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>Graves’disease)

• 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 α 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 bone-rich 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, high-sensitive 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 TSH≥10 mU/L, pregnancy, anti-thyroperoxidase antibody

References• S. Cooper, B Biondi. Subclinical thyroid disease

seminar. Lancet 2012; 379: 1142-54• สมาคมต่�อมไร้ท่�อแห่�งปร้ะเท่ศไท่ย.โร้คต่�อมไร้ท่�อ

ในเวชปฏิ�บั�ต่� คร้��งท่� 26• www.chatlert.worldmedic.com

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