AMBULATORY CARE CLERKSHIP

1. AMBULATORY CARE CLERKSHIP SUPERVISED BY: DR. HALA AL-KALIDI

2. Thyroid disorders DONE BY: AMAL ALZAHRANI, Pharm.D. Candidate

3. Outline: • Thyroid Hormone regulation • Hypothyroidism • Hyperthyroidism • Case Study

4. Thyroid hormones: The thyroid gland removes iodine from the blood (which comes mostly from a diet of foods such as seafood, bread, and salt) and uses it to produce thyroid hormones. The two most important thyroid hormones are thyroxine (T4) and triiodothyronine (T3) representing 99.9% and 0.1% of thyroid hormones respectively.

5. …cont’d The hormone with the most biological activity (i.e., the greatest effect on the body) is actually T3. Once released from the thyroid gland into the blood, a large amount of T4 is converted to T3--the more active hormone that affects the metabolism of cells.

6. Thyroid hormone regulation: The thyroid itself is regulated by another gland located in the brain, called the pituitary. In turn, the pituitary is regulated in part by thyroid hormone that is circulating in the blood (a "feedback" effect of thyroid hormone on the pituitary gland) and in part by another gland called the hypothalamus, also a part of the brain.

7. …cont’d • The hypothalamus releases a hormone called thyrotropin releasing hormone (TRH), which sends a signal to the pituitary to release thyroid stimulating hormone (TSH). In turn, TSH sends a signal to the thyroid to release thyroid hormones.

8. …cont’d • The rate of thyroid hormone production is controlled by the pituitary gland. If there is an insufficient amount of thyroid hormone circulating in the body to allow for normal functioning, the release of TSH is increased by the pituitary in an attempt to stimulate the thyroid to produce more thyroid hormone.

9. …cont’d In contrast, when there is an excessive amount of circulating thyroid hormone, the release of TSH is reduced as the pituitary attempts to decrease the production of thyroid hormone.

10. Hypothyroidism • Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone. • The patient's presentation may vary from asymptomatic to, rarely, coma with multisystem organ failure (myxedema coma). • The most common cause in the Unites States is autoimmune thyroid disease (Hashimoto thyroiditis). • ٍٍSubclinical hypothyroidism, also referred to as mild hypothyroidism, is defined as normal serum free T4 levels with slightly high serum TSH concentration.

11. …cont’d • Myxedema coma is a severe form of hypothyroidism that results in an altered mental status, hypothermia, bradycardia, hypercarbia, and hyponatremia. Cardiomegaly, pericardial effusion, cardiogenic shock, and ascites may be present.

12. …cont’d Myxedema coma most commonly occurs in individuals with undiagnosed or untreated hypothyroidism that are subjected to an external stress such as cold exposure, surgery, infection, hypnotics, or other medical interventions.

13. Most common symptoms: Slow heart rate Tiredness Inability to tolerate cold Weight gain Emotional depression Drowsiness, even after sleeping through the night Heavy or irregular menstrual periods Muscle cramps Constipation Later symptoms include: Dry, flaky skin Hair loss Impaired memory and difficulty in thinking Voice becomes deeper A numb sensation in the arms and legs Puffiness in the face, especially around the eyes (a condition called myxedema, which is an indication that the disease has become serious) Symptoms

14. Physical finding • Thin brittle nails • Pallor • Puffiness of face , eyelids • Peripheral edema • Thickening of the tongue • Bradycardia • Hypertension • Goiter (1ry )

15. …cont’d Causes Primary hypothyroidism Secondary – Tertiary hypothyroidism Peripheral hypothyroidism

16. Primary hypothyroidism • Congenital hypothyroidism • Antithyroid drugs • Hashimoto’s thyroiditis • Postpartum hypothyroidism • Spontaneous hypothyroidism in Graves’ disease • Postoperative hypothyroidism • Hypothyroidism after radioactive iodine • External radiation

17. Secondary hypothyroidism: Pituitary adenoma Selective thyroid-stimulating hormone deficiency • Tertiary hypothyroidism: Hypothalamic disorders • Peripheral hypothyroidism: It is due to tissue insensitive to the action of thyroid hormone

18. Investigation : 1) serum T4 & T3 both will be low . 2) serum TSH will high except in hypopituitrism . 3) Thyroid antibodies like antithyroglobin are raised in Hashimoto's disease

19. Treatment Treatment of hypothyroidism is simple. It involves taking daily thyroid hormone replacement medication. This supplies the body with thyroid hormone to replace what isn't being produced by the thyroid gland.

