Subclinical

thyroid disease
By Suporn travanichakul

Outlines

Introduction
Subclinical hyperthyroidism
Subclinical hypothyroidism
Conclusion

Introduction
Subclinical thyroid disease is
defined biochemically, in the present
or absent of symptoms
Subclinical hyperthyroidism =
low TSH, but normal free T3 and T4
Subclinical hypothyroidism = high
TSH, but nomal free T3 and T4

Subclinical
hyperthyroidism

Disease form
Exogenous disease
Most common
Caused by thyroid hormone therapy or iodine
containing drug/radiographic contrast agents

Endogenous disease
Graves disease
Toxic adenoma
Toxic multinodular goiter
Thyroiditis

Epidemiology
Prevalence was inconclusive
According to NHANES,
1.8% of peoples had serum TSH <0.4 mU/L
0.7% of peoples had serum TSH <0.1 mU/L

Mild subclinical hypothyroid is more

common
The frequency of subclinical
hyperthyroidism increase with ages,
female, iodine-deficient populations

Diagnosis
Serum TSH low limit of the reference
range and free T4 and T3
concentrations are normal
Low serum TSH might due to a
change in set point of the HPT axis
Elderly, black people, cigarette smokers

Low serum TSH values are often

transitory

Diagnosis
40-60% - return to normal TFT
4.3% -Progress to overt
hyperthyroidism within 4 yrs (solitary
nodule/multinodula
goiters>Gravesdisease)
Autonomously functioning thyroid
adenomas turn to overt
hyperthyroidism 4%/yr

Diagnosis
The most common cause in
subclinical hyperthyroidism
Graves disease in the youngs
Toxic multinodular goiter in the elderly
(>55 yrs)
Nodular goiters iodine-deficient country,
female, elderly

Differential diagnosis

Severe nonthyroidal illness

Pituitary insufficiency
Pregnancy
Drug: ASA, steroids, dopamine,
furosemide
After treatment of hyperthyroidism
Laboratory error

Effects of subclinical
hyperthyroidism
Cardiovascular system
Smooth muscle
Cardiac pacemaker

Skeleton
Quality of life and cognitive function

Cardiovascular system
T3 has major effect on cardiac
pacemaker, vascular smooth muscle
and mycardial contraction through
regulatory gene transcription

Cardiovascular system
Increased frequency of PAC/PVC and
mean 24hr heart rates
Studies examining systolic and
diastolic function have yield mixed
results -> due to different in age,
degree of TSH, duration
Increased frequency of carotid artery
plaques and stroke

Cardiovascular system
Increase frequency of atrial
fibrillation
Increase all-cause mortality

Skeleton
Thyroid hormone stimulate bone
resorption by osteoclast activation
In post-menopausal women with
subclinical hyperthyroidism, BMD
decreased especially in cortical bonerich sites such as radius, increased
risk of fractures

Skeleton
In post-menopausal women with
exogenous/endogenous
subclinical hyperthyroidism , the
increased risk of fracture are
uncertain

Quality of life and

cognitive function
No symptoms or change of mood or
cognitive function
In elderly, subclinical
hyperthyroidism has been associated
with dementia

Treatment
Improvement in
Mean HR, SVR, Lt ventricular mass
index, frequency of PVC/PAC,
spontaneous conversion of AF to NSR

Post-menopausal women,
stabilzation and mild improvement of
BMD, but not fracture rate

Subclinical
hypothyroidism

Subclinical hypothyroidism
Asymptomatic
Only mild nonspecific symptoms
Fartique, reduced exercise tolerance

= Mild thyroid failure

Epidemiology

3-10% in general populations

20% of more than 65 aged women
75% have TSH level < 10 mU/L
50-80% have anti-thyroidperoxidase
antibodies

Risk factors
Hx of neck radiation or iodine ablation
Postpartum/subacute/autoimmune
thyroiditis
DM type I
Iodine containing drug ( amiodarone,
lithium)
Immune mediator exposure : Interferon
Iodine deficiency

