Physiology of Puberty

• Puberty is the transition from childhood to adulthood
• Puberty is characterized by the development of secondary sexual characteristics
• Puberty involves gonadal maturation and the attainment of reproductive capacity

Physiology of Puberty

• Puberty is a developmental period that allows for the maturation of the reproductive system and the attainment of fertility
• The developmental stages of the human reproductive system include fetal life, childhood, and puberty
• Fetal life transitions into early infancy (3-6 months), where the hypothalamic-pituitary-gonadal (HPG) axis is active
• Childhood progresses to a quiescent period during adolescence
• Puberty (adolescence) reactivates and matures the HPG axis

Minipuberty

• Mini-puberty occurs in males at 3-6 months
• Mini-puberty occurs in females at 2 years (3-4 years)
• Females primarily exhibit FSH dominance
• Males show primarily LH dominance

Gonadarche

• Skeletal maturation, body fat mass, psychosocial-environmental stimulants, stress, nutrition, and metabolic rate influence gonadarche
• There are unidentified or unknown centers in the central nervous system (CNS), or gonadostat
• Decreased activity in centers that suppress GnRH leads to increased pulsatile secretion of GnRH by the hypothalamus
• Increased secretion of FSH and LH by the pituitary leads to gonadal maturation
• Increased secretion of sex steroids by the gonads (T/E2) occurs

Kisspeptin, Neurokinin B, Makorin Ring Finger Protein 3

• Kisspeptin stimulates
• Neurokinin B (NKB)
• Makorin ring finger protein 3 has an inhibitory effect on hormones
• Metabolic factors, such as leptin and ghrelin, affect GnRH

Adrenarche

• Adrenarche is regulated differently than gonadarche
• DHEAS elevation usually begins 2 years before the initial rise in FSH and LH
• Pubic hair development typically occurs 3-6 months after breast budding or testicular enlargement
• The precise start of the hormone releasing process can start earlier than the appearance of pubic hair and axillary hair
• There is increased responsiveness of the adrenal gland to ACTH
• DHEA, DHEA-S, and androstenedione are involved

Effects of Hormonal Changes During Puberty

• Estrogen leads to changes in breast tissue and nipple/areola size, vaginal mucosal color (Estrogen causes cornification), more prominent labia minora, accelerated somatic growth, and uterine enlargement with endometrial proliferation
• Androgens results in acnea, oily skin, body odor, voice break, pubic and axillary hair, facial hair, penile enlargement, increased scrotal rugation, thinning and pigmentation, increase in muscle mass and accelerated somatic growth, and deepening of voice

Evidence of Gonadotropic Stimulation

• The characteristics of true precocious puberty include
  • Testicular enlargement in boys (>4 cc in volume)
  • Ovarian enlargement and development of follicles in girls

Tanner Staging

• Size guides exist to assess the tanner staging of girls breast and pubic region during puberty
• Tanner staging also exists to assess puberty in males, mainly focusing on testicular enlargement
• Orchidometers can accurately test the volume of the testicles

Ovarian and Uterine Growth

• Ovarian and uterine growth occurs during puberty
• These can be monitored by ultrasound
• The average and standard range of both can be compared against age
• There is also an increase in height during this time

Bone Age

• Bone age, estimated using X-rays of the left hand and wrist, indicates the remaining growth potential before epiphyseal fusion
• Bone growth stops usually around ten years after puberty

Definition of Precocious Puberty

• Precocious puberty is the development of sexual characteristics 2.5 standard deviations before the average age
• In girls, this means breast development and pubic hair before 8 years, or vaginal bleeding without menstruation before 10 years
• In boys, precocious puberty is defined as testicular enlargement before 9 years (volume >4 ml or length > 2.5 cm)
• Precocious Puberty is associated in both genders with accelerated growth and bone maturation

