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R Abs

Publications and source records attributed to R Abs.

At least 19 recordsLinked to original sources
PubMed1999

Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in parathyroids, enteropancreatic endocrine tissues, anterior pituitary, and other tissues. The gene for MEN1 has recently been cloned and shown to code for a 610-amino acid protein of enigmatic function which probably acts as a tumor suppressor. Several mutations causing the MEN1 phenotype have been recently identified. In order to determine the spectrum of MEN1 gene mutations in a sample of 25 Belgian patients, we have systematically screened the 10 exons and adjacent sequences of the MEN1 gene by means of an automatic sequencing protocol. Twelve different mutations were identified including nonsense, frameshift, splicing, and missense mutations. Two of these mutations (D172Y and 357del4) occurred more than once. A missense mutation was also found in a kindred with familial hyperparathyroidism. We observed no significant correlation between the nature or position of mutation and the clinical status. We have also detected 6 intragenic polymorphisms and DNA sequence variants and have analyzed their frequencies in our population.

Belgium↗
PubMed1998

Obstructive hydrocephalus as complication of a giant nonfunctioning pituitary adenoma: therapeutical approach.

We report the case of a 61-year-old male presenting with a giant nonfunctioning pituitary tumour extending into the third ventricle and thereby causing obstructive hydrocephalus. The main complaints consisted of disturbed vision and somnolence. The patient was initially treated by ventriculoperitoneal shunting, with immediate improvement of his mental status. Transcranial resection of the tumour was performed shortly thereafter, but only a limited part of the tumour could safely be removed. By immunohistochemistry the diagnosis of gonadotroph adenoma was made. After the operation, the patient's vision deteriorated temporarily. Because of the risk of further damage to the optic nerve, radiation therapy was postponed. Instead, treatment with the long-acting dopamine agonist cabergoline was instituted, which resulted in a gradual improvement of vision. Two years later a transsphenoidal operation was performed because of acute worsening of the visual fields due to central tumour necrosis with slight volume expansion. Vision improved considerably after surgery. Radiotherapy is scheduled in the near future. This case is an illustration of the complications of giant nonfunctioning pituitary adenomas. The therapeutical approach to obstructive hydrocephalus in these instances is reviewed.

Adenoma↗
PubMed1998

Cabergoline in the treatment of acromegaly: a study in 64 patients.

Cabergoline is a new, long acting, dopamine agonist that is more effective and better tolerated than bromocriptine in patients with hyperprolactinemia. Because dopamine agonists still have a place in the medical management of acromegaly, cabergoline might be a useful treatment. We, therefore, evaluated the effect of long term administration of cabergoline in a large group of unselected acromegalic patients. Sixty-four patients were included in a multicenter, prospective, open labeled study. A subgroup of 16 patients had GH-/PRL-cosecreting pituitary adenomas. Cabergoline was started at a dose of 1.0 mg/week and was gradually increased until normalization of plasma insulin-like growth factor I (IGF-I) levels, occurrence of unacceptable side-effects, or a maximal weekly dose of 3.5 mg (7.0 mg in 1 case) was reached. Treatment with cabergoline suppressed plasma IGF-I below 300 micrograms/L in 39% of cases and between 300-450 micrograms/L in another 28%. With pretreatment plasma IGF-I concentrations less than 750 micrograms/L, a suppression of IGF-I below 300 micrograms/L was obtained in 53% of cases, and a suppression between 300-450 micrograms/L was obtained in another 32%. By contrast, with pretreatment plasma IGF-I concentrations above 750 micrograms/L, only 17% of cases showed a suppression of IGF-I below 300 micrograms/L, and there was IGF-I suppression between 300-450 micrograms/L in another 21%. In GH-/PRL-cosecreting adenomas, 50% of cases suppressed plasma IGF-I levels below 300 micrograms/L, and another 31% did so between 300-450 micrograms/L, in contrast to only 35% and 27%, respectively in GH-secreting adenomas. Similar results were obtained concerning the secretion of GH. Tumor shrinkage was demonstrated in 13 of 21 patients, with a mass reduction by more than half in 5 GH-/PRL-cosecreting adenomas. Except for slight gastrointestinal discomfort and orthostatic hypotension in a few patients at the beginning of therapy, cabergoline treatment was well tolerated. Only 2 patients stopped medication because of nausea. The weekly dose of cabergoline ranged between 1.0-1.75 mg. A further increase in the dose was only effective in 1 GH-/PRL-cosecreting adenoma. The results of this study suggest that cabergoline is an effective, well tolerated therapy that should be considered in the management of acromegaly, especially if the pituitary adenoma cosecretes GH and PRL or if pretreatment plasma IGF-I levels are below 750 micrograms/L.

