Transcript Treatment Options and Their Expected Outcomes

How To Decide Which Is The Best Therapy
Option For Hyperthyroid Patients: Guidance For
The Practicing General Radiologist and Nuclear
Medicine Physician
European Society of Radiology ESR
2011 Annual Meeting in Vienna, AT
March 3-7, 2011
Educational Exhibit, ID Number: 5722
****
B Rodgers, MD
University of Southern California, Los Angeles, CA
Disclosure of Commercial Interest
Neither I nor my immediate family members have a
financial relationship with a commercial organization that
may have a direct or indirect interest in the content.
Learning Objectives
After reviewing this presentation, General Radiologists and Nuclear
Medicine Physicians should feel comfortable:
1. Discussing various modes of therapy for hyperthyroid patients.
These include medical - pharmacologic management, surgery, and
radionuclide therapy with 131 - Iodine
2. Working with Clinicians who refer hyperthyroid patients for
radionuclide therapy
3. Taking the lead role in managing hyperthyroid patients, especially in
locations where specialists in thyroid disease are not available. This
will provide a highly valuable patient service.
Background Information:
Many physicians are not comfortable treating and managing patients with
hyperthyroidism. In many parts of the world, physicians highly trained in the diagnosis
and treatment of thyroid disease are not readily available, if at all. Even in the US, many
areas do not have adequate Endocrine Medicine nor Nuclear Medicine / Radiologist
coverage. In this light, we hope to educate General Radiologists and Nuclear Physicians
about the treatment of hyperthyroid patients. In many parts of the world, Radiologists
would have to treat these patients. Various options and methods will be reviewed in light
of evidence based medicine.
Only the treatment of Graves (diffuse, non-focal) hyperthyroidism will be reviewed in this
presentation.
For further information please contact:
Brian Rodgers, M.D.
LAC + USC Medical Center
1200 North State Street, D&T 3D321
Los Angeles, CA 90033
323 409 7257 via Residency program Co-ordinator
[email protected] personal email
This material is presented
for the sole purpose of
educating the reader and
is not intended for copying
nor downloading.
Please contact the author
if you wish copies of
portions of this exhibit.
Imaging Findings or Procedure
This exhibit will review:
- Clinical and biochemical identification of hyperthyroid patients
- The differential diagnosis of hyperthyroidism
- Types of hyperthyroidism
- Imaging of hyperthyroid patients
- Treatment options and their expected outcomes
- How to assist in managing hyperthyroid patients both during medical
therapy and after 131 - Iodine therapy
- Links to more detailed procedural, informed consent, and regulatory
information
Also included are multiple examples of how to perform dose
calculations (often an area of confusion to those unfamiliar with
therapy) using example cases. Other information on practice patterns
is also included.
Example Case – Why We Need To
Know How To Manage These Cases and a Great Case For Board Exams
17 year old female that has a 3 month history of:
10 lb weight loss/month
Palpatations
Muscle weakness
Insomnia
She weighs 73 kgs or 160 lbs and is 1.73 m or 5’8” tall.
HR: 88 BP:130/90
The primary care provider asks you in the elevator what should be done to
work up this patient.
What do you suggest and why?
Let’s Begin – With the Conclusion
Remember: General Radiologists can be valuable members
of a team treating and caring for patients with
hyperthyroidism.
Once you understand the principles (which follow), the
following will seem like common sense:
- Treat each patient individually based upon severity of
hyperthyroidism when they present to you.
This means offering patients with severe signs and symptoms
a higher dose of 131-I and those patients with lower levels of
clinical disease a more moderate dose. Low dose therapy
might be reserved for patients with minor signs and
symptoms and/or for those in whom maintaining euthyroidism
is thought to be very important.
The actual doses used can be based on the methodologies
explained in the slides which follow. See table on the next
page.
131-I Dosing Recommendations
Low
Dose
250 MBq
7 mCi
Finnish
method,
others
~66-80%
Tx success
~20-33%
Tx failure
Average
Dose
~370-555 MBq
~15 mCi
(typically
~10-15 mCi)
~1100 MBq
Up to 29 mCi
Based on
Michigan,
UK NHS, and
Mass Gen’l
methodologies
~ 85%
~15 %
Tx success
Tx failure
Tx dose
based on
severe signs
and / or
symptoms
Expect
almost
100% tx
success
High
Dose
For
Tx of Hypercomparison: tensive pts
Only 1/3
tx success
About 2/3
fail tx
Remember tx success is often defined in the literature as those pts who
become euthyroid or hypothyroid after tx. (Tx = treatment or therapy)
Basic Principles of Pathophysiology
These are reviewed elsewhere and are beyond the scope of this exhibit.
Many Internal Medicine textbook chapters cover this well. Internet search
engines will also yield well written web and journal articles, such as this one:
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1787885&blobtype=pdf
G. Davies, Thyroid Physiology, Scientific Basis of Clinical Practice, Medical Practice,
BMJ: 1972 (2): 22 April 1972, pp 206-9.
What concerns us here is when thyroid hormone overproduction is due to
Graves’ Disease. TSH regulates thyroid hormone production. Graves
Hyperthyroidism may be associated with elevated levels of TSH. However,
long active thyroid stimulator (LATS) can also play a role.
Incidence: Graves Disease is the most common etiology for hyperthyroidism
in the US. It is an immune mediated / auto-immune disease process. It is 7
times more common in women than men. It is also more common over age
20.
http://www.mayoclinic.com/health/graves-disease/DS00181
http://www.endocrineweb.com/hyper1.html
Part 1: Clinical and Biochemical
Identification of Hyperthyroid Patients
Common signs and symptoms suggesting hyperthyroidism may include:
Anxiety, disturbance of sleep patterns, fatigue, weight loss, increased
perspiration, feeling hot, tacchycardia, fine tremor, change in menstrual
cycle, blurred vision, and, exopthalmos.
Levels of free and bound T3 and T4, along with TSH and anti-thyroid
antibodies might need to checked as part of assessing patients with
clinical hyperthyroidism. Thyroid-peroxidase antibodies (TPA) are elevated
in 75% of Graves' disease patients. TPA is a marker of thyroid
autoimmune activity. Nuclear medicine 4 and 24 hour uptake and scan are
also used for this purpose.
“In Graves' disease, your immune system mistakenly attacks your thyroid gland, but
instead of destroying the gland, an antibody called thyrotropin receptor antibody (TRAb)
stimulates the thyroid to make excessive amounts of thyroid hormone. “
http://www.mayoclinic.com/health/graves-disease/DS00181/METHOD=print
and
http://www.medifocushealth.com/ND004/Diagnosis-of-Graves-Disease_Diagnostic-Testing-for-GravesDisease.php
Common Clinical Findings In
Hyperthyroid Patients
The following can found in Graves Disease. However, the same findings
can also be seen in Toxic Multinodular Goitre, along with other causes;
please see Part 2 of this exhibit for differential diagnosis.
“Common symptoms and
signs of hyperthyroidism:
http://www.endocrineweb.com/hyper1.html
Palpitations
Fatigue
Heat intolerance
Fast heart rate
Nervousness
Trembling hands
Insomnia
Weight loss
Breathlessness
Muscle weakness
Increased bowel movements Warm moist skin
Light or absent menstrual
Hair loss
periods
Staring gaze”
Biochemical Identification of Hyperthyroid Patients
Work up for suspected hyperthyroidism:
-measure the thyrotropin (TP) and free thyroxine (F TX):
-if both are normal, the patient is not hyperthyroid
-low TP; normal F TX – measure the serum free triiodothyronine (F T3), if that is normal,
consider subclinical hyperthyroidism such as early Graves Disease or Toxic nodular goitre.
