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Biomedical subjects

A Beckers

Publications and source records attributed to A Beckers.

At least 37 records · Page 2Linked to original sources

[Cushing's disease and corticotroph adenoma: anterior pituitary function before and after trans-sphenoidal microsurgery].

BACKGROUND AND PURPOSE: Cushing's disease is characterized by an overproduction of ACTH inducing an hypersecretion of corticosteroids. We assessed the non-corticotrophic pituitary functions before and after microsurgical resection of the corticotrophic adenoma. METHODS: We reviewed retrospectively a series of 98 patients (19 males, 79 females) undergoing transsphenoidal surgery between 1974 and 2001. Prolactin levels, somatrotrophic, gonadotrophic and thyroidotrophic functions were assessed and compared before and after resection of the adenoma. RESULTS: Before surgery, we observed an elevation of prolactin and a reduction of the GH, TSH, LH and FSH levels. These modifications were not linked to the volume of the adenoma but depended on the systemic effect of the hypercorticism or on local paracrine mechanisms. Selective adenomectomy usually restored altered corticotrophic and also, unlike (partial or total) hypophysectomy, the non-corticotrophic functions. CONCLUSIONS: Non-corticotrophic functions are often altered in Cushing's disease but can be restored after selective adenomectomy.

Adenoma↗

[Cushing's disease and corticotrophic adenoma: results of pituitary microsurgery].

Between November 1994 and June 2001, 194 patients with Cushing's disease underwent transsphenoidal surgery: 167 patients had adenomectomy, 14 had ante hypophysectomy, 5 had subtotal hypophysectomy, 4 had hemihypophysectomy 4 had central hypophysectomy. Complications occurred in 18 patients (9.3%), including 4 deaths (three were apparently not related to surgery). Remission of disease was achieved in 162 of 190 (85.3%) patients analyzed. Surgical failures were associated with lack of pituitary adenoma, size of the tumor and invasiveness. Among patients with confirmed adenomas, the rate of remission was significantly higher (p<0.01) in patients with microadenomas (92.6%) than in patients with macroadenomas (66.7%). Reoperation in 6 failures was followed by remission in 4 cases. The overall remission rate was 87.4%. In the 162 patients with immediate success, duration of follow-up was 10.0 +/- 5.9 years (m +/- DS; median=10.0). Recurrence of the disease occurred in 24 (14.8%) of 162 patients at a mean 4.8 years (range: 0.8-12.0 years). Our longest sustained remission is 25.6 years. Actuarial analysis indicates that the probability of a patient remaining well 12 years after surgery is 80.0%. It is 86.2% in microadenomas versus 52.5% in macroadenomas and 94.5% in the patients with postoperative hypocortisolism versus 59.2% in the others.

Adenoma↗

[Pituitary diseases in elderly patients with chronic renal insufficiency].

Chronic renal failure (CRF) in the elderly is a cause of multiple endocrine dysfunctions. The three most common pituitary axes involved are the thyrotrope, lactotrope and gonadotrope axes. Thyroid dysfunction may be the consequence of thyroid or pituitary failure. Hyperprolactinemia results in gonadal failure and is present in 30% of patients. Early presentation of menopause and andropause are common in patients with CRF. Sexual hormonal replacement is controversial and must be individually tailored. We propose a systematic screening in the elderly with CRF: determination of TSH, TPO antibodies and cervical palpation, measures of PRL, LH, FSH and testosterone to explore lactotrope and gonadotrope axis.

Aged↗

[Acromegaly and pregnancy].

Acromegaly usually results from GH hypersecretion by a somatotroph adenoma. The fertility of acromegalic patients is often impaired. Several factors may impact the course of pregnancy in acromegaly. Disturbed pituitary function might lead to infertility or spontaneous abortion. GH is a powerful insulin antagonist, and pregnant acromegalic patients are prone to added glucose intolerance and diabetes. Pregnancy itself might also impact the course of the pituitary tumor. During pregnancy, the normal pituitary increases in size due to estrogens-mediated hyperplasia. Therefore, tumors are at risk for hemorrhage due to enhanced vascularity, and might compress the optic chiasm. In this article we summarize the data on the literature on the reciprocal influences between acromegaly and pregnancy, we discuss therapeutic options and advance diagnostic and surveillance schedules of acromegaly during pregnancy.

Acromegaly↗

[Inflammatory diseases of the pituitary during pregnancy].

