Thyroid Disorders

Front 1

Goal of tx of Grave's syndrome

Back 1

relieve or prevent the symptoms of thyrotoxicosis for a sustained period of time (months) until the conditions goes into remission.

Front 2

3 effective and relatively safe initial treatment options for Grave’s

Back 2

1. antithyroid drugs (thioamides)
2. radioactive iodine (I131)
3. surgery (thyroidectomy)

Front 3

2 general tx options for hashimoto's thyroiditis

Back 3

1. Replace thyroid hormones
2. Synthetic thyroid hormones

Front 4

Goals of tx for hashimoto's thyroiditis

Back 4

achieve a euthyroid state

Others: relief of sxs, normal growth & development of infants and children

Front 5

Name the 2 Antithyroid drugs (Thioamides)

Back 5

1. Methimazole
1. Propylthiouracil (PTU)

Front 6

Brand name for Methimazole

Back 6

Tapazole

(no brand name listed for PTU)

Front 7

Dosing and administration of antithyroid drugs (Thioamides)

Back 7

• Initial therapy is to achieve euthyroidism
• Maintenance therapy is continued until remission is achieved

Front 8

Indication for methimazole (Tapazole)

Back 8

Should be used for every patient EXCEPT:
1. 1st trimester of pregnancy
2. tx of thyroid storm (use PTU)
3. If side effects occur

Front 9

Initial and maintenance dosing for methimazole (Tapazole)

Back 9

Initial: 10-20 mg daily for 6-8 weeks or until patient is euthyroid
Maintenance: 5-10 mg daily
Duration: usually 12-18 months

Front 10

Initial and maintenance dosing for PTU

Back 10

Initial: 50 to 150 mg TID
Maintenance: 50 mg two to three times/day
Duration of therapy: 12-18 months.

Front 11

Before starting therapy with thioamides obtain the following:

Back 11

• Complete blood count including white count with differential
• Liver profile including bilirubin and transaminases

Front 12

Major Adverse Reactions to thioamides

Back 12

1. Benign transient leukopenia
2. Agranulocytosis
3. Drug-induced hepatotoxicity

Front 13

Benign transient leukopenia

Back 13

• WBC count < 4000 mm3
• Occurs in 12% of adults and 25% of children
• Does not lead to agranulocytosis- so therapy can be continued

Front 14

Agranulocytosis

Back 14

• PTU may rarely cause agranulocytosis. Low doses of methimazole may be less likely to do so.
• Agranulocytosis is defined as neutrophils < 500/mm3
• Prevalence is 0.5 to 6%
• Most severe adverse hematological reaction
• Patients should be instructed to report immediately the following symptoms: rash, fever, sore throat, flu-like symptoms. A differential white blood cell count should be obtained during febrile illness and at the onset of pharyngitis.
• Usually occurs in the first three months of therapy but can occur as last as 12 months. Delayed reaction most likely to occur with methimazole.
• Routine serial WBC are not recommended
• Cause: allergic reaction (idiosyncratic) or toxic (dose-related)
• If diagnosed, discontinue drug, monitor for signs of infection and initiate antibiotics
• Granulocytes reappear within days to 3 weeks
• If death occurs it is due to overwhelming infection
• Do not rechallenge patient with same or other thioamide

Front 15

Drug-induced hepatotoxicity

Back 15

• PTU can cause fulminant hepatic necrosis that can be fatal
• Methimazole hepatotoxicity is typically cholestatic
• Usually occurs in the first three months of therapy
• Can occur with either drug
• Prevalence 1.3%
• Transient elevations in liver transaminases occur in 30% of asymptomatic patients in first 2 months on PTU—usually returns to normal within three months of reducing dose to maintenance therapy
• Symptoms: nausea, vomiting, diarrhea, fatigue and abdominal tenderness
• Drug should be discontinued if clinical symptoms of hepatitis occur

Front 16

Goal of therapy with the thioamides

Back 16

to render the patient euthyroid as quickly and safely as possible.

