A 7-year-old boy is brought to the office for severe facial acne that has developed over the past few months. His mother tried treating it with topical benzoyl peroxide and a salicylic acid face wash with no improvement. She also noticed a significant increase in her son's growth, and he is now much taller than his fraternal twin brother. The patient is otherwise healthy with no chronic medical conditions and takes no medications. Height is at the 98th percentile and weight is at the 85th percentile for age and sex. Neurologic examination is normal. Skin examination shows severe cystic acne involving the face and shoulders. Examination reveals coarse pubic and axillary hair. Testicular volume is 2 mL. Bone age is 2 standard deviations higher than chronological age. Baseline LH levels are low and do not increase after stimulation with a GnRH agonist. Which of the following is the most likely diagnosis in this patient?

Question

A 7-year-old boy is brought to the office for severe facial acne that has developed over the past few months.  His mother tried treating it with topical benzoyl peroxide and a salicylic acid face wash with no improvement.  She also noticed a significant increase in her son's growth, and he is now much taller than his fraternal twin brother.  The patient is otherwise healthy with no chronic medical conditions and takes no medications.  Height is at the 98th percentile and weight is at the 85th percentile for age and sex.  Neurologic examination is normal.  Skin examination shows severe cystic acne involving the face and shoulders.  Examination reveals coarse pubic and axillary hair.  Testicular volume is 2 mL.  Bone age is 2 standard deviations higher than chronological age.  Baseline LH levels are low and do not increase after stimulation with a GnRH agonist.  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d65a_bb0c_bc81_ddef1461b0af_MD0003_00 Precocious puberty is the onset of secondary sexual characteristics (eg, pubic/axillary hair, cystic acne, accelerated growth) in girls age <8 and boys age <9. Patients with precocious puberty are initially assessed by obtaining a bone age, which differentiates true precocious puberty (advanced bone age) from an isolated premature thelarche/adrenarche (normal bone age). In patients with advanced bone age (>2 standard deviations above chronological age), LH levels differentiate between peripheral and central precocious puberty. Patients with peripheral (gonadotropin-independent) precocious puberty have a low/normal LH level due to inhibition of the hypothalamus by high circulating androgen levels from the adrenal glands or testes. This patient's early onset of secondary sexual characteristics, advanced bone age, and low LH level are suggestive of peripheral precocious puberty, likely nonclassic congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase (CYP21A2) deficiency. Similar to classic CAH, the 21-hydroxylase deficiency impairs the conversion of 17-hydroxyprogesterone to 11-deoxycortisol; 17-hydroxyprogesterone is shunted toward adrenal androgen overproduction (ie, precocious puberty). However, in patients with nonclassic CAH, sufficient glucocorticoid and mineralocorticoid levels are maintained; therefore, patients have normal electrolytes (no salt wasting). 21-hydroxylase (CYP21A2) deficiency (Choice A) Severe, untreated primary hypothyroidism can cause gonadotropin-dependent precocious puberty; however, boys typically have premature testicular enlargement and short stature, not accelerated linear growth. (Choices B and F) Idiopathic precocious puberty (premature activation of the hypothalamic-pituitary-gonadal axis) and pituitary microadenomas cause gonadotropin-dependent (central) precocious puberty. Due to continuous activation of the hypothalamus, patients with central precocious puberty have either a high basal LH or an LH level that increases with GnRH stimulation. (Choice C) Klinefelter syndrome (47,XXY) causes primary hypogonadism, which is characterized by low testosterone and elevated LH levels. Patients have a tall stature; however, puberty is typically delayed. (Choice D) McCune-Albright syndrome is a rare cause of gonadotropin-independent precocious puberty that presents with irregular café-au-lait macules and fibrous dysplasia of bone, which are not seen in this patient. Educational objective: Nonclassic congenital adrenal hyperplasia is a cause of gonadotropin-independent precocious puberty. Patients can have premature secondary sexual characteristics (eg, pubic hair, cystic acne), accelerated growth and bone age, and low/normal LH levels. References: Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome. (http://www.ncbi.nlm.nih.gov/pubmed/26082286) Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene. (http://www.ncbi.nlm.nih.gov/pubmed/27180336)

A 7-Year-Old Boy Is Brought to the Office for Severe