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T Brue

Publications and source records attributed to T Brue.

At least 37 records · Page 2Linked to original sources
PubMed1999

[An immunologic etiology for hyperprolactinemia: macroprolactinemia].

Besides classical etiologies of hyperprolactinaemia (pregnancy, pharmacological treatments, pituitary or hypothalamic perturbations), another less known cause may explain a spectacular idiopathic elevation of plasma concentrations of prolactin hormone. Macroprolactinaemia is characterized by the presence of a circulating high molecular weight complex of prolactin with an immunoglobulin G. In this article, we report the cases of 3 female patients for whom size exclusion chromatography technique permitted to give a precise biological diagnosis and to avoid heavy, expensive, time consuming and unnecessary clinical investigations or therapeutic actions. Patients with macroprolactinaemia do not exhibit clinical features of classical hyperprolactinaemia, notably as regard to menstrual and fertility disturbances.

Adult↗
PubMed1998

The hormonal response to stress is not modified by the dramatic decrease in prolactin plasma concentration during surgery for microprolactinoma.

OBJECTIVES: To determine the endocrine response to surgical stress in a homogeneous population of 36 women with microprolactinomas, particularly to evaluate the effect of the sharp decrease in plasma prolactin on stress induced hormonal secretion. In addition, the effects of exogenous opiates on prolactin secretion were studied. METHODS: The plasma kinetics of cortisol, prolactin, ACTH, GH, and beta-endorphin like immunoreactivity (beta-ELI) were analysed by including patients operated on with strict anaesthetic and surgical protocols, and by sampling blood every 10 minutes, starting at premedication up to 3 hours after induction. RESULTS AND CONCLUSIONS: (a) Surgical stress or opiate administration did not induce prolactin release in patients with microprolactinoma. (b) The dramatic decrease in prolactin concentrations have apparently no effect on the release of other hormones involved in stress. (c) The existence of an early GH peak, independently of any surgical procedure, strongly suggests that GH is released by surgical stress whereas beta-endorphin is secreted in response to pain. Thus GH may be a useful marker of surgical stress.

Adolescent↗
PubMed1997

[Cushing syndrome disclosing bronchial neuroendocrine carcinoma: value of scintigraphy with octreotide].

A 44-year-old man presenting with atypical maniac behavior and hypokaliemia was diagnosed with Cushing's syndrome and treated in emergency by bilateral adrenalectomy. Endocrine investigations were suggestive of an ectopic adrenocorticotropic (ACTH) secretion, both at baseline (mean ACTH levels = 215 pg/mL, beta-lipotropic hormone = 2329 pg/mL; molar ratio > 5) and after pharmacodynamic testing (lack of inhibition of ACTH by dexamethasone, blunted ACTH response to corticotropin releasing hormone). Ectopic ACTH secretion was investigated while pituitary ACTH secretion was suppressed by dexamethasone. A paradoxical rise of ACTH from 384 to 717 pg/mL was observed after subcutaneous administration of 500 micrograms octreotide. A right lung tumor that remained occult for 7 years was only revealed by octreotide scintigraphy, despite annual chest tomodensitometric examinations. Right inferior lung lobectomy allowed allowed for removal of a 13 mm tumor corresponding to a bronchial neuroendocrine carcinoma with positive immunostaining for ACTH. Mediastinal lymph nodes were histologically normal. Perioperative ACTH measurements, showing a more than 50% decrease from baseline at 15 minutes after tumor resection, were suggestive of complete tumor removal. This was confirmed 10 days postoperatively by undetectable ACTH levels and by a negative octreotide scintigraphy after surgery. This case report of an occult ACTH secreting bronchial neuroendocrine carcinoma illustrates the diagnostic value of octreotide scintigraphy, and the prognostic value of perioperative ACTH measurements in such cases.

ACTH Syndrome, Ectopic↗
PubMed1997

[Congenital multiple anterior pituitary hormone deficiencies. An approach of pituitary ontogenesis].

