PUBERTY Preetha Krishnamoorthy Division of Pediatric Endocrinology
Case 1 8-year-old girl referred for breast development noted by mom What do you want to know? Normal or abnormal? What if this was an 8-year-old boy with penile enlargement and pubic hair? Normal or abnormal?
Definitions: Precocious Puberty Girls: 2º sexual development < 7 y.o. in Caucasian girls, < 6 y.o. in African- American girls Boys: 2º sexual development < 9 y.o. regardless of ethnicity
2º Sexual Development Girls Breast development Growth acceleration Enlargement of labia Vaginal secretions Change in uterus Pubic/axillary hair Boys Testicular enlargement Penile size Pubic/axillary hair Growth acceleration Voice change
Case 1 8 y.o. girl with breast development Normal or abnormal?
Case 1 8 y.o. girl with breast development Normal or abnormal?
Case 1 8 y.o. girl with breast development Normal or abnormal? 8 y.o. boy with penile enlargement and pubic hair Normal or abnormal?
Case 1 8 y.o. girl with breast development Normal or abnormal? 8 y.o. boy with penile enlargement and pubic hair Normal or abnormal?
Case 2 2 y.o. girl who has had breast development What do you want to know? Associated features: growth acceleration, vaginal discharge or bleeding, pubic/axillary hair Access to exogenous estrogens?
Case 2 Physical exam Growth curve Tanner Stage and breast volume Vaginal mucosa
Variations in Pubertal Development Premature thelarche unilateral or bilateral usually < 3 y.o. no other signs of estrogenization (areolar development, vaginal discharge, growth), normal bone age may regress within months or remain Premature adrenarche early appearance of pubic or axillary hair without other signs of virilization or puberty usually > 6 y.o., more common in girls mildly elevated DHEAS, slightly advanced bone age
Case 3 5 y.o. girl with breast development What else? + growth acceleration + vaginal discharge Normal or abnormal?
Case 3 5 y.o. girl with breast development What else? + growth acceleration + vaginal discharge Normal or abnormal?
Puberty Hypothalamus LHRH Pituitary LH/FSH Gonads
Approach to Precocious Puberty CENTRAL activation of the hypothalamic pituitary axis tumour, hamartoma, optic glioma, cyst, radiation, infection idiopathic PERIPHERAL no activation of hypothalamicpituitary axis at the level of the gonads, adrenals, tumour, exogenous
Central vs. Peripheral Precocious Puberty Test to distinguish between the two: LHRH stimulation test If LH rises above ~7 IU/L Prepubertal pituitary is quiescent so LH levels should remain low despite exogenous LHRH
Case 3 5 y.o. girl with breast development LHRH stimulation test LH max 12 IU/L central next step? MRI treatment: LHRH agonist
Case 4 4 y.o. boy with pubic hair What else? + axillary hair + penile enlargement + growth spurt no testicular enlargement normal or abnormal?
Case 4 4 y.o. boy with pubic hair What else? + axillary hair + penile enlargement + growth spurt no testicular enlargement normal or abnormal?
Case 4 Central vs. peripheral? Testicular enlargement usually points to a central cause
Case 4 Central vs. peripheral? Testicular enlargement usually points to a central cause
Case 4 Central vs. peripheral? Testicular enlargement usually points to a central cause Peripheral gonads (testes) adrenals tumours exogenous
Case 4 Exceptions to the rule that testicular enlargement usually points to a central cause: testicular tumour (unilateral, large, asymmetric) testotoxicosis hcg or LH-secreting tumour
Case 4 No testicular enlargement: likely peripheral Measure adrenal androgens, testosterone If adrenal androgens high, consider CAH, adrenal tumour If testosterone high, consider testosterone producing tumour
21-OH deficiency Salt-wasting (75%) - present in first few weeks of life Boys normally virilized, present in crises Girls have ambiguous genitalia Non salt-wasting forms
21-OH deficiency Precocious puberty in boys and girls PCOS-like picture in older girls with menstrual irregularity, acne, hirsutism Fertility problems Cryptic CAH
Prenatal Rx of CAH Who? Previous child affected Parents known to be carriers Goals Prevention of genital ambiguity in a girl Lessen surgical intervention required
Prenatal Rx of CAH Start Rx as soon as pregnancy is diagnosed Mom is given dexamethasone 20 μg/kg Dx of fetus is made by CVS at 9-11 weeks or amniocentesis Rx is stopped if it is a boy or an unaffected girl
Prenatal Rx of CAH - PROS Prenatal diagnosis prevent crisis in a boy who may have otherwise been undiagnosed anticipatory guidance for parents May lessen degree of surgery needed Potential avoidance of surgery? Effect of high androgen levels on female brain
Prenatal Rx of CAH - CONS Unnecessary Rx of 7/8 Risks of CVS/amniocentesis Effects of high-dose steroids on mom Long-term effects of fetal treatment unknown
RECAP: Precocious Puberty Normal or abnormal? If precocious, is it one of the benign variants of normal? If not, is it central or peripheral? LHRH stimulation test may be the only way to tell If central, MRI needed!
Case 5 13 y.o. girl who has not shown any signs of puberty? Normal or abnormal? What if this was a 13 y.o. boy? Normal or abnormal?
