Endocrine CVT Flashcards
1
Q
What is another name for growth hormone?
A
Somatotropin
2
Q
Somatomedin C is also known as….
A
Insulin-like growth factor (IGF-1)
3
Q
Name 2 disorders that are treated with growth hormone in dogs.
A
- Hypopituitary dwarfism in puppies
2. GH-Responsive Dermatosis in Adult dogs
4
Q
Name 2 breeds in which hypopituitary dwarfism is inherited (autosomal recessive trait).
A
- GSD
2. Carelian Bear Dog
5
Q
What is the proposed pathogenesis of GH- responsive dermatosis in Pomerians?
A
Hyperprogestinism OR Hyperandrogenism = Resulting in decreased GH production
6
Q
What other treatments have been used in dogs with GH- responsive dermatosis?
A
- GH supplementation
- Lysodren
- Castraion
- Spontaneously resolution!
7
Q
What is the recommended supplementation of growth hormone?
A
Porcine recombinant product (antigentically similar to canine GH and thus less likely to form antibodies)
8
Q
What is a side effect of administration of porcine GH in dogs?
A
Diabetogenic Effects!! Monitor glucose weekly and glucosuria daily
9
Q
What is desmopressin?
A
DDAVP - Synthetic analogue of arginine vasopressin
Used to treat central diabetes insipidus
10
Q
How can you quickly calculate urine osmolality (if no protein or glucose is present)?
A
Last 2 digits of USG x 36 = mOsm/L
11
Q
What can occur with an unsuspected case of HAC with a DDAVP trial?
A
- Complete ability to concentrate urine after dehydration = Psychogenic polydipsia
- Incomplete ability to concentrate urine after dehydration followed by increased of 10-50% USG after DDAVP = Central DI
- Decreased in water intake >50% after DDAVP (central DI)
= = Thus need to rule out HAC before a vasopressin trial
12
Q
What is a potential complication with DDAVP administration?
A
Induction of water intoxication (hyponatremia)
13
Q
What is the difference between hypersomatotropism and acromegly?
A
Hypersomatotropism = State of excessive growth hormone production Acromegy = Syndrome that results from state of excessive GH production
14
Q
What diagnostic is used to diagnose hypersomatotropism in cats?
A
IGF-1 > 1000 ng/mL
15
Q
When a diabetic cat has weight gain, what should you be thinking?
A
Consider hypersomatotropism (acromegly)
16
Q
What is the Wolff-Chaikoff Block?
A
High levels of I- (iodide) inhibit organification and synthesis of thyroid hormones = Autoregulation (intrathyroidal)
Thought behind iodinated radiographic contrast agents (hyperthyroid tx), and nuclear melt-downs!
17
Q
What 3 tissues concentrate the most thyroid hormones?
A
- Liver
- Kidney
- Muscles
18
Q
What are the 2 most common causes of canine primary hypothyroidism?
A
- Lymphocytic thyroiditis (50%) - Immune mediated dz
2. Idiopathic Atrophy (50%) - Replaced by fat, no inflammation, no thyroid antibodies
19
Q
How much of the thyroid gland needs to be gone to have clinical signs assoicated with hypothyroidism?
A
about 75%
20
Q
What are Graham et al porposed stages of lymphocytic thyroiditis in dogs?
A
- Subclinical thyroiditis: No CS; normal T4, fT4; normal TSH; Positive thyroglobulin antibodies
- Subclincial hypothyroidism: NO CS; normal T4, fT4; increased TSH; Positive thyroglobulin antibodies
- Overt hypothyroidism: CS present, decreased T4, fT4; increased TSH; Positive thyroglobulin antibodies
- Non-inflammatory atrophic hypothyroidism: CS present, decreased T4, fT4; increased TSH; NEGATIVE thyroglobulin antibodies
21
Q
What is the classic signalment for canine primary hypothyroidism?
A
Middle aged (mean = 7 yrs) No gender predisposition Breed = ANY!
22
Q
Which breeds have hypothyroidism often associated with thyroglobulin autoantibodies?
A
- English Setter
- Chesapeake Bay Retriever
- Golden
- Rhodesian Ridgeback
- Boxer
- Siberian Husky
- Irish Setter
- Cocker Spaniel
23
Q
What are the most common CS of canine hypothyroidism?
A
Lethargy (48%)
Weight Gain (49%)
Alopecia (Derm signs = 88%) - Bilaterally symmetric non-pruirtic truncal; hair loss at pressure/wear points = ““Rat - tail””
Pyoderma
Seborrhea
Based on Panciera et al 162 dogs (Vet Clinics 2001)
24
Q
Why do dogs with hypoT4 have a “tragic expression”?
A
Myxedema - Increased skin thickeness due to accumulation of mucopolysaccharides and hyaluronic acid - binds water in skin = Puffiness of face and extremities,
25
What are common neuro signs with hypoT4 in dogs?
1. Cranial nerve defs = Vestibular disease and facial n. paralysis
2. Polyneuropathy = Neuromuscular signs
??MG, Megaesophagus (weak association, rarely respond with supplementation), Lar Par (controversial)
26
Are coagulopathies noted in dogs with hypoT4?
VERY rare!!! But reported in humans (subclincial von Willebrand disease?)
27
What is myxedema coma?
Rare condition with hypoT4 in dogs
Severe hypoT4!! = Weakness, lethargy, dullness, hypothermia, bradycardia, hypotension, hypoventilation, non-pitting edema
Decreased Na and BG
Tx: IV Levothyroxine
28
Discuss the value of TT3 and fT3.
TT3: Very little is secreted by thyroid gland; cannot distinguish btwn normal and hypothyroidism from euthyroid sick = MINIMAL VALUE
fT3: Diagnostic value unknown
29
What does the MSU Thyroid panel contain?
fT4 by ED, TSH, autoantibodies
30
Which breed has total T4 (and free T4) RR that are normally lower than other breeds?
Greyhounds (maybe other sight hounds) - Also noted in conditioned sled-dogs
T3 is unchanged - maybe this could be useful in this breed???
31
Can TT4 be normal in dogs with hypoT4?
YES! Could miss about 10% of cases - since the sensitivity of TT4 is 89-100%
May be affected by T4 autoantibodies
32
What is the specificity of TT4 for diagnosing hypoT4?
POOR!!! TT4 can be low in other disease or drugs (euthyroid sick syndrome)
33
When should you run a TT4?
When you are trying to RULE OUT hypoT4 (if > 2 ug/dl = Very unlikley hypoT4; if < 0.5 ug/dl = Very likely (with no other systemic dz))
34
Which thyroid test correlates best with thyroid status in dogs?
Free T4 (measured by equilibrium dialysis) - SINGLE BEST TEST (bets combined sensitivity, specificity, accuracy)
35
What can lower fT4 in dogs?
Chronic steroids, HAC, Phenobarb, TMS, carprofen, clomipramine
36
Discuss measuring TSH in dogs?
Expected to have elevated TSH in dogs with hypoT4
BUT…..
Up to 25% hypoT4 dogs have NORMAL TSH
Up to 8% of normal dogs have HIGH TSH
TSH high as autoimmune thyroiditis occurs!
Sensitivity 0.76-0.87 = NOT good screening test for dogs (unlike in humans)
3 different assays
In dogs - consider: pulsatile release, pituitary ""exhuastion, glycolysation patterns (affect assay)
37
What percentage of dogs with thyroglobulin antibodies will become hypoT4?
About 20% may become hypoT4 within 1 year - need to monitor a panel q3-6 months
38
What percentage of dogs with hypoT4 have thyroglobulin autoanitbodies?
```
About 50-60%
In 234 dogs for 1 yr:
20% become hypoT4 in 1 yr
15 % become negative
57% stayed + and euthyroid
8% + to borderline
```
39
What percentage of dogs with hypoT4 have T3 autoanitbodies?
33% of hypoT4 dogs
40
What percentage of dogs with hypoT4 have T4 autoanitbodies?
15% of hypo T4 dogs
NOTE: 5% had no effect on T4, 9% kept T4 in RR (BAD), 1% elevated TT4 (BAD)
= = Need to measure fT4 with ED since this is NOT affected by T4AA
41
What are the best tests for sensitvity for hypoT4?
