrenal tumour, find mets
130
Skull CT in canine PDH?
Abnormal around half.
131
Neuro signs canine PDH?
Develop approx 10 - 25 %, > 6m later usually
132
Mechanism gall bladder mucocoele in canine HAC?
Increased unconjugated bile acids, increased leptin? No difference cholecystokinin concentrations.
133
UTI in canine HAC?
10 - 50 %, urinary tract signs < 5 %, active sediment around half
134
Ectopic/food associated HAC?
Ectopic 2 x GSD, 1 x Dachs - neoplastic
Food-dependent - GIP receptor zona fasciculata - vizsla. Octreotide blocks.
135
Trilostane canine HAC ACTH goals?
41 - 150 post ACTH
Trough ACTH post 55 - 280
Pre-pill cortisol 40 - 139
Post-pill cortisol < 40
136
Hypophysectomy outcome in canine HAC?
Survival > 85 % one year, recurrence 27 % (median 500d), MST 2y, most relapse free one year.
Negative factors - large tumour, old, high eACTH, extension into cavernous sinus and circle of willis or past inter thalamic adhesion, increased pituitary transforming gene 1
Recurrence - large tumour, thicken sphenoid, high UCCR, high alpha MSH
137
XRT canine HAC?
More rapid imp neuro cf HAC. MST 500 d, less clinical improvement cf hypophysectomy.
Worse outcome - macro tumour > 2cm/neuro signs
138
Adrenalectomy canine FAT HAC?
MST 700 - 900 d. Recurrence 30 %
Negative px - tumour > 5cm/mets
Increased mortality if thrombus (past hepatic hilus) but no decreased survival time if no periop death.
139
Genetic predisposition hAC dog?
Standard poodle, leonberger, bearded collie, NSDTR, Portuguese water spaniel, Gt dane, , Rottweilers, wheaten terrier, westies
Female 2x risk
140
What adrenal enzyme are antibodies directed at in canine hAC?
21betahydroxylase
141
hAC inheritance?
Autosomal recessive standard poodle and Portuguese water dog
142
Why might atypical hAC develop?
Less 21 beta hydroxylase in zona glomerulosa, relatively spared?
143
ECG in hyperkalaemia?
Bradycardia, decreased P waves, spiked T waves, wide QRS, increased PR/decreased QT interval. Potassium can't move out of cardiomyocytes in phase 3 depolarisation
144
T/F - a dog with hAC is less sensitive to insulin?
False - more sensitive, no steroid
145
NA:K ratio to aim for with DOCP therapy?
28 - 32
146
TSH in hAC dogs?
Increases female dogs, with normalisation after manage hAC
147
What makes up juxtaglomerular apparatus?
Afferent arterioles macula densa distal tubule
148
What stimulates renin secretion?
Decrease in afferent perfusion pressure, decreased sodium in glomerular filtrate, sympathetic neutron activity after cardiac baroreceptor stimulation
149
What effects does ATII have?
Vasoconstriction, promote tubular sodium reabsorption, , stimulate aldosterone release
150
Aldosterone effects?
Promote sodium reabsorption in exchange for potassium and H+ - salivary glands, renal tubule, colon
Promotion of calcium, magnesium and phosphate loss (? secondary PTH?)
151
Hypokalaemic polymyopathy in hyperaldosteronism?
Less common in adrenal hyperplasia (arterial hypertension more common those)
152
Concurrent hormone secretion in feline hyperaldosteronism?
Progesterone - thin skin PUPD DM
Might also have increased corticosterone
153
Proportion of azotaemic primary hyperaldosteronism cats?
50 %, usually not hyperphosphataemic
154
What factors have been shown not to impact likelihood of haemorrhage for hyperaldosteronism adrenalectomy in cats?
Benign/malignant, presence of tumour extension, hypertension
155
Best confirmatory test for feline primary hyperaldosteronism?
Fludricortisone suppression of urine aldosterone:creatinine ratio - consistently suppresses in normal cats.
156
When does hypokalaemic myopathy occur?
K < 3
157
Percentage of cats with primary hyperaldosteronism and hypertension?
> 80 %
158
What predicts survival in adrenalectomy with feline primary hyperaldosteronism?
Long GA decreases survival
No sig diff adenoma versus carcinoma (although adenoma numerically longer MST).
Can also get long survival medical management (900d vs 1200 surg)
159
Feline CKD - prevalence of increased calcium?
Ionised 30 % total 10 - 15 %
160
When would total calcium and ionised not agree?
Renal/neoplasia
161
Risk factors idiopathic feline hypercalcaemia?
Long haired overrepresented, mean age 9y
162
T/F: PUPD is common in cats with hypercalcaemia
False - still can concentrate urine
163
Management of feline idiopathic hypercalcaemia?
