Disorders of Adrenals Flashcards

1
Q

hyperadrenocorticism broad types, and how the appearance of the adrenals differs between them

A
  • pituitary dependent: Bilaterally enlarged adrenals
  • adrenal dependent: Unilaterally enlarged adrenal usually
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2
Q

what is the most common form of naturally occurring hyperadrenocorticism?

A

Pituitary Dependent HAC
§ “Cushings syndrome”

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3
Q

Pituitary Dependent Hyperadrenocorticism
- how common? what animal is it most common in? what animals is it less common in?
- usual cause?

A

§ “Cushings syndrome”
§ Most common form of naturally- occurring HAC
§ Most commonly seen in dogs
> However, iatrogenic HAC makes up the majority of cases !!
§ Rare in cats
§ Also seen in horses
§ Usually a Pituitary adenoma that ignores negative feedback of cortisol on ACTH

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4
Q

adrenal dependent hyperadrenocorticism
- usual cause
- how common?

A

§ Functional adrenal tumors occur less frequenty than pituitary tumors
§ FAT secretes cortisol independent of ACTH regulation
<><>
§ ~15-20% of HAC cases in cats/dogs
§ adenomas and carcinomas

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5
Q

hyperadrenocorticism clinical signs

A

§Polyuria, polydipsia, polyphagia
§ Alopecia
§ Pendulous abdomen from weakened abdominal muscles
§ Hepatomegaly
§ Urinary tract infections

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6
Q

clinical pathology values for hyperadrenocorticism

A

§ Elevated ALP, ALT
§ Hyperlipidemia
§ Hyperglycemia

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7
Q

options for management of hyperadrenocorticism

A
  • surgical > adrenalectomy
  • medical > drugs acting on adrenal cortex, or Hypo-Pit-Axis
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8
Q

what surgical options exist for management of hyperadrenocorticism in animals? how effective are they? when are they used?

A

§ Surgery can be curative
<><>
§ Adrenalectomy
> Treatment choice for adrenal tumors
> Can be used as treatment for cats with PDH
§ Surgical hypophysectomy used to treat PD-HAC in humans; limited use in animals

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9
Q

medical management of hyperadrenocorticism options
- 2 categories of drugs based on what they target
- what important drugs are in these categories

A
  1. Drugs acting on the adrenal cortex
    § Mitotane
    § Trilostane
    § Ketoconazole
    <><><>
  2. Drugs acting on the Hypo-Pit-Axis
    § Pergolide
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10
Q

mitotane
- what is this drug for? what does it do?
- admin instructions
- how does it work for pituitary vs adrenal dependent hyperadrenocorticism

A

Drug that acts on the adrenal cortex to manage hyperadrenocorticism
<><>
§ Adrenocorticolytic agent similar to the insecticide DDT
> Relatively selective necrosis of z. fasciculata and reticularis
> Fat soluble; administer with fatty meal
<><>
In Pituitary-dependent:
§ BALANCE between pituitary mediated adrenal hyperplasia and
adrenocorticolytic effect of mitotane therapy
§ Goal of therapy is usually partial corticolysis, so not all cortisol production is halted
<><>
In Adrenal-dependent:
§ Often reserved for inoperable adrenal tumors
§ Adrenal tumors more resistant to mitotane therapy

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11
Q

mitotane dosing regimen

A

Induction/loading phase
§ 25 - 50 mg/kg daily in divided doses
§ ~7-10 days or until change in appetite noted
§ Also monitor water intake
<><><>
Maintenance
§ 25 - 50 mg/kg once or twice weekly
§ Supplementation with prednisolone may be required temporarily until stable

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12
Q

mitotane adverse effects

A

§ Adrenal insufficiency if dosing is too high, or too rapid a fall in cortisol
> Weakness, lethargy, vomiting, diarrhea, anorexia
§ Relapses can occur !!

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13
Q

what is trilostane?
- mechanism of action
- when is it effective?
- adverse effects?

A

drug acting on the adrenal cortex to manage hyperadrenocorticism
> works via enzyme inhibition
<><>
§ Approved for use in dogs for PD-HAC and FAT
§ Blockade of 3ß-17-hydroxysteroid dehydrogenase enzyme in adrenal cortex
§ Inhibits conversion of pregnenolone to progesterone inhibiting glucocorticoid, androgen and mineralocorticoid production
<><>
§ Considered highly effective in PD-HAC
§ Well-tolerated with limited adverse effects
§ Same indications as mitotane

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14
Q

ketoconazle can be used for what adrenal-related conditin?
- mechanism of action?
- efficacy?
- adverse effects?
- when to use

A

drug acting on the adrenal cortex to manage hyperadrenocorticism
> works via enzyme inhibition
<><><>
§ Cytochrome P450 3A4 enzyme inhibitor
§ inhibits androgen and glucocorticoid production
§ Generally less effective than mitotane, trilostane
§ Adverse effects > anorexia and elevated liver enzymes
§ Use is reserved for those cases not responding to mitotane or trilostane

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15
Q

pituitary dependent hyperadrenocarticism involving the pars intermedia
- how common is this form of PD-HAC in dogs an horses?
- mechanism of action, and general medical treatment options

A

PD-HAC can involve the intermediate anterior pituitary
§ ~20 of PD-HAC in dogs
§ Most cases of HAC in horses
<><>
Dopamine normally inhibits stimulation of ACTH by the
intermediate Anterior Pituitary
§ Decreased dopamine levels can reduce block and increase ACTH
release—PD-HAC
§ Increasing dopamine levels can re-establish ACTH block in affected individuals
<><>
Treatment:
§ MAO-B inhibitors
§ Dopamine receptor agonists

