1. This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration of Prof. Jamal Al Wakeel, Head of Nephrology Unit, Department of Medicine and Dr. Abdulkareem Al Suwaida, Chairman of Department of Medicine. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. HYPERTHYROIDISM Presented by: Muteb Al-Rowaili Medical Student
August 2008

3. 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.
Prevalence
Women 2%
Men %
15% of cases occur in patients older than 60 years of age

4. Clinical Symptoms
Older patient presents with lack of clinical signs and symptoms, which makes diagnosis more difficult
Thyroid storm is a rare presentation, occurs after stressful illness in under treated or untreated patient.
Characteristics
-Delirium Dehydration
-Severe tachycardia Vomiting
-Fever
-Diarrhea

5. Clinical symptoms Skin -Warm
-May be erythematous (due to increased blood flow)
-Smooth- due to decrease in keratin
-Sweaty and heat intolerance
-Onycholysis –softening of nails and loosening
of nail beds

6. Clinical symptoms Hyperpigmentation
-Due the patient increase ACTH secretion
Pruritis
-mainly in graves disease
Thinning of hair
Vitilago and alopecia areata
-mainly due to autoimmune disease
Infilterative dermopathy
-Graves disease, most common on shins

7. Clinical symptoms
Eyes
Stare
Lid lag
*Due to sympathetic over activity
*Only Grave’s disease has ophthalmopathy
-Inflammation of extraocular muscles, orbital fat and connective tissue.
-This results in exopthalmos
-More common in smokers

8. Clinical symptoms Eyes Impaired eye muscle function (Diplopia)
Periorbital and conjunctival edema
Gritty feeling or pain in the eyes
Corneal ulceration due to lid lag and proptosis
Optic neuritis and even blindness

9. Clinical symptoms Cardiovascular System
Increased cardiac output (due to increased oxygen demand and increased cardiac contractibility.
Tachycardia
Widened pulse pressure
High output – heart failure

10. Clinical symptoms Cardiovascular System
Atrial fibrillation, 10-20% of patients. More common in elderly
Atrial ectopy
60% of A-fib will convert to normal sinus rhythm with treatment (4-months of becoming euthyroid)
Mitral valve problems
LVH and cardiomyopathy

11. Serum Lipids Low total cholesterol Low HDL
Low total cholesterol/HDL ratio

12. Respiratory System Dyspnea on rest and with exertion
Oxygen consumpation and CO2 production increases.
Hypoxemia and hypercapnea, which stimulates ventilation
Respiratory muscle weakness
Decreased exercise capacity
Tracheal obstruction
May exacerbate asthma
Increased pulmonary arterial pressure

13. GI System -Weight loss due to increased calorigenesis -Malabsorption
-Steatorrhea
-Celiac Disease (in Grave’s Disease)
-Hyperphagia (weight gain in younger patient)
-Anorexia- weight loss in elderly
-Dysphagia
-Abnormal LFT especially phosphate

14. Hematological System Normochromic normocytic anemia
Serum ferritin may be high
Grave’s disese
ITP
Pernicious anemia
Anti-neutrophiliac antibody

15. GU System Urinary frequency and nocturia
Enuresis is common in children
Women
High serum estradiol
Low free estradiol
High LH
Oligomenorrhea and amenorrhea
Anovulatory infertility

16. GU System…cont Men High total testosterone Low free testosterone
High serum LH
High serum estradiol
Gynecomastia
Decreased libido
Decreased or abnormal sperm

17. Clinical symptoms Skeletal System Bone resorption
Increased porosity of cortical bone
Reduced volume of trabecular bone
Serum alkaline phosphate is increased
Increased osteoblasts
Inhibit PTH secretions
Decreased calcium absorption and increased excretion
Osteoporosis, Fractures

18. Skeletal System Grave’s disease is associated with :
-Clubbing of nails
-Periosteal bone formation in metacarpal bone or phalanges

19. Neuromuscular System Tremors-outstretched hand and tongue
Hyperactive tendon reflexes

20. Psychiatric Hyperactivity Emotional lability Anxiety
Decreased concentration
Insomnia

21. Muscle Weakness Proximal muscle weakness in 50% pts.
Decreased muscle mass and strength
May take up to six months after euthyroid state to gain strength
Myesthenia Gravis, especially in Grave’s disease.

22. Endocrine Increased sensitivity of pancreatic beta cells to glucose
Increased insulin secretion
Antagonism to peripheral action of insulin
Latter effects usually predominate leading to intolerance.

23. Etiology 1 Grave’s disease
Autoimmune disease caused by antibodies to TSH receptors
Can be familial and associated with other autoimmune diseases
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

24. More common in young patients Autonomically functioning nodule
Etiology
3 Toxic adenoma
More common in young patients
Autonomically functioning nodule

25. Etiology 4 Thyroiditis Subacute
Abrupt onset due to leakage of hormones
Follows viral infection
Resolves within eight months
Can re-occur
Lymphatic and postpartum
Transient inflammation
Postpartum can occur in 5-10% cases in the first 3-6 months
Transient hypothyroidism occurs before resolution

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. Etiology Amiodarone Induced Thyroiditis
Up to 12% of patients, especially in iodine deficient cases
Most common cause of iodine excess in US.
Amiodarone contains % iodine.

