leuprolide and Hamartoma

Obesity, age and hormone imbalances including hypothyroidism and growth hormone deficiency and therapy, but not gonadotropin-releasing hormone agonist (GnRHa) therapy, have been identified as risk factors for slipped capital femoral epiphysis (SCFE). Five of 7 reported cases describe SCFE in children shortly after GnRHa therapy cessation.. We report 3 cases of SCFE that occurred in children on GnRHa therapy for the treatment of central precocious puberty (CPP) and discuss possible promoting factors.. An otherwise healthy 8.75-year-old girl [body mass index (BMI) Z score +1.75] developed SCFE 6.75 years into GnRHa therapy for idiopathic CPP. A second girl (with a history of acute lymphoblastic leukemia requiring total body irradiation) was 10.6 years old (BMI Z score +1.06) when she developed SCFE 3.3 years into GnRHa therapy. The third case was an 8.75-year-old female with CPP secondary to a hypothalamic hamartoma (BMI Z score +1.65) who developed bilateral SCFE 5.6 years into therapy.. Increasing evidence suggests an association between GnRHa therapy for CPP and the occurrence of SCFE. We suggest that a lack of adequate sex hormone exposure at a 'critical period' of bone formation may result in a weakened epiphysis that becomes susceptible to slipping. © 2013 S. Karger AG, Basel.

Topics: Age Determination by Skeleton; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Infant; Leuprolide; Overweight; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Puberty, Precocious; Slipped Capital Femoral Epiphyses

Central precocious puberty (CPP) is defined as pubertal development caused by activation of the hypothalamic-pituitary-gonadal axis before 8 years of age in girls and 9 years in boys. Failure to recognize and/or treat this condition can result in short adult stature.. To determine the etiology, clinical presentation and near-final height (NFH) of Thai children with CPP with or without gonadotropin-releasing hormone analog (GnRHa) treatment.. In a longitudinal observational study, 73 CPP patients who attended Songklanagarind Hospital between 1995 and 2009 were followed up every 3-6 months until they attained their NFH.. The etiologies observed were idiopathic CPP, hypothalamic hamartoma and central nervous system diseases. The mean age at time of diagnosis was 6.4 +/- 2.9 years. Bone age was on average 4 years more advanced than chronological age. Of the 52 patients who reached their NFH during the study, 32 were treated with GnRHa and 20 were not. The mean age at menarche was significantly greater for GnRHa-treated than for untreated girls (11.6 +/- 0.8 vs 10.1 +/- 1.1 years, p < 0.001). The median NFH of GnRHa-treated girls was 152.4 +/- 5.2 cm, which was significantly greater than the 144.4 +/- 5.0 cm for untreated girls (p < 0.001).. GnRHa treatment can preserve the genetic height potential of children with CPP.

Topics: Age Determination by Skeleton; Body Height; Central Nervous System Diseases; Child; Child Development; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Growth Disorders; Hamartoma; Humans; Hypothalamic Diseases; Leuprolide; Longitudinal Studies; Male; Menarche; Puberty, Precocious; Thailand; Treatment Outcome

A 1-year-old male child with isosexual central (gonadotropin-dependent) precocious puberty caused by hypothalamic hamartoma is reported. Details of the diagnosis based solely on neuromaging characteristics, and satisfactory results of medical treatment with gonadotropin releasing hormone agonist analogues, are highlighted.

Topics: Hamartoma; Humans; Hypothalamic Diseases; Infant; Leuprolide; Magnetic Resonance Imaging; Male; Puberty, Precocious

The gonadotropin releasing hormone (GnRH) secreting hypothalamic hamartoma (HH) is a congenital malformation consisting of a heterotopic mass of nervous tissue that contains GnRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle. HH is a well recognised cause of gonadotropin dependent precocious puberty (GDPP). Long term data are presented on eight children (five boys and three girls) with GDPP due to HH. Physical signs of puberty were observed before 2 years of age in all patients. At presentation with sexual precocity, the mean height standard deviation (SD) for chronological age was +1.60 (1.27) and the mean height SD for bone age was -0.92 (1.77). Neurological symptoms were absent at presentation and follow up. The hamartoma diameter ranged from 5 to 18 mm and did not change in six patients who had magnetic resonance imaging follow up. All patients were treated clinically with GnRH agonists (GnRH-a). The duration of treatment varied from 2.66 to 8.41 years. Seven of the eight children had satisfactory responses to treatment, shown by regression of pubertal signs, suppression of hormonal levels, and improvement of height SD for bone age and predicted height. One patient had a severe local reaction to GnRH-a with failure of hormonal suppression and progression of pubertal signs. It seems that HH is benign and that GnRH-a treatment provides satisfactory and safe control for most children with GDPP due to HH.

