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EV ACVD Study > Endocrinopathy (NAVDF 2021 Outerbridge) > Flashcards

Endocrinopathy (NAVDF 2021 Outerbridge) Flashcards

1
Q

Thyroid hormone pathway

A

Hypothalamus -> TRH -> Pituitary -> TSH -> Thyroid gland -> T3, T4

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2
Q

How is most T4 found in the blood

A

Most is bound to transport proteins.

Only 0.1% is fT4

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3
Q

How is most T3 made in the body

A

Peripheral tissue deiodinization of T4 (from I4 to I3)

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4
Q

How does T4 enter the cell

A

1) Passive diffusion
2) Active receptor-mediated transport

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5
Q

Which thyroid hormone binds the nuclear receptor

A

T3

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6
Q

What is primary hypothyroidism

A

At level of the thyroid
1) Lymphocytic thyroiditis (AA)
2) Idiopathic atrophy (degenerative)
—
3) Neoplastic
4) Congenital, iodine deficiency, I131, Drug (like TMS)

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7
Q

How much thyroid function must be destroyed prior to seeing clinical signs

A

75%

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8
Q

Which type of hypothyroidism is most common (primary, secondary, tertiary)

A

Primary

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9
Q

What is secondary hypothyroidism

A

At the level of the pituitary gland

Lack of TSH
1) Tumors, congenital, trauma, surgery

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10
Q

What is tertiary hypothyroidism

A

At the level of the hypothalamus

Lack of TRH

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11
Q

What clinical signs would you expect to see in a congenital hypothyroidism case

A

Poor growth and development

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12
Q

Signalment of hypothyroidism

A

Middle-aged (4-10yr)
Medium-large breed dogs

Dog leukocyte antigen (DLA) haplotypes associated with hypothyroidism
1) Doberman pinscher
2) Giant Schnauzer
3) Rhodesian Ridgeback
4) English Setter

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13
Q

Non-skin clinical signs of hypothyroidism

A
  • Muscle weakness
    -Myopathy
    -Peripheral neuropathy
    -Laryngeal paralysis
    -Megaesophagus
  • CNS signs with myxedema
  • Ocular: corneal lipid deposits
  • Reproductive
    -Prolonged anestrus
    -Prolonger parturition, higher puppy mortality
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14
Q

What causes myxedema coma in hypothyroid patients

A

Increase in myxedema in the brain itself!

Fatal!

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15
Q

Microscopic findings of hypothyroidism

A

*Sebaceous gland and follicular gland atrophy
*Failure to initiate anagen
*Disturbances to cornification

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16
Q

What causes facial myxedema in hypothyroid dogs

A

Increase in glycosaminoglycans in the dermis

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17
Q

Labwork findings in hypothyroidism

A

*Hypercholesterolemia
*Normocytic, normochromic, nonregenerative anemia
+/-
*ALP elevation
*CK elevation

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18
Q

What is the best test for hypothyroid diagnosis

A

fT4 + TSH

TSH increases the specificity of fT4

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19
Q

Which breed experiences “tiger striping” with hypothyroidism

A

Rhodesian ridgebacks

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20
Q

What is the value of a TT4 test

A

Screening tool

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21
Q

Why may a TT4 be low without true hypothyroidism

A

1) Old dog
2) Sight hound
3) Drugs
4) Concurrent illness

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22
Q

Why is TT3 not a good gauge for thyroid function

A

Most T3 is actually made by deiodination in the peripheral tissues, NOT by the thyroid

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23
Q

Clinical sign seen in 6/7 cats with spontaneous hypothyroidism

A

Bilateral goiter
Not all had skin lesions (but if they do, looks similar to dogs)

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24
Q

Which thyroid hormone has the most influence on TSH

A

fT4

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25
Q

T or F: fT4 is the predominant circulating hormone produced by the thyroid gland

A

False

TT4 decreases before fT4, so fT4 is more resistant to NTI influence

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26
Q

Is fT4 or TT4 more affected by non-thyroidal illness

A

TT4

TT4 decreases before fT4, so fT4 is more resistant to NTI influence

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27
Q

Which test is most accurate for fT4 quantification

A

Equilibrium dialysis.
RIA (radioimmunoassay) alone is not accurate enough

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28
Q

Is TSH more sensitive or specific

A

TSH is very specific, but not very sensitive for hypothyroidism

If you add TSH to fT4, it increases fT4 specificity!! Ideal!