Excess or surreptitious use of T4 (as in the example case) can also do this. Illness not
from the thyroid also possible. Synthroid ® is the trade name of T4 thyroid hormone
commonly used in the US, made by Abbott Laboratories. Unlike many prescription
medications, many physicians prefer the use of Synthroid over generic medication.
From 2008 package insert
Consider repeating these labs in 2-3 months with annual follow up if findings do not
progress.
-low TP; high F TX –hyperthyroid patient or if the F T3 is high (with NL F TX) T3 hyperthroidism.
Here the differential diagnosis includes:
Graves Disease; Toxic nodular goitre, including adenomas; thyroiditis; excess or
surreptitious use of T4; gestational hyperthyroidism; thyroid cancer; struma ovarii; chorionic
gonadotropin secreting tumors; Albright’s syndrome, and familial non-auto immune
hyperthyroidism.
-Nl or high TP and high F TX: consider a thryrotropin secreting adenoma of the pituitary gland or
thyroid hormone resistance syndrome.
suggested from: Anthony P. Weetman, M.D., D.Sc., Graves' Disease,
NEJM, 343:1236-1248, October 26, 2000.
Parts 2 and 3: Differential Diagnosis
and Types of Hyperthyroidism
Graves Disease / Hyperthyroidism needs to be separated from other etiologies for
hyperthyroidism.
If the thyroid gland is nodular on physical exam, ultrasound, and /or nuclear scan:
--single nodule, consider autonomously functioning thyroid nodule (AFTN) or Plummer’s
Disease (NB: Plummer did not distinguish between AFTN and TMNG in his original 1913
paper).
--multiple nodules, consider toxic multi-nodular goitre (TMNG)
These can be treated somewhat differently than Graves Disease and are therefore not
discussed further here.
The signs and symptoms for Graves Disease are non-specific, therefore we must also exclude:
anxiety, surreptitious use of thyroid hormone, other drug abuse, some types of drug or
medication withdrawal, pheochromocytoma, auto-immune thyroiditis – including Hashimoto’s
thyroiditis, infection in the thyroid bed, signs of menopause, myopathy, and hypoglycemia. Both
Hashimoto and Graves patients may have enlarged tender glands and have thyroid peroxidase
antibodies.
http://www.medifocushealth.com/ND004/Diagnosis-of-GravesDisease_Differential-Diagnosis-of-Graves-Disease.php
Part 4: Imaging of Hyperthyroid
Patients
Ultrasound can be used to assess for nodularity either apparent or not apparent on physical
exam and to find solid and cystic masses. When present, such nodules may require further
assessment; for example, via fine needle aspiration (FNA).
CT and MRI may find abnormalities of the thyroid gland on neck, chest, cardiac, or spine
exams. However, the use of iodinated CT contrast may delay the use of nuclear imaging
and / or therapy by 4-8 weeks, due to saturating the thyroid follicular cells with iodine.
Nuclear imaging is usually performed about 4 hours post ingestion of 123-I or about 10 min
post injection of TcO4. Grave’s patients demonstrate even uptake throughout the thyroid
gland without hot spots nor cold defects.
Uptake measurements are usually made at 4 and 24 hours post ingestion of 131-I or 123-I.
Normal uptake values are 5-15% and 10-30% respectively. These values can also help
support the diagnosis of clinically suspected Graves Disease – or even support the likelihood
of an alternative diagnosis, such as Hashimoto’s Thyroiditis.
However, the relative values obtained at 4 and 24 hours are often not similar. Most practices
in the US which use an iodine uptake value as part of calculating a therapy dose, use the 24
hour value. For Graves patients, this is often around 40% in the authors practice; though
numbers may vary widely (35-70%) around the world.
Imaging of Hyperthyroid Patients – 2
Nuclear Medicine and Radiation Dose Information
Nuclear medicine imaging of the thyroid is commonly done via 1 of 3 methods. Both
uptake and scan are commonly performed at the same time using:
both 131-I (for uptake) and 99m TcO4 (for scan). Lower cost method (but higher
radiation dose to the patient).
123-I (for both uptake and scan). Higher cost, lower radiation dose method.
99m TcO4 washout (for both uptake and scan). Unlike the above, not commonly
used. Poor reproducibility.
131-I (for uptake) and 99m TcO4 (for scan):
Technetium is used for imaging; typically 185-370 MBq, 5-10 mCi. The very small
amount of 131-I, about 0.2 MBq or 5 micro (µ) Ci, is roughly at the lower range of
utility of the well counter used to check doses. However, the radiation dose from
131-I is quite high: Dose rate at 1m from 37 MBq or 1 mCi = 2.20 mSv/hr (~2.2
mGy).
123-I uptake and scan. Typical dose is about 12.3 MBq = 350 µCi or 1/3 mCi.
131-I ~1 rad/ µCi = 270 mGy/mBq
123-I ~1 rad/100 µCi, or 1% of the 131-I dose. (since about 70 x more µCi used,
dose reduction is a minimum of about 30%. However, β particles of 131-I are more
energetic than gammas or 123-I.)
99m TcO4 ~1 rad/5000uCi, or 1/5000th the 131-I dose
Part 5: Treatment Options and Their Expected Outcomes
1. No TX, XRT, Surgery
No Tx: The natural history of Graves Hyperthyroidism is for the thyroid to
eventually “burn itself out”. However, this can exact a great toll on the body
before this occurs. Cardiac and other effects can be debilitating and require
alterations of lifestyle. For most patients, doing nothing is the worst option.
External Beam Radiation Therapy (XRT): Was used many years ago as a
primary therapy for hyperthyroidism. However, like surgery, XRT is rarely
used as a primary therapy for Graves hyperthyroidism today.
Surgery could be considered as a primary Graves therapy when significant
tracheal compromise due to marked thyroid gland enlargement is present.
Perhaps its one advantage over other any other therapy approach is the
immediate removal of thyroid hormone reserves. (Circulating hormones have
a half life of about 1 week and cannot be removed). Yet, at least 1 recent
study found that this only cured ~90+% (reason for such a low cure rate not
given, but might be due to the surgeon leaving significant tissue behind).
Laurberg P. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid
drugs, surgery, or radioiodine: a 5-year prospective randomized study. European Journal of
Endocrinology (2008) 158 69–75.
Treatment Options and Their Expected Outcomes – 2
2. Surgery and Medical TX
Success rate by surgical therapy will likely be directly related to the
experience of the surgeon. Those that “commonly” perform
thyroidectomies should get excellent results.
Regardless of method used, patients with cardiac symptoms are often first
placed on β blocker therapy, such as propranolol (dose range varies, but
20-80 mg/day PO in divided doses would be common).
In Europe, medical therapy is most common. This works by preventing
production of new thyroid hormone-but there is no effect on hormone
already in the thyroid gland. These medications are usually not expensive.
The most commonly used anti-thyroid drugs include:
-Methimazole (MMI) or Tapazole, qD. Easiest to use due to single daily
dose, works quickly, and side effects (at low dose) are less common. It
may take 6 weeks for patient to reach a normal T4 value; often 8 weeks
with PTU. It takes a long time to reduce the circulating amount of thyroid
hormone due the thyroid gland’s large reserves.
http://www.medifocushealth.com/ND004/Treatment-Options-for-Graves-Disease_Drug-Therapy-for-Graves-Disease.php,
http://www.medifocushealth.com/ND004/Treatment-Options-for-Graves-Disease_Drug-Therapy-for-Graves-Disease2.php
Treatment Options and Their Expected
Outcomes – 3, Medical TX
-Propylthiouracil (PTU), tid. For people who cannot tolerate MMI. Also less
likely to cross placenta and less likely to be part of breast milk.
