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
Q

Why does hyperlipidemia occur in hyperadrenocorticism?

A

Gluconeogenesis –> hyperglycemia –> increased insulin secretion –> increased fat synthesis

26
Q

What is iatrogenic hypercotisolism?

A

Can happen with treatment of steroids
-most common cause for canine hypercortisolism

27
Q

What is reversible hypothyroidism?

A

Cortisol excess causes suppression of TSH which causes hypothyroidism. This can be reversed, if the excess cortisol is removed/treated.

28
Q

What four hormones (other than ones directly involved with cortisol) are affected by excess cortisol?

A

TSH –> reversible hypothyroidism

FSH –> No estrus
LH –> Testicular atrophy

GH –> retarted growth in puppies

29
Q

Hematologic findings in hypercortisolism

A

Stress leucogram

-Neutrophilia (without left shift)
-Eosinopenia
-Lyphopenia
-Monocytosis

30
Q

Biochemistry findings in hypercorticosism

A

-High ALP
-CIALP - cortisol-induced alkaline phosphatase
-Hyperglycemia

31
Q

If leukogram is normal and ALP is in reference range..?

A

Dog is unlikely to have hypercortisolism

32
Q

Urinalysis findings in hypercortisolism?

A

-Low urine specific gravity
-Low-grade proteinuria
-Hematuria
-Bacteruria
Pyuria (WBCs in urine)
-Glucosuria

33
Q

What are screening tests?

A

Designed to determine if hypercorticolism is present:
-LDDST
-ACTH stimulation test
-UCort:UCrea

34
Q

What are differentiation tests?

A

Done after screening tests (HC diagnosis) to determine if PDH or FAT is present:
-LDDST
-HDDST
-eACTH
-Diagnostic imaging (ultrasound, CT, MRI)

35
Q

Tricky thing about HC diagnostics

A

Diagnostic tests have all quite low sensitivity and speficity –> lots of false positives and negatives

Performing multiple tests is not always helpful

36
Q

How is UCort:UCrea used?

A

Owner collects urine sample at home (low stress environment)

-Used as an exclusion test. If ratio is normal, HC is unlikely.

37
Q

What do we inject the dog with in LDDST test?

A

Dexamethasone

38
Q

What do we measure in LDDST test?

A

Cortisol-levels in blood

39
Q

How many blood tests do we take in LDDST test?

A

Three: t0, t4, t8

40
Q

How do normal dogs react to LDDST test?

A

Dexamethasone will feedback and turn off ACTH secretion from pituitary –> cortisol will be low 4 and 8 hours later

41
Q

How do dogs with PDH react to LDDST test?

A

Feedback does not work normally. No or partial suppression of ACTH.

42
Q

How do dogs with FAT react to LDDST test?

A

The tumor secretes cortisol autonomously of ACTH influence. Suppression has little to no effect on cortisol concentrations.

43
Q

How can you diagnose hypercortisolism with LDDST? (without differentiation)

A

If cortisol is still above breaking point after 8 hours (lack of suppression)

44
Q

When can you use LDDST as a differentiation test?

A

With certain results, e.g.

-If there is suppression at 4h and/or 8h, where cortisol levels are <50% of baseline –> PDH

45
Q

Diagnosis?

A

-Dog has hyperadrenocorticism
-Dog has PDH

46
Q

Diagnosis?

A

-Dog has hyperadrenocorticism
-Dog has PDH

47
Q

Diagnosis?

A

-Dog has hyperadrenocorticism
-PDH and ADH cannot be differentiated

48
Q

Diagnosis?

A

Can be HC but probably not.

Next dgn step:
-ACTH stimulation
-Repeat in 4-6 weeks

49
Q

How does ACTH-stimulation test work?

A

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
Q

Problems with ACTH stimulation test

A

-Lack of sensitivity
-Not used in human medicine
-Less sensitive than LDDST and UC:CR

51
Q

What is good about ACTH-stimulation test?

A

-It’s the only test that can diagnose iatrogenic HC

52
Q

What is HDDST?

A

Same as LDDST but dexamethasone dose is higher

-The higher dose should cause more suppression and it might be better to diagnose PDH

53
Q

In HDDST which two responses are consistent with PDH?

A

-Complete suppression at 4h and/or 8h post mexamethasone
-Concentration are <50% of baseline 4h and/or 8h post mexamethasone

54
Q

Can HDDST confirm the presence of FAT?

A

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
Q

How can we interpret eACTH?

A

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
Q

What are some differential diagnosis for hyperadrenocorticism without cutaneous signs?

A

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
Q

What are some differential diagnosis for hyperadrenocorticism with cutaneous signs?

A

-Hypothyroidism
-Adrenal sex hormone dermatosis
-Sex hormone imbalances

58
Q

Treatment options for hyperadrenocorticism

A

Surgical:
-Hypophysectomy
-Adrenalectomy

Medical therapy:
-Lysodren, mitotane –> partial or complete destruction of adrenal glands
-Trilostane (Vetoryl) –> inhibits synthesis of steroids

Monitoring!!

59
Q

Take-home messages!

A

-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)