Well-known pituitary inflammatory diseases (sarcoidosis, Wegener granulomatosis, Langerhans and non-Langerhans histiocytosis, inflammatory pseudotumors) may occur during pregnancy or apart from it. Moreover, some inflammatory diseases, such as lymphocytic hypophysitis occur most of the time during pregnancy. In this chapter, we shall consider these different pathologies as well as the specific treatment of lymphocytic hypophysitis.

Female↗

Biomechanical and morphological types of the linea alba and its possible role in the pathogenesis of midline incisional hernia.

OBJECTIVE: To review the tensile strength of the different histological types of fibres in the linea alba and correlate the anatomical features of the anterior abdominal wall with the tensile strength of the linea alba to see whether the tensile strength of the linea alba might contribute to the development of midline incisional hernias. DESIGN: Laboratory study. SETTING: University hospital, Germany. SUBJECTS: 46 cadavers in part one, and 9 freshly frozen and 38 formalin-fixed cadavers in part two. INTERVENTIONS: In the first part of the study the histological examination was by binocular dissection microscopy, magnification x10, but this was not sufficiently reproducible so in the second part we used an Olympus BX50 microscope, magnification x20, and Optimas 5.22 picture processing software. Tensile strength was measured using a Loosenhausen ZHP 1-6 tensiometer. MAIN OUTCOME MEASURES: Correlation between anatomical features and tensile strength. RESULTS: The method used in part one of the study failed to differentiate between the three types of fibres in the linea alba (weak, intermediate, and compact). In the second part of the study we found that the fibres were irregular, with no systematic crossing of the fibres of the aponeurosis. There was a significant correlation between the thickness and density of fibres in the linea alba and its tensile strength (r = 0.9). The thickness of fibres ranged from 21.9-38.2 microm and the density from 48% to 90%. The tensile strength ranged from 3-25 kp. CONCLUSION: A combination of low density and thin fibres in the linea alba could be a predisposing factor for development of midline incisional hernias

Abdominal Muscles↗

Extensive inflammatory pseudotumor of the pituitary.

A 40-yr-old female presented with an extensive lesion of the sellar area and the sphenoid sinus, spreading to the optic nerves and associated with pachymeningitis. Histological findings were consistent with an inflammatory pseudotumor, and steroid treatment allowed the disappearance of all the lesions. Inflammatory pseudotumors of the pituitary are very rare. This case appears unique with regard to the extension of the lesions and the dramatic response to medical treatment. The differential diagnosis of inflammatory lesions of the pituitary is difficult. It relies mainly on histological analysis and includes sarcoidosis, Wegener's granulomatosis, histiocytosis (Langerhans, Rosai-Dorfman, and Erdheim-Chester diseases) and lymphocytic hypophysitis.

Adrenal Cortex Hormones↗

ACTH silent adenoma shrinking under cabergoline.

OBJECTIVES: The authors present a case report that proposes the use of cabergoline treatment in silent ACTH adenoma, an unusual member of the heterogeneous group of the so-called clinically non-functioning pituitary adenomas. DESIGN: Following the clinical and radiological improvement of a recurrent silent ACTH adenoma in a 77-year-old patient treated with cabergoline (0.5 mg every 2 days for 2 years), in vitro studies of the original tumor were performed. METHODS: The original tumor from the patient was studied by in situ hybridization and dopamine D2 receptor autoradiography. It was compared with four macroprolactinomas and two macroadenomas from patients with Cushing's disease. RESULTS: The D2 receptor mRNA signal of the reported case was intense and of the same order of magnitude as that observed in control prolactinomas. Dopamine D2 receptor autoradiography was twice that of control corticotroph adenomas and was close to that observed in prolactinomas. CONCLUSIONS: This is the first description of an in vivo shrinkage of an ACTH silent adenoma under cabergoline. We demonstrate in vitro, the presence of D2 receptors in the primitive tumor in concentrations similar to those found in control prolactinomas. These results suggest that therapeutic trials with cabergoline might be undertaken in recurring cases of ACTH silent tumors and more generally, non-functioning pituitary adenomas.

Adenoma↗

[Pituitary pathology and MEN 1].

Multiple Endocrine Neoplasia type 1 (MEN 1) is an autosomal dominant syndrome characterized by neoplasia of the parathyroid glands, the endocrine pancreas and the anterior pituitary gland. Recently the identification on chromosome 11 (locus q13) of the gene responsible for MEN 1 has allowed direct genetic diagnosis of MEN 1-affected family members. To date almost 300 families have been described and genetically characterized. The genetic etiology of most pituitary tumours remains unknown. Pituitary adenomas can develop sporadically or as a part of multiple endocrine neoplasia type 1. In this review, the recently published data on the pathology of the MEN 1 syndrome will be summarized. The clinical, morphological and genetic aspects of sporadic and MEN 1-associated pituitary adenomas will be outlined.