-Carbimazole, commonly used in Europe, but not available in the US.
MMI and PTU can be given either:
Short term - to prepare the patient for another treatment such as surgery or
radioiodine treatment
Long term - for definitive treatment of Graves' disease. Having patients on
medication for over a year is not unusual. Yet, even here 60% of patients
may fail after 2 years of medical therapy. Remission rate appears to be
higher if thyroid antibody levels fall. “If levels of TSH receptor antibodies
are normal at 6 months post treatment, the rate of relapse is
approximately 8-10%.”
http://www.medifocushealth.com/ND004/Treatment-Options-for-Graves-Disease_DrugTherapy-for-Graves-Disease.php,
http://www.medifocushealth.com/ND004/Treatment-Options-for-Graves-Disease_DrugTherapy-for-Graves-Disease2.php
Treatment Options and Their Expected
Outcomes – 4, Medical TX
However, medical therapy only yields a medium to long term remission in 2590% of patients. The wide range of results here may be due to duration of
use of medications.
Lucas A. Medical Therapy of Graves’ Disease: Does Thyroxine Prevent Recurrence of
Hyperthyroidism? The Journal of Clinical Endocrinology & Metabolism 1997, 82:8, 2410-2413.
and
Raber W. Medical therapy of Graves’ disease: effect on remission rates of methimazole alone and
in combination with triiodothyronine. European Journal of Endocrinology (2000) 142 117–124.
Disadvantages of medical therapy:
permanent cure is not likely;
patients must take meds for a year or more;
some patients have significant side effects from the meds (for example, PTU
induced liver failure, reported from the US Food and Drug Administration
(FDA) in June 2009)
FDA ALERT [06/04/2009]:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/
DrugSafetyInformationforHeathcareProfessionals/ucm162701.htm
Case 1
Small masses seen at CT not
noted on planar thyroid scan.
This is a 43 year old male with a diagnosis of
small thyroid masses by CT and
Hyperthyroidism secondary to Graves disease
and has failed medical therapy with PTU. The
patient has persistently elevated LFT’s. Please
see FDA advisory on PTU induced liver failure
(6/4/2009). Surgery was advised in order to
exclude any malignancy in the thyroid masses.
10-30%
He was scheduled for a total
thyroidectomy. In selected pts
including those with both
thyroid masses (or goiter) and
Graves Disease, this can be
the optimal tx. Post operatively
the patient has been doing well
and taking Synthroid and
Calcium supplementation.
Case 1
This is a 43 year old male with a diagnosis of small thyroid masses by CT
and Hyperthyroidism secondary to Graves disease and has failed medical
therapy with PTU. The patient has persistently elevated LFT’s. Please see
the FDA advisory on PTU induced liver failure (6/4/2009). Surgery was
advised in order to exclude any malignancy in the thyroid masses.
This case highlights the fact that not all patients should be offered the same
treatment.
This patients has 3 major issues: thyroid masses, Graves Disease, and a
reaction to medical therapy for Graves Disease. The patient did not wish to
have multiple fine needle aspirations (FNAs) to assess his multiple thyroid
nodules for possible cancer, due to discomfort and the chance of a false
negative cytology result. Also, surgery can “cure” both any local malignancy
(via thyroidectomy and compartmental lymph node dissection) and his
Graves Disease at the same time. He had a bad experience with medical
therapy too. He simply wanted to be “done with it”.
He was scheduled for a total thyroidectomy. In selected pts including those with
both thyroid masses (or goiter) and Graves Disease, this can be the optimal tx. Post
operatively the patient has been doing well and taking Synthroid and Calcium
supplementation.
Treatment Options and Their Expected Outcomes – 5
Variance of Practice Patterns
Standards of practise vary around the world.
For example, as noted in a study from Germany, medical therapy for hyperthyroidism
is tried first. Patients had to be over 30 years old to be eligible for 131-I therapy. In
patients 30-40 years old, failure of either medical therapy or surgery had to occur
before using 131-I. In patients over 40 years old 131-I could be a primary therapy for
hyperthyroidism.
In this paper treatment success was the elimination of hyperthyroidism, regardless of
how many patients were made hypothyroid due to treatment.
H. PETERS, C. FISCHER, U. BOGNER, C. REINERS H. SCHLEUSENER , Radioiodine therapy of
Graves' hyperthyroidism: standard vs. calculated 131 iodine activity. Results from a prospective,
randomized, multicentre study. European Journal of Clinical Investigation 1995, 25:3,186 - 193.
Although it is uncommon to use 131-I for children and young adults as the standard of
care in Germany, in the US, even children are treated with 131-I. There was a dose
dependent success rate in this study from Yale. For example, 8.14 MBq/g = 220 µCi/g
or 200 Gy yielded hypothyroidism in 70% at 1 year.
Rivkees SA and Cornelius EA. Influence of Iodine-131 Dose on the Outcome of Hyperthyroidism In
Children. Pediatrics 2003; 111; 745-749.
Practice patterns in the US are often determined by the methods learned in residency
and local expertise. Thus, even in the US, treatment methods for hyperthyroidism
may vary greatly – even in the same city.
Treatment Options and Their Expected Outcomes – 6
Some Areas of Controversy
The potential need for using a b blocker, such as propranolol, is common to all
forms of therapy. This may provide symptomatic relief for cardiac issues.
In the US and UK, iodine deficient diets are not common. But elsewhere in the
world this may not be the case. In iodine deficient patients, the 131-I dose may
need adjusting. Patients from regions of low iodine availability may have larger
glands.
Controversies persist regarding when to discontinue use of anti thyroid
medication (ATM) -both in general and before use of 131-I therapy; how much
ATM to use; dose of 131-I; risk and effect of mild post treatment hyperthyroidism.
A recent Swedish study did randomize patients with hyperthyroidism to surgery,
medical therapy, and 131-I. But the purpose of this study was to assess thyroid
antibody levels post treatment and their potential effects on the patients. At 4
years follow up, under 10% of the surgically treated group remained hyperthyroid.
In the medically treated group, about 40% remained hyperthyroid at 4 years, as
did 21% treated with 131-I. Of course, all of these results are influenced by the
details of the therapeutic regimens used.
Laurberg P. TSH-receptor autoimmunity in Graves’ disease after therapy with antithyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study.
European Journal of Endocrinology (2008) 158 69–75.
Case 2
This is a 35 year old female with a
history of infertility and progressive
symptoms of hair loss, fatigue,
palpitations, heat intolerance, and a
pruritic rash. Patient wishes to have a
child. The patient was placed on PTU
and had a reaction to it.
So, for this patient optimal
therapy would be surgical or
methimazole treatment. 131-I is
less optimal as the patient would
be advised not to begin a family
in the year following tx.
Treatment Options and Their Expected Outcomes – 7
131-Iodine
131-I has been used in the treatment of hyperthyroidism since around 1941.
CLARK T. SAWIN, DAVID V. BECKER, Radioiodine and the Treatment of
Hyperthyroidism: The Early History. Thyroid. April 1997, 7(2): 163-176.
