16 Y/o girl with lack of breast development &

primary amenorrhea high FSH

Asymptomatic low ca/high ph/NL PTH

what is diagnosis/prognosis/chance of fertility?

Any intervention eg ovarian BX?

Any survilance?

What is treatment? Is steroid indicated?

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)
Primary/premature gonadal failure
1-ovarian follicle depletion

2-ovarian follicle dysfunction

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
Follicle depletion major mechanism of POF

Disruption 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 inheritance

Adolescents with primary amenorrhea 50% have abnormal

karyotype
Ovarian follicle dysfunction
• Steroidogenic enzyme defects
17alphahydroxylase deficiency
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)
30% prevalence of autoimmune POF in one report

In autoimmune oophoritis ovaries are normal size or are

enlarged Spontaneous POF has been described as part of
polyglandular autoimmune syndromes type 1 and 2

Spontaneous POF can be associated with autoimmune

endocrine and non endocrine diseases outside of the PGS
most common is Hashimoto thyroiditis

2%-6% of spontaneous POF may develop Addison disease

Autoantibodies test by immunofluorescence efficient screen for
Autoimmune adrenal insufficiency(100% sensitivity/ 67% ppv
+AB annual ACTH test
Neufeld and Blizzard Classification of 1980
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%).
Low Ca /high phosphate/Nl PTH

Primary hypoparathyroidism

Idiopathic
Aut dom activating mutation of Ca sensing receptor
Autoimmune
DX:

1-Autoimmune POF + Hypopara

2-Gonadal dysgenesis +
Idiopathic hypopara

Anti 21 Ohlase may be diagnostic

Treatment : HRT