Adenoma↗

[Primary hyperparathyroidism: etiology, diagnosis and treatment].

Primary hyperparathyroidism is a not so infrequent disease that is often overlooked by physicians. Its incidence is estimated to be about 28 in 100.000 subjects, mainly women over seventy years old. Three to four percents of women over seventy are affected. Hyperparathyroidism can be isolated or be a component of a more complex syndrome like multiple endocrine neoplasms (MEN). Patients can be asymptomatic or present with symptoms like asthenia, hypertension or nephrolithiasis. The biological investigation requires the combined measurements of plasmatic ionized calcium and parathormone. In some cases, more specific explorations like calcium loading tests have to be performed in order to confirm the diagnosis.

Age Distribution↗

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↗

Prognostic factors in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. Groupe d'Etude des Néoplasies Endocriniennes Multiples (GENEM and groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison (GRESZE).

BACKGROUND & AIMS: Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. These factors were retrospectively determined in 77 patients. METHODS: Data chart review was performed. RESULTS: Median follow-up was 102 months (range, 12-366). Surgery was performed on 48 patients, including 9 of the 10 patients with large pancreatic tumors (>/=3 cm). Liver metastases developed in 4 patients (40%) with large pancreatic tumors, in 3 (4.8%) without, and in 1 of the 4 patients with pancreatic tumors of unknown size; all had previously undergone surgery. The only independent factor associated with development of liver metastases identified by multivariate analysis was large pancreatic tumors (risk ratio, 29.0; 95% confidence interval [CI], 3. 2-260.7). Surgery was not selected. The probability of being free of liver metastases in the 63 patients without large pancreatic tumors was 96% (95% CI, 88-100) at 10 and 15 years. Thirteen (16.9%) patients died. The only independent factors of death selected by multivariate analysis were Zollinger-Ellison syndrome diagnosis before 1980 (risk ratio, 8.2; 95% CI, 1.7-40.6) and age at diagnosis (risk ratio/year, 1.08; 95% CI, 1.03-1.14). CONCLUSIONS: Large pancreatic tumors are predictive of the development of metachronous liver metastases, and surgery does not seem to prevent them.

Adult↗

Familial acromegaly: case report and review of the literature.

Familial acromegaly is an exceptional clinical entity when not associated with features of multiple endocrine neoplasia type 1 (MEN1). We report here 3 pedigrees in each of which 2 patients have been shown to develop acromegaly. In 4 patients, clinical follow-up, and biological screening allowed to confidently exclude MEN1. Absence of mutation in the MEN1 gene after direct DNA analysis in 2 pedigrees reinforces the conviction that the families do not have MEN1. In families 1 and 2, diagnosis was made at a very early age and voluminous adenomas with suprasellar expansion were already present at the time of diagnosis. We review the 20 previous reports of familial acromegaly, some of them questionable. Our 3 families, combined with some other published pedigrees, allow the delineation of a familial form of acromegaly, distinct from MEN1. Dominant inheritance with reduced, age-dependant penetrance is the most parsimonious model to explain the recurrences. Gs protein pathway could be the site of action of the gene responsible of familial acromegaly, but no data have been published to sustain or reject this hypothesis.

Acromegaly↗

Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients.

