Disorders of Adrenals Flashcards
(29 cards)
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
