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A Beckers

Publications and source records attributed to A Beckers.

At least 19 recordsLinked to original sources
PubMed2006

Clinical characterization of familial isolated pituitary adenomas.

CONTEXT: Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). OBJECTIVE: Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA). DESIGN AND SETTING: We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands. RESULTS: Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases. CONCLUSIONS: Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.

Adenoma↗
PubMed2006

[Cutaneous signs of endocrinopathies].

Some cutaneous lesions accompany or reveal endocrine disorders. Identifying the endocrinopathy is very important because it sometimes allows corrective rather than symptomatic treatment. The most frequenly involved diseases include thyrotoxicosis, hypothyroidism, the auto-immune disorders of thyroid, Cushing syndrome, Addison disease, acromegaly, androgen-dependent disorders, hypopituitarism, hypoparathyroidism, pseudohypoparathyroidism and diabetes mellitus.

Endocrine System Diseases↗
PubMed2006

[How do you investigate an elevated calcitonin level?].

This article describes a case of lung cancer with associated hypercalcitoninemia in a man with a goitre. The case raises the problem of the differential diagnosis between medullary thyroid carcinoma and a neuroendocrine neoplasm with ectopic calcitonin secretion. The article first reviews the physiology of calcitonin, then outlines the diagnostic tests that are required to investigate hypercalcitoninemia and finally discusses the interpretation of test results.

Aged↗
PubMed2005

Clinical and genetic features of familial pituitary adenomas.

Inherited or familial pituitary tumor syndromes such as multiple endocrine neoplasia type 1 and Carney complex provide an important insight into the genetics and molecular pathology of endocrine cancers. Our understanding of these conditions is expanding rapidly due to the identification of the genes and proteins affected and the availability of murine knockout models. The successes achieved to date in understanding multiple endocrine neoplasia type 1 and Carney complex have helped in the identification and study of new inherited pituitary tumor syndromes such as isolated familial somatotropinomas. This review assesses the current status of research into the clinical features, genetics and molecular pathologies of multiple endocrine neoplasia type 1, Carney complex, and isolated familial somatotropinomas, and details ongoing work to delineate familial isolated pituitary adenomas, a potentially new clinical entity.

Adenoma↗
PubMed2005

Tensegrity and type 1 dermal dendrocytes in acromegaly.

BACKGROUND: Skin is enlarged and doughy in acromegaly. Alterations have been reported in the structure of the extracellular matrix (ECM) and in the mechanical properties of the dermis. It is recognized that internal tensions in the dermis give rise to active cell-ECM and cell-cell mechanical interactions. This mechanobiological aspect can lead to functional and conformational changes in the cells. Such alterations in connective tissue cells have not been explored so far in acromegaly. The aim of the study was to assess structural changes in the dermal ECM, and in the number and shape of factor XIIIa-positive type I dermal dendrocytes (DDs) in acromegaly. MATERIALS AND METHOD: A total of 32 patients with acromegaly (three untreated, 17 with active disease under somatostatin analogues and 12 cured) were examined. Both the maximum and the most recent IGF-1 (insulin-like growth factor) dosages recorded in the patients' files were retrieved. Skin biopsies were taken from their forearms. Histochemistry, immunohistochemistry, morphometry and electron microscopy were used. RESULTS: Collagen-bundle coarsening and acidic glycosaminoglycan deposits were found irrespective of the current endocrine status. Dermal dendrocytes were often markedly reduced in numbers, but those present were plump with few dendrites. A negative correlation was found between DD numbers and the maximum IGF-1 dosages recorded in the patients' files. A similar although weaker trend was found with the most recent IGF-1 dosages. CONCLUSIONS: Collagen, glycosaminoglycans and DDs appeared affected in acromegaly, even when the hormonal status was controlled after surgery and/or somatostatin analogue treatment. The persisting conformational change of DDs suggests a modification in cellular tensegrity, perhaps initiated by hormonal effects and probably maintained by alterations in the ECM interactions.

Acromegaly↗
PubMed2005

An overview of the epidemiology and genetics of acromegaly.

