HYPERTHYROIDISM

1. HYPERTHYROIDISM Ryan Manaloto, M.D. Senior Intern

2. Agenda We will discuss: - Anatomy & Physiology - Pathophysiology - Signs and symptoms - Clinical Statistics - Diagnosis - Treatment - Clinical outcomes of undertreatment and overtreatment - Follow-up care

3. Locations of major endocrine glands

5. Thyroid gland. A.) Consists of 2 lobes connected anteriorly by an isthmus. B.) Follicular cells secrete thyroid hormones.

6. The parathyroid glands are embedded in the posterior surface of the thyroid gland.

7. Thyroid Physiology • Uptake of Iodine by thyroid • Coupling of Iodine to Thyroglobulin • Storage of MIT / DIT in follicular space • Re-absorption of MIT / DIT • Formation of T3, T4 from MIT / DIT • Release of T3, T4 into serum • Breakdown of T3, T4 with release of Iodine

8. Iodine uptake

9. MIT / DIT formation • Thyroid Peroxidase (TPO) • Apical membrane protein • Catalyzes Iodine organification to Tyrosine residues of Thyroglobulin • Antagonized by methimazole • Iodine coupled to Thyroglobulin • Monoiodotyrosine (Tg + one I-) • Diiodotyrosine (Tg + two I-) • Pre-hormones secreted into follicular space

10. Thyroid Hormones • Majority of circulating hormone is T4 • 98.5% T4 • 1.5% T3 Regulation is based on the free component of thyroid hormone

12. Thyroid-stimulating Hormone (TSH) controls thyroid gland secretions Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the anterior pituitary gland to release thyroid-stimulating hormone (TSH), which stimulates the thyroid gland to release hormones. These thyroid hormones reduce the secretion of TSH and TRH. Step through Slides

13. Parathyroid hormone (PTH) stimulates bone to release calcium (Ca+2) and the kidneys to conserve calcium. It indirectly stimulates the intestine to absorb calcium. The resulting increase in blood calcium concentration inhibits secretions of PTH

14. As a result of negative feedback, hormone concentrations remain relatively stable, although they may fluctuate slightly above and below average concentrations.

15. Iodine states • Normal Thyroid • Inactive Thyroid • Hyperactive Thyroid

16. Wolff-Chaikoff • Increasing doses of I- increase hormone synthesis initially • Higher doses cause cessation of hormone formation. • This effect is countered by the Iodide leak from normal thyroid tissue. • Patients with autoimmune thyroiditis may fail to adapt and become hypothyroid.

17. Jod-Basedow • Aberration of the Wolff-Chaikoff effect • Excessive iodine loads induce hyperthyroidism • Observed in several disease processes • Graves’ disease • Multinodular goiter

18. Introduction What is Hyperthyroidism? “Hyperthyroidism” refers to overactivity of the thyroid gland leading to excessive synthesis of thyroid hormones and accelerated metabolism in the peripheral tissues. The secretion of thyroid hormone is no longer under the regulatory control of the hypothalamic-pituitary center.

19. CLINICAL SYMPTOMS Depends on - Age of patient - Magnitude of hormonal excess - Presence of co-morbid condition

20. Signs and Symptoms • - Deterioration in handwriting • - Menstrual irregularities • - Muscle weakness/wasting manifested as exercise intolerance or difficulty climbing stairs • - Eye symptoms, which may include pain or diplopia • - Nervousness • - Tachycardia • - Goiter • - Elevated plasma levels of thyroxin and/or triiodothyronine • - Tremulousness or jitteriness • - Exophthalmos • - Weight loss despite excellent appetite – hypermetabolic state • - Insomnia • - Fatigue • - Palpitations • - Heat intolerance • - Sweating • - Diarrhea

21. GOITER Exopthalamos in Graves Disease Lid Lag

22. Prevalence Women 2% Men 0.2% 15% of cases occur in patients older than 60 years of age

23. Etiology • Graves Most common cause of hyperthyroidism Result of anti-TSH receptor antibodies Diagnosis • Symptoms of hyperthyroidism • Clinical exopthalmos and goiter • Low TSH, normal/high FT4, anti-TSH Ab (Optional) If no clinical findings I123 may demonstrate increased uptake.]

24. Etiology 2. Toxic multi-nodular goiter - 5% of all cases - 10 times more common in iodine deficient area - Typically occurs in older than 40 with long standing goiter 3. Toxic adenoma - More common in young patients Autonomically functioning nodule

25. 4. Subacute Thyroiditis(DeQuervain’s, Granulomatous) • Acute viral infection of thyroid gland • Presents with viral prodrome, thyroid tenderness, and hyperthyroid symptoms • Lab values • Variable TSH, T4 • High ESR • No antibodies

26. Etiology 5. Treatment Induced Hyperthyroidism Iodine Induced - Excess iodine indirect - Exposure to radiographic contrast media - Medication - Excess iodine increases synthesis and release of thyroid hormone in iodine deficient and older patients with pre-existing goiters

27. Thyroid Hormone Induced - Factitious hyperthyroidism in accidental or intentional ingestion to lose weight Tumors -Metastatic thyroid cancer -Ovarian tumor that produces thyriod hormone (struma ovarii) -Trophoblastic tumor -TSH secreting tumor

