Hyperthyroid Disease

What are Signs of Hyperthyroid disease?

• Flushed moist skin

• Thinning of hair

• Proptosis, lid lag

• Pretibial myxedema

• Brisk DTR’s

• Goiter

• Tremor

What are symptoms of hyperthyroid disease?

• weakness & fatigue

• nervousness

• muscle aches

• weight loss

• heat intolerance

• palpitations

• amenorrhea

• diarrhea

List types of hyperthyroid disease

• Grave’s disease

• Toxic uninodular goiter

• multinodular goiter

• Jod-Basedow

• Factitious

• Drugs

• Thyroiditis

• Tumor

What is Pretibial Myxedema and where is it seen?

chubby ankles

edema at the bottom of tibia

looks bumpy, red, and squishy

• seen with Grave’s disease (eyes too)

What are some drugs that can induce hyperthyroidism?

Iodine-containing contrast dyes

Amiodarone

Iodinated glycerol

Alpha-Interferon

Alemtuzumab (anti-CD52)

TH (T3, T4)

What are the advantages of surgery to treat hyperthyroidism?

• Definitive

• TOC - Malignancy

• TOC - Respiratory or swallowing difficulties

• Existence of CI’s to RAI/Thioamides

• Non-compliant pt

What are the disadvantages of surgery to treat hyperthyroidism?

• Risks of hypothyroidism

• surgical risks

• Cosmetic consequences

  • Must safeguard against Thyroid Storm

What are the advantages of Radioactive Iodine therapy for hyperthyroidism?

• Definitive

• Alternative for non-surgical candidates

• Pts who fail or experience ADR to drug therapy

• Pts in which disease recurrence would complicate other diseases

• Non-compliant pt

What are the disadvantages of radioactive iodine therapy for hyperthyroidism?

• Risk of hypothyroidism

• CI in pregnant or nursing mothers

• Concern of use in children

• possible radiation thyroiditis

• must safeguard against Thyroid Storm

What are the advantages of drug therapy for hyperthyroidism?

• Noninvasive

• Minimize chances of hypothyroidism

• Use in pts with CI to surgery/RAI

What are the disadvantages of drug therapy for hyperthyroidism?

• Not definitive treatment

• possible medication SE

• requires long term compliance

What is functional unit of the thyroid gland?

FOLLICLES

What are the key elements that function within the follicle?

• Thyroglobulin (Tg)

• Tyrosine

• Iodine

• Thyroxine (T4)

• Triiodotyrosine (T3)

What are the 4 steps in natural thyroid hormone synthesis ?

1. Iodide Trapping

2. Organification

3. Coupling

4. Release

Which three processes of natural thyroid hormone synthesis do thioamides inhibit?

• Organification

• Coupling

• Release

What is the MOA of thioamides?

Inhibit Organification and Coupling

Immunosuppressive effect? → good for graves

PTU- inhibits peripheral T4 conversion

What are the SE of thioamides?

Benign (rash, fever, GI issues, arthralgia)

Severe (agranulocytosis, hepatitis)

What is an important counseling point for thioamide therapy?

• Must report fever, sore throat, flu-like symptoms

• any potential infection get CBC w/ differential - help determine neutropenia

What are the two thioamides?

• Propylthiouracil (PTU)

• Methimazole (Tapazole)

When is PTU preferred and how is it dosed?

Preferred: Preganacy (1st trimester), lactation, thyroid storm

dosed three times daily & bitter taste

added MOA inhibits peripheral T4 conversion

When is Methimazole preferred?

Considered thioamide of choice

Longer T 1/2 & better compliance & no bitter taste

How is Methimazole dosed?

30-60 mg/d in 1-3 doses

can be taken once daily

Name three birth defects that can be caused my methimazole use in the 1st trimester?

1. Aplasia cutis (scalp defect)

2. Esophageal atresia (ends & doesn’t connect to stomach)

3. Choanal atresia (nasal passages blocked by tissues or cartilage

Which medication has greater protein binding Methimazole or PTU?

PTU

What thioamide is preferred in children with hyperthyroidism?

