hypo and hyperthyroidism causes , clinical finding diagnosis treatment
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Prof. Dr. Naseer HOD pathology THYROID (HYPOTHYROIDISM)
HYPOTHYROIDISM It is a condition caused by structural or functional derangement that interferes with the production of the thyroid hormone. This is a common disorder. Prevalence increases with age. 10 folds more common in women than men. Defect may occur anywhere in hypothalamus – pituitary- thyroid axis.
It is of two types: Primary (intrinsic abnormality in thyroid) Secondary (it is a result of pituitary and hypothalamus disease) PRIMARY HYPOTHYROIDISM: can be, 1. congenital : it is a result of iodine deficiency in diet, other rare forms include * inborn error of metabolism that is any step leading to thyroid hormone synthesis may be defective as , Iodine transport to thyrocytes for organification of iodine. Binding of iodine to tyrosine residue of storage protein thyroglobulin. Iodotyrosine coupling to form hormonally active T3 and T4. In rare stances complete absence of parenchyma (thyroid agenesis)OR gland may be greatly reduced (hypoplasia).
2. AUTO IMMUNE HYPOTHYROIDSM : Most common cause of hypothyroidism in iodine sufficient areas of the world. Vast majority of cases of autoimmune hypothyroidism are due to Hashimoto thyroiditis. Circulating auto antibodies including antimicrosomal antithyroid peroxidase and antithyroglobulin antibodies are found in this disorder. The thyroid is typically enlarged (goitrous).
3 . IOTROGENIC HYPOTHYROIDISM : It is caused by surgical or radiation induced ablation, 1. thyroidectomy for hyperthyroidism can lead to hypothyroidism. 2. the gland can also be ablated by radiation by radio iodine administration for the treatment of hypothyroidism or exogenous irradiation such as external radiation therapy to neck. 3. drugs given intentionally to decrease thyroid secretion (for e.g methimezole and propylthiouracil can also cause acquired hypothyroidism, agents use to treat non thyroid condition for e.g lithium , p-amino salicylic acid can cause hypothyroidism.)
3 . SECONDARY HYPOTHYROIDISM: Deficiency of TSH or TRH due to pituitary tumor of post partum pituitary necrosis or trauma. hypothalamic damage from tumor, trauma or irradiation therapy.
CRETINISM Refers to hypothyroidism that develops in infancy or early childhood. They are unfortunately mentally retarded. CLINICAL FEATURES : Impaired development of skeletal system and central nervous system manifests severe mental retardation, short stature, coarse facial features, protruding tongue and umbilical hernia. Mental retardation is related to thyroid deficiency in utero as T3 and T4 cross placenta is critical for fetal brain development. If maternal thyroid deficiency is before he development of fetal thyroid gland , mental retardation is severe. While thyroid deficiency later in pregnancy after fetal thyroid is functional does not effect normal brain development.
MYXEDEMA It develops in older child or adults. Myxedema is marked by, Slowing of physical and mental activity. Initial symptoms include generalized fatigue, apathy, mental sluggishness. Speech and intellectual functions are slowed. Patient of myxedema are listless cold intolerant and frequently overweight. Decrease sympathetic activity has constipation and decrease sweating. Reduced cardiac output leads to shortness of breath and decrease exercise capacity. In addition hypothyroidism promote atherogenic profile for e.g increased in cholesterol and LDL levels contributes to increase cardiovascular mortality.
Histologically there is a increased accumulation of glycosaminoglycan's and hyaluronic acid in subcutaneous tissue of skin and other viscera results in non pitting edema, broadening and coarsening of facial features. Enlargement of tongue and deepening of voice. Unexplained Increased in weight or hypocholesteremia should be assessed for potential hypothyroidism. Measurement of TSH levels is the most sensitive screening test for this disorder. TSH level is increased in primary hypothyroidism. TSH level is not increased in persons with hypothyroidism due to primary hypothalamic or pituitary disease. T4 is decreased with individuals with hypothyroidism.