20. Levothyroxine • In active form, influences growth and maturation of tissues. • Produces stable levels of T3 and T4. • Administered as a single dose in the morning on an empty stomach. • May be administered PO/IV/IM. • Has long half-life (7-10 d), and parenteral dosing is rarely needed (except when PO is unavailable, patient is on continuous enteral feeds, or in emergency, such as myxedema coma). • Initial subtherapeutic doses are recommended to avoid the stress of rapid metabolic change in elderly patients and in those with coronary artery disease or severe COPD.

21. …cont’d • Adult Dos: • 1.6 mcg/kg/d PO; initial dose usually 50-100 mcg/d, higher doses may be required in pregnancy; in elderly and those with coronary disease, start at 25-50 mcg/d PO, increase by 25-50 mcg/d q4-8wk until desired response achieved. • Maintenance: 50-200 mcg PO qam. • Subclinical hypothyroidism: If treated an initial dose of LT4 25-50 mcg/d can be used and titrated q6-8wk to achieve a target TSH. • Myxedema coma: 200-250 mcg IV bolus, followed by 100 mcg the next day and then 50 mcg/d PO or IV along with T3; use smaller doses in patients with cardiovascular disease.

22. …cont’d • Pediatric Dose: • Neonate to 6 months: 25-50 mcg/d PO • 6-12 months: 50-75 mcg/d PO • 1-5 years: 75-100 mcg/d PO • 6-12 years: 100-150 mcg/d PO • >12years: 150 mcg/d PO

23. weight loss tremor headache upset stomach vomiting diarrhea stomach cramps nervousness irritability insomnia excessive sweating increased appetite Fever ADR

24. …cont’d • Contraindications:Documented hypersensitivity, uncorrected adrenal insufficiency; acute MI uncomplicated by hypothyroidism; untreated thyrotoxicosis • Interactions:cholestyramine, sucralfate, iron may decrease absorption; estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands. • Pregnancy:A - Fetal risk not revealed in controlled studies in humans. • Precautions:Caution in elderly patients and patients with renal insufficiency, hypertension, ischemia, angina, and other cardiovascular diseases; periodically monitor thyroid status

25. Liothyronine • Synthetic form of the natural thyroid hormone T3 converted from T4. • Used when a rapid effect is desired perioperatively or for nuclear medicine studies. • Not intended as sole maintenance therapy. • Can be used in combination with levothyroxine in small doses (5-15 mcg/d).

26. …cont’d • Duration of activity is short (half-life is 12-24 h) and allows for quick dosage adjustments in event of overdosage. • May be preferred when GI absorption is impaired or if peripheral conversion is impaired.

27. …cont’d • Adult Dose: Initial: 25 mcg/d PO in divided bid; increase by 12.5-25 mcg/d PO q1-2wk until desired response achievedMaintenance: 50-100 mcg/d POMyxedema coma: 10 mcg IV and repeated q8 -12h until patient can take PO maintenance oral dose of T4 (see aboveElderly patients or patients with suspected or known coronary disease: Avoid because of high risk of cardiovascular manifestations • Pediatric Dose: 5 mcg/d PO; increase by 5 mcg q3d until desired response achieved

28. …cont’d • Contraindications: Documented hypersensitivity; uncorrected adrenal insufficiency; acute MI uncomplicated by hypothyroidism; untreated thyrotoxicosis; cardiac arrhythmias; suspected or known coronary disease • Interactions: as Levothyroxine • Pregnancy:A - Fetal risk not revealed in controlled studies in humans • Precautions:Caution in elderly patients and patients with renal insufficiency, hypertension, ischemia, angina, and other cardiovascular diseases; periodically monitor thyroid status

29. Hyperthyroidism • The term hyperthyroidism refers to inappropriately elevated thyroid function. • Hyperthyroidism presents as a constellation of symptoms due to elevated levels of circulating thyroid hormones. Because of the many actions of thyroid hormone on various organ systems in the body, the spectrum of clinical signs produced by the condition is broad. The presenting symptoms can be subtle and nonspecific, making hyperthyroidism difficult to diagnose in its early stages without the aid of laboratory data.

