A 7-year-old boy is brought to the clinic for a well-child visit. Over the past year, the patient has become fidgety, impulsive, inattentive, and restless, leading to a progressive decline in his grades. Height and weight are at the 50th and 5th percentiles for his age, respectively. The patient takes no medications or supplements. The thyroid gland is diffusely enlarged to palpation without tenderness or bruit. Neurologic examination reveals no focal findings. Results of thyroid function tests are as follows: Which of the following is the most likely etiology of this patient's thyroid function test abnormalities?

Question

A 7-year-old boy is brought to the clinic for a well-child visit.  Over the past year, the patient has become fidgety, impulsive, inattentive, and restless, leading to a progressive decline in his grades.  Height and weight are at the 50th and 5th percentiles for his age, respectively.  The patient takes no medications or supplements.  The thyroid gland is diffusely enlarged to palpation without tenderness or bruit.  Neurologic examination reveals no focal findings.  Results of thyroid function tests are as follows:  Which of the following is the most likely etiology of this patient's thyroid function test abnormalities?

Quizplus · Accepted Answer

11ec160b_3cad_6340_9249_fb78dea4a6f4_MD0001_00 This patient's increased levels of thyroxine (T4), triiodothyronine (T3), and TSH are concerning for thyroid hormone resistance. Most cases are due to an inherited mutation affecting thyroid hormone receptor beta, which results in decreased thyroid hormone sensitivity in the hypothalamic-pituitary-thyroid axis and peripheral tissues. Increased levels of T3 and T4 normally provide negative feedback to the pituitary to decrease TSH production. However, because pituitary cells are also resistant to thyroid hormone in this condition, TSH rises, driving further production of T3 and T4. The presentation of thyroid hormone resistance varies greatly due to fluctuating thyroid hormone sensitivity in different target tissues; patients may be asymptomatic (ie, euthyroid) or develop hypothyroid or hyperthyroid symptoms (eg, low weight, as in this patient). The most common finding is goiter due to overstimulation of the thyroid gland by TSH. Attention deficit hyperactivity disorder (ADHD) and tachycardia are also common due to the preponderance of alpha thyroid hormone receptors (with normal sensitivity) in the CNS and heart. (Choice A) Chronic autoimmune (Hashimoto) thyroiditis leads to autoantibody-mediated thyroid gland destruction characterized by goiter and symptoms of hypothyroidism (eg, fatigue, constipation, dry skin). Low T3 and T4 production results in increased TSH. (Choice B) Thyroxine-binding globulin (TBG) binds thyroid hormones and maintains a constant pool of free T3 and T4. Increases in TBG (eg, pregnancy) result in a clinically euthyroid, asymptomatic state characterized by an increased total T3 and T4 but normal levels of free hormones and TSH. (Choice C) TSH receptor-stimulating antibodies in Graves disease cause increased T3 and T4 production with signs of hyperthyroidism, including goiter. In contrast to this patient, those with this condition have appropriate negative feedback to the pituitary, leading to low TSH levels. (Choice D) Defective thyroid hormone synthesis leads to overt hypothyroidism starting in infancy; symptoms include lethargy, hypotonia, and constipation. Laboratory evaluation shows low T3 and T4 and elevated TSH. Educational objective: Thyroid hormone resistance is characterized by decreased sensitivity of peripheral tissues to thyroid hormones due to a defect in the thyroid hormone receptor. Levels of thyroxine, triiodothyronine, and TSH are increased. Patients classically have goiter and frequently develop attention deficit hyperactivity disorder.

A 7-Year-Old Boy Is Brought to the Clinic for a Well-Child