Delayed Puberty

Delayed Puberty

Delayed puberty is the absence of any signs of pubertal development at an age where it is expected to have begun. In the UK, this is defined as a lack of testicular enlargement (testicular volume of 4 ml or more) by age 14 in boys, or the absence of breast development (Tanner stage B2) by age 13 in girls. While most cases are a normal variant of development, a thorough assessment is crucial to rule out a pathological cause.

 

Aetiology and Classification

Delayed puberty can be classified into two main categories:

  1. Constitutional Delay of Growth and Puberty (CDGP): This is the most common cause. It’s a normal variant where the hypothalamic-pituitary-gonadal (HPG) axis is fully functional but matures later than average. These children have delayed bone age but a normal height velocity for their bone age and will eventually achieve normal adult height.

  2. Hypogonadism: This is a pathological cause where the HPG axis is not functioning correctly.

    • Hypergonadotropic Hypogonadism: This is a primary failure of the gonads to produce sex hormones. Gonadotropin levels (LH and FSH) are high.

      • Boys: Klinefelter syndrome (47, XXY) or testicular damage from chemotherapy, radiotherapy, or trauma.

      • Girls: Turner syndrome (45, X) or ovarian damage.

    • Hypogonadotropic Hypogonadism: This is a central failure of the hypothalamus or pituitary gland to produce GnRH, LH, and FSH. Gonadotropin levels are low.

      • Isolated GnRH deficiency: Can be sporadic or syndromic (e.g., Kallmann syndrome, which also has anosmia or hyposmia).

      • Hypothalamic-Pituitary Disorder: Tumours (e.g., craniopharyngioma), cranial radiotherapy, or chronic systemic illnesses.

 

Clinical Assessment

History

  • Growth: A key part of the history is to review previous growth charts and assess the child’s height velocity.

  • Family History: A family history of delayed puberty (e.g., a father who had a late growth spurt) strongly suggests a diagnosis of CDGP.

  • Systemic Symptoms: Ask about any symptoms of an underlying chronic illness (e.g., weight loss, fatigue) or intracranial pathology (e.g., headaches, visual disturbances).

 

Examination

  • Accurate Measurements: Plot height and weight on a growth chart and calculate the mid-parental height.

  • Pubertal Staging: Use Tanner staging to assess the presence and progression of puberty. In boys, measure testicular volume using an orchidometer. A volume of less than 4 ml is prepubertal.

  • Systemic Exam: Perform a full systemic examination to look for signs of a chronic illness.

  • Dysmorphic Features: Look for any syndromic features, such as those seen in Turner syndrome (e.g., short stature, webbed neck).

 

Investigations

  • First-line:

    • Bone Age: An X-ray of the left wrist is a key investigation. A delayed bone age is a characteristic feature of CDGP.

    • Endocrine Bloods: Baseline blood tests should include LH, FSH, TSH, and T4.

  • Further Investigations:

    • Karyotype: A karyotype should be considered in girls with short stature and suspected delayed puberty to rule out Turner syndrome.

    • GnRH Stimulation Test: A key test to differentiate between CDGP and hypogonadotropic hypogonadism. In CDGP, the pituitary will respond to GnRH, while in hypogonadotropic hypogonadism, it will not.

    • MRI Brain: An MRI of the brain is required if there are any signs of intracranial pathology or if hypogonadotropic hypogonadism is diagnosed to rule out a tumour.

 

Management

  • CDGP:

    • Reassurance: The primary management is reassurance to the child and family that this is a normal variant and that puberty will occur naturally.

    • Hormone Therapy: A short course of sex hormone therapy may be considered in severe cases for a psychological boost, but it does not change the final adult height.

  • Hypogonadism: Management is directed at the underlying cause.

    • Hormone Replacement: Long-term hormone replacement therapy is required to induce puberty and maintain secondary sexual characteristics.

    • Tumours: Tumours will require surgical or medical management.