30. Weight loss Irritability and behavior change Malaise Tremor Palpitation Itching Vomiting Loss of libido Sweating Increased appetite Restlessness Muscle weakness Breathlessness Heat intolerance Thirst Diarrhea Oligomenorrhea Eye complaints Symptoms

31. Physical finding • Thinning of the hair • Prominence of the eyes, lid lag, lid retraction • Diffusely enlarged goiter • Wide pulse pressure • Flushed moist skin • Palmer erythema

32. Causes • Common: • Graves’ disease (autoimmune) • Toxic nodular goiter • Uncommon: • Acute thyroiditis • Post-irradiation • Post-partum • Gestational thyrotoxicosis • Exogenous iodine • Drugs (amiodarone, lithium, interferon-alpha) • Rare: • TSH-secreting pituitary tumors • Metastatic differentiated thyroid carcinoma • Hyperfunctioning ovarian teratoma

33. Investigation • TSH usually low. • FT4 elevated in more than 90% of patient. • Positive thyroid antibodies confirm autoimmune origin of hyperthyroidism.

34. Treatment Antithyroid drugs (thioamide) Iodine Radioactive iodine Beta blocker Surgery

35. Antithyroid medications • Mechanism of action: Blocks oxidation of iodine in thyroid gland, thereby inhibiting thyroid hormone synthesis • Propylthiouracil:It is more potent than carbimazole. It inhibits conversion of T4 to T3, while carbimazole does not. • Carbimazole • Methimazole:It is a metabolite of carbimazole.

36. Propylthiouracil • DOC in severe thyrotoxicosis • Readily absorbed and has a serum half-life of 1-2 h. • Highly protein-bound in the serum. • Duration of action is longer than half-life and should be dosed q6-8h (but can be administered bid). • If patient compliance is an issue, methimazole is better choice because of qd dosing. • Thyroid hormone levels (TSH, free T4, and T3) should be reassessed in 4 wk and increased if thyroid hormone levels have not significantly fallen or decreased if thyroid hormone levels have fallen by 50% or more . • Usually after thyroid function improves, gradually decrease the dose to 50-150 mg/d in divided doses (or the patient will become hypothyroid).

37. …cont’d • Adult Dose: Initial dose: 100-150 mg PO TID(decrease in dose is virtually always required in 4-8 wk when using this starting dose)Thyroid storm: 150-200 mg PO q4-6h • Pediatric Dose: Neonates: 5-10 mg/kg/d PO divided TID Children: 2-7 mg/kg/d PO divided TIDdose must be carefully monitored to prevent hypothyroidism

38. …cont’d • Contraindications:Documented hypersensitivity, known liver disease • Interactions:Antivitamin K activity; may potentiate activity of oral anticoagulants • Pregnancy:B - Usually safe but benefits must outweigh the risks. • Precautions:Monitor oral anticoagulant therapy closely caution in breastfeeding women (monitor infants for hypothyroidism); urticaria, pruritus, and arthralgias occur in 5%; agranulocytosis & aplastic anemia occurs in 0.2-0.5%; severe hepatitis is a rare complication.

39. Methimazole • Inhibits thyroid hormone by blocking oxidation of iodine in thyroid gland. However, not known to inhibit peripheral conversion of thyroid hormone. • Readily absorbed and has serum half-life of 6-8 h. • Less protein-bound than PTU and generally is not used in pregnancy because of increased placental transfer. • Has higher transfer rate into the milk of lactating women. • Duration of action is longer than half-life and should be dosed q12-24h.Usually after thyroid function improves, dose must be decreased or patient will become hypothyroid.