However, early access to 131-I was limited to Berkeley, California, and the area
near MIT in Boston. Wider use outside the academic setting only occurred by
the 1960s. Concerns about 131-I causing cancer have been allayed in multiple
studies. However, a slight increase in some cancers, whether due to the
hyperthyroidism itself or due to 131-I or anti thyroid medications has been
noted. The reasons for this remain unclear.
Cooper, DS. Radioiodine for Hyperthyroidism Where Do We
Stand After 50 Years? JAMA: 280, 4: 375-6, 1998
The low cost of 131-I, its low morbidity, few side effects, and the potential for a
very high success rate favor its use.
Use of 131-I is also considered safe in patients reporting iodine allergy, due to
the miniscule amount of radioactive iodine present; 0.05-0.18 µg. Average daily
intake, >150 µg/day.
Royal College of Physicians. Radioiodine in the management of benign thyroid
disease: clinical Guidelines. Report of a Working Party. London: RCP, 2007
The only absolute contraindications for 131-I use are pregnancy and breast
feeding.
Treatment Options and Their Expected Outcomes – 8
Graves Disease and Ophatlmopathy
Controversy remains regarding 131-I therapy possibly worsening Graves
Opthalmopathy. However, it is possible that hyperthyroidism and
opthalmopathy run somewhat separate and independent courses,
thought both may occur via auto-immune processes. Weetman, in
referencing others notes concern for those with pre existing
opthalmopathy or even causing it.
Anthony P. Weetman CLINICAL PRACTICE UPDATE Radioiodine treatment for benign
thyroid diseases Clinical Endocrinology 2007, 66:6, 757-764.
This risk may be 4 X more likely in smokers. Although, this might be 1
factor favoring medical therapy in Europe, in the US there is no
established practice pattern in this regard. Steroid protocol is given in
Weetman’s article on p. 760. The RCP White Paper, suggests using
ATDs and not 131-I therapy in newly diagnosed Graves’ patients with
active opthalmopathy.
Royal College of Physicians. Radioiodine in the management of benign thyroid disease:
clinical Guidelines. Report of a Working Party. London: RCP, 2007
Treatment Options and Their Expected Outcomes – 9
Special Considerations: Children (131-I vs Surgery) and
Dialysis Patients (Reduced Dose of 131-I)
In pediatric Graves patients, most seem to favor 131-I therapy, though
surgery is still advocated by some, even in the recent literature.
as noted in:
Anthony P. Weetman CLINICAL PRACTICE UPDATE Radioiodine treatment for
benign thyroid diseases Clinical Endocrinology. 2007, 66:6, 757-764.
Lucignani notes that some still believe that surgery is more ideal for pediatric
hyperthyroid therapy. However, local expertise will usually decide which type
of treatment will be used.
Giovanni Lucignani Long-term risks in hyperthyroid patients treated with radioiodine: is there
anything new? Eur J Nucl Med Mol Imaging (2007) 34:1504–1509,
quoting a group in San Francisco,
James A. Lee, Melvin M. Grumbach, and Orlo H. Clark CONTROVERSY IN CLINICAL
ENDOCRINOLOGY The Optimal Treatment for Pediatric Graves’ Disease Is Surgery The Journal of
Clinical Endocrinology & Metabolism 92(3):801–803
In dialysis patients the dose of 131-I needs to be greatly reduced; perhaps
only using 1/7-1/4 the normal dose.
Jennifer P. Holst, Kenneth D. Burman, Frank Atkins, Jason G. Umans,
Jacqueline Jonklaas. Radioiodine Therapy for Thyroid Cancer and
Hyperthyroidism in Patients with End-Stage Renal Disease on
Hemodialysis. Thyroid. December 2005, 15(12): 1321-1331.
Treatment Options and
Their Expected Outcomes – 10
Thus we left trying to decide the best way to perform 131-I therapy.
First: decide on the reason for and thus the goal of treatment. Often the goal
of therapy is to quickly and permanently end hyperthyroidism. However, is
euthyroidism required? Is post therapeutic hypothyroidism acceptable or
even desirable? These are as yet unresolved controversies in the literature
and clinical practice.
Expected outcomes for the 4 methods of radio – iodine therapy are
summarized in the table at the beginning of this exhibit (slide 8).
Treatment Options and
Their Expected Outcomes – 11
For patients with severe signs and symptoms of Graves Disease, a “high
dose” therapy will lead ending hyperthyroidism with a higher degree of
certainty and possibly sooner. However, the likelihood of hypothyroidism as a
result of treatment will increase. Areas of further controversy include how to
treat the patient prior to 131-I “curing” the hyperthyroidism and the possible
significance of causing early post therapy hypothyroidism. Keep in mind that
thyroid hormone replacement can usually be easily managed post therapy in
nearly all hypothyroid patients – if they seek medical assistance. The
problem here is that many hypothyroid patients might not feel bad - and thus
might not seek further physician assistance; although many are symptomatic
and seek further medical attention for this reason. Therefore, maintaining
contact with previously treated patients is very important.
For patients with “lesser” clinical degrees of Graves Disease a “lower dose”
131-I therapy may be acceptable. Keep in mind that lower doses of 131-I
often correlate with lower treatment response.
Part 6: How to Assist in Managing Hyperthyroid Patients Both
During Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I
Currently, there are 4 methods of 131-I therapy for hyperthyroidism commonly
reported in the literature:
1.
Fixed dose per gram of thyroid tissue. Thyroid size is usually estimated
by physical exam; sometimes by ultrasound. Accuracy of estimating
thyroid size is a major problem with this method. Often 5.55 Mbq/gm
(150 µCi/gm) of thyroid tissue multiplied by estimate of thyroid size is
used. Common values for thyroid size: 20 gm-normal; 40 gm- 2x normal;
80 gm-very large gland. This value is then divided by the % uptake usually a recent 123-I 24 hour uptake value is used. As iodine uptake in
hyperthyroid patients is variable, performing the 4 and 24 hour uptakes
and scans within 1 week of therapy is strongly suggested.
Van Isselt JW, et al. Iodine-131 uptake and turnover rate vary over short intervals
in Graves’ disease. Nucl Med Commun. 2001:21; 609-616.
For example (5.55 MBq/gm or 150 µci/gm * 40 gm thyroid gland size
estimate, a moderately enlarged gland) = 222 MBq or 6000 µCi = 6 mCi
Then divide this by the 50% 24 hour 123-I uptake. So, 222 MBq/50% or 6
mCi/50% = 444 MBq or 6/.5 = 6 * 2 = 12 mCi.
How to Assist in Managing Hyperthyroid Patients Both During
Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 2
To repeat:
For example (5.55 MBq/gm or 150 µci/gm * 40 gm thyroid gland size
estimate, a moderately enlarged gland) = 222 MBq or 6000 µCi = 6 mCi
Then divide this by the 50% 24 hour 123-I uptake. So, 222 MBq/50% or 6
mCi/50% = 444 MBq or 6/.5 = 6 * 2 = 12 mCi.
(NB: in the US 24 hr 123-I uptake values of 40% are more common, thus a
555MBq or15 mCi 131-I dose would be commonplace via this method.)
In this example, the patient would receive 444 MBq or12 mCi of 131-I to treat
his hyperthyroidism. For lack of better terminology, this might be
considered a “medium dose”. Various reports in the literature will quote
widely varying response rates, as is true with the other methods
described on the following slides.
How to Assist in Managing Hyperthyroid Patients Both
During Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 3
1. Continued, Fixed dose per gram of thyroid tissue, slide 3.
This is the method suggested by Dr. Beierwaltes at the University of
Michigan from many years ago and favoured by the main author for most
patients.
reviewed in:
Beierwaltes WH: The Treatment of Hyperthyroidism With Iodine131. Seminars in Nuclear Medicine. 8 (1) Jan 1978, 95-103.
Interestingly, it is quite similar to the earliest methods I have found reported,
where errors of 50% in thyroid radiation were expected (in part due to errors
in gland size estimation and the need for using a mixture of iodine isotopes).
Hertz S, Roberts A: Radioactive Iodine In The Study of Thyroid Physiology. VII. The Use of
Radioactive Iodine Therapy in Hyperthyroidism. JAMA: 131 (2) May 11, 1946, 81-6.
Chapman EM, Evans RD: The Treatment of Hyperthyroidism With Radioactive Iodine.
JAMA: 131 (2) May 11, 1946, 86-91.
How to Assist in Managing Hyperthyroid Patients Both
During Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 4
1. Continued, Fixed dose per gram of thyroid tissue, slide 4.
Millicurie doses from the 1940s are also different from today’s doses as
nodular goiter was very common back then, and uncommon now in the US.
Yet, even in Hertz’s article a dose range of 125.8-1036 MBq (3.4 – 28 mCi)
was used. Chapman used much higher doses, 518-2913 MBq (14 – 79 mCi).
Both authors had many patients requiring more than 1 130-I, 131-I combined
isotope therapy. Inducing myxedema was 1 of Dr. Chapman’s goals. Many of
these early patients had isotope therapy followed by surgery – which was
standard therapy at this time
How to Assist in Managing Hyperthyroid Patients Both
During Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 5
Methods 2 and 3:
Offer a either a fixed amount (MBq or mCi ) for all patients (EG, 259 MBq or 7 mCi
total amount, Finland)
Saara Metso , Pia Jaatinen, Heini Huhtala, Tiina Luukkaala, Heikki Oksala and
Jorma Salmi Long-term follow-up study of radioiodine treatment of
hyperthyroidism.
Clinical Endocrinology 61:5, 641 - 648, 2004.
or adjust an otherwise fixed base amount contingent on the 24 hour 123-I uptake.
(EG 296 MBq or 8 mCi, as the amount delivered to the thyroid gland. This method
requires more than 296 MBq or 8 mCi as the oral dose (540.2 MBq or 14.6 mCi mean
amount of 131-I. Thus mean 24 hour uptake was 54.8%). This is the method
suggested by Alexander from Massachusetts General Hospital. (Also see last section
for special cases).
Erik K. Alexander and P. Reed Larsen High Dose 131I Therapy for the
Treatment of Hyperthyroidism Caused by Graves’ Disease The Journal of
Clinical Endocrinology & Metabolism 2002, 87:3, 1073-1077.
Neither of these methods requires assessment of thyroid gland size.
In this way we deliver a certain number of MBq or mCi to the entire gland, as opposed
to method 1, where we deliver a certain number of MBq or mCi to each gram of
thyroid tissue.
How to Assist in Managing Hyperthyroid Patients Both
During Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 6
To review, in Methods 2 and 3, no assessment of thyroid gland size is used.
In this way we deliver a certain number of MBq or mCi to the entire gland, as
opposed to method 1, where we deliver a certain number of MBq or mCi to
each gram of thyroid tissue - which requires measurement of gland size, no
matter how imprecise.
Method 4:
Deliver a fixed radiation dose (Gy) to the thyroid gland. In this method
(suggested by Peters) we use a calculated amount (MBq or mCi) in order to
deliver about 200 Gy to the thyroid gland.
Peters H et al. Radioiodine therapy of Graves' hyperthyroidism:
standard vs. calculated 131 iodine activity*. Results from a
prospective, randomized, multicentre study. European Journal of
Clinical Investigation 1995, 25:3, 186 - 193. Per Figure 4, p.190.
How to Assist in Managing Hyperthyroid Patients Both
During Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 7
4. cont. While there are some conversions available between MBq or mCi and Gy, in “typical”
patients (555 MBq or 15mCi is about 200 Gy in Peters patients), there may be wide variations in
individual patients.
Only the review by Dr. Beierwaltes (For reference see Method 1, which included patients with
multinodular goitre) contradicts the results found by others: the higher the 131-I dose, the higher
the treatment success rate and the higher the rate of post therapy hypothyroidism. The following
graphs are suggested by Peters H et al and demonstrate the point.
Peters H et al. Radioiodine therapy of Graves' hyperthyroidism: standard vs. calculated
131 iodine activity*. Results from a prospective, randomized, multicentre study.
European Journal of Clinical Investigation 1995, 25:3, 186 - 193. Per Figure 4, p.190.
555 MBq =15 mCi ~ 208 Gy
80%
This 131-I dose would be in the
commonly used range in typical
Graves patients in the US (via
Beierwaltes method).
50%
100 200
Success rate % vs Radiation Dose
absorbed by the thyroid gland (Gy)
250 MBq ~ 7 mCi ~ 100 Gy
would be more typical of a “low
dose” therapy.
How to Assist in Managing Hyperthyroid Patients Both During Medical Therapy
and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 8
An Unresolved Factor: Residence Time of 131-I in the Thyroid Gland
Most 131-I dosing calculations are based on 24 hour values, without determining the
exact residence time of iodine in the gland. References for Iodine mean effective
iodine t ½:
- German patients, = 4.7d (+/-1.7d) Peters pp 188-9.
- Sisson and Gross at the University of Michigan, quoting others, note that,
“determinations of the effective half-life of 131-I in hyperthyroid glands have been
reasonably consistent at 5 – 5.5 days….”
Peters H et al. Radioiodine therapy of Graves' hyperthyroidism: standard vs. calculated 131 iodine
activity*. Results from a prospective, randomized, multicentre study. European Journal of Clinical
Investigation 1995, 25:3, 186 - 193.
and
James C. Sisson, Anca M. Avram, Domenico Rubello, Milton D. Gross. LETTER TO THE EDITOR,
Radioiodine treatment of hyperthyroidism: fixed or calculated doses; intelligent design or science?
Eur J Nucl Med Mol Imaging (2007) 34:1129–1130.
Around the world, there is great variation in the amount of iodine available in the diet.
Also, low iodine diets are usually recommended in the US prior to use of 131-I for
therapy of hyperthyroidism or to treat thyroid cancer. However, many patients do not
follow iodine restrictions. While beyond the scope of this presentation, both of these
factors can influence the effectiveness of radio iodine therapy.
How to Assist in Managing Hyperthyroid Patients Both During
Medical Therapy and After 131 - Iodine Therapy
4 Methods Used to Determine Dose of 131-I - 9
Patients at Higher Risk for Treatment Failure, Part 6, slide 9
Alexander at MGH also notes groups at higher likelihood for 131-I treatment
failure:
Younger patients
Larger thyroid glands
Higher T4
Higher 24 hour uptake values
Erik K. Alexander and P. Reed Larsen High Dose
131I Therapy for the Treatment of Hyperthyroidism
Caused by Graves’ Disease The Journal of Clinical
Endocrinology & Metabolism 2002 Vol. 87, No. 3
1073-1077.
Worse opthalmopathy
Prior use of antithyroid medication
On this basis, they suggested using a target of 407 MBq or 11 mCi (not 296
MBq or 8 mCi) delivered to the thyroid gland in selected patients <20 gm,
gland size > 4x nml, > 70% 24 hour uptake, or prior use of ATD for more
than 4 months. Yet, they still expect failure rates at initial therapy of 5-10%
(p. 1076)
Expected Outcomes and How Long To Wait For These
Results, Use of ATDs post 131-I Therapy
Depending on the patient’s condition at the time of therapy, worsening of thyroid
related signs and symptoms may occur in the weeks to months following 131-I
therapy. In frail elderly patients and/or those with significant cardiac problems, close
follow up and additional care might be needed.
