Thyroid Therapeutics

What are the three classifications of hypothyroidism

Primary, Subclinical, and Secondary

What does primary hyperthyroidism mean?

the thyroid gland itself is causing the disease/state

What does Secondary hypothyroidism mean?

the thyroid gland IS NOT causing the disease/state

- there's a SECONDARY problem

can either be the pituitary gland (secondary) or hypothalamus (tertiary)

What are the three main causes of primary hypothyroidism?

1. Chronic Autoimmune Thyroiditis

2. Iatrogenic Hypothyroidism (treatment-induced)

3. Iodine Defficiency (not common in the US)

What autoimmune disease is associated with primary hypothyroidism?

Hashimoto's Disease

What causes Iatrogenic Hypothyroidism?

Drugs, Radioactive iodine treatment, and Thyroidectomy

What drugs can cause Iatrogenic Hypothyroidism?

- AMIODARONE

- Lithium

- Carbamazepine

- interferons

- tyrosine kinase inhibitor (Suntinib)

What gland causes secondary hypothyroidism?

pituitary disease

What can causes pituitary disease (Secondary Hypothyroidism)?

tumors in pituitary gland, autoimmune (affecting the pituitary gland), radiation, trauma

What gland causes teritiary hypothyroidism?

hypothalamus

What can cause hypothalamic disease (tertiary hypothyroidism)

Radiation therapy, trauma, neoplasm

What's the main labratory value we look at with hypothyroidism?

TSH levels

What TSH levels indicate PRIMARY hypothyroidism?

ELEVATED (>4.5)

What TSH levels indicated elevated?

>4.5 mIU/L

Besides TSH, what lab value confirms primary hypothyroidism?

LOW T4

What is the normal range for T4 levels?

0.8-2.7 mcg/dL

What T4 level indicates primary hypothyroidism (with TSH being elevated)?

<0.8

Explain why you would see elevated TSH and low T4 levels in primary hypothyroidism

T4 and T3 levels are low so there is NO NEGATIVE FEEDBACK inhibiton

As a result, TSH levels will increase because there's nothing telling it to stop

Explain the normal physiology of the HPT axis

Under normal circumstances, T4 and T3 NEGATIVELY FEEDBACK to the hypothamus to regulate the release TRH and to regulate the pituitary to release TSH

If T4 and T3 levels are messed up, that interefers with the regulatory process since thyroid levels utimately control the release of TRH and TSH

What TSH and T4 levels would you see with SECONDARY Hypothyroidism?

Normal or low TSH

HIGH T4

Explain why TSH is elevated and T4 is high in Secondary hypothyroidism?

Secondary means the problem is with the pituitary

The pituitary is responsible for releasing TSH so that will be low

TSH regulates the release of thyroid horomes from the thyroid gland, TSH is not communicating with the thyroid gland and since the thyroid gland is not recieving the signal, T4 and T3 INCREASE (doesn't know when to stop)

What TSH and T4 levels indicate Subclinical Hypothyroidism?

HIGH TSH

NORMAL T4

T/F Clinical symptoms are always present with subclincal hypothyroidism

FALSE

NO SYMPTOMS- T4 and T3 are normal

When is treatment considered for subclinical hypothyroidism?

AGE

Clinical Symptoms PRESENT

TSH >10 (TOO HIGH)

For age, do we treat younger or older patients?

YOUNGER this is because they have LOW CV risk

What are clinical symptoms of hypothyroidism?

1. Cold Intolerance

2. Weight GAIN

3. Fatigue

4. Depression

5. constipation

6. irregular or heavy periods

7. dry skin

8. memory decline

joint and muscle aches

What are the treatment options for overt (primary) hypothyroidism?

1. Liothyronine (cytomel)

2. Levothyroxine (Synthroid)

3. Thyroid USP (Thyroid Armour)

we want to GIVE thyroid hormones

What treatment option only contains T3?

Liothyroxone (Cytomel)

What treatment option contains T4?

Levothyroxine (Synthroid)

What treatment option contains T3 and T4?

Thyroid USP (Thyroid Armour)

Out of all the thyroid therapeutics, which one is GOLD STANDARD for hypothyroidism?

LEVOTHYROXINE (SYNTHROID)!!!!

What is Levothyroxine?

Synthetic T4 hormone

What is the half-life of levothyroxine?

7 days

What are the available dosage forms for Levothyroxine?

1. Oral

2. IV

When is IV levothyroxine considered?

in patients who either can't tolerate PO or MYXEDEMA COMA (SERIOUS HYPOTHYROIDISM CRISIS)

What is the IV:PO ratio?

0.5:1

so 1/2 IV from PO

What is Levothyroxine dosing dependent on?

1. AGE

2. presence of Coronary Heart Disease (CHD)

What is the age cut off for levothyroxine when deciding treatment?

60

When should we use WEIGHT-BASED dosing for Levothyroxine?

Patient UNDER 60 years

this is because they can have MORE!

What Levothyroxine treatment is recommended in patients LESS THAN 60?

