Raj Shah

University of Connecticut School of Medicine

Farmington, CT

Imaging and Therapy Using Nuclear Medicine in Graves’ Disease

I. Our Patient - Clinical Scenario & Evaluation: Physical Exam, Laboratory

Results, Diagnostic Imaging - Differential Diagnosis - Findings/Discussion

II. Radiopharmaceuticals - I-123 in Imaging – Indications - I-131 in Therapy – Indications, Course, Side Effects,

Contraindications - Alternatives to Radiopharmaceutical Therapy in the

Treatment of Graves’ Disease - Research Developments

Outline

• ID/CC: 65-year-old male presents with a several-month history of heat intolerance, fine tremor, sense of globus, and change in the pitch of his voice.

• PMH: Benign prostatic hyperplasia, peptic ulcer disease, hyperlipidemia, depression, recurrent right ear infections with associated right-sided hearing loss, an isolated episode of atypical chest pain, history of positive PPD.

• FH: Daughter was recently treated for ‘abnormal thyroid function with weight loss’ and is currently on Levothyroxine.

• SH: Smoker; occasional EtOH use. Retired mechanical engineer.

• Medications: Citalopram, Doxazosin, Finasteride

Clinical Scenario

• Physical Exam: Enlarged non-tender thyroid

• Labs

TSH <0.02 uIU/L (.27-4.2 uIU/mL)

Free T4: 2.1 ng/dL (.93-1.7 ng/dL)

Anti-TPO Antibodies: 202 IU/mL (0-35 IU/ml)

Antithyroglobulin Antibodies: < 1 IU/ml (a negative test is normal)

• Imaging

Thyroid Ultrasound: Heterogeneous thyroid gland with small subcentimeter-sized nodules of decreased echogenicity, without suspicious features.

Endocrine Evaluation

Normal Thyroid Gland on Ultrasound

Source:

Ultrasoundpaedia

Sagittal Ultrasound Image – Homogenous echotexture

Our Patient’s Thyroid Gland on Ultrasound

Left Lobe

Right Lobe

Source:

BIDMC

PACS

Source:

BIDMC

PACS

Sagittal Ultrasound Images – Diffusely heterogeneous gland with

subcentimeter nodular areas of decreased echogenicity, suggestive of

thyroiditis.

• Subacute thyroiditis Vs. • Hashimoto thyroiditis Vs. • Graves’ disease -No involvement of extraocular muscles, or a lack of thrill/bruit - suggests subacute thyroiditis -Presence of anti-TPO antibodies and potential familial traits - suggests Hashimoto thyroiditis -Possibility of Graves’ disease cannot be completely ruled out without a thyroid scan

Differential Diagnosis/ Preliminary Assessment

Thyroid Gland on I-123 Uptake Scan

Source:

BIDMC

PACS

Thyroid Gland on I-123 Uptake Scan

Large Gland

with Intense

Homogenous

Activity

Visualization

of the

Pyramidal

Lobe

Source:

BIDMC

PACS

Findings:

- This patient’s large thyroid gland demonstrates intense homogenous activity.

- There is visualization of the pyramidal lobe.

- I-123 uptake over 24 hours: 27%

Discussion:

- In addition to diffusely increased uptake of I-123 by the thyroid gland, in a small proportion of patients, a pyramidal lobe can be identified; it arises from the isthmus or medial aspect of one lobe, and extends superiorly and medially.

- Although this is a common variation, it may be accentuated in diffuse thyroid abnormalities such as Graves’ disease.

Findings/Discussion

I-123:

-Decays by electron capture

-Photon energy: 159 keV

-t1/2: 13 hours

-Provides a considerably lower dose of radiation to thyroid in comparison to I-131

-Agent of choice for thyroid imaging

-Normal range: 10-30% for 24-hour uptake

Radiopharmaceuticals: Imaging

-Relate general structure of gland to function

-Locate ectopic tissue

-Assist in evaluation of congenital hypothyroidism or organification defects

-Determine if a cervical or mediastinal mass is thyroid tissue

-Differentiate from causes of thyrotoxicosis- Graves’ disease from silent/postpartum/subacute/factitious thyrotoxicosis

Indications for Scintigraphic Thyroid Imaging

I-131:

-Decays by beta emission

-Photon energy: 364 keV

-t1/2: 8.04 days

-Undesirable for routine imaging due to high radiation dose to thyroid

-High thyroid dose and relatively low whole-body dose make I-131 an ideal therapeutic agent for treating certain thyroid disorders – hyperthyroidism caused by diffuse/nodular goiter, postsurgical ablation of thyroid gland remnants, treatment of functioning thyroid metastasis

Radiopharmaceuticals: Therapy

Source: Australian Nuclear Science

And Technology Organization (ANSTO)

Propylthiouracil and Methimazole

-Both agents inhibit the enzyme, thyroperoxidase. In addition, Propylthiouracil inhibits the peripheral conversion of T4 to T3.

-Medical therapy is usually prescribed for 12 to 18 months.

