Subclinical hypothyroidism.
Introduction: Thyroid dysfunction is to be detected at subclinical level as it has major health impact. Subclinical hypothyroidism is associated with morbidity, risk of cardiac dysfunctions, lipid disorders and consequences from development of overt hypothyroidism.
Definition: Subclinical hypothyroidism is present when an asymptomatic patient present with low normal free T4 but a slightly elevated serum TSH level. Serum TSH values range between 5 and 15 mIU/L.
Nomenclatures: Other names for subclinical hypothyroid includes mild hypothyroid, preclinical hypothyroid, failing gland syndrome, biochemical hypothyroidism and decreased thyroid reserve.
Etiology: Causes of subclinical hypothyroid are like overt hypothyroidism. a) Chief: Hashimoto’s thyroiditis. It is associated with antiTPO and antithyroglobulin antibodies. Thyroid is also enlarged.Antithyroid antibodies may also be associated with atrophy of the thyroid and hypothyroidism. b) After radio active iodine (RAI) treatment for Grave’s disease. c) Lithium and amiodarone therapy. d) Excessive dose of antithyroid medication. e) Infection (viral), silent or postpartum thyroiditis. f) Inadequate T4 replacement in overt hypothyroidism (may be intentional in patients with co-existent heart disease or due to poor compliance).
Prevalence: If TSH level of 5 mIU/L is bottom cut off level, 8% of women and 4% of men have subclinical hypothyroidism. In > 60 years of age group 15% of women and 8% of men have subclinical hypothyroidism. TSH level >2 mIU/L reflects a disturbance of thyroid- pituitary axis. So values above the upper level of typical reference range (4.5mIU/L) are highly significant and number of subclinical hypothyroidism cases are larger if reference range is considered slight lesser (2-3 mIU/L). Screening: Routine screening of population is not cost effective. But screening is useful in pregnant women, women aged greater than 60 years and high risk groups.
Course: a) Resolved: In silent thyroiditis with a transient hypothyroid stage. Resolution is not related to age, sex and anti-TPO level. b) Unchanged. c) Many cases progress to overt hypothyroidism. Rate is 5% per year with high TSH and antithyroid antibodies. In selected cases, e.g., elderly women with high rise of antithyroid antibody titer the risk of overt disease may be closer to 20% per year. d) As symptoms may wax and wane in autoimmune disease, TSH level might be elevated sometimes and normal in next time.
Clinical features: The term subclinical may not strictly correct. Some cases have clinical symptoms. There may be dry skin, cold intolerance, weight gain, easy fatigability which may improve with levothyroxine treatment. There are greater than average incidence of problem with muscles and nerves e.g., weakness, muscle fatigue and tingling extremities. Nonspecific symptoms like depression and fatigue in elderly women may or may not be due to subclinical hypothyroidism. Patients may have mild abnormalities of serum lipoproteins and cardiac functions. Lipid disorder: Triglyceride, total cholesterol and LDL cholesterol are elevated, but less marked and less prominent than overt hypothyroidism, but still there is risk of atherosclerosis and coronary vascular disease.Levothyroxine treatment reduces total cholesterol and LDL cholesterol level. In subclinical hypothyroidism, there is 2-3 times more chance of increased total cholesterol. Total cholesterol only slightly rises (0-30%) above normal with subclinical hypothyroidism. There is also increased lipoprotein (a) level. Cardiac function: Subclinical hypothyroidism has adverse cardiac end points. A sensitive marker of myocardial contractility, the ratio of pre-ejection period to left ventricular ejection time (PEP: LVET) improves significantly after treatment of subclinical hypothyroidism with levothyroxine. Increased C-reactive protein in subclinical hypothyroidism predicts heart disease due to low grade inflammation and atherosclerosis. Fasting hyperinsulinaemia may be predictor of later insulin resistance.
