Board Review 3/7/2013

1. Board Review 3/7/2013 ADOLESCENT (part 1): Adolescent Development

2. Test Question Who remembered that daylight savings is this weekend?? • I did! • Nooooooooo!!!

3. Pubertal Development:Physical changes

4. Puberty • Developmental stage characterized by: • Maturation of gametogenesis • Secretion of gonadal hormones • Development of secondary sexual characteristics and reproductive functions • Pediatricians are constantly faced with questions about what is “normal” during puberty Changes in GnRH secretion (increased pulsatility) result in puberty

5. Normal Puberty • Age of onset: • Girls: 8-13 years • Thelarche can occur at age 7 in African-American and Mexican American girls • Boys: 9-14 years • Sexual Maturity Rating (SMR) • Used to document a child’s development through puberty • Consists of inspection of breast, genital, and pubic hair development • Limitation: does not have specific measurements

6. Stages of sexual development • Stage 1: prepubertal • Stage 2: girls: thelarche boys: testicular enlargement (≥4mL) • Stage 3: ongoing • Stage 4: nearly complete • Stage 5: adultlike • Pubertal progression from stage 2 to stage 5 can take between 2.5-5 years to complete

8. Question #1 Which is the correct sequence of pubertal events in a female? • Menarche  thelarche  peak height velocity  pubarche • Thelarche  pubarche  peak height velocity  menarche • Pubarche  thelarche  menarche  peak height velocity • Thelarche  pubarche menarche  peak height velocity

9. Predictable Progression of Puberty • Males: • Testicular growth  pubarche  penile growth  peak height velocity • Testicular volume < 4mL (2.5cm) is prepubertal • Reach SMR4 prior to attainment of peak height velocity • Females: • Thelarche pubarche  peak height velocity  menarche • Peak height velocity is typically 1 year before menarche • Girls height will typically increase ~6-8cm after menarche has occurred

10. Question #2 A mother brings in her 13 year old son at his request due to his concerns about breast tissue. He has noticed he has a small amount of breast tissue and wants to know if it can be removed. He is otherwise developing appropriately and does well in school. On exam, he is SMR3 for genital growth and pubic hair. You also notice a small amount of breast tissue bilaterally under his nipples. What is the most appropriate course of action? • Refer the patient to a plastic surgeon • Refer the patient to an endocrinologist for hormone therapy • Order a brain MRI to rule out malignancy • Reassure the patient that this is a normal part of puberty and follow up in 6 months • Order FSH and LH levels

11. Normal variations in pubertal development • Asymmetric breast or testicular development • Can see up to 1 stage advance of unilateral development at onset of puberty • Gynecomastia • 50% of boys will have some degree of breast tissue during puberty • Typically during pubic hair stage 3 or 4 • Gynecomastiawithout onset of puberty is concerning • Lasts less than 1 year • Can just be observed for resolution

12. Linear growth • Peak height velocity in girls occurs earlier chronologically and in pubertal staging than in boys • Boys growth spurt is typically 2 years after girls • Peak height velocity is more closely correlated with SMR than chronologic age

13. Linear Growth • Average prepubertal height velocity • 5-6cm/yr • Average pubertal height velocity: • Boys = 9-10cm/yr • Girls = 8-9cm/yr • Completion of this growth spurt takes 2-4 years • Longer period of prepubertal growth and greater pubertal height velocity account for the typical height discrepancy between males and females • Longitudinal growth chart is much more useful in determining abnormality of growth versus a single point in time

14. Question #3 A boy comes in with his parents for his 12 year old well-child check and wants to know how tall he is going to be. His mother reports that he has been growing but that he is shorter than most of his peers. His mother is 160 cm (63 in) tall and his father is 172 cm (68 in) tall. With the exception of his relative short stature, his medical history is unremarkable. You advise him that the best way to estimate his potential for growth is to calculate his midparental target height and compare it to his current height and his skeletal maturity. Of the following, what is the BEST estimate of his midparental target height? • 160 cm (63in) • 165.5cm (65in) • 172.5cm (68in) • 177.5cm (70in) • 182.5cm (72in)

15. Predicting height • Height is largely determined genetically • Target height can be crudely estimated: • Average of parents heights in cm • +6.5cm for boys • -6.5cm for girls • Bone age can also be used predict height • Best performed by an endocrinologist • Keep in mind a bone age can be off from chronologic age by as much as 2 years and still be normal (ie constitutional growth delay)

