Controlling precocious puberty--surgical excision of hypothalamic hamartoma causing precocious puberty

Among the causes of precocious puberty, hypothalamic hamartoma comprises a small percentage. However, the frequency of precocious puberty in the presence of hypothalamic hamartoma is quite high. Recently, results of surgery in 14 cases of hypothalamic hamartoma were reported. Precocious puberty completely subsided in three cases and slight improvement was achieved in another three cases. We performed surgery in four patients with hypothalamic hamartomas, with the goal of decreasing the symptoms of precocious puberty. The patients were two females (aged 1 yr, 3 mo and 6 mo) and two males (aged 3 yr, 7 mo and 1 yr, 9 mo). The main symptoms were precocious puberty and mental retardation of varying degrees. The males had excessive growth of body and external genitalia, while the females had genital bleeding and premature breast development. In each case, computed tomographic scans disclosed a round, isodense mass in the interpeduncular cistern, attached to the base of the hypothalamus. Contrast enhancement was negative. Endocrinologically, in case 1, testosterone was 92.6 ng/ml, FSH was 16 mIU/ml, and LH was 2.2 mIU/ml. Although LH was within normal limits, it overresponded to LH-RH stimulation. In case 2, estrogen was 13.5 ng/day, LH was 5.2 mIU/ml, FSH was 5.3 mIU/ml, and LH showed an exaggerated response to LH-RH stimulation. In case 3, testosterone was 362 ng/ml, LH was 8.8 mIU/ml, FSH was 4.8 mIU/ml, and LH showed an abnormally high response to LH-RH stimulation. In case 4, LH was 18.4 mIU/ml, FSH was 12.0 mIU/ml, and both hormones were stimulated abnormally strongly by LH-RH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gonadotropin-secreting pineal teratoma causing precocious puberty

A case of precocious puberty in a 7-year-old boy with a tumor of the pineal region is reported. Human chorionic gonadotropin levels were elevated in the serum and cerebrospinal fluid. Endocrinological evaluation of the hypothalamic-pituitary axis demonstrated a normal prepubertal response. The tumor was resected and proved to be an immature teratoma. Human chorionic gonadotropin levels were markedly elevated in the tumor cyst fluid. Sexual precocity regressed and human chorionic gonadotropin levels in the serum and cerebrospinal fluid fell to normal after surgery, suggesting that the precocious puberty was secondary to ectopic human chorionic gonadotropin production by the pineal teratoma.     

Galenic arteriovenous malformation with precocious puberty

Pineal lesions may appear with precocious puberty. In this report, a patient with precocious puberty and macrogenitosomia caused by an arteriovenous malformation in the pineal region is presented. This vascular malformation was not visualized during investigations 3 years before the present series. It appears that the vascular malformation increased considerably in size within a 3-year period. This case suggests that some arteriovenous malformations may take a malignant course, increasing rapidly in size and behaving like tumors by causing destruction and compression of surrounding structures. This case seems to be unique because, to the best of our knowledge, an arteriovenous malformation associated with precocious puberty has never been described previously.     

Treatment of precocious puberty by GnRH agonists

The objective of GnRH agonist treatment in precocious puberty is to block pubertal development, and to reduce the action of sex steroids on bone maturation in order to restore normal long-term growth of the skeleton. Currently available studies show a positive benefit-risk ratio of GnRH analogs in the treatment of precocious puberty. Adult heights obtained are in average greater than those predicted in the absence of treatment and close to the normal target height. The side effects observed during treatment such as headaches, asthenia or hot flushes, are related to sex steroid deprivation and are observed in 20 to 30% of cases. Questions remain concerning the impact of these treatments on intellectual development and body composition. Finally, to assess the impact on fertility, IPSEN laboratories decided to organize a prospective study on patients treated in the 1980-1990s. In pediatrics, a reduction in the number of injections is an important objective to improve compliance. "Depot" formulations with prolonged release over three months, already used in adult indications, represent a useful progress in pediatrics and have recently been assessed. The efficacy and safety of triptorelin acetate (Decapeptyl) administered at a dose of 11.25 mg every trimester for one year were evaluated in a European multicentre open trial including 54 girls and 10 boys. The LH peak during the GnRH test at three months was used as primary end-point. This slow release triptorelin was shown to be effective, similarly to delayed-acting leuprorelin. The auxological effects, in particular on adult height, were not evaluated in this study.     

