Thyroid Disease PDF

# Thyroid disease By Dr: DALIA HASSAN ## Development - The fetal thyroid arises from an outpouching of the foregut at the base of the tongue (foramen cecum). It migrates to its normal location over the thyroid cartilage by 8-10 weeks of gestation. - Thyroglobulin synthesis occurs from 4 weeks, io...

# Thyroid disease By Dr: DALIA HASSAN ## Development - The fetal thyroid arises from an outpouching of the foregut at the base of the tongue (foramen cecum). It migrates to its normal location over the thyroid cartilage by 8-10 weeks of gestation. - Thyroglobulin synthesis occurs from 4 weeks, iodine trapping occurs by 8-10 weeks. - Thyroxin (T4) and, to a lesser extent, triiodothyronine (T3) synthesis and secretion occur from 12 weeks of gestation. - Hypothalamic neurons synthesize thyrotropin-releasing hormone (TRH) by 6-8 weeks, the pituitary portal vessel system begins development by 8-10 weeks. - Thyroid-stimulating hormone (TSH) secretion is evident by 12 weeks of gestation. ## Regulation of Thyroid Hormone - The thyroid hormones, T3 and T4, are regulated by negative feedback. When levels of T3 and T4 decrease below normal, the hypothalamus releases thyroid-regulating hormone (TRH), stimulating the pituitary gland to produce thyroid-stimulating hormone (TSH), which acts on the thyroid gland to produce more hormones and raise the blood levels. - Once the levels rise, the hypothalamus shuts off and stops secreting TRH, which in turn inhibits the pituitary gland release of TSH. ## Functions of Thyroid Hormones - Growth and development (required for somatic and neuronal growth). - Thermogenesis. - Mental development - Sexual maturation. - Affect carbohydrate, lipid, and vitamin metabolism. - Potentiate action of catecholamine. ## Thyroid disorders - Hypothyroidism. - Thyrotoxicosis. - Thyroid neoplasia. ## Hypothyroidism May be primary (thyroid gland) or secondary (central-hypothalamic pituitary). However, the most common cause of thyroid dysfunction is iodine deficiency disorder. - Salt iodization is a cost-effective solution. The disorder may be manifested from birth (congenital) or acquired. ### 1. Congenital Hypothyroidism - Dyshormonogenesis. - Dysgenesis. - Ectopic (Lingual thyroid, Thyroglossal) - Most cases of congenital hypothyroidism are not hereditary and result from thyroid dysgenesis (aplasia, hypoplasia, or an ectopic gland) no goiter. - Some cases are familial; these are usually caused by one of the inborn errors of thyroid hormone synthesis (dyshormonogenesis) and may be associated with a goiter. - Other causes: - Iodine deficiency (endemic goiter) - Maternal medications - Iodides, amiodarone - Propylthiouracil, methimazole - Radioiodine - Clinical features: - Most infants with congenital hypothyroidism are asymptomatic at birth, even if there is complete agenesis of the thyroid gland. - Posterior fontanel larger than 0.5 cm. - Prolongation of physiologic jaundice. - Feeding difficulties. - Sluggishness, lack of interest, somnolence, and choking spells during nursing, are often present during the 1st month of life. - Low-pitched coarse cry. - Respiratory difficulties, partly caused by the large tongue, include apneic episodes, noisy respirations, and nasal obstruction. - Constipation that does not usually respond to treatment. - Umbilical hernia is usually present, generalized hypotonia. - Cold and mottled skin. - Edema of the genitals and extremities may be present. - Heart murmurs. - Cardiomegaly, and asymptomatic pericardial effusion are common. - Approximately 10% of infants with congenital hypothyroidism have associated congenital anomalies. Cardiac anomalies are most common, but anomalies of the nervous system and eye have been reported. - Also may be