HYPERTHYROIDISM . it is due to excessive release of thyroid hormone. . THYROTOXICOSIS: it is a hypermetabolic state caused by elevated circulating levels of T3 T4. CAUSES: Excessive release of pre form thyroid hormone in e.g thyroiditis or from extra thyroid source. PRIMARY HYPERTHYROIDISM : hyperthyroidism arising from intrinsic thyroid abnormality. SECONDARY HYPERTHYROIDISM : arising from process outside thyroid as TSH secreting pituitary tumors. Three most common causes of thyrotoxicosis are, Diffuse hyperplasia. (graves disease responsible for 80 % cases) Hyperfunction of multinodular goiter Hyperfunctional thyroid adenoma.
CLINICAL COARSE: It is hypermetabolic state, induced excess thyroid hormone and over activity of sympathetic nervous system. Excessive thyroid causes in crease in metabolic rate, ski tends to be soft, warm, flushed due to increased blood flow and peripheral vasodilation, A. heat intolerance is common B. sweating is increased C. weight loss despite increase in appetite. CARDIAC MANIFESTATION : are the most constant and earliest feature. Elevated cardiac contractility and increased cardiac output as there is increased peripheral oxygen requirement so, A. tachycardia B. palpitation C. cardiomegaly D. arrhythmias (atrial fibrillation is more common in elderly patient) E. congestive heart failure. THYROTOXIC CARDIOMYOPATHY : its reversible left ventricular dysfunction leads to low cardiac output and heart failure.
OVERACTIVITY OF SYMPATHETIC NERVOUS SYSTEM: produce, A. tremors B. hyperactivity C .emotional liability D .Anxiety E. inability to concentrate F. insomnia Proximal muscle weakness and decrease muscle mass. GIT DISTURBANCES, hyper motility, diarrhea and malabsorption.
OCCULAR CHANGES : these changes often call attention to hyperthyroidism. A. wide staring gazed B. lid lag due to sympathetic overs stimulation of superior tarsals muscle. C. proptosis (it occurs only graves disease) SKELETAL SYSTEM : thyroid hormone stimulates bone resorption results in, Osteoporosis with increased risk of fracture. Atrophy of skeletal muscle with fatty infiltrations. Minimal liver enlargement due to fatty infiltration. Generalized lymphoid hyperplasia and lymph adenopathy in patient with graves disease.
THYROID STORM : It refers to abrupt onset of severe hyperthyroidism, Occurs in patient with graves disease. Probably results from acute elevation of catecholamine's during infections, surgery, cessation of ant thyroid drugs or any stress . Patient id often febrile with tachycardia , out of proportion of fever. Thyroid storm is a medical emergency, a significant number of untreated patient die of arrhythmias. APATHETIC HYPERTHYROIDISM: It refers to thyrotoxicosis in older adults in whom comorbidities may blunt the features of hyperthyroidism.
DIAGNOSIS: TSH concentration is the most useful screening test for hyperthyroidism. TSH levels are decreased even at the earliest stage. Confirm with the measurement of free T4 which is increased. SECONDARY HYPERTHYROIDISM : (PITUITATRY ASSOCIATION) TSH levels are either normal or raised. TSH levels are determined after injection of thyrotropin releasing hormone (TRH) is used. Normal rise in TSH after administration of TRH exclude secondary hyperthyroidism.
Once diagnosis of thyrotoxicosis is confirmed by TSH assay and free thyroid hormone levels, measurement of radioactive iodine uptake can determine the etiology. 1. diffuse increase uptake in whole gland means graves disease. 2. increase uptake in solitary nodule indicates toxic adenoma. 3. decrease uptake indicates thyroiditis.
THERAPEUTIC OPTIONS: 1. beta blockers to control the symptoms induced by increased adrenergic tone. 2. Athionamide to block the new hormone synthesis. 3. iodine solutions to block the release of thyroid hormone. 4. thyroid hormones and agents that inhibit the peripheral conversion of t4 to t3. 5. Radio iodine is incorporated to thyroid tissue resulting in ablation of thyroid function over a period six to eighteen weeks.