Hyperthyroidism: Diagnosis, Management and
Long-term Consequences
Kristien Boelaert
Senior Lecturer in Endocrinology
Consultant Endocrinologist
Queen Elizabeth Hospital Birmingham, UK
Centre for Endocrinology, Diabetes & Metabolism
University of Birmingham, UK
Overview

Diagnosis of hyperthyroidism/thyrotoxicosis

Influence of endogenous/environmental factors on
phenotype
Symptoms and signs of hyperthyroidism according to age

Co-existing autoimmune diseases



Management: Treatment with 131I – The Birmingham
experience
Long-term consequences:

Association with mortality

Weight changes following Rx
Family history


Family history: 47.7% females – 40.0% males
Inverse relationship between age at diagnosis –
number of relatives with thyroid dysfunction
Median age at diagnosis (y)
50
45
No FH
40
1 relative
35
2+ relatives
30
25
Females

Males
FH of hyperthyroidism more common than
hypothyroidism (p<0.001)
Manji, Boelaert et al. (2006) JCEM 91, 4873
Associated autoimmune diseases

2791 subjects with Graves’ disease
Boelaert et al. (2010) Am J Med 123, 183.e1
Median age at presentation (y)
Age at diagnosis of Graves’ Disease
60
50
*
***
**
***
***
*
40
30
20
10
0
N
T1DM
RA
PA
CD Vitiligo
IBD
None
31
88
39
25
25
2571
Boelaert et al. (2010) Am J Med 123, 183.e1
40
Number of reported symptoms
according to age
P < 0.001
Number of patients (%)
60
50
18-32 y
40
33-44y
30
45-60y
20
over 61 y
10
0
0-2 symptoms
Boelaert et al. (2010) JCEM 95, 2715
3-4 symptoms
5 or more symptoms
Outcome following

therapy
1278 patients treated with 131I for hyperthyroidism
Single fixed dose of 131I
Outcome according to dose regimen (%)

131I
90
80
**
***
***
70
**
***
60
***
50
40
370 MBq
600 MBq
30
20
10
0
185 MBq
Cure
Boelaert et al. (2009) Clin End 70, 129
Hypothyroidism
Factors predicting cure of hyperthyroidism
Boelaert et al. (2009) Clin End 70, 129
Hyperthyroidism and mortality Outstanding questions