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29
Q

T or F: TSH is always elevated in hypothyroid dogs

A

False

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30
Q

T or F: Dogs with nonthyroidal illness can have an elevated TSH

A

True

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31
Q

T or F: euthyroid dogs can have an elevated TSH

A

True. Transient when telling thyroid to make more T4

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32
Q

T or F: TgAA varies by breed

A

True
(low in Dobies, even with hypothyroidism)

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33
Q

T or F: Dogs with elevated TgAA but normal thyroid function should be monitored but NOT treated

A

True. Do not treat unless abnormal thyroid function

Lymphocytic thyroiditis can be slow– don’t need to treat yet

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34
Q

T or F: TgAA can interfere with other thyroid quantification assays

A

True, esp autoantibodies against T4 can be measured as elevated T4!

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35
Q

What thyroid values would you expect in a dog with nonthyroidal illness (like HAC)

A
  • Low TT4
    *Low T3 (less deiodination from T4 to T4)
  • TSH is normal, possibly increased
  • fT4 is normal, possibly decreased
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36
Q

Why is Total T4 decreased with nonthyroidal illness

A

1) Decreased T4 binding to transport proteins; reduced concentrations of transport proteins

2) Decreased TRH or TSH leads to decreased T4 production

3) Direct effects on thyroid gland -> suppressed T4 production

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37
Q

Next step in a dog you suspect has a nonthyroidal illness

A

Treat the nonthyroidal illness, then reassess thyroid once resolved

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38
Q

Effect of corticosteroids on thyroid

A

Decreased TT4

fT4, TSH is either decreased or no change

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39
Q

T or F: Glucocorticoid effect on thyroid function testing is dose and duration dependent

A

True

Longer on GCs, more impact on TT4

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40
Q

How long prior to thyroid testing should glucocorticoids be discontinued

A

At least 4 weeks

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41
Q

Effect of Sulfonamides on thyroid

A

*TT4, fT4, T3: Low
*TSH: High

TRUE HYPOTHYROIDISM –> reversible

TMS will decrease follicle function
Increase in TSH because no negative feedback from fT4

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42
Q

How long off Sulfa antibiotic prior to evaluating thyroid

A

3 weeks

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43
Q

T or F: KBr will influence thyroid values

A

FALSE. KBr should not affect thyroid values

PHENOBARB will (like GCs)

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44
Q

T or F: Response to thyroid supplementation can happen in a euthyroid dog

A

True

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45
Q

Which type of dog is more likely to develop iatrogenic hyperthyroidism

A

Large breed
(less likely if you do body surface area dosing)

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46
Q

Impact of estrogen on hair cycle

A

Estrogen inhibits anagen –> alopecia

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47
Q

Causes for hyperestrogenism in dogs

A
  • Testicular tumors (Sertoli, Seminoma, Interstital cell). Usually cryptorchid!
  • Cystic ovaries, granulosa cell tumors
  • Iatrogenic- estrogen (Incurin, estriol) for USMI
  • 2nd hand exposure to human topical estrogens, esp in small dogs
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48
Q

Clinical sign common in testicular tumor dogs

A

Linear preputial erythema or hyperpigmentation

Often cryptorchid

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49
Q

Pattern of alopecia on hyperestrogenism dogs

A

Perineal/perigenital –> progress to ventrum

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50
Q

Labwork finding of hyperestrogenism dogs

A

Bone marrow suppression
-Thrombocytopenia
-Anemia
-Leukopenia

51
Q

Hypothalamic-Adrenal pathway

A

Hypothalamus -> CRH -> Pituitary chromophores -> ACTH -> Adrenal gland -> Cortisol

