Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children

The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age advancement (3.4 +/- 1.5 years) and negative height standard deviation for bone age (-2.7 +/- 1.5) than those with PPP (1.9 +/- 1.6 years and -1.3 +/- 1.3) and premature thelarche (0.4 +/- 0.4 years and -0.8 +/- 0.8). Patients with neurogenic CIPP had significantly higher levels of baseline and GnRH-stimulated levels of LH and FSH and LH:FSH ratio than those with idiopathic CIPP. Occurrence of neurogenic CIPP in seven girls with an age of onset after 6 years emphasizes the need for CNS imaging in these girls contrary to the current recommendations. The fact that 65.6% cases of idiopathic CIPP presented after the age of 6 years raises the possibility that these patients may be physiological variants of normal puberty. Pointers to neurogenic CIPP included early age of onset in girls, clinical features of CNS involvement, and elevated basal and stimulated LH levels and LH:FSH ratio.