16. Timing of puberty: effect on height • There is a genetic influence on the timing of puberty • ?autosomal dominant • Earlier puberty: will have tall stature during puberty compared to peers • Will complete their growth prematurely and have a lower peak adult height than expected • Rapid fusion of their growth plates • Later puberty: short stature in youth but an adult height that is slightly above expectations • Slow but constant prepubertal growth of long bones without rapid maturation of the growth plate • Timing of puberty affects both linear growth rate and skeletal maturity

17. Question #4 A mother brings in her 9 year old daughter because she saw some blood in her underwear and is concerned that her daughter has started her period. Menarche for mom was achieved at age 11. On exam, the girl is well appearing with no dysmorphic features or rash. She has SMR stage 1 breast development and no pubic hair development. Of the following, which is MOST likely going to elicit a cause for her vaginal bleeding? • Obtaining a bone age radiograph • Plotting the child’s height and weight on a growth chart • Obtaining serum LH and FSH levels • Obtaining a serum estradiol concentration • Examination of the genetalia for a foreign body

18. Menarche • Genetic influence on age of menarche • Typically occurs at SMR 4 breast development • Vaginal bleeding at SMR 1-2 is not likely to represent menarche or be hormonally mediated • Average age of menarche: 12.6 yrs • Range: 11-14 yrs • Average time of menarche after thelarche: 2 yrs • Range 0.5 – 5 yrs • No menarche by age 16 warrants investigation

19. Menarche • Physiologic leukorrhea precedes menses by 3-6 months • Immature hypothalamic-pituitary-gonadal axis at the beginning of menstruation • 50% of menstrual cycles are anovulatory in first 2 years after menarche • Can cause menstrual irregularity that is normal

20. Question #5 A 15 yo boy comes to the ER because of crampy abdominal pain, diarrhea, and body aches. His siblings also have diarrhea. Exam reveals no icterus or organomegaly, although he has increased bowel sounds and mild diffuse abdominal tenderness. His genetalia are at SMR4. Amount the results of his lab tests are the following: Total bilirubin: 0.6mg/dL ALT: 18U/L Alkaline phosphatase: 460IU/L AST: 22U/L Of the following, what is the MOST likely explanation for these lab results? • Physiologic growth spurt • Bone malignancy • Infectious hepatitis • Inflammatory bowel disease • Viral gastroenteritis

21. Effects of puberty on other body systems • Hematocrit increases in males when the growth spurt beings • After puberty, males normal Hgb= 14-18g/dL • Females remain lower: 12-15g/dL • Alkaline phosphatase can increased during a growth spurt • Result of rapid bone growth (high osteoblastic activity) • Can be up to 500IU/L • Cholesterol concentrations peak in early puberty • Blood pressure gradually increases • Based on height, sex, age • <95% requires evaluation

22. Puberty and Sleep • Sleep: 50% decrease in intensity of deep sleep • Difficulty initiating and maintaining sleep • Environmental factors play a role as well • Television, computer, texting in bedroom • Require 9-9.5 hrs of sleep per night

23. Disorders of Puberty: Precocious Pubery

24. Precocious Puberty • Girls: • Thelarche or pubarche before 8yrs • Thelarche before 7 years for African-American or Mexican- American • Boys: • Pubarche or genital development before 9yrs • Clinically significant precocious puberty is suggested if puberty advances rapidly or if it is accompanied by a growth spurt

25. Precocious Puberty • Most sexual precocity is not serious and does not need to be treated • Precocity in the 6-8 year range • Usually not rapidly progressive • May not require treatment • May be due to obesity • Idiopathic premature thelarche • Unilateral or bilateral • NO pubic hair; NO growth spurt • Caused by early activation of the hypothalamic-pituitary-ovarian axis (FSH secretion) • Exogenous estrogen source should be considered

26. Question#6 You are examining at 6 year old boy during a health supervision visit. Exam reveals SMR 3 pubic hair. Of the following, what is the MOST important initial step to guide your management? • Investigate possible exposure to androgens • Inquire about the age of puberty in family members • Order an FSH and LH • Order a testosterone level • Examine the boy’s testicular size

27. Precocious Puberty • Idiopathic premature pubarche • Slowly progressive pubic or axillary hair development • NO breast or testicular enlargement • Can be idiopathic (hypersensitivity of hair follicles to circulating androgens) or due to premature adrenarche or anabolic steroid exposure • Premature adrenarche: elevated DHEAS • Occasionally precursor for PCOS or evidence of virilizing disorder

