Delayed puberty

2. 16 Y/o girl with lack of breast development &primary amenorrhea high FSHAsymptomatic low ca/high ph/NL PTHwhat is diagnosis/prognosis/chance of fertility?Any intervention eg ovarian BX?Any survilance?What is treatment? Is steroid indicated?

3. Delayed puberty Absence of testicular enlargement in boys or Breast development in girls at an age that is 2 to 2.5 SD later than the population mean (traditionally, the age of 14 years in boys and 13 years in girls) Classified by Gonadotropins 1-Low /NL FSH/LH 2-High FSH/LH (primary gonadal failure)

5. Primary/premature gonadal failure1-ovarian follicle depletion2-ovarian follicle dysfunction

6. Ovarian follicle depletion Low initial follicle number Pure gonadal dysgenesis Thymic aplasia/hypoplasia Autosomal recessive disorders(ataxia telangiectasia ment retardation) 　Idiopathic Accelerated follicle atresia X chromosome related (Turner syndrome, X chromosome deletions and translocations) Galactosemia Viral oophoritis Autoimmunity Environmental toxins Iatrogenic Idiopathic

7. Follicle depletion major mechanism of POFDisruption in any step of germ cell formation, migration, oogonia proliferation, and meiosis result in deficient initial follicle number streak gonads and primary amenorrhea(gonadal dysgenesis)Two thirds of cases with gonadal dysgenesis & 46,XX have genetic defect with autosomal recessive inheritanceAdolescents with primary amenorrhea 50% have abnormal karyotype

8. Ovarian follicle dysfunction • Steroidogenic enzyme defects 17alphahydroxylasedeficiency 17-20desmolase deficiency Aromatase enzyme deficiency • Autoimmunity Lymphocytic oophoritis with positive adrenal antibodies/Addison Gonadotropin receptor antibodies • Signal defects Abnormal gonadotropin receptor Abnormality in the G protein signaling pathway • Specific genetic defects (blepharophimosis epicanthus ptosis sx) • Idiopathic (resistant ovary syndrome)

9. 30% prevalence of autoimmune POF in one reportIn autoimmune oophoritis ovaries are normal size or are enlarged Spontaneous POF has been described as part of polyglandular autoimmune syndromes type 1 and 2Spontaneous POF can be associated with autoimmune endocrine and non endocrine diseases outside of the PGSmost common is Hashimoto thyroiditis2%-6% of spontaneous POF may develop Addison diseaseAutoantibodies test by immunofluorescence efficient screen for Autoimmune adrenal insufficiency(100% sensitivity/ 67% ppv +AB annual ACTH test

10. Neufeld and Blizzard Classification of 1980

14. Iranian Journal of Pediatrics 2007. 17(Suppl 2):255-260.Etiology of Delayed Puberty in the Institute for Endocrinology and Metabolism Farzaneh Rohani, Abbas Rashad Findings: Patients (32 boys and 16 girls) were divided into 3 groups based on clinical and laboratory information. 24 patients (50%) were categorized in the group of hypogonadotropic hypogonadism (including 18 cases with isolated hypogonadotropic hypogonadism, 2 cases of Kallmann_syndrome, 3 cases with hypopituitarism, 1 case with hypogondism and thalassemia). 14 (29.2%) patients including 13 boys and 1 girl were categorized in the group with constitutional delay of growth and puberty. 10 patients (20.8%) were categorized in the group with hypergonadotropic hypogonadism (including 6 cases with Turner syndrome, 2 cases with Klinefelter syndrome, 2 cases with 46XX pure gonadal dysgensis). The most common cause of hypogonadism in boys was constitutional delay of growth and puberty (40.6%) and hypogonadotropic hypogonadism (40.6%) while in girls it was Turner syndrome (37.5%). The most common cause for patients to be referred was short stature (43/5%) and then non appearance of pubertal signs (37.5%).

15. Low Ca /high phosphate/Nl PTHPrimary hypoparathyroidismIdiopathicAut dom activating mutation of Ca sensing receptorAutoimmune

16. DX:1-Autoimmune POF + Hypopara2-Gonadal dysgenesis + Idiopathic hypoparaAnti 21 Ohlase may be diagnosticTreatment : HRT