Affects BOTH zona fasciulata and zona reticularis. BUT cortisol is only from fasciculata

52
Q

Which region of the adrenal gland makes cortisol

A

Zona fasciculata

53
Q

Which region of the adrenal gland responds to ACTH from pituitary gland

A

BOTH Zona fasciculata (cortisol) and Zona glomerulosa (sex hormones)

54
Q

Product of the Zona glomerulosa in the adrenal gland

A

Mineralcorticoids

55
Q

What percent of HAC is due to pituitary tumors

A

85%
Usually adenoma
High cortisol and high ACTH
Bilateral adenomegaly

56
Q

What percent of HAC is due to adrenal tumors

A

15%
May be adenoma OR adenocarcinoma
High cortisol, low ACTH
Unilateral adenomegaly

57
Q

T or F: The likelihood of HAC in cats being due to a pituitary tumor is the same as in dogs

A

True. Both ~85% pituitary origin

58
Q

Why does cortisol cause increased PUPD in dogs (2)

A

1) Increased GFR, increased vascular volume + renal blood flow
2) Steroids inhibit responsiveness to ADH, resulting in decreased resorption of H2O by the renal tubules –> polyuria w/compensatory polydipsia
*ADH change does NOT occur in cats!!

59
Q

Why do cats with HAC have PUPD

A

1) Increased GFR, vascular volume
2) 2’ to concurrent diseases. Over 60% of HAC cats have concurrent DM! r/o CKD

ADH resistance does NOT happen in cats!

60
Q

What percent of cats with HAC have concurrent diabetes

A

60%!

61
Q

What are 2 cutaneous clinical signs associated with steroids/HAC in cats

A
  • Acquired skin fragility
  • “Ear tipping”- weak cartilage on pinnae result in curling. Usually iatrogenic
62
Q

Impact of hyperthyroidism on adrenal gland AUS

A

Bilateral adrenomegaly! Can make it challenging to see if cat has pituitary or adrenal HAC

63
Q

T or F: the best test to confirm adrenal HAC is the HDDST

A

FALSE! HDDST cannot confirm adrenal tumor.

eACTH is better

64
Q

What results of endogenous ACTH test would you expect with a pituitary tumor derived AHC

A

+ ACTH if pituitary origin

-ACTH if adrenal origin (negative feedback)

65
Q

What dose of dexamethasone do you use for LDDST testing in cats

A

10x the dexamethasone dose as you’d use in dogs!

(0.01mg/kg in dogs, 0.1 mg/kg in cats)

66
Q

Causes of enlarged abdomen in HAC patients

A

1) Enlarged liver
2) Weak abdominal musculature
3) Fat redistribution to the ventral abdomen

67
Q

What causes calcinosis cutis

A

Dystrophic mineralization
Abnormal Ca:Phos

68
Q

Which species have calcinosis cutis

A

Dogs and chinchillas

69
Q

What breeds are predisposed to calcinosis cutis

A

Labs
Rottweilers
Boxers
Staffordshire terriers

70
Q

What is the mineral in calcinosis cutis

A

Calcium apatite

71
Q

Labwork findings in dogs with HAC

A

Stress leukogram (increased neut, decreased lymph, eos)

Thrombocytosis
Increased ALP, ALT
Hypercholesterolemia
Decreased BUN (high GFR, medullary washout)

Dilute USG
Proteinuria

72
Q

Labwork findings in cats with HAC

A

Stress leukogram
Anemia

Do NOT have elevated ALP, no steroid isoenzyme for this!

Increased BUN: concurrent CKD common

Hyperglycemia: concurrent DM common

Normal USG, more mild proteinuria

73
Q

Expected thyroid panel in dogs with HAC

A

Low TT4, Low FT4, but NOT ACTUALLY hypothyroid! Low TSH

DO NOT TEST THYROID IF NONTHYROIDAL ILLNESS IS PRESENT

74
Q

Sensitivity, specificity of ACTH stim

A

Poor sensitivity, moderate specificity

Non-adrenal illness will increase your cortisol! False +

Useful for iatrogenic HAC, because you will have a lack of response 2’ adrenocortical atrophy

75
Q

Expected findings on ACTH stim of a dog with PDH

A

Look at 8hr first. If ABOVE 40nmol/L: consistent with HAC.