Historical data indicate that pituitary tumors represent 10% of intracranial tumors, while adenomas are noted in approximately 14-23% of normal subjects on autopsy or magnetic resonance imaging (MRI). About 2.5% of these tumors stain positive for GH in histopathologic studies. In contrast, the prevalence of clinically diagnosed acromegaly is lower at 36-69 per million population. Ongoing studies indicate that the actual prevalence of acromegaly in the community may be higher than previous epidemiologic data suggest. Acromegaly can occur both sporadically and in the setting of familial conditions, such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Isolated familial somatotropinoma has been described and newer data suggest that acromegaly may also occur in non-MEN1/CNC families in combination with other pituitary tumor phenotypes.

Acromegaly↗
PubMed2004

Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study.

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication.

Delayed-Action Preparations↗
PubMed2004

Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma.

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism, and the efficacy of medical therapy and chemo- and radiotherapy is poor in recurrent or metastatic disease. We report the first case of PTH immunization in which tumor shrinkage accompanied hormonal, biochemical, and clinical improvements in a patient with metastatic parathyroid carcinoma.A 50-yr-old woman with refractory parathyroid carcinoma and pulmonary metastases was immunized eight times between February 2001 and December 2003 with bovine and modified human PTH fragments and intact human PTH, mixed with Freund's adjuvant. Total and ionized calcium and PTH levels were assayed weekly for 6 months and regularly thereafter. Thoracic computed tomography scans were performed regularly. Antibodies to all PTH fragments were detected after two immunizations. Baseline PTH and total calcium were 213.0 ng/liter and 13.96 mg/dl, respectively, and remained elevated during the first three immunizations. From the fourth immunization onward, PTH and calcium decreased, and the patient's clinical condition improved markedly. PTH and calcium levels have remained controlled for more than 24 months, and the sizes (surface area) of pulmonary metastases decreased from baseline by 39-71%. This is the first evidence that PTH immunization not only can improve clinical, hormonal, and biochemical measures in parathyroid carcinoma but also has an antitumor effect.

Animals↗
PubMed2003

Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency.

OBJECTIVE: Little is known of the usefulness of GH secretagogues (GHSs) in GH-deficient (GHD) adults. The objective of this study was to determine the number of responders to treatment with NN703 in GHD adults. DESIGN: A multicentre, randomized, double-blind, and placebo-controlled study. PATIENTS: Ninety-seven GHD adults were included. MEASUREMENTS: The GH response before and after 1 week of oral treatment with NN703 (n = 83) or placebo (n = 14) was determined. The first and last dose of NN703 was 3 mg/kg, whereas the dose of NN703 was 1.5 mg/kg/day during the 6 days between the first and last doses. Furthermore, all 97 patients received 1 micro g/kg GH-releasing hormone (GHRH) 3 weeks after the last dose of NN703. RESULTS: Serum GH peak and area under curve (AUC) values after the first NN703 administration were greater than those after placebo administration (P < 0.05). However, after correction for the lower body mass index (BMI) in the NN703 group, this difference lost statistical significance. After 1 week of therapy, GH peak and AUC values were similar following the final doses of NN703 and placebo. Serum peak and AUC values of other anterior pituitary hormones were similar between the NN703 and placebo groups both after the first and last administration of study drug. Nine of the 83 patients (11%) responded with a serum peak GH concentration >or= 5 micro g/l after the first and/or last NN703 administration, whereas no patient responded after placebo administration. Serum IGF-I was unaffected by 1-week NN703 treatment, whereas serum IGFBP-3 was increased (P < 0.05 vs. placebo) also after correction for BMI. Mean serum peak GH concentration after GHRH administration was 2.1 micro g/l (+/-0.3, SEM), which was higher than that after the first NN703 administration (1.32 +/- 0.3, P < 0.05). CONCLUSION: NN703 administration was generally well tolerated. Eleven per cent of the GHD adult patients responded with a peak GH response >or= 5 micro g/l after the first and/or last administration of oral NN703. Although a majority of GHD adults will not respond to NN703, the present results suggest that oral NN703 treatment could be useful in some adult patients with moderately severe GHD. These patients may be identified by a test dose of GHS.

Administration, Oral↗
PubMed2003

The treatment of sporadic versus MEN1-related pituitary adenomas.