TT4, fT4 (ED), TSH
42
What are the best tests for specificity for hypoT4?
fT4 (ED), TSH
43
What are the best tests for drugs or non-thyroid illness for hypoT4?
fT4 (ED), TSH, TgAA (autoantibodies)
44
Name a breed with congential hypothyroidism with goiter.
Tenterfield Terrier - Mutation in thyroid peroxidase gene
45
What is thought to be a sensitive marker of thyroid inflammation?
Antithyroglobulin antibodies
46
Since clinical progression of hypoT4 varies by breed, name a breed that progresses slowly and one that progresses rapidly?
```
Beagles = SLOW (middle age or later)
Goldens = RAPID!! Peak age 5 yrs (as young as 2 yrs)
```
47
Which 2 breeds have a high risk of hypoT4?
Goldens and Dobermans
48
Name 2 diseases that are reported in association with hypoT4 but that treatment with levothyroxine does not consistently result in resolution of CS?
Laryngeal paralysis and megaesophagus (causal relationship)
49
Name 2 breeds in which goiter caused by thyroid peroxidase deficiency has been documented.
Toy Fox Terrier
| Rat Terrier
50
How do anti-T4 antibody affect the TT4 measurement?
Spurious ↑ measured T4 concentration (normally value above RR)
51
What is the gold standard for testing thyroid function in dogs?
TSH Stimulation Test (administer bovine TSH - measure T4)
| If no response = Hypothyroid
52
What combination of test results is highly specific for diagnosis of hypoT4 in dogs?
Low TT4, low fT4 with high TSH
53
Do Anti-T3 and Anti-T4 antibodies interfere with response to L-thyroxine supplementation?
NO!
54
What sample should be obtained to monitor therapeutic levothyroxine supplementation?
4-6 hours post pill = Should be within upper RR or slightly above (up to 6 mcg/dl)
Can also consider measuring TSH (needs to have been elevated previously, it should normalize with treatment)
55
What is a common complication of hypothyroidism in dogs that can be seen on a chemistry panel?
Hyperlipidemia (elevated cholesterol and triglycerides - elevated in 75% of affected dogs)
56
How does hyperlipidemia occur in dogs with hypoT4?
Decreased clearence of cholesterol from circulation, reduced cholesterol utilization, and increased production of cholesterol
57
What disease process can occur with hypercholesterolemia in hypoT4 dogs?
Atherosclerosis - Which can lead to ischemia or TE of multiple organs
Signs of organ dysfunction = Pancreatitis
Rare complication
58
What abnormality is seen on CBC of hypoT4 dogs?
Mild nonregenerative anemia (25-30% of hypoT4 dogs)
59
Name 2 breeds that are predisposed to myxedema comas?
Rotties and Dobermans
60
What is an immune-mediated disease that leads to destruction of multiple endocrine glands?
Polygranular endocrinopathy - Thyroid, adrenal cortex, pancreatic islet cells, parathyroid gland
61
What are the 2 most common manifestations of polygranular endocrinopathy in dogs?
Concurrent hypoadrenocorticism and hypoT4
| CS of hypoadrenocorticism will predominate but hypercholesterolemia should alert you to hypoT4 too
62
What is the value of measuring a total thyroxine?
TT4 = Rule out diagnosis of hypothyroidism, (if within RR unlikely to have hypoT4)
63
What are 2 drugs that can lower fT4 (even with equilibrium dialysis method)?
1. Phenobarb
| 2. Steroids
64
When should you suspect that autoantibodies to thyroid hormones may be present?
When TT3 or TT4 are high in a dog that is being evaluated for hypoT4
65
The total T4 concentration in a dog suspected of having hypothyroidism is less than normal. How certain can I be that this dog is hypothyroid?
· Low TT4 → Dog MAY be hypothyroid OR a nonthyroidal factor can be depressing T4, or dog lower than “normal” circulating TT4 concentrations (and be euthyroid)
o Evaluating this patient:
§ FT4 (dialysis method) and TSH → More definitive than total T4 (BEST OPTION)
§ TT4 retested in 6-8 wks: If dog hypothyroid T4 should continue to decline, CS more profound
§ Trial thyroid hormone replacement therapy. Recheck after 5-10 wks of T4 therapy using objective criteria (regrowth of hair)
66
If the T4 level is normal but I am still suspicious of hyperthyroidism, what can I do?
· If T4 < 25nmol/L → Unlikely cat is hyperthyroidism
· If T4 upper normal range (25-50nmol/L) → Need further evaluation
o FT4 measured by equilibrium dialysis (Peterson et al., 2001)
o TT4 measured repeatedly, T4 will fluctuate in and out of normal range in hyperthyroid cats
o T3 suppression or thyrotropin-releasing hormone stimulation
67
What is the value of measuring FT4 in cats suspected of being hyperthyroid?
Rational of FT4 to diagnose hyperthyroidism in cats concentration of FT4 is less affected by nonthyroidal factors
o BUT FT4 can be elevated in 12% of sick euthyroid cats (Mooney, Little, and Macrae, 1996)
§ Need to use TT4 with FT4 to discriminate btwn hyperthyroidism and euthyroid sick syndrome
§ Hyperthyroid cats tend to TT4 concentrations in upper half of normal range
Sick euthyroid cats have TT4 in lower half of normal range, even if they have elevated FT4 (Mooney et al., 1996)
68
What are the 3 options for management of hyperT4 in cats?
1. Radioiodine therapy
2. Thyroidectomy
3. Antithyroid drugs (methimazole)
69
What is the MOA of methimazole?
· Methimazole blocks thyroid hormone synthesis by inhibiting thyroid peroxidase (enzyme involved in oxidation of iodide to iodine, incorporation of iodine into thyroglobulin, and coupling of tyrosine residues to form T4 and triiodothyronine (T3))
o Does NOT block release of performed thyroid hormone → Explains delay of 2-4 wks before serum T4 fully normalize after starting tx in cats
o Dose NOT decrease goiter size (goiter may become larger over time despite tx)
70
Why is there a 2-4 week delay before serum T4 fully normalizes after starting methimazole in cats?
Since methimazole is a thyroid peroxidase inhibitor it does NOT block release of performed thyroid hormones that can be released and used during this time
71
Name 7 potential side effects of methimazole.
1. Blood Dyscrasias
2. Facial Excoriation
3. Hepatotoxicity
4. GI upset
5. Coag abnormalities
6. Acquired Myasthenia gravis
7. Renal Decompensation
72
What are the most common blood dyscrasias with methimazole?
1. Neutropenia
2. Thrombocytopenia
(3-9%) - Recover within weeks of stopping methimazole
73
What percentage of cats will develop facial excoriations with methimazole?
2-3% on face and neck (unknown mechanism in humans)
74
Discuss the hepatotoxicty that can be seen in cats on methimazole?
2% of cats = Reversible in several weeks after stopping drug (increased ALP, bilirubin, and ALT)
But rechallenge can lead to recurrent hepatopathy
75
What are the most common side effects of methimazole in cats?
1. Renal Decompensation (15-20%) - New onset of azotemia since the abnormally high GFR from hyperT4 and treating it will decreased GFR
2. GI Upset (10%) - Anorexia, vomiting (can resolve with dose reduction - direct gastric irritation)
76
Discuss the coagulation abnormalities that can be seen with methimazole in cats?
· Methimazole and (propylthiouracil, lesser extent) inhibit K-dependent clotting factor activation ((γ-carboxylation) and epoxide reductase (necessary for vitamin K recycling, and the same enzyme targeted by warfarin) at high concentrations
· 20 cats tx with methimazole: No significant changes in PT or PTT; 1 cat has prolonged protein-induced by vitamin K antagonism (PIVKA) clotting time (Randolph et al., 2000)
§ No cats had clinically bleeding
§ Apparently uncommon “warfarin-like” effect of methimazole in cats = BUT consider if hemorrhage in cat on methimazole
77
How does the transdermal form of methimazole work?
· Compounding in pluronic lecithin organogel (PLO): Acts as permeation enhancer to allow drug absorption across stratum cornea
o Poor absorption after single dose in cats → chronic dosing effective in lower T4
78
Discuss the incidence of SE with the transdermal methimazole.
