Gonadotrophin-Independent Precocious Puberty

GIPP occurs more commonly in boys (described as testotoxicosis) than in girls. However, when it does occur in girls, it is due to either McCune-Albright syndrome or hypomelanosis of Ito. McCune-Albright syndrome consists of pigmented skin lesions (often referred to as a 'Coast of Maine' appearance) and fibrous dysplasia of the bones. However, the most common presentation is with GIPP and the characteristic skin lesions. The bony lesions often present at a later date and the usual distribution is sphenoid and femur, but any bone can be involved. There may be hypersecretion of numerous endocrine glands, including the ovaries, adrenal glands, thyroid gland, parathyroids and pituitary.

Severe McCune-Albright syndrome presenting in the neonatal period almost always presents with Cushing's syndrome from adrenal disease even before the appearance of the classical skin lesions at approximately 6 weeks of age.

The ovarian ultrasound appearances have been characterised and the ovaries are large, cystic and usually asymmetric. Because of the gonadotrophin independence, GnRH analogues are unhelpful and treatment should be with a combination of drugs, including cyproterone acetate, medroxyprogesterone, spironolactone, ketoconazole and testolactone. In severe cases, it is usually the bone disease that predominates with both early fracturing and arteriovenous fistulae, causing heart failure.

To summarise: Girls with adrenal causes of premature sexual maturation are usually easy to distinguish. Premature adrenarche is common and is a diagnosis of exclusion. Of disorders of premature sexual maturation of a gonadal aetiology, the commonest is isolated premature thelarche, which is usually a clinical diagnosis. Retention of the normal harmony of puberty suggests central precocious puberty, and this can be confirmed by an intravenous GnRH test and pelvic ultrasound assessment. Once it has been demonstrated that a girl has central precocious puberty, then neuroradiological imaging will be mandatory.

Treatment with a GnRH analogue both suppresses sexual maturation and improves psychological problems. Other variants of premature sexual maturation of a gonadal cause only require reassurance.

Acknowledgement

We are grateful to the Child Growth Foundation for their support of CT, as well as to Novo Nordisk Pharmaceuticals Ltd, UK.

References

Dr. R. Stanhope
Department of Endocrinology, Great Ormond Street Hospital for Children
Great Ormond Street, London WClN 3JH (UK)