A case of hypothalamic astrocytoma with precocious puberty]

A case of hypothalamic astrocytoma with precocious puberty is presented. In July 1989, a 2-year-old girl was admitted to our hospital because of vaginal bleeding and enlargement of breasts. Breast development was Tanner's stage 3 and no pubic hair was present. Endocrinological evaluation revealed a slightly high level of LH, but the responses of LH and FSH to LH-RH test resulted in exceedingly high values similar to those in adults. Plain CT scan showed an isodense mass in the suprasellar cistern which was not enhanced following administration of contrast medium. MR imaging revealed the precise location of the mass attached to the posterior hypothalamus between the pituitary stalk and the mamillary bodies in sagittal view. The signal intensity of the mass was homogenous and isointense relative to the gray matter on T1 weighted image. But on T2 weighted image, it showed high signal intensity compared with the normal brain parenchyma. A right fronto-temporal craniotomy was performed and the tumor was partially removed. Histological examination disclosed moderate hypercellularity of glial cells but no neurons were visible. This appeared to be astrocytoma grade II. In the literature, CT and MRI behaviour of hypothalamic hamartomas are almost similar to our case. Therefore we think it is not possible at the present time to differentiate a low grade astrocytoma from hamartoma when using CT and MRI alone. In this case, the mechanism of development of precocious puberty seemed to be due to hypothalamic compression by the tumor.     

Gonadoblastoma presenting as isosexual precocious puberty in a genetic female

A 6 1/2-year-old female with pseudoprecocious puberty was found to have a gonadoblastoma. Her karyotype was 46, XX; serum estradiol level was markedly elevated; and androgens were within the range of normal. The importance of the Y chromosome and dysgenetic gonad in the predisposition to development of a gonadoblastoma is reviewed. A further categorization of gonadoblastomas based on the presence or absence of the Y chromosome is suggested.     

Klinefelter's syndrome and precocious puberty: a harbinger for tumor

Boys with Klinefelter's syndrome are at an increased risk of precocious puberty. Most cases are either idiopathic or due to a mediastinal tumor. Patients with Klinefelter's syndrome are at a high risk of primary, extragonadal germ cell tumors, which are usually nonseminomatous, but can be a mixed type with seminomatous elements. The differential diagnosis of precocious puberty includes mediastinal tumors, especially in boys with Klinefelter's syndrome.     

Microsurgical treatment for hypothalamic hamartoma in children with precocious puberty

BACKGROUND: We review the surgical treatment of hypothalamic hamartoma causing precocious puberty. METHODS: Six children (three girls and three boys) with precocious puberty secondary to hypothalamic hamartoma were recruited for our study. The mean age of the patients was 30 months old (range 13 months to 5 years), and the mean age of the onset of puberty was 7.3 months. All patients were treated by microsurgery. RESULTS: All patients had higher then normal stature, body weight, bone growth, and serum levels of sexual hormones. The boys presented with mature external genitalia, pubic hair, frequent erection, and acne, while the girls presented with growth of breasts and menarche. Magnetic resonance image (MRI) revealed an isointense mass below the tuber cinereum extending into the supersellar and interpeduncular cistern, ranging from 4 to 12 mm in diameter, consistent with pedunculate hamartoma. The hamartoma was removed completely via a right pterional approach. The symptoms and signs of precocious puberty resolved completely, and sexual hormone levels decreased to the pre-pubertal range in all six patients without any postoperative complications. CONCLUSION: We report a series of six children with hypothalamic hamartoma-induced precocious puberty who underwent microsurgical treatment. All of them recovered completely to their age-appropriate state. Microsurgery is a good choice of treatment for pedunculate hypothalamic hamartoma.     