· Fewer GI SE (4%) compared to oral
| · No incidence in facial excoriations, neutropenia, thrombocytopenia, hepatotoxicity
79
Discuss the efficacy of the transdermal methimazole compared to oral methimazole.
· Transdermal associated with lower efficacy by 4 weeks (only 67% euthyroid) compared to oral (82% euthyroid)
o May be related to lower bioavailability
80
Discuss the issues with administering methimazole prior to I131 treatment.
· Methimazole does NOT inhibit iodide uptake by thyroid = Does NOT impair technetium 99 (pertechnetate thyroid scanning in hyperthyroid cats)
· Methimazole DOES inhibit iodine organification which may decrease contact time or radioiodine within thyroid
ats: No association btwn time of discontinuation before radioiodine and long term radiodine efficacy (Chun et al., 2002, Forrest et al., 1996) § Recommend discontinuation of methimazole prior to radioiodine therapy → 1-2 wks washout period (may be longer than needed)
81
What is carbimazole?
Substituted derivation of methimazole = Prodrug
| · Carbimazole is converted to methimazole = THUS not recommended if cat is having SE with methimazole
82
What is propranolol used for in hyperT4 cats?
Inhibiting conversion of T4 to T3 (useful in short term if cat is intolerant to methimazole) § Nonselective B-blocker = Bronchospams in some cats
83
What percentage of cats with hyperT4 will have bilateral thyroid involvement?
70% of hyperT4 cats
84
What percentage of cats will NOT respond to a single dose of I131?
· <5% cats may NOT respond to single treatment and may require re-treatment later (most respond well to second treatment)
85
What is the MOA of radioiodine treatment?
· Thyroid hormones are the only iodinated orangic compounds in body, only function of ingested iodine is thyroid hormone synthesis
o In thyroid cell, iodide is oxidized to iodine which is incorporated into tyrosine residues of thyroglobulin (organifications) to form thyroid hormones (thyroxine, T4, and 3.5.3 triiodithyronine, T3)
· Radioiodine-131 (131I): Thyroid gland cannot differentiate btwn stable and radioactive iodine – thus it is concentrated in thyroid gland
o Hyperthyroid cats: Radioiodine concentrated in hyperplastic or neoplastic thyroid cells = Irradiates and destroys hyperfunctioning tissue
§ Large % accumulates in thyroid (20-60%)
§ Excreted in urine and lesser degree in feces
§ T1/2: 8 days
§ Emits β-particles (80% tissue damage, max 2 mm in tissue, length 400um) and γ-radiation
o Normal thyroid tissue “protected” since uninvolved thyroid tissue is suppressed and received a very small dose of radiation (unless large dose administered)
86
How is normal thyroid tissue protected from I131 treatment?
o Normal thyroid tissue “protected” since uninvolved thyroid tissue is suppressed and received a very small dose of radiation (unless large dose administered)
87
Discuss what is known about uptake of I131 and concurrent methimazole treatment?
§ Thyroidal uptake of I131 is enhanced in healthy cats after recent methimazole withdrawal; short term rebound effect may be potentially beneficial when treating hyperthyroidism with I131
□ Enhanced uptake lead to higher incidence of I131 hypothyroidism
§ Discontinuing methimazole for less than or greater than 5 days before I131 has no effect on tx outcome
o Discontinue antithyroid drugs at least 1 wks before I131 tx
§ May not do this with severe hyperthyroid cats
88
What are the 3 methods for calculating the optimal dose of I131 for hyperT4 cats?
Method 1 : Use tracer kinetic studies (estimate % of iodine uptake and rate of disappearance from gland, thyroid imaging to estimate weight of thyroid) = NOT used
Method 2: Fixed, relatively high dose of I131 in all cats (4 or 5 mCi) regardless of the severity of hyperthyroidism or size of tumor
Method 3: o Method 3: Scoring System that takes into consideration severity of CS, size of cat’s thyroid gland (based on palpation or imaging), serum T4
89
What percentage of hyperT4 cats have thyroid carcinomas and what is the best treatment for them?
<2.5%: I131 BEST chance for successful cure of tumor; concentrates in ALL hyperactive thyroid cells (carcinomatous tissue + metastasis) o Carcinomas concentrate and retain iodine less efficiently than adenomas (hyperplasia)
o Larger → Need larger doses (10-30mCi) to destroy all malignant tissue = Longer hospitalization dt prolonged radioiodne excretion
o Sx debulking followed by I131high dose - Successful
90
Name 4 side effects of I131 treatment.
· SE are extremely RARE since I131 specific in site of action
o Rare: Dysphagia and fever (radiation thyroiditis) – Self-limited, resolves spontaneously
o Rare: Vocal change (some cases permanent)
o Permanent hypothyroidism (few months after tx in few cats)
o Worsening of renal dz (WOREST): Dt correcting hyperthyroid state and altering GFR and renal blood flow
§ Hyperthyroidism may contribute to development of renal dz in cats
§ Hypertension (increase glomerular capillary pressure and proteinuria) = Glomerular sclerosis and progression of renal dz
§ “Mask hidden” renal disease since hyperdynamic circulation is beneficial to sustainable renal function and delaying renal failure in cats with CKD
§ Development of azotemia independent of tx modality
§ Occur in 25% of treated cats (develops within 30 days after tx)
91
What percentage of cats will develop hypothyroidism after I131 treatment?
5% will develop permanent hypothyroidism = CS within 2-4 months of tx (lethargy, nonpruritic seborrhea sicca, matting of hair, and marked weight gain; NO alopecia) o Diagnosis based on CS, low serum TT4, FT4 with high TSH, response to replacement tx
§ Life-long thyroid hormone supplementation needed (0.1 mg of L-T4 per day)
92
Do normal results on an ACTH stimulation test or a low-dose dexamethasone suppression test rule out hyperadrenocorticism?
· ACTH Stim within normal range in at least 20% of dogs with hyperadrenocorticism (false negative)
· LDDST within normal range in about 5% of dogs with hyperadrenocorticism (false negative)
o More prone to error
o 50% of nonadrenal illness had abnormal results (inadequate suppression of cortisol) – NONE had CS consistent with Cushings (Kaplan, Peterson, and Kemppainen, 1995)
93
What are the risks of not treating HAC?
PTE, Diabetes mellitus, CaOx urolithiasis, secondary infections
94
What are 2 ways that treating PDH can result in neurologic signs and what are these neurologic signs?
Rapid growth of pituitary tumor (ataxia, depression, blindness, inappetance, aimless walking, seizures) - From sudden reduction in cortisol
Unilateral facial nerve paralysis (unclear mechanism)
95
What are the 3 effective tx for PDH?
1. Surgical - transsphenoidal hypophysectomy
2. Mitotane
3. Trilostane
96
What is the MOA for mitotane?
Cytotoxic agent that causes necrosis of the zona fasiculata and reticularis of the adrenal glands - No production of steroids
97
What is the MOA for trilostane?
competitive inhibitor of 3B-hydroxysteroid dehydrogenase (short acting)
98
What is the efficacy of trilostane in dogs with PDH?
Effective in 75% of dogs
99
What 2 drugs should be used with caution with trilostane?
Aldosterone antagonists (spironolactone) and may potentiate ACEi
100
What electrolyte abnormality can be seen with trilostane?
Mild hyperkalemia
101
Is there a difference in the survival times of animals treated with mitotane vs trilostane for PDH?
• No difference (even in twice daily trilostane) - Baker et al 2005
○ Trilostane: Median survival 662 days
○ Mitotane: Median Survival 708 days
102
Name 2 other (less common) treatments for PDH.
1. Ketoconazole (at high doses will inhibit steroid synthesis)
2. Selegiline (L-deprenyl) - Increased dopamine in brain to slow ACTH production
103
What are the 3 options for adrenal dependent HAC?
1. Surgery (unilateral adrenoectomy - high risk sx but excellent outcome possible)
2. Mitotane: Cytotoxic to primary adrenal tumor and mets (most tumors are resistant to cytotoxic effects)
3. Trilostane: Comparable median survival with mitotane, only 1 dog officially in literature
104
What percentage of dogs with PDH had large pituitary masses causing clinical signs?