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16
Q

Pergolide
- what is this drug? use?
- used for what animal? duration?
- admin instructions
- adverse effects

A

Used to treat Pituitary Dependent HAC involving the pars intermedia
<><>
Dopamine (D1, D2) receptor agonist
§ Binds to dopamine receptors in the
intermediate anterior pituitary to block ACTH release
§ Long-acting agonist……elimination half-life (T1/2) around 24 hrs
<><>
Licensed for use in horses for the treatment of equine Cushing’s disease (Pituitary Pars Intermedia Dysfunction)
§ Treatment is for life of horse; not a cure
> Tablets can be mixed with water or molasses/sweetener……syringe
> Pergolide has been previously obtained from compounding pharmacies
> Generally safe……some anorexia, lethary, diarrhea, colic and rare hyperexcitability noted

17
Q

what is addison’s disease and how common is it?
- what are possible causes?

A

primary hypoadrenocorticism
- Natural disease is uncommon
§ Idiopathic Adrenocortical Atrophy
> Autoimmune destruction of adrenal cortex

  • Drug-induced (mitotane, trilostane)
    § Usually spares the z. glomerulosa
  • Bilateral adrenalectomy
    § Supplement therapy needed for life
18
Q

secondary hypoadrenocorticism
- how can this arise?
- minaralocorticoid function

A

§ Deficiency of ACTH
> Iatrogenic from glucocorticoid therapy or progestins
> Destructive lesions (hypo, pituitary)
<><>
§ Mineralocorticoid function usually reduced but adequate
> Supplement often not needed

19
Q

Therapy of Acute Addison’s (addisonian crisis)

A
  • Resuscitate intravascular volume
    > Intravenous fluids to rehydrate and correct electrolytes > hypovolemia, hyponatremia, hyperkalemia
    <><><>
  • Glucocorticoids. Options:
    > dexamethasone
    > prednisolone sodium
    > hydrocortisone
    <><><>
    Mineralocorticoids often not
    needed for acute crisis
    § Na+-K+ ratio (normal 27:1-40:1)
20
Q

in a case of acute addisons, which glucocorticoids that we administer as therapy will interfere with an ACTH stimulation test? which will not?

A

§ Dexamethasone SP will NOT interfere
§ Prednisolone sodium and hydrocortisone will interfere

21
Q

Therapy of Chronic Addison’s
- drug options

A
  • Mineralocorticoids are usually needed for life
    § Desoxycorticosterone pivalate for dogs
    § Fludrocortisone acetate
    <><><>
  • Glucocorticoids
    § Often not required if fludrocortisone used
    § DOCP treated animals usually need glucocorticoids
22
Q

Desoxycorticosterone pivalate
- what is this drug for?
- what animal?
- what activity?
- combined with?

A

Mineralocorticoid for chronic addison’s therapy
§ Approved for use in dogs
§ Injection every ~25 days
§ Mineralocorticoid activity only
<><><>
§ DOCP treated animals usually need glucocorticoids > prednisolone

23
Q

Fludrocortisone acetate
- what is this drug for?
- effect?
- monitor what
- adverse effect

A

Mineralocorticoid for chronic addison’s therapy
§ Oral daily
§ Mixed effects with predominate mineralocorticoid properties
§ Monitor serum electrolytes (Na+, K+)
§ Iatrogenic hyperadrenocorticism possible
<><>
concurrent glucocorticoids often not required

24
Q

Iatrogenic Adrenal Dysfunction often manifests how?
how can we avoid it?

A

result of exogenous glucocorticoid administration for other conditions
- can have hyperadrenocorticism, and can have hypoadrenocorticism if abrupt stoppage of drugs
<><>
Adverse effects of steroid therapy can be minimized
§ lowest dose possible
§ low potency vs high potency
§ alternating day therapy
§ tapered reduction-prevent withdrawal

25
Q

what effects do glucocorticoid vs mineralocorticoid drug have

A

glucocorticoid - antiinflammatory
mineralocorticoid - salt-retaining

26
Q

what are short-medium acting steroid drugs, and their relative glucocorticoid and mineralocorticoid potency

A

Activity less than 24h
<><><>
Hydrocortisone (cortisol) 1 1
Cortisone 0.8 0.8
Prednisolone 4 0.3 Methylprednisolone 5 0
<><>
ie. Hydrocortisone and Cortisone have approximately equal potency as glucocorticoids and mineralocorticoids
whereas prednisolone and methylprednisolone are primarily glucocorticoids

27
Q

what are intermediate acting steroid drugs, and their relative glucocorticoid and mineralocorticoid potency

A

Intermediate Acting (24-48 hr)
<><>
Triamcinolone 5 0
Isoflupredone 17 ?
<><>
ie. both primarily glucocorticoid

28
Q

what are long acting steroid drugs, and their relative glucocorticoid and mineralocorticoid potency

A

Long-Acting (>48 hr)
<><>
Flumethasone 15 0
Dexamethasone 30 0
<><>
ie. both primarily glucocorticoid

29
Q

Mineralocorticoid drugs and their relative glucocorticoid vs mineralocorticoid potency

A

Fludricortisone 10 250 Desoxycorticosterone Acetate/pivalate 0 20