Classification of Precocious Puberty

• True precocious puberty (gonadotropin-dependent, central PP) results from early triggering of the normal pubertal mechanism and occurs in an orderly fashion
• Pseudo precocious puberty (gonadotropin-independent, peripheral PP)results from early secretion of sex steroids due to factors other than the normal pubertal mechanism (i.e., gonadal/adrenal)
• Isosexual PP involves pubertal changes consistent with the child's gender
• Heterosexual PP involves changes that are not in agreement with the gender
• Incomplete precocious puberty (partial PP) involves the occurrence of isolated breast development (premature thelarche), premature pubic hair development (premature adrenarche), or premature menstruation

Etiology of Precocious Puberty

• In girls, 95% are idiopathic, involving premature triggering of the normal pubertal mechanism for unknown reasons
• In boys, 20% are idiopathic, and organic lesions are more common
• There are 2 types: True and Pseudoprecocious
• Secondary conditions result from CNS disorders
  • Intracranial cysts, tumors, hamartomas, hydrocephalus, other malformations, epilepsy, radiotherapy, meningitis, encephalitis, or trauma, and CP

Etiology of Gonadotropin-independent Precocious Puberty

• Benign Ovarian Follicular Cysts: This can result in increased estrogen
• Mc-Cune Albright Syndrome: Caused by a somatic activating mutation in the α-subunit of the G protein, characterized by multiple symptoms

Etiology of Heterosexual Precocious Puberty in Girls

• Congenital adrenal hyperplasia
• Masculinizing tumors
  • Arrhenoblastoma
  • Dysgerminoma

Testotoxicosis in Boys

• In boys, a Familial autosomal dominant mutation causes increased sex hormones: There are also mutations of the LH receptor that causes constitutive activation and premature maturation of Leydig/Sertoli cells.
• There is also enlargement of the penis

Diagnosis of Precocious Puberty

• Sequence of pubertal changes should be assessed, noting that in true PP the progression is appropriate with normal puberty while in pseudo PP it is out of order
• The patient's Family and Medical history is required
• Sex Hormones may be tested

Radiologic Evaluation

• Bone age assessment: Assess if bone development is ahead of schedule (Advanced for stage of puberty)
• Pelvic Ultrasound: Assess ovaries (Tumors or cysts)
  • Uterine evaluation: Is uterus/cervix ratio advanced?

Management of Precocious Puberty

• Detect the presence of Organic Disorders
  • Tumors: Neureosurgery, or Radiotherapy
  • Mennigitis: Medication
  • Hydrocephalus: Stunt Growth
• Treat Sexual Precosity
  • Aim for bone age preservation
  • Attempt to preserve height and prevent early closure of the growth plate
  • Look after children to prevent negative Psychological Consequences

Central PP Treatment

• GnRH Analogs for Puberty arrest (Opposite of what happens within the body)
  • Inibit gonadotrophin
    • Lower Puberty hormone levels
    • Bone growth stagnates
  • Height increases by 1.5cm for each treated year

Delayed Puberty Definition

• Definition: >2.5 sd from normal
• Boys; No testical growth after age 13
• Girls; No breast /public hair Growth after 13 years old or menarche by age 16
• Transitory, Reversible, and Irreversible
• Causes;
  • Low Gonadatropin -Malnutrition
    • Lack of LH RH
• Transitory and Reversible cases • -Treat Hypothalamus to induce puberty
  • give LH, FSH, or sex hormones

Categories Of Delayed Puberty

• Low Gonadatropin (No sex hormone production) and High gondaotropins(hormones produced, but insensitive to the hormone

Diagnosis in Delayed Puberty

• Look for causes during normal puberty such as :
  • Steroid production issues • If not working
• Look for issues in the Gonadotropins • Are producing Low levels • If this is the case, - Test for chromosomal (Hypo pituitarism)

Radiology - Lab test/bone age

• Delays growth for most cases except for “TURNER” syndrome
• If both are delayed, consider head abnormalities or problems