Thyroid Disorders. Hypothyroidism. Low Total T4 Antiseizure meds Glucocorticoids. Free T4. Howard J. Sachs, MD.

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1 Thyroid Disorders Free T4 Low Total T4 Antiseizure meds Glucocorticoids Hypothyroidism Howard J. Sachs, MD

2 Primary Hypothyroidism High TSH Low free T4 Primary = End organ failure Autoimmune Thyroiditis Hashimoto s Lymphocytic Thyroidectomy T4 = F

3 Primary Hypothyroidism High TSH Low free T4 TSH TSH: Come on! Make hormone! Autoimmune Thyroiditis Hashimoto s Lymphocytic Thyroidectomy T4 = F

4 Primary Hypothyroidism TSH High TSH Low free T4 Autoimmune Thyroiditis: Hashimoto s Neonatal Germinal Center Anti: TPO TGB T4 = F

5 Primary Hypothyroidism High TSH Low T4 TSH = F Secondary Hypothyroidism Low TSH Low T4 Autoimmune Thyroiditis Hashimoto s Lymphocytic Thyroidectomy Pituitary Failure Ischemic Necrosis (Sheehan s Syndrome) Panhypopituitarism (especially failure to lactate) T4 = F TRH TSH = F

6 The Language of Hypothyroidism Basal Metabolic Rate Matrix b-adrenoreceptor Cold intolerance Weight Gain Hyporeflexia Constipation Fatigue Hypertension Metrorrhagia Myxedema Macroglossia Dry Skin Brittle Hair Bradycardia T3 and mucopolysaccharides: Inhibits synthesis Increases degradation

7 The Language of Hypothyroidism Basal Metabolic Rate Matrix b-adrenoreceptor Cold intolerance Weight Gain Hyporeflexia Constipation Fatigue Hypertension Metrorrhagia Myxedema Macroglossia Dry Skin Brittle Hair Bradycardia Myxedema Coma Hypothermia, hypotension, hyponatremia, hypoglycemia ADH

8 Autoimmune (Hashimoto s) Thyroiditis Background Autoimmune disorder with progressive destruction of the gland Pathogenesis Breakdown in self tolerance to thyroid autoantigens The inciting events have not been elucidated Pathology Depletion of epithelial cells with follicular atrophy and fibrosis Intense lymphocytic/mononuclear infiltration with well formed germinal centers

9 Autoimmune (Hashimoto s) Thyroiditis Background Autoimmune disorder with progressive destruction of the gland Pathogenesis Breakdown in self tolerance to thyroid autoantigens The inciting events have not been elucidated Pathology Depletion of epithelial cells with follicular atrophy and fibrosis Intense lymphocytic/mononuclear infiltration with well formed germinal centers Germinal Center Atrophy/Fibrosis

10 Germinal Centers may also be seen in Graves disease and Lymphocytic Thyroiditis.

11 Hurthle cells: Represent a metaplastic response to ongoing injury of the thyroid epithelium. Description: epithelial cells with abundant eosinophilic cytoplasm. Seen also in follicular adenoma/neoplasm

12 Autoimmune (Hashimoto s) Thyroiditis Clinical Diffuse, nontender glandular enlargement Signs and symptoms of hypothyroidism May present with initial hyperthyroid phase: hashitoxicosis Diagnostics Elevated TSH, low free T4 Antibodies: TPO, TGB, Microsomal Imaging: F Notes Rx: Replacement therapy T4; long ½ life v T3 Associated with other autoimmune syndromes/polyglandular syndromes (endo: DM1, adrenalitis; non-endo: SLE, myasthenia) Increased risk of thyroid lymphoma

13 Autoimmune (Hashimoto s) Thyroiditis Clinical Diffuse, nontender glandular enlargement May present with initial hyperthyroid phase (hashitoxicosis) en route to glandular destruction (as do other thyroiditis) Diagnostics Antibodies: TGB, TPO, Microsomal Elevated TSH, low T4 Imaging: F Notes Increased risk of thyroid lymphoma Rx: Replacement therapy T4, long ½ life v T3 Associated with other autoimmune syndromes/polyglandular syndromes (endo: DM1, adrenalitis; non-endo: SLE, myasthenia)

14 Cretinism (neonatal hypothyroidism due to maternal hypothyroidism) Background Hallmark is impaired development of skeletal system and CNS Seen in iodine deficient regions of the globe Pathogenesis T3/T4 normally cross the placenta AND is required for normal fetal brain development. After week 12, the fetus synthesizes their own T4 If there is maternal deficiency, before development of fetal thyroid gland, mental retardation will develop. Clinical MSK: course facial features, short stature, umbilical hernia CNS: mental retardation, protruding tongue Notes If the mother develops hypothyroidism later in the pregnancy, after the fetal thyroid has become functional, there is NO affect on normal brain development.

15 Cretinism (neonatal hypothyroidism due to maternal hypothyroidism) Background Hallmark is impaired development of skeletal system and CNS Seen in Iodine deficient regions of the globe Pathogenesis T3/T4 normally cross the placenta AND is needed for normal fetal brain development. After week 12, the fetus synthesizes their own T4 If there is maternal deficiency, before development of fetal thyroid gland, mental retardation will develop. Clinical MSK: course facial features, short stature, umbilical hernia CNS: mental retardation, protruding tongue Notes If the mother develops hypothyroidism later in the pregnancy, after the fetal thyroid has become functional, there is NO affect on brain development.

16 Thyroid Disorders Hypothyroidism

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