Diet (high fibre? controversial, acidifying in general and more calcium added to offset the decreased gi transit time, CKD diets less acidifying and calcium/phos restricted but could inc vit d production due to phos restrict. canned diets more calcium restricted. diet for caox stones?)Evidence high fib and caox diet
Alendronate
Prednisolone
Therapy perhaps not required if < 0,25 above upper end of RI and no renal complications, clinical signs or stones
164
Bisphosphonate mechanism of action?
Reduce activity and number of osteoclasts binding hydroxyapatite, Prevent bone breakdown..
Can be nephrotoxic. Oesophageal necrosis (alendronate sodium > free acid in presence of gastric juice). Jaw necrosis (high basal turnover rate, prone to necrosis bone matrix - more common if chronic admin. Zolendronate > alendronate. Dog reports not cats.).
Absorption decreased by food.
165
How might steroids decrease calcium?
Decreased intestinal absorption, tubular absorption and skeletal mobilisation
166
Magnesium in critical illness?
Common, with hypoK and hypoNa, longer hosp
167
Purpose of Mg?
```
Metabolism/synth of CHO, lipid, protein, nucleic acid
Oxphos/anaerobic glycolysis
Neuromuscular, cardio
Signal transduction
Intracell K/Ca conc
Immunological function
```
168
Mg complexes with?
Phosphate compounds - imp cellular phosphorylation
ATP must complex with Mg for activity
169
Where does Mg live?
99 % intracell - 70 % bone rest other tissue,.
Extracell - ionised 60 %, 25 % protein bound, 15 % complexed - less protein bound than albumin
170
Where is most dietary Mg absorbed?
Ileum - only crosses if ionised
171
What makes Mg translocate to cells?
Insulin, catecholamine, amino acids
FAs, citrate, can chelate Mg. Can be sequestered in saponified fat.
172
Mg assoc arrhythmias?
Vtach/fib, SVT, AFib, prolong PR/widen QRS/peak T
173
Pumps impaired by hypoMg?
NaKATPase, NaK, Na/K-chloride, Ca ATPase - extracell K accum and loss, urine Na loss, Ca loss, phosphate loss, impaired PTH function
174
Divalent cation conversion?
2mEq/l = 1mmol/l=2.48mg/dL
175
Mg dose in azotaemia?
Excreted by kidney - reduce dose by 50 %
176
Mg supp cardiac SEs?
AV block/bundle branch block
177
What Mg salt to use?
Sulfate can chelate Ca, use chloride
178
Mechanism for excreting/increasing absorption of K other than renal?
Colon if renal compromised
179
What does hypokalaemia due to cell membranes?
Hypopolarise - weakness and ileus
180
Cardiac effects hypoK?
Prolong AP, increase automaticity, prolong ventricular repol - atrial/vent arrhythmia
Increase P decrease T wide QRS refractory class I antiarrthythmics and exacerbate digitalis cardiotox
181
Breed associated hyperlipidemia?
Mostly triglyceride - mini schnauz
Chol and/or trig - beagle
Mostly Chol - sheltie
Chol - doberman, rotate, briard, rough collie, pyrenees mountain dog, cats
Postprandial increase trig Burmese
Hyperchylomicronemia cat lipoprotein lipase deficiency
182
Manifestations of hyperlipidemia?
Mostly trig directed but atheroclerosis, arcus lipids and mucocoele chol also
183
Evidence for manifestations of hyperlipidemia?
Pancreatitis - mini schnauzers with hypertrig increased prevalence pancreatitis, increased trig in mini schnauz with pancreatitis, hyperlip mini schnauzers increased PL.
Hepatic dz (vac hep/steatitis) - increased hepatic enzymes in hyperlip mini schnauzers
GBM seen in breeds predisposed to hyperlip, hyperlip more common in GBM
30 % hyper trig mini schnauz had insulin resistance
Proteinuria documented in hyper trig minio schnauz
184
When to implement dietary management for hyper trig? Goals?
2.2, if severe aim < 4,5 to prevent glomerular damage
Diet in mini schnauz decreased < 5.6 in all, normal 30 %
185
Mechanism omega 3 in hyperlipidemia?
Eicosapentaenoic acid and docosahexaenoic acid.
Decrease lipogenesis, increase beta oxidation, activate lipoprotein lipase
186
Mechanism fibrates in hyperlipidaemia?
Weak agonist peroxisome proliferator activated receptor a (PPARalpha) which reg lipid and lipoprotein synth and catabolism.
Suppress FA synth, stim FA oxidation, activate lipoprotein lipase, inhibit diacylglycerol acyltransferase (convert diglyc to trigs). Increase hepatic VLDL/LDL update.
