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PubMed2001

Central precocious puberty: clinical and laboratory features.

OBJECTIVE: To determine whether the initial presentation of patients with central precocious puberty (CPP) varies according to the aetiology, whether this permits the differentiation between idiopathic and organic forms, and whether the body mass index (BMI) and plasma leptin concentrations are linked to gonadotrophin secretion. DESIGN: The clinical and laboratory features of 256 patients (26 boys and 230 girls) with CPP were studied separately in boys and girls. We compared patients with idiopathic CPP (seven boys and 186 girls) to those with organic CPP, whose pubertal development revealed a central nervous system (CNS) lesion (five boys and 11 girls), and to patients with organic CPP associated with a previously treated CNS lesion (14 boys and 33 girls). RESULTS: Boys with organic CPP, having revealed or treated CNS lesions, started their puberty earlier (3.0 +/- 1.0 years and 6.7 +/- 0.5 years) than boys with idiopathic CPP (8.5 +/- 0.2 years, P < 0.01 and < 0.05). Boys with organic CPP associated with a treated CNS lesion had lower luteinizing hormone (LH)/follicle stimulating hormone (FSH) peaks ratio after stimulation with gonadotrophin releasing hormone (GnRH) (1.6 +/- 0.5) than did boys with idiopathic CPP (2.2 +/- 0.3, P < 0.05). Girls with organic CPP revealing a CNS lesion started their puberty earlier (3.6 +/- 0.9 years) than girls with idiopathic CPP (6.6 +/- 0.1 years, P < 0.0 l) and had higher LH (P < 0.01) and FSH peaks (< 0.05). Girls with organic CPP associated with a treated CNS lesion had higher BMI (1.8 +/- 0.2 z-score) than did girls with idiopathic CPP (1.3 +/- 0.1 zs, P < 0.05), higher leptin concentrations (11.7 +/- 1.8 microg/l vs. 7.7 +/- 0.5 microg/l, P < 0.0 l), LH peak (P < 0.01), FSH peak (P < 0.05) and LH/FSH peaks ratio (1 +/- 0.1 vs. 0.8 +/- 0.1, P < 0.05). Only 12.4% of the girls with idiopathic CPP had BMI-zs < 0, and their plasma leptins were positively correlated with BMI (P < 0.0001). CONCLUSIONS: The features of central precocious puberty vary according to the aetiology, but it is impossible to exclude a central nervous system lesion in a given patient with central precocious puberty without performing central nervous system imaging. This imaging remains necessary in all cases of central precocious puberty. Most of the girls with idiopathic central precocious puberty had increased BMI, but we found no correlation between plasma leptin concentrations and gonadotrophin secretion.

Age of Onset↗
PubMed1997

Differential LHRH secretion, dye coupling, and protein expression in two morphologically distinct cell types identified in GT1-7 cultures.

The immortalized neuronal cell line, GT1-7, has been shown to secrete LHRH in a pulsatile manner and to possess many other characteristics of hypothalamic LHRH neurons in vivo, and thus provides a potential model system for studying biochemical and physiological mechanisms regulating LHRH secretion. In the present study, two morphologically and functionally distinct types of cells have been identified in GT1-7 cultures and each type purified to over 95% homogeneity. One type (N cells) appeared more neuronal with extended neurites and somewhat rounded cell perikarya, while the other type (G cells) had flatter cell perikarya that contained filopodia but no neurites. Growth properties of the two cell types also differed. The doubling time for proliferation of N cells was nearly two-fold shorter than that for G cells and N cells displayed 'piling up' whereas G cells exhibited contact inhibition. Functionally, N cells, but not G cells, were dye-coupled as measured by a fluorescence photobleaching assay. While both cell types expressed LHRH, N cells released significantly higher levels of LHRH into the culture media and exhibited more intense LHRH immunostaining. The two cell types also showed differences in immunostaining for other proteins. N cells, unlike G cells, immunostained positive for neuron-specific enolase (NSE), whereas G cells, unlike N cells, stained immunopositive for vimentin. Both cell types expressed SV-40 T antigen protein, indicating that they were derived from the same transgenic mouse hypothalamic tumour. The physiological significance of these two cell types in GT1-7 cultures remains to be determined, but elucidation of their morphological and biochemical properties is intended to contribute to better understanding and application of this experimentally important neuroendocrine cell line.

Adenylyl Cyclases↗
PubMed2002

Hypothalamic obesity in humans: what do we know and what can be done?

Obesity is a common sequel to tumours of the hypothalamic region and their treatment with surgery and radiotherapy. The prevalence of hypothalamic obesity has been underestimated because it may take some years to develop, and the problem has been under-recognized by physicians. Weight gain results from damage to the ventromedial hypothalamus which leads, variously, to hyperphagia, a low metabolic rate, autonomic imbalance, growth hormone (GH) deficiency and various other problems that contribute to weight gain. However, with the exception of GH replacement, few clinical trials have evaluated significant numbers of patients and so the roles of various behavioural, dietary, pharmacological and obesity surgery approaches are controversial. Sufficient knowledge exists to identify those at high risk of hypothalamic obesity so that weight gain prevention approaches can be offered. In those who are already obese, we propose that the principal causal mechanisms in individual patients should be considered as a basis for guiding clinical management.