1.6 mcg/kg/day

How do we decide the dosing for patients <60?

use IBW and 1.6 mcg/kg/day

IBW for females formula

45.5 + (2.3 x inches over 60 (5ft))

IBW for males formula

50 + (2.3 x inches over 60 (5ft))

What is the levothyroxine treatment for patients > 60 (older)?

25-50 mcg/day

LOWER because they have more heart complications

What is the levothyroxine dosing for patients with coronary heart disease?

12.5-25 mcg/day

EVEN LOWER because they already have heart issues!

With Levothyroxine treatment, how often should TSH be monitored initially?

EVERY 4-6 WEEKS

this is because the t 1/2 life is 7 days and it takes 5 cycles of half life to reach steady state

What TSH level is too low for levothyroxine and how do you change the current dose?

TSH <0.5 (TOO LOW- gave them HYPERTHYROIDISM)

DECREASE dose by 12.5-25 mcg/day (not too much at first)

What TSH level indicates an INCREASE in dose and by how much?

TSH >4.5 (still HYPO- means we aren't taking care of the problem)

INCREASE dose by 12-25 mcg/day (again start low, can always titrate up!)

Once TSH levels are normal and patient is experiencing no symptoms, when should we monitor?

6 months after initial then yearly

- unless patients symptoms return sooner!

What are s/sx that levothyroxone cause hyperthyroidism (LOW TSH)

- Increased HR

- Palpitations

- Sweating

- Weight LOSS

- Arrythmias

- Irritability

OPPOSITE OF HYPO symptoms

What are precautions for levothyroxine?

1. Those with CVD- require LOW initial dose (12.5 mcg/day)

- this is because of Levo's CV side effect profile

2. OSTEOPOROSIS- may DECREASE BMD

What's an absolute contraindicated for Levothyroxine?

UNCORRECTED adrenal insufficiency

Treat adrenal insufficiency FIRST

What are counseling points for levothyroxine?

1. take this medication on an EMPTY STOMACH 60 min prior to meal

2. If can't in am take at bedtime 4 hours AFTER last snack/meal

3. Drugs that impair absorption of levothyroxine- seperate doses for AT LEAST 4 HOURS

4. Levothyroxine can interfere with Warfarin and Theophyline levels

5. DO NOT SWITCH BETWEEN BRANDS (not interchangeable)

What drugs impair absorption of levothyroxine and why?

Anything that makes the pH in the stomach more alkaline since Levothyroxone is absorbed in the stomach

- PPIs

- calcium carbonate (tums)

- aluminum hydroxide

- ferrous sulfate

- phosphate binders

- oral BISPHOSPHONATES (alendronate)

When do we consider Liothyronine(cytomel) and Thyroid USP (Thyroid Armour) when treating hypothyroidism?

if patient doesn't respond to Levothyroxine (not first-line)

What are the considerations for Liothyronine (cytomel)?

take in COMBO with Levothyroxine due to RAPID onset and short t1/2 life (1.5 days)

should ONLY be used SHORT-TERM

What does Thyroid USP consist of in the formulation? Who shouldn't take Thyroid USP

Descicated pork thyroid gland

- consider to AVOID in patients who don't consume animal/pork (vegan, religious belief)

What is the T4:T3 ratio for Thyroid USP (Thyroid Armour)?

4:1

T/F the generic Thyroid USP is bioequivalent to the brands

FALSE

SAME WITH LEVOTHYROXINE!

For ALL of the medications used to treat hypothyroidism, they contain a box warning for what?

WEIGHT REDUCTION

- no bitch you cannot use this to lose weight or you'll die

What can untreated maternal hypothyroidism cause?

Spontaneous abortion, stillbirth, premature birth, low birth wght, impaired neurcognitive development, gestational HPTN, preeclampsia

NOT ENOUGH THYROID HORMONE HARMS THE BABY!

What is the preferred drug for hypothyroidism in pregnancy?

LEVOTHYROXINE

T/F Levothyroxine is safe to use during breast feeding

TRUE

If a patient ALREADY HAS HYPOTHYROIDISM and becomes pregnant, what should we do to their current dose?

20-30% dose INCREASE

this is because we now have a fetus so need more thyroid hormone for fetal developement

If a patient becomes pregnant and is NEWLY DIAGNOSED with OVERT (primary) HYPOTHYROIDISM, what dose of leveothyroxine do we recommended?

the usual for primary: 1.6 mcg/kg/day

What is a patient becomes pregnant and developes SUBCLINICAL Hypotension, what do we do?

High TSH but normal T4

TEST FIRST: thyroid peroxidase antibody

THEN: 1mcg/kg/day or 25-50 mcg/day

recheck thyroid levels as appropriate

What is the Hypothyroidism crisis?

MYEDEMA COMA

What is myxedema coma?

The end-stage of long-standing uncorrected hypothyroidism

EMERGENCY- body is unable to maintain critical functions!

What is the mortality rate of myxedema crisis?

60-70%

What are the RISK factors associated with myxedema coma?

1. Females

2. > 60 years

3. Winter

What are the PRECIPITATING factors associated with myxedema coma?

1. cold weather/hypothermia

2. stress

3. illness

How is myxedema coma presented?