Definitions: Delayed Puberty Girls: absence of any signs of pubertal development by age 13 Boys: absence of any signs of pubertal development by age 14
Case 5 13 y.o. girl who has not shown any signs of puberty? Normal or abnormal?
Case 5 13 y.o. girl who has not shown any signs of puberty? Normal or abnormal?
Case 5 13 y.o. girl who has not shown any signs of puberty? Normal or abnormal? What if this was a 13 y.o. boy? Normal or abnormal?
Case 5 13 y.o. girl who has not shown any signs of puberty? Normal or abnormal? What if this was a 13 y.o. boy? Normal or abnormal?
Case 5 13 y.o. girl with no signs of puberty What do you want to know? Previously healthy Shorter than peers No meds Review of systems normal Mother had menarche at age 17
Constitutional Delay of Puberty History of being shorter than agematched peers, normal growth velocity delayed bone age family history Key: good follow-up!
Turner Syndrome 45 XO karyotype Mosaicism Presentation prenatal dx (karyotype, U/S) lymphedema short stature delayed puberty/amenorrhea
Turner Syndrome Cardiovascular Renal Growth Eyes Ears Muscolskeletal Autoimmune GI Puberty Fertility Gonadoblastoma Neuropsychological
Turner Syndrome JCEM 2001 Recommendations for Adult Care of Turner Syndrome Transition after completion of puberty Multidisciplinary team Gyne with expertise in fertility
Turner Syndrome Annual history P/E BP cardiac thyroid breast PAP
Turner Syndrome Regular otologic exam Sensorineural HL, >35 y.o. rapid progression If a dip q3-5 y, otherwise q10y
Turner Syndrome Obesity Lifestyle recommendations Aim for a BMI <25 Osteoporosis BMD q3-5y, if stable, can space it out
Turner Syndrome Labs q2y Hgb BUN, creat ac gluc, lipids liver enzymes TSH, free T4 If known GU abn, screen for UTI prn
Turner Syndrome Cardiac if N in childhood, echo q5y if echo poor quality do CT or MRI take chest pain seriously! Careful monitoring for pregnancy, do echo preconception for aortic root dimensions
Turner Syndrome E2 replacement Estrace 0.5 mg q2d x 3 mos, qd x 3-6 mos, increase to 1 mg qd x3-6 mos, then to 2 mg qd Switch to OCP once she has a bleed Most need at least 2 mg 17β estradiol Androgen concentration is decreased, may consider replacement
Turner Syndrome Fertility cardiac, renal, thyroid and glucose tolerance pre-pregnancy Functional ovaries think of conception early because of POF oocyte cryopreservation (under investigation) risk of miscarriage
Turner Syndrome Non functional ovaries oocyte or embryo donation may be considered uterus will need special prep with E2 to be 7 mm thick Vaginal delivery is an acceptable option, C/S more common because of narrow pelvis
Turner Syndrome Psych Female gender ID is unambiguous Dating and sex - delayed and less frequent, same as a woman who is short and has primary amenorrhea
Turner Syndrome More problems in school and with peers Cognitive no decreased IQ, except with small ring X chromosome selective impairment of visual-spatial and nonverbal programming
Turner Syndrome Turner Syndrome Society Career planning Independent living Sex education
Case 6 17 y.o. girl who moved here from St. Vincent Had some breast development at age 12, did not progress No vaginal discharge, no menarche Short (height < 3 rd percentile) What else do you want to know? Normal or abnormal?
Case 6 17 y.o. girl who moved here from St. Vincent Had some breast development at age 12, did not progress No vaginal discharge, no menarche Short (height < 3 rd percentile) What else do you want to know? Normal or abnormal?
Approach to Delayed Puberty Central = HPA axis problem hypogonadotropic hypogonadism low LH and FSH illness, tumour, prolactinoma, anorexia, radiation, Kallman s, T4, syndromes (PWS) other hormone deficiencies Peripheral = gonadal failure hypergonadodtropic hypogonadism high LH and FSH gonadal dysgenesis mumps chemo, radiation to gonads boys: XXY, anorchia, cryptorchidism girls: XO, POF
Case 6 No underlying illness No excess exercise, no anorexia No sx or sx of hypothyroidism No galactorrhea Normal sense of smell Headaches Normal exam
Case 6 Work-up: LH, FSH, E2, prolactin, TSH, T4, am cortisol + LHRH stim test Bone age X-ray Image head - skull films, CT or MRI Delayed bone age Skull film: enlarged sella turcica, calcifications Dx: craniopharyngioma
Case 7 16 y.o. boy with no signs of puberty PMHx normal Mild developmental delay, behavioural problems in school Review of systems otherwise unremarkable Physical exam reveals small, firm testes
Case 7 Likely central or peripheral?
Case 7 Likely central or peripheral?
Case 7 Likely central or peripheral? Work-up: LH, FSH, testosterone, prolactin, thyroid function LH = 65 IU/L, FSH > 100 Confirms gonadal failure (peripheral) Karyotype: 47, XXY
RECAP: Delayed Puberty Normal or abnormal? Could it just be constitutional delay? Is it central (HYPOgonadotropic hypogonadism)? Is it peripheral (HYPERgonadotropic hypogonadism)?