Testosterone-producing hepatoblastoma in a 3-year-old boy with precocious puberty

The syndrome of isosexual precocious puberty (PP) associated with a primary malignant hepatic tumor is rare and previously reported in only 17 cases with poor prognosis. Twelve cases are well-documented gonadotropin-producing tumors. We here describe a new case of virilizing hepatoblastoma in a 2-year-10-month-old boy with evidence of testosterone (T) production by the tumor itself, and survival with a 3 1/2-year follow-up after an extended right hepatic lobectomy. Preoperative laboratory findings showed high levels of serum alpha-fetoprotein (AFP) and T:350,000 ng/mL and 4.92 ng/mL, respectively, which normalized after surgery. There was no circulating gonadotropin nor stimulation of the hypothalamic-pituitary axis. Testicular biopsy showed neither interstitial-cell maturation nor Leydig-cell hyperplasia. Moreover, demonstration of T secretion by tumor cells and T synthesis in presence of C14 progesterone was performed in an in vitro culture system. These data seem to provide supportive evidence of a T-producing hepatoblastoma.     

延续护理对特发性中枢性性早熟患儿治疗依从性的影响

目的探讨延续护理对特发性中枢性性早熟(ICPP)患儿治疗依从性的影响。方法制订ICPP延续护理方案,将92例ICPP患儿随机分为观察组(48例)和对照组(44例),观察组接受延续护理,对照组接受常规护理,分别于确诊当日和接受治疗1年后比较患儿治疗依从性及护理满意度。结果观察组治疗依从性,满意度显著高于对照组(均P0.01)。结论延续护理有利于改善ICPP患儿治疗依从性,提高护理满意度。     

Gamma knife radiosurgery for hypothalamic hamartomas in patients with medically intractable epilepsy and precocious puberty. Report of two cases

Hamartoma of the hypothalamus represents a well-known but rare cause of central precocious puberty and gelastic epilepsy. Due to the delicate site in which the tumor is located, surgery is often unsuccessful and associated with considerable risks. In the two cases presented, gamma knife radiosurgery was applied as a safe and noninvasive alternative to obtain seizure control. Two patients, a 13-year-old boy and a 6-year-old girl, presented with medically intractable gelastic epilepsy and increasing episodes of secondary generalized seizures. Abnormal behavior and precocious puberty were also evident. Magnetic resonance (MR) imaging revealed hypothalamic hamartomas measuring 13 and 11 mm, respectively. After general anesthesia had been induced in the patients, radiosurgical treatment was performed with margin doses of 12 Gy to 90% and 60% of isodose areas, covering volumes of 700 and 500 mm3, respectively. After follow-up periods of 54 months in the boy and 36 months in the girl, progressive decrease in both seizure frequency and intensity was noted (Engel outcome scores IIa and IIIa, respectively). Both patients are currently able to attend public school. Follow-up MR imaging has not revealed significant changes in the sizes of the lesions. Gamma knife radiosurgery can be an effective and safe treatment modality for achieving good seizure control in patients with hypothalamic hamartomas.     

Isosexual precocious puberty associated with multilocular arachnoid cysts at the cranial base

Summary A case of precocious puberty associated with a multilocular arachnoid cyst at the base of the skull is reported. The extent of the cyst occupying the suprasellar region and middle and posterior fossae was best demonstrated by biplane computed tomography. Clinical and computed tomographic improvements followed cysto-peritoneal shunts.     

A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma associated with precocious puberty

Summary We treated a 1-year-old female with a hypothalamic hamartoma and precocious puberty with leuprolide acetate depot, a super long-acting hormone-releasing hormone analogue (Tap-144-SR; [D-Leu⁶-[des-Gly¹⁰-NH₂]-LH-RH ethylamide acetate). The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH analogue (30 g/kg) was injected subcutaneously once every 4 weeks. Clinical and laboratory manifestations of precocious puberty showed marked improvement. A follow-up after 16 months of treatment, the size of the tumour decreased significantly and remained unchanged for 2 years of further follow-up. To the best of our knowledge, this is the first hypothalamic hamartoma case in whom a decrease of tumour size under treatment with LH-RH analogue has been documented. But, because diagnosis of hamartoma is only based on neuroradiological and not on histological examinations, the possibility of a gangliocytoma cannot be excluded with certainty.