10-20%
105
Of dogs that have or will have neurologic signs associated with their PDH, what is the breakdown?
1. 15% have neurologic signs at diagnosis (due to large pituitary tumor)
2. 35% will exhibit signs in 30-120 days after medial treatment started
3. 50% exhibit signs more than 6 months after medical tx
106
What percentage of dogs with PDH developed seizures?
Less than 50%
107
What helps you determine whether to use MRI or CT for PDH large pituitary tumor?
MRI for small tumors (8mm)
108
When is radiation therapy the best for pituitary tumors in dogs with PDH?
Most effective in dogs with no or minimal CS and relatively small pituitary tumors (<15 mm)
109
Do dogs still require medical management for PDH if they undergo radiation?
Yes, so do! Transient resolution of CS but NOT permanently resolved!
110
Besides cortisol, what can result in CS of HAC?
Excess progesterone or 17-hydrozyprogesterone = Marked intrinsic glucocorticoid activity
111
What is the general principle behind the ACTH stimulation test?
○ Relies on assumption that hyperplastic or neoplastic adrenals have large reserves of cortisol and therefore respond to ACTH administration with maximal stimulation
112
What percentage of dogs with PDH and ADH will have a positive ACTH stimulation test?
85-90% PDH dogs
| 50% of ADH
113
What are the 2 main advantages of the ACTH stimulation test?
1. Differentiate iatrogenic from spontaneous HAC
| 2. Less affected by stress than LDDS
114
What are the 2 main disadvantages of ACTH stimulation test?
1. Cannot distinguish btwn PDH from ADH
| 2. Low sensitivity (cannot be used to exclude HAC, so if it is normal this does NOT rule out HAC)
115
Why is the LDDST a better screening test for HAC compared to an ACTH stimulation test?
More sensitive, 95%
116
What is the basis of the LDDST?
Adrenal tumors function independently of ACTH
Hyperplastic or neoplastic pituitary gland is resistance to feedback
THUS BOTH conditions should FAIL TO SUPPRESS, compared to a normal dog that will exhibit negative feedback on ACTH when dex (steroid) given
117
Why can the urine cortisol:creatinine ratio be used to rule out HAC?
High sensitivity but low specificity (many nonadrenal illnesses can result in an increase) – use this to rule out HAC
118
What will occur with adrenal steroid hormones after ACTH stim in a dog with classical HAC?
Along with elevation in cortisol, you will see Typically have at least 1 sex hormone that is increased along with cortisol Usually 2-3 sex hormones are increased (rare to have all of them increased)
119
What is known about 17-Hydroxyprogesterone compared to cortisol in dogs with classical HAC?
○ Elevated after ACTH stim in 55-85% of HAC dogs (less sensitivity than cortisol with ACTH)
120
What will occur with adrenal steroid hormones after ACTH stim in a dog with nonadrenal illness?
• 17-Hydroxyprogesterone after ACTH stim - Elevated in 31% of dogs with nonadrenal illness
○ LOWER specificity
• Cortisol after ACTH-stim - Elevated in 9% of dogs with nonadrenal illness
• Pheochromocytomas - Can also have elevations in sex hormones (more studies are needed)
121
What will occur with adrenal steroid hormones after ACTH stim in a dog with atypical HAC?
• Serum cortisol – assessed by UC/C, ACTH-stim and LDDST – is within or below the RR
○ Reason for hypocortisolenia is poorly understood
§ If adrenal tumor: Maybe mutation that blocks cortisol production
• Other adrenal steroid hormones, however, are increased (1.5 to 2x above RR) in at least 2, preferably 3 adrenal steroid hormones is consistent with diagnosis of atypical hyperadrenocorticism
122
In what tumor type is it more likely to be insufficient conversion of cholesterol to cortisol, but elevation in other adrenal steroid hormones?
```
Adrenocortical carcinomas (reported in humans too)
Interesting that adrenocortical adenoma are VERY good at making cortisol!
```
123
What is Alopecia X?
• Adult-onset alopecia that may be caused by mild HAC
• Affects Nordic breeds (Malamute, Chow, Keeshond, Pomeranian, Samoyed, Siberian Husy) and the miniature poodle
• Mild form of HAC suspected as cause
○ Many dogs have increased serum sex hormone concentrations – basally and after ACTH-stim
124
What are common breeds that get Alopecia X?
Nordic breeds (Malamute, Chow, Keeshond, Pomeranian, Samoyed, Siberian Husy) and the miniature poodle
125
What are 3 indications for performing an adrenal steroid panel?
1. Dogs with CS and lab evidence of HAC but inconsistent or borderline test results
2. Animals with adrenal masses that do not respond to ACTH stim or LLDST
3. Dogs with suspected Alopecia X
126
What does the UT Adrenal Panel include?
Androstenedione, estradiol, progesterone, 17-hydroxyprogesterone, aldosterone
127
Is melatonin an effective treatment for atypical HAC?
There is no evidence at this time
| It may be helpful in dogs with alopecia X
128
What treatment options are available for dogs with atypical HAC?
Medical (mitotane, trilostane, +/- melatonin)
| Surgical (if adrenal mass)
129
What is relative adrenal insufficiency?
Transient inability of adrenal gland to mount an appropriate cortisol response to sever stress of illness
130
What occurs in septic humans with relative adrenal insufficiency?
• Septic humans = Refractory hypotension and death
| ○ Supraphysiologic steroids can be life saving
131
What value has been suggested to be measures in cases of relative adrenal insufficiency?
Delta cortisol (change in cortisol from baseline to post-ACTH)
132
What ACTH stim result is suggestive of relative adrenal insufficiency?
A high cortisol to start and blunted response is diagnostic for RAI
133
What is the treatment for relative adrenal insufficiency?
Supraphysiologic steroids
134
What is hypoadrenocorticism?
• Deficiency of mineralocorticoid and/or glucocorticoid production by the adrenal cortices
135
What percentage of the adrenocortical function must be gone to have clinical signs of hypoadrenocorticism?
At least 90% (under nonstressful conditions)
136
What are the 2 types of hypoadrenocorticism?
1. Primary: idiopathic and spontaneous, likely due to immune mediated destruction ○ Iatrogenic – due to mitotane or trilostane therapy
○ Destruction – very rare, due to granulomatous disease, metastatic neoplasia or hemorrhage
○ Atypical – subset of dogs with primary hypoadrenocorticism
§ Selective glucocorticoid deficiency
§ Mineralocorticoid deficiency usually develops
2. Secondary: ue to insufficient pituitary ACTH production and atrophy of the adrenal cortices ○ Affects regions that synthesize glucocorticoids and mineralocorticoids usually normal
137
What is atypical hypoadrenocorticism?
Subset of dogs with primary hypoadrenocortisim
§ Selective glucocorticoid deficiency
§ Mineralocorticoid deficiency usually develops (some dogs)
§ Due to: iatrogenic rapid discontinuation of long-term or high dose of steroids, pituitary or hypothalamic lesions, idiopathic isolated ACTH deficiency
138
What 2 breeds have a genetic predisposition to hypoadrenocorticism?
Standard poodle and beared collie
139
What other breeds may have a predisposition to hypoadrenocorticism?
NSDTR, Leonbergers, PWD, Great Danes, Rottweilers and Wheaten and WHW terriers
140
Which sex is more likely to have hypoadrenocorticism?
Females (2X more likely)
141
What test is the gold standard for diagnosing hypoadrenocorticism?
ACTH stimulation test
| Over 75% will have post - < 2 mcg/dl
142
How can plasma ACTH help to differentiate from primary to secondary hypoadrenocorticism?
If high ACTH = Primary hypoadrenocorticism
| If low ACTH = Secondary
143
What 2 other tests can help to differentiate from primary to secondary hypoadrenocorticism?
Cortisol to ACTH level (secondary>primary)
| Aldosterone to renin ratio (secondary > primary)
144
What percentage of hypoadrenocorticism dogs will have a N/K ratio < 27?
About 95%
145
What are the two options for mineralocorticoid supplementation in dogs with hypoadrenocorticism?