Front 17

Indications for use of Radioactive iodine therapy (RAI)

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o Poor surgical candidates
o People who did not respond to drug therapy or had unacceptable adverse reactions
o People who developed recurrent hyperthyroidism after surgery

Front 18

Contraindication for RAI

Back 18

PREGNANCY

Front 19

Adverse effects of RAI

Back 19

1. Transient increases in thyroid hormone- usually w/in the first 10 days
2. Thyroid storm (from leakage of thyroid hormone from damaged thyroid cells)
3. Later on: Hypothyroid

Front 20

Administration form of RAI

Back 20

Colorless and tasteless liquid, t1/2 of 8 days

Front 21

What can be given prior to RAI to prevent sxs from transient increases in thyroid hormone release?

Back 21

BBs or thioamides

Front 22

Generic name for RAI

Back 22

Sodium iodide 131

Front 23

What is surgery considered in tx of grave's dz?

Back 23

treatment of choice when there is a contraindication to the use of thioamides or RAI or a large goiter is present that does not regress with other therapy

Front 24

Indication for synthetic thyroid hormone products

Back 24

Considered drug of choice for the treatment of hypothyroidism

Front 25

Brand names for Levothyroxine, L-thyroxine or L-thyronine

Back 25

1. Synthroid
2. Levothroid
3. Tirosint

Front 26

Dosing for L-thyroxine in an adult w/ little residual thyroid fx

Back 26

1.6 mcg/kg/day

Front 27

Dosing for L-thyroxine in pt 50-60 y/o w/out coronary heart disease

Back 27

50 mcg/day

Front 28

Dosing for L-thyroxine in older pts or those w/ known cardiac dz

Back 28

Initial: 12.5 to 25 mcg/day
Trate by 12.5 to 25 mcg at monthly intervals to avoid cardiac stress or exacerbating angina

Front 29

Monitoring in pts with known cardiac dz

Back 29

onset of angina symptoms very important

Front 30

Dosing scheme for subclinical hypothyroidism based on TSH:

Back 30

• 25 mcg for TSH 4-8 mIU/L
• 50 mcg for TSH 8-12 mIU/L
• 75 mcg for TSH >12 mIU/L

Front 31

What should dosage adjustments be based on for pts with primary hypothyroidism?

Back 31

serum TSH determinations

Front 32

When should a trough TSH serum concentration be checked for primary hypothyroidism?

Back 32

4-8 weeks

Front 33

What should be assessed for pts w/ pituitary or hypothalamic failure?

Back 33

Free T4, not TSH should guide dosing

Front 34

Doses of thyroid hormone over what dose are rarely necessary

Back 34

200 mcg

*may be a result of non-adherence to prescribed dose

Front 35

Adverse effects of overtreatment w/ thyroid hormone:

Back 35

o Possible atrial fibrillation in the elderly
o Accelerated bone loss in postmenopausal women

Front 36

Goal of thereapy with synthetic thyroid hormone products

Back 36

TSH within normal limits. The upper limit of normal is controversial with a range of 2.5 to 4.12 mIU/L.

Front 37

Considerations for maintenance therapy with Levothyroxine

Back 37

1. T4 dose usually remains stable once a person becomes euthyroid
2. Reduce dose as patient ages
3. Monitor TSH (most sensitive indicator of T4 therapy). Check every 4-8 weeks until euthyroid state is attained. An elevated TSH indicates insufficient treatment if adherence to medication regimen is good.

Front 38

Adverse effects of synthetic thyroid hormones

Back 38

thyrotoxic symptoms can occur with over-replacement – angina, high output failure, MI, tremors, anxiety, nervousness, weight loss. Allergic reactions very rare to levothyroxine

Front 39

Drugs that may interfere with absorption of synthetic thyroid hormones

Back 39

aluminum hydroxide
calcium carbonate
cholestryramine
ferrous sulfate
fiber supplements
soybean formula

Administer thyroid agents first; separate administration of these drugs by at least 2 hours (best to take levothyroxine in the morning on an empty stomach one hour before a meal or other medications)

Front 40

Drugs that increase T4 clearance:

Back 40

rifampin, carbamazepine, and phenytoin

Front 41

What effect does Amiodarone have on synthetic thyroid hormone products?