Is mortality related to underlying aetiology - ? higher in
toxic nodular hyperthyroidism (Metso et al. (2007) JCEM 92, 2190)
Is outcome affected by treatment modality?
What is the influence of biochemical control of
hyperthyroidism on outcome?
How do pre-existing co-morbidities affect outcome?
Brandt et al. (2011) Eur J Endo 165, 491
SMR according to treatment modality
Cause of death
Overall
Whilst on
Thionamide Rx
Following 131I
Not hypothyroid
Following 131I
Hypothyroid
SMR
SMR
P
SMR
P
SMR
P
1.15
1.26
1.11
1.30
1.36
1.27
0.006
0.10
0.07
1.24
1.34
1.21
0.02
0.11
0.06
1.02
1.1
0.95
0.85
0.57
0.60
Comorbidity absent
Comorbidity present
0.95
1.52
1.03
1.68
0.84
<0.001
1.09
1.48
0.48
0.002
0.81
1.43
0.08
0.01
Sinus Rhythm
Atrial fibrillation
1.07
1.59
1.18
1.74
0.18
0.006
1.17
1.53
0.11
0.02
0.92
1.51
0.43
0.08
Circulatory deaths
1.20
1.37
0.05
1.19
0.22
1.12
0.45
All causes
Males
Females
Boelaert et al. (2012) JCEM resubmitted
Multivariate within cohort analysis
HR (95% CI)
P- Value
Gender
Male
Female
1.00
0.72 (0.55-0.93)
0.01
Cause of hyperthyroidism
Graves’ disease
TN hyperthyroidism
Indeterminate
1.00
0.92 (0.63-1.18)
0.86 (0.67-1.28)
0.36
0.64
Cardiac rhythm at presentation
Sinus rhythm
Atrial fibrillation
1.00
1.50 (1.08-2.08)
0.02
Co-morbidities
Absent
Present
1.00
1.58 (1.23-2.03)
<0.001
Serial fT4
per 10 pmol/l increment
1.21 (1.03-1.42)
0.02
Treatment
Whilst on antithyroid drugs
After 131I – not taking T4
After 131I – on T4
1.00
0.94 (0.69-1.27)
0.72 (0.54-0.97)
0.67
0.03
Boelaert et al. (2012) JCEM resubmitted
Control of hyperthyroidism
Serum ft4 concentration (pmol/l)
Thionamide only
Thionamide + 131-I
Thionamide + 131-I + T4
Years of follow-up
Boelaert et al. (2012) JCEM resubmitted
Comparison with background population
PRESENTATION
West Midlands population
Thyrotoxic patients
Proportion of males (%)
Proportion of females (%)
Thyrotoxic patients
60
50
40
30
20
10
Overweight
*
50
40
30
20
10
0
Normal BMI
West Midlands population
0
Normal BMI
Obese
Overweight
Obese
DISCHARGE
50
***
40
30
20
10
0
Thyrotoxic patients
West Midlands population
Proportion of males (%)
Proportion of females (%)
Thyrotoxic patients
Normal BMI Overweight
Obese
Boelaert et al. (2012) in preparation
West Midlands population
***
50
40
30
20
10
0
Normal BMI
Overweight
Obese
Weight change during FU
Boelaert et al. (2012) in preparation
Multi-level model to predict weight
Variable
Coefficient
95% CI
P-value
131I treatment
No
Yes
0
0.81
Levothyroxine RX
No
Yes
0
0.36
0.11 to 0.61
Serial fT4 (pmol/l)
10-22
22-30
> 30
0
-0.66
-2.01
-0.90 to -0.41
-2.30 to -1.71
<0.001
<0.001
Serial TSH
<0.1
0.1-0.3
0.3-4.5
4.5-10.0
>10.0
-1.21
-0.40
0
0.65
1.00
-1.42 to -0.99
-0.76 to –0.33
<0.001
0.03
0.39 to 0.91
0.71 to 1.28
<0.001
<0.001
Boelaert et al. (2012) in preparation
<0.001
0.57 to1.04
<0.001
Parameters associated with weight gain
Interaction with 131I
Interaction
Interaction with levothyroxine
Coefficient
95% CI
Gender
Male
Female
2.09
0.43
1.7-2.47
0.18-0.68
<0.001
1.25
0.04
0.82-1.68
-0.24-0.32
<0.001
Aetiology
GD
TN
1.55
0.34
1.24-1.86
-0.08-0.75
<0.001
0.89
-0.24
0.54-1.24
-0.81-0.32
<0.001
BMI category
Normal
Overweight
Obese
0.57
1.05
1.02
0.28-0.86
0.70-1.40
0.60-1.44
fT4 (pmol/l)
22-29.6
29.7-39.8
39.9-58.2
>58.2
-0.20
0.52
1.23
1.69
-0.60-0.19
0.12-0.93
0.85-1.61
1.33-2.05
Boelaert et al. (2012) in preparation
P-value Coefficient
95% CI
P-value
0.016
0.052
0.05
0.70
0.63
-0.27-0.37
0.30-1.10
0.13-1.14
0.007
0.042
0.005
<0.001
<0.001
-0.05
0.05
0.93
0.84
-0.52-0.41
-0.40-0.49
0.50-1.35
0.40-1.29
0.75
0.001
0.004
Summary of weight gain study




Treatment of hyperthyroidism associated with
significant weight gain
131I treatment and hypothyroidism associated with
small amount of excess weight gain
Uncontrolled hyperthyroidism results in less weight
gain
Males, GD subjects, higher BMI category and more
severe hyperthyroidism associated with higher risk of
weight gain from 131I
Boelaert et al. (2012) in preparation
Conclusions





Clinical presentation of hyperthyroidism widely varied –
may be missed in elderly
Think of associated autoimmune diseases if response to
treatment poor
Higher doses of 131I may be required in certain patient
groups
131I-induced hypothyroidism is associated with reduced
risk of mortality
131I associated with small but definite increase in weight
gain