The treatment of pituitary tumours strongly depends on their clinical presentation. In general, the treatment aims are reducing tumour volume and/or decreasing hormone hypersecretion. It relies on single or a combination of three different methods: surgery, medication and radiotherapy. The rationale for deciding the treatment are many but include the aggressiveness of the tumour. The aetiologies of sporadic pituitary adenomas are not fully understood. However, several causes have been identified resulting in specific familial phenotypes like multiple endocrine neoplasia type I (MEN1). MEN1 is related to mutations in the MEN1 gene, a tumour suppressor gene localized on chromosome 11q13 and which encodes menin, a 610 amino acid protein. During the last years, an evidence progressively emerged that MEN1-related adenomas were more aggressive and less responsive to therapy than their sporadic counterparts. In this article, we review the differences between sporadic and MEN1-related adenomas and suggest specific ways of treatment and follow-up for MEN1-related tumours.

Acromegaly↗
PubMed2003

The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients.

OBJECTIVE: Our aim was to report the recent changes in diagnosis and management of TSH-secreting pituitary adenomas. METHODS: We retrieved 43 consecutive patients with TSH-secreting pituitary tumors (23 male and 20 female) among 4400 pituitary adenomas followed between 1976 and 2001 in six Belgian and French centers. RESULTS: TSH was elevated in 18/43 and alpha subunit in 13/32 patients. In patients with intact thyroid (n=30), mean free tri-iodothyronine was 13.1 pmol/l (range 3.5-23) and mean free thyroxine was 38.4 pmol/l (range 10.2-62.7). Hyperprolactinemia and acromegaly were associated in 9/43 and 8/43 cases. The number of associated hypersecretions was higher in macroadenomas than in microadenomas (Chi square = 11.2, P<0.01). Two women had sporadic multiple endocrine neoplasia type 1-associated syndrome. The proportion of microadenomas versus macroadenomas was 1/11 (period 1974-1986) and 8/32 (period 1987-2001). Bilateral petrosal sinus sampling, (111)In-pentreotide scintigraphy and ((11)C)-l-methionine positron emission tomography scan confirmed diagnosis in four questionable microadenomas. Macroadenomas with extrasellar extension (31 cases) had a tendency to be medially located. Medical treatment with somatostatin analogs was initiated as first-line treatment in 26 patients. TSH levels were reduced by more than 50% in 23/26 cases. A tumoral shrinkage of more than 20% was observed in 5/13 cases. Surgery was performed in 36 patients. After 1 year, 21 of them (58.3%) met the criteria of surgical favorable outcome. Pituitary radiotherapy (n=8) and somatostatin analogs allowed normalization in cases not cured by surgery. CONCLUSION: Ultrasensitive methods for TSH measurement led to an earlier recognition of TSH-secreting pituitary tumors. In this series, we observed that TSH-secreting pituitary tumors are today more frequently found at the stage of microadenomas, medially located, without associated hypersecretions and needing new exploration methods as compared with older series. This changing spectrum in the presentation of TSH-secreting pituitary tumors and the excellent response to somatostatin analogs has been accompanied by an improvement in the prognosis of the disease.

Acromegaly↗
PubMed2003

[Medullary thyroid cancer: how tumor markers and genetics determine preventive measures].

Medullary thyroid cancer (MTC) arises from parafollicular C cells secreting calcitonin. MTC occurs both as sporadic tumors and as part of specific inherited autosomal dominant syndromes in which point mutations within a discrete set of RET codons were described. Total thyroidectomy and aggressive neck dissection represents the only chance for cure in the affected patients. Therefore, all patients with thyroid nodular disease should undergo measurement of calcitonin plasma levels to allow preclinical diagnosis of the disease and early appropriate surgery ("secondary prevention"). In case of proband patient for inherited disease, all the family members should be genetically screened to detect the disease gene carriers. Patients with germline mutation would benefit either from earlier surgery at the stage of C-cell hyperplasia or microcarcinoma or prophylactic surgery (total thyroidectomy without neck dissection) (primary prevention) before the onset of any C-cells pathology. The ideal age for performance of such prophylactic surgery is determined by the genotypic features of the disease.

Biomarkers, Tumor↗
PubMed2003

[Clinical case of the month. Anterior mediastinal mass in a patient with acromegaly].

The discovery of an anterior asymptomatic mediastinal mass with acromegaly creates a dilemma for the clinician. As acromegaly can be due to a pituitary tumor but also to an ectopic production of GHRH, the first diagnostic step consists of finding the etiology of the disease in order to use adequate treatment. This can be complicated by the fact that acromegaly can be associated with other tumors (for instance in MEN-1 disease and Carney Complex) and because chronic GH hypersecretion can stimulate tumor overgrowth and perhaps tumor formation. We describe the case of a 44-year-old acromegalic woman with an anterