Transcript Radioiodine Therapy for Graves disease

Radioactive iodine (RAI)
Therapy of Graves’Disease(GD)
: Practical Points of View
Jaetae Lee
Kyungpook National University Hospital,
Daegu, Korea
RadioIodine Therapy for Hyperthyroidism
• 1942, first RI therapy by Hertz & Roberts of
MGH using I-130 (Tp = 12.4 h)
• 1946, I-131 (Tp = 8.1 h) from Oak Ridge Natl. Lab.
I-131
γ ray
364 keV
eβ ray
2 mm
I-127
Proton
Neutron
β particle
How to treat patients with GD,
when first diagnosed.
• Influenced by
- Geographical location (social environment)
- Size of the goiter
- Age of the patients
- Personal experiences of treating physicians
- Patients’ preference
(a 43-year old woman)
moderate signs of hyperthyroidism of 2- to 3-mo
two children, ages 5 and 10 yr
diffuse goiter of 40-50 g
pulse rate of 106 beats/min and regular
Therapeutic choices (Thyroid, JKSE 1992)
I-131 Tx
ATD
Surgery
Korea
11%
81%
8%
USA Japan
69% 11%
30% 88%
1%
1%
EU
22%
77%
1%
* Over 95% physicians preferred ATD in Korea, 2011
Indications of RAI Tx for Hyperthyroidism
(ATA guideline 2011)
Determination of I-131 Dosage
• Small fixed doses repeated as necessary
• Large ablative dose
• “Sliding scale” based on thyroid size
• Approximation dosimetry
• Precise dosimetry for the administered dose
Basic Parameters to Determine
Radiation Dose to the Thyroid
• RAIU at 24-hr (checked within several days)
• Effective half life of I-131 in Thyroid (Teff)
(Graves ds : mean Tb : 20 d, Teff : 5.4-6.4 d)
• Goiter size
• Radiosensitivity of Thyroid Tissue: microdosimetry
• Renal function
Method of Administration (I)
• Fixed Dose :
- 3-5 mCi I-131 q 3-6 mo.
- Decreased incidence of hypothyroidism,
inconvenient
• Single, Higher Dose : less than 30 mCi
- Rapid control of symptoms, higher incidence of
hypothyroidism
• Based on Size of the Thyroid and Symptomatology
- small goiter, mild Sx: 5 mCi
- moderate goiter and Sx: 10 mCi
- huge goiter and severe Sx: 15-30 mCi
Method of Administration (II)
• Based on Dosimetry
– 50 –200 Gy (5000-20000 rad) to thyroid
* 3.7 MBq/g (100 mCi/g) = 83 Gy (8300 rad)
* ablative dose: > 250 Gy
– Increase for large goiter
* Normal size: 40 mCi/g
* over 80gm : 80-120 mCi/g
* 160-200 mCi/g to increase success rate
( pts with severe toxic Sx, re-treatment, cardiovascular Cx)
– Increase for pts with ATD Tx, inorganic iodide
Calculation of administered Dose
Based on Absorbed Dose
gland weight (g) x 150 uCi/g
Activity (uCi) =
24 hour uptake on % of dose
* Gland wt. estimated by USG, palpation, scan, CT
* To achieve a hypothyroid state, needs >150 uCi/g
Selection of Dose of I-131 in Practice
- Sufficient radiation in a single does to render
GD hypothyroid. 1/+00 for ATA guideline
- 370–555 MBq (10–15 mCi)
• Calculated administered dose :
- 5.55–7.4 MBq/gm (150–200 μCi) not to re-treat
Hypothyroidism after I-131 Tx
Dose & Time dependent
%
mCi/gm
80
70
Euthyroid
Hypothyroid
60
50
40
30
20
10
Hyperthyroid
0
1 2 3 4 5 6 7 8 9 10 11
(Becker et al, 1971)
Years
Treatment of Graves’ with RAI
• Aim of The Treatment
– Eliminate hyperthyroidism at the cost of
high rate of hypothyroidism?
– Euthyroidism without L-thyroxine
substitution?
• Treatment Failure
– Persistent hyperthyroidism?
– Post-therapy hypothyroidism?
Tx. Results of I-131 for GD
1yr
Cure rate
(Hypothyroidism)
10 mCi
69%
(1-yr)
15 mCi
75%
(6 mo)
Most of Data showed a dose related outcome
1. fixed (15mCi) & 100 Gy dose: similar results
2. 60 Gy versus 90 Gy
- 6 Mo: 59%, 61% hyperthyroid
- 38 Mo: 46% euthy, 47% hypo, 7% hyper
3. 250-300 Gy: 3 Mo 86%, 1 yr 100% success
- Hypo: 63% at 3 Mo, 93% at 18 mo, 100% at 2yr
4-18
6-29
Transient increase in
TBII followed by a
decrease in patients
treated with 131I.
Graves’ disease following RI Tx
for Toxic Nodular Goiter
* German multi-center study (n:2867)
–0.3%: TSHR-Ab(+) & developed hyperthyroidsim
– due to autoAg release by RAI Tx
Female wants to have pregnancy
- Fetal & neonatal Graves’ hyperthyroidism : 2%
(positively associated with a higher TRAb & the
efficacy of transplacental transfer)
- Increased risks of fetal or neonatal
hyperthyroidism developing during pregnancy.
which normalized to baseline at 1 yr.