Acromegaly↗
PubMed1997

Serum creatine, creatinine, and other guanidino compounds in patients with thyroid dysfunction.

Serum levels of creatine (CT), creatinine (CTN), urea, guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), arginine (Arg), homoarginine (Harg), argininic acid (ArgA), and alpha-keto-delta-guanidinovaleric acid (alpha-K-delta-GVA) were measured in 54 patients with hyperthyroidism, 56 with subclinical hyperthyroidism, 28 with subclinical hypothyroidism, and 51 with hypothyroidism compared with 62 euthyroid controls. In agreement with previous reports, serum CT increased (+35%) and CTN decreased (-17.6%) in hyperthyroidism as compared with normal thyroid function, whereas the opposite was seen in hypothyroidism (-17.7% and +11%, P < .0001). Original findings from this study are a highly significant decrease in GSA (-41.7%) and GAA (-36.8%) in hyperthyroidism and an increase in GSA (+36%) in hypothyroidism (P < .0001). In addition, a slight decrease in hyperthyroidism and hypothyroidism was noted for Arg (-6.2% and -13.2%, P = .001) and Harg (-14.8% and -18.1%, P = .05). By contrast, no significant change was seen in levels of urea, G, ArgA, and alpha-K-delta-GVA. No major differences were found for any of the compounds between subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism. There was a highly significant positive linear correlation between urea and GSA levels in hyperthyroidism, euthyroidism, and hypothyroidism (r = .68, r = .77, and r = .75, P < .0001), taking into account that for the same increase in urea, GSA increased threefold more in hypothyroid versus hyperthyroid patients. In conclusion, apart from CT and CTN, significant changes can be found in serum levels of GSA, GAA, Arg, and Harg in patients with thyroid dysfunction. Subclinical thyroid dysfunction does not seem to induce changes in serum levels of guanidino compounds. Decreased serum GSA and GAA levels might be an additional indicator of hyperthyroidism.

Adolescent↗
PubMed1997

125I-Tyr0-hCRH labelling characteristics of corticotropin-releasing hormone receptors: differences between normal and adenomatous corticotrophs.

The presence of corticotropin-releasing hormone (CRH) receptors has been previously demonstrated in corticotrophs from normal pituitaries using a method combining immunocytochemistry and liquid emulsion autoradiography. The aim of this study was to compare the characteristics of the 125I-Tyr0-hCRH binding in corticotrophs from normal pituitaries (three obtained at autopsy and one obtained at surgery) with corticotrophs from pituitary adenomas (six corticotroph adenomas responsible for Cushing's disease and two silent corticotroph adenomas secreting a biologically inactive ACTH molecule). In normal corticotrophs, the larger part of the 125I-Tyr0-hCRH binding was localised in patchy conglomerates at the centre of the cell and, to a much lesser degree, in a diffuse pattern at the cell periphery. In adenomatous corticotrophs, CRH receptor expression is disturbed both quantitatively and qualitatively. Except for a minority of cells in one adenoma, all adenomatous corticotrophs showed only peripherally bound 125I-Tyr0-hCRH and no centrally localised binding. Furthermore, adenomatous corticotrophs revealed a statistically significant lower signal intensity when compared to normal corticotrophs and a strongly negative correlation was found between the labelling area in adenomatous corticotrophs and both the basal and CRH-stimulated plasma ACTH levels. These findings suggest defective processing of CRH receptors and could be relevant to the sustained ACTH secretion by adenomatous corticotrophs in Cushing's disease and, more generally, provide an explanation to its pathology. The silent corticotrophs secreting a biologically inactive ACTH molecule were characterised by a very faint signal intensity, although present on almost every cell.

Adenoma↗
PubMed1997

Treatment of macroprolactinoma with cabergoline: a study of 85 patients.

OBJECTIVE: Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficiency and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis. STUDY DESIGN AND PATIENTS: Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 micrograms/I and tumour maximum diameters were between 11 and 42 mm. MEASUREMENTS: Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n = 62). RESULTS: Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment. CONCLUSIONS: Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Adolescent↗
PubMed1997

Two years of replacement therapy in adults with growth hormone deficiency.

