Download Thyroid disorders Lecture

Thyroid Disorders
PHCL 442
Hadeel Al-Kofide MS.c
Topics to be covered
• Thyroid physiology
• Hypothyroidism
• Hyperthyroidism
Thyroid Physiology
Hypothyroidism
• Causes
• Clinical presentation
• Goals of therapy
• Treatment options
• Monitoring
• Special considerations
Hypothyroidism
Causes
• Primary:
 Autoimmunue disease: Genetic, more common in female
 Iatrogenic destruction of thyroid: Example: in surgey
 Drug induced: example: Iodine & lithium
• Secondary:
 Due to deficiency in TSH or TRH
Hypothyroidism
Clinical Presentation
• Increase weight
• Loss of appetite
• Cold intolerance
• Headache
• Muscle cramps & pain
• Weakness, tiredness & fatigue
• Dyspnea
• Constipation
Symptoms
Hypothyroidism
Clinical Presentation
• Thin brittle nails
• Puffiness of face & eyelid
• Yellowish skin
• Thinning of outer eyebrow
• Peripheral edema
• Bradycardia
• Hypertension
Physical Findings
Hypothyroidism
Clinical Presentation
• High TSH
• Low T3 & T4
• Positive antibodies
• Anemia (decrease Hct & Hgb)
Laboratory
Hypothyroidism
Goal of Therapy
• Normalize thyroxin level
• Provide symptomatic relief
• In a child, or infant we want to maintain normal growth &
development
Hypothyroidism
Treatment
1) Natural thyroid products: Desiccated thyroid (T3 & T4)
• Problems with these preparations is that they can cause severe
allergy
• There is no bioequivalence: different content from batch to
batch
• It losses its potency by time
NO more used
Hypothyroidism
Treatment
2) Triiodothyroxine (T3)
• Not recommended for routine use due to:
 Short acting given 4 times a day
 Because this drug contains the active form T3 this can
cause fast supra-physiological levels then soon go back to
normal & so on (fluctuation)
 This is considered a major problem specially in elderly
patients & patients with cardiac problems
Hypothyroidism
Treatment
2) Triiodothyroxine (T3)
• Used only in the following situations:
 Myxedema coma
 Patients with impaired conversion from T4 to T3
Hypothyroidism
Treatment
3) Liotrix (T3 & T4)
• Combination of T4 & T3 (4:1)
• It has same disadvantages of any preparation containg T3
• Expensive
• Not commonly used
Hypothyroidism
Treatment
4) Levothyroxine
• Drug of choice in hypothyroidism
• Advantages:
 Stability & uniform potency
 Low cost
 No allergy
 Long half life (7 days so can give once daily)
Hypothyroidism
Treatment
4) Levothyroxine
• Due to problems in drug absorption we advice patients to take
it on empty stomach (at least 60 minutes before meals)
• Cholestyramine, sucralfate, aluminum containing antacid can
decrease absorption so must space between them
• Also it is affected by enzyme inducers & inhibitors (ex:
rifampicin)
• Dose: 1.6 – 1.7 mcg/kg/day
Hypothyroidism
Monitoring
• Improvement in symptoms
• Improvement in lab findings
• Improvement will start in 2-3 weeks but maximum effect after
4 -6 weeks
• Monitor patients for TSH, T3 & T4 every 6-8 weeks
Hypothyroidism
Special Considerations
Pregnancy:
• Usually pregnant women require larger doses of thyroxine,
around 20-50% increase in dose
• After delivery can go back to usual dose
Hypothyroidism
Special Considerations
Subclinical hypothyroidism:
• Normal T3 & T4 but high TSH
• Only mild symptoms
• Look at each patient individually then it depends if you will
treat him or not
• Patients with TSH more than 10 mIU/L must be given
thyroxine even in the absence of symptoms
Hypothyroidism
Special Considerations
Myxedema coma:
• The end stage of long standing uncorrected hypothyroidism
• It can lead to coma, hypoxia & psychosis
• Mortality from 60-70%
• Treatment of choice: could use products with T3 (fast action)
but better is IV L-thyroxine 400-500 mcg
Hyperthyroidism
• Causes
• Clinical presentation
• Goals of therapy
• Treatment options
• Monitoring
• Special considerations
Hyperthyroidism
Causes
1) Graves’ disease:
• Autoimmune disease: the presence of antibodies affecting TSH
• All gland is hyperactive producing large amounts of thyroid
hormone
• Ocular symptoms common in graves’ disease
Hyperthyroidism
Causes
2) Other causes:
• Tumors: could be benign or malignant
• Thyroditis: inflammation (may be due to viruses)
• Drug induced: exogenous thyroid hormone replacement
Hyperthyroidism
Clinical Presentation
• Heat intolerance
• Weight loss with increased appetite
• Palpitation
Symptoms
• Nervousness
• Tachycardia
• Hypertension (but here due to increase sympathetic tone)
Hyperthyroidism
Clinical Presentation
• Diarrhae (due to increased GI activity)
• Tremor
• Weakness
• Fatigue
• Amenorrhea in female
Symptoms
Hyperthyroidism
Clinical Presentation
• Exophthalmos: lid lag, lid retraction, chemosis, conjunctivitis,
periorbital edema, & loss of extraorbital movement
• Thinning of hair
• Moist skin
Physical
Findings
Hyperthyroidism
Clinical Presentation
• Increase T3 & T4
• Increased Free T3 & T4
• Low TSH
• Thyroid receptor antibodies (TPO antibodies)
• Increase liver enzymes
• Radioactive iodine uptake, how?