1. DOPC (desoxycortiosterone) - Given every 3-4 wks
| 2. Fludrocortisone (Florinef) - Given daily
146
What needs to occurs in animals in times of stress that have hypoadrenocorticism?
They need to be given 2-10 times their normal prednisone/prednisolone dose! Owner should have plenty of extra steroid at home
147
How does acidosis result in hyperkalemia?
With severe acidosis = hyperkalemia result because of intracellular buffering of H+
148
What are the majority categories of disease that can result in hyponatremia and hyperkalemia?
```
Hypoadrenocorticism
Renal Disease (AKI, CKD, urethral obstruction, urinary tract rupture)
Vomiting and diarrhea
Acidosis
Cellualr Trauma (injury, tumor lysis syndrome, extensive sx)
Effusions
CHF
Diuretic therapy
Syndrome of Inappropriate ADH secretion
```
149
Which lab artifact can result in hyponatremia?
Lipemia (hyperlipidemia)
150
Which breed of dog RBCs can have high intracellular K+ levels?
Akita
151
What sex is canine diabetes more common in?
Females
152
What is the hallmark of canine diabetes?
Absolute insulin deficiency associated with increased glucagon concentration = Hyperglycemia (increased hepatic production and lack of peripheral use of glucose) o When BG exceeded renal threshold (180-220 mg/dl) = Osmotic diuresis → secondary polydipsia
o Fatty acid mobilization = Increased production of ketoacids (liver) because peripheral tissue is energy starved
o Lack of effects of insulin on lipoprotein lipase and hormone-sensitive lipase (facilitate storage of FA in adipocytes) = Increased production of keotacids
o When ketoacids exceed quantity used for energy metabolism → acidemia (spillover of ketones into urine = Polyruia)
o Reduces FA deposition into adipocytes and decreases incorporation of AA to form protein → Catabolic State (weight loss despite adequate or excessive food consumption)
153
What occurs with glucagon in canine diabetics?
Increased glucoagon: Glucagon is thought to be increased since the alpha cell response to hyperglycemia (normally would be decrease) but this progress likely needs insulin
154
What percentage of uncomplicated diabetes will have ketonuria?
66% of dogs
155
What type of insulin will result in 2 peaks of insulin activity?
Lente insulin: contains 30% short acting insulin (Semilente) and 70% long acting insulin (Ultralente) – Absorbed in dogs = 2 peaks of insulin activity (earlier peak leading to high insulin concentration)
156
What is required by virtually ALL diabetic dogs?
INSULIN
157
How does recombinant human insulin compare to canine insulin?
1 AA difference from canine insulin
158
How does porcine insulin compared to canine insulin?
Identical AA sequence to canine insulin = Less antigenic in dogs!
159
What does NPH stand for?
Neutral Protamine Hagedorn (NPH) - recombinant human insulin
160
Name 2 types of intermediate duration insulins.
1. NPH (Neutral protamine hagedorn - recombinant human insulin
2. Porcine lente insulin (Vetsulin) - Approved in dogs
161
Name 2 types of long duration insulins.
1. Protamine Zinc Insulin (PZI) - NOT recommended in dogs
| 2. Glargin (Lantus) - Human insulin analog
162
What does PZI stand for?
Protamine Zinc Insulin
| Contains 90% beef and 10% porcine insulin (more antigenic!!)
163
What is Lantus?
Glargine - Human insulin analog (AA asparagine replaced by glycine with α-chain and 2 arginine molecules added to C-terminus of β-chain)
164
Which insulin cannot be mixed and why?
Glargine (Lantus)
| In vial pH 4 (insulin solution forms crystals that are absorbed slowly when injected SQ into environment that has pH 7)
165
What s the ideal starting of insulin in dogs?
Start with intermediate duration insulin (NPH or porcine lente/Vetsulin) = 0.25 U/kg SQ q12hrs
166
What is important to note about the handheld glucose meters?
Can underestimate serum/plasma glucose by 10-15%
167
What are the goals for nadir and maintaining BG in diabetic dogs?
§ Nadir: 80-150mg/dl
| § Maintain BG: <250-300 mg/dl
168
What is a limitation of fructosamine levels in diabetic dogs?
Can have overlap in fructosamine in well controlled dogs and in poorly controlled dogs
169
What is a limitation of glucose curves?
There can be day to day variation in glucose curves
170
What is considered to be adequate glycemic control in diabetic dogs?
Resolution of PU/PD, maintence of BW, normal appetite, lack of hypoglycemia
171
What are the goals in canine diabetes?
Maintain acceptable pet and prevent formation of diabetic cataracts
172
What is the average life span of dogs with diabetes?
About 3 yrs
173
What percentage of dogs will develop cataracts?
Most within 5-6 months of diagnosis, 80% by 16 months of diagnosis
174
How is Type II diabetes in humans different than feline diabetes?
Humans have persistent BG > 126 (dt microvascular complications at high BG) - thus majority of humans can be managed with oral hypoglycemic drugs (NOT TRUE IN CATS)
175
What is the problem with BG being below the renal threshold but persistently above normal (180-216 mg/d)?
Adverse effects = glucotoxic damage to b cells in cats
176
What type of diet is recommended in feline diabetes?
Low carbohydrate, high protein diet (unless renal disease) - diets can significantly reduce BG
177
What the major disease in feline diabetes?
Failure of b cells (stage depends on the number of Beta cells that have been lost)
178
What type pf diabetes do the majority of cats have?
Type II Diabetes = Relative lack of insulin secretion and insulin resistance (estimated to be about 6X less sensitive to insulin - similar to humans = MULTIPLE mechanisms)
179
What are less common causes of feline diabetes?
Beta cell destruction from pancreatitis or neoplasia, marked insulin resistanbce from excessive growth hormone or corticosteroids
180
Name 4 things that influence insulin resistance.
1. Obesity: Marked decreased in insulin sensitivity in cats (4-6 kg increased can result in 1/2 of insulin sensitivity)
2. Physical Inactive
3. Genetics: Burmese cats (underlying insulin resistance)
4. High BG contribute to insulin resistance (decreased BG = Increased insulin sensitivity)
181
What breed is at an increased risk of diabetes?
Burmese cats (Australia, NZ, UK) - Underlying insulin resistance
182
What results in beta cells in Type 2 diabetes?
Apoptosis is triggered by chronic hyperfunction secondary to insulin resistance AND islet amlyoid deposition
183
Name 4 processes that result in impaired insulin secretion.
1. Loss of beta cells (apoptosis triggered by chronic hyperfunction secondary to insulin resistance AND islet amyloid deposition)
2. Reversible suppression of insulin secretion (Glucotoxicity and lipotoxicity)
3. Chronic hyperglycemia irreversibly damages Beta cells = LOST - - insulin dependent diabetes
4. Loss of Beta cells = Pancreatitis (about 50% have evidence of pancreatitis) - May contribute to Beta cell loss
184
If there is no insulin resistance, when will CS of diabetes occur?
When 80-90% of Beta cells are lost (if insulin resistance = CS sooner with smaller loss of beta cells)
185
What percentage of more insulin is required to maintain fasting BG in a obese cat compared to when they were lean?
Estimated to be about 30% more insulin would be required to overcome the obesity-induced insulin resistance
186
What is diabetic remission in cats?
Within days to months o starting insulin - proportion of diabetic cats will maintain euglycemia WIHTOUT tx
Requires that functional Beta cells to attain remission - thought to be reversal of glucotoxicity and lipotoxicity leading to remission
187
Can cats that have achieved diabetic remission relapse?
YES! Can be in weeks to months - Need to monitor closely, but if early reinstitution of insulin - MANY cats can again achieve remission
188
What are the mainstays in management of feline diabetes?
1. Dietary modification (low carb)
2. Insulin
3. Address risk factors (obesity, physical activity)
4. Oral hypoglycemic drugs
189
What is the ideal diet for feline diabetes?
Low carbohydrate diet, needs diet that spares Beta cell function
190
What is the preferred long acting insulin in cats?
Glargine
191
What combination leads to remission rates >80-90% in feline diabetes?
Glargine and low carb diet (5% carbs, Purina DM canned)
192
Which insulin should be selected in feline diabetes to try to get remission?