OBJECTIVES: Although several studies have shown beneficial short-term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated. DESIGN: 148 adult GHD patients were enrolled in a multicentre 2-year rhGH replacement study which was placebo controlled for the first six months. rhGH (Genotropin/Genotonorm Pharmacia & Upjohn) was given in a dose of 0.25 IU/kg/week sc (1.5 IU/m2/day). MEASUREMENTS: Every 3-6 months body composition was measured using body impedance analysis and general well being was assessed using the Nottingham Health Profile (NHP) and social self-reporting questionnaire. At the same time patients had a full clinical examination and blood was sampled for glucose, HbA1c, IGF-1, creatinine, full blood count, thyroid hormones and liver function tests. RESULTS: With rhGH therapy IGF-1 levels increased from -2.00 +/- 2.60 SDS to 1.47 +/- 2.6 SDS after six months (P < 0.001), continued to rise despite no change in dose to 1.84 +/- 2.8 SDS after one year and remained constant thereafter (1.98 +/- 2.4 after 2 years). 56% of patients ultimately attained supranormal IGF-1 levels (+2 SD), 22% had levels below the mean, of which 9% were below -2 SD. Within 3 months lean body mass (LBM) increased by +5.09% (P < 0.001), total body water (TBW) by +5.40% (P < 0.001), while body fat (BF) dropped by -10.89% (P < 0.001) and waist circumference by -1.42% (P < 0.004). These effects were maintained during the first year of therapy, but the effect was attenuated after 24 months: LBM, +3.91% (P < 0.001); TBW, +3.28%, P < 0.001, BF, -6.42% (P < 0.001) and waist -2.22% (P < 0.009). Individual differences in response were large and could not be predicted by any of the baseline parameters, except for a better response in males. Treatment resulted in a large and progressive improvement on the NHP scale, especially energy, emotions and sleep, but a similar change was also found in patients during placebo treatment. With rhGH the number of full days of sick leave/6 months decreased from 12.17 +/- 3.90 days (SEM) to 7.15 +/- 3.50 days after six months (P = 0.009), 2.93 +/- 1.55 days after 12 months (P = 0.01), 0.39 +/- 0.17 days after 18 months (P < 0.001) and 3.3 +/- 2.51 days after 24 months (P = 0.026). Similarly, the hospitalization rate went down from 14.9 to 7% after 6 months and remained at this level thereafter (P = 0.12). About one third of patients on rhGH experienced fluid-related adverse events, most often within the first 3 months. They usually disappeared spontaneously or responded well to dose reduction. Cumulative dropout rates were 29% after 1 year and 38% after two years. Two thirds of these patients stopped treatment because of insufficient subjective improvement. Neither drop-outs nor fluid retention could not be predicted by any of the baseline parameters. CONCLUSIONS: We confirmed in a large group of patients the beneficial effects of rhGH therapy on body composition, metabolic parameters and general well-being and found a consistent drop in number of sick days and hospitalization rate. These effects were maintained during two years of therapy, except for an attenuation in body composition changes after 24 months. The high incidence of fluid-related adverse events suggests that it may be better to start with lower doses of rhGH and to increase the dose more slowly over a number of weeks. The finding of suboptimal high or low IGF-1 levels in many patients reinforces guidelines not to give rhGH in a weight-dependent dose but to titrate it individually for each patient.

Adult↗
PubMed1996

Thyrotoxic periodic paralysis, an unusual cause of hypokalemic periodic paralysis.

Over a two-year period two patients were admitted to the hospital with episodes of paralysis and hypokalemia. In the first patient, familial hypokalemic periodic paralysis was initially suspected. Only several months later was Graves' disease diagnosed and this diagnosis linked to thyrotoxic periodic paralysis. The second patient came to notice after treatment with thyreostatic drugs was stopped prematurely and paralysis together with hypokalemia developed. Thyrotoxic periodic paralysis, being rare outside Asia, closely mimics the clinical presentation of familial hypokalemic periodic paralysis. Mainly men in the third decade with a negative family history are affected. Graves' disease is the most common cause of hyperthyroidism. This disorder is not always clinically apparent since signs of hyperthyroidism may be easily missed. Therefore thyroid function tests are part of the diagnostic workup of hypokalemic periodic paralysis. Correction of thyroid function is essential to treatment. The pathophysiology is still controversial.

Antithyroid Agents↗
PubMed1995

The effect of naloxone and metoclopramide on the secretion of luteinizing hormone in a hyperprolactinemic hypogonadotropic postmenopausal woman.

