Hyperthyroidism: Diagnosis, Management and Hyperthyroidism: Diagnosis, Management and Long-term ConsequencesLong-term Consequences

Kristien Boelaert

Senior Lecturer in EndocrinologyConsultant Endocrinologist

Queen Elizabeth Hospital Birmingham, UK

Centre for Endocrinology, Diabetes & MetabolismUniversity 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

FH of hyperthyroidism more common than hypothyroidism (p<0.001)

Manji, Boelaert et al. (2006) JCEM 91, 4873

Associated autoimmune diseases

Boelaert et al. (2010) Am J Med 123, 183.e1

2791 subjects with Graves’ disease

Age at diagnosis of Graves’ DiseaseM

edia

n ag

e at

pre

sent

ation

(y)

T1DM RA PA CD Vitiligo IBD None

N 31 88 39 25 40 25 2571

****

*** *****

*

Boelaert et al. (2010) Am J Med 123, 183.e1

Number of reported symptoms according to age

0

10

20

30

40

50

60

18-32 y

33-44y

45-60y

over 61 y

Nu

mb

er

of

pa

tie

nts

(%

)

0-2 symptoms 3-4 symptoms 5 or more symptoms

P < 0.001

Boelaert et al. (2010) JCEM 95, 2715

Out

com

e ac

cord

ing

to d

ose

regi

men

(%)

Cure Hypothyroidism

******

***

***

**

**

1278 patients treated with 131I for hyperthyroidism Single fixed dose of 131I

Outcome following 131I therapy

Boelaert et al. (2009) Clin End 70, 129

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 131INot hypothyroid

Following 131IHypothyroid

SMR SMR P SMR P SMR P

All causes Males Females

1.151.261.11

1.301.361.27

0.0060.100.07

1.241.341.21

0.020.110.06

1.021.1

0.95

0.850.570.60

Comorbidity absent Comorbidity present

0.951.52

1.031.68

0.84<0.001

1.091.48

0.480.002

0.811.43

0.080.01

Sinus Rhythm Atrial fibrillation

1.071.59

1.181.74

0.180.006

1.171.53

0.110.02

0.921.51

0.430.08

Circulatory deaths 1.20 1.37 0.05 1.19 0.22 1.12 0.45

Boelaert et al. (2012) JCEM resubmitted

HR (95% CI) P- Value

Gender Male Female

1.000.72 (0.55-0.93) 0.01

Cause of hyperthyroidism Graves’ disease TN hyperthyroidism Indeterminate

1.000.92 (0.63-1.18)0.86 (0.67-1.28)

0.360.64

Cardiac rhythm at presentation Sinus rhythm Atrial fibrillation

1.001.50 (1.08-2.08) 0.02

Co-morbidities Absent Present

1.001.58 (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

1.000.94 (0.69-1.27)0.72 (0.54-0.97)

0.670.03

Multivariate within cohort analysis

Boelaert et al. (2012) JCEM resubmitted

Control of hyperthyroidism

Thionamide only Thionamide + 131-I Thionamide + 131-I + T4

Years of follow-up

Se

rum

ft4

conc

entr

atio

n (p

mo

l/l)

Boelaert et al. (2012) JCEM resubmitted

Comparison with background populationPr

opor

tion

of fe

mal

es (%

)

Normal BMI Overweight Obese

***

Normal BMI Overweight Obese

Normal BMI Overweight Obese

Prop

ortio

n of

mal

es (%

) ***

Normal BMI Overweight Obese

*

Prop

ortio

n of

mal

es (%

)

Prop

ortio

n of

fem

ales

(%)

Boelaert et al. (2012) in preparation

PRESENTATION

DISCHARGE

Weight change during FU

Boelaert et al. (2012) in preparation

Boelaert et al. (2012) in preparation

Variable Coefficient 95% CI P-value131I treatment No Yes

00.81 0.57 to1.04

<0.001

Levothyroxine RX No Yes

00.36 0.11 to 0.61

<0.001

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

00.651.00

-1.42 to -0.99-0.76 to –0.33

0.39 to 0.910.71 to 1.28

<0.0010.03

<0.001<0.001

Multi-level model to predict weight

Parameters associated with weight gain

Boelaert et al. (2012) in preparation

Interaction with 131I Interaction with levothyroxineInteraction Coefficient 95% CI P-value Coefficient 95% CI P-value

Gender Male Female

2.090.43

1.7-2.470.18-0.68

<0.001 1.250.04

0.82-1.68-0.24-0.32

<0.001

Aetiology GD TN

1.550.34

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

0.571.051.02

0.28-0.860.70-1.400.60-1.44

0.0160.052

0.050.700.63

-0.27-0.370.30-1.100.13-1.14

0.0070.042

fT4 (pmol/l) 22-29.6 29.7-39.8 39.9-58.2 >58.2

-0.200.521.231.69

-0.60-0.190.12-0.930.85-1.611.33-2.05

0.005<0.001<0.001

-0.050.050.930.84

-0.52-0.41-0.40-0.490.50-1.350.40-1.29

0.750.0010.004

Summary of weight gain study

Boelaert et al. (2012) in preparation

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

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