Treatment: Indications of treatment: 1) Presence of symptoms 2) Chance of overt disease e.g., patients with Hashimoto’s disease [a) antibodies to TPO or thyroglobulin, b) presence of goiter] 3) TSH>10 mIU/L, especially if titer of antithyroid antibodies rise. There is chance to develop overt hypothyroidism. 4) Fatigue, dry skin, constipation, muscle cramp etc may benefit even if TSH 5-10 mIU/L. 5) Dyslipidaemias. Unfavourable factors of treatment: • Expense. • Bother of daily medication • Overdose with levothyroxine may exacerbate osteoporosis or cause cardiac arrhythmias. • A common error in levothyroxine therapy is the failure to reduce levothyroxine dosages if TSH decreases below normal without free T4 rising above normal. There is chance of subclinical hyperthyroidism and as a consequence osteoporosis and cardiac dysfunction. Risk if not treated: 1) Increased heart attack and atherosclerosis. 2) Increased cholesterol, lipoprotein a and triglyceride level. 3) Increased risk of depression, anxiety and panic attack. 4) Increased chance of miscarriage in pregnancy. 5) Increased chance of developmental delay in infants born of mothers with subclinical hypothyroidism. Benefits of treatment: 1) Prevent further worsening of thyroid dysfunction. 2) Prevent growth of goiter. 3) May eliminate symptoms and risks of subclinical hypothyroidism. 4) The abnormal cholesterol levels will likely to improve with thyroid hormone replacement. 5) Improvement of neuropsychiatric symptoms including mental lethargy. Some mood disturbances in subclinical hypothyroidism have immunological rather than endocrinological basis, in which cases, treatment would not help.
Evaluation: Patient should be evaluated before starting treatment. If initial TSH report is raised with normal T4(free), repeat thyroid function tests at minimum of 2 weeks interval, but no longer than 3 months. Enquire for family history, drug history, symptoms, and pregnancy status. Look signs of obesity / goiter. Send blood for anti-TPO, anti thyroglobulin antibodies and lipid profile. Treat with 25-50 microgram /day of levothyroxine. Repeat TSH after 6-8 weeks (TSH lag is 6 weeks periods).Increase or decrease dose according to TSH level. Once dose established, evaluate TSH level 6-12 months interval. 1) If treatment given, TSH level monitored regularly and should not be below normal. 2) If no treatment, monitoring at 6 to 12 months interval, both clinically and measuring TSH level. Conclusion: Subclinical hypothyroidism is to be detected early and managed individually to prevent cardiac dysfunctions, lipid disorders and consequences from development of overt hypothyroidism.
Subclinical hypothyroidism. Introduction: Thyroid dysfunction is to be detected at subclinical level as it has major health impact. Subclinical hypothyroidism is associated with morbidity, risk of cardiac dysfunctions, lipid disorders and consequences from development of overt hypothyroidism. Definition: Subclinical hypothyroidism is present when an asymptomatic patient present with low normal free T4 but a slightly elevated serum TSH level. Serum TSH values range between 5 and 15 mIU/L. Nomenclatures: Other names for subclinical hypothyroid includes mild hypothyroid, preclinical hypothyroid, failing gland syndrome, biochemical hypothyroidism and decreased thyroid reserve. Etiology: Causes of subclinical hypothyroid are like overt hypothyroidism. a) Chief: Hashimoto’s thyroiditis. It is associated with antiTPO and antithyroglobulin antibodies. Thyroid is also enlarged.Antithyroid antibodies may also be associated with atrophy of the thyroid and hypothyroidism. b) After radio active iodine (RAI) treatment for Grave’s disease. c) Lithium and amiodarone therapy. d) Excessive dose of antithyroid medication. e) Infection (viral), silent or postpartum thyroiditis. f) Inadequate T4 replacement in overt hypothyroidism (may be intentional in patients with co-existent heart disease or due to poor compliance). Prevalence: If TSH level of 5 mIU/L is bottom cut off level, 8% of women and 4% of men have subclinical hypothyroidism. In > 60 years of age group 15% of women and 8% of men have subclinical hypothyroidism. TSH level >2 mIU/L reflects a disturbance of thyroid- pituitary axis. So values above the upper level of typical reference range (4.5mIU/L) are highly significant and number of subclinical hypothyroidism cases are larger if reference range is considered slight lesser (2-3 mIU/L). Screening: Routine screening of population is not cost effective. But screening is useful in pregnant women, women aged greater than 60 years and high risk groups. Course: a) Resolved: In silent thyroiditis with a transient