Childhood. Unknown. Minimal gonadotrophin stimulation. Signal that dampens GNRH stimulation? Signal that dampens GNRH stimulation?

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1 Normal Pubertal Development Childhood Minimal gonadotrophin stimulation Due to dampening of GNRH stimulation Signal that dampens GNRH stimulation? Signal that dampens GNRH stimulation? Unknown Any interference with this inhibitory signal can result in early puberty Congenital CNS disorder Acquired CNS disorder

2 Normal Pubertal Development Adolescent-puberty Puberty is a two part event Gonadarche and adrenarche Triggers for initiation of puberty-still unknown Theories include weight, fat, stress Adrenal hormonal changes DHEA, DHEAS increase Occurs 2 years prior to maturation of the HPG axis Gonads LH predominance-first indication of puberty

3 Normal Female Development Adrenal cortex Control->????? Hormones Androstenedione DHEAS Testosterone Physical Exam Body odor Acne Pubic Hair Axillary Hair Gonads->Ovary Control Hypothalamus- GNRH Pituitary-FSH/LH Hormone Estradiol Physical Exam Breast development Menses

4 Normal Female Development First sign of puberty-breast enlargement Menarche Occurs 2 ½-3 years after breast enlargement Peak growth velocity at tanner 3-4 Menarche tanner 4, average age 12.8 years With menses-90% of growth is completed Mean duration of puberty-4.2 years

5 Normal Male Development Adrenal Cortex Control ->???? Hormones Androstenedione DHEAS Testosterone Physical Exam Body odor Acne Pubic Hair Axillary Hair Gonads->Testes Control Hypothalamus-GNRH Pituitary-FSH/LH Hormone Testosterone Physical Exam Increased testicular size >3cc or 2.5 cm length

6 Normal Male Development First sign of puberty Testicular enlargement; Greater than 3 cc/2.5 cm Peak growth velocity tanner stage 4 Axillary hair 1-2 years later than pubic hair LH-leydig cells-10% of testicular volume FSH-seminiferous tubules-90% of volume Gynecomastia-65% of males, tanner 3-4

7 Precocious puberty Previous definition was evidence of any secondary sexual characteristics before age 8 in a female and age 9 in a male 1999-Lawson Wilkins Pediatric Endocrine Society published new recommendations Precocious puberty is the appearance of any secondary sexual characteristics before age 6 in an African American female, 7 in white female, 9 in a male Based on findings of Pediatric Research in Office Settings (PROS) Network-studied females Not 100% accepted Should evaluate if patient s pubertal progression is rapid, patient with neurological problems, bone age advanced > 2 years, predicted adult height < 59 in, family concerned

8 Precocious Puberty Cause Brain tumor 10% in females Brain tumor 50% time in males Definition Must have adrenal & gonadal changes in female Only need gonadal changes in the male Remember.no such thing as premature testelarche!!!

9 Delayed puberty Absence of any secondary sexual characteristics by age 13 in females and 14 in males; OR if more than 5 years pass between the first signs of puberty and the onset of menarche in girls or the completion of genital growth in boys

10 Variants of Normal Puberty Definition Premature Thelarche Isolated breast development Females < 6-7 YO (AA vs. Caucasian) Patient profile Chief complaint-breast development, lump under breast, chest pain BA within 2SD of CA, BA=HA No other signs of puberty, normal GV GNRH-FSH predominant Normal estradiol levels-< 10 pg/ml

11 Variants of Normal Puberty Premature Thelarche Natural history 40% regress 50% persist 10% precocious puberty Reason you follow patients for months Normal pubertal development Normal adult height Differential diagnosis Estrogen excess-intrinsic Vs extrinsic Rule out early central precocious puberty

12 Variants of Normal Puberty Premature Thelarche Evaluation and management History-estrogen exposure Physical exam Growth velocity, tanner stage, skin exam Lab/X-ray-estradiol, LH/FSH, bone age Follow-up-exam every 3-4 months Further evaluation if initial screen abnormal Head MRI, PUS and GNRH stimulation test Only if concerned about precocious puberty

