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Hypothyroidism

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Hypothyroidism

  1. 1. HYPOTHYROIDISM -Binod timalsina
  2. 2. Hypothyroidism ■ Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormones. ■ There is a generalized slowing down of metabolic processes. ■ In newborn infants – Cretinism ■ In adolescents – short stature, mental retardation, precocious puberty ■ In adults – symptoms largely reversible after therapy
  3. 3. Interpretation for Thyroid Function Test High T4 Normal T4 Low T4 High TSH In vivo or in vitro artefact Pituitary hyperthyroidism Thyroid hormone resistance Subclinical hypothyroidism Primary hypothyroidism Normal TSH As above Sampling within 6 h of thyroxine dose Normal Pituitary or hypothalamic hypothyroidism Severe non-thyroidal illness Low TSH Hyperthyroidism Subclinical hyperthyroidism Subtle thyroxine overreplacement Autonomous functioning thyroid nodule Non-thyroidal illness Pituitary or hypothalamic hypothyroidism Severe non-thyroidal illness
  4. 4. Etiology of Hypothyroidism ■ Primary – thyroid failure ■ Secondary – pituitary TSH deficit (Hypopituitarism due to pituitary adenoma, apoplexy, infiltrative disease-sarcoidosis) ■ Tertiary – hypothalamic deficiency of TRH (rare) ■ Peripheral resistance to the action of thyroid hormone
  5. 5. Hashimoto’s Thyroiditis ■ Chronic lymphocytic thyroiditis ■ Probably the most common cause of hypothyroidism ■ With (younger patients) or without goiter (older patients – atrophy gland after destruction by immunologic process) ■ High titer of autoantibodies to thyroidal antigens (Thyroglobulin Ab, Thyroperoxidase Ab = TPO Ab = Antimicrosomal Ab = AMA)
  6. 6. Pathogenesis of Hypothyroidism ■ Characteristic finding: accumulation of glycosaminoglycans – mostly hyaluronic acid – in interstitial tissues ■ The accumalation is due not to excessive synthesis but to decreased destruction of glycosaminoglycans. ■ Accumulation of this hydrophilic substance and increased capillary permeability to albumin account for this interstitial edema that is particularly evident in the skin, heart muscle, and striated muscle.
  7. 7. Clinical Manifestations of Hypothyroidism ■ Symptoms and signs vary in relation to the magnitude of the thyroid hormone deficiency, and the acuteness with which the deficiency develops. ❖ Less prominent clinically and better tolerated when gradual loss of thyroid function (as in most cases of primary hypothyroidism) ❖ Symptoms develop acutely after thyroidectomy or abrupt withdrawal of exogenous thyroid hormone
  8. 8. Clinical Manifestations of Hypothyroidism -- Skin ■ Cool and pale skin  blood flow  ■ Dry roughness of skin  the epidermis has an atrophied cellular layer and hyperkeratosis ■ Decreased sweating  calorigenesis and acinar gland secretion  ■ Generalized nonpitting edema (myxedema) in severe hypothyroidism  infiltration of the skin with glycosaminoglycans and associated water retention
  9. 9. Clinical Manifestations of Hypothyroidism -- Eyes ■ Periorbital edema -- as a manifestation of generalized nonpitting edema or Graves' ophthalmopathy. ■ Graves' ophthalmopathy may persist or worsen when hypothyroidism develops after treatment of Graves' hyperthyroidism. Patients will have variable degrees of stare, protrusion of the eyes, and extraocular muscle weakness.
  10. 10. Clinical Manifestations of Hypothyroidism -- Cardiovascular System ■ Bradycardia  reductions in heart rate ■ Impaired muscular contractility ■ Reduced cardiac output decreased exercise capacity and shortness of breath during exercise ■ ECG: low voltage of QRS complexes and P and T waves ■ CXR: cardiomegaly  interstitial edema, myofibrillary swelling, LV dilatation, pericardial effusion
  11. 11. Clinical Manifestations of Hypothyroidism -- Cardiovascular System ■ Myxedema induces coronary artery disease ?? ■ CAD more common in p’ts with hypothyroidism ■ Symptoms and signs of congestive heart failure are usually absent in patients who have no other cardiac disease ■ Congestive heart failure or angina may worsen when hypothyroidism develops in patients with heart disease
  12. 12. Clinical Manifestations of Hypothyroidism -- Cardiovascular System ■ Hypertension  peripheral vascular resistance  ❖ In normotensive patients, BP increases are small (<150/100 mmHg). ❖ The BP of patients with established hypertension may increase further with the development of hypothyroidism.
  13. 13. Clinical Manifestations of Hypothyroidism -- Respiratory System ■ Fatigue, shortness of breath on exertion, and decreased exercise capacity  impaired respiratory function + cardiovascular disease ■ Hypoventilation (shallow and slow respirations)  respiratory muscle weakness + reduced pulmonary responses to hypoxia and hypercapnia ■ Obstructive sleep apnea  macroglossia