Use of ATDs post 131-I is controversial and might be best limited to those patients
with significant hyperthyroid related medical issues. Perhaps, as suggested by the
RCP White Paper, using a B blocker, such as propranolol to treat mild to moderate
symptoms could be considered in place of using ATDs. However, if an ATD is
needed, waiting as long as possible after 131-I therapy is preferred. As the t ½ for
131-I is about 1 week, waiting at least 1 week after 131-I therapy before re-starting
ATDs might be prudent.
Effects of 131-I therapy typically occur very gradually. It is the author’s experience
that those with only weekly (or more in-frequent) contact of the patient have the
greatest likelihood of determining significant changes in the patient’s medical status. It
may take 2 months or more for clinical changes to occur and/or be notable.
Expected Outcomes – Opthalmopathy and Post – Tx Labs
However, as stated earlier, opthalmopathy may run an independent course to 131-I
therapy. Should the patient note findings suggesting a change in opthalmopathy in the
week to months following 131-I therapy, dedicated opthalmology consult is suggested.
However, very few practitioners have expertise in this area.
The author councils patients not to buy expensive new contact lenses nor glasses in the
weeks to months following 131-I therapy as visual acuity changes may also occur, and
may vary over time as well. Buy inexpensive ones until the visual acuity has been stable
for at least several months. (Then buy the expensive new designer lenses and frames.)
Follow up thyroid hormone levels are often obtained no earlier than 4 weeks post 131-I
therapy. Obtaining T4 and TSH levels at 8-12 weeks post therapy would seem
reasonable in most patients. Further follow up labs can be obtained every 2 months or
so during the first year if the patient is doing well clinically. If the patient is not
significantly symptomatic nor hypothyroid, continued follow up clinic visits can take
place at 1 year post 131-I therapy.
Patients may become transiently hypothyroid within the first few months after 131-I
therapy. Only continued follow up labs and/or clinic visits can tell if the hypothyroidism is
temporary or permanent.
Persistent hyperthyroid signs and symptoms or the occurrence of hypothyroidism
demand further care.
Expected Outcomes – Some Patients Need a Second 131-I
Therapy, Others Will Need Synthroid Replacement
Hyperthyroid patients might need a second 131-I therapy. A minimum 6 month wait is
advised. Most practitioners would wait at least 12 months post initial therapy. Many
practitioners will also use a purposely high dose in order to increase the likelihood of
ending the patients hyperthyroid state, regardless of the principle of ALARA.
All patients and/or their close friends and associates know when the patient remains
hyperthyroid.
Hypothyroidism post 131-I therapy is not necessarily a complication per se, as this
may be the end result of untreated hyperthyroidism anyway (as the thyroid gland may
eventually “burn itself out”). Of the 131-I treated patients who become euthyroid at 1
year, several percent per year will become hypothyroid. Thus, all patients treated with
131-I will need to have at least yearly checks of thyroid hormone levels.
Many patients DO NOT KNOW when they become and remain hypothyroid. Thus,
patient-physician interaction MUST be maintained – through the days, weeks,
months, and years following 131-I therapy.
Lifelong follow up and laboratory testing is required
Case 3
11.4 MBq or
309 uCi 123-I
LAO
This is a 35 year old man with a 3 month
history of emesis, diarrhea, palpitations,
tremors with a TSH level of .004. The
patient’s symptoms normalized upon taking
propylthiouracil (PTU), propanolol, and
hydrochlorothiazide, when compliant.
10-30%
However pt was non
compliant for 3 months.
So, in this case 131 – I
might be the best tx
option. (Although pt
may require Synthroid
replacement at a later
time.)
Case 3
This is a 35 year old man with a 3 month history of emesis, diarrhea,
palpitations, tremors with a TSH level of .004. The patient’s symptoms
normalized upon taking propylthiouracil (PTU), propanolol, and
hydrochlorothiazide, when compliant - which he has not been for 3 months.
Optimal 131-I oral dose, by method used:
Method 1: 5.55 MBq/gm or 150 µCi/gm * 30 gm thyroid gland (mildly
enlarged) = 166.5 MBq or 4500 µCi = 4.5 mCi 131-I
then divide by 24 hour % uptake, so 4.5 mCi / 0.74 = 225 MBq or 6
mCi 131 – I
Method 2: 259 MBq or 7 mCi 131-I (all patients)
Method 3: (for 296 MBq or 8mCi delivered dose: 296 MBq / 0/74 = 400 MBq
or 8 mCi / 0.74 (the 24 hour uptake) = 10.8 mCi 131 –I)
However, per Part 6, slide 9, this patient merits a dose escalation to
407 MBq or11 mCi delivered dose due to: prior use of ATDs and 24 hour
uptake > 70%
for 407 MBq or11 mCi delivered dose to the thyroid gland: 407 MBq
/ 0.74 = 550 MBq or 11 mCi / 0.74 = 14.9 mCi 131-I
Case 3
This is a 35 year old man with a 3 month history of emesis, diarrhea,
palpitations, tremors with a TSH level of .004. The patient’s symptoms
normalized upon taking propylthiouracil (PTU), propanolol, and
hydrochlorothiazide, when compliant - which he has not been for 3 months.
Optimal 131-I oral dose, by method used:
Method 4: Without additional calculations, in part based on residence time of
131-I in the thyroid gland (not done here), estimated dose would be (all pts)
~555 MBq or ~15 mCi 131-I
Thus, in the 4 methods we have a wide range of recommended dose:
225-555 MBq or 6-15 mCi 131-I
Due to compliance issues and the fear that the patient might not follow up
properly post 131-I therapy, a lower dose of 222 MBq or 6 mCi 131-I was
suggested. This would make post tx hypothyroidism less likely, although
percent treatment success at 1 year would also be reduced. The patient can
put back on PTU and  blocker 1 week after 131-I oral therapy.
Expectation of Resultant Eu- vs Hypo-thyroidism
In an editorial, Ross McDougall at Stanford seems to provide a concise
summary:
“The optimal outcome after 131I therapy for hyperthyroidism is obviously euthyroidism
without postablative hypothyroidism and the need for lifelong thyroid hormone
replacement. It is now well accepted, however, that there is no single radioiodine dose or
treatment method that can reliably accomplish that goal. This is not surprising considering
the number of variables affecting the outcome, including characteristics of the patient (i.e.
age, gender, and gland size); severity and duration of the underlying autoimmune thyroid
stimulus; radiation delivered to the gland (i.e. 131I fractional uptake, homogeneity of
distribution, and effective half-life); and preceding antithyroid drug therapy (i.e. whether
thionamides were used, which one, and the time that the drug was stopped before
radioiodine treatment) (7, 8, 9). Nonetheless, two facts are apparent. First, the higher the
prescribed dose, the higher the fractions of patients who are cured and who develop
postablative hypothyroidism (10, 11, 12). Second, some patients become hypothyroid
after treatment with even small doses of 131I.”
He also notes that the lowest effective 131-I dose to rid hyperthyroidism
should be our goal, even if hypothyroidism would be a common outcome.
This can be achieved via both fixed and calculated dose regimens.