OBJECTIVE: To determine the role of opioidergic and dopaminergic activity in the suppression of GnRH0LH in a hyperprolactinemic state. DESIGN: Case report. SETTING: University hospital. PATIENT: A 68-year-old woman with a macroprolactinoma. INTERVENTIONS: Serial 10-hour IV infusions of naloxone and metoclopramide. MAIN OUTCOME MEASURE: Serum LH concentration. RESULTS: Naloxone induced a small but significant rise of serum LH levels, which displayed a pulsatile pattern. By contrast, metoclopramide elicited no significant response in LH secretion. CONCLUSION: Opioidergic but not dopaminergic neurotransmission plays a direct role in the suppression of LH secondary to hyperprolactinemia.

Aged↗
PubMed1995

Pituitary metastasis mimicking a pituitary adenoma. A description of two cases.

The cases of two elderly women treated for temporal hemianopsia due to a large pituitary mass with suprasellar extension are presented. In both cases, the clinical picture, without diabetes insipidus and cranial nerve paralysis, as well the neuroimaging and endocrinological investigation showing hypopituitarism, were suggestive of a non-secreting pituitary adenoma. In the first patient malignant tissue was unexpectedly encountered during transsphenoidal surgery. Anatomopathological investigation confirmed the presence of a metastasis of a breast carcinoma for which she had been treated 17 years earlier. In the second patient, a preoperative chest X-ray before transsphenoidal surgery revealed an asymptomatic bronchial tumour. Subsequently a squamous cell carcinoma with a metastasis in the pituitary was confirmed. These two cases illustrate the fact that a pituitary metastasis can closely mimic a pituitary adenoma. Even in the absence of suggestive symptoms such as diabetes insipidus and/or cranial nerve paralysis the possibility of metastatic disease in the differential diagnosis of a pituitary mass should always be considered.

Adenocarcinoma↗
PubMed1995

The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients.

Patients with acromegaly are reported to be at risk of developing adenomatous colonic polyps, which are considered to be preneoplastic lesions. This assumption is, however, usually drawn from results obtained in rather small series of patients or without a control group. We, therefore, undertook a prospective colonoscopic and pathological study comprising 103 acromegalic patients and 138 nonacromegalic control subjects referred for irritable bowel syndrome. The prevalence of adenomatous colonic polyps was significantly increased in acromegalic patients compared to that in control subjects (22.3% vs. 8.0%; P = 0.0024). The significance was similarly present in male acromegalic patients (28.6% vs. 5.5% in male control subjects; P = 0.0026), but was absent in female acromegalic patients. The prevalence of colonic polyps was also significantly increased in the group of acromegalic patients under 55 yr of age (20.0% vs. 3.0% in the control group of the same age; P = 0.0026). Other characteristics of adenomatous colonic polyps in acromegaly were the multiplicity and the presence proximal to the splenic flexure. No difference in the duration of acromegaly was found between patients with or without adenomatous polyps. The prevalence of hyperplastic colonic polyps was also significantly increased to 24.3% in acromegalic patients vs 4.4% in control subjects (P < 0.001). In conclusion, in view of the increased incidence of adenomatous colonic polyps, colonoscopy should be part of the follow-up examination in acromegaly.

Acromegaly↗
PubMed1995

Intrasellar bony spine, a possible cause of hypopituitarism.

A 39-year-old male patient with long-standing pituitary deficiency is reported. The onset of hypopituitarism was probably at about the age of 12 years, but diagnosis was not made until 6 years later. Since then he has received substitutive hormonal treatment and was referred with complaints suggestive of growth hormone deficiency. Retrospective study of a skull radiography performed at the age of 18 years revealed a calcified lesion in the sellar region. Additional radiological examinations showed the presence of a 9-mm intrasellar bony spine. Magnetic resonance examination showed a ventrally extending arrow-shaped bone deformation in continuity with the dorsum sellae, consisting of a hyperintense structure comparable with the intensity of the bone marrow of the dorsum and clivus. Computed tomography scanning confirmed in detail the morphology of the bony spine. This deformity probably represents the non-regressed cephalic segment of the notochord. Only in four reports has the existence of this congenital abnormality been described, but this is the first one in which hypopituitarism can be regarded as a complication of the intrasellar spine.

Adult↗
PubMed1995

Subcutaneous octreotide treatment of a growth hormone-releasing hormone-secreting bronchial carcinoid: superiority of continuous versus intermittent administration to control hormonal secretion.