Glargine
193
What is the remission rate for other insulins in feline diabetes?
Remission rates of about 20-30% with standard diets
194
What is the remission rate for PZI or lente insulin with low card diet?
Remission rate of about 60%
195
Why is a ultra-rapid insulin unlikely to be used in cats?
Cats have a prolonged postprandial period (12-24 hours)
196
How is Glargine produced?
Recombinant DNA technology using E. coli
197
What results in glargine's LONG duration of action?
Glargine forms hexamers and microprecipitates that depost in tissue → slowly breaks down = releasing monomeric glargine into solution = LONG duration of action
® CANNOT be diluted or mixed with other insulins
198
What is the ideal starting dose of glargine in cats?
0.5 U/kg q12hrs, NOT to exceed 3U/cat q12hrs (if able to monitor for hypoglycemia)
If no monitoring - consider starting at 1U/cat q12hrs
199
If you have a cat on >25U insulin per cat q12hrs, what should you consider?
Hyperadrenocorticism or acromegaly (hypersomatotropinism)
200
What does of insulin can cats with almost normal Beta cell function tolerate?
0.5-1U q12-24hrs and rarely develop CS of hypoglycemia
| · Do NOT stop insulin within 2 weeks of starting it → To facilitate β-cell recovery from glucotoxicity
201
What are alert you that a diabetic remission may be present?
· Once pre-insulin BG ≤180 mg/dl and total dose decreased 0.5-1U q12hrs → Reduce dose to q24hrs
202
If using water drunk by feline diabetic what values are important?
<60 ml/kg/24 hour with dry food
203
What are the general mechanisms of oral hypoglycemic agents?
· Stimulating β-cells to secrete insulin, ↑ insulin sensitivity, or ↓glucose absorption from GIT
204
Name 2 hypoglycemic agents for feline diabetes?
1. Glipizide → Acts by stimulating β-cells (lower diabetic remission, consider for patients that need very little insulin or owners that cannot give injections)
2. Acarbose → Inhibits brush-border glycosidase activity in intestine and reduces postprandial BG (esp if given low carb diet) - Consider in patient that needs low protein igh carb diet (renal dz)
205
If you aim to keep BG <200 mg/dl in diabetic cats and feed low carb high protein diet, what percentage will achieve diabetic remission?
About 90% of newly diagnosed diabetic cats
206
Name the 4 MOA of oral hypoglycemic agents?
1. Supress hepatic glucose production = Thiazolidinediones
2. Promotes insulin secretion from pancreas = Sulfonylureas (glipizide)
3. Impairs starch digestion and glucose absorption from intestine = Acarbose
4. Improved insulin sensitivity = Vanadium/chromium
207
What can occur in canine diabetes that is a risk factor for development of pancreaitis?
§ Diabetic = Abnormalities in Lipid Metabolism (due to lack of insulin production) – Hypertriglyceridemia, hypercholesterolemia, increased lipoproteins, chylomicrons, free fatty acids
o Hypertriglyceridemia = RISK OF PANCREATITIS (complicating management of diabetes)
208
What micronutrient is needed for synthesis, storage, and secretion of insulin?
Zinc
209
What are considerations in feeding a dog with diabetes?
Low fat and high fiber (need to consider fiber type) diet
Feeding based on insulin administration
Most dogs are thin, so need to consider this as well
210
Which AA can act as a potent insulin secretagogue?
Arginine (some other AA too) - May lead to remission
211
What is serum fructosamine?
§ Indicator of glycemic control in dogs and cats (on serum) – Product of irreversible reaction btwn glucose and amino groups of plasma proteins = Assumes that concentration reflects the mean blood glucose concentration in proceeding 1-2 wks
212
What can decreased fructosamine values in dogs?
Hypoproteinemia, hyperlipidemia, azotemia
213
What can decreased fructosamine values in cats?
Hyperthyroidism
214
What is considered to be a significant difference in fructosamine values?
§ Difference btwn values need to exceed 50 umol/L to reflect a clinically significant difference in glycemic control
215
What range of fructosamine is associated with good control?
360-450 umol/L
216
What range of fructosamine is associated with moderate control?
450-550 umol/L
217
What range of fructosamine is associated with poor control?
> 600 umol/L
| Consider insulin underdosage, too short duration of insulin, dz resulting in insulin resistance, Somogyi phenomenon
218
What should you give priority to CS, glucose curve, or fructosamine?
CS over fructosamine
219
What is the corenerstone of glycemic control on humans?
```
Glycated hemoglobin (formed by nonenzymatic, irreversible attachment of glucose to protein amino groups)
Reflects average BG over lifespan of RBC (100-120 days in dogs, 70 days in cats) = Not validated in cats and dogs
```
220
Name 5 goals of a 12 hour glucose curve.
Enable the assessment of insulin efficacy, glucose nadir, time of peak insulin effect, duration of effect of insulin, degree of fluctuation in BG
221
How long can the counter-regulatory hormone phase of Somogyi phenomenon last?
LAST up to 72 hours
222
What is the renal threshold in dogs and cats?
renal threshold (180 mg/dl in dogs; 300 mg/dl in cats)
223
Name 5 risk factors associated with obesity?
1. Peak age = middle age
2. High associated with gonadectomy
3. Gender: FS in dogs, and MC in cats
4. Breeds: Goldens, dachshund, Shetland Sheepdogs, Labs, Cocker spaniel, Dalmatian
5. Environmental: Sedentary lifesytle, ad lib feeding
224
What disease can contribute to obesity?
Hypothyroidism (decreased metbaolic rate and energy output)
225
How are adipose tissue consider an endocrine organ?
Over 50 proteins/hormones needed to be secrete by adipocytes (leptin - maintaining satiety; resisin; decreased adiponectin which may have beneficial effects)
226
What are the two forumlas to calculate RER?
□ RER=70(BWkg0.75) OR RER = (30 × BWkg) + 70 (if > 2kg)
227
What are the ideal factors to multiple RER by for weight loss in dogs and cats?
○ Canine DER for weight loss=1to1.2×RER
| ○ Feline DER for weight loss=0.8×RER
228
What is the main control center for controlling satiety?
Hypothalamus = Influenced by nutrients, hormones, intestinal peptides, nerve signals (vagal and sensory nn)
229
What drugs have been shown in dogs to be effective tool for weight loss and what is their MOA?
§ Slentrol (Dirlotapide, Pfizer) and Yarvitan (Mitrataide) → Microsomal triglyceride transfer protein (MTP) inhibitors = Selective for the intestine (blocking MTP activity and intraluminal transport of fat across enterocyte – loss of fat into feces)
® Lipid accumulation in enteroctes = Increased release of potent satiety signals (pancreatic peptide YY; PYY) and inhibition of voluntary eating
® 90% wt loss attributed to appetite control
230
Why can slentrol or yarvitan be used in cats?
These medications control microsomal triglyceride transfer protein that selectively black intestinal transport of fat across enterocytes = Species SPECIFIC!!!
Result in Hepatic lipid accumulation in cats (and humans)
231
What are the 6 major categories for diabetic complications?
1. Diabetic nephropathy
2. Diabetic Neuropathy (peripheral and autonomic)
3. Susceptibility to infection (urinary, pulmonary, etc)
4. Hepatic and pancreatic disease
5. Diabetic ocular problems = Cataracts
6. Hypoglycemia complications
232
Which species is more likley to get diabetic nephropathy?
Cats - microalbuminemia, systemic hypertension
233
Which species is more likely to get diabetic neuropathy?
Cats - plantigrade stance (motor and sensory defects, nerve conduction abnormalities and myelin degeneration on nerve biopsy)
234
What percentage of dogs with DM had evidence of an occult UTI?
50% - NO evidence of pyruia or bacteria = Need to culture EVERY diabetic dog!!
235
What percentage of diabetic patients have concurrent pancreatitis?
About 40% of dogs and about 50% of cats
236
What is the classic ocular complications of diabetes?
Cataract formation in dogs (rare in cats)
237
What is the pathogenesis of cataract formation in diabetic dogs?