A number of transcription factors evidenced in the pituitary may play a part in the development of this gland, namely Pit-1, Prop-1, P-Lim, Ptx1, Rpx, Dax-1, SF-1. Several of these factors are involved in animal models of hypopituitarism, while up to now only Pit-1 gene alterations have been shown to be responsible for hypopituitarism in man. These factors are briefly presented, and current data on genetically determined uni- or multi-hormonal pituitary deficiencies are reviewed. In particular, data on combined somatotroph, lactotroph and thyrotroph deficiencies due to Pit-1 gene alterations are detailed. Analysis of phenotype-genotype relationships in this syndrome and in other pathological models of multiple pituitary hormone deficiencies will provide useful information on the complex sequence of events that contribute to the development of the pituitary gland and to differentiation and regulation of the different pituitary cell lines.

Animals↗
PubMed1996

[Prolactin-secreting adenoma].

Prolactinoma, a benign tumor originating from the lactotroph cells of the anterior pituitary, is responsible for signs and symptoms related to both hypersecretion of prolactin and tumor mass. Hyperprolactinemia frequently causes menstrual cycle disturbances, galactorrhea and infertility in women, sexual disorders in men. Microadenomas, characterized by a largest diameter less than 10 mm, may induce frontal headaches, and macroadenomas (more than 10 mm in diameter) may also impair visual function through chiasma compression. Treatment modalities include dopamine agonist therapy such as bromocriptine which allows normalization of prolactin levels, restoration of gonadal functions and tumor shrinkage in most cases. In microadenomas a definitive cure may be achieved by transsphenoidal total selective adenomectomy.

Bromocriptine↗
PubMed1996

A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency.

The pituitary-specific transcription factor Pit-1/GHF1 regulates the expression of PRL, GH, and TSH beta genes through binding to specific regions of the promoters of these genes. Mutations of the Pit-1 gene have been shown to be responsible for a syndrome of combined pituitary hormone deficiency (CPHD), including complete GH and PRL deficiencies and central hypothyroidism. We studied four siblings presenting with CPHD born to healthy consanguinous parents. All four affected children had complete GH deficiency diagnosed in early childhood. They later developed hypothyroidism and were found to have undetectable PRL levels. The pituitary gland was hypoplastic at magnetic resonance examination in one of the patients. Amplification of genomic DNA and subsequent sequencing of the six exons of the Pit-1 gene allowed identification in the four patients with CPHD of an as yet undescribed mutation in exon 3. A substitution of T go G induced a change from a Phe to a Cys residue at position 135 within the hydrophobic core of the POU-specific DNA-binding domain of the Pit-1 protein. All affected children were homozygous for the mutation, whereas the mother was heterozygous, suggesting a recessive mode of inheritance. Molecular studies in other affected families will allow instructive genotype-phenotype correlations concerning the Pit-1 gene.

Adolescent↗
PubMed1996

Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy.

