SUBCLINICAL HYPOTHYROIDISM

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SUBCLINICAL HYPOTHYROIDISM

• Chou Chien-Wen M.D.
• Division of Endocrinology and Metabolism
• Chi-Mei Medical Center

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Definition

• Elevated serum TSH associated with normal total
  or free T4 and T3 values
• Mild thyroid failure, compensated, early, latent,
  mild, minimally symptomatic and preclinical
  hypothyroidism
• Extended the definition subjects with normal FT4
  and TSH, but exaggerated TSH responses to TRH

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Prevalence

• 1-10 general population
• Risk of developing SH increases with female
  gender, advanced age and greater dietary iodine
  intake
• 7-26 in elderly

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Half-life of Thyroid Hormones

• T4 7 days
• T3 1 day
• TSH lt 1 hour

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Natural History

• 154 female patients 10 years
• 57 continued mild thyroid failure
• 34 progressed to overt hypothyroidism
• 9 reverted to normal TSH level
• Progression 3-18 per year

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Strongest Predictors of Progression

• Antithyroid antibodies
• Serum TSH gt 20 uU/ml
• History of radioiodine ablation for Graves
  disease
• History of external radiation for nonthyroid
  malignancies
• Chronic lithium treatment

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Clinical manifestations

• Often asymptomatic 30 have symptoms
• Colorado Thyroid Disease prevalence Study
• 2336 subjects with mild thyroid failure
• Dry skin, poor ,memory, slow thinking, muscle
  weakness, fatigue,muscle cramps, cold
  intolerance, puffy eyes, constipation and
  hoarseness

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Swiss Study

• 323 women hypothyroidism
• 24 of 93 subjects with mild thyroid failure
  exhibited typical symptoms of hypothyroidism

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Neurobehavioral Abnormalities and Neuromuscular
Function

• Depression, Memory loss, Cognitive impairment
• Peripheral nerve dysfunction decreased
  conduction amplitude in peripheral nerves and an
  abnormal stapedial reflex
• Skeletal muscle abnormalities including elevated
  serum CPK, increased circulating lactate levels
  during exercise and repetitive discharges on
  surface EMG

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Cardiac-pulmonary Function

• Impaired myocardial contractility and diastolic
  dysfunction at rest or with exercise
• Impairment of exercise-related stroke volume,
  cardiac index and maximal aortic flow velocity
• Pulmonary testing Decreased vital capacity,
  reduced anaerobic thresholds and decreased oxygen
  uptake at the anaerobic threshold

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Cardiovascular Risk Factor

• Increased serum levels of TC and LDL
• Reduced HDL
• Increase in the serum TSH level of 1 uU/ml is
  associated with a rise in serum TC of 3.5 mg/dl
  in women and 6.2 mg/dl in men
• Rotterdam Study increased prevalence of aortic
  atherosclerosis and MI
• Independent and equivalently important risk
  factor for MI

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Benefits of Treatment

• Symptoms
• Neurobehavioral abnormalities and neuromuscular
  function
• Cardio-pulmonary function
• Cardiovascular risk factor

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Treatment Goals

• High normal TSH values associated with modest
  increases in cholesterol levels
• Endothelial dysfunction
• Optimal goal TSH range for L-thyroxin-treated
  patients is 0.5-2 uU/ml

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Summary

• Mild thyroid failure particularly those who have
• Symptoms
• Other cardiovascular risk factors
• Goiters
• Positive antithyroid antibodies
• Who are pregnant

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Whickham Survey

• Most extensive longitudinal study
• No association between SH and ischemic heart
  disease

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Five Distinct Situations

• Mild unrecognized thyroid failure
• Undertreated overt hypothyroidism
• Overtreated overt hyperthyroidism
• Transient disturbances of thyroid axis
• Euthyroid outliers

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Epidemiology of SH