A Dilemma: Premature Thelarche or Normal Pubertal Development

To The Editor:

We have read with interest the recently published article entitled “Premature thelarche in an 8-year-old girl following prolonged use of risperidone” by White et al. (2014). White et al. presented an 8-year-old girl with premature breast development and no galactorrhea after ∼ 1 year of risperidone usage for psychotic disorder not otherwise specified. They concluded that the implications of antipsychotic use were not well-known, and that more long-term studies were indicated for antipsychotics in terms of side effects in children.

Premature sexual development in girls may result from isolated premature thelarche or central precocious puberty. Isolated premature thelarche is a common self-limiting disorder characterized by breast development, usually at <2 years of age, with no other signs of puberty. Precocious puberty can result in early activation of the hypothalamo–pituitary–gonadal axis prior to 8 years of age, and is usually idiopathic in girls (Quigley and Pescovitz 1997). It is crucial to describe the precise time that thelarche began, to distinguish premature thelarche from normal sexual development. This patient had started risperidone when she was 7.5 years old, and had used this prescription for 9 months. However, she was at least 8 years and 3 months old when an emergency appointment was made because of thelarche. We think that the patient may probably have been in normal puberty, because the thelarche of the patient was noticed after she was 8 years old. In addition, the authors did not mention the pubic hair, vaginal bleeding, and increased growth velocity of the patient at Tanner stage 3 thelarche in the initial evaluation.

The authors reported that basic laboratory testing was within normal limits. Sampling time and luteinizing hormone/estradiol level and bone age results are very important in the differential diagnosis of precocious puberty and premature thelarche. A luteinizing hormone-releasing hormone (LHRH) test may be needed to assure that there is central precocious puberty. Moreover, the patient underwent a magnetic resonance imaging (MRI) of her brain to evaluate the possibility of a pituitary tumor, although brain or hypophysis MRI is not indicated in a differential diagnosis of premature thelarche. If central precocious puberty is confirmed with an LHRH test, MRI may be considered, especially for younger girls (Brauner et al. 2005).

In a symptomatic patient with suspected drug-induced hyperprolactinemia, discontinuation of the drug for 3 days, or substitution with an alternative one and remeasurement of serum prolactin, are recommended. If drug discontinuation is impossible, and the onset of the hyperprolactinemia does not coincide with therapy initiation, obtaining a pituitary MRI to differentiate between drug-induced hyperprolactinemia and symptomatic hyperprolactinemia caused by a pituitary or hypothalamic mass is recommended. Mild hyperprolactinemia caused by risperidone may be followed up without hypophysis MRI (Melmed et al. 2011). In premature thelarche or precocious puberty, pelvic ultrasonography may be performed to rule out an ovarian cyst.

Finally, we are curious what happened after the aripiprazole treatment. Did the thelarche regress, was it stable or did it progress in this patient?

We think that these additional data could provide clearer information for evaluation of premature thelarche to the readers of this journal.