Education Resource from the Society for Endocrinology

Radioiodine therapy in thyrotoxicosis: how much to give and how to give it

M Keir

Royal Victoria Infirmary, Newcastle upon Tyne

Summer School 5-8 July 2005
St Aidan’s College, Durham University, Durham, UK


1. Radioiodine - What is it ?

I-131 emits two types of radiation :

b particles :

. average energy ~ 190 keV (89 % of emissions)

. mean particle range ~ 0.8 mm

g rays

. 365 keV g rays (80% of emissions) - very penetrating. It takes about 2.5 cm of Pb to gain a 1000 fold reduction in intensity

Physical half life is 8 days, but with biological excretion the effective half life is less than this by about 2 to 3 days.

 

b particles give rise to a radiation dose to thyroid, while the g rays irradiate the rest of the body and other persons in the vicinity. It is the b particles which result in cell death within the thyroid.

Target doses to achieve this range typically from about 100 Gray for Graves disease up to 400 Gray for an autonomous toxic nodule.

The overall effect of radioiodine administration is decreased thyroid function and reduce thyroid bulk.

Due to its radioactive nature, I-131 is subject to regulatory control :

2. How much to give ?

The activity administered to the patient determines the radiation dose to the thyroid. The required dose depends on the treatment strategy, whether to aim for enough reduction in function to render the patient just euthyroid, or whether to use a dose which rapidly results in a hypothyroid state. There is no clear consensus on this issue. The three main approaches to determining the activity administered are :

. Calculated activity

. Becquerel / gram

. Fixed activity

 

i. Calculated activity

The radiation dose to the thyroid will depend on the following factors :

a. the volume of the thyroid

b. the uptake of the I-131 by the thyroid – varies with the disease process, typically around 60% for Graves disease, 40% for toxic multinodular goitre and 20 % for autonomous toxic nodules.

c. effective half life of the I-131, which will vary from about 5 - 7 days

 

Strategy :

measure the uptake of tracer dose of iodine, assume or measure the effective half life over the next week or so, and assess thyroid volume, using ultrasound or palpation.

Use equation -

Activity administered = a constant x target dose (Gray) x thyroid volume (ml) /(max uptake (%) x effective half life (days))

 

ii. Becquerel / gram

Administration generally given as ‘low dose’ ~ 3 MBq/gram thyroid tissue up to ‘high dose’ ~ 4.5 MBq/gram thyroid tissue, with thyroid mass being estimated by palpation or measurement.

 

iii. Fixed activity administered for all patients.

How much ? - RCP Guidelines (1995)  say :

. ‘Standard’ dose (usually for Graves) : 400 MBq

. TMNG : at least 550 MBq

. Toxic adenoma : 300 - 500 MBq

. Guide activity for ablation : 800 MBq

This approach is expected to ‘render the patient rapidly euthyroid . . . [and] limit the incidence of hypothyroidism’ (RCP guidelines)

 

Comparison between the approaches :

A ‘tailored’ activity should provide the least radiation dose to the patient for the required therapeutic effect. However that is often at the expense of a longer time in the hyperthyroid state and multiple treatments.

A fixed activity is usually chosen to render most patients euthyroid in a very short time. This tends to be the more convenient approach for most patient as it removes the need for uptake or volume measurements and provides a potentially more predictable outcome. It will generally result in higher rates of hypothyroidism, although there is good evidence of an increasing incidence of hypothyroidism with time for all patients receiving I-131, irrespective of the strategy used.

RCP says – ‘There is no evidence that precision dosimetry leads to an improved clinical outcome.

 

3. Problems for Patients

Iodine is excreted by patients in both urine and sweat. I-131 also emits energetic g rays. These two factors mean that patients need to modify their behaviour to ensure that people around them do not receive radiation doses above the statutory maximum (IRR 99).

Behaviour modifications for patients - sources of guidance :

. Radiation Protection 97 (EC, 1998)

. Medical and Dental Guidance notes (IPEM 2002)

 

Aim of behaviour modifications :

Keep radiation dose to the public < 0.3 mSv

 

Potential hazards from patients with radioiodine :

Excretion :

urine will contain 30 - 90 % of administered activity over next 2 days

On day 0 may be 100- 200 kBq / ml ie an ingestion of 20 ml will give rise to 0.3 mSv

Sweat : first 24 hours will give rise to about 150 Bq cm-2 of skin, hence would need to ingest the sweat from about 200 cm2 for 0.3 mSv dose

Saliva : first 24 hours ~ 30kBq/gm, so ingestion of about 1 gm of saliva for 0.3 mSv dose detriment

Main requirement is for good toilet hygiene

 

External irradiation :

Typical dose rate (for 400 MBq) on 1st day –

500 mSv hr-1 at 10 cm

80 mSv hr-1 at 0.5 m

25 mSv hr-1 at 100 cm

Regular contacts - limit time spent within arms reach, no bed sharing

One off contacts - no restriction

 

Other potential problems with this sort of treatment :

. Regulatory issues :

. Radioactive Substances Act will be relevant for IP treatments – care in disposal of urine and solid waste

. Ionising Radiations Regulations will be relevant if discharged to a care home or with home help

. need to avoid pregnancy before and following therapy

. contact with small children in the family can be a major stumbling block

. pets are not an issue – outside of regulatory control

. cramped working conditions may be relevant

. foreign travel can cause problems due to radiation detectors

 

One factor which may ease situation :

‘Comforters and Carers’, who are knowingly and willingly exposed, can receive radiation doses above the national limits. These are generally subject to a 5 mSv dose constraint and require documenting and prior consent – this requires involvement of the MPE or RPA

 

4. Therapy Outcome

Many published studies on the outcome of Radioiodine therapy, and many factors affect outcome and make comparison difficult, e.g. :

. range of disease types represented, sometimes mixed

. natural iodine intake varies and not often known

. use of ATD not always documented

. variable activity administered, sometimes in a subjective way

 

The Newcastle experience

Patients categorised as GD or TMNG and treated with fixed activity, 400 MBq

GD – 218 patients, 133 at first presentation

TMNG – 77 patients, 67 at first presentation

Included results from second centre using a variable activity, 200 – 600 MBq

GD – 137 patients, 123 at first presentation.

 

Results for Graves disease patients on first treatment  (all figures in %) :

Outcome

6 – 8 weeks

3 months

6 months

9 months

12 months

Hypo

25

70

85

88

90

Eu

65

29

14

11

10

Hyper

10

1

1

1

0

 

results for TMNG patients, first treatment with 400 MBq

Outcome 6 – 8 weeks 3 months 6 months 9 months 12 months
Hypo 7 18 25 30 30
Eu 88 78 72 67 67
Hyper 5 4 3 3 3

 

results for Graves disease, graded dose, first treatment 200 – 600 MBq

Outcome

6 – 8 weeks

3 months

6 months

9 months

12 months

Hypo

8

39

52

54

59

Eu

70

50

36

33

27

Hyper

22

11

12

13

14

 

5. Conclusions

Radioiodine therapy is an effective treatment option

BUT,

need to decide on the most appropriate treatment strategy

consideration of patient compliance with behaviour restrictions required

 


Revised: 30-Oct-2006

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