In the eye glucose is rapidly converted to sorbitol (aldose reductase) and slowly to fructose (polyol dehydrogenase)
Dogs - accumulation of sorbitol within lens fibers = Imbibing water = swelling and opacity to lens
Older cats = Reduced aldose reducatase activity (less likely to get cataracts if diabetic)
238
Describe the pathogensis of DKA.
○ Hepatic lipid metabolism becomes deranged with insulin deficiency
§ Nonesterified FAs are converted to acetyl-CoA rather than being incorporated into TGs
§ Acetyl-CoA accumulates in the liver (acetoacetyl-CoA) and is converted to acetoacetic acid, beta hydroxybuturate (main ketone body in dogs and cats) and acetone
§ Accumulation of ketones, loss of electrolytes and water in urine à hypovolemia, metabolic acidosis and shock
□ Ketonuria and osmotic diuresis à loss of K+ and Na+ in the urine
□ Ketonemia triggers CRTZ – nausea, anorexia and vomiting
§ Stress hormones contribute to hyperglycemia
239
What are the 4 mainstays in treatment of DKA?
* **In order of importance***
1. Fluid therapy (0.9% saline with 2.5-5% dextrose as BG falls)
2. Insulin therapy (low dose IM or IV regular insulin)
3. Electrolyte supplementation (K+, Phosphorus, Mg)
4. Reversal of Metabolic Acidosis
240
What are the main electrolytes that are affected during DKA?
Potassium, Phosphorus, Magnesium
241
Which electrolyte can complicate refractory hypokalemia?
Hypomagnesemia
242
What is nonketotic hyperosmolar diabetes?
Extreme hyperglycemia (>600 mg/dl), hyperosmolality (>350 mOsm/L), severe dehydration, CNS depression, without ketone formation with no or only mild metabolic acidosis
243
What underlying diseases can common in patients with nonketotic hyperosmolar diabetes?
Underlying renal or CV disease
244
Name potential medical management of insulinomas?
1. Streptozotocin (destroys pancreatic beta cells) - Results in acute renal failure (need diuresis)
2. Alloxan (direct toxic effect on beta cells) - Renal tubular necrosis (diuresis)
3. Doxorubicin
4. Feed frequent meals (high in protein, fat, and complex carbs)
5. Glucocorticoids (low dose) - Increased glyconeolysis
6. Diazoxide (decreased insulin secretion, promotes gluconeogensis and glycogenolysis, inhibits cellular uptake of glucose)
7. Octreotide (somatostatin analogue) - Inhibits secretion of insulin, glucagon, gastrin, secretin, motilin
245
What are the 2 substances that allow insulin analoges to form hexamers?
Zinc and protamine
246
Name 3 rapid-acting insulin analogs.
Lispro, aspart, and glulisine
247
What can result in glargine's relatively unpredictable action?
The precipitation-deprecipitation process (soluble at pH4 and precipates are pH 7 in tissue)
248
What allows for detemir's protracted and more predictable effect?
It has a myristic acid residue that allows it to interact with fatty acids and albumin = acting as a buffer for the concentration of detemir in the blood and tissue
249
What result in detemir's ability to have higher concentrations in the liver compared to other insulin analoges?
Interaction with albumin (in organs that have fenestrated capillaries like the liver)
250
What is idiopathic hypercalcemia?
Abnormally elevated serum ionized Ca (iCa), the cause of which remains unknown
251
How accurate is the prediction of iCa status from tCa measurement?
NOT accurate!
252
What occurs in parathyroid independent hypercalcemia?
Suppression of PTH from elevated iCa
253
What are the 2 most common diagnoses in cats with hypercalcemia?
Idiopathic hypercalcemia and malignancy (PTHrp)
254
Is iCa elevated in renal failure?
Although tCa is elevated, iCa is rarely elevated
255
Which cat breed is over-represented in idiopathic hypercalcemia?
Long-haired cats
256
What is the serum phosphorus of cats with idiopathic hypercalcemia?
Normal range; unless increased as a result of concurrent CRF
257
Which cells find calcium toxic?
CNS, GIT, heart, kidney
258
When is the risk of soft tissue mineralization high?
When the Ca x Phos > 60
259
How do glucocorticoids reduce iCa?
§ Decrease intestinal absorption of Ca++
§ Decrease renal tubular Ca++ reabsorption
§ Decrease skeletal mobilization of Ca+
260
What is the risk of CaOx stone formation in cats that are given a glucocorticoid?
Unknown how increased urinary 2+ excretion affects risk of CaOx stone formation
261
What is the MOA of alendronate?
Bisphosphate - reduces number and function of osteoclasts after they bind to hydroxyapatite in bone
262
What are potential side effects of bisphosphates?
```
Neprhotoxicity
Erosive esophagitits (seen in humans)
```
263
What is a calcimimetic?
A drug that interacts with Ca2+ receptors directly and lower iCa, phosphorus, and PTH (used in human dialysis patients)
264
Name the mainstays of treatment of hypercalcemia.
1. Diet change (renal diet, CaOx diet, +/- high fiber diet?)
2. Glucocorticoids (low dose)
3. Bisphosphonates (pimidronate, alendronate)
4. Others: fluids, lasix (acute only), calcimimetics
265
What are the hallmarks signs of hypoparathyroidism?
Low PTH → Hypocalcemia, hyperphosphatemia, decreased calcitriol
266
What is hungry bone syndrome?
Hypocalcemia unrelated to low PTH, may arise from uptake of Ca into bone following rapid correction of long-standing hyperparathyroidism or hyperthyroidism
267
What are the 2 main ways that Mg2+ plays a role with PTH?
Hypomagnesemia may result in:
1. Blunts maximal PTH secretion
2. Increased end-ogran response to PTH
3. May impair calcitriol synthesis
268
What is the most common cause of hypoparathyroidism in dogs and cats?
Absence or destruction of parathyroid gland
269
How does hypocalcemia affect neuromusclar tissue?
Hypocalcemia results in increased excitability of neuromuscular tissue
270
What are common CS of hypocalcemia?
Muscle tremors/fasiculations, muscle cramping, stiff gait, focal facial twitching, seizures, pawing at face
271
Which electrolyte abnormality as you are correcting it can worsen CS of hypocalemia?
Hypokalemia
272
What is the classic panel for primary hypoparathryoidism?
Hypocalcemia, hyperphosphatemia, low PTH with normal renal function
273
Name 3 conditions that can result in low Ca2+ and high phorphorus. What is the PTH in these conditions?
1. Nutritional or renal secondary hyperparathyroidism
2. Phosphate containing enema
3. Tumor Lysis Syndrome
In all examples the PTH will be INCREASED
274
What electrolyte should be measured if you are concerned about a functional hypoparathyroidism?
Magnesium - iMg can be low in 75% of dogs and cats with primary hypoparathyroidism
275
What percentage of dogs and cats with primary hypoparathyroidism have concurrent low Mg?
About 75%!!! Make sure to check Mg in hypoparathyroidism patients
276
What is essential following a post-sx hypoparathyroid animal?
You need to keep that serum calcium on the low side to maximize compensatory hypertrophy of remaining parathyroid glands
277
What are the two mainstays in treatment of hypoparathyroidism?
Calcium Salts and calcitriol
278
What are the 3 risk factors for development of severe hypocalcemia following parathyroidectomy?
1. High levels of Ca2+
2. High levels of PTH
3. Elevated bone ALP
= Results from chronic suppression of other parathyroid glands and Ca2- uptake into ""hungry bones""
279
What should be given to a patient undergoing parathyroidectomy and when should it be given?
Calcitriol should be given
If pre-op severe hypocalcemia - consider giving calcitriol several days before since there is a lag time until maximal effect with calcitriol
280
What is important to consider when administering IV calcium salts?
Need to dose based on the available elemental calcium in the solution
281
What are CS that cardiac toxicity may be occurring during Ca infusion?
○ Bradycardia, sudden ST elevation, shortening of QT or VPCs
Suggests that you are giving the Ca2+ too quickly, may take 30-60 mins to see these CS resolve, even if stopping the infusion
282
What is the treatment of choice for tetany or seizures from hypocalcemia?
IV calcium salts (Ca gluconate or Ca chloride)
283
What is recommended until oral medications provide calcium control for hypocalcemia?
