Download Imaging and Therapy Using Nuclear Medicine in Graves` Disease

Imaging and Therapy Using Nuclear
Medicine in Graves’ Disease
Raj Shah
University of Connecticut School
of Medicine
Farmington, CT
Outline
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
Clinical Scenario
•
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
Endocrine Evaluation
•
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.
•
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.
Differential Diagnosis/ Preliminary
Assessment
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
Thyroid Gland on I-123 Uptake Scan
Source:
BIDMC
PACS
Thyroid Gland on I-123 Uptake Scan
Visualization
of the
Pyramidal
Lobe
Large Gland
with Intense
Homogenous
Activity
Source:
BIDMC
PACS
Findings/Discussion
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.
Radiopharmaceuticals: Imaging
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 24hour uptake
Indications for Scintigraphic
Thyroid 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
Radiopharmaceuticals: Therapy
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
Source: Australian Nuclear Science
And Technology Organization (ANSTO)
Medical Alternative to
Radiopharmaceutical Therapy
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.
Surgical 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.
Indication for I-131 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
Course of Treatment
-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
Graves’ Ophthalmopathy
-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
Side Effects and Contraindications
of I-131 Therapy
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
The Latest - Study #1
•
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 #2
•
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.
Acknowledgements
Dr. J. Anthony Parker
Dr. Gillian Lieberman
Dr. Elizabeth Asch