40. …cont’d • Adult Dose: Initial dose: 20-40 mg/d PO or PR (suppository or retention enema) qd or divided bidUsual maintenance dose: 2.5-15 mg/d PO or PR (suppository or retention enema) • Pediatric Dose: 0.2 mg/kg/d PO

41. …cont’d • Contraindications: Documented hypersensitivity; breastfeeding women; known liver disease • Interactions: Inhibits vitamin K activity and may potentiate activity of oral anticoagulants; toxicity increased with coadministration of lithium and potassium iodide • Pregnancy: D - Unsafe in pregnancy • Precautions: Monitor oral anticoagulant therapy closely caution in breastfeeding women (monitor infants for hypothyroidism); urticaria, pruritus, and arthralgias occur in 5%; agranulocytosis occurs in 0.2-0.5%

42. Iodine • In severe thyrotoxicosis from Graves disease or subacute thyroiditis, iodine or iodinated contrast agents have been administered to block T4 conversion to T3 and the release of thyroid hormone from the gland. This therapy is reserved for severe thyrotoxicosis because its use prevents definitive therapy of Graves thyrotoxicosis with radioactive iodine for many weeks. Either a saturated solution of potassium iodide (SSKI) at 10 gtt twice daily or iopanoic acid/ipodate (1 g/d) can be administered with rapid reduction in T3 levels. • Preoperative preparation iodine treatment (to decrease gland vascularity), An additional benefit from stable iodide therapy, besides the reduction in thyroid hormone excretion, is a demonstrated decrease in thyroid blood flow and possible reduction in blood loss during surgery.

43. Radioactive iodine therapySodium iodide I-131 (Iodotope) • the mostcommon treatment of hyperthyroidism in adults in the US. • it is effective, safe, and does not require hospitalization. It is administered orally as a single dose, in capsule or liquid form. • The patient is given a capsule or a drink of water containing radioactive iodine. After being swallowed, the "radioiodine" is rapidly absorbed by the overactive thyroid cells No other tissue or organ in the body is capable of retaining radioactive iodine; therefore, few adverse effects develop. and over a period of several weeks, the radioactive iodine damages the cells. • The result is the thyroid shrinks in size, thyroid production falls and blood levels return to normal. The radioactivity disappears from the body within a few days. Hyperthyroidism can reoccur from several months to many years after this therapy

44. …cont’d • Adult Dose:75-200 µCi/g of thyroid multiplied by estimated thyroid gland size/24-h radioiodine uptake • Pediatric Dose:Not established • Contraindications:Documented hypersensitivity; pregnant or breastfeeding women • Interactions:Coadministration with lithium may result in hypothyroid effects • Pregnancy:X - Contraindicated in pregnancy • Precautions:Discontinue antithyroid therapy for 3-4 d before administration; not usually administered to patients with severe ophthalmopathy because good clinical evidence indicates that usually mild, but occasionally severe, worsening of thyroid eye disease occurs after radioactive iodine therapy

45. Beta-adrenergic receptor blockers • Reduce many of the symptoms of thyrotoxicosis, including tachycardia, tremor, and anxiety. • Usually propranolol 20-80 mg PO TID is recommended because of CNS penetration. • Calcium channel blockers for tachycardia sometimes are used when beta-blockers are contraindicated or not tolerated.

46. Surgery Because of excellent effectiveness in regulating thyroid function with antithyroid medications and radioactive iodine, thyroidectomy is reserved for special circumstances, including the following: • Severe hyperthyroidism in children • Pregnant women who are noncompliant or intolerant of antithyroid medication • Patients with very large goiters or severe ophthalmopathy • Patients who refuse radioactive iodine therapy • Refractory amiodarone-induced hyperthyroidism • Patients who require normalization of thyroid functions quickly, such as pregnant women, women who desire pregnancy in the next 6 months, or patients with unstable cardiac conditions

47. Case study

48. Case study • AM is a 40 years old female came to endocrine clinic on 18/03/2008 for follow up, she is a known case of hypothyroidism, she was thyrotoxicosis & took radioactve iodine then, she became hypothyroidism. • She was complained of malaise, palpitation, general weakness & slight wt loss. • She diagnosed with Microcytic Hypochromic Anemiain this visit.

49. …cont’d Past medical history (PMH): • Hypothyroidism for 4 years • Hyperlipidemia for 2 years Family history (FH): • Unremarkable Social history (SH): • Married , non-smoker Current medication: • Thyroxine 150 mcg QD • Simvastatin 20 mg QD

50. Vital signs: Temp. 37C RR.15\min, BP.129\65 mmHg HR.75 bpm Calculation: IBW = 47.8 kg ABW= 66 kg Pt. 37.5 % over wt Objective: