Hyperthyroidism Year 4 Paediatrics Notes OmpathStudy

Hyperthyroidism Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / ENDOCRINOLOGY -- Slide 1 Hyperthyroidism Dr Rose Munge Slide 2 Hyperthyroidism specifically refers to the synthesis and secretion of excess thyroid hormone from the thyroid gland Thyrotoxicosis refers to any state of excess circulating thyroid hormone (and its clinical manifestations) regardless of its source.\n This distinction is physiologically and clinically relevant because different therapies may be indicated depending on the mechanism of thyroid hormone excess. Slide 3 Graves disease is the most common cause of hyperthyroidism in children Graves disease is an autoimmune disorder that results in the production of thyrotropin (TSH) receptor–stimulating antibodies (TRSAbs) that bind and activate the G protein–coupled TSH receptor (TSHR ) to cause increased thyroid hormonogenesis and diffuse glandular growth.\nAetiologies of nonautoimmune hyperthyroidism include hyperfunctioning thyroid nodules and germline gain-of-function mutations in the TSHR (either autosomal dominant or sporadic).\nHyperthyroidism can also occur in patients with McCune-Albright syndrome. Rare causes of hyperthyroidism include iodine-induced hyperthyroidism, TSH secreting adenomas, toxic multinodular goiters, and hyperfunctioning thyroid carcinoma.\nThyrotoxicosis not due to hyperthyroidism can be caused by thyroiditis or ingestion of exogenous thyroid hormone (thyrotoxicosis factitia). Slide 4 Laboratory evaluation of primary hyperthyroidism reveals suppression of serum TSH and elevation of serum total thyroxine (T4 ) and total triiodothyronine (T3 ) levels.\nHyperthyroidism caused by inappropriate TSH secretion is usually due to a dominant-negative mutation in thyroid hormone receptor-β (THRB) resulting in resistance to thyroid hormone (RTH).\nTSH secreting pituitary tumors are extremely rare in the pediatric population.\nIn infants born to mothers with Graves disease, hyperthyroidism is transitory and resolves when TRSBAb are cleared from the neonate's circulation. Choriocarcinoma, hydatidiform mole, struma ovarii, and functional thyroid cancer can cause hyperthyroidism in adults but are rarely diagnosed in children. Slide 5 Graves Disease Graves disease occurs in approximately 0.02% of children (1: 5,000) and is the most common cause of pediatric hyperthyroidism.\nOnly 5% of all patients with hyperthyroidism are younger than 15 yr of age. Graves disease has a peak incidence in the 11-15 yr old age group, and there is a 5: 1 female:male ratio. Many children with Graves disease have a family history of autoimmune thyroid disease.\nAlthough rare, Graves disease has been reported between 6 wk and 2 yr of age in children born to mothers without a history of hyperthyroidism. Slide 6 Aetiology Enlargement of the thymus, splenomegaly, lymphadenopathy, peripheral lymphocytosis, and infiltration of the thyroid gland and retro-orbital tissues with lymphocytes and plasma cells are well-established findings in Graves disease.\nIn the thyroid gland, T-helper cells (CD4+ ) predominate in dense lymphoid aggregates; in areas of lower cell density, cytotoxic T cells (CD8+ ) predominate. The percentage of activated B lymphocytes infiltrating the thyroid is higher than in peripheral blood.\nA postulated failure of T suppressor cells allows expression of T helper cells sensitized to the TSH antigen to interact with B cells.\nThese cells differentiate into plasma cells that produce TRSAbs. Slide 7 TRSAbs bind to the TSHR and stimulate production of cyclic adenosine monophosphate (cAMP), resulting in thyroid hyperplasia and unregulated thyroid hormone synthesis.\nIn some patients with Graves disease, TSH receptor–blocking antibodies (TRBAbs) are produced that bind to but do not activate the TSHR.\nThe clinical course of the disease correlates to the ratio between stimulating and blocking antibodies. Slide 8 The ophthalmopathy that occurs in Graves disease appears to be caused by antibodies against antigens shared by both the thyroid and retro-orbital tissue. TSHR have been identified in retro-orbital adipocytes and might represent a target for antibodies.\nTRSAbs bind to the extraocular muscles and orbital fibroblasts and stimulate the synthesis of glycosaminoglycans and cytokines. Although 50–75% of children with Graves disease have some eye finding, the symptoms are much milder than in adults. Slide 9 Graves disease is associated with human leukocyte antigen (HLA)- B8 and HLA-DR3; the latter carries a 7-fold relative risk for Graves disease. Graves disease is also associated with other HLA-D3–related disorders, such as Addison disease, type 1 diabetes mellitus, myasthenia gravis, and celiac disease. Systemic lupus erythematosus, rheumatoid arthritis, vitiligo, idiopathic thrombocytopenic purpura, and pernicious anemia have also been described in children with Graves disease.\nIn family clusters, the condition associated most commonly with Graves disease