Cabergoline is a new long-acting dopamine agonist that is very effective and well tolerated in patients with pathological hyperprolactinemia. The aim of this study was to examine, in a very large number of hyperprolactinemic patients, the ability to normalize PRL levels with cabergoline, to determine the effective dose and tolerance, and to assess the effect on clinical symptoms, tumor shrinkage, and visual field abnormalities. We also evaluated the effects of cabergoline in a large subgroup of patients with bromocriptine intolerance or -resistance. We retrospectively reviewed the files of 455 patients (102 males and 353 females) with pathological hyperprolactinemia treated with cabergoline in 9 Belgian centers. Among these patients, 41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic hyperprolactinemia; and 1%, an empty sella. The median pretreatment serum PRL level was 124 microg/L (range, 16-26,250 microg/L). A subgroup of 292 patients had previously been treated with bromocriptine, of which 140 showed bromocriptine intolerance and 58 showed bromocriptine resistance. Treatment with cabergoline normalized serum PRL levels in 86% of all patients: in 92% of 244 patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 macroadenomas. Pretreatment visual field abnormalities normalized in 70% of patients, and tumor shrinkage was seen in 67% of cases. Side effects were noted in 13% of patients, but only 3.9% discontinued therapy because of side effects. The median dose of cabergoline at the start of therapy was 1.0 mg/week but could be reduced to 0.5 mg/week once control was achieved. Patients with a macroprolactinoma needed a higher median cabergoline dose, compared with those with idiopathic hyperprolactinemia or a microprolactinoma: 1.0 mg/week vs. 0.5 mg/week, although a large overlap existed between these groups. Twenty-seven women treated with cabergoline became pregnant, and 25 delivered a healthy child. One patient had an intended abortion and another a miscarriage. In the patients with bromocriptine intolerance, normalization of PRL was reached in 84% of cases, whereas in the bromocriptine-resistant patients, PRL could be normalized in 70%. We confirmed, in a large-scale retrospective study, the high efficacy and tolerability of cabergoline in the treatment of pathological hyperprolactinemia, leaving few patients with unacceptable side effects or inadequate clinical response. Patients with idiopathic hyperprolactinemia or a microprolactinoma, on average, needed only half the dose of cabergoline as those with macroprolactinomas and have a higher chance of obtaining PRL normalization. Cabergoline also normalized PRL in the majority of patients with known bromocriptine intolerance or -resistance. Once PRL secretion was adequately controlled, the dose of cabergoline could often be significantly decreased, which further reduced costs of therapy.

Adenoma↗

Somatic MEN1 gene mutation does not contribute significantly to sporadic pituitary tumorigenesis.

Pituitary adenomas are a common manifestation of multiple endocrine neoplasia type 1 (MEN1) but most of them occur sporadically. There are only a few well defined genetic abnormalities known to occur in these sporadic tumours. The MEN1 gene located on 11q13 has recently been cloned and allelic deletion and mutation analysis studies have implicated the MEN1 gene in a significant fraction of the sporadic counterparts of typical MEN1 neoplasms (parathyroid tumours, insulinomas and gastrinomas). To determine if MEN1 gene inactivation is also involved in the development of sporadic pituitary adenomas, allelic deletions of chromosome 11q13 and MEN1 gene mutations and polymorphisms were assessed in 35 sporadic tumours of the anterior pituitary (9 prolactin-secreting, 8 GH-secreting, 3 TSH-secreting, 2 TSH/GH-secreting, 4 Cushing, 9 silent). Thirty-one tumours were found to be heterozygous for at least one MEN1 intragenic polymorphism (25 cases) or for a flanking gene polymorphism (6 cases). The remaining tumours were not informative. No mutations were found in any tumour except in one prolactinoma which was homozygous or hemizygous for a mutation (1-117 C-->T) in a region close to the promoter. Unfortunately, blood or normal tissue was not available in this case. Our data show that somatic MEN1 mutations do not contribute significantly to tumorigenesis of sporadic pituitary adenomas and suggest that mutation of other genes are likely to contribute to the pathogenesis of these tumours.

Adenoma↗

[Hyperandrogenism: clinical aspects, investigation and treatment].

Androgen excess (AE) is one of the most common endocrine disorders, affecting 10% of adult women before the menopause. The clinical picture varies widely depending on the etiology of AE. Most of these women are suffering from hirsutism, acne, menstrual disturbances, anovulation and obesity. Virilization is unusual, except in patients with ovary or adrenal cancer. Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are the most frequent causes of androgen excess, accounting for more than 90% of the cases. The pathogenesis of PCOS is still an unresolved problem. A hereditary predisposition has been suggested. Enzymatic deficiency is a less frequent cause of AE, the most common deficiency being the non classic 21-OH deficiency (NCAH). AE has been implicated as a side effect of many drugs. Ovary and adrenal tumours are unusual, however, they must be considered especially in case of severe hirsutism or virilization. Complementary investigations are selected based on the result of clinical examination. Pharmacologic therapy, usually with anti-androgens, is the most widely used treatment for PCOS, IH and NCAH. Surgical therapy should be considered only when there is a particular indication such as Cushing's syndrome, ovary or adrenal tumours.

Adrenal Glands↗

[Therapeutic controversies: the treatment of Graves' disease].

Hyperthyroidism is a common clinical condition with an annual incidence of about 1%. Approximately, 1 in every 20 women will develop this condition during a lifetime. Most cases are due to Graves'disease. Solitary toxic nodules and toxic multinodular goiters are also important but less frequent causes. In this article, we will consider only the treatment of Graves'disease. Anti-thyroid drugs, surgery and radio-iodine, all represent effective forms of treatment. There is, however, little consensus regarding the treatment of choice for specific cases. This article discusses the advantages and disadvantages of each treatment.

Antithyroid Agents↗