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

Causes Primary: Autoimmunue disease: Genetic, more common in female 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

Clinical Presentation Hypothyroidism Clinical Presentation Increase weight Loss of appetite Cold intolerance Headache Muscle cramps & pain Weakness, tiredness & fatigue Dyspnea Constipation Symptoms

Clinical Presentation Hypothyroidism Clinical Presentation Thin brittle nails Puffiness of face & eyelid Yellowish skin Thinning of outer eyebrow Peripheral edema Bradycardia Hypertension Physical Findings

Clinical Presentation Hypothyroidism Clinical Presentation High TSH Low T3 & T4 Positive antibodies Anemia (decrease Hct & Hgb) Laboratory

Goal of Therapy Normalize thyroxin level Provide symptomatic relief 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

Treatment 2) Triiodothyroxine (T3) 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

Treatment 2) Triiodothyroxine (T3) Hypothyroidism Treatment 2) Triiodothyroxine (T3) Used only in the following situations: Myxedema coma Patients with impaired conversion from T4 to T3

Treatment 3) Liotrix (T3 & T4) Combination of T4 & T3 (4:1) 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

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)

Treatment 4) Levothyroxine 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

Monitoring Improvement in symptoms Improvement in lab findings 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

Special Considerations 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

Special Considerations 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

Special Considerations 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

Causes 1) Graves’ disease: 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

Causes 2) Other causes: Tumors: could be benign or malignant Hyperthyroidism Causes 2) Other causes: Tumors: could be benign or malignant Thyroditis: inflammation (may be due to viruses) Drug induced: exogenous thyroid hormone replacement

Clinical Presentation Hyperthyroidism Clinical Presentation Heat intolerance Weight loss with increased appetite Palpitation Nervousness Tachycardia Hypertension (but here due to increase sympathetic tone) Symptoms

Clinical Presentation Hyperthyroidism Clinical Presentation Diarrhae (due to increased GI activity) Tremor Weakness Fatigue Amenorrhea in female Symptoms

Clinical Presentation Hyperthyroidism Clinical Presentation Exophthalmos: lid lag, lid retraction, chemosis, conjunctivitis, periorbital edema, & loss of extraorbital movement Thinning of hair Moist skin Physical Findings

Clinical Presentation 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

Goals of Therapy Decrease amount of thyroid hormone Hyperthyroidism Goals of Therapy Decrease amount of thyroid hormone Improve symptoms of the disease

Hyperthyroidism Treatment Modalities Surgery Drugs Radioactive iodine

Surgery Treatment of choice in: Suspected malignancy Hyperthyroidism Surgery Treatment of choice in: Suspected malignancy Patients with goiter with difficulty of breathing Contraindications to other modalities (ex: pregnancy) 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

Surgery Advantages: Quick & no lag time 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)

Drugs used in Hyperthyroidism Thioamides: Propylthiouracil Methimazole Mechanism of actions: They inhibit thyroid hormone synthesis They also suppress autoantibody synthesis

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

Drugs used in Hyperthyroidism Thioamides: Monitoring therapy: Baseline FT4 & TSH before treatment then measure every 4- 6 weeks, then when normal every 3 months, if normal for 2 times then measure yearly They can cause agranulocytosis: make baseline WBC & differentials before treatment & during therapy Liver function test

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

Drugs used in Hyperthyroidism Thioamides: Side effects: Rash: if mild continue therapy but give antihistamine or topical steroids. If more severe rash change to other thioamide (cross allergy is uncommon)

Drugs used in Hyperthyroidism Thioamides: Side effects: 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

Drugs used in Hyperthyroidism Thioamides: Side effects: 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

Radioactive Iodine The only organ which traps iodine (advantage) 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)

Radioactive Iodine Treatment of choice in: 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

Radioactive Iodine Advantages: Hyperthyroidism Radioactive Iodine Advantages: Safe, effective treatment, painless & economic Disadvantage: Takes long time 10-12 months for total affect to appear Patients fear from radiation Patients will have hypothyroidism

Radioactive Iodine Advantages: Hyperthyroidism Radioactive Iodine Advantages: Safe, effective treatment, painless & economic Disadvantage: Takes long time 10-12 months for total affect to appear Patients fear from radiation 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: Used as adjunct to surgery & radioactive iodine to control symptoms In pregnant women until she delivers to control symptoms

Iodinated Contrast Media 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)

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)

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

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