Judith E. Kalinyak and I. Ross McDougall. EDITORIAL: How Should the Dose of Iodine-131
Be Determined in the Treatment of Graves’ Hyperthyroidism? The Journal of Clinical
Endocrinology & Metabolism 2003, 88:3, 975-977.
Practice Patterns: Some UK Guidelines
Weetman reviews the treatment practices for hyperthyroidism in the UK.
While these are only guidelines, as you can see the range of 131-I used
varies.
Anthony P. Weetman CLINICAL PRACTICE UPDATE Radioiodine treatment for benign
thyroid diseases Clinical Endocrinology 2007, 66:6, 757-764. Table from p. 758.
NB:
370 MBq = 10mCi,
555 MBq = 15 mCi,
800 MBq = 30 mCi, the maximum
outpatient dose allowable in many
states in the USA.
These guidelines are meant to help
provide more uniform treatment of
patients, based on published data,
while keeping overall costs low.
Practice Patterns: Some Finnish Guidelines –
Low Dose (vs Medium Dose) Therapy With 131-I
In this Finnish study, which looked at 2043 patients from 1965-2002, with a
median follow up of 9.8 years, a fixed dose of about 259 MBq or 7 mCi was
used in most patients. Patient population included toxic nodular goitre. One
infers that the quoted 80% “cure” rate is at 1 year post 259 MBq or 7 mCi
131-I therapy.
Saara Metso , Pia Jaatinen, Heini Huhtala, Tiina Luukkaala, Heikki Oksala and Jorma
Salmi Long-term follow-up study of radioiodine treatment of hyperthyroidism.
Clinical Endocrinology 61:5, 641 - 648, 2004.
It should be noted, that in some other studies the low dose amounts used
often had similar or even better results than higher dose techniques. (Inferred
from Leslie, McDougall, and others.)
WILLIAM D. LESLIE, LINDA WARD, ELIZABETH A. SALAMON,
SORA LUDWIG, RICHARD C. ROWE, AND ELIZABETH A.
COWDEN. A Randomized Comparison of Radioiodine Doses in
Graves’ Hyperthyroidism. The Journal of Clinical Endocrinology &
Metabolism 88(3):978–983, 2003.
Practice Patterns: Some Finnish Guidelines –
Low Dose (vs Medium Dose) Therapy With 131-I
In this author’s experience of almost 20 years in practice, I would estimate
my average patient dose to be approximately 555 MBq or 15 mCi. This is in
line with dosages of 131-I used in my community. I do not have the long term
results data reported from Finland, nor do I expect to, given changes in
practice location.
Unpublished verbal communications to the primary author here, have
indicated a low dose therapy response rate of only about 67% (in patients
without goiter). This is less than the expected ~80% cure rate from the
Finnish study.
Perspective:
EURATOM 97/43, a European Union Directive, published in 1997, states the
importance of individualization of therapy in order to reduce dose exposures
and increase specified targeting benefits of radiation therapy including the
use of nuclear sources.
Case 4
This is an 83 year old female with a history of
thyrotoxicosis with hypercalcemia and impaired
fasting glucose. The patient is to continue on 10
mg of methimazole every day. The patient has a
diagnosed parathyroid adenoma.
10-30%
So in this case, medical
therapy worked well.
131-I therapy can follow
at a later date, should
this patient subsequently
fail medical therapy.
Case 4
This is an 83 year old female with a history of thyrotoxicosis with hypercalcemia and
impaired fasting glucose. The patient is to continue on 10 mg of methimazole every
day, as she is doing well on this regimen. The patient also has a diagnosed
parathyroid adenoma – but this does not effect our hyperthyroid treatment, unless she
needs surgery for treating the adenoma. If she subsequently fails medical therapy for
Graves Disease, here are the calculations for optimal 131-I oral dose, by method
used. Results vary widely:
Method 1: 5.55 MBq/gm or 150 µCi/gm * 20 gm thyroid gland (not enlarged) = 111
MBq or 3000 µCi = 3 mCi 131-I
then divide by 24 hour % uptake, so 11.1 MBq / 0.389 = 285 MBq or 3 mCi /
0.389 = 7.7 mCi 131 – I
(***Remember – this is the only method which varies by thyroid gland size,
so if her gland was enlarged at 40 gm, a 570 MBq or 15.4 mCi 131-I tx would be
recommended.)
Method 2: 259 MBq or 7 mCi 131-I (all patients)
Case 4
This is an 83 year old female with a history of thyrotoxicosis with hypercalcemia and
impaired fasting glucose. The patient is to continue on 10 mg of methimazole every
day, as she is doing well on this regimen. The patient also has a diagnosed
parathyroid adenoma – but this does not effect our hyperthyroid treatment, unless she
needs surgery for treating the adenoma. If she subsequently fails medical therapy for
Graves Disease, here are the calculations for optimal 131-I oral dose, by method
used. Results vary widely:
Method 3: (for 296 MBq or 8mCi delivered dose: 8 mCi / 0.389 (the 24 hour uptake) =
761 MBq or 20.6 mCi 131 –I)
However, per Part 6, slide 9, this patient merits a dose escalation to 407 MBq or
11 mCi delivered dose to the thyroid gland due to: prior use of ATDs
11 mCi delivered dose: 407 / 0.389 = 1047 MBq or 11 mCi / 0.389 = 28.3 mCi
131-I
Method 4: Without additional calculations, in part based on residence time of 131-I in
the thyroid gland (not done here), estimated dose would be (all pts) ~ 555 MBq or
~15 mCi 131-I
Thus, in the 4 methods we have a wide range of recommended dose:
259-1047 MBq or 7-28.3 mCi 131-I
Relative Cost of Therapeutic Options
In a recent review of hyperthyroid therapy looked at the cost of various
methods used to treat hyperthyroid patients.
Lucignani G Long Term Risks In Hyperthyroid Patients Treated With Radioiodine: Is
There Anything New? Eur J Nucl Med Mol Imaging (2007) 1504-1509
$9,826.00: Surgical thyroidectomy
$5,644.00: Medical (thionamides: Propylthiouracil (PTU) and methimazole
(Tapazole®, MMI) are the thionamide drugs available in the United States ):
$2,063.00: 131-I - by far, the lowest cost
Perspective:
With most radioiodine therapeutic methodologies used, a “cure” rate of over
2/3 would be expected. This is far greater than medical therapy, though lower
than surgery.
How does this compare to treating common diseases?
Do we expect at least 2/3 of hypertensive patients to be well maintained on
medication?
Relatively High Success Rate for 131-I Therapy
When Compared to Treatment for a Common
Disease - Hypertension
Context of patient therapy:
As you can see, compared to treating hypertension (only 34% are
controlled), we do a great job treating hyperthyroidism with 131-I.
But remember, all patients, including those made hypothyroid need lifelong
care and follow up.
U.S. DEPARTMENT OF HEALTH AND HUMAN
SERVICES
National Institutes of Health
National Heart, Lung, and Blood Institute
National High Blood Pressure Education Program
The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure - Complete
Report
JNC 7 Complete Report: The Science Behind the
New Guidelines
NIH Publication No. 04-5230
August 2004
http://www.nhlbi.nih.gov/guidelines/hypertension/jnc
7full.pdf
Pre 131-I Therapy Planning
As with all nuclear medicine therapy procedures we need to make sure that:
-Proper informed consent must be obtained from the patient or legal guardian. This requires
knowledge of the relative strengths and weaknesses of other therapeutic modalities. Also review
the possibility of hypothyroidism as a therapy result and the possibility of therapy failure.
In those patients under age 18, parental consent is also required.