Laboratory
Hyperthyroidism
Goals of Therapy
• Decrease amount of thyroid hormone
• Improve symptoms of the disease
Hyperthyroidism
Treatment Modalities
• Surgery
• Drugs
• Radioactive iodine
Hyperthyroidism
Surgery
Treatment of choice in:
1. Suspected malignancy
2. Patients with goiter with difficulty of breathing
3. Contraindications to other modalities (ex: pregnancy)
4. Failure to respond to medications
Hyperthyroidism
Surgery
•
Subtotal thyroidectomy: avoid risk of hypothyroidism, but
risk of recurrent hyperthyroidism
•
If hyperthyroidism occurred after surgery, do not do it again
but use other treatment modalities
Hyperthyroidism
Surgery
•
Advantages: Quick & no lag time
•
Disadvantages: expensive, complications
•
Before surgery must be in euthyroid state, because with
surgical manipulation there may be release of high amount of
thyroid hormones leading to severe hyperthyroidism (thyroid
storm)
Hyperthyroidism
Drugs used in Hyperthyroidism
Thioamides:
1. Propylthiouracil
2. Methimazole
•
Mechanism of actions:
 They inhibit thyroid hormone synthesis
 They also suppress autoantibody synthesis
Hyperthyroidism
Drugs used in Hyperthyroidism
Thioamides:
•
Methimazole: drug of choice because only one tablet is
requires, less expensive & no bitter taste
•
Propylthiouracil: needs 7 tablets 2-3 times/day, but it is safer
in pregnant & lactation; have the advantage of inhibiting
converting T4 to T3 so decreasing the active form & this is
an advantage for patients with thyroid storm
Hyperthyroidism
Drugs used in Hyperthyroidism
Thioamides:
•
Monitoring therapy:
1. Baseline FT4 & TSH before treatment then measure every 46 weeks, then when normal every 3 months, if normal for 2
times then measure yearly
2. They can cause agranulocytosis: make baseline WBC &
differentials before treatment & during therapy
3. Liver function test
Hyperthyroidism
Drugs used in Hyperthyroidism
Thioamides:
•
Duration of therapy: 1- 2 years but patients may need it for
life, so duration of treatment depends on individual patient
Hyperthyroidism
Drugs used in Hyperthyroidism
Thioamides:
•
Side effects:
1. Rash: if mild continue therapy but give antihistamine or
topical steroids. If more severe rash change to other
thioamide (cross allergy is uncommon)
Hyperthyroidism
Drugs used in Hyperthyroidism
Thioamides:
•
Side effects:
2. Hepatitis: Increase in liver function test, with
propylthiouracil it is not dose related but with methimazole
doses more than 40 mg increase risk of hepatitis. If liver
functioned increased early in therapy then went to normal can
continue on same treatment but if kept increasing then must
DC the drug
Hyperthyroidism
Drugs used in Hyperthyroidism
Thioamides:
•
Side effects:
3. Agranulocytosis: decrease in neutophils, usually develops
within the first 3 months of treatment. Tell the patient to
watch for symptoms such as: unexplained fever, blue like
symptoms & sore throat
Hyperthyroidism
Radioactive Iodine
•
The only organ which traps iodine (advantage)
•
This radioactive iodine causes death of cells
•
Minimum side effects because don’t go to other sites in the
body
•
Before treatment patient must be in euthyroid state (use
drugs)
Hyperthyroidism
Radioactive Iodine
Treatment of choice in:
•
Patients failed other treatment modalities
•
Debilitated patient (or patients with poor surgical candidates)
•
Recurrent hyperthyroidism after surgery
Contraindication:
•
Pregnancy
Hyperthyroidism
Radioactive Iodine
Advantages:
•
Safe, effective treatment, painless & economic
Disadvantage:
1. Takes long time 10-12 months for total affect to appear
2. Patients fear from radiation
3. Patients will have hypothyroidism
Hyperthyroidism
Radioactive Iodine
Advantages:
•
Safe, effective treatment, painless & economic
Disadvantage:
1. Takes long time 10-12 months for total affect to appear
2. Patients fear from radiation
3. Patients will have hypothyroidism
Hyperthyroidism
Beta-Blockers
•
Because increase sympathetic activity, beta-blockers may
help in reducing symptoms
•
Propranolol have the advantage of inhibiting the conversion
of T4 to T3 (useful in thyroid storm)
Advantages:
1. Used as adjunct to surgery & radioactive iodine to control
symptoms
2. In pregnant women until she delivers to control symptoms
Hyperthyroidism
Iodinated Contrast Media
•
Effective short term treatment
•
They have the advantage of inhibiting the conversion of T4 to
T3
•
Used in: Pre-surgery& after radioactive iodine (not before)
•
Not used in: pregnancy
•
Must give with it thioamides (need around 8 weeks to work)
Hyperthyroidism
Monitoring Therapy in Hyperthyroidism
•
T3, T4 & TSH: every 4-6 weeks then every months then
yearly
•
Watch signs & symptoms of hypothyroidism (specially after
surgery or radioactive iodine)
Hyperthyroidism
Pregnancy & Hyperthyroidism
•
Hyperthyroidism can happen during early pregnancy &
symptoms decrease after 2nd or 3rd trimester
•
So at this stage patients may not take their medication so after
delivery there will be exacerbation leading to thyroid storm
•
Treatment of choice: surgery or thioamides
Hyperthyroidism
Thyroid Storm
•
Acute onset of fever, tachycardia, tachypnea, confusion,
psychosis & coma
•
Mortality rate can reach 50%
•
Needs acute & immediate treatment
•
Treatment: Please look at table 49-11 at applied therapeutics
Thank you