Overview
Definition:
Delayed puberty is defined as the absence of secondary sexual characteristics by age 13 in girls and age 14 in boys, or by the absence of menarche within 5 years of thelarche in girls.
Epidemiology:
The incidence varies, with functional hypothalamic amenorrhea and constitutional delay being the most common causes
Approximately 1-2% of the population may experience delayed puberty
Genetic factors play a significant role in some cases.
Clinical Significance:
Delayed puberty can have significant psychosocial implications and can be indicative of underlying organic pathology, including genetic disorders, endocrine deficiencies, or chronic illnesses
Timely diagnosis and management are crucial for optimal physical and psychological development and long-term health outcomes.
Clinical Presentation
Symptoms Girls:
Absence of breast development (thelarche) by age 13
Absence of pubic hair (pubarche) by age 14
Absence of menarche by age 15 or within 5 years of thelarche
Primary amenorrhea
Poor growth velocity
Short stature.
Symptoms Boys:
Absence of testicular enlargement and scrotal development by age 14
Absence of pubic hair (pubarche) by age 15
Lack of deepening of voice
Poor muscle mass development
Short stature
Sparse facial hair.
Signs:
Lack of secondary sexual characteristics (e.g., breast buds, pubic hair, axillary hair, voice deepening, testicular enlargement)
Short stature with a normal or elevated BMI
High-pitched voice in boys
Visual field defects or anosmia may suggest central causes
Gynecomastia in boys can be a sign of underlying hormonal imbalance.
Diagnostic Criteria:
For girls: No breast development by age 13 or menarche by age 15
For boys: No testicular enlargement by age 14
WHO classification criteria for puberty staging (Tanner stages) are essential for objective assessment.
Diagnostic Approach
History Taking:
Detailed birth history (e.g., birth weight, congenital anomalies)
Family history of delayed puberty or short stature
History of chronic illnesses (e.g., inflammatory bowel disease, cystic fibrosis)
Nutritional status and dietary intake
History of CNS insults (e.g., trauma, irradiation, meningitis)
Psychological history (stress, eating disorders)
Medication history (e.g., GnRH agonists, steroids)
Any previous medical interventions.
Physical Examination:
Complete physical examination including height, weight, BMI, and plotting on growth charts
Tanner staging of pubic hair, genitalia (boys), and breasts (girls)
Assessment for anosmia or visual field defects
Palpation of testes in boys (size and consistency)
Examination for dysmorphic features or stigmata of genetic syndromes
Assessment for galactorrhea or thyromegaly.
Investigations:
Initial investigations: Bone age X-ray (hand and wrist)
Complete blood count (CBC)
Erythrocyte sedimentation rate (ESR)
Thyroid function tests (TSH, fT4)
Prolactin
Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), Estradiol (E2) in girls, and Testosterone (T) in boys (basal and stimulated)
Karyotyping for suspected genetic abnormalities
In suspected central hypogonadism: GnRH stimulation test to differentiate primary from secondary hypogonadism
Imaging: MRI of the pituitary and hypothalamus if central causes are suspected
Pelvic ultrasound in girls to assess uterine and ovarian development.
Differential Diagnosis:
Constitutional delay of growth and puberty (CDGP)
Hypogonadotropic hypogonadism (Kallmann syndrome, Prader-Willi syndrome, CNS tumors, infiltrative diseases)
Hypergonadotropic hypogonadism (Klinefelter syndrome in boys, Turner syndrome in girls)
Primary ovarian insufficiency
Androgen insensitivity syndrome
Chronic illnesses
Malnutrition
Functional hypothalamic amenorrhea.
Management
Initial Management:
Identification and management of any underlying medical condition contributing to delayed puberty
Nutritional support and counseling if malnutrition is present
Addressing psychosocial concerns.
Hormone Replacement Therapy:
Hormone replacement therapy (HRT) is indicated for true hypogonadism to induce puberty and maintain bone health
Girls: Low-dose estrogen therapy (e.g., ethinylestradiol 0.05-0.1 mcg/kg/day, gradually increased) followed by progesterone to induce menstruation
Boys: Testosterone therapy (e.g., intramuscular testosterone enanthate or cypionate, starting with low doses and gradually increasing).
Referral:
Referral to a pediatric endocrinologist is essential for all cases of confirmed delayed puberty to establish the etiology and initiate appropriate management
Genetic counseling may be required for specific syndromes
Psychological support and counseling for affected individuals and their families are often necessary.
Monitoring:
Regular follow-up with endocrinologist to monitor growth, pubertal progression, bone age, and hormone levels
Adjustments in HRT doses based on clinical response and Tanner staging
Bone density monitoring may be indicated in select cases.
Complications
Early Complications:
Psychosocial distress: anxiety, depression, low self-esteem due to delayed development
Impaired bone mineralization leading to osteopenia or osteoporosis
Reduced fertility potential
Infertility due to untreated hypogonadism.
Late Complications:
Long-term consequences of untreated hypogonadism include osteoporosis, cardiovascular disease, and impaired sexual function
Infertility can be a significant long-term issue.
Prevention Strategies:
Early recognition and prompt referral for evaluation
Timely initiation of appropriate hormone replacement therapy
Management of underlying chronic illnesses
Nutritional support and counseling.
Key Points
Exam Focus:
Distinguish constitutional delay from true hypogonadism
Understand the diagnostic algorithm for delayed puberty
Recognize the specific hormonal assays and stimulation tests
Know the indications and principles of hormone replacement therapy.
Clinical Pearls:
Always plot growth parameters on growth charts
Consider GnRH stimulation test for ambiguous cases
Family history is crucial
Early intervention can significantly improve outcomes.
Common Mistakes:
Overlooking chronic illnesses as a cause of delayed puberty
Delaying referral to endocrinology
Inappropriate initiation or titration of hormone replacement therapy without proper evaluation
Confusing constitutional delay with true hypogonadism.