Differential diagnosis
Inadequate treatment of overt
hypothyroidism or drug interactions
Obesity
Isolated pituitary resistance to thyroid
hormone
Impair renal function
Recovery from severe non-thyroidal illness
Outside of the reference range, diurnal
variation, Laboratory analytical problems

Progression to overt
hypothyroidism
Subclinical hypothyroidism is
reversible, especially when serum
TSH < 10 mU/L
Serum TSH> 10 mU/L, female, the
presence of antithyroid peroxidase
are associated with increased risk of
overt hypothyroidism

Progression to overt
hypothyroidism
From Whickham survey involving 2800
adults,20 years of follow-up
Female with antithyroid peroxidase with
TSH level > 10 mU/L : 4.3% annual rate of
progression to overt hypothyroidism
But whom only mildly elevated TSH: 2.6%
annual rate of progression to overt
thyroidism
NNT to prevent one case from overt
hypothyroidism 4.3-14.3

Progression to overt
hypothyroidism
Female + antithyroid antibodies +
raised serum TSH : 4% annual rate of
progression to overt hypothyroidism
Only Raised serum TSH : 2-4% annual
rate of progression to overt thyroidism
Only antithyroid antibodies : 1-3%
annual rate of progression to overt
thyroidism

Effects of subclinical
hypothyroidism

Cardiovascular risk
Risk of heart failure
Lipid profiles
Pregnancy
Quality of life

Cardiovascular system
Depressed Lt. ventricular
systolic/diastolic function at rest and
during exercise -> reduced exercise
tolerance
Impair relaxation of vascular smooth
muscle cells->increased arterial
stiffness and SVR

Cardiovascular system
Diastolic hypertension,
hypercholesterolaemia, insulin
resistance, weight gain, isolated
diastolic dysfunction were higher in
subclinical hypothyroidism

Cardiovascular system
But risk of cardiovascular disease and
all cause mortality were controversial
Increased incidence of heart failure,
only in patients with serum TSH>10
mU/L
Meta-analysis : the risk of CHD
increased with the severity of thyroid
hormone deficiency

Lipid profile
Increased total and LDL cholesterol
were controversial
Not significant in homocystein, highsensitive C-reactive protein,
fibrinogen, factor VIII, vWF

Pregnancy
Can lead to serious obstetric
complications
Miscarriage, placental abruption, preterm
delivery, GIH, IUGR

Fetal thyroid gland does not produce

thyroid hormone until 13 wks of
gestation
Thyroid hormone is essential for fetal
brain development and maturation

Quality of life
Be useful in improve anxiety,
depression, cognitive function and
memory, althrough contrasting
findings have been reported

Effect of replacement
therapy
To prevent progression to overt
hypothyroidism and its morbidity
To improve serum lipid profile and
cardiovascular causes of death
To reverse the symptoms of mild
hypothyroidism

Effect of replacement
therapy
Does not improve mood, cognition or
symptoms in patients with subclinical
hypothyroidism unless serum TSH >
10 mU/L
May improved systolic and diastolic
function, endothelial function
Lower risk of heart failure, lowering
all-cause mortality

Effect of replacement
therapy
Meta-analysis showed
If total cholesterol 240 mg/dl and TSH
> 10 mIU/L -> mean reduction after
treatment 7.9 mg/dl
If total cholesterol < 240 mg/dl -> mean
reduction after treatment 0.7 mg/dl and
statistically insignificant

Lower miscarriage rates

Screening
Population screening for subclinical
hypothyroidism is controversial

Phamacokinetic

Conclusion
Experts do not agree about whether
screening to diagnose the disease is
worthwhile
To recommend treatment in subclinical
hyperthyroidism who are older than 65
years , serum TSH<0.1 mU/L , multinodular
goiter or toxic adenoma
To recommend treatment in subclinical
hypothyroidism who are TSH10 mU/L,
pregnancy, anti-thyroperoxidase antibody

References
S. Cooper, B Biondi. Subclinical
thyroid disease seminar. Lancet
2012; 379: 1142-54
.
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www.chatlert.worldmedic.com

Thanks for your

attention