28. Etiology 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

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

30. Low TSH (> 0.1mu/ml ) 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

31. Etiology Hyperthyroidism with high RIU - Grave’s disease
- Toxic adenoma
- Toxic multinodular goiter
- TSH- producing pituitary adenoma

32. Etiology Hyperthyroidism with low RIU - Subacute thyroiditis
- Exogenous harmone intake
- Ectopic ovarii
- Metastatic follicular thyroid CA
- Radiation thyroiditis
- palpation thyroiditis
- Amiodarone induced

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

34. Treatment
The goal of therapy is to correct hyper-metabaolic state with fewest side effects and lowest incidence of hypothyroidism.

35. Options Anti-thyroid drugs Radioactive iodine Surgery
Beta-blocker and iodides are adjuncts to above treatment

36. Beta Blockers Prompt relief of adrenergic symptoms:
such as palpitation , tremor , and anxiety
Propranolol widely used
Increase progressively until symptoms are controlled
Most cases mg qd is sufficient
Ca-CB can be used if beta blocker not tolerated or contraindicated.
Verapamil cab be used to control tachycardia in pt
with CI to β-adrenergic antagonists.

37. Iodides
Iodide blocks peripheral conversion of T4 to T3 and inhibits hormone release. These are used as adjunct therapy
Before emergency non-thyroid surgery
Beta blockers cannot curtail symptoms
Decrease vascularity before surgery for Grave’s disease

38. Iodides
Iodides are not used for routine treatment because of paradoxical increase of hormone release with prolonged use
Commonly used:
Radiograph contrast agents
-Iopanoic acid
-Ipodate sodium
Potassium iodide (SSKI)
Dose 1 gram/ 12 weeks

39. Anti-thyroid Drugs Thionamides :
They interfere with organification of iodine—suppress thyroid hormone levels
Thionamides :
two agents:
- (methimazole)
-PTU (propylthiauracil)

40. Anti-thyroid Drugs
Remission rate: 60% when therapy continued for two years
Relapse in 50% of cases.
Relapse more common in
-smokers
-elevated TS antibodies at end of therapy

41. 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 mg/day

42. Anti-thyroid Drugs Methimazole: Starting dose: 10-40 mg PO daily
Monthly evaluation of
* clinical finding.
* plasma T until euthyroid.
then the dose adjusted to maintain plasma T4 within the normal range.
Maintenance dose 5-10 mg/day
TSH levels may remain undetectable for months after euthyroid and not to be used to monitor the therapy

43. Anti-thyroid Drugs Methimazole
At one year if patient is clinically and biochemically euthyroid and TS 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
If relapse occurs, iodide or surgery although anti-thyroid drugs can be restarted

44. Anti-thyroid Drugs PTU Prefered for pregnant patients
Methimazole is associated with rare genetic abnormalities
Dose 100 mg t.i.d
Maintenance mg/day
Goal: Keep Free T4 at upper level of normal

45. Anti-thyroid Drugs Complications Agranulocytosis up to 0.5%
minor S/E: rash , urticaria , arthralgias , transient leukopenia.
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 immediately if they develop (sudden fever , chills or sore throat)

46. Radioactive Iodine
Treatment of choice for Grave’s disease and toxic nodular goiter
Inexpensive
Highly effective
Easy to administer
Safe
Dose depends on estimated weight of gland
Higher dose increases success rate but higher chance of hypothyroidism
Some studies have shown increase of hypothyroidism irrespective of dose

47. Radioactive Iodine Follow up:
Usually , several months are needed to restore euthyroidism . Patients are evaluated at 4-6 week interval , with assessment of clinical finding and plasma free T4
If thyroid function stabilizes within the normal range, the interval between follow up visits is gradually increased to annual intervals
If symptomatic HYPOthyroidism develops, thyroxine Rx is started.
If symptomatic HYPERthyroidism persists after 6 months,
RAI treatment is repeated.

48. Radioactive Iodine Higher dose is favored in older patient
A pregnancy test is done immediately before therapy in potentially fertile women.
A 24-hour RAIU is usually measured and used to calculate the dose.
Thionamides interfere with RAI therapy and should be stopped 3 days before Rx.

49. Radioactive Iodine Side effects
50% of Grave’s ophthalmology can develop or worsen by use of radioactive iodine
Use mg Prednisone for at least three months can prevent or improve severe eye disease in 2/3 of patients
Use lower dose in ophthalmology because post Tx hypothyroidism may be associated with exacerbation of eye disease
Smoking makes ophthalmopathy worse.

50. Surgery
Radioactive iodine has replaced surgery for Tx of hyperthyroidism
Subtotal thyroidectomy is most common
This limits incidence of hypothyroidism to 25%
Total thyroidectomy in large goiter or severe disease
The pts should be prepared for surgry by:
* a Thionamide which given until the pt is nearly euthyroid.
* supersaturated KI (SSKI) 40-80mg PO BID
both drugs are stopped postoperatively.
* atenolol ( mg daily) is started 1-2 weeks before surgry.
if needed, increase the dose to reduce the resting H.R. below 90 bpm & continued 5-7 days postop

51. New Treatment Endoscopic subtotal thyroidectomy
Embolization of thyroid arteries
Plasmaphoresis
Percutaneous ethanol injection into toxic nodule
L-Carnitine supplementation may improve symptoms and may prevent bone loss

52. Thank you