28. Precocious Puberty • Premature thelarche or pubarche could be first sign of progressive true sexual precocity • Must monitor pubertal development, height velocity, bone age • If rapidly progressive, associated with a growth spurt, or significantly increased bone age  more concerning • Complete precocious puberty: • Early activation of the HPG axis • 5 times more common in girls • 90% of cases are idiopathic • In boys, only 50% are idiopathic – more often have organic cause • CNS disorders , testicular tumors, adrenal hyperplasia/tumor • Examining testicles can lead the evaluation: if large – they are likely the source of androgen

29. Precocious Puberty: red flags • Rapidly progressive precocity: • Especially before age 6 years • Always requires investigation • Intrinsic adrenal or gonadal disorders • CAH, McCune-Albright, testotoxicosis, neoplasms • Exogenous hormones • Precocious puberty  risk for premature epiphyseal fusion • Short adult stature despite tall stature in childhood

30. Question #7 A 7 year old girl is being treated for precocious puberty by an endocrinologist. On exam she is at SMR 3. Her parents are pleased with her medical treatment but are concerned because she does not fit in with her 7-year-old peers that she used to play with and seems withdrawn around them. She is now gravitating towards playing with older children in the neighborhood. The parents ask for advice regarding her behavior. What is the BEST response to their concerns: • Explain that having older friends is beneficial to her self-esteem, has no risks, and should be encouraged • Explain that their daughter should be treated more maturely because her body is maturing faster • Recommend counseling to help the girl deal with changes in her body and to help her learn positive social interactions with her peers • Suggest the parents call her peers and scold them for teasing her • Suggest the parents buy her a pet to keep her happy

31. Precocious Puberty: psychosocial risks • Girls: emotional problems, low self-image, higher rate of depression, anxiety, disordered eating • Shy, withdrawn with same-age peers • Prefer to be with older individuals • Risks of premature sexual activity, drug use, etc • Parents should encourage positive self-image, social interactions with same-age peers, may need counseling • Boys: higher risk for antisocial/aggressive behaviors, precocious sexual activity; but high self-esteem

32. Sex steroid excess • Hirsutism – excessive hair development in a female • Normal variant when mild and isolated • When accompanied by menstrual abnormality or when severe consider hyperandrogenism • PCOS accounts for 85% of cases • Gynecomastia • Transient gynecomastia is normal during puberty • Breast development in a boy BEFORE puberty is abnormal • Must rule out feminizing disorder: ie. neoplasm • Degree of gynecomastia matters • Mid-adolescent degree of breast tissue can persist (SMR 3-4) • Can indicate estrogen excess, androgen deficiency, or liver dysfunction

33. Disorders of Puberty: Delayed Puberty

34. Delayed Puberty • Definition: • Girls: lack of breast development by age 13 • Boys: lack of testicular development by age 14 • Prepubertal testicular volume is < 4mL • Prepubertal penile length is < 7cm • Typically accompanied by slowed growth velocity and short stature • Pubic/axillary hair and body odor are due to increases in adrenal androgens (not the HPG axis) • So can still have pubertal delay with the presence of pubic hair

35. Question #8 A 13 yo boy presents for his annual well child visit. His father is concerned about his son’s stature and pubertal development. The boy is doing well in school, plays soccer competitively, and is not concerned about his growth or development. The boy’s father did not start shaving until he was a senior in high school and recalls that he continued to get taller during his first 2 years of college. On exam, you note SMR 2 pubic hair and testicles 3 cm in length. The remainder of his exam is normal. A bone age radiograph demonstrates skeletal maturity of 11 years. What is the MOST likely diagnosis? • Klinefelter syndrome • Constitutional growth delay • Primary gonadal failure • Isolated gonadotropin deficiency • Anorexia nervosa

36. Delayed Puberty • Most delayed puberty is NOT serious • Majority is constitutional delay of pubertal growth and development (CDP) • Especially in BOYS • Boys : 63% of those with delayed puberty • Girls :30% • Strong genetic component • Mother with menarche at <14yrs old • Father with growth spurt at 15-16 yrs

37. ConstitutionalGrowth Delay • Variation of normal growth • Normal or near normal growth rate during prepubertal years • Then reduced tempo of development • Height and weight both cross percentiles • Caused by a delay in the onset of HPG activation  delayed puberty • Once puberty begins, its course and tempo are normal • Bone age is delayed • Catch-up growth to target height occurs (might be slightly lower than MPH)

39. Question #9 A 15yo girl presents for her annual health supervision visit. She has no complaints, and her review of systems is negative. Her mother is concerned that her daughter has not yet had menarche. The girl’s height is at the 5th percentile and her weight is at the 25th percentile. On physical examination, she has SMR stage 1 breast development and SMR stage 3 pubic hair. Examination of the external genitalia reveals a patent vagina and pink mucosa. Of the following, the BEST next step in evaluation of this patient is to: • Measure serum estradiol • Obtain a karyotype • Obtain a pelvic ultrasound • Reassure the family and see them again in 1 year • Obtain more information about the mother’s age of menarche

