Drugs Used to Treat Endocrine Disorders

What are the indications for thyroid hormone?

Thyroid deficiency

How can you give thyroid hormone replacement?

Oral tablets usually

IV for emergency rase

DOSE IS MUCH HIGHER THAN HUMAN DOSE

How should you monitor the patient after thyroid hormone replacement?

Post-Pill T4 concentration in serum 4-6 hours after last dose

Want it to be at high end of reference range 4-6 hours later

What are the indications for methimazole?

Thyroid excess

How can you give methimazole?

Oral or compounded transdermal

How do you monitor methimazole?

Monitor TT4 in serum (sample is not timed since last dose)

Start 14 days after starting medication for first month biweekly tests

What should you monitor for on methimazole CBC/Chem?

Hematologic changes

Monitor renal function

Monitor liver function

What are the adverse effects of methimazole that will respond to dose reduction?

GI reactions like reactions and vomiting

T/F side effects to methimazole are common?

True

What are the adverse effects of methimazole that indicate the drug needs to be stopped?

Skin reactions: alopecia, pruritis, skin scaling of face and head

Immune reaction like polyarthritis, lupus like syndrome

Hematologic: thrombocytopenia, agranulocytosis, bone marrow suppression

Hepatopathy

What gets hypo and hyperadrenocorticism?

Common in the dog

Rare in the cat

What are indications for glucocorticoids?

Hypocortisolemia (addisons)

What are the side effects of glucocorticoids?

Lots, reflects hypercortisolemia

What is the main steroid used to replace cortisol during Addisons?

Prednisone, prednisolone, and dexamethasone

What are the indications for mineralocorticoids?

Hypoadrenocorticism (Addisons), Hypoaldosteronism

What are the adverse effects of mineralocorticoids

Hypokalemia and hypertension

Can worsen renal or cardiac disease

What are the mineralocorticoids

DOCP

Fludrocortisone acetate

What is DOCP?

Depot drug that is long acting mineralocorticoid for 3-4 weeks

What is fludrocortisone acetate?

Short acting mineralocorticoid that has some glucocorticoid activity too

What are indications for drugs that inhibit adrenal cortical function?

Treatment of adrenocortical hypersecretion associated with pituitary or adrenal dependent hyperadrenocorticism

What is trilostane

used for PDH and ADH

Decreased cortisol but also other adrenal hormones progesterone, androgens, aldosterone)

What is mitotane?

Not approved for vet use but adrenolytic that destroys cortex layers of fasiculata (cortisol) and retuclaris (androgens)

Spares z. glomerulosa (aldosterone)

What are adverse reactions of trilostane and mitotane?

General malaise, lethargy

GI effects: vomiting, decreased appetite

Hypoadrenocorticism: decreased aldosterone production creating hyponatremia and hyperkalemia

Adrenal necrosis

How do you treat hypo-functioning gland?

Hormone replacement

What is hormone replacement?

Pharmacologic replacement of a deficient hormone

What is anti-hormone therapy?

Pharmacologic inhibition of hormone secretion OR pharmacologic interference with hormone selection

How do you treat a hyper-functioning gland?

Anti-hormone therapy

What are some examples of adverse effects due to over treatment?

Hyperthyroid signs caused by excessive thyroid hormone

Hypoglycemia signs caused by excess insulin administration

What is an example of an adverse effect that is caused in non-targeted pathways?

GI side effects

What are some other interventions that are used to treat endocrine disorders?

Ablative therapy

Diet therapy

Non-endocrine drugs

What is ablation therapy?

Removal or destruction of abnormal tissue

Ex: surgical parathyroidectomy to treat hyperparathyroidism

What is diet therapy?

Diet/nutritional intervention to modulate an endocrine disorder

Ex: iodine restriction for feline hyperthyroidism

What are some non-endocrine drugs used to treat endocrine disorders?

Beta blockers for hyperthyroid storm
Phenoxybenzamine for hypertension from a pheochromocytoma

What is an example of an endocrine drug having non-endocrine uses?

Prednisone to treat a lymphosarcoma

What species get hypothyroidism?

Dog

What species gets hyperthyroidism?

Cats

How do you treat hypothyroidism?

Hormone replacement with L-thyroxine (synthetic T4)

What is the presentation for hypothyroidism?

Primary hypothyroidism in dogs

Hypothyroidism after treatment for hyperthyroidism in cats

How do you treat hyperthyroidism?

Anti-thyroid drugs like methimazole or potassium iodate

What is the presentation for hyperthyroidism?

