A 13-year-old boy is evaluated for abnormal growth. His mother says that he has grown rapidly over the past 10 months and is much taller than his older brother and other children his age. During this time, she has had a hard time finding clothes that fit him and has had to buy new shoes for him each month due to increasing foot size. The patient says that he feels well except for excessive sweating. He has no history of major medical illness and takes no medications. Both parents are of average height and have normally proportioned limbs. The patient is above the 99th percentile for height and at the 90th percentile for weight. On physical examination, he has long extremities with large hands and feet; the lower jaw is protruding. Heart sounds are normal. Sexual development is Tanner stage 4. Which of the following is the most likely underlying cause of this patient's condition?

Question

A 13-year-old boy is evaluated for abnormal growth.  His mother says that he has grown rapidly over the past 10 months and is much taller than his older brother and other children his age.  During this time, she has had a hard time finding clothes that fit him and has had to buy new shoes for him each month due to increasing foot size.  The patient says that he feels well except for excessive sweating.  He has no history of major medical illness and takes no medications.  Both parents are of average height and have normally proportioned limbs.  The patient is above the 99th percentile for height and at the 90th percentile for weight.  On physical examination, he has long extremities with large hands and feet; the lower jaw is protruding.  Heart sounds are normal.  Sexual development is Tanner stage 4.  Which of the following is the most likely underlying cause of this patient's condition?

Quizplus · Accepted Answer

11ec160b_3aad_4da1_9249_dd7f2c87c7f5_MD0001_00 This patient most likely has gigantism, a condition caused by hypersecretion of growth hormone (GH) during childhood. GH is a peptide hormone secreted by the anterior pituitary that acts as both a growth promoter and stress hormone (increasing glucose and free fatty acid levels). Although GH has direct effects on target tissue (eg, chondrogenesis, myocyte protein synthesis), its growth-promoting effects are primarily mediated by insulin-like growth factor-1 (IGF-1), which is released from the liver following stimulation of hepatic GH receptors. IGF-1 binds to a specific receptor tyrosine kinase and stimulates cell growth and proliferation in bone, cartilage, skeletal muscle, and other soft tissues. Gigantism occurs in children and adolescents before fusion of the epiphyseal growth plates, resulting in rapid linear growth along with large hands and feet, thickening of the calvarium, protrusion of the jaw (prognathism), excessive sweating, and oily skin. The adult variant, acromegaly, has no effect on stature because the epiphyseal growth plates have already fused. (Choices A and B) Klinefelter syndrome is caused by a nondisjunction of sex chromosomes (47,XXY). Patients are phenotypically male with hypogonadism and infertility. Marfan syndrome is caused by a defect in fibrillin-1 and presents with joint hypermobility, increased limb length, and arachnodactyly. These disorders are associated with tall stature but do not exhibit prognathism or bony enlargement of the hands and feet. (Choice C) Defects in the GH receptor cause Laron dwarfism, characterized by decreased linear growth, high serum GH concentrations, and low levels of circulating IGF-1. (Choice E) Excessive thyroxine production (ie, hyperthyroidism) presents with weight loss, heat intolerance, and tremor. Sweating is common, but hyperthyroidism in children causes short stature, not accelerated growth. (Choice F) Circulating levels of IGF-1 are produced primarily in the liver. Although IGF-1 is also produced locally in the hypothalamus to regulate central nervous system activity, this source does not contribute significantly to bone and soft-tissue growth. (Choice G) Increased pituitary gonadotropin release causes central precocious puberty. This patient has appropriate sexual development for age. Educational objective: Gigantism is caused by excess growth hormone (GH) during childhood and is characterized by accelerated linear growth, prognathism, and bony enlargement of the hands and feet. GH excess after closure of the epiphysial growth plates causes acromegaly. GH has direct effects on target tissues and indirect effects mediated by insulin-like growth factor-1 secretion from the liver. __________ References: Pituitary gigantism: causes and clinical characteristics. (http://www.ncbi.nlm.nih.gov/pubmed/26585365)

A 13-Year-Old Boy Is Evaluated for Abnormal Growth