12th April 2024

Precocious puberty

Precocious puberty is defined as the development of secondary sexual features before the age of 8 in females and 9 in males. It also causes an accelerated rate of skeletal development and leads to a reduced adult height. Precocious puberty can be divided into whether it is gonadotrophin-releasing hormone (GnRH) dependent.

• Central or true precocious puberty is GnRH-dependent
• Peripheral precocious puberty is GnRH-independent

Central (true) precocious puberty

This occurs due to the early maturation of the HPA axis and is known as gonadotrophin-dependent precocious puberty. This leads to the release of gonadotropins (LH and FSH) and subsequent production of sex steroids. The most common cause is idiopathic and familial, which is found more frequently in females because the ovaries are sensitive to secretion of gonadotrophins. Often, they have a family history of precocious puberty. It may also be due to a tumour that produces GnRH or human chorionic gonadotropin (hCG). Other less common causes include other CNS diseases such as hydrocephalus, encephalitis, trauma, cranial radiotherapy or CNS hamartomas.

Peripheral precocious puberty

This is due to the overproduction of sex hormones; therefore, it is also known as gonadotrophin-independent precocious puberty. This may be due to a cyst or tumour, genetic conditions such as McCune-Albright Syndrome, dysfunction of other endocrine organs such as thyroid or adrenal glands or exposure to exogenous sex hormones such as the contraceptive pill or testosterone gels.

McCune-Albright syndrome (MAS)

MAS is caused by G-activating protein mutation in the adenylyl cyclase-cyclic adenosine monophosphate (cAMP) pathway. It plays an important role in the production and excretion of hormones. The mutation results in the pathway being constantly activated. The mutation occurs after the formation of the zygote; therefore, not all cells have the mutation. The clinical presentation is variable in different tissues.

It is associated with fibrous dysplasia and causes replacement of bone tissue with scar tissue. This may result in pathologic fractures, pain and limp. The degree of clinical manifestation depends on the affected individual. Patients will often have café au lait spots with irregular borders like “coast of Maine.” They become more numerous and darker with age. Other clinical features of MAS include hyperthyroidism, Cushing’s syndrome and growth hormone excess due to the constant activation of the cAMP pathway.

References

• Precocious Puberty. BMJ Best Practice. Last Reviewed 19ᵗʰ December 2023
• Lissaue, Tom, Will Carroll, Keir Shiels, and Ranj Singh. Illustrated textbook of paediatrics. Amsterdam: Elservier, 2022
• Klatt, Edward C., and Vinay Kumar. Robbins and COTRAN Review of Pathology. London: Elsevier Health Sciences, 2015