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Subclinical Thyroid Disease
Citation preview
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
Thanks for your attention