Elevated luteinizing hormone in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology

In women, chronically elevated androgens have been associated with polycystic ovarian syndrome and infertility. Recently, we described transgenic mice with elevated serum LH secondary to targeted expression of a transgene encoding a chimeric LH beta-subunit. Mature transgenic females exhibit elevated androgens, anovulation, and a range of ovarian phenotypes including cysts, widespread luteinization, and tumors. In the present study we have examined serum levels of LH and testosterone and the concurrent development of the reproductive system in prepubertal mice. Serum LH in prepubertal females was elevated despite increased serum testosterone and estradiol, indicating a relative insensitivity to steroid negative feedback. Elevated serum LH and hyperandrogenemia resulted in accelerated vaginal opening and ovarian follicular development in transgenic females. Precocious antral follicle formation and conspicuous hypertrophy of the theca-interstitium preceded the development of large cysts with marked hemorrhage. Based on these studies we conclude that chronic prepubertal elevation of serum LH results in gonadotropin-dependent hyperandrogenemia, leading to abnormal sexual development and significant ovarian pathology.     

Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome

An 8-year-old boy presented with precocious puberty and a mediastinal mass. A computer search showed that this rare presentation is most common with germ cell tumor of the mediastinum in children with Klinefelter syndrome. The tumor was completely resected after preoperative chemotherapy, and the patient is well 2 years after the operation. In patients with Klinefelter syndrome, germ cell tumors are 50 times more common than in patients without Klinefelter syndrome, usually contain nonseminomatous elements, present at an earlier age, and are seldom testicular in location.     

Use of an ultrasensitive recombinant cell bioassay to determine estrogen levels in girls with precocious puberty treated with a luteinizing hormone-releasing hormone agonist

Although treatment of girls with precocious puberty should ideally restore estradiol levels to the normal prepubertal range, treatment effectiveness has usually been monitored by gonadotropin levels because estradiol RIAs have lacked sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a recently developed ultrasensitive recombinant cell bioassay for estradiol would have sufficient sensitivity to demonstrate a dose-dependent suppression of estradiol during LH-releasing hormone agonist treatment and to determine whether currently used doses are able to suppress estradiol levels to the normal prepubertal range. Twenty girls with central precocious puberty were assigned randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 micrograms/ kg.day. A significant dose-response relationship was observed, with mean +/- SD estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the doses of 1, 2, and 4 micrograms/kg.day, respectively (P < 0.01). The highest dose suppressed estradiol levels to just above the 95% confidence limits for normal prepubertal girls (< 0.07-6.3 pmol/L). We conclude that the ultrasensitive bioassay for estradiol has sufficient sensitivity for monitoring the response to LH-releasing hormone agonist treatment of central precocious puberty. Additionally, the observation that the deslorelin dose of 4 micrograms/kg.day did not fully restore estradiol levels to the normal prepubertal range suggests that some girls with precocious puberty may require higher doses to receive the maximal benefit of treatment. We suggest that restoration of estradiol levels to the normal prepubertal range should be the ultimate biochemical measure of efficacy, as estradiol is the key hormone that accelerates growth rate, bone maturation rate, and breast development in girls with precocious puberty.     

Echographic and sonographic study of ovaries in girls with precocious puberty

The aim of this study is the biometrical and morphological evaluation of the ovaries by sonography and the study of the haemodynamics of the ovarian artery flow by doppler ultrasound in 14 girls with precocious puberty and in 33 control subjects. All people ranged in age from 5 to 7 years. The gonadian mean volume and the mean pulsatility index have been evaluated. A significant difference in the ovarian volume has been found between patients and controls. No index between the two groups. We conclude that the doppler ultrasound needs a larger number of cases to evaluate its validity in girls with precocious puberty.     

A female case of the HCG-producing ectopic pinealoma associated with precocious puberty

Report on a 5 year old girl with the caracteristic features of the partial trisomy of the short arm of a chromosome no.4: short stature, microcephaly, hydrocephaly, enophthalmus, bulbous nose, deep set malformed ears, hypertrichosis, brachydactyly, hypoplastic ribs, abnormal EEG, imbecility. Trisomy originated from a reciprocal translocation in the father (46, XY, rcp (4;11) (p 13; q23)). q23)).     

Integrated concentrations of luteinizing hormone and puberty

Integrated serum concentrations of luteinizing hormone have been compared among 30-minute collections from 10 boys (6-18 years old) and 5 girls (5-11 years old). This study suggests that perpubertal as well as pubertal boys have greater mean integrated concentrations of LH during sleep than during waking. One of two pubertal girls had greater concentrations of LH during sleep, while three prepubertal girls did not.     

