Therapeutics Exam 2: hypERthyroidism

thyrotoxicosis

any syndrome resulting from excess thyroid hormone

Hyperthyroidism

excess thyroid hormone production and secretion by the thyroid gland (>4.5)

What is the most common cause of hyperthyroidism in non-elderly adults?

Graves disease

What are examples of primary hyperthyroidism?

graves disease

toxic multinodular goiter

toxic adenoma

thyroid cancer

struma avarii

iodine excess (including radiocontrast, amiodarone)

What are examples of secondary hyperthyroidism?

TSH-secreting pituitary tumors

trophoblastic (hCG-secreting) tumors

gestational thyrotoxicosis

What are examples of Thyrotoxicosis without hyperthyroidism?

subacute thyroiditis

silent (painless) thyroiditis

postpartum thyroiditis

excess thyroid hormone intake (thyrotoxicosis facititia)

drug- induced

What are some drugs that can induce thyrotoxicosis?

amiodarone

iodine

lithium

interferons

tyrosine kinase inhibitors

immune checkpoint inhibitors

What are the symptoms of hyperthyroidism

nervousness

fatigue/weakness

increased perspiration and heat intolerance

tremor, hyperactivity, irritability

palpitations

increase appetite

weight loss

menstural disturbances (oligomenorrhea- infrequent periods)

frequent bowel movements/diarrhea

What are the signs of hyperthyroidism?

hyperactivity

tachycardia

Afib

hyperreflexia

warm, moist skin

ophthalmopathy, demopathy (Graves)

goiter

muscle weakness

What lab finding signifies thyrotoxicosis?

low TSH levels (<0.5 mIU/L)

What lab finding signifies overt hyperthyroidism?

FT4 is elevated with low TSH

What lab finding would signify mild hyperthyroidism?

FT4 may be normal

What signifies increased hormone production by the thyroid gland?

increased radioiodine uptake in the thyroid

What are unique clinical features with Grave’s disase?

positive TSHRSAbs and antiTPOAbs

ophhalmopathy

dermopathy

thyroid clubbing of digits

hyperpigmentation, non pitting induration of the skin

Ophthalmopathy examples

exophthalmos- one eye bulge

proptosis- both eyes protrude

chemosis-swelling of thin membrane

conjectival injection

periorbital edema

eyelid retraction

vague eye discomfort, excess tearing

compression of optic nerve

Why do we use beta blockers in hyperthyroidism?

many manifestations of it appear to be mediated by beta-adrenergic system

used to rapidly relieve palpitations, tremor, anxiety, and heat intolerance

BUT does not reduce synthesis of thyroid hormones (only a short term solution)

Which beta blockers are used and Why?

propranolol and nadolol

nonselective agents can impair the conversion of T4 to T3

In what pts should beta blockers be avoided for treating hyperthyroidism?

those with decompensated heart failure or asthma

can use more B-1 specific for certain contraindications

What to use for hyperthyroidism if absolute contraindication to beta blockers?

clonidine, verapamil, or diltiazem (heart rate control)

MOA of iodide (SSKI or Lugol’s solution)

inhibit synthesis and release of thyroid hormones

commone uses of Iodide

In grave’s disease pts before surgery

quickly reduce hormone release for thyroid storms

can protect the thyroid from radioactive iodine fallout

duration of iodide

usually 7-14 days before surgery

advantages of iodide

protect thyroid from radioactive iodine fallout

serum T4 levels may be reduced within 24 hours

effects may last for 2-3 weeks

disadvantages of iodide

iodism: palpitations, depression, weight loss, pustular skin eruptions

gynecomastia

DO NOT give iodide before radioacive iodine treatment

MOA of antithyroid drugs (PTU and MMI)

inhibit thyroid hormone synthesis by interfering with thyroid peroxidase–mediated iodination of tyrosine residues in thyroglobulin

