1. Assistant Professor and Consultant Paediatric Endocrinologist
Abnormal Puberty
Dr. Amir Babiker
MBBS (U of K), FRCPCH (UK), CCT (UK), MSc Endocrinology and Diabetes (UK)
Assistant Professor and Consultant Paediatric Endocrinologist 
Program Director, Paediatric Endocrinology Fellowships at King Saud University
King Saud University (KSU) and King Saud University Medical City (KSUMC)
Riyadh, Saudi Arabia

2. Overview • Physiology of normal puberty • Pubertal assessment
• Early puberty:
Causes
Diagnosis
management
• Delayed puberty:

5. Timing of puberty

7. Incomplete Puberty Premature thelarche Premature Adrenarche
Premature menarche

9. CAUSES OF CPP Idiopathic (F>>M) Organic CNS disruption:
Tumours of the hypothalamic-pituitary region
Post head injury / meningitis
Neurofibromatosis
Williams syndrome
Prematurity / Cerebral Palsy
Hydrocephalus
Post cranial surgery or radiotherapy
Hypothyroidism
Priming

10. Precocious pseudopuberty in females
Isosexual (feminizing) conditions
McCune – Albright syndrome
Autonomous ovarian cyst
Ovarian tumors
Feminizing adrenocortical tumor
Exogenous estrogens
Heterosexual (masculinizing)
Congenital adrenal hyperplasia
Adrenal tumor
Ovarian tumor
Glucocorticoid receptor defect
Exogenous androgens.

11. Precocious pseudopuberty in males
Isosexual (Virilizing)
Congenital adrenal hyperplasia
Adrenocortical tumor
Leydig cell tumor
Familial male precocious puberty
HCG secreting tumor
Teratoma
Heterosexual
Feminizing adrenocortical tumor
Exogenous estrogens

12. Causes of Pseudo-Precocious Puberty
Sex steroids from the adrenal: • Congenital adrenal hyperplasia • Adrenal tumour • Premature adrenarche (<8-9 yr) • Cushing’s Syndrome Sex steroids from the gonad: • Ovarian tumour, cysts • McCune-Albright Syndrome • Testotoxicosis • HCG – secreting (germ cell) tumours Exposure to exogenous steroids

13. Assessment
History: timing, Family history, associated symptoms Physical examination: •Cutaneous lesions e.g neurofibromatosis, McCune Albright syndrome • CNS examination - Fundi Auxology: Pubertal staging (Tanner) + size of testes Height, weight, MPH, growth velocity Bone age

14. Investigations
Endocrine tests: • Testosterone / oestradiol • LH / FSH • Adrenal androgens (DHEA-S, androstenedione) • 17 –OH progesterone ± synacthen test • β HCG • GnRH test (central or pseudo-precocious) Radiology: • Pelvic ultrasound • MRI hypothalamic – pituitary region DNA analysis: • For known genetic disorders (testotoxicosis, McCune Albright Syndrome)

15. The goals of treatment for CPP
Improvement of adult height
Prevention of social and psychological problems.
Treatment of Pseudopuberty – by treating the cause (e.g adrenal tumour or CAH)

16. Delayed puberty/Pubertal failure

17. classification
1. Central (Hypogonadotrophic Hypogonadism) Physiological central delay and true GnRH /gonadotrophin deficiency 2. Peripheral (Hypergonadotrophic Hypogonadism) Primary gonadal failure

18. Hypogonadotrophic hypogonadism
Constitutional delay of puberty
Chronic illness/systemic disease
Malnutrition (including anorexia nervosa, Dieting, over-exercise)
Hypothyroidism
Impaired H-P axis:
Tumours H-P axis
Congenital: SOD, Genetic defects
Acquired : CNS Radiotherapy/trauma

19. Hypergonadotrophic hypogonadism: Girls
• Gonadal dysgenesis/Turner’s syndrome • Autoimmune ovarian failure • Gonadal failure following chemotherapy or abdominal irradiation, Toxic damage (iron overload) • 46 XY DSD including CAIS • PCOS

20. Hypergonadotrophic hypogonadism: Boys
Testicular damage: cryptoorchidism, orchidopexy, torsion
Bilateral anorchia
Syndromes: Noonans’s, P-W S, L-M-B-B S
Gonadal dysgenesis: Klinefelter’s syndrome, other XY aneuploidy, XO / XY
Gonadal failure following chemotherapy or testicular irradiation

21. When should you investigate?
Delay of more than 2-3 standard deviations from the mean age of pubertal onset.
Delayed : no sexual maturity by 14 years in boys & 13 years in girls.
Absence of menarche by 16 years of age, or within 5 years of pubertal onset.
Pubertal development begins, but progression stalls, the duration of a given characteristic is longer than expected

22. Assessment Careful History : Anosmia, galactorrhea, hypothyroidism
Excessive exercise
Chronic illness or psychiatric disease.
Family history.
Physical examination:
Growth parameters.
Sexual maturity.
Stigmata of congenital syndromes.
Chronic illness, Fundal examination

24. CONSTITUTIONAL DELAY
Constitutional delay explains % of pubertal delay.
It is a normal variant that results from persistence of the prepubertal hypogonadotropic state.
Boys present more often than girls.
It may be superimposed on constitutional short stature.

25. CDP More than 60% of patients have positive family history.
Findings on physical examination are unremarkable.
Delayed bone age that is consistent with the pubertal maturation.
Sexual maturity & final height are not affected.

26. BILATERAL GONADAL FAILURE
Uncommon.
Markedly elevated serum gonadotropins.
Congenital :
–Turner Syndrome
–Klinefelter Syndrome
Other congenital & acquired causes are rare.

27. OTHER CONGENITAL syndromes
Androgen Resistance.
Prader-Willi Syndrome.
Laurence-Moon & Bardet-Biedl Syndrome.
Noonan Syndrome.
Vanishing Testes Syndrome
Resistant Ovaries Syndrome.

28. Delayed PUBERTY & GROWTH

29. Investigations

30. Other INVESTIGATIONS Chromosomal analysis.
Screen for occult chronic: CBC, ESR
First morning urinary testosterone

31. MANAGMENT Treat the underlying cause + induction +/- HRT
Constitutional delay may be managed by reassurance alone, expectant management.
“ jump start” hormonal therapy may be used if delay has led to psychosocial dysfunction.
Objectives:
Final adult height
Secondary sexual characteristics
Physical and psychological wellbeing

32. Treatment of delay/failure

33. THANK YOU