Resistance to bromocriptine, defined as the absence of normalization of prolactin (PRL) levels despite a 15-30 mg daily dose of bromocriptine during at least 6 months, has been observed in 5-17% of the prolactinomas according to the literature. The recent availability of a new potent dopamine agonist, quinagolide, prompted us to analyze its long-term therapeutic effects in 28 patients with prolactinomas resistant to bromocriptine. Before bromocriptine, their PRL levels were 520 +/- 185 micrograms/l (mean +/- SEM) and decreased to 291 +/- 154 micrograms/l after a 6-21 month period of bromocriptine treatment. All the women (N = 20) remained amenorrheic and hypogonadism was not improved in men (N = 8). Subsequently, after 1 year of 150-300 micrograms/day quinagolide, 12/28 patients of the present series recovered normal gonadal function and their initial mean baseline PRL value (404 +/- 180 micrograms/l) was 16 +/- 2 micrograms/l after 1 year of treatment. A significant tumor shrinkage was observed in 5/8 macroadenomas (62%). During the 3-year follow-up period under quinagolide, a similar good control was achieved in these patients, with the exception of one man presenting with a secondary rise of PRL under quinagolide. In contrast, 15 other patients (one patient interrupted quinagolide at 6 months because of poor tolerance) were not normalized under 150-450 micrograms/day quinagolide. Their initial PRL levels (606 +/- 298 micrograms/l) were reduced to 343 +/- 187 micrograms/l (versus 463 +/- 265 micrograms/l under bromocriptine after the same duration of treatment). Despite such a partial inhibitory effect of quinagolide, 7/12 women resumed menstrual cycles and three pregnancies occurred. In no case was any tumor shrinkage noticed during the 3-4-year follow-up. Three patients even presented, after 2 years of quinagolide treatment, with a secondary rise of PRL values associated with a further tumor growth in two patients. During the 3-year follow-up period, nine pregnancies occurred in seven women. In five women, after quinagolide withdrawal, the plasma PRL baseline values ranged from 52 to 158 micrograms/l and from 65 to 192 micrograms/l, respectively, at the first trimester and at the end of uneventful pregnancies. In contrast, in two women a rapid increase of PRL (240-400 micrograms/l) correlated with tumor growth during the first trimester. Such a tumor progression was blocked by quinagolide treatment but not by bromocriptine. These data, although observed in a limited series, justify the careful follow-up of pregnancies in this subclass of patients at risk. Finally, in the whole population, long-term control of hyperprolactinemia by quinagolide was obtained in 11/28 patients (39%) previously resistant to bromocriptine, and 15/20 women (75%) resumed normal gonadal function with a quinagolide daily dose of 300 micrograms in most of them.

Aminoquinolines↗
PubMed1996

Insulin-induced lipoatrophy in type I diabetes. A possible tumor necrosis factor-alpha-mediated dedifferentiation of adipocytes.

OBJECTIVE: To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions. RESEARCH DESIGN AND METHODS: An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied. RESULTS: The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone. CONCLUSIONS: In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.

Adipocytes↗
PubMed1995

Glycosylated and non-glycosylated prolactin forms are increased after opioid administration as part of surgical anaesthesia.

OBJECTIVE: Previous studies have shown that non-glycosylated prolactin (NG-PRL) increased more markedly than glycosylated hormone (G-PRL) after TRH or metoclopramide stimulation. The aim of the present study was to determine whether such results could be extended to opioid-induced PRL stimulation. DESIGN: Open and prospective study. Using a newly developed IRMA specific for NG-PRL, we determined G-PRL and NG-PRL immunoreactivities after administration of 0.8-1.2 mg of the opioid drug phenoperidine as part of an anaesthesia. PATIENTS: Ten male patients anaesthetized for surgical treatment of a prolapsed lumbar intervertebral disc. MEASUREMENTS: Samples were obtained hourly pre and post-operatively, and every 15 minutes during operation for determination of plasma PRL, NG-PRL and G-PRL. Plasma cortisol, ACTH and GH levels were measured in an attempt to differentiate the respective roles of stress and opiate agonists in the variations of PRL levels during surgery. RESULTS: A dramatic increase in PRL levels was observed in all patients from an average of 300 +/- 90 to 1200 +/- 330 mU/l (mean + SEM) 30 minutes after drug administration. The proportion of G-PRL immunoreactivity was not significantly different when basal (25.2%) and stimulated (27%) values were compared (P > 0.05), and when mean increments of NG-PRL and G-PRL were compared (345 and 348%, respectively). The opioid drug induced a significant decrease in cortisol levels after injection and during operation (from 585 +/- 63 to 99 +/- 51 nmol/l) with a concomitant decrease in ACTH levels. GH levels were not significantly altered during anaesthesia but were significantly greater (P < 0.05) after than before surgery (5.0 +/- 1.3 vs 0.98 +/- 0.54 mU/l, respectively). CONCLUSIONS: We conclude from the present and from previous data that opioid induced anaesthesia is accompanied by an increase in both glycosylated and non-glycosylated PRL and that different PRL secretagogues may induce distinct responses in terms of PRL molecular forms.

Adult↗
PubMed1995

Pattern of prolactin diurnal secretion in normal humans: evidence for nonlinear dynamics.