Gemfibrozil, only trig.
Urolithiasis? Liver?
187
Niacin mechanism hyperlip?
Inhibits hormone sensitive lipase and diacylglycerol transferase. Decreased trig biosynth
NB DM (inc BG). Monitor hepatic enzymes.
188
Statins in hyperlip?
BetaOHbetamethylglutarylCoA (HMGCoA) reductase inhibitor - blocks rate limiting step for cholesterol biosynthesis.
Atorvastatin.
Only chol. NG hepatic steatosis. Fibrates increase statin tox.
189
Mutation in what breed causes hyperparathyroidism?
Autosomal dominant mutation Keeshond. Tumour suppressor gene?
190
Prevalence of calcium oxalate calculi in dogs with primary hyperparathyroidism?
30 % (most asymptomatic, same with UTI which is present as frequently)
191
Renal disease risk in primary hyperparathyroidism?
Don't seem to be at increased risk
192
Primary hyperparathyroidism recurrence rate?
10 %, more in Keeshond
193
Distribution of histopathology in primary hyperparathyroidism?
87 % solitary adenoma, 8 % hyperplasia, 5 % carcinoma
90 % single gland
194
What assay should be used to measure PTH?
Whole or intact so no fragment cross reaction
195
How many primary hyperparathyroidism dogs have a nodule on cervical US?
95 %
196
Management options for primary hyperparathyroidism? Success?
Surgery (up to 3 glands at a time) - 94 % efficacy
| Percutaneous heat/ethanol ablation - both around 90 %
197
Risk factors for post op hypocalcaemia after primary hyperparathyroidism?
> 1 gland removal, total/ionised calcium > 3.5/1.8
Very high PTH/bone ALP
One study found positive correlation of calcium pre and post op, another found increased likelihood post op Ca <1 if pre op was > 1.72
198
How is vitamin D2/3 transported from intestine?
Digestive enzymes, chylomicrons, bile acids, transcalciferon, vit D binding protein
199
Advantages of subcutaneous DDAVP?
More efficacious, longer duration of action, decreased cost as smaller dose, compliance
200
What supports a diagnosis of CDI during a DDAVP trial?
> 50 % decrease in water intake
201
How often does CDI develop after hypophysectomy in dogs and how often is it permanent?
50 %, 40 %
202
What breeds have congenital CDI described?
Afghan, GSHP, schnauzer
203
What breeds have primary NDI described?
Husky (X linked V2 receptor mutation)
204
What do V2, V1A and V1B ADH receptors do?
V2 = increase aquaporin/coag changes, V1A systemic vasoconstriction renal /CNS vasodilation/platelet activation/glycogenolysis, V1B ACTH catecholamine and insulin release
205
When should a water deprivation test be stopped?
Na > 165, 3 - 5 % BW loss, osmolality > 350, USG > 1.025 - 1.030 (dog) 1.035 (cat)
Problems with water deprivation test - partial CDI might respond to dehydration, NDI might respond to high dose DDAVP
206
Mechanism of action of chlorpropamide in partial CDI?
Unmask constitutive receptor signalling and increase ADH receptors
207
What drugs potentiate ADH action?
Aspirin/thiazides, may cause SIADH
208
Diabetic neuropathy nerve changes?
Splitting/ballooning myelin and demyelination, Schwann cell injury.
Axonal degeneration only in severe
209
UTI in diabetic cats?
50 %
210
Definition of hyperosmolar hyperglycaemic DM?
Glucose > 30 Osm > 350
211
Pathophys DKA?
No HSL inhibition, no lipoprotein lipase stim, increased FA production, hepatic ketogenesis (decreased malonyl CoA stimulation and therefore increased translocation of carnitine by carnitine palmitoyl transferase). Citric acid cycle overwhelmed.
212
Cats - CKD and CHF more common which DM complication?
HHS, Panc/heptic dz less common
213
When is acetoacetate transformed into betahydroxybutyrate?
In presence of hydrogen ions.
214
When should a pituitary mass in PDH dogs have additional management?
> 8 mm
215
ECG changes in hypocalcaemia?
Prolonged QT interval, tachyarrhythmia
216
Proportion of animals with MG change in primary hypoparathyroidism?
75 % low - causes functional decrease in PTH activity
217
ECG changes to monitor for during calcium supplementation?
Short QT/bradycardia/VPC/ST elevation
218
Why is calcium carbonate useful in primary hypoparathyroidism?
Carbonate binds intestinal phosphate, stim endogenous calcitriol production
219
Problems with ergocalciferol?
Long time to saturate (very fat soluble), long half life, minimal vit D receptor affinity. But is cheap.