Topics: Antineoplastic Agents, Hormonal; Child; Child, Preschool; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Hamartoma; Humans; Hypothalamic Diseases; Leuprolide; Magnetic Resonance Imaging; Male; Puberty, Precocious

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 micrograms/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.

Topics: Delayed-Action Preparations; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Infant; Injections, Subcutaneous; Leuprolide; Puberty, Precocious

The LHRH-secreting hypothalamic hamartoma (HH), a congenital malformation consisting of a heterotopic mass of nervous tissue that contains LHRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle, can cause true or central precocious puberty (TPP). We have suggested that it functions as an ectopic LHRH pulse generator independent of the central nervous system inhibitory mechanism that normally restrains the hypothalamic LHRH pulse generator. TPP associated with a hamartoma has all of the hormonal hallmarks of puberty, including a pubertal pattern of pulsatile LH and a pubertal plasma LH response to LHRH administration. Little is known about the natural history of HH. We present long term data on 10 children (5 females and 5 males) with TPP due to HH. Physical signs of puberty were observed at a mean age of 2.2 +/- 1.6 yr (range, 0.5-5.1). Two of 10 had a pedunculated mass, and 8 of 10 had a sessile mass. The hamartoma varied in diameter from 4-25 mm and did not change with time (3.5-8.7 yr). Four patients have a seizure disorder, 3 with gelastic seizures (1 with mental retardation) and 1 with tonic-clonic seizures. The shape of the hamartoma, sessile or pedunculated, did not correlate with the occurrence of seizures. At presentation with sexual precocity, the mean height SD for chronological age was +3.5 +/- 0.4, the mean height SD for bone age was -1.9 +/- 0.4, and the mean bone age SD for chronological age was +6.8 +/- 0.7. Baseline data were comparable to those of 10 females with idiopathic TPP. Nine of 10 HH patients and all idiopathic TPP patients were treated with a LHRH agonist. The response to therapy was excellent in both groups and indistinguishable. Nine of 10 HH children attend school regularly and, aside from those with seizures, have no neurological handicap. While surgical resection of the hamartoma has been recommended, it carries an increased risk of morbidity and mortality and, if removal is incomplete, does not arrest the sexual precocity. In our experience, LHRH agonist therapy for TPP due to HH is the preferable approach.

Topics: Child, Preschool; Female; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Neoplasms; Infant; Leuprolide; Magnetic Resonance Imaging; Male; Nafarelin; Puberty, Precocious

We describe four male patients with hypothalamic hamartomas associated with sexual precocity. Our assessment of their management suggests that resection using current microsurgical techniques is a valid treatment option if the patient has a normal pubertal endocrine makeup, if the hamartoma is pedunculated, and if the patient is young enough to require years of parenteral medical treatment. Such surgical treatment can be curative, and subsequent growth and development can be normal (patients 1 and 2). However, if the patient is near to pubertal age (patient 3) or if neurosurgical or gonadotropin releasing hormone analogue treatment is not available, the natural history (patient 4) suggests that the only undesirable effects are accelerated growth, tall stature for age, and premature sexual development during childhood, as well as the psychosocial problems that may accompany them. Adult height may be compromised, although the two patients who did not undergo a surgical procedure and did not receive gonadotropin releasing hormone analogue therapy are above the lower limits of the normal range of adult male height. Therefore, if the hamartoma is pedunculated and cessation of pubertal development is desired, resection of the hamartoma is a reasonable therapeutic option.

Topics: Antineoplastic Agents; Child; Child, Preschool; Danazol; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Neoplasms; Infant; Leuprolide; Luteinizing Hormone; Male; Puberty, Precocious; Testosterone