associated with hearing loss (Pendered syndrome). - Symptoms in infants and older children: - Stunted growth (short stature), delayed bone age. - Anterior fontanel is large, and the posterior fontanel may remain open. - Development is usually delayed, mental retardation. - Delayed sexual maturation (precocious puberty, delayed puberty). - Dentition will be delayed. - Short and thick neck. - Bradycardia. - Diagnosis: - Newborn screening programs (Guthrie test) Day2 to day5 of life. - Thyroid function test (TFT): - Serum levels of free T4 are low, elevated TSH, often to >100 mU/L. - Radiology: - Thyroid scan Technetium or 1123 - U/S - Bone age - Epiphyseal dysgenesis - Urinary iodine - Maternal antibodies - Hypothalamic pituitary hypothyroid: - Low T4. Normal or low TSH. - Isolated. - Panhypopituitarism: - Sporadic - Familial - MRI brain -TRH stimulation test? - Treatment: - Treatment with thyroxin should be started before 2 weeks to 3 weeks of age to reduce the risk of impaired neurodevelopment. - Treatment is lifelong with oral replacement of thyroxin. - Thyroxin 10-15 µgm/kg/day od titrating the dose to maintain T4 levels at higher normal. - Follow up for growth and development (occasionally IQ). - Prognosis: - With neonatal screening, the results of long-term intellectual development have been satisfactory and intelligence should be in the normal range for the majority of children. - Delayed diagnosis or inadequate treatment, and poor compliance in the 1st 2-3 yr of life result in variable degrees of brain damage. - Without treatment, affected infants are profoundly intellectually challenged and growth retarded. ### 2. Acquired Hypothyroidism - Primary: - Common (Lymphocytic thyroiditis (Hashimotos)). - Iodine deficiency - Partial forms of congenital causes - Surgery - Radiation - Metabolic - Drugs - ioding (amiodarone) - Food (millet/cabbage) - Pituitary. Hypothalamic. - Autoimmune thyroid disease: associated with: - Down syndrome. - Turner syndrome. - Klinefelter syndrome. - Celiac disease and DM. - Other Presentations of Hashimotos/hypothyroidism - Encephalopathy - Renal impairment - Dilated cardiomyopathies - Thyrotoxicosis - PCP (precocious puberty) - Pituitary mass - Investigations: - Free T4, TSH - Thyroid antibodies (TPO - Thyroglobulin). - Bone age - Thyroid scan/US - Urinary iodine - MRI brain - Treatment: - L-thyroxine - Follow up: - T4, TSH 2-3 monthly then 6 monthly - Bone age - Growth - Toxic effects overdose ## Thyrotoxicosis - Causes: - Thyroid: - Autoimmune (Graves/Hashimotos) - Toxic Nodule - McCune Albright syndrome - Mutation in TSH Receptor gene - Thyroiditis - Neonatal thyrotoxicosis - Pituitary: - Adenoma - Pituitary Resistance to Thyroxine - Exogenous Thyroxine - Clinical features: - Hyperthyroidism is less common in children than adults and can present with nonspecific symptoms. - Goiter - Toxic symptoms &signs/sympathetic - Anxiety, restlessness - Increased appetite, Weight loss - Sweating - Diarrhoea - Rapid growth in height - Advanced bone maturity - Tremorr - Tachycardia, wide pulse pressure - Warm, vasodilated peripheries - Learning difficulties/ behavior problems - Ophthalmophathy (lid lag - lid retraction-exophthamous) - Dermopathy - Acropachy - Puberty issues - CNS & behavior (restlessness, irritable, psychosis) - Investigations: - Free T4, TSH,T3 - US - Antibodies (TPO, immunoglobulin) - Scan if US shows a nodule - Rarely molecular genetics for TSH receptor mutation (diffuse gland with negative antibodies) - Treatment: - Using antithyroid drugs rather than radioiodine or surgery (subtotal thyroidectomy) although radioiodine is gaining acceptance as initial treatment in children older than 10 yr of age (cheap and safe). - Medical drugs : - No more PTU - NMZ