40. Delayed Puberty: other causes • Primary hypogonadism (gonadal failure) • “Hypergonadotropichypogonadism” • Elevated gonadotropins • Particularly FSH • Secondary or teritiatryhypogonadism • Hypogonadotropichypogonadism • Low gonadotropins (FSH, LH) • Or “normal” but inappropriately low for patient age • Use a bone age to determine if patient has prepubertal or pubertal bone age • Helps determine if FSH, LH levels are appropriate for that bone age

41. Primary Hypogonadism • Girls: • Turner syndrome (gonadaldysgenesis) • Can present for the first time as pubertal delay • Ovarian damage • radiation, chemo, autoimmune • Boys: • Klinefelter syndrome • Small testes with normal pubic hair/penile length • Testicular damage • radiation, torsion, mumps

42. Question #10 You are following a 14 year old boy who has prepubertal testicular volume and penile length. All of the following would distinguish an isolated gonadotropin deficiency from constitutional growth delay, EXCEPT • Pubertal development that has not started by age 17 • Penile length ≤ 5cm • Small or difficult to palpate testicles • Delayed bone age • Anosmia

43. Hypogonadotropichypogonadism • Isolated gonadotropin deficiency • Complete or partial deficiency of GnRH • Leads to decreased or absent secretion of LH and FSH • Can resemble CDP except: • Puberty does not start by age 17 • May have micropenis(≤ 5cm) • Testes are small and difficult to palpate • Kallman syndrome (anosmia) • Relatively rare in both males and females

44. Hypogonadotropichypogonadism • Functional gonadotropin deficiency • More common in females • Unusually thin • Under-nutrition: • Anorexia, chronic illness, excessive exercise • Mechanism: Excessive exercise: decreased body fat  decreased leptin concentration  reversible gonadotropin deficiency • Also at risk for low bone mass due to chronic low estrogen • In males: more often due to chronic illness

45. Hypogonadotropichypogonadism • Functional gonadotropin deficiency • Chronic illnesses: sickle cell, celiac, JIA, CF, Chron’s, CRF, severe asthma • Other causes: • Hypothyroidism • Panhypopituitarism • Midline defects, trauma, tumor

46. Delayed puberty red flags • Absence of any signs of puberty after the age of 13 years in girls or 14 years in boys merits investigation • Premature arrest of previously normal growth rate in an adolescent demands thorough evaluation

47. Diagnostic evaluation • Bone age • Typically delayed 2 years in CDP • Can help predict adult height • LH and FSH • Elevated in primary hypogonadism • Girls  order karyotype • If not elevated, consider CDP or gonadotropin deficiency • Can measure after GnRH stimulation • Total testosterone (boys) • Delayed puberty <40ng/dL • Puberty underway >50ng/dL • Estradiol (girls) • Other: thyroid studies, IGF-1, head imaging • Referral to endocrinologist

48. Question #11 Parents of a 15yo boy diagnosed with constitutional growth delay are concerned that their son is being bullied by his 10th grade classmates. His grades have declined from As to Bs, and he says he dislikes school. He is in good health; he exercises and eats in moderation. On exam his height and weight are at the 10th percentile, and his genitalia are SMR 1. When you speak to him in private he becomes tearful and explains that he is afraid to change for gym and that his friends wonttalk to him. He and his parents ask for advice. Of the following, the BEST response is to: • Offer reassurance and arrange for 6 month follow up • Recommend caloric supplements • Refer the family for behavioral counseling • Refer the boy for a psychoeducational evaluation • Refer the boy to an endocrinologist for re-evaluation and possible hormonal therapy

49. Delayed Puberty: psychosocial risks • Boys: concern about being short and underdeveloped • Report teasing, low self-esteem • May drop out of sports • Occasionally see declining academic performance and school avoidance • Girls: fewer concerns than boys • Report feeling “different” • Some report feeling the delay affected their success at school, work, or socially • But typically not a problem

50. Delayed puberty: Management • Referral to endocrinologist • CDP: Short physiologic courses of androgen replacement therapy may help the self-image of delayed boys • Injections preferred • Brief therapy (4-5 months), then stop • Re-assess linear growth, testicular size • For girls: oral estrogens for 4-6 months • Permanent hypogonadism • Boys: testosterone injections/patch/gel • Girls: estrogens (oral/patch)