Causes of Failure of RAI Therapy
– A fixed dose was too small for the size of the gland
– Less able to trap iodine than expected
– The size was underestimated when a dose per gram
corrected for uptake was administered
– A rapid turnover of iodine must be considered and
can be adjusted for by measuring 24-h uptake rather
than uptake at 4–6 h
– ‘‘spat up’’ the capsule, & a high level of serum iodine
Possible Factors Influencing Hypothyroidism
• Administered I-131 Dosage
• Age
• Gender
• Size of thyroid gland
• Initial FT4/TfT3
• Initial TSH
• Pretreatment with antithyroid drugs
• RAIU
• Duration of disease
Preparation of pts with GD for I-131 Tx
• Beta-adrenergic blocker (1/+00), methimazole
Pre-Tx (2/+00) prior to RAI
- pts with increased risk for Cx due to worsening of
hyperthyroidism
(extremely symptomatic, fT4>2-3 times of baseline)
- MMI Tx before/after RAI Tx
• Medical Tx of any co-mobidity 1/+00
- cardiovascular (AF, heart failure), infection, trauma,
pulmonary hypertension, poorly controlled DM,
CVA, pulmonary ds.
Thionamides (MMI)
• Symptomatic relieve and decrease
aggravation of hyperthyroidism after I-131 Tx
– Insufficient data
• Reduce the efficacy of RAI (radio-resistance)
• In practice
– Discontinue 3-5 d before RAI
– Restarted 3-7 d later & taper 4-6 wks
Course after RAI Tx
• Decrease of serum T4, Clinical improve:
start from 2-4 wk & max. at 2 mo
• Regressing goiter at 6-8 wk
• Hypothyroidism : 2- 6 mo (from 4 wk)
• Improved at 10-12 (6-18 wks) in most pts.
• Cure : 75% with single Tx, two Tx for 10-20%
Follow-up after RAI Tx
• During first 3 mo:
– fT4, T3, (TSH) at 1-2 mo
(ATD Tx before RI Tx  can be resumed at 3-7 days after RI)
– TSH levels may remain suppressed for a mo or longer
– Biochemical monitoring at 4-6 wk, if remain thyrotoxic
• Remain hyper at 6 mo, minimal response at 3 mo :
rec. re-RAI Tx : 2/+00
• Euthyroid at 2-3 mo, then F/U at 1-yr
• Borderline hyperthyroidism at 3-6 mo
– Lugol, SSKI or low dose ATD for 6-12 mo
Physiologic uptakes of
131I
Thyroid
Salivary gland
Stomach
GIT
Urinary tract
* Breast
Side Effects (I)
• Early Side Effects
– Exacerbation of Hyperthyroidism (radiation thyroiditis)
– new or worsening ophthalmopathy(GO)
• Carcinogenesis
– leukemia, neoplasm ?
( stomach, kidney, breast : Metso et al cancer 2007)
– Thyroid cancer: rather low incidence (!!)
Side Effects (II)
• Pregnancy and infertility
- delay pregnancy to ensure euthyroid state
1. at least 6 mo. for women
2. 3-4 mo for men (sperm turnover)
– Ovarian dose: 1-3 rad with 10 mCi
(similar to Ba study, IVP)
• Delay RAI for at least 6 wks after lactation
stop
Radiation Thyroiditis
• Incidence : 0.4-3%
• Due to follicular destruction and subsequent
release of thyroid hormone into circulation
• peak between 10 –14 days after dosing
• can rarely be “thyroid storm”
• Tx with thiourea in pts with old age,
pre-existing heart ds, fever, severe systemic
illness, debility
Controversies in I-131 Therapy
1. Dose Calculation: 250 Gy? --- ATA guideline
2. Anti-thyroid drugs in relation to I-131 therapy
3. I-131 therapy and the course of Graves’
opthalmopathy
4. I-131 therapy in Children Adolescence
I-131 Therapy and Ophthalmopathy
Meta-analysis
• Non-randomized Studies:
– Aggravation of GO : 3%-53%
– Associated with Post I-131 hypothyroidism
• Randomized, Prospective Studies
– Aggravation of GO : 15-37%
– Inhibited with co-Tx of glucocorticoid
(0.5mg/kg for 1mo. and tapering over 3 mo.)
• Long-term improve due to deprivation of thyroid
Ag, activated T-Lc ?
Factors related to Aggravation of GO
after RAI-Tx
• Mod/severe Pre-existing GO : corticosteroid
• Smoker: corticosteroid
• Severity of pre-RI hyperthyroidism
• High TSH, high TSHR Ab (?)
• Late correction of post-radioiodine
hypothyroidism with T4
(Also for inactive GO)
How Long Should ATD Be
Stopped Before RAI Tx?
Relation of RAI target dose c 1-yr outcome in GD
The vertical line : target dose with the highest probability to achieve
euthyroidism 1 yr after RAI Tx
Walter et al. Eur J Clin Invest 2009; 39 (1): 51–57
Dunkelmann et al.
ATD Tx before RAI Tx
- Propylthiouracil increases the resistance of
the thyroid to radiation; while, methimazole
and carbimazole do not.
- The outcome achieved after RAI Tx is equal
to or better than that achieved than no ATD
- Propylthiouracil is discontinued for 3 d;
methimazole for 5 d
RAI TX in Children/Adolescents with GD
• Children with GD can be treated with RAI Tx, & others
- RAI therapy should be avoided in children <5 years.
- RAI Tx in pts between 5 & 10 yrs is acceptable
if the calculated I-131 activity is <10 mCi.
- RAI Tx in pts older than 10 years is acceptable
if the activity is >150 uCi/g of thyroid tissue.
(hypothyroidism rates : about 95%)
* Increase in cancer risk??
Conclusion
RAI Tx of Graves’ Disease
• Efficient & Safe Method for over 60 yrs
• Eliminate hyperthyroidism at the cost of a
high rate of hypothyroidism : “Trade-Off”