Prolactin (PRL) circadian profiles were analyzed using methods of nonlinear dynamics, directly from the experimental data, by combining in a single time-series (432 measurements), six individual 24-hour PRL profiles (72 measurements per profile, sampling interval = 20 min), obtained from young healthy human volunteers (4 males, 2 females), under basal conditions. Significant autocorrelation exists between any given point of the time series and a limited number of its successors. Fourier analysis showed a dominant frequency of 1 cycle/24 h, without sub-24-hour harmonics. Poincaré section indicated the presence of a fractal attractor and a sketch of the attractor revealed a highly convoluted geometric structure with a conical contour. The box-counting dimension (D0), information dimension (D1) and correlation dimension (D2) of the attractor had low, fractal values, did not differ significantly from each other, and exhibited saturation at an embedding dimension of 2. The evidence taken together suggests that, under basal conditions, the daily changes in the peripheral blood levels of PRL are governed by nonlinear deterministic dynamics, with a dominant rhythm of 1 cycle/day mixed with a higher-frequency, low-amplitude signal.

Adult↗
PubMed1994

3D-FT thin sections MRI of prolactin-secreting pituitary microadenomas.

We studied 76 patients with endocrinological features of prolactin-secreting microadenoma by MRI, using three dimensional (3D) gradient echo acquisition (FLASH) sequences. MRI revealed a focal signal abnormality in the pituitary in all 37 patients who had not previously taken bromocriptine. However, focal abnormality was shown in only half the patients had been on dopamine agonist therapy; the MRI findings in these 39 patients were not affected by the duration and dosage bromocriptine, nor by the time elapsed since its discontinuation. The microadenoma gave spontaneous high signal on the unenhanced T1-weighted images in 8 cases; it was not seen on unenhanced images in 25 cases. It appeared as low signal within the enhancing gland in 51 cases but enhanced in 7 cases. The 3D technique gives thin (1 mm) slices and therefore facilitates detection of small focal abnormalities in the pituitary gland (2 x 2 mm). In the 19 previously treated patients in whom MRI did not demonstrate a focal abnormality, it showed localised atrophy of the gland in 3, a large, round gland with homogeneous signal in 1, and a heterogeneous appearance in 11; it was normal in 4 cases.

Adolescent↗
PubMed1994

[Etiopathogenesis of pituitary tumors].

In this present work, the authors discuss some recent advances in the pathogenesis of pituitary tumours. The model of transgenic mice suggest that chronic hormonal stimulation and some growth factors could sustain pituitary tumour development. However, these data are not suitable for human pituitary adenomas. The evidence that most pituitary adenomas are monoclonal in origin has prompted a search for somatic mutations. The mutated Gs alpha are found in only 30-40% of somatotroph adenomas and the ras mutations seem to be associated with the malignant transformation. In some prolactinomas resistant to the bromocriptine treatment, quantitative and qualitative alterations of the dopamine receptor D2, have been described. Mutations of protein kinase C have been identified in some invasive pituitary tumours. Molecular abnormalities have been reported in some cases (allele loss at the 11q13 locus, retinoblastoma gene mutation, aberrant expression of hst gene, Pit-1 overexpression) but none by itself can explain the tumour formation. The pituitary tumorigenesis is certainly a multistep process with the intervention of multiple promoting factors.

Adenoma↗
PubMed1994

[Evaluation of vertebral bone mass in anorexia nervosa].

Lumbar bone mineral content (BMC) of 33 female patients aged 14-30 years (19 +/- 4.1 (mean +/- SD) with anorexia nervosa (duration 31 +/- 37 months) was studied using dual X-ray absorptiometry. Results were compared with the data obtained in a population of 26 women aged 17-38 years without bone disease. BMC was significantly decreased (0.872 +/- 0.107 g/cm2 hydroxyapatite) in anorectic patients as compared to controls (1.008 +/- 0.098 hydroxyapatite). A single patient had a non traumatic vertebral compression fracture. A statistically significant negative correlation was found between BMC and duration of amenorrhea (r = 0.48; p < 0.01). There was no significant correlation between BMC and body mass index or daily calorie intake. Ovarian steroid deficiency might thus be a major factor--among other ones--in the development and the degree of bone loss in anorexia nervosa.