hypothyroid stage. Resolution is not related to age, sex and anti-TPO level. b) Unchanged. c) Many cases progress to overt hypothyroidism. Rate is 5% per year with high TSH and antithyroid antibodies. In selected cases, e.g., elderly women with high rise of antithyroid antibody titer the risk of overt disease may be closer to 20% per year. d) As symptoms may wax and wane in autoimmune disease, TSH level might be elevated sometimes and normal in next time. Clinical features: The term subclinical may not strictly correct. Some cases have clinical symptoms. There may be dry skin, cold intolerance, weight gain, easy fatigability which may improve with levothyroxine treatment. There are greater than average incidence of problem with muscles and nerves e.g., weakness, muscle fatigue and tingling extremities. Nonspecific symptoms like depression and fatigue in elderly women may or may not be due to subclinical hypothyroidism. Patients may have mild abnormalities of serum lipoproteins and cardiac functions. Lipid disorder: Triglyceride, total cholesterol and LDL cholesterol are elevated, but less marked and less prominent than overt hypothyroidism, but still there is risk of atherosclerosis and coronary vascular disease.Levothyroxine treatment reduces total cholesterol and LDL cholesterol level. In subclinical hypothyroidism, there is 2-3 times more chance of increased total cholesterol. Total cholesterol only slightly rises (0-30%) above normal with subclinical hypothyroidism. There is also increased lipoprotein (a) level. Cardiac function: Subclinical hypothyroidism has adverse cardiac end points. A sensitive marker of myocardial contractility, the ratio of pre-ejection period to left ventricular ejection time (PEP: LVET) improves significantly after treatment of subclinical hypothyroidism with levothyroxine. Increased C-reactive protein in subclinical hypothyroidism predicts heart disease due to low grade inflammation and atherosclerosis. Fasting hyperinsulinaemia may be predictor of later insulin resistance. Treatment: Indications of treatment: 1) Presence of symptoms 2) Chance of overt disease e.g., patients with Hashimoto’s disease [a) antibodies to TPO or thyroglobulin, b) presence of goiter] 3) TSH>10 mIU/L, especially if titer of antithyroid antibodies rise. There is chance to develop overt hypothyroidism. 4) Fatigue, dry skin, constipation, muscle cramp etc may benefit even if TSH 5-10 mIU/L. 5) Dyslipidaemias. Unfavourable factors of treatment: • Expense. • Bother of daily medication • Overdose with levothyroxine may exacerbate osteoporosis or cause cardiac arrhythmias. • A common error in levothyroxine therapy is the failure to reduce levothyroxine dosages if TSH decreases below normal without free T4 rising above normal. There is chance of subclinical hyperthyroidism and as a consequence osteoporosis and cardiac dysfunction. Risk if not treated: 1) Increased heart attack and atherosclerosis. 2) Increased cholesterol, lipoprotein a and triglyceride level. 3) Increased risk of depression, anxiety and panic attack. 4) Increased chance of miscarriage in pregnancy. 5) Increased chance of developmental delay in infants born of mothers with subclinical hypothyroidism. Benefits of treatment: 1) Prevent further worsening of thyroid dysfunction. 2) Prevent growth of goiter. 3) May eliminate symptoms and risks of subclinical hypothyroidism. 4) The abnormal cholesterol levels will likely to improve with thyroid hormone replacement. 5) Improvement of neuropsychiatric symptoms including mental lethargy. Some mood disturbances in subclinical hypothyroidism have immunological rather than endocrinological basis, in which cases, treatment would not help. Evaluation: Patient should be evaluated before starting treatment. If initial TSH report is raised with normal T4(free), repeat thyroid function tests at minimum of 2 weeks interval, but no longer than 3 months. Enquire for family history, drug history, symptoms, and pregnancy status. Look signs of obesity / goiter. Send blood for anti-TPO, anti thyroglobulin antibodies and lipid profile. Treat with 25-50 microgram /day of levothyroxine. Repeat TSH after 6-8 weeks (TSH lag is 6 weeks periods).Increase or decrease dose according to TSH level. Once dose established, evaluate TSH level 6-12 months interval. 1) If treatment given, TSH level monitored regularly and should not be below normal. 2) If no treatment, monitoring at 6 to 12 months interval, both clinically and measuring TSH level. Conclusion: Subclinical hypothyroidism is to be detected early and managed individually to prevent cardiac dysfunctions, lipid disorders and consequences from development of overt hypothyroidism.