Advantages of PTU

added effect of inhibiting conversion of T4 to T3

Disadvantages of PTU

TID dosing

increase failure rate of radioactive iodine therapy

Advantages of MMI

given as single dose

less hepatotoxicity

Disadvantages of MMI

increase failure rate of radioactive iodine therapy

Uses of antithyroid drugs

treat hyperthyroidism

grave’s disease

preparative therapy before surgery or radioactive iodine administration

PTU- 1st trimester of pregnancy

MMI- 2nd and 3rd trimester of pregnancy

Duration of antithyroid drugs

remission of Grave’s disease occurs in 40-60% of patients after 1-2 years of therapy

When to taper antithyroid therapy

after 12-24 months, taper allows natural build up and not durastic change in hormones

Adverse effects of antithyroid drugs

agranulocytosis is one of the most serious adverse effects

MOA of radioactive iodine

produces thyroid ablation without surgery

Use of radioactive iodine

treat hyperthyroidism, make it smaller

Duration of radioactive iodine

after a single dose, 40-70% of pts will be euthyroid in 6-8 weeks

80% will be cured

Advantages of radioactive iodine

no surgery

hyperthyroidism is cured

no long term carcinogenic effect

Disadvantages of radioactive iodine

hypothyroidism will develop

contraindicated in pregnancy and breastfeeding

acutely worse Graves ophthalmopathy

painful thyroiditis (use anti-inflammatory therapy)

MOA of surgery

surgical removal of thyroid

subtotal or total thyroidectomy

Why surgery?

very large goiter

thyroid malignancies

other therapies not working

Advantages of surgery

cured

low complication rate

Disadvantages of surgery

10% of pts have postoperative hypothyroidism

What to monitor for with treatment of hyperthyroidism

any S/S of adverse effects (esp. agranulocytosis)

skin rash or development of arthralgias

TSH levels - reduce dose or if removal of thyroid add like levothyroxine

duration of therapy (usually stopping after 12-24 months)

S/S of thyroid storm

high fever

tachycardia

dehydration

delirium

coma

GI disturbances

Precipitating factors of thyroid storm

previously hyperthyroid pt by: infection, trauma, radioactive iodine treatment, or sudden withdrawal from antithyroid drugs

Treatment of thyroid storm

short acting B-blockers such as IV esmolol

IV or oral iodide

large dose PTU

large MMI dose

What are supportive care measures for thyroid storm?

acetaminophen: fever

fluid and electrolyte management

antiarrhythmic agents

IV hydrocortisone 300 mg initially and then 100 mg every 8 hours is used often because of the potential presnece of adrenal insufficiency

Why is LT4 used in thyroid cancer treatment?

growth and dissemination of thyroid carcinoma are stimulated by TSH, LT4 suppresses TSH secretion

pts may receive the lowest LT4 dose sufficient to fully supporess TSH to undetectable levels —> reduces tumor growth and improves survival

What is the mechanism of amiodarone’s thyroid effects?

each 200 mg dose of amiodarone provides 75 mg of iodide

amiodarine deiodination releases about 6 mg of free iodine daily (20-40 times more than daily average intake)

blocks conversion of T4 to T3

inhibits entry of T3 into cellsH

How are serum T3 free and T4 total affected by amiodarone?

decreases T3 receptor binding

T3 levels = reduction

free T4 = increases

TSH = increases

What thyroid related labs should be performed for those taking amiodarone?

baseline measurements of serum TSH, FT4, FT3, antiTPOAbs and TSHRSAbs

What monitoring should be done for pts taking amiodarone?

TSH, FT4, and FT3 should be checked 3 months after initiation of it and then TSH at least every 3 to 6 months

What is Lithium’s effect on thyroid?

appears to inhibit thyroid hormone synthesis and secretion (hypOthyroidism in 34% of pts)

pts w/ underlyding autoimmune thyroiditis are more likely to develop hypOthyroidism while taking lithium

pts may still require LT4 replacement even if lithium is stopped

What is Interferon-a’s effect on thyroid?

hypOthyroidism (but may cause thyroiditis w/ hyperthyroidism before going hypo)

if LT4 replacement is initiated, stop after 6 months to reevaluate

asian pts and pts with preexisting antiTPOAbs are more likely to develop interferon-induced hypothyroidism