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

in Human Mutation (1999), 13(1), 54-60

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 ... [more ▼]

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. [less ▲]

Acromegalie : Onderzoeken

in Medical News (1998), 51

Acromégalie : Diagnostic différentiel

in Medical News (1998), 50

The burden of illness of hypopituitary adults with growth hormone deficiency.

in PharmacoEconomics (1998), 14(4), 395-403

Objective: The negative metabolic and psychosocial consequences of growth hormone deficiency (GHD) in adults are now well established. In the present study, an attempt was made to quantify the burden of ... [more ▼]

Objective: The negative metabolic and psychosocial consequences of growth hormone deficiency (GHD) in adults are now well established. In the present study, an attempt was made to quantify the burden of illness, in terms of lost productivity and increased medical consumption, associated with hypopituitarism and untreated GHD. Design and Setting: The study population consisted of 129 Belgian adults with untreated GHD associated with hypopituitarism after pituitary surgery. The Short-Form 36 Health Survey (SF-36) was used to assess health status, and the Health and Labour Questionnaire was used to measure production losses and labour performance. Data on medical consumption were also collected. Main Outcome Measures and Results: Hypopituitary patients reported a lower health status than that of the general population in all but two dimensions of the SF-36 (pain and physical functioning). Nearly 11% of the patients reported being incapacitated for paid employment due to health problems, compared with 4.8% of the general Belgian population. Patients in paid employment reported a mean of 19.8 days of sickness leave per year, which is twice that in the general population. The annual number of visits to general practitioners and specialists was also higher in the patients (9.6 and 6.5 visits, respectively, for the patients compared with corresponding figures of 2.1 and 1.5 for the general Belgian population). The average annual number of days spent in hospital was 3.5 for the patients compared with 2.3 in the general population. The annual healthcare costs and costs due to production losses calculated for hypopituitary patients who had received pituitary surgery amounted to 135 024 Belgian francs (BeF) or $US4340 (1995 values). This compares with the mean annual cost per person for the Belgian population as a whole of BeF68 569 or $US2204. Conclusions: Hypopituitary patients with untreated GHD therefore have a higher cost to society in terms of lost production and medical consumption than the average Belgian population. [less ▲]

Acromégalie : Consultation

in Medical News (1998), 49

Les néoplasies endocriniennes multiples

Scientific conference (1998, March 05)

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

in Journal of Clinical Endocrinology and Metabolism (1998), 83(2), 374-8

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 ... [more ▼]

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. [less ▲]

Overview of presurgical somatostatin analog treatment in acromegaly

in IV european Congress of Endocrinology - Abstract book (1998)

Somatic MEN1 gene mutation does not significantly contribute to tumorigenesis in 35 anterior pituitary adenomas not associated with the MEN1 syndrome

in 5th International Pituitary congress - abstract book (1998)

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

in IV european Congress of Endocrinology - Abstract book (1998)