220
Calcitriol mechanism of action?
Programs undifferentiated enterocytes to increase intestinal calcium transport (twice daily is useful)
221
Thiazide diuretic and calcium?
Decrease calciuresis
222
Histopath neuro changes from prolonged hypoglycaemia?
Necrosis in cerebral cortex
Also cerebral oedema
223
% mets in insulinoma?
50 %
224
Streptozoocin mechanism of action?
Selective beta cell destruction.
NB nephrotox
225
Where is diazoxide metabolised?
Liver
226
What diuretics enhance diazoxide action?
Thiazide
227
Ki67 in insulinoma?
Index prognostic - positive have shorter symptom free interval
228
What osmolality would you expect in SIADH?
Low - < 275
229
What gene mutation causes congenital hyposomatotropism in dogs?
LHX3, autosomal recessive, GSD, sarloos wolfdog, czechoslocakian wolfdog, Karelian bear dog
230
What tests could diagnose canine hypersomatotorpism?
Measure GH, measure IGF1, GHRH/somatostatin/glucose suppression tests
231
What tests could diagnose canine hyposomatotropism?
IGF1, GHRH/clonidine/xylazine/ghrelin stim, genetic test
232
What concurrent hormone deficiencies might be present with hyposomatotropism in dogs (congenital)?
TSH, prolactin, gonadotropin (rare ACTH)
233
How might you treat congenital hyposomatotropism?
Porcine GH, medroxyprogesterone
234
What impact does lack of GH have on kidneys?
Poor glomerular development, get azotaemia
235
How many cats with HAC have detectable pituitary masses?
50 %
236
How many cats with HAC are hypertensive?
20 %
237
How to diagnose feline HAC?
LDDST (but with 0.1mg/kg) 10 - 20% normal cats don't suppress with reg dose. This can distinguish HAC from DM..
ACTH has poor sensitivity and affected by HT4
UCCR poor spec
238
How to differentiate feline PDH from FAT?
LDDST: escape or partial (4 or 8)
HDDST
UCCR LDDST combo(> 50 % PDH suppress)
AUS (93 % sens)
eACTH (not affected by DM or hypersomato) - 73 % sens PDH
239
Management of feline HAC?
Medical MST 617 d, 36 % will have decreased insulin requirements
Mitotane MST 2 - 63m
Metyrapone (11 betahydroxylase inhibitor)
Adrenalectomy (high mort - 50 - 70 % survival > 1y)
XRT - MST 17m, imp neuro, HAC and DM
240
T/F: measurement of urine aldosterone is useful to diagnose hyperaldosteronism in dogs?
False - no aldosterone and no aldosterone-18-glucuronide
Measure aldosterone
241
What catecholamine requires steroids?
Epinephrine - cortisol in adrenal venous effluent stimulates PNMT
242
What might cause a false positive normetanephrine in a dog?
HAC - use 4x upper RI to dx phaeochromocytoma
243
T/F: phaeochromocytomas are often mineralised
False, usually not
244
What positive stain is found in pheochromocytoma?
Chromogranin A
Only mets distinguish malignancy
245
MST phaeo post adrenalectomy?
350d
246
How to diagnose zollinger Ellison syndrome?
Gastrinoma. Increased gastrin decreased gastric pH. Calcium/secretin stim.
247
What amino acids might be decreased with glucagonoma?
Arginine, lysine, histidine
248
What breeds of cats have congenital hypothyroidism described?
Abyssinian and DSH - dysmorphogenesis, autosomal recessive
249
What skeletal changes are identified in congenital hypothyroidism?
Epiphyseal dysgenesis in the vertebral bodies and long bones
250
How many canine thyroid masses are carcinomas? Follicular?
90 % (size not predictor)
70 % (thyroglobulin staining), remainder medullary ?(calcitonin)
251
How many beagles with thyroiditis get thyroid neoplasia?
50 %
252
How many thyroid neoplasia in dogs are productive?
10 %
253
What predicts malignancy in thyroid neoplasia dog?
Capsular invasion
254
Management of canine thyroid neoplasia?
Surgery MST 3y (similar bilateral)
RT - variable but can be years PFI, max tumour reduction at 8 - 22m 50 % die of metastatic disease
Chemo - cisplatin MST 11m
I131 - stage 2 - 4, 12 - 34m MST, longer if combine with surgery
255
Sensitivity of imaging for insulinoma?
AUS 56 % CT 71 %
256
Negative prognostic factors for insulinoma?
Post op hypoglycaemia, stage II/IIIM, lack of addition of pred, postop pancreatitis
Diazoxide less MST
257
What percentage of dogs with insulinoma will be normoglycemic at 14m?
50 % stage I, 20 % stage 2/3