Then we need to know if PDH or uncertain origin:

PDH confirmed if:
* 4-hr: <40 nmol/L (in normal range)
* 8-hr: >40 nmol/L BUT >50% reduction from baseline

76
Q

Urine cortisol creatinine ratio: sensitivity and specificity

A

A good test to rule out cushings

Very sensitive, not specific

Stress will increase cortisol

(Cats have a naturally higher UCCR, need to use a cat range for HAC cats)

77
Q

Urine cortisol: creatinine ratio combiend WITH oral low dose dexamethasone suppression test can tell us _____

A

Differentiates PDH from ADH. PDH cat will suppress UCCR w/oral dexamethasone

Day 1, Day 2: AM free catch urine
Day 2: give dexamethasone PO q8hr
Day 3: AM free catch

Interpretation:
*If Day 1, 2 are WNL: NOT HAC
*If Day 1,2 are elevated –> likely HAC. AND If Day 3 UCCR is <50% of average of Days 1,2 –> cat has PDH

78
Q

What treatment can be pursued in PDH cats refractory to oral treatments

A

Bilateral adrenalectomy

79
Q

MOA: Trilostane inhibits _____

A

3-beta hydroxysteroid dehydrogenase

Cannot convert:
1) Pregnenolone to progesterone
2) 17-OH prenenolone to 17-OH progesterone

ACTH stim 2-3hr post dose

80
Q

Best tests to perform prior to changing trilostane dose

A

Combo UCCR with ACTH stim

81
Q

Severe AE of trilostane

A

Rare, IRREVERSIBLE coagulation necrosis of adrenal glands

Hypocortisolemia

82
Q

MOA mitotane

A

Adrenocorticolytic
Cytotoxic to Zona fasciculata and Zona reticularis

As efficacious as trilostane in dogs

INFERIOR to trilostane in cats

83
Q

What metabolic changes cause the clinical signs of HAC

A

1) Gluconeogenesis
2) Lipolytic
3) Immunosuppressive effects of GC
4) Protein catabolism

84
Q

How do glucocorticoids affect thyroid levels

A

Decreased TSH secretion

Decreased TT4, fT4
Normal TSH

85
Q

How does phenobarbital affect thyroid levels

A

Changes hepatic metabolism, so increased clearance of thyroid hormones

Decreased TT4, fT4
Normal TSH

86
Q

How does TMS affect thyroid levels

A

Inhibits thyroid peroxidase/TPO (which adds iodine to tyrosine). Results in true, reversible hypothyroidism

Low TT4, fT4
High TSH

May result in a goiter

87
Q

How does clomipramine, aspirin affect thyroid levels

A

Low TT4, fT4

88
Q

How does phenylbutazone affect thyroid levels

A

Alters serum binding

Low TT4

89
Q

How does euthyroid sick syndrome affect thyroid levels

A

1) Inhibits 5’/3’ deiodinase, which converts T4 to T3 in the peripheral tissue
2) Decreased TSH secretion
3) Decreased thyroid protein binding

Low TT4, fT4
Normal to low TSH

90
Q

Which breed is more predisposed to myxedema coma

A

Doberman pinscher

91
Q

Which breed has reported autosomal recessive inherited lymphocytic thyroiditis

A

Borzoi

92
Q

What protein is most T4 bound to in circulation

A

Thyroxine-binding globulin

(not in cats)

93
Q

Most common cause of equine hypothyroidism

A

Congenital

Low dietary Iodine by mom (or endophyte infested fescue, high nitrate diet)