13 Definition Variants of Normal Puberty Premature Adrenarche Presence of adrenarche Body odor, pubic hair, axillary hair, acne <8YO females or <9YO males Patient profile Chief Complaint: PH, AH, BO,acne No virilization No breast development or menses in girls No testicular enlargement in boys Often associated with obesity & CNS insults

14 Variants of Normal Puberty Natural history Premature Adrenarche Normal puberty, fertility and growth PCO? Differential diagnosis Congenital adrenal hyperplasia Tumor-adrenal, Gonadal Cushings

15 Variants of Normal Puberty Premature Adrenarche Evaluation and management History and physical exam Androgen exposure, family history Vital signs, tanner stage, growth velocity Lab/x-ray DHEAS, androstenedione, testosterone, 17OHP Bone age-normal Follow-up q 4 months Further evaluation if initial screen abnormal ACTH stimulation test Adrenal/pelvic imaging 24 hour 17-Keto steroids

16 Variants of Normal Puberty Definition Premature Menarche Isolated menses in a female Normal growth, bone age and gonadotrophins Patient profile Presents 9 months-9 years; Cycling may persist Normal growth velocity and tanner 1 Natural history Normal onset of central puberty Normal adult height

17 Variants of Normal Puberty Premature Menarche Differential diagnosis Must rule out Trauma, sexual abuse, GI and GU bleeding Foreign body, vulvovaginitis, tumor Study of 50 females 1/2 with local lesions 1/2 of which were rhabdomyosarcoma Another report-25% with foreign body If presentation of precocious puberty Must rule out McCune Albright syndrome

18 Variants of Normal Puberty Premature Menarche Patient evaluation History-estrogen exposure PE-general exam, tanner stage, skin, pelvic Labs-estradiol, FSH/LH Xray-bone age Follow-up-every 4 months Additional evaluation PUS, head/pituitary MRI

19 Variants of Normal Puberty Premature Testelarche No such diagnosis!!! Enlarged testes (> 3 cc or 2.5 cm) Less than 9 YO is ABNORMAL!!!!!! This is an endocrine emergency!!!! 50% of patients have a brain tumor!

20 Approach to pubertal disorders Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate?

21 Case #1 6 YO female with early pubic hair development. No body odor, acne or axillary hair. Denies breast development or menses Labs-allall normal ft4, TSH, BHCG, 11DOC, Estradiol, FSH/LH, Free and total testosterone, SHBG 17OHP

22 Case #1 Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate? Do you agree with the evaluation? Additions? Subtractions?

23 Case #2 17 MO WF presented for first endocrinology evaluation for early breast development. Breast tissue first noted at 1 year FSH 8.8, LH 0.1, estradiol < 30 pg/ml. Over the year, her breast development has increased. On exam, T3 breast, T1 GU, normal growth velocity

24 Case # 2 Do you agree with the initial evaluation? Any concerns? Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate?

25 Case # 3 7 6/12 YO BF Evaluated at age 5 for early puberty. She was T2 breast and GU at that time. Nl TFTs, nl 17OHP, testosterone, DHEAS LH 1.0 FSH 3.4, nl head MRI, nl PUS Lost to follow-up Seen by me 2 1/2 years later On exam-4 9, T4 breast and GU

26 Case # 3 Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate? Thoughts/comments on evaluation?

27 Case # 4 16 YO male presents for routine PE PMH-healthy PE-Tanner 3 PH, 3 cc testes

28 Case # 4 Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate?

29 Case # 5 7 YO male with early puberty History of early PH and growth spurt Denied any body odor or acne Exam Tanner 2 PH and 5 cc testes with increased growth velocity PMH-HealthyHealthy

30 Case # 5 Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate?

31 Case # 6 8 YO male-ah and BO at 18 months Presence of pubic hair for 1 year Evaluated in past-no records PMH-RAD tx intal and proventil PE-T3 PH, + axillary hair, 3 cc testes, increased growth velocity

32 Case # 6 Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate?

33 Case # /12 YO male with height at 3% and decreasing growth velocity PMH-healthy PE-Height and weight <3% with decreasing velocity Tanner 1 PH and 3 cc testes

34 Case # 7 Is there a problem? Where is the problem? What is the differential diagnosis? How do you evaluate?