-All female patients must be checked for possible pregnancy. If planning to have children,
waiting 6 -12 months post 131-I therapy before attempting conception is encouraged.
-Breast feeding is not allowed for a minimum of 3 months (approx 10 half lives of 131-I). Most
would insist that breast feeding be halted permanently for that child.
-For Graves Disease, doses used usually do not require hospitalization in the US. However, as
regulations vary around the world, local practitioners might need to either adjust maximal dose
usable in the outpatient setting or admit the patient until their total body burden of 131-I falls
below certain levels (mR/hr).
-ATDs need to be stopped prior to 131-I therapy? Well, not all agree. A 2008 article from the
Netherlands look at practices in Holland and suggested that:
G.S. Mijnhout*, A.A.M. Franken
ATDs be withdrawn at least 4 days before use of 131-I
Antithyroid drug regimens before
PTU use should be stopped at least 15 days before 131-I
and after 131I-therapy for
hyperthyroidism: evidence-Resumption of ATD use post therapy should be limited to
based? The Netherlands Jnl of
high risk groups including those > 70 years old and those
Med 2008; 66:6:238-241.
with significant cardiac issues.
Pre 131-I Therapy Planning - 2
Performing the therapy:
-Before even ordering the dose, please make sure that the patient will be able to
participate in taking the 131-I. Is the patient continent for urine? Patient must also be
in a suitable home and work setting. This can be an issue; for example where young
children are at home or work; use of public transport; when the patient provides care
for total care need elderly relatives. After dosing the patient needs to comply with
certain guidelines (see below).
-Use of a low iodine diet prior to and following therapy is encouraged.
-Use of radiologic (X-ray, CT) iodinated contrast must be avoided for a minimum of 4
weeks before 131-I therapy. The author prefers an 8 week or 2 month wait, in part
due to the long circulating t ½ of thyroid hormone. MRI gadolinium based contrast is
not an issue.
-Effects of lithium are controversial.
-Most countries have specific isotope training requirements beyond general medical
training before one can be the “authorized user” of 131-I for therapeutic purpose. In
the US, only an authorized user can be responsible for giving or dosing the 131-I for
treatment purpose. Nuclear medicine physicians and many-most radiologists will
qualify. However, many endocrinologists will not qualify without additional training.
Pre 131-I Therapy Planning - 3
Performing the therapy, cont:
-Assure that the 131-I dose is received intact. The nuclear medicine
technologist usually does this.
-Assay it in the hot lab to confirm the dose. It must be +/- 10% of the
prescribed dose in the US. Although the technologist must do this, in the US,
the physician is ultimately responsible for this too, so good form dictates that
physicians are present during the assay in the well counter. In some places,
both techs and doctors are required to sign off on this. Records of this must
be maintained.
-131-I comes in both liquid and solid (capsule) forms. As a liquid it is highly
volatile. Therefore, all medical personnel involved in the therapy need to
have their thyroid glands assayed for 131-I, both before and 1-2 days post
therapy. This additional personnel assay is not needed when capsules are
used in the US. Thus, most prefer using capsules. In the US, these
regulations are part of 10 CFR 20, but require your radiation safety officer
(RSO, often a physicist) to decipher.
Records must also be kept of these measurements.
Potential Complications of 131-I Therapy
Early complications may include:
- Day of therapy:
a - nausea and vomiting. Not common, but if the patient vomits the dose in the
hospital or clinic it must be properly cleaned up. There will also be all of the
necessary record keeping for radioactive spills.
Remember, making certain that the patient is stable comes first.
If this occurs at home, most of the 131-I should have passed beyond the stomach by
this time.
b – anxiety. Not common as a major problem; though most patients have some
anxiety about “nuclear” agents. This can be addressed per symptoms. Physician
reassurance is helpful.
- In the days to weeks following therapy:
Sialadenitis – inflammation of the salivary glands, possibly including damage to or
destruction of the salivary glands is along known potential complication of 131-I
therapy. Temporary or permanent “dry mouth” may result. This is prevented by having
the patient suck on sour candies that promote salivary flow. There is a recent paper
on this subject. Edward B. Silberstein. Reducing the Incidence of 131I-Induced Sialadenitis: The Role of
Pilocarpine THE JOURNAL OF NUCLEAR MEDICINE, April 2008, 49:4, 546-9.
131 – I Dose Used
So, how much 131-I should we use to treat Graves Hyperthyroidism?
This, in part, is the art of medicine. Based on the data presented here the
following may be useful:
--Patients with mild-moderate signs and symptoms and mildly enlarged
thyroid glands: 259-555 MBq or 7-15 mCi. These patients might need
retreatment, but the lack of a rapid end to their hyperthyroidism should not
cause them significant harm. Retreatment might be needed.
--Patients with some significant signs and symptoms and/or those with large
thyroid glands: 555-740 MBq or 15-20 mCi. Yes, a larger dose and there is a
greater likelihood of post 131-I treatment hypothyroidism. However, the
likelihood of ending hyperthyroidism is greater.
--Patients with severe signs and symptoms and/or those with very large
glands: 740-1210 MBq or 20-30 mCi of 131-I. The higher dose, although it
does not follow the concept of ALARA, should allow for the highest certainty
of ending hyperthyroidism and thus alleviating signs and symptoms caused
by it. Time to eradicate the hyperthyroid condition might be the same as in
lower doses; often requiring several months following treatment. However,
post therapy hypothyroidism is very likely.
Part 7: Links to More Detailed Procedural, Informed
Consent, and Regulatory Information
- Regulations Regulations vary between states in the US (Agreement vs non-Agreement states)
and between countries. Many states in the US allow a maximal outpatient dose of 3033 mCi. LA is an agreement state. In the US, per The Code of Federal Regulations,
10CFR35, Ҥ 35.75 Release of individuals containing unsealed byproduct material or
implants containing byproduct material. (a) A licensee may authorize the release from
its control of any individual who has been administered unsealed byproduct material
or implants containing byproduct material if the total effective dose equivalent to any
other individual from exposure to the released individual is not likely to exceed 5 mSv
(0.5 rem).1” http://www.nrc.gov/reading-rm/doc-collections/cfr/part035/full-text.html
http://www.nrc.gov/reading-rm/doc-collections/cfr/part035/part035-0075.html
In practice, for 131-I, the maximum outpatient dose would be 1.2 GBq or 33 mCi, 0.07
mSv/hr or http://www.scdhec.gov/health/radhlth/ReleasePatients.pdf,
7 mrem/hr
REGULATORY GUIDE Bureau of Radiological Health Division of Radioactive Material
Licensing and Compliance February 2006 “Release of Patients Administered Radioactive
Materials”, pp 8-9, Table 1. Activities and Dose Rates for Authorized Patient Release Ψ
Don’t forget, there are record keeping requirements for use of radio isotopes in the
US. Elsewhere in the world, regulations will vary, but may be even more strict.
Practitioners will need to know the regulations in place at their location.
Follow-up Management and Conclusion
Hypothyroid patients are placed on Synthroid ® replacement therapy.
Taken orally 3-7 times per week, this provides for maintenance of
euthyroid thyroid hormone levels. Children, pregnant women, athletes, and
average adults can be easily and successfully treated.
But again, lifelong follow up and laboratory testing is required.
General Radiologists and Nuclear Medicine Physicians can be valuable
members of a team treating and caring for patients with hyperthyroidism.
This concludes this presentation. Thank you for your attention.
I hope you will enjoy being involved in the care of hyperthyroid patients as
much as I am.
FIN