Leads to congenital goiter, limb abnormalities

94
Q

Which caprine breed has autosomal recessive congenital hypothyroidism

A

Saanan Dwarf crossbreeds

Issue with thyroglobulin synthesis

95
Q

Which ovine breed has autosomal recessive congenital hypothyroidism

A

Merino sheep

Issue with thyroglobulin synthesis

96
Q

MOA methimazole

A

Inhibit TPO

97
Q

Most common cause of hyperthyroidism in cats

A

Thyroid adenoma

98
Q

Clinical sequelae of hyperthyroidism in cats

A

Thyrotoxic cardiomegaly
(Hyperthyroidism masks CKD too! Careful when starting tx)

99
Q

Which test should you do to diagnose a cat with hyperthyroidism

A

Ideally both TT4 and fT4

fT4 is more sensitive but less specific than TT4
fT4 is less affected by nonthyroidal illness than TT4

100
Q

Other name for growth hormone

A

Somatotrophin

101
Q

What hormones regulate somatotrophin (GH)?

A

GnRH and stomatostatin

102
Q

Anabolic downstream molecule of GH

A

IGF

103
Q

Best indirect measurement of GH?

Result in acromegaly vs GH deficiency?

A

IGF-1 levels

Acromegaly: High IGF-1
GH deficiency: Low IGF-1

104
Q

Impact of glucocorticoids and estrogens on IGF

A

IGF is decreased by GCs, estrogens

105
Q

Breeds predisposed to pituitary dwarfism

A

GSD
Carnelian Bear Dog

106
Q

Most common etiology of pituitary dwarfism

A

Cyst in Rathke’s cleft of pituitary gland

107
Q

Hormone changes in pituitary dwarfism

A

Low TSH, GH, Prolactin, Gonadotropin

108
Q

Which breed has a hereditary immunodeficient dwarfism

A

Weimeraner

109
Q

Impact of clomipramine, aspirin on thyroid values

A

Low TT4, fT4

110
Q

Which enzyme is NOT present in the zona glomerulosa, resulting in its inability to make cortisol or androgens

A

17-alpha hydroxylase

111
Q

Gene, mode of inheritance for GSD pituitary dwarfism

A

LHX3
Autosomal recessive

112
Q

How can ketoconazole be effective for HAC treatment

A

Can inhibit steroidogenesis at high doses (20 mg/kg/d) by DIRECTLY suppressing ACTH

113
Q

MOA of selegiline hydrochloride

A

IRREVERSIBLE inhibitor of monoamine oxidase (MAO)
-Increase in dopamine
-Downregulate ACTH secretion

-Best in dogs with pars intermedia tumor

DOES NOT WORK FOR HAC. But owners like it bc selegiline is metabolized to amphetamine –> increased alertness

114
Q

MOA of Cabergoline

A

D2 dopaminergic receptor agonist

Anti-proliferative, pro-apoptotic

Affects cleavage of ACTH to form alpha-MSH

Most effective in dogs with pars intermedia tumors

115
Q

Impact of retinoic acid on HAC

A

Suppresses tumor synthesis POMC ad ACTH

Suppresses tumor growth

Teratogenic risk

116
Q

Which cells of the pars intermedia stimulate melanin production

A

A cells, make alpha-MSH

117
Q

Which cells of the pars intermedia produce POMC

A

B cells

Controlled by dopamine inhibition

118
Q

CRH secretion is stimulated by _____ (7)

A

IL-1
IL-6
TNFa
Leptin
Dopamine
ADH
Angiotensin II

119
Q

CRH secretion is inhibited by ______ (2)

A

Glucocorticoids
Somatostatin

120
Q

Precursors of ACTH

A

POMC
MSH

121
Q

What hormone competes with the cortisol receptor, which can lead to acquired skin fragility syndrome in cats

A

Progesterone

Increased progesterone (from tumor) = more unbound cortisol –> fragile skin

122
Q

Which enzyme is NECESSARY for cortisol AND sex hormone production

A

17-alpha hydroxylase

123
Q

Which enzyme is necessary for sexhormone production

A

17,20 lyase

124
Q

Congenital hypothyroidism breeds

A

Giant schnauzers, toy fox terriers, scottish deerhounds

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