hyperthyroidism and graves’ disease

55
HYPERTHYROIDISM AND GRAVES’ DISEASE Anthony Yin, MD Sutter Pacific Medical Foundation Division of Endocrinology, Diabetes and Osteoporosis

Upload: vicky

Post on 24-Feb-2016

107 views

Category:

Documents


1 download

DESCRIPTION

Hyperthyroidism and Graves’ Disease. Anthony Yin, MD Sutter Pacific Medical Foundation Division of Endocrinology, Diabetes and Osteoporosis. No financial disclosures. Case presentation. - PowerPoint PPT Presentation

TRANSCRIPT

Page 1: Hyperthyroidism  and  Graves’ Disease

HYPERTHYROIDISM AND

GRAVES’ DISEASE

Anthony Yin, MD

Sutter Pacific Medical FoundationDivision of Endocrinology, Diabetes and Osteoporosis

Page 2: Hyperthyroidism  and  Graves’ Disease

• No financial disclosures

Page 3: Hyperthyroidism  and  Graves’ Disease

CASE PRESENTATION

• 62 year old woman presents with fatigue and occasional palpitations for 3 months. Past medical history notable for long-standing hypertension and osteopenia based on a bone density study performed two years ago. She went through menopause at the age of 55 and has had no fractures. She has been an avid gardener for many years but has lost pleasure in this activity lately.

• She is a non smoker and only occasionally drinks alcohol. There is no family history of thyroid disease or malignancy

• Her medications are hydrochlorothiazide 25 mg/d, aspirin 81 mg/d, calcium 500 mg BID and vitamin D 800 IU/d

• No known medication allergies

Page 4: Hyperthyroidism  and  Graves’ Disease

CASE PRESENTATION

• BP 135/82, HR 110, BMI 24• NAD, flat affect• No proptosis, lid lag or periorbital edema• Minimally enlarged smooth goiter with no palpable

nodules; bruits are present• CV: regular with occasional premature beats, no

murmurs• Mild tremor in both hands• Moderate khyposcoliosis without paravertebral

tenderness• No dermatologic abnormalities

Page 5: Hyperthyroidism  and  Graves’ Disease

LABORATORY DATA

• CBC wnl• CMP notable for AST 62 and ALT 65 with

normal bilirubin and alkaline phosphatase

• 25-OH vit D3 is 22• TSH 0.03 (normal 0.45-4.5 uIU/mL), anti

TPO ab 22 (normal <35)• ESR 16

Page 6: Hyperthyroidism  and  Graves’ Disease

QUESTIONS

• What is the differential diagnosis?• What further studies are

recommended?• How should she be treated?

Page 7: Hyperthyroidism  and  Graves’ Disease

OUTLINE OF DISCUSSION

• What’s normal?• Scope of the Problem• Causes • Diagnostic Approach• Management

Page 8: Hyperthyroidism  and  Graves’ Disease

WHAT’S NORMAL?

http://www.sciencedirect.com/science/article/pii/S0003986110002407

Page 9: Hyperthyroidism  and  Graves’ Disease

SCOPE OF THE PROBLEM: HYPERTHYROIDISM• U.S.: prevalence 1.2%

- Overt 0.5%, 0.7% subclinical- Women 5x > men- More common in smokers

• Graves’ disease (GD) most common• Toxic multinodular goiter (TMNG) &

toxic adenoma (TA)

1. Singer PA, Cooper DS, Levy EG, Ladenson PW, Braverman LE, Daniels G, Greenspan FS, McDougall IR, Nikolai TF 1995 Treatment guidelines for patients with hyperthyroidism and hypothyroidism. JAMA 273:808–812.

2. 1Hollowell JG, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Heatlh and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87:489

3. Asvold BIO, et al. Tobacco smoking and thyroid function: a population-based study. Arch Intern Med 2007; 167:1428.4. Holm IA, et al. Smoking and other lifestyle factors and the risk of Graves’ hyperthyroidism. Arch Intern Med 2005;

165:1606

Page 10: Hyperthyroidism  and  Graves’ Disease

CLINICAL MANIFESTATIONS

• Anxiety• Emotional lability• Weakness• Tremor• Palpitations• Increased

perspiration• Weight loss (gain)• Normal or increased

appetite

Page 11: Hyperthyroidism  and  Graves’ Disease

CLINICAL MANIFESTATIONS

• Anxiety• Emotional lability• Weakness• Tremor• Palpitations• Increased

perspiration• Weight loss (gain)• Normal or increased

appetite

• Hyperdefecation• Urinary frequency• Oligomenorrhea or amenorrhea

(women)• Gynecomastia and erectile

dysfunction (men)• New onset atrial fibrillation• Myopathy• Elderly patients may be