Primary hyperthyroidism from thyroid adenoma in cats or thyroid carcinoma in cats/dogs

Thyroid excess due to over treatment for hypothyroidism (dog/cat) or contamination of diet with thyroid tissue (dog)

What is the MOA of thioamide (methimazole)?

Inhibitor of TPO (thyroid peroxidase) and new hormone production

How do you treat an acute thyroid storm in cats?

Potassium iodide

BUT it is more common to use a beta blocker to protect the cardiac effects

How does potassium iodide treat a thyroid storm?

Reduce hormone secretion, prevent iodine organification, and block some hormone conversion

What is the general approach to treating hyperadrenocorticism?

Drugs that inhibit ACTH (anti-pituitary drugs) or drugs that inhibit adrenal function (anti-adrenal drugs)

What is the general approach to treating hypoadrenocorticism?

Hormone replacement

How do you treat hypoadrenocorticism?

Glucocorticoids like prednisone or dexamethason

Mineralocorticoids like DOCP (desoxycorticosterone pivulate) or fludrocortisone

What are the presentations for hypoadrenocorticism?

Addisons (primary hypoadrenocorticism)

Hypoadrenocorticism after a adrenalectomy

Adrenal suppression from chronic glucocorticoids

What drugs are used to treat hyperadrenocorticism?

Trilostane (anti-adrenal)

MItotane (anti-adrenal)

Selegiline akja Selegiline (Anti-pituitary)

What are the common clinical manifestations of hyperadrenocorticism?

Pituitary-dependent hyperadrenocorticism due to pituitary micro or macroadenoma

Adrenal dependent hyperadrenocorticism due to adrenocortical adenoma or adenocarcinoma

What is an alternative glucocorticoid that can be used to treat hypoadrenocorticism?

Hydrocortisone

How do you treat an acute hypoadrenocorticism crisis?

Injectable dexamethasone or prednisolone sodium succinate

How do you treat chronic hypoadrenocorticism or hypocortisolemia?

Daily oral glucocorticoids like prednisone at physiologic dose

Increase dose if stress situations will arrive

What is a hypoadrenal disease that is only required to be treated with glucocorticoids?

Atypical addison’s (hypocortisolemia)

What is the difference between DOCP and fludrocortisone acetate?

DOCP is long acting and only has mineralocorticoid activity

Fludrocortisone acetate is short acting but has some mineralocorticoid activity and might not need prednisone at the same time

What is the inhibition of 3Beta-Hydroxysteroid DH so important for anti-adrenal therapy?

It is used in both major pathways that form cortisol

MOA of mitotane

Inhibits mitochondrial enzymes (all steroid pathways)

MOA of trilostane

Reversible inhibitor of 3beta-hydroxysteroid DH

MOA of ketoconazole?

Reversible inhibitor of 17,20-lyase and 11-beta-hydroxylase

What species get diabetes mellitus?

Dogs and cats

What species get insulinoma?

Uncommon in dog

Rare in cat

What is the pharmacologic approach to insulin deficiency?

Hormone replacement

Glucose lowering agents

What drugs are used to treat insulin deficiency?

Insulin

Also, oral hypoglycemic, incretin therapy, insulin sensitizers

What are the manifestations of insulin deficiencyu?

Diabetes mellitus that causes beta cell injury and loss or pancreatic islet atrophy

What is the pharmacologic approach to treating insulin excess?

Beta cell inhibitors

Beta cell toxins

Induction of insulin resistance

What drugs are used to treat insulin excess?

Diazoxide (inhibitor)

Streptozotocin (toxin)

Glucocorticoids

What is the clinical manifestation of insulin excess?

Insulinoma: functional pancreatic tumor with upregulated insulin production causing hypoglycemia

What is the indication for insulin?

Diabetes mellitus due to insulin deficiency and or insulin resistance

What insulin type is used for emergency treatment?

Ultra-short and short-acting given IV, IM, or SQ

What insulin type is used for daily treatment?

Intermediate and long-acting given SQ

T/F replacement insulin has the same effects as the endogenous hormone?

True

T/F commerical insulins are effective in all species?

True

What are SGLT (sodium glucose linked transporter 2) inhibitors?

New class of oral hypoglycemic drugs used for treatment of FELINE diabetes

What SGLT2 inhibitors are approved for diabetic cats?

Bexagliflozin and velagliflozin

How do SGLT2 inhibitors work?

Lower blood glucose by inhibiting glucose resorption at renal tubules

PROMOTES glucosuria

Hypoglycemia is rare with use

What is a complication of SGLT2 use?

Euglycemic diabetic ketoacidosis (DKA)