Precocious puberty

Central Precocious Puberty (CPP)

Etiology Category	Male Manifestations	Female 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 Category	Male Manifestations	Female 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 Category	Male Manifestations	Female Manifestations
Incomplete Precocity	Premature adrenarche.	Premature thelarche Premature pubarche/adrenarche Premature menarche

Delayed Puberty

Etiology Category	Male Manifestations	Female 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)