Disorders of Adrenals Flashcards
hyperadrenocorticism broad types, and how the appearance of the adrenals differs between them
- pituitary dependent: Bilaterally enlarged adrenals
- adrenal dependent: Unilaterally enlarged adrenal usually
what is the most common form of naturally occurring hyperadrenocorticism?
Pituitary Dependent HAC
§ “Cushings syndrome”
Pituitary Dependent Hyperadrenocorticism
- how common? what animal is it most common in? what animals is it less common in?
- usual cause?
§ “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
adrenal dependent hyperadrenocorticism
- usual cause
- how common?
§ Functional adrenal tumors occur less frequenty than pituitary tumors
§ FAT secretes cortisol independent of ACTH regulation
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§ ~15-20% of HAC cases in cats/dogs
§ adenomas and carcinomas
hyperadrenocorticism clinical signs
§Polyuria, polydipsia, polyphagia
§ Alopecia
§ Pendulous abdomen from weakened abdominal muscles
§ Hepatomegaly
§ Urinary tract infections
clinical pathology values for hyperadrenocorticism
§ Elevated ALP, ALT
§ Hyperlipidemia
§ Hyperglycemia
options for management of hyperadrenocorticism
- surgical > adrenalectomy
- medical > drugs acting on adrenal cortex, or Hypo-Pit-Axis
what surgical options exist for management of hyperadrenocorticism in animals? how effective are they? when are they used?
§ Surgery can be curative
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§ 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
medical management of hyperadrenocorticism options
- 2 categories of drugs based on what they target
- what important drugs are in these categories
- Drugs acting on the adrenal cortex
§ Mitotane
§ Trilostane
§ Ketoconazole
<><><> - Drugs acting on the Hypo-Pit-Axis
§ Pergolide
mitotane
- what is this drug for? what does it do?
- admin instructions
- how does it work for pituitary vs adrenal dependent hyperadrenocorticism
Drug that acts on the adrenal cortex to manage hyperadrenocorticism
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§ Adrenocorticolytic agent similar to the insecticide DDT
> Relatively selective necrosis of z. fasciculata and reticularis
> Fat soluble; administer with fatty meal
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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
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In Adrenal-dependent:
§ Often reserved for inoperable adrenal tumors
§ Adrenal tumors more resistant to mitotane therapy
mitotane dosing regimen
Induction/loading phase
§ 25 - 50 mg/kg daily in divided doses
§ ~7-10 days or until change in appetite noted
§ Also monitor water intake
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Maintenance
§ 25 - 50 mg/kg once or twice weekly
§ Supplementation with prednisolone may be required temporarily until stable
mitotane adverse effects
§ Adrenal insufficiency if dosing is too high, or too rapid a fall in cortisol
> Weakness, lethargy, vomiting, diarrhea, anorexia
§ Relapses can occur !!
what is trilostane?
- mechanism of action
- when is it effective?
- adverse effects?
drug acting on the adrenal cortex to manage hyperadrenocorticism
> works via enzyme inhibition
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§ 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
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§ Considered highly effective in PD-HAC
§ Well-tolerated with limited adverse effects
§ Same indications as mitotane
ketoconazle can be used for what adrenal-related conditin?
- mechanism of action?
- efficacy?
- adverse effects?
- when to use
drug acting on the adrenal cortex to manage hyperadrenocorticism
> works via enzyme inhibition
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§ 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
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
PD-HAC can involve the intermediate anterior pituitary
§ ~20 of PD-HAC in dogs
§ Most cases of HAC in horses
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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
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Treatment:
§ MAO-B inhibitors
§ Dopamine receptor agonists
Pergolide
- what is this drug? use?
- used for what animal? duration?
- admin instructions
- adverse effects
Used to treat Pituitary Dependent HAC involving the pars intermedia
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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
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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
what is addison’s disease and how common is it?
- what are possible causes?
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
secondary hypoadrenocorticism
- how can this arise?
- minaralocorticoid function
§ Deficiency of ACTH
> Iatrogenic from glucocorticoid therapy or progestins
> Destructive lesions (hypo, pituitary)
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§ Mineralocorticoid function usually reduced but adequate
> Supplement often not needed
Therapy of Acute Addison’s (addisonian crisis)
- Resuscitate intravascular volume
> Intravenous fluids to rehydrate and correct electrolytes > hypovolemia, hyponatremia, hyperkalemia
<><><> - Glucocorticoids. Options:
> dexamethasone
> prednisolone sodium
> hydrocortisone
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Mineralocorticoids often not
needed for acute crisis
§ Na+-K+ ratio (normal 27:1-40:1)
in a case of acute addisons, which glucocorticoids that we administer as therapy will interfere with an ACTH stimulation test? which will not?
§ Dexamethasone SP will NOT interfere
§ Prednisolone sodium and hydrocortisone will interfere
Therapy of Chronic Addison’s
- drug options
- 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
Desoxycorticosterone pivalate
- what is this drug for?
- what animal?
- what activity?
- combined with?
Mineralocorticoid for chronic addison’s therapy
§ Approved for use in dogs
§ Injection every ~25 days
§ Mineralocorticoid activity only
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§ DOCP treated animals usually need glucocorticoids > prednisolone
Fludrocortisone acetate
- what is this drug for?
- effect?
- monitor what
- adverse effect
Mineralocorticoid for chronic addison’s therapy
§ Oral daily
§ Mixed effects with predominate mineralocorticoid properties
§ Monitor serum electrolytes (Na+, K+)
§ Iatrogenic hyperadrenocorticism possible
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concurrent glucocorticoids often not required
Iatrogenic Adrenal Dysfunction often manifests how?
how can we avoid it?
result of exogenous glucocorticoid administration for other conditions
- can have hyperadrenocorticism, and can have hypoadrenocorticism if abrupt stoppage of drugs
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Adverse effects of steroid therapy can be minimized
§ lowest dose possible
§ low potency vs high potency
§ alternating day therapy
§ tapered reduction-prevent withdrawal
what effects do glucocorticoid vs mineralocorticoid drug have
glucocorticoid - antiinflammatory
mineralocorticoid - salt-retaining
what are short-medium acting steroid drugs, and their relative glucocorticoid and mineralocorticoid potency
Activity less than 24h
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Hydrocortisone (cortisol) 1 1
Cortisone 0.8 0.8
Prednisolone 4 0.3 Methylprednisolone 5 0
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ie. Hydrocortisone and Cortisone have approximately equal potency as glucocorticoids and mineralocorticoids
whereas prednisolone and methylprednisolone are primarily glucocorticoids
what are intermediate acting steroid drugs, and their relative glucocorticoid and mineralocorticoid potency
Intermediate Acting (24-48 hr)
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Triamcinolone 5 0
Isoflupredone 17 ?
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ie. both primarily glucocorticoid
what are long acting steroid drugs, and their relative glucocorticoid and mineralocorticoid potency
Long-Acting (>48 hr)
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Flumethasone 15 0
Dexamethasone 30 0
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ie. both primarily glucocorticoid
Mineralocorticoid drugs and their relative glucocorticoid vs mineralocorticoid potency
Fludricortisone 10 250 Desoxycorticosterone Acetate/pivalate 0 20