-Potential complications include agranulocytosis and hepatitis (extremely rare); a minor skin rash may also occur.

Medical Alternative to Radiopharmaceutical Therapy

Subtotal thyroidectomy; it leaves 3 -5 grams of residual thyroid tissue attached to an intact inferior thyroid artery.

-Potential complications include hemorrhage, recurrent nerve palsy, permanent hypocalcemia, and recurrent hyperthyroidism.

-Surgical treatment plays a minimal role in treatment of Graves’ disease due to potential complications and cosmetic effects; it is only recommended when other therapies are contraindicated, or refused by the patient.

Surgical Alternative to Radiopharmaceutical Therapy

-For definitive initial treatment and for patients who do not go into remission after initial treatment with antithyroid drugs. • Weetman AP. Radioiodine treatment for benign thyroid diseases. Clin Endocrinol (Oxf)2007;66:757-764

-Antithyroid drugs, when used, are generally discontinued for 3 to 7 days before radioiodine therapy, since the effectiveness of radioiodine may be diminished when antithyroid drugs are given concurrently. • Walter MA, et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of

randomised controlled trials. BMJ 2007;334:514-520

Indication for I-131 Therapy

-Once a radioactive form of iodine has been taken up by functioning tissue, its therapeutic effects are made possible by delivery of destructive ionizing radiation. • Mettler, Jr. and Guiberteau. Essentials of Nuclear Medicine Imaging 6th Edition, Page 116

-Hypothyroidism develops in about 80% of patients within 2-6 months, and lifelong T4 replacement is then required. • Leslie WD, et al. A randomized comparison of radioiodine doses in Graves' hyperthyroidism. J Clin Endocrinol Metab

2003;88:978-983

Course of Treatment

-The use of radioiodine in patients with Graves ophthalmopathy is controversial due to potential for exacerbation. • Bartalena L, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J

Med 1998;338:73-78

-Presence of ophthalmopathy should not impact the selection of therapy for hyperthyroidism.

-Patients with mild progressive ophthalmopathy should receive a course of steroids (prednisone up to 1 mg/kg) for 2-3 months, tapering a few days before radioiodine therapy. • Sai-Ching Jim Yeung and Alice Cua Chin. Graves disease; eMedicine Journal, Jan 2002, Volume 3

Graves’ Ophthalmopathy

Side Effects:

-A form of radiation thyroiditis that causes neck tenderness and in some cases, a transient increase in thyroid hormone levels. • Weetman AP. Radioiodine treatment for benign thyroid diseases. Clin Endocrinol (Oxf)2007;66:757-764

Contraindications:

-Therapeutic doses of I-131 are contraindicated in women who are or may become pregnant, as they may cause fetal harm. • Guidelines for the use of radioactive iodine in the management of hyperthyroidism.J R Coll Physicians Lond

1995;29:4649

-Note: Optimal therapeutic targets in women with Graves' disease during pregnancy are uncertain, since both low and high serum levels of T4 in the mother are associated with risks to the fetus. • Chan GW, Mandel SJ. Therapy insight: management of Graves' disease during pregnancy. Nat Clin Pract Endocrinol

Metab 2007;3:470-478

• Kempers MJ, et al. Loss of integrity of thyroid morphology and function in children born to mothers with inadequately treated Graves' disease. J Clin Endocrinol Metab 2007;92:2984-2991

Side Effects and Contraindications of I-131 Therapy

• Bogazzi, F. et al. Impact of lithium on efficacy of radioactive iodine therapy for Graves' disease: a cohort study on cure rate, time to cure, and frequency of increased serum thyroxine after antithyroid drug withdrawal. J Clin Endocrinol Metab 2010 Jan;95(1):201-8.

-298 patients were treated with radioactive iodine + lithium (900 mg/day for 12 days) and 353 with radioactive iodine alone; patients were followed for 1 year.

-Patients treated with radioactive iodine + lithium had a higher cure rate (91.0%) than those treated with radioactive iodine alone (85.0%, P = 0.030).

-Patients treated with radioactive iodine + lithium were cured more rapidly (median 60 days) than those treated with radioactive iodine alone (median 90 days, P = 0.000).

The Latest - Study #1

• Plazinska, et al. Lithium carbonate pre-treatment in 131-I therapy of hyperthyroidism. Nucl Med Rev Cent East Eur. 2011;14(1):3-8

-Investigation of the influence of lithium carbonate on the kinetics of radioiodine in the thyroid gland.

-Control group was treated without lithium; the second group was pre-treated with lithium carbonate at a dose of 1.0 g/day for 6 days before radioiodine and 3 days thereafter.

-A significant increase in iodine uptake in the thyroid gland was observed during intake of lithium carbonate in 106 out of 128 patients; a decrease of T3, FT3, T4, and FT4 levels and no significant changes in concentration of TSH were observed as an effect of lithium carbonate treatment.

The Latest – Study #2

Dr. J. Anthony Parker

Dr. Gillian Lieberman

Dr. Elizabeth Asch

Acknowledgements