Methimazole

When is PTU considered?

pregnant women in their 1st trimester

pts w/ life-threatening thyrotoxicosis

pts with a toxic reaction to MMI or not candidates for RAI or surgery but require anti-thyroid therapy

What thioamide has increased chances of hepatitis?

PTU

What is the difference between hepatocellular vs cholestatic hepatitis?

hepatocellular: increase in transaminases and bilirubin

cholestatic: problem w/in billiary tract & harder to reverse bc theres an obstruction in the liver

What is the MOA of beta blockers?

manage sympathetic-mediated symptoms

inhibit peripheral T4 conversion

When would beta blockers CI and what is used instead?

asthma

COPD

CHF

Use CCBs diltiazem, or verapamil

What are advantages and disadvantages of beta blockers?

+: symptomatic control quickly & effective for preparation of surger/RAI

-: doesn’t help underlying thyroid disease & CIs

What is the MOA of Iodides?

Blocks TH release

Inhibits organification

Inhibit peripheral T4 conversion*

decrease gland size & vascularity

What are SE of Iodide therapy?

Allergic reactions

Dose-related toxicity (Iodism) → mouth irritation

Metallic taste

”Escape” phenomenon → thyroid hormone escapes short term

Name 3 preparations of Iodides?

SSKI (38 mg/drop) - better palatability

Lugol’s Solution (6 mg/drop)

Thyro-Block (potassium iodide 130mg)

What are advantages and disadvantages of Iodide therapy?

+: prompt effectiveness, effective adjunct for surgery

-: can’t use alone, escape, CI: pregnancy, pts with nodular goiter or adenomas prior to RAI (will just use to make more)

What is potassium iodide usually used for and what are the names it goes by?

radiation exposure

• Iosat

• ThyroSafe

• Thyro Shield

What is an important clinical pearl for potassium iodide?

do not give prior to RAI therapy otherwise therapy is not effective because Wolff-Chaikoff effect

When should a patient be checked after starting TH replacement?

3-6 weeks in intervals early-on

How often are pts on TH replacement therapy checked once they reach a euthyroid state?

annually

What is the treatment of choice for Grave’s Disease and for how long?

Thioamides

18-24 months (try normalize slowly then see if in remission)

What percent of Grave’s pts have Grave’s ophthalmopathy?

50%

What part of the eye breaks down in 3-5% of patients threatening their sight?

corneal breakdown or optic neuropathy

What is the brand name for Teprotumumab?

Tepezza

What type of medication is Teprotumumab?

Humanized human monoclonal antibody

What is the MOA of Teprotumumab?

IGF-1R inhibitor (insulin growth factor receptor

decreases initiation of thyrotropin receptor & IGF-1R

How many doses are needed, how is it administered, and what is the cost?

8 Doses

Intravenous

18,200 per vial x 23 vials for treatment

What does Teprotumumab treat?

teary red eyes

Grave’s opthamopathy

What is the treatment of choice for Toxic Nodular Goiters?

RAI therapy → usually gets to euthyroid

Surgery

• avoid Iodides - nodules just eat it up

What is the treatment of choice for thyroiditism?

usually self-limited

inflammatory → treat w/ NSAIDs or BB as needed

look for subsequent transient hypothyroidism - 10% of postpartum women

What is the treatment of choice for neonatal thyrotoxicosis?

Treat w/ thioamides or beta blockers

Prevalence is 1:100 births to mothers with a history of Grave’s disease (> chance of passing antibody to newborns)

Who receives testing for hyperthyroidism?

every newborn

What is the treatment of choice for Iodine-induced HTR disease?

from excessive iodine ingestion

d/c source of iodine -usually self-limited

What is the treatment of choice for thyrotoxicosis factitia?

Due to excessive TH administration

d/c or decrease dose of TH

What is the treatment of choice for a pituitary adenoma?

Requires neurosurgical resection

CT/MRI → plucked through nose

What is the treatment of choice for a subclinical hyperthyroidism?

usually don’t treat unless TSH <0.1 mL

What is the treatment of choice for a thyroid storm?

supportive therapy: fluids, fever, nutrition

Treat precipitating event

High dose PTU

Iodide therapy

Beta blocker therapy

IV Glucocorticoids → in case of Grave’s disease