Autonomic Nervous System↗
PubMed2000

Central nervous system metastasis of a cutaneous epitheliotropic lymphosarcoma in a dog.

This report describes an uncommon case of a cutaneous epitheliotropic T-cell lymphosarcoma with central nervous system (CNS) manifestations in a 9-year-old mixed breed German shepherd dog. The animal had a history of sudden blindness, pyrexia and multifocal areas of hyperaemia in the oral mucosa. A biopsy from the muco-cutaneous junction of the lips led to the diagnosis of an epitheliotropic lymphosarcoma and the animal was humanely destroyed. At necropsy, hyperaemia in the oral mucosa was no longer detectable. In the brain, a mass effacing the optic chiasm and invading the hypothalamic area was found; histological examination revealed lymphoid tumour cell infiltration. In the epithelium of the oral mucosa, intra-epithelial lymphoid tumour cells, sometimes arranged in small clusters (Pautrier's microabscesses), in combination with a mild inflammation in the superficial dermis were observed. Skin and brain tumour cells expressed CD3 antigen, indicating their T-cell origin. This is, to our knowledge, the first report of a cutaneous epitheliotropic lymphosarcoma with CNS metastasis in a dog.

Animals↗
PubMed2001

Surgical strategy for cavernous angioma in hypothalamus.

A very rare case of cavernous angioma in the hypothalamus is presented. The patient was successfully treated by total excision of the haematoma and angioma, and there was no regrowth of the lesion on follow-up MRI. Complete excision of the angioma is the recommended surgical strategy even for patients with deep-seated lesions.

Adult↗
PubMed2003

Endocrine findings in patients with optico-hypothalamic gliomas.

OBJECTIVES: Optico-hypothalamic gliomas (OHG) are an important differential diagnosis in suprasellar tumors. Visual impairment and hydrocephalus are the most frequent findings at presentation. However, only limited data are available about endocrine disturbances in these lesions. PATIENTS AND METHODS: 38 consecutive patients (19 children) were studied retrospectively. Clinical assessment and endocrinological evaluation of pituitary and hypothalamic functions (combined pituitary stimulation test, ITT, CRH-GRH test) were performed before and after (1 week and 3 months) the neurosurgical procedure. RESULTS: Only three patients showed clinical features of endocrine deficiency initially. 16 children and 15 adults out of the 38 patients (31/38, 81.6 %) showed no abnormality in their hormone values when assessed with the combined pituitary stimulation test alone or using more sophisticated investigations such as ITT and CRH-GRH test (72.2 %). Patients with hypothalamic disturbances (8 out of 38, 21 %) had endocrine abnormalities more frequently than those without (57.1 % vs. 9 %, p < 0.05), as assessed by ITT and CRH-GRH-test. CONCLUSIONS: In contrast to other suprasellar tumors, endocrine deficiencies are surprisingly rare in optico-hypothalamic gliomas despite their large size, especially in the absence of hypothalamic disorders. This may be used as a criterion in the differential diagnosis of these lesions, in addition to the radiological findings.

Adolescent↗
PubMed2005

Linear accelerator stereotactic radiosurgery for the treatment of gelastic seizures due to hypothalamic hamartoma.

PURPOSE: There are reports of successful gamma-knife stereotactic radiosurgery (SRS) for the treatment of gelastic seizures associated with a hypothalamic hamartoma. The authors reviewed the results of linear accelerator (LINAC) radiosurgery for patients with medically refractory gelastic seizures due to a sessile hypothalamic hamartoma. METHODS: Three patients with gelastic seizures received SRS between 2003 and 2004. All patients had associated partial complex and/or generalized seizures. One patient demonstrated aggressive behavior. Sessile hamartomas varying in diameter from 6 to 14 mm were identified by MRI. SRS was delivered to a single isocenter by a dedicated LINAC equipped with either a circular beam collimator or a micromultileaf collimator. Patients received 1500 to 1800 cGy prescribed at the 90 to 95 % isodose line. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. These patients remain free of seizures at 17 and 15 months, respectively, after treatment (Engle Class IA). One patient experienced a decline in gelastic seizure frequency nine months after treatment (Engle Class II) without significant reduction in aggressive behavior. Follow-up MRI demonstrated no change in the size or signal characteristics of any tumor. No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. CONCLUSIONS: LINAC SRS represents a safe and effective therapeutic alternative for patients with medically refractory gelastic seizures due to unresectable hypothalamic hamartomas. Radiosurgery is associated with a latency of several months from treatment to reduction in seizure frequency. Further follow-up is required to establish the duration of seizure control following radiosurgery.