Back 41

may block the peripheral conversion of T4 to T3

Front 42

Why is it so important to monitor for liver toxicity and agranulocytosis w/ thioamides?

Back 42

PTU may rarely cause agranulocytosis. Can be fatal.
*pts should report rash, fever, sore throat, flu-like sxs and a differential wbc count should be optained during febrile illness and at onset of pharyngitis

Either drug can cause fulminant hepatic necrosis that can be fatal.

Front 43

Beta blocker use for tx of sxs of hyperthyroidism

Back 43

Beta blockers without intrinsic sympathetic activity (propranolol, atenolol, metoprolol) are used:
• As adjunctive treatment during thyroid storm (IV esmolol can be used in an ICU setting)
• To prepare patients for surgery
• To manage pregnant patients with thyrotoxicosis in the short-term
• Primary therapy for thyroiditis or iodine-induced hyperthyroidism

Front 44

What symptoms can BBs decrease rapidly in hyperthyroidism?

Back 44

Nervousness, palpitations, fatigue, weight loss, excessive sweating, heat intolerance, and tremor

Front 45

Dosage for BBs in hyperthyroidism

Back 45

Propanolol 10 to 40 mg QID (heart rate < 90 beats/minute)

Front 46

Contraindications to use of BBs

Back 46

decompensated heart failure, asthma, COPD, concomitant MAO inhibitors, or tricyclic antidepressants use

Front 47

If BBs are contraindicated, what drug can be used instead?

Back 47

Diltiazem 120 mg TID or QID can be used

Front 48

Thyrotoxicosis factitis

Back 48

hyperthyroidism produced by the ingestion of exogenous thyroid hormone

Front 49

Most common non-thyroid disorder for which thyroid hormone is prescribed

Back 49

Obesity

Front 50

When to suspect thyrotoxicosis factitis

Back 50

when a patient presents with a symptoms of thyrotoxicosis without gland enlargement or eye symptoms

Front 51

Long term effects of hyperthyroidism

Back 51

anxiety, heart palpitations, tremor, emotional instability, easy fatigability, muscle atrophy and weakness, diarrhea, excessive sweating, heat intolerance and preference for cold. Warm, moist skin, fine hair, goiter, gynecomastia in men, hyperreactive deep tendon reflexes.

In patients over age 60, heart and muscle complaints are most common.

In children, rapid growth with increased bone maturation occurs.

Cardiac: refractory a fib

Front 52

Tx of myxedema coma

Back 52

• T4 replacement:
-400 to 500 mcg IV (intravenous; IV preferred over IM because of erratic absorption) given initially in younger patients without cardiac disease.
-Reduce dose to 300 mcg daily IV until patient can take PO.
-Begin with 50 to 100 mcg daily and titrate to response.
•Supportive measures: ventilation, IV hydrocortisone, manage blood glucose, maintain plasma volume, eliminate precipitating factors
•With proper treatment, patient is conscious and TSH ↓ within 24 h

Front 53

Importance of treating thyroid dz during pregnancy

Back 53

untreated maternal hypothyroidism can lead to increased rate of miscarriage, stillbirths, congenital defects, and mental retardation

Front 54

Tx of hypothyroidism in pregnancy

Back 54

1. Levothyroxine is drug of choice
2. Monitor TSH and total T4 should be monitored every four weeks during the first half of pregnancy. The TSH should be checked at least once between 26 and 32 weeks gestation. Adjust dose as needed.
3. The goal of therapy in pregnancy is to normalize the serum TSH values within a trimester-specific pregnancy range (first trimester, 0.1-2.5 mIU/L; second trimester 0.2-3.0 mIU/L; third semester 0.3-3.0mIU/L).
4. Coadministration of iron and calcium may decrease thyroxine absorption. Levothyroxine should be taken first thing in the morning at least one hour before a meal is eaten.
5. For women who have treated hypothyroidism prior to pregnancy should increase their levothyroxine dose by ~25-30% upon a missed menstrual cycle or positive pregnancy test and notify their provider. This can be done by increasing levothyroxine from 7 doses/week to 9 doses/week (~29% increase).
6. All pregnant women with treated-hypothyroidism who are planning a pregnancy should optimize thyroid status prior to conception (TSH < 2.5 mIU/L)

