Hyperadrenocorticism Flashcards

1
Q

Common type of hyperadrenocoticism diagnosis

A

Cushing syndrome or Cushing’s disease

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2
Q

In most simple terms, what does hyperadrenocorticism refer to?

A

Elevated cortisol concentrations

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3
Q

Two common types of hyperadrenocorticism

A

-Pituitary-dependent hyperadrenocorticism (PDH; Cushing disease) - 80% of cases

-Adrenal-dependent/pituitary independent/functional adrenocortical tumor (FAT) hyperadrenocorticism - 20% of cases

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4
Q

What happens in adrenal-dependent hyperadrenocosticism?

A

Uni- or bilateral tumor in adrenal gland(s) secretes extra cortisol

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5
Q

Most common clinical signs of hyperadrenocosticism

A

Clinical signs are often not noticed by the owner especially in early stages of disease.

-Polyuria
-Polydipsia
-Weight gain
-Alopecia
-Muscle atrophy
-“Pot-belly”

Other signs:
-Thin skin
-Hepatomegaly
-Lethargy
-Polyphagia
-Anestrus
-Excessive panting
-Testicular atrophy
-Hyperpigmented macules
-Neurologic signs

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6
Q

ACTH

A

adrenocorticotropic hormone

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7
Q

ALP

A

alkaline phosphatase

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8
Q

CLIP

A

corticotropin-like intermediate lobe peptide

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9
Q

cPLI

A

canine pancreatic lipase immunoreactivity

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10
Q

CRH

A

corticotropin releasing hormone

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11
Q

CIALP

A

cortisol induced alkaline phosphatase

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12
Q

eACTH

A

endogenous ACTH

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13
Q

FAT

A

functional adrenocortical tumor

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14
Q

HAC

A

hyperadrenocorticism

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15
Q

HC

A

hypercortisolism

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16
Q

HDDST

A

high dose dexamethasone suppression test

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17
Q

LDDST

A

low dose dexamethasone suppression test

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18
Q

PDH

A

pituitary dependent hyperadrenocorticism

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19
Q

SIALP

A

steroid induced alkaline phosphatase

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20
Q

UCCR

A

urine cortisol creatinine ratio

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21
Q

How can the basal cortisol concentration be used as a diagnostic test?

A

If the basal cortisol is <55nmol/l, hypercontisolism is unlikely - could be used in exclusion

For diagnosis of HC, basal plasma concentration is not a good test alone, because cortisol could rise because of physiologic reasons/stress

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22
Q

What is the HPA-axis?

A
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23
Q

Excess cortisol causes increased gluconeogenesis. How does this further affect the body?

A

Hyperglycemia –> Increased insulin secretion –> Increased fat synthesis –> Obesity, hyperlipidemia

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24
Q

Why does muscle atrophy happen in hyperadrenocorticism?