“apathetic”; depression

Page 12: Hyperthyroidism  and  Graves’ Disease

STARE & LID LAG

http://www.patient.co.uk/doctor/Thyroid-Eye-Disease.htm

Page 13: Hyperthyroidism  and  Graves’ Disease

EXOPHTHALMOSSPECIFIC TO GRAVES’ DISEASE

http://jnnp.bmj.com/content/75/suppl_4/iv2.full

http://www.myhousecallmd.com/archives/3761

Expected normal ranges:Caucasian males 12 - 21 mmCaucasian females 12 - 20 mmAfrican American males 12 - 24 mmAfrican American females 12 - 23 mm

http://www.opt.indiana.edu/riley/HomePage/External_Eye_Exam/Text_External_Eye_Exam.html

Page 14: Hyperthyroidism  and  Graves’ Disease

GRAVES’ OPHTHALMOPATHY (GO)

• 50% of all with GD• 5% severe • Risk factors:

- radioiodine therapy for hyperthyroidism (318,319)

- smoking- high pretreatment T3 values (>325 ng/dL) (319)

- high serum pretreatment TRAb levels (>50% TBII inhibition or TSI >8.8 IU/Liter) (320)

- hypothyroidism following radioiodine treatment

Page 15: Hyperthyroidism  and  Graves’ Disease

ACROPACHY & PRETIBIAL MYXEDEMA: SPECIFIC TO GRAVES’ DISEASE

http://jcem.endojournals.org/content/87/2/438/F1.expansion

http://see.visualdx.com/diagnosis/thyroid_acropachy

Page 16: Hyperthyroidism  and  Graves’ Disease

CAUSES• GD• TMNG or TA• Thyroiditis• Iodine-induced

• Trophoblastic disease and germ cell tumors

• Extrathyroidal

Page 17: Hyperthyroidism  and  Graves’ Disease

DIAGNOSTIC APPROACH

• Goiter + opthalmopathy + moderate to severe hyperthyroidism = GD

• Radioactive iodine uptake (RAIU)• Antibodies (TSI or TSH-R ab)• ESR (subacute thyroiditis)

Page 18: Hyperthyroidism  and  Graves’ Disease

4 hour uptake 24 hour uptake Scan appearance

Graves’ disease

(Highly) Elevated

(Highly) Elevated

Page 19: Hyperthyroidism  and  Graves’ Disease

4 hour uptake 24 hour uptake Scan appearance

Graves’ disease

(Highly) Elevated

(Highly) Elevated

Subacute, silent thyroiditis

Extremely low

(Typically not measured)

Page 20: Hyperthyroidism  and  Graves’ Disease

4 hour uptake 24 hour uptake Scan appearance

Graves’ disease

(Highly) Elevated

(Highly) Elevated

Subacute, silent thyroiditis

Extremely low

(Typically not measured)

Autonomous nodule or toxic multinodular goiter

(Slightly) Elevated

(Slightly) Elevated

Page 21: Hyperthyroidism  and  Graves’ Disease

4 hour uptake 24 hour uptake Scan appearance

Graves’ disease

(Highly) Elevated

(Highly) Elevated

Subacute, silent thyroiditis

Extremely low

(Typically not measured)

Autonomous nodule or toxic multinodular goiter

(Slightly) Elevated

(Slightly) Elevated

Exogenous hyperthyroidism

Low

Page 22: Hyperthyroidism  and  Graves’ Disease

4 hour uptake 24 hour uptake Scan appearance

Graves’ disease

(Highly) Elevated

(Highly) Elevated

Subacute, silent thyroiditis

Extremely low

(Typically not measured)

Autonomous nodule or toxic multinodular goiter

(Slightly) Elevated

(Slightly) Elevated

Exogenous hyperthyroidism

Low

Euthyroidism Normal Normal

Page 23: Hyperthyroidism  and  Graves’ Disease

GRAVES’ DISEASE (GD)

Page 24: Hyperthyroidism  and  Graves’ Disease

TSI

Page 25: Hyperthyroidism  and  Graves’ Disease

GD: TREATMENT

Medical Radioactive Iodine Surgery

Page 26: Hyperthyroidism  and  Graves’ Disease

BETA BLOCKADE

PEARL:Beta-adrenergic blockade should be given to elderly patientswith symptomatic thyrotoxicosis and to other thyrotoxicpatients with resting heart rates in excess of 90 bpmor coexistent cardiovascular disease. RECOMMENDATION 2

Page 27: Hyperthyroidism  and  Graves’ Disease

ANTI THYROID DRUGS (ATDS)

Methimazole(MMI)

Propylthiouracil(PTU)

