Why is my body not changing? Murthy Korada Pediatrician, Pediatric Endocrinologist Ridge Meadows Hospital Surrey Memorial Hospital None Conflicts of interest Overview Overview of normal pubertal timing and progression Causes of delayed puberty Understanding constitutional delay of puberty Evaluation and management of delayed puberty 1
Case review James is a 14-year old boy wants to know: why is my body not changing like my friends? His peers are all much bigger than him and this is affecting his confidence His growth velocity is 5.1 cm / year His height has dropped from the 10th to < 3rd percentile and his weight has been stable along the 5th percentile Mom: 158cm Dad: 174cm Mom: Menarche at age 14 Case review On examination: - No acne - Absent axillary hair - Tanner stage 1 pubic hair - Testes that are 3 ml in volume - Prepubertal phallus 2
INVESTIGATIONS: Hemoglobin 12.8 g/dl Electrolytes normal ESR 4 mm/hr TSH 1.6 miu/l ALT 27 U/L Celiac antibodies (TTG) <1.0 IGF-1 145 µg/l (-2.0 SDS for chronologic age) 0.15 miu/l (0.15 IU/L) 2.6 miu/l (2.6 IU/L) Testosterone 16 ng/dl (0.56 nmol/l) Bone age 12 years (-2.0 SDS) Case review James is a 14-year old boy wants to know: why is my body not changing like my friends? His peers are all much bigger than him and this is affecting his confidence His growth velocity is 5.1 cm / year His height has dropped from the 10th to < 3rd percentile and his weight has been stable along the 5th percentile Timing of Puberty Pubertal delay in boys (- 2 SDS): Testicular size <4mL or absent pubic hair by age 14 years Pubertal delay in girls (- 2 SDS): No breast development by age 13 years No menstruation by age 15 years 3
BOYS Tanner JM 1975 GIRLS Tanner JM 1975 Tanner staging 4
The hypothalamic-pituitary-gonadal (HPG) axis Pulsatile GnRH secretion stimulate & Ovarian follicle or Seminiferous tubule Theca cells (ovary) or Leydig cells (testes) Inhibin Sperm/egg Androgen/ Estrogen Brian Bordini, and Robert L. Rosenfield Pediatrics in Review 2011;32:223-229 Testes descent, penile growth Isolated premature thelarche: No other puberty signs predominance Normal growth, bone age For 2 yrs before puberty, in adrenal androgens early pubic hair and spots Puberty: (Re)activation of the HPG axis 2 nd,3 rd Trimester Post-natal Childhood Puberty (3-6 months) Quiescence Nocturnal > > Diurnal INFANCY CHILDHOOD PUBERTY 5
Case review James is a 14-year old boy wants to know: why his body is not changing rapidly like his peers His peers are all much bigger than him and this is affecting his confidence His growth velocity is 5.1 cm / year His height has dropped from the 10th to < 3rd percentile and his weight has been stable along the 5th percentile BOYS: Peak height velocity is 10 cm/yr at 13.5 years [Late in puberty] Brian Bordini, and Robert L Rosenfield Pediatrics in Review 2011;32:281-292 BOYS: Peak height velocity is 10 cm/yr at 13.5 years [Late in puberty] Brian Bordini, and Robert L Rosenfield Pediatrics in Review 2011;32:281-292 6
INVESTIGATIONS: Hemoglobin 12.8 g/dl Electrolytes normal ESR 4 mm/hr TSH 1.6 miu/l ALT 27 U/L Celiac antibodies (TTG) <1.0 IGF-1 19.1 nmol/l (-2.0 SDS for chronologic age) Testosterone Bone age 0.15 miu/l (0.15 IU/L) 2.6 miu/l (2.6 IU/L) 16 ng/dl (0.56 nmol/l) 12 years (-2.0 SDS), (hypogonadotropic hypogonadism) Constitutional delay of puberty & (growth) Kallman syndrome: > Anosmia Delayed bone age Isolated, Small phallus Renal, CNS Chronic illness Malnutrition Exercise Hypothyroidism Panhypopituitarism Prader Willi sy, (hypergonadotropic hypogonadism) Turner Syndrome 45 XO most common Short stature Primary amenorrhea Congenital anomalies Primary ovarian failure Klinefelter s Syndrome 45 XXY most common Pubertal delay Small, fibrotic testes Gynecomastia 90-100% are infertile Acquired: Irradiation Chemotherapy Surgery Torsion, trauma Infection Autoimmunity 7
Constitutional Delay of Puberty Most common cause of pubertal delay Boys > girls Bone age: Delayed & consistent with degree of pubertal maturation, : Pre-pubertal levels Family: Delayed puberty often found in siblings or parents Height: Often associated with constitutional short stature Final height: Is generally not impaired CONSTITUTIONAL DELAY OF PUBERTY Identify & Manage any underlying cause(s) Stimulating Puberty : e.g. Constitutional delay Boys: (Testosterone injections / tablets) Around 14 yrs of age For Constitutional delay Boys with psychological distress Low dose, regular assessments (beware premature epiphyseal closure) Rx stopped once puberty established (6-12 months) Final height not affected Girls: (Estrogen replacement) Less often than boys. Gradual over 2-3 years 8
TAKE HOME MESSAGE(S) Family History & Mid-parental height (MPH) helpful Bone Age: Important for accurate assessment Gonadotropin levels (, ) help with differential diagnoses ( high vs low) Exclude chronic illness / hypopituitarism with low and Referral to Ped. Endocrinologist if diagnosis uncertain or contemplating Rx with Testosterone / Estrogen QUESTIONS? 9