A

Excess cortisol increases protein breakdown

25
Why does hyperlipidemia occur in hyperadrenocorticism?
Gluconeogenesis --> hyperglycemia --> increased insulin secretion --> increased fat synthesis
26
What is iatrogenic hypercotisolism?
Can happen with treatment of steroids -most common cause for canine hypercortisolism
27
What is reversible hypothyroidism?
Cortisol excess causes suppression of TSH which causes hypothyroidism. This can be reversed, if the excess cortisol is removed/treated.
28
What four hormones (other than ones directly involved with cortisol) are affected by excess cortisol?
TSH --> reversible hypothyroidism FSH --> No estrus LH --> Testicular atrophy GH --> retarted growth in puppies
29
Hematologic findings in hypercortisolism
Stress leucogram -Neutrophilia (without left shift) -Eosinopenia -Lyphopenia -Monocytosis
30
Biochemistry findings in hypercorticosism
-High ALP -CIALP - cortisol-induced alkaline phosphatase -Hyperglycemia
31
If leukogram is normal and ALP is in reference range..?
Dog is unlikely to have hypercortisolism
32
Urinalysis findings in hypercortisolism?
-Low urine specific gravity -Low-grade proteinuria -Hematuria -Bacteruria Pyuria (WBCs in urine) -Glucosuria
33
What are screening tests?
Designed to determine if hypercorticolism is present: -LDDST -ACTH stimulation test -UCort:UCrea
34
What are differentiation tests?
Done after screening tests (HC diagnosis) to determine if PDH or FAT is present: -LDDST -HDDST -eACTH -Diagnostic imaging (ultrasound, CT, MRI)
35
Tricky thing about HC diagnostics
Diagnostic tests have all quite low sensitivity and speficity --> lots of false positives and negatives Performing multiple tests is not always helpful
36
How is UCort:UCrea used?
Owner collects urine sample at home (low stress environment) -Used as an exclusion test. If ratio is normal, HC is unlikely.
37
What do we inject the dog with in LDDST test?
Dexamethasone
38
What do we measure in LDDST test?
Cortisol-levels in blood
39
How many blood tests do we take in LDDST test?
Three: t0, t4, t8
40
How do normal dogs react to LDDST test?
Dexamethasone will feedback and turn off ACTH secretion from pituitary --> cortisol will be low 4 and 8 hours later
41
How do dogs with PDH react to LDDST test?
Feedback does not work normally. No or partial suppression of ACTH.
42
How do dogs with FAT react to LDDST test?
The tumor secretes cortisol autonomously of ACTH influence. Suppression has little to no effect on cortisol concentrations.
43
How can you diagnose hypercortisolism with LDDST? (without differentiation)
If cortisol is still above breaking point after 8 hours (lack of suppression)
44
When can you use LDDST as a differentiation test?
With certain results, e.g. -If there is suppression at 4h and/or 8h, where cortisol levels are <50% of baseline --> PDH
45
Diagnosis?
-Dog has hyperadrenocorticism -Dog has PDH
46
Diagnosis?
-Dog has hyperadrenocorticism -Dog has PDH
47
Diagnosis?
-Dog has hyperadrenocorticism -PDH and ADH cannot be differentiated
48
Diagnosis?
Can be HC but probably not. Next dgn step: -ACTH stimulation -Repeat in 4-6 weeks
49
How does ACTH-stimulation test work?
a) collect blood sample (measure cortisol) b) give synthetic ACTH c) new blood sample 60mins later -If cortisol levels increase a lot --> hyperadrenocorticism -if cortisol levels increase a little bit --> normal -if cortisol levels don't increase --> hypoadrenocorticism
50
Problems with ACTH stimulation test
-Lack of sensitivity -Not used in human medicine -Less sensitive than LDDST and UC:CR
51
What is good about ACTH-stimulation test?
-It's the only test that can diagnose iatrogenic HC
52
What is HDDST?
Same as LDDST but dexamethasone dose is higher -The higher dose should cause more suppression and it might be better to diagnose PDH
53
In HDDST which two responses are consistent with PDH?
-Complete suppression at 4h and/or 8h post mexamethasone -Concentration are <50% of baseline 4h and/or 8h post mexamethasone
54
Can HDDST confirm the presence of FAT?
Hddst can never confirm the presence of FAT. If criteria for PDH are not met, there is a 50/50 chance for either PDH or FAT
55
How can we interpret eACTH?
If eACTH is high --> PDH (secresion from the tumor) If aACTH is low --> FAT (negative feedback from the adrenocortical tumor/inhibition of ACTH secretion) eACTH can be used to confirm presence of FAT!
56
What are some differential diagnosis for hyperadrenocorticism without cutaneous signs?
Without clinical signs, the differential diagnosis is usually that of polyuria/polydipsia: -chronic kidney disease -chronic liver disease -diabetes mellitus -diabetes insipidus -hypoadrenocorticism -psychogenic polydipsia
57
What are some differential diagnosis for hyperadrenocorticism with cutaneous signs?
-Hypothyroidism -Adrenal sex hormone dermatosis -Sex hormone imbalances
58
Treatment options for hyperadrenocorticism
Surgical: -Hypophysectomy -Adrenalectomy Medical therapy: -Lysodren, mitotane --> partial or complete destruction of adrenal glands -Trilostane (Vetoryl) --> inhibits synthesis of steroids Monitoring!!
59
Take-home messages!
-Plasma cortisol concentration alone is a valueless test -Endocrine testing should only be performed and interpreted in dogs with appropriate clinical signs and laboratory anomalies -Differentiation tests should never be performed before a diagnosis of HC is made via screening tests -Urine cortisol:creatinine ratio is a reasonable screening test to begin with (normal values usually rule out HC)