CRI of calcium salt (Ca Gluconate = 9.3 mg elemental Ca2+ per ml)
284
Name 4 things that Ca2+ cannot be in fluids with.
1. Lactate
2. Phosphate
3. Bicbaronate
4. Acetate
All will result in precipitation!!
285
Why is q12hrs dosing recommended for calcitriol?
○ Calcitriol only programs undifferentiated cells in the crypts of Lieberkuhn, which turn over q24hrs, thus q12hrs dosing is recommended to ensure sustained priming effects on intestinal epithelium for calcium transport
286
What is another drug that used to be used in place of calcitriol?
Ergocalciferol (Vitamin D2) - decreased avidty to Vit D receptors, long T1/2 (bad for hypcalcemia and dose corrections)
287
Supplemenation with which electrolyte can result in decreased required doses of calcium and calcitriol?
Magnesium!!!
288
What can be given to a patient to reduce hypercalciruia seen in hypoparathyroid patients?
Can give thiazide diuretics = Debatable effect in dogs, unknown in cats
289
What is the target calcium level when treating hypoparathyroidism?
Target – just below RR of total serum Ca2+
○ Prevent hyperCa2+ and minimize hypercalciuria since these patients are missing renal effects of PTH, also maintain stimulus for any remnant PTG tissue
290
What CS would owners see in a patient on calcitriol that may indicate hypercalcemia?
PU/PD, anorexia, vomiting, depression = They should have the iCa checked ASAP!!
291
What are the mainstays in treatment of hypercalcemia secondary to calcitriol supplementation?
Stop calcitriol
Hospitalize on IVF, furosemide, steroids, +/- bisphosphates or calcitonin
Need to restrict dietary calcium!
292
After thyroidectomy (cats) or parathyroidectomy (dogs) when can you expect to start tapering calcitriol?
Try within 1 month
○ When does function usually return (if at all)
§ Cats – within 2 weeks, but sometimes as long as 3 months
§ Dogs – 6 to 12 weeks
293
When is permanent hypoparathyroidism likely?
If patient cannot maintain normoCa2+ following taper of calcitriol at 3 months post-op
294
Name several carcinomas that can result in hypercalcemia.
Lung, mammary, nasal, pancreas, thymus, thyroid, vaginal and testicular
295
What do most hypercalemic lymphoma dogs have?
Mediastinal mass with no peripheral lymphadenopathy
296
What are the most common granulomatous diseases that result in hypercalcemia?
Blastomycosis, histoplasmosis, schistosomiasis
297
What percentage of primary hyperparathyroid dogs get cystic calculi?
About 30%
298
What is the classic signalment for canine primary hyperparathyroidism?
6 yr old (mean 11.2 yrs) with hypercalcemia found incidentally
299
What percentage of primary hyperparathyroid dogs will have no specific PE findings or CS?
About 71%
300
What are the two most common CS in hyperparathyroid dogs?
CS associated with urolithiasis or UTI and PU/PD
301
Why do most rDVMs refer dogs that are ultimately diagnosed with primary hyperparathyroidism?
Concern for development of renal failure = But in study this is NOT supported and some dogs went 2-3 yrs without treatment and did not develop renal failure!
302
What two abnormalities are noted in about 30% of dogs with primary hyperparathyroidism?
UTI (30%)
Cystic calculi (30%)
Both are reasons that a patient should be treated!
303
Which is neoplasias will result in an increased serum PTHrp?
Lymphoma and apocrine gland carcinoma of anal sac
304
What noninvasive diagnostic can be performed to localize parathyroid tissue causing hyperparathyroidism?
Cervical ultrasound (depends on skill of the imager)
305
What are the 2 main treatments for primary hyperparathyroidism?
1. Surgery (96% complete resolution)
| 2. Percutaneous US Guided Heat Ablation)92% complete resolution with 1 treatment)
306
What is the recurrence of hyperparathyroidism after treatment?
About 10% regardless of histology
| Classified as adenoma, carcinoma, or hyperplasa = ALL biologically similar!
307
Name 3 reasons to start calcitriol in patients with primary hyperparathyroidism.
1. Total Ca2+ < 8mg/dL or iCa++ 15mg/dL – start calcitriol day of or after surgery
308
What % of CKD cases have increases in tCa and iCa?
tCa: 10-15% of CKD
iCa: 30% (cats), 10% (dogs)
309
What is appropriate for a presumptive dx of idiopathic hyperCa in cats?
Low PTH and high iCa
310
What is the current tx for idiopathic hyperCa in cats?
Diet change (renal or CaOX prevent diet)
Bisphosphonates (alendronate PO, zoledronate IV)
LAST - Steroids!
311
What complication has been seen in humans taking alendronate?
Erosive esophagitis (not seen in cats, but need to fast and follow with water)!
312
What is the current tx for idiopathic hyperCa in cats?
Diet change (renal or CaOX prevent diet)
Bisphosphonates (alendronate PO, zoledronate IV)
LAST - Steroids!
Unknown effects: adding NaCl to diet, Fluids (SQ), calcimimetics
313
What complication has been seen in humans taking alendronate? What is a long term complication?
```
Erosive esophagitis (not seen in cats, but need to fast and follow with water)!
NOTE: Tuna juice will decreased absorption
```
Long term: Osteonecrosis of jaw (25% beagles given it for 3 yrs, more with IV zoledronate than alendronate PO, not seen in cats that have been on it for several yrs)
314
What is the inly known function of iodine in the mammals?
Synthesis of thyroid hormones
315
Why should methimazole NOT be used with idonine restricted diets?
Risk of hypoT4
316
What is a diet that is used to manage feline hyperT4?
Hills y/d
iodine restricted to 0.3ppm (ok in early CKD)
90% cats had normal TT4 within 4-8 wks of feeding (no change in renal parameters)
317
What is the most common reason for treatment failure with dietary management of hyperT4?
Access to idodine (food, treats, meds, water, etc)
318
What are the long term affects of feeding a iodine restricted diet?
Unknown (need to monitor)
| Goiter (same as methimazole)
319
Has hypoT4 been reported in cats feed Hills y/d?
HypoT4 has not been reported in hyperT4 or healthy cats that have been feed y/d for up to one year
320
What is the prognosis with feeding y/d?
Unknown (reported up to 6 years)
321
What is a product that may be used in the future to prevent DM cataracts?
Kinostat (aldose reductase inhibitor) - Stop the formation of sorbitol from glucose and thus prevent cataract formation (NOT in US yet)
322
Which AA is consider an insulin secretogogue in cats?
Arginine (found in meat)
323
Which cats in the US are prone to DM?
Main Coon, DLH, Russian Blue, Siamese
324
Which cats in the US are prone to DM?
Main Coon, DLH, Russian Blue, Siamese
325
Which insulin when administered IM has similar effects to regular insulin?
Glargine (can be used in combination with SQ glargine for tx of DKA)
326
What are the most common dz that results in insulin resistance in DM cats?
Diabetogenic drugs (steroids), severe obesity, chronic pancreatitis, kidney failure, HyperT4, oral infections, acromegaly, hyperadrenocorticism
327
What are the most common dz that results in insulin resistance in DM dogs?
Diabetogenic drugs (steroids), severe obesity, HAC, dietrus, chronic pancreatitis, kidney failure, oral and urinary infections, hyperlipidemia, insulin antibodies (if beef insulin)
328
When comparing cats feed a low Carb diet and either PZI or glipizide, what was found?
Cats on glipizide responded the same as PZI (about 70%)
329
What are incretins?
GI hormones that increased insulin secretion (this is why PO glucose releases more insulin than IV glucose)
Glucagon like pepetide 1
Gastric Inhibitory Peptide
330
What is an example of an incretin and how does it work in cats?
Exenatide (analog of incretin) - Increased insulin release in healthy cats
331
What are incretins?
GI hormones that increased insulin secretion (this is why PO glucose releases more insulin than IV glucose)
Glucagon like peptide 1
Gastric Inhibitory Peptide
332
What is the only endocine dz that results in pruritic bilateral alopecia?
Hyperestrongenism
333
When using CT, what is the ratio of adrenal diameter that is suggestive of ADH?
>2.08