  14. 14. Clinical Manifestations of Hypothyroidism -- Gastrointestinal Disorders ■ Constipation, even ileus  gut motility  ■ Decreased taste sensation ■ Gastric atrophy  presence of antiparietal cell antibodies. Pernicious anemia occurs in 10% of patients with hypothyroidism caused by chronic autoimmune thyroiditis. ■ Weight gain  decreased metabolic rate + accumulation of fluid (nonpitting edema) that is rich in glycosaminoglycans ■ Ascites, rare
  15. 15. Clinical Manifestations of Hypothyroidism -- Renal Function ■ Decreased glomerular filtration rate (GFR ) ■ Impaired ability to excrete a water load ■ The drug clearance (ex, antiepileptic, anticoagulant, hypnotic and opioid drugs), is decreased. Drug toxicity may occur if drug dosage is not reduced. ■ During T4 replacement, drugs that are administered at effective doses in patients who are hypothyroid may become less effective.
  16. 16. Clinical Manifestations of Hypothyroidism -- Anemia ■ Impaired hemoglobin synthesis  thyroxine deficiency ■ Iron deficiency  increased iron loss with menorrhagia + impaired intestinal absorption of iron ■ Folate deficiency  impaired intestinal absorption of folic acid ■ Pernicious anemia  vitamin B12 -deficient megaloblastic anemia
  17. 17. Clinical Manifestations of Hypothyroidism -- Reproductive Abnormalities ■ Women with hypothyroidism may have either oligo- or amenorrhea or hypermenorrhea-menorrhagia. ■ Decreased fertility ■ Increased likelihood for early abortion ■ Hyperprolactinemia may occur, and is occasionally sufficiently severe to cause amenorrhea or galactorrhea ■ The serum sex hormone-binding globulin concentration may be low in hypothyroidism. This will lower serum total but not free sex hormone concentrations.
  18. 18. Clinical Manifestations of Hypothyroidism -- Neurological Dysfunction ■ General depression of central nervous system function ■ Sleepiness, inability to concentrate ■ Sluggish thought processes ❖ Respond slowly to questions ❖ Less able to retrieve information from memory ■ Agitated psychosis, rare (“myxedema madness”) ■ PET: 23% reduction in cerebral blood flow and a 12% reduction in cerebral glucose metabolism
  19. 19. Clinical Manifestations of Hypothyroidism -- Neuromuscular Abnormalities ■ A delay in the relaxation phase of deep tendon reflexes ■ Carpal tunnel syndrome ■ Paresthesia ■ Asymptomatic elevation in serum CPK level to muscle hypertrophy (which may be accompanied by muscle cramps) to proximal muscle weakness to, in rare cases, rhabdomyolysis.
  20. 20. Clinical Manifestations of Hypothyroidism -- Metabolic Abnormalities ■ Hyponatremia may result from a reduction in free water clearance ■ Reversible increases in serum creatinine occur in 20 ~ 90% of hypothyroid patients ■ lipid clearance may be decreased, resulting in an elevation in the serum concentrations of free fatty acids and total and low-density lipoprotein cholesterol ■ Plasma homocysteine concentrations are increased in some hypothyroid patients,
  21. 21. Common Signs and Symptoms of Hypothyroidism Sign or symptom Weakness Skin changes (dry or coarse skin) Lethargy Slow speech Eyelid edema Cold sensation Decreased sweating Cold skin Thick tongue Facial edema Coarse hair Skin pallor Forgetfulness Constipation Affected patients (%) 99 97 91 91 90 89 89 83 82 79 76 67 66 61
  22. 22. Serum FT4, TSH Normal FT4, TSH TSH , FT4 FT4 , TSH normal or  Primary hypothyroidism Euthyroid Secondary hypothyroidism TRH test Excessive response Normal type response No response Pituitary lesion Hypothalamic lesion Primary hypothyroidism
  23. 23. Treatment of Hypothyroidism ■ Replacement of Triiodothyroxine (T3): unsatisfactory due to rapid absorption, short half-life, and transient effect ■ Levothyroxine (T4): ❖ Converted to T3 intracellularly ❖ Once daily, half-life: 7 days ❖ Well-absorbed ❖ Easily monitored by following serum TSH and T4 levels
  24. 24. Treatment of Hypothyroidism ■ Replacement does of levothyroxine in adults range from 0.05 to 0.2 mg/d. It varies according to the patient’s age and body weight. ■ In young children: 4-5 ug/kg/d ■ In adults: average 1.7 ug/kg/d ■ In elders, start with lower dose, ex. 0.025mg daily, increase the dose at 4- to 6-week intervals based on serum FT4 and TSH levels ■ Dose should be increased about 25% during pregnancy
  25. 25. Drugs Potentially Altering Thyroid Hormone Replacement Requirements Increase replacement requirements Drugs that reduce thyroid hormone production Lithium Iodine-containing medications Amiodarone (Cordarone) Drugs that reduce thyroid hormone absorption Sucralfate (Carafate) Ferrous sulfate (Slow Fe) Cholestyramine (Questran) Colestipol (Colestid) Aluminum-containing antacids Calcium products Drugs that increase metabolism of thyroxine Rifampin (Rifadin) Phenobarbital Carbamazepine (Tegretol) Warfarin (Coumadin) Oral hypoglycemic agents Increase thyroxine availability and may decrease replacement requirements Drugs that displace thyroid hormone from protein binding Furosemide (Lasix) Mefenamic acid (Ponstel) Salicylates

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