Diagnosis of ectopic acromegaly was made in a 21-year-old female patient who 3 years before had undergone a right pneumectomy for a disseminated bronchial carcinoid. Plasma growth hormone-releasing hormone (GHRH) concentrations were markedly elevated (6440 ng/l; normal value < 100 ng/l), as were serum GH (187 micrograms/l; normal < 5 micrograms/l) and plasma insulin-like growth factor I (IGF-I) levels (6.7 U/ml; normal < 2 U/ml). Retrospective immunohistochemical examination of the carcinoid tumor was positive for GHRH and the tumoral content of GHRH was 2130 ng/g wet weight. Subcutaneous treatment with octreotide was begun and first resulted in a profound inhibition of GH hypersecretion, normalization of plasma IGF-I and only partial reduction of GHRH concentrations. However, the initial dose of 3 x 100 micrograms had to be increased gradually to 4 x 750 micrograms because of a progressive deterioration of the hormonal control. After 15 months of intermittent therapy, octreotide was administered by continuous sc infusion. This treatment improved compliance, allowed the daily dose of octreotide to be reduced to 1500 micrograms and normalized serum GH levels. A near-normalization of the plasma IGF-I concentrations was also obtained, whereas the suppression of plasma GHRH concentrations remained incomplete. Despite favorable evolution of the endocrine parameters, intramedullar metastases were diagnosed and required radiation therapy. This observation emphasizes the superiority of continuous over intermittent administration of octreotide in the treatment of ectopic acromegaly. It also shows that the somatostatin analog acts more at the pituitary level to inhibit GH secretion than at the site of the neuroendocrine tumor.

Acromegaly↗
PubMed1995

[Surgery and curietherapy of keloids].

Postoperative irradiation of keloids allows a decrease of the recurrence rate by about 50%, compared to surgery alone. A review of the literature illustrates the benefits due to the irradiation, and describes the techniques available. The Iridium 192 interstitial brachytherapy, with per-operative implantation of the plastic tubes and immediate irradiation of 20 Gy at 5 mm depth, is detailed as used by French teams. The analysis of the published results allows to recommend this technique which is tailored to each clinical situation, safe, and easy to perform by the surgeon.

Brachytherapy↗
PubMed1994

Association of isolated hypogonadotropic hypogonadism, pronounced hypodontia and the Wolff-Parkinson-White syndrome.

Diagnosis of idiopathic isolated hypogonadotropic hypogonadism was made in a 22-year-old female patient referred for primary amenorrhoea. It was considered a separate entity from Kallmann's syndrome, because it was not accompanied by anosmia or other specific pleiotropic features. On the other hand, the patient showed severe hypodontia and an intermittent Wolff-Parkinson-White syndrome. To our knowledge, this association has never been reported before. This unusual phenotype points to a nonrandom association. However, no information in the literature is available to consider a new single gene defect or a contiguous gene syndrome.

Adult↗
PubMed1994

Variable regions of chromosome 11 loss in different pathological tissues of a patient with the multiple endocrine neoplasia type I syndrome.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by nodular proliferation of the parathyroid glands and tumors of the anterior pituitary gland, the endocrine pancreas, and the neuroendocrine cell system of the gut. Loss of the putative tumor suppressor effect of the MEN1 gene is probably responsible for the development of MEN1-associated tumors. We report here a genetic study of a female MEN1 patient with the association of nodular hyperplasia of two parathyroid glands, an insulinoma, multiple duodenal gastrinomas, a prolactinoma, and a gastric carcinoid. We performed loss of heterozygosity (LOH) studies of chromosome 11 on all affected tissues except the insulinoma. Allelic losses of chromosome 11 were detected in several tumors, but the chromosomal regions of LOH were different, suggesting that different somatic mutational events are involved in the pathogenesis of these tumors. LOH of chromosome 11 was also detected in the prolactinoma of this patient, which indicates that the MEN1 gene has a tumor suppressor effect in the pituitary.

Calcium↗
PubMed1994

Autonomously functioning thyroid nodules in a patient with a thyrotropin-secreting pituitary adenoma: possible cause--effect relationship.

A 51-year-old female patient with long-standing hyperthyroidism due to a thyrotropin-secreting pituitary adenoma is reported, who became thyrotoxic again shortly after successful pituitary surgery. Functional testing and scintigraphy suggested the diagnosis of autonomous functioning thyroid nodules, which was confirmed by pathological examination of the resected thyroid tissue. This is the first report revealing the transition from a pituitary-dependent to a thyroid-dependent hyperthyroidism. Autonomous functioning thyroid nodules are, however, considered an intrinsic thyroid defect. In similarity with other disorders, in which trophic hormones may induce an autonomous secretion by the target gland, this report opens the possibility that a humoral factor may play a role in the development of autonomous functioning thyroid nodules.

Adenoma↗