1. Thyroid Disorders PHCL 442
Hadeel Al-Kofide MS.c

2. Topics to be covered
Thyroid physiology
Hypothyroidism
Hyperthyroidism

3. Thyroid Physiology

4. Hypothyroidism Causes Clinical presentation Goals of therapy
Treatment options
Monitoring
Special considerations

5. 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

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

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

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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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)

15. 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

16. 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 weeks
Monitor patients for TSH, T3 & T4 every 6-8 weeks

17. 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

18. 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

19. 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 mcg

20. Hyperthyroidism Causes Clinical presentation Goals of therapy
Treatment options
Monitoring
Special considerations

21. 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

22. 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

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

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

25. 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

26. 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

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

28. Hyperthyroidism
Treatment Modalities
Surgery
Drugs
Radioactive iodine

29. 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

30. 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

31. 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)

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

33. 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

34. Drugs used in Hyperthyroidism
Thioamides:
Monitoring therapy:
Baseline FT4 & TSH before treatment then measure every 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

35. 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

36. 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)

37. 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

38. 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

39. 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)

40. 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

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

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

43. 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

44. 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)

45. 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)

46. 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

47. 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 at applied therapeutics

48. Thank you