Ann Pediatr Endocrinol Metab.  2016 Sep;21(3):136-142. 10.6065/apem.2016.21.3.136.

Etiology and therapeutic outcomes of children with gonadotropin-independent precocious puberty

• Kang E
• Cho JH
• Choi JH
• Yoo HW

• KMID: 2366788
• DOI: http://doi.org/10.6065/apem.2016.21.3.136

Abstract

PURPOSE
This study was performed to investigate the etiology, clinical features, and outcomes of patients with gonadotropin-independent precocious puberty (GIPP).
METHODS
The study included 16 patients (14 female and 2 male patients) who manifested secondary sexual characteristics, elevated sex hormones, or adrenal androgens with prepubertal luteinizing hormone levels after gonadotropin releasing hormone stimulation diagnosed between May 1994 and December 2015. Patients with congenital adrenal hyperplasia were excluded. Clinical features, laboratory findings, treatment modalities, and outcomes were retrospectively reviewed.
RESULTS
The median age at diagnosis was 2.6 years (range, 0.7-7.9 years) and median follow-up duration was 4.6 years (range, 1 month-9.8 years). Patients with McCune-Albright syndrome (n=5) and functional ovarian cysts (n=4) presented with vaginal bleeding and elevated estradiol levels (23.3±17.5 pg/mL); adrenocortical tumors (n=4) with premature pubarche and elevated dehydroepiandrosterone sulfate levels (87.2-6,530 µg/dL); and human chorionic gonadotropin (hCG)-producing tumor (n=1) with premature pubarche and elevated β-human chorionic gonadotropin levels (47.4 mIU/mL). Two patients were idiopathic. Six patients transited to gonadotropin-dependent precocious puberty median 3.3 years (range, 0.3-5.1 years) after the onset of GIPP. Initial and follow-up height standard deviation scores (0.99±0.84 vs. 1.10±1.10, P=0.44) and bone age advancement (1.49±1.77 years vs. 2.02±1.95 years, P=0.06) were not significantly different.
CONCLUSION
The etiologies of GIPP are heterogeneous, and treatment and prognosis is quite different according to the etiology. Efficacy of treatment with aromatase inhibitors needs to be evaluated after long-term follow-up.

Keyword

Precocious puberty; Gonadotropin-independent; Etiology; Treatment outcome

MeSH Terms

Adrenal Hyperplasia, Congenital
Androgens
Aromatase Inhibitors
Child*
Chorionic Gonadotropin
Dehydroepiandrosterone Sulfate
Diagnosis
Estradiol
Female
Fibrous Dysplasia, Polyostotic
Follow-Up Studies
Gonadal Steroid Hormones
Gonadotropin-Releasing Hormone
Humans
Luteinizing Hormone
Male
Ovarian Cysts
Prognosis
Puberty, Precocious*
Retrospective Studies
Treatment Outcome
Uterine Hemorrhage
Androgens
Aromatase Inhibitors
Chorionic Gonadotropin
Dehydroepiandrosterone Sulfate
Estradiol
Gonadal Steroid Hormones
Gonadotropin-Releasing Hormone
Luteinizing Hormone

Figure

• 

  Fig. 1 Imaging findings of patients with gonadotropin-independent precocious puberty. (A) Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid bone scan (right lateral view) of a patient with McCune-Albright syndrome (MAS) (patient 5) revealed diffuse symmetrical increased uptake along the skull base and occipital bone (arrows), suggesting fibrous dysplasia. (B) 3.6×2.6-cm-sized left ovarian cyst (circle) demonstrated by pelvic ultrasonography in a patient with MAS. (C) Abdominal computed tomography demonstrated an 8.4×6.4-cm left adrenal gland mass with heterogeneous enhancement and calcification (circle) in an 8-month-old girl with premature pubarche (patient 13). (D) Brain magnetic resonance imaging revealed a 2.2×1.9×2.2-cm lobulated mass involving the left basal ganglia (circle) with thickening of the pituitary stalk, indicating germinoma in an 8-year-old boy with premature adrenarche (patient 14).

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