28. Signs and symptoms of hyperthyroid TSH level Low TSH High TSH (rare) Measure T4 High Secondary hyperthyroidism Image pituitary gland

29. Low TSH Measure Free T4 Level Normal High Primary hyperthyroidism Thyroid uptake Measure Free T3 Level High Normal -Subclinical hyperthyroidism -Resolving Hyperthyroidism -Medication -Pregnancy -New thyroid illness T3 Toxicosis Low High Measure thyroglobulin DIffuse Nodular decreased Increased Graves Multiple areas One “hot” area disease Exogenous hormone Thyroiditis Toxic adenoma Toxic multinodular goiter Iodide exposure Exrtraglandular production

30. TREATMENT Treatment depends upon - Cause and severity of disease - Patients age - Goiter size - Comorbid condition - Treatment desired

31. TREATMENT - Medical therapy with antithyroid drugs such as propylthiouracil or methimazole - Ablation of the thyroid gland with radioactive iodine - Subtotal thyroidectomy - Self-limited causes of hyperthyroidism, such as subacute thyroiditis, iodine-induced hyperthyroidism, and exogenous administration of T4, can be treated symptomatically. For more significant cardiovascular symptoms, beta-adrenergic blockade with propranolol can be helpful.

32. Anti-Thyroid Drugs They interfere with organification of iodine—suppress thyroid hormone levels Two agents: -Tapazole (methimazole) -PTU (propylthiauracil)

33. Anti-Thyroid Drugs Methimazole - Drug of choice for non-pregnant patients because of : - Low cost - Long half life - Lower incidence of side effects - Can be given in conjunction with beta-blocker - Beta-blockers can be tapered off after 4-8 weeks of therapy - Dose 15-30 mg/day - Maintenance dose 5-10 mg/day

34. - At one year if patient is clinically and biochemically euthyroid and TSH antibodies are not detectable, therapy can be discontinued - Monitor every three months for first year then annually - Relapses are more common in the first year but can occur years later

35. PTU - Preferred for pregnant patients - Methimazole is associated with rare genetic abnormalities:increase scalp defects in newborn(aplasia cutis) - Dose 100 mg t.i.d - Maintenance 100-200 mg/day Goal: Keep Free T4 at upper level of normal

36. COMPLICATIONS - Agranulocytosis up to 0.5% (fever & sore throat – first sign) - High with PTU - Can occur suddenly - Mostly reversible with supportive Tx - Routine WBC monitoring controversial - Some people monitor WBC every two weeks for first month then monthly - Advised to stop drug if they develop sudden fever or sore throat

37. Thyroidectomy Surgical removal of the thyroid gland Thyroidectomy is a surgical procedure in which all or part of the thyroid gland is removed. The thyroid gland is located in the forward (anterior) part of the neck just under the skin and in front of the Adam's apple. The thyroid is one of the body's endocrine glands, which means that it secretes its products inside the body, into the blood or lymph. The thyroid produces several hormones that have two primary functions: they increase the synthesis of proteins in most of the body's tissues, and they raise the level of the body's oxygen consumption. All or part of the thyroid gland may be removed to correct a variety of abnormalities. If a person has a goiter, which is an enlargement of the thyroid gland that causes swelling in the front of the neck, the swollen gland may cause difficulties with swallowing or breathing. Hyperthyroidism (overactivity of the thyroid gland) produces hypermetabolism, a condition in which the body uses abnormal amounts of oxygen, nutrients, and other materials. A thyroidectomy may be performed if the hypermetabolism cannot be adequately controlled by medication, or if the condition occurs in a child or pregnant woman. Both cancerous and noncancerous tumors (frequently called nodules) may develop in the thyroid gland. These growths must be removed, in addition to some or all of the gland itself.

39. Clinical Outcomes of Inadequately treated Hyperthyroidism Thyrotoxicosis. A life-threatening thyrotoxic crisis (ie, thyroid storm) can occur: fever, tachycardia, neurologic abnormalities, and hypertension, followed by hypotension and shock. It can be Fatal. Thyroid stormoccurs in patients who have unrecognized or inadequately treated thyrotoxicosis and a superimposed precipitating event such as thyroid surgery, nonthyroidal surgery, infection, or trauma. Initially the acute mortality rate was nearly 100%. In current practice, with aggressive therapy and early recognition of the syndrome, the mortality rate is approximately 20%. Severe Weight loss with catabolism of bone and muscle. Cardiac complications and psychocognitive complications Osteoporosisin men and women. The effect can be particularly devastating in women, in whom the disease may compound the bone loss secondary to chronic anovulation or menopause.Bone loss is accelerated in patients with hyperthyroidism

40. Follow-up Care Patients who have been treated for hyperthyroidism need to be followed closely because they may develop HYPOthyroidism or recurrent hyperthyroidism. Follow-up care includes the following: - Reducing medications after 4-6 weeks; the patient should be totally off anti-thyroid medication in 12-18 months - Check thyroid function tests every 4-6 weeks - Monitor closely for remission.

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