Absorptiometry, Photon↗
PubMed1993

Evaluation of three-dimensional MRI exploration of prolactin-secreting microadenomas.

Over an 8-month period (July 1990-to February 1991), we explored 21 women presenting with a clinical and laboratory profile of prolactin-secreting microadenoma of the pituitary gland. Magnetic resonance imaging (MRI) is undoubtedly the most efficient method to explore microadenomas, especially when carried out in the absence of any treatment. In 8 cases, MRI was performed in the absence of medical treatment and gave a positive result, i.e. always showed a focal lesion. In the remaining 13 cases the patients had been treated before the exploration, and MRI detected a microadenoma in only 4 cases. The duration of treatment and the time elapsed between its withdrawal and the MRI examination did not seem to influence the positivity or negativity of the imaging results. Among the 9 cases where MRI failed to show a focal lesion, the image was normal in 3 cases and displayed an arachnoidocele in 3 cases; the pituitary gland was convex and homogeneous in 1 case and convex and heterogenous in 3 cases, which raised the problem of the effects of bromocriptine on the MRI images. As regards signals, in 5 cases the microadenoma was hyperintense on the spin-echo sequence without contrast injection; it was undetectable on the same sequence in 2 cases. In 4 cases the lesion was contrast-enhanced after gadolinium injection. Using millimetric sections enables small-size adenomas (2.5 x 3 mm) to be visualized.

Adolescent↗
PubMed1992

Prolactinomas and resistance to dopamine agonists.

Among 288 patients with prolactinoma (aged 12-62 years; 242 women), 27 were diagnosed as resistant to bromocriptine as their plasma prolactin (PRL) levels remained elevated despite long-term (3 months or more) treatment at high doses (> or = 15 mg daily). These 18 women and 9 men, aged 29 +/- 9 years (mean +/- SD, range 13-50), followed-up for 8 +/- 4 years, had microadenomas (n = 6) or macroadenomas. They were treated by dopamine agonists alone (n = 6) or associated with surgical or radiation therapy. In 8 cases repetitive surgical treatments were necessary. Among the 24 patients who were treated with the nonergot dopamine agonist CV 205-502 after unsuccessful bromocriptine treatment, half of them (9 women, 3 men) resumed normal PRL levels on doses ranging from 0.15 to 0.45 mg/day. Despite daily doses of CV 205-502 from 0.3 to 0.525 mg, the remaining patients were not normalized by this drug which did not prevent tumor growth in 4 of them. Two patients died from invasive cerebral extensions of their tumor and a third had vertebral metastases with positive anti-PRL immunostaining. It is concluded that bromocriptine-resistant prolactinomas represent the most severe aspect of this disease and that a more powerful dopamine agonist like CV 205-502 is effective in only a fraction of these patients.

Adolescent↗
PubMed1992

Prolactin isoforms secreted by human prolactinomas.

Prolactin (hPRL) secreted by human prolactinoma cells in culture was purified by gel filtration, lectin affinity chromatography and gel electrophoresis in order to identify the different isoforms of the hormone and to test their respective immunoreactivities and bioactivities. The nonglycosylated hPRL (NG-hPRL), unbound to lectins, was the major form and was a species (NG1-hPRL), of 23,000 (M(r)) apparent molecular weight. The lectin-bound glycosylated hPRL (G-hPRL) consisted of three forms, G1-, G2- and G3-hPRL, of identical molecular weights (25,000 M(r)). Endoglycosidase treatment indicated that these three forms differed by the heterogeneity of their carbohydrate chains. These G-PRLs proved to be 68% less immunoreactive and 50% less bioactive than NG-hPRL. It is concluded from these data that, in prolactinomas, the main variant of the hormone is the nonglycosylated form of PRL.

Antibodies, Monoclonal↗