Page 28: Hyperthyroidism  and  Graves’ Disease

Cooper, David. Antithyroid Drugs. N Engl J Med352;9

Page 29: Hyperthyroidism  and  Graves’ Disease

Cooper, David. Antithyroid Drugs. N Engl J Med352;9

Page 30: Hyperthyroidism  and  Graves’ Disease

ANTI THYROID DRUGS (ATDS)Methimazole

(MMI)Propylthiouracil

(PTU)

• Initial dose: 10–20 mg/d• Maintenance dose:

generally 5–10 mg/d• Easier for patients• Side effects less

common• 15 mg/d $360/yr

• Initial dose: 300 mg/d• Preferred in

pregnancy• Higher potential for

side effects• 300 mg/d $408/yr Now only FDA

approved for treating hyperthyroidism during pregnancy

“should be used in virtually every patient who chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy when propylthiouracil is preferred, in the treatment of thyroid storm, and in patients with minor reactions to methimazole who refuse radioactive iodine therapy or surgery”*RECOMMENDATION 13

Page 31: Hyperthyroidism  and  Graves’ Disease

POSSIBLE SIDE EFFECTS

• pruritic rash• jaundice• acolic stools or dark urine• arthralgias• abdominal pain• nausea• fatigue• fever• pharyngitisRecommendation 14

Page 32: Hyperthyroidism  and  Graves’ Disease

ANTI THYROID MEDICATIONS: TIMELINE & MONITORING

Start ATD

Week 0

Page 33: Hyperthyroidism  and  Graves’ Disease

ANTI THYROID MEDICATIONS: TIMELINE & MONITORING

Start ATD

Week 4

q 4-8 week

sq 2-3

months

Week 0

Free T4 +T3

Page 34: Hyperthyroidism  and  Graves’ Disease

ANTI THYROID MEDICATIONS: TIMELINE & MONITORING

Start ATD

Week 4

q 4-8 week

sq 2-3

months

Week 0

Free T4 +T3

12-18 month

s

Stop ATD

Page 35: Hyperthyroidism  and  Graves’ Disease

ANTI THYROID MEDICATIONS: TIMELINE & MONITORING

Start ATD

Week 4

q 4-8 week

sq 2-3

months

Week 0

Free T4 +T3

12-18 month

s

Stop ATD

TSHFree

T4 T3

q 2 mo x 6 mo

Page 36: Hyperthyroidism  and  Graves’ Disease

ANTI THYROID MEDICATIONS: TIMELINE & MONITORING

Start ATD

Week 4

q 4-8 week

sq 2-3

months

Week 0

Free T4 +T3

12-18 month

s

Remission?

Stop ATD

TSHFree

T4 T3

q 2 mo x 6 mo

No

I-131 ablation

No

TSHFree

T4 T3

q 12 mo

Yes

Page 37: Hyperthyroidism  and  Graves’ Disease

• Radioactive Iodine Ablation

Page 38: Hyperthyroidism  and  Graves’ Disease

ATDS GENERALLY NOT NECESSARY PRIOR TO 131I

• insufficient evidence for radioactive iodine worsening either the clinical or biochemical aspects of hyperthyroidism

• “it only delays treatment with radioactive iodine”

Page 39: Hyperthyroidism  and  Graves’ Disease

PRETREATMENT MAY REDUCE THE EFFICACY OF SUBSEQUENT RADIOACTIVE IODINE THERAPY

Marcocci C, Gianchecchi D, Masini I, Golia F, Ceccarelli C, Bracci E, Fenzi GF, Pinchera A 1990 A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves’ hyperthyroidism. J Endocrinol Invest 13:513–520

Page 40: Hyperthyroidism  and  Graves’ Disease

WHEN TO USE MMI PRIOR TO 131I

- Risk for CV complications such as atrial fibrillation, heart failure, or pulmonary hypertension

- renal failure- infection- trauma- poorly controlled diabetes mellitus- cerebrovascular or pulmonary disease

If given as pretreatment, MMI should be discontinued 3–5 days before the administration of radioactive iodine, restarted 3–7 days later, and generally tapered over 4–6 weeks as thyroid function normalizes.

Page 41: Hyperthyroidism  and  Graves’ Disease

GO: WORSENING WITH I-131

Traisk F, et al. Thyroid-Associated Ophthalmopathy after Treatmentfor Graves’ Hyperthyroidism with Antithyroid Drugsor Iodine-131. J Clin Endocrinol Metab 94: 3700–3707, 2009

Page 42: Hyperthyroidism  and  Graves’ Disease

GO AND I-131: INCREASED PROPTOSIS

Traisk F, et al. Thyroid-Associated Ophthalmopathy after Treatmentfor Graves’ Hyperthyroidism with Antithyroid Drugsor Iodine-131. J Clin Endocrinol Metab 94: 3700–3707, 2009