Efficacy of the subcutaneous reformulated triptorelin depot in children with central precocious puberty

The efficacy, safety and acceptance of newly formulated triptorelin s.c. (Decapeptyl Depot, DDsc) was compared to triptorelin i.m. (DDim) in seven children with central precocious puberty (CPP) in a prospective study. Both formulations were given for 6 months consecutively. During both treatment periods suppression of basal and gonadotropin-releasing hormone (GnRH)-stimulated levels of luteinizing hormone and follicle-stimulating hormone, suppression of sex steroids, arrest of the maturation of gonads and uterus, and slowing of bone maturation were achieved. The height standard deviation score for bone age increased significantly during DDsc treatment (-1.33+/-0.90 to 1.07+/-0.92, p < 0.05). The ratio bone age/chronological age decreased significantly during both treatment periods (1.25+/-0.24 to 1.20+/-0.23,p < 0.05, and 1.20+/-0.23 to 1.16+/-0.22, p < 0.05). With the injection of DDsc in the abdominal wall, a palpable, non-irritating resistance which gradually decreased in size occurred in one patient. With injection into the thigh no indurations were seen. No allergic reactions were encountered. Five of the patients considered DDsc therapy as more pleasant and described a definite decrease in fear of injections. All parents considered DDsc treatment as equal or better than DDim in respect to the suppression of their child' s puberty. It was concluded that DDsc is equipotent to DDim in the treatment of CPP. For the majority of patients DDsc was more acceptable than DDim. The thigh is recommended for the subcutaneous application of DD.     

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

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.     

Irreversible increase of serum IGF-1 and IGFBP-3 levels in GnRH-dependent precocious puberty of different etiologies: implications for the onset of puberty

Contemporary prostheses have developed from small iterations on moderately successful archetypes. This has resulted in modern designs that can either be termed cosmetic or functional, with neither attribute being fully satisfied. A new strategy is needed to develop a generation of upper-limb prostheses that will integrate both cosmetic and functional requirements in a single device. It is hypothesized that design principles applicable to a new generation of prostheses will result from exploring close analogies to the human upper limb. A method of practice led design research has been adopted to explore appropriate analogies, using the production of physical models to elucidate the design problem to the design team and other interested parties. This method uses a consciously iterative approach whereby criticisms and lessons learnt in the development of early models are embodied in subsequent models. This paper describes the first iterative cycle. It includes a critical review of the devices currently available and a study of mechanical analogies to original anatomy which form two of the inputs to the development of a skeletal model hand. It details the lessons learnt from this study and concludes on the wider application of practice led design research in medical engineering.     

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.     

Tuberculosis presenting as a solitary splenic tumour

The authors presented a case of ethmoid glioma which had performed as nasal polyp. They also discussed about problems of classification and treatment this type of neoplasm.     

Role of growth hormone in ovarian physiology and onset of puberty

To evaluate the usefulness of transendoscopic sonography, we have studied the use of a new sonographic probe of 6 F diameter in 11 fresh specimens. We achieved a precise imaging of well known anatomic structures and, moreover, obtained an additional dimension in endoscopy, since the sonographic probe adds a transverse scan to the endoscopic view, like a mini-CT at the tip of the probe. In this way, we also examined the guiding characteristics of this imaging technique, both in real time and on-line. Our results promise further interesting aspects of this technique in minimally invasive neurosurgery and suggest that further development and clinical experience seem to be justified.     

Middle-ear lipoma as a cause of otomastoiditis

We present a case report which describes a rare cause of a common clinical problem; eustachian tube dysfunction. A seven-year-old child presented with a history of chronic draining ears, despite rigorous medical therapy and multiple ventilation tubes. At myringotomy a mass was noted in the middle ear, and she was taken to the operating room for exploration. The patient was found to have a pedunculated lipoma arising from the anterior medial aspect of the middle-ear cleft producing intermittent obstruction of the eustachian tube orifice. This case represents the fourth case of a middle-ear lipoma in the world literature. We present a review of the literature and an exploration of possible aetiologies of this unusual entity in the differential diagnosis of eustachian tube dysfunction.     

Sacral haemangioma as a cause of coccydynia

We report a 55-year-old woman with coccydynia due to a sacral mass. The histological diagnosis was haemangioma. The MRI findings and the unusual location of this lesion are discussed.     

Systemic mastocytosis as a cause of osteoporosis

Out of 21 male patients with osteoporosis who visited an outpatient clinic for endocrine diseases in two years (1994-1995), three had systemic mastocytosis as diagnosed histopathologically. Two of these had characteristic features of urticaria pigmentosa, consisting of multiple brown nodules on the skin of trunk and extremities, and a positive Darier sign. In all of them the excretion of the histamine metabolites methylhistamine and methylimidazoleacetic acid in a 24-hour urine specimen was increased. When osteoporosis is diagnosed in men or premenopausal women, underlying pathology could be considered. Cautious investigation of signs and symptoms of systemic mastocytosis in such patients might prove this disease be less rare than is often assumed.