Precocious puberty

Central Precocious Puberty (CPP)

Etiology CategoryMale ManifestationsFemale Manifestations
Idiopathic
  • Less common.
  • Most common etiology.
  • Accounts for 90-95% of cases.
  • CNS /
    Congenital Lesions
  • Acquired:
    • Severe head trauma
    • Postencephalitic scars
    • Tuberculous meningitis
    • Brain abscesses
    • CNS radiation
  • Congenital:
    • Hydrocephalus
    • Arachnoid cysts
    • Suprasellar cysts
  • Acquired:
    • Severe head trauma
    • Postencephalitic scars
    • Tuberculous meningitis
    • Brain abscesses
    • CNS radiation
  • Congenital:
    • Hydrocephalus
    • Arachnoid cysts
    • Suprasellar cysts
  • Genetic / Monogenic Causes
  • Pathogenic variants in:
    • MKRN3
    • DLK1
    • KISS1
    • KISS1R/GPR54
  • Pathogenic variants in:
    • MKRN3
    • DLK1
    • KISS1
    • KISS1R/GPR54
  • Peripheral Precocious Puberty (PPP)

    Etiology CategoryMale ManifestationsFemale Manifestations
    Gonadal Pathology
  • Leydig cell tumors
  • hCG-secreting tumors:
    • germinomas
    • chorioepitheliomas
    • teratomas
    • hepatoblastomas
  • Autonomous estrogen-secreting ovarian follicular cysts
  • Ovarian neoplasms:
    • juvenile granulosa cell tumors
    • thecomas
    • luteomas
    • dysgerminomas
    • gonadoblastomas
  • Adrenal Pathology
  • Virilizing Congenital Adrenal Hyperplasia (CAH)
  • Virilizing adrenal adenomas/carcinomas
  • Feminizing adrenal tumors:
    • isosexual
  • Virilizing adrenal tumors/classic CAH:
    • contrasexual
  • Syndromic & Genetic Causes
  • Familial male-limited precocious puberty (Testotoxicosis)
  • McCune-Albright syndrome
  • McCune-Albright syndrome
  • Aromatase Excess Syndrome
  • Severe Primary Hypothyroidism
  • Van Wyk-Grumbach Syndrome (macroorchidism).
  • Van Wyk-Grumbach Syndrome (multicystic ovaries, breast enlargement, galactorrhea).
  • Exogenous Exposure
  • Accidental systemic absorption of testosterone.
  • Topical estrogen creams, oral contraceptives, anabolic steroids, environmental phytoestrogens.
  • Variations of Normal / Incomplete Precocity

    Etiology CategoryMale ManifestationsFemale Manifestations
    Incomplete Precocity
  • Premature adrenarche.
  • Premature thelarche
  • Premature pubarche/adrenarche
  • Premature menarche
  • Delayed Puberty

    Etiology CategoryMale ManifestationsFemale Manifestations
    Constitutional Delay of Growth & Puberty (CDGP)
  • Most common male etiology
  • 65-80% referral cases.
  • Most frequent cause overall.
  • Diagnosed less frequently than in boys.
  • Functional / Transient Hypogonadotropic Hypogonadism
  • Systemic:
    • Celiac
    • IBD
    • cystic fibrosis (CF)
    • sickle cell
    • thalassemia
    • chronic renal failure
  • Nutritional:
    • Malnutrition
    • severe weight loss
    • anorexia nervosa
    • excessive physical training
  • Endocrine:
    • Uncontrolled T1DM
    • profound hypothyroidism
    • Cushing syndrome
    • hyperprolactinemia
  • Systemic:
    • Celiac
    • IBD
    • cystic fibrosis (CF)
    • sickle cell
    • thalassemia
    • chronic renal failure
  • Nutritional:
    • Malnutrition
    • severe weight loss
    • anorexia nervosa
    • excessive physical training
  • Endocrine:
    • Uncontrolled T1DM
    • profound hypothyroidism
    • Cushing syndrome
    • hyperprolactinemia
  • Permanent Central Hypogonadotropic Hypogonadism
    • Kallmann syndrome
    • Normosmic IHH
    • Multiple Pituitary Hormone Deficiencies (MPHD)
    • CNS lesions:
      • Craniopharyngiomas
      • germinomas
      • gliomas
      • irradiation
      • trauma
      • infiltrative diseases
    • Defects:
      • Septo-optic dysplasia
    • Syndromes:
      • Prader-Willi
      • Laurence-Moon-Biedl
      • CHARGE
    • Kallmann syndrome
    • Normosmic IHH
    • Multiple Pituitary Hormone Deficiencies (MPHD)
    • CNS lesions:
      • Craniopharyngiomas
      • germinomas
      • gliomas
      • irradiation
      • trauma
      • infiltrative diseases
    • Defects:
      • Septo-optic dysplasia
    • Syndromes:
      • Prader-Willi
      • Laurence-Moon-Biedl
      • CHARGE
    Hypergonadotropic Hypogonadism (Primary Gonadal Failure)
  • Klinefelter syndrome (47,XXY) (most common)
  • Structural:
    • Congenital anorchia
    • cryptorchidism
    • Noonan syndrome
  • Enzymatic:
    • StAR
    • CYP17A1
    • HSD17B3 mutations
  • Acquired:
    • Torsion
    • trauma
    • viral/autoimmune orchitis
    • chemotherapy
    • irradiation
  • Turner syndrome (45,X/variants) (most common)
  • Dysgenesis:
    • 46,XX pure gonadal (Perrault)
    • 46,XY gonadal (Swyer)
  • Enzymatic:
    • Aromatase deficiency
    • 17-alpha-hydroxylase/17,20-lyase deficiency
    • Savage syndrome
  • Acquired:
    • Cytotoxic chemotherapy
    • irradiation
    • autoimmune oophoritis
    • galactosemia
  • Structural / End-Organ Abnormalities (Eugonadism)
  • Not applicable.
  • Normal ovarian endocrine function
  • Primary amenorrhea via anatomical defects
  • Mayer-Rokitansky-Kuster-Hauser syndrome
  • Obstructive anomalies:
    • imperforate hymen
    • complete transverse vaginal septum
  • Complete Androgen Insensitivity Syndrome (CAIS)