Page 43: Hyperthyroidism  and  Graves’ Disease

GO: EFFECTS OF I-131 AND SMOKING

Traisk F, et al. Thyroid-Associated Ophthalmopathy after Treatmentfor Graves’ Hyperthyroidism with Antithyroid Drugsor Iodine-131. J Clin Endocrinol Metab 94: 3700–3707, 2009

Page 44: Hyperthyroidism  and  Graves’ Disease

RADIOACTIVE IODINE ABLATION: TIMELINE & MONITORING

I-131

Week 0

*Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med 2011;364(6):542–50

**RECOMMENDATION 11***RECOMMENDATION 12

Page 45: Hyperthyroidism  and  Graves’ Disease

RADIOACTIVE IODINE ABLATION: TIMELINE & MONITORING

I-131

Weeks 4-8

Week 0

Free T4 and T3

*Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med 2011;364(6):542–50

**RECOMMENDATION 11***RECOMMENDATION 12

(expect normalization)

q 4-6 weeks**

Page 46: Hyperthyroidism  and  Graves’ Disease

RADIOACTIVE IODINE ABLATION: TIMELINE & MONITORING

I-131

Weeks 4-8

Week 0

Free T4 and T3

6 months

No***

initiate LT4

Yes

*Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med 2011;364(6): 542–50

**RECOMMENDATION 11***RECOMMENDATION 12

(expect normalization)

q 4-6 weeks**

Hypothyroid?

q6 weeks

TSH + free T4

Page 47: Hyperthyroidism  and  Graves’ Disease

GD:TREATMENT

Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG,Taube A, Saaf M, Hamberger B 1996 Graves’ hyperthyroidism:treatment with antithyroid drugs, surgery, or radioiodine—a prospective, randomized study. Thyroid Study Group. J ClinEndocrinol Metab 81:2986–2993.

Page 48: Hyperthyroidism  and  Graves’ Disease

GD:TREATMENT

Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG,Taube A, Saaf M, Hamberger B 1996 Graves’ hyperthyroidism:treatment with antithyroid drugs, surgery, or radioiodine—a prospective, randomized study. Thyroid Study Group. J ClinEndocrinol Metab 81:2986–2993.

Page 49: Hyperthyroidism  and  Graves’ Disease

Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG,Taube A, Saaf M, Hamberger B 1996 Graves’ hyperthyroidism:treatment with antithyroid drugs, surgery, or radioiodine—a prospective, randomized study. Thyroid Study Group. J ClinEndocrinol Metab 81:2986–2993.

37%

6%21%

Page 50: Hyperthyroidism  and  Graves’ Disease

CHOSING THERAPY

Radioactive iodine ablation

1. Females planning a pregnancy in the future > 4–6 months following RAI

2. Comorbidities increasing surgical risk3. Previous neck surgery or external radiation4. Lack of access to a high-volume thyroid

surgeon5. Contraindications to ATD use

• Pregnancy, lactation• Coexisting thyroid cancer, or suspicion cancer• Individuals unable to comply with radiation safety

guidelines• Women planning a pregnancy within 4–6 months

Thyroidectomy

Page 51: Hyperthyroidism  and  Graves’ Disease

TSH, FT4/T3Eye findings+

goiter

Graves’ disease

Beta blockade

RAIU

PrednisoneYes

No

Active GO

TMNG or TA

Minimal

Elevated+

“hot” foci

Thyroiditis

Elevated, uniform

I-131 ablation Surgery

Consider patient preferences and comorbidities

MMI 10-20 mg/d

Page 52: Hyperthyroidism  and  Graves’ Disease

PEARLS (TAKE-HOME MESSAGES FOR PRIMARY CARE PROVIDERS)

• ATDs• Methimazole is drug of choice; PTU only if

pregnant in 1st trimester Counsel on potential adverse reactions Baseline CBC, LFTs; routine monitoring

not formally recommended TSH not particularly helpful initially Allow 12-18 months to achieve remission

Page 53: Hyperthyroidism  and  Graves’ Disease

PEARLS (TAKE-HOME MESSAGES FOR PRIMARY CARE PROVIDERS)

• RADIOACTIVE IODINE ABLATION• Contraindicated in pregnancy,

breastfeeding• Consider presence eye disease• Special diet and pretreatment with ATDs

usually not necessary and may make treatment less effective

• Takes several months to achieve therapeutic effect

TSH may remain low

Page 54: Hyperthyroidism  and  Graves’ Disease

CASE DISCUSSION

• Graves’ disease• propranolol 20 mg TID • MMI 10 mg/d or I-131• If treated medically: free T4 and T3 now

and again in 4 weeks• Once euthyroid, monitor levels q3

months• Taper MMI after 12 months

Page 55: Hyperthyroidism  and  Graves’ Disease

QUESTIONS

• Thank you