Front 55

Tx of hyperthyroidism during pregnancy

Back 55

1. Thyrotoxic women need to be euthyroid before attempting pregnancy
2. PTU is the preferred thioamide for the treatment of hyperthyroidism in the first trimester. Patients on methimazole should be switched to PTU if pregnancy is confirmed in the first trimester. Following the first trimester, consider switching to methimazole.
3. PTU and methimazole cross the placenta. In order to avoid deleterious effects on the baby, the goal is to maintain the free T4 level at or just above the upper limits of normal. Free T4 and TSH should be monitored every 2 to 6 weeks.

Front 56

Tx of congenital hypothyroidism

Back 56

1. infants routinely screened for hypothyroidism
2. levothyroxine is drug of choice. T4 tablets can be crushed and mixed with formula or breast milk
3. initial dose 12 to 17 mcg/kg/day. Therapy needs to begin as soon as possible to maintain normal neurological development. A delay of weeks to a few months can result in significant drops in the child’s IQ
4. goal of therapy is to keep the T4 in the upper normal range from 10 to 18 mcg/dL during the first 2 weeks of therapy and then 10 to 16 mcg/dl thereafter.

Front 57

Tx of hyperthyroidism during breast-feeding

Back 57

1. Methimazole in doses up to 20-30 mg/day is safe for lactating mothers and their infants.
2. Administer following a feeding and in divided doses.

Front 58

How does lithium effect thyroid levels?

Back 58

-chronic lithium therapy inhibits the release of thyroid hormone from the gland
- T4 and T3 levels fall and TSH rises
- hypothyroidism
-most patients with lithium induced hypothyroidism have a family history of thyroid disease; obtain baseline before initiating lithium and check every 6 mo once lithium started

Front 59

Why can amiodarone cause hypo or hyperthyroidism?

Back 59

- high iodine content- 12 mg of free iodine is released per 400 mcg dose of amiodarone
- also prevents the peripheral conversion of T4 to T3 (high free T4 levels and low T3 levels)

Front 60

- How do you treat amiodarone induced hypothyroidism?

Back 60

- occurs in 6-10% of patients
- can occur at any time and is not dose related
- lab findings are a normal free T4 with an elevated TSH
- use T4 replacement and continue amiodarone

Front 61

How does amiodarone inducehyperthyroidism? What will thyroid function test show?

Back 61

- it occurs early and suddenly
- patient will have thyrotoxic symptoms
- tests will show elevated thyroid hormone levels; low TSH

Front 62

What is Type I Hyperthyroidism from amiodarone?

Back 62

- related to iodine load in susceptible patients (preexisting thyroid disorders)
-large amounts of thyroid hormone produced in response to large iodine load

Front 63

What is Type II Hyperthyroidism from amiodarone?

Back 63

- direct destruction of thyroid cells by amiodarone and leads to a large release of thyroid hormone (no preexisting thyroid disorder)

Front 64

How do you treat type I induced hyperthyroidism?

Back 64

-methimazole or PTU to block hormone synthesis
- potassium perchlorate can be used by only in patients who can't tolerate methimazole or PTU alone

Front 65

How do you treat type II induced hyperthyroidism?

Back 65

- beta blockers for the symptoms (metoprolol, atenolol, propanolol)
- prednisone for its anti-inflammatory action

Front 66

What are risk factors for patient to develop interferon gamma induce hypothyroidism? how do you treat it?

Back 66

-patient risk factors that can lead to development of hypothyroidism are
1. presence of antithyroid antibodies present before therapy with interferon gamma
2. female gender
3. Asian
-tx with T4 if symtoms warrant
- problem usually resolves 2-3 mo. after interferon stopped

Front 67

What are the types of hyperthyroidism from interferon gamma?

Back 67

-less common than hypothyroidism from interferon gamma
-Graves disease like disorder
- hyperthyroid thyroiditis (similar to type II) due to toxic effect on the gland
-Tx with beta blockers if symptoms are bothersome