Adult↗
PubMed1988

Plasma transferrin levels in abnormal endocrine states. I. The changes in hypophysial diseases before and after treatment.

The concentrations of plasma transferrin (Tf), which has been described possessing growth promoting activity in vitro, were determined in patients with hypophysial diseases before and after treatment. Plasma Tf levels in 74 healthy subjects were 269 +/- 3 (mean +/- SE) mg/dl. In 11 patients with active acromegaly, they were elevated to 353 +/- 11 mg/dl (P less than 0.001), while they were reduced to 168 +/- 14 mg/dl in 8 patients with hypopituitarism (P less than 0.001). They were normalized after appropriate treatment. These data indicate that plasma Tf varies according to endocrine status in relation to that of plasma somatomedin-C, and therefore its measurement may be useful clinically for the evaluation of the status of growth factors. However, the values should be assessed carefully in cases with proper Tf abnormalities, such as hematological, hepatic or renal disorders.

Acromegaly↗
PubMedDate not supplied

[Gelastic epilepsy and precocious puberty in hamartoma of the hypothalamus].

Four cases of hypothalamic hamartoma leading to gelastic epilepsy, precocious puberty and behavioural disorders are reported. Cerebral neuroradiologic examinations revealed a tumor-like mass attached to the hypothalamus in the region of the mamillary bodies in all cases. Precocious puberty developed in the two girls at 4 and 13 months but in neither of the two boys, who both suffered behaviour disturbances in the form of aggressive outbursts. A total resection of the tumors of both boys led to histologic confirmation of hamartoma. One boy was free of seizures upon follow-up, whereas seizure frequency in the other boy was reduced, while his aggressivity increased. The cases are discussed in context of current therapeutic conceptions of gelastic epilepsy and central precocious puberty.

Aggression↗
PubMed1996

Serum leptin levels following hypothalamic surgery.

To study a potential alteration of hypothalamic centers involved in the negative feedback action of leptin on body weight, serum leptin levels were measured in relation to BMI in 18 patients following surgery for a hypothalamic craniopharyngioma (Ctx), and were compared to levels found in 21 patients operated for a pituitary adenoma (Ptx) or in healthy control subjects. All subjects with Ptx received rhGH replacement therapy (0.5 to 2 IU/m2/d), and serum leptin levels were followed in 3 months intervals over 24 months. Serum leptin levels in patients with Ptx were comparable to controls, whereas 7 of the 18 patients with Ctx had higher than expected concentrations for their BMI. GH treatment in Ptx subjects did not alter serum leptin levels. In 5 Ctx patients where preoperative samples were available, weight gain in parallel to an increase in serum leptin levels was observed but only minimal changes in 4 others. Our data support the role of leptin as an important marker of body weight. The rapid increase in serum leptin levels observed in some Ctx subjects suggests that early postoperative measurement of serum leptin levels may help to identify patients at risk of weight gain following hypothalamic destruction.

Adenoma↗
PubMed1987

Hamartoma of the tuber cinereum in a six-month-old boy, causing isosexual precocious puberty.

A case of hamartoma of the tuber cinereum causing isosexual precocious puberty in a six-month-old boy, in whom the lesion was successfully extirpated, is presented. Our patient was relatively young, since hamartomas causing sexual precocity most often occur between the ages of one and three years. Hamartomas are discussed from the clinical and pathological points of view. The mechanisms of initiating pubertas praecox in cases of cerebral tumours, particularly hamartomas, are reviewed.

Hamartoma↗
PubMed1984

Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome. A clinical, morphologic, and biochemical study.

Corticotropin-releasing factor, a hypophyseo-tropic hormone that stimulates adrenocorticotropic hormone (ACTH) secretion, has recently been isolated, characterized, and synthesized in the sheep and rat. We report on a patient with metastatic carcinoma of the prostate presenting with anterior and posterior pituitary hormone deficiency together with ACTH-dependent Cushing's syndrome. At postmortem examination, large areas of the median eminence and pituitary stalk were replaced by tumor, but the corticotrophs were markedly hyperplastic. Immunostaining of tumor cells was positive for corticotropin-releasing factor and was negative for ACTH and a wide range of other hormones. Radioimmunoassay and bioassays showed that tumor extracts and further purified fractions were active in corticotropin-releasing factor, and the tumor material coeluted with corticotropin-releasing factor on high-pressure liquid chromatography. These studies demonstrate that ectopic secretion of corticotropin-releasing factor is a cause of Cushing's syndrome in human beings. The features of this syndrome include hypercortisolism, pituitary corticotroph hyperplasia, elevation of circulating ACTH levels, and failure to suppress the pituitary-adrenal axis with exogenous glucocorticoids.

ACTH Syndrome, Ectopic↗