1. LOW body temp (HYPOTHERMIA, <95.9 F)

2. ALTERED MENTAL STATUS (delirium, coma)

3. Advanced stages of hypothyroidism symptoms

4. LAB ABNORMALITIES

What lab abnormalities are present with myxedema coma?

1. VERY ELEVATED TSH (>10 or even higher)

2. Abnormally LOW (almost nonexistent) T4 and T3

3. Anemia (low BC), Hyponatremia(low Na), hypoglycemia (low glucose), elevated total creatinine (CPK)

What are the supportive therapy options for myxedema coma?

1. Ventillation

2. BP

3. Temperature (warming the patient)

4. glucose

What are the therapeutic drugs used to treat myxedema coma?

1. IV LEVOTHYROXINE (Bolus then maintenance)

- can trasition to PO once stable

2. Glucocorticoids

- myxedema coma clears glucocorticoids so want to gove it back!

3. Treantment for the underlying disorder (mainly long-standing hypothyroidism but can be due to acute illnesses such as infection, MI, surgery)

What is the goal for myxedema coma?

NORMAL TSH and T4 levels

What TSH levels do you expect for primary HYPERthyroidism?

LOW TSH levels

What TSH level indicates primary hyperthyroidism?

<0.5

What T4 levels do you expect for primary hyperthyroidism?

HIGH (>2.7)

Explain why TSH is low and T4 is elevated for primary hyperthyroidism

the thyroid hormones is producing INCREASED levels to T3 and T4 (HYPER)

- Negative feedback OCCURS so it communicates to the hypothalamus and pituitary to LOWER TRH and TSH

Unlike secondary hypothyroidism, there is NO PROBLEM with the pituitary gland so TSH levels will respond!!

What are the three common causes of overt (primary) hyperthyroidism

1. Grave's disease (Autoimmune)

2. Thyroid storm

3. Drug-induced

What drug induces primary hyperthyroidism?

AMIODARONE

What autoimmune disorder is associated with primary hyperthyroidism?

Grave's disease

What are clinical presentations (common findings) with Grave's Disease?

1. Exophthalmos (bulging of eye)

2. Goiter (enlarged thyroid)

3. Pretibial myxedema (lower legs have flakey flaps of scaley skin with edema (swelling))

What TSH and T4 levels do you expect to see with SECONDARY hyperthyroidism?

1. ELEVATED TSH

2. HIGH T4

Explain the reason behind secondary hyperthyroidism having elevated TSH and high T4

Dysfunction with the hypothalamus or pituitary gland causes TRH and TSH to be ELEVATED leading the thyroid gland to produce MORE T3 and T4

What do you expect Subclinical Hyperthyroidism TSH and T4 levels to be

LOW TSH

NORMAL T4

WITH SUBCLINICAL, T4 IS ALWAYS NORMAL!!!! (Doesn't matter hypo or hyper!)

Secondary means opposite TSH of what you'd expect!!!

What are common causes for secondary hyperthyroidism?

1. TSH- producing Tumors

- pituitary adenoma

2. HCG-mediated

- Chroriocarcinoma (rare agressive cancer in the placenta)

- Hyperemesis gravidarum (EXCESSIVE nausea/vomitting during pregnancy NOT related to morning sickness)

emesis= vomitting

What is the most common cause of hyperthyroidism?

Graves disease (autoimmune)

What are the risk factors associated with Grave's Disease?

- 30-50 years of age

- Female gender (us females are COOKED)

- Family history

- Presence of another autoimmune disease (mainly Type I DM, RA, lupus, celliac's and MS)

What are the drug treatment choices for hyperthyroidism?

ANTI-thyroid drugs: THIONAMIDES

Adjuvent therapy: beta blockers, potassium iodide

What are other therapeutic options for hyperthyroidism?

- Ablation therapy

- Radioactive iodine

- Thyroidectomy (removal of thyroid gland)

What are the thionamides used to treat hyperthyroidism?

1. Methimazole (MMI)

2. Propylthiourcil (PTU)

What is the preferred first-line thionamide agent and why?

Methimazole because:

1. it is 10x more potent than Propylthiouricil (PTU)

2. Propylthiouricil also has a worse side effect profile

3. Patient's have better adherence with Methimazole (dosed once daily vs TID)

When is Methimazole NOT first line (exceptions)

1. 1ST TRIMESTER PREGNANCY

2. THYROID STORM (EMERGENCY)

What is the initial and maintanence dose for Methimazole?

initial: 10-20 mg/day (or BID)

maintenance: 5-10 mg/day

What is the initial and maintenance dose for Propylthiouracil?

initial: 50-150 mg TID

maintanence: 50 mg BID-TID

What are commone side effects associated with Thionamides (Methiazole and Propylthiouracil)?

- Diarrhea

- Headache

- Fever

- loss of taste

What are the RARE side effects with Thionamides (Methiazole and Propylthoiuracil)?

1. HEPATOTOXICITY (only one)

2. AGRANULOCYTOSIS (BOTH)

3. DRUG-INDUCED LUPUS ERYTHEMATOSUS (BOTH)

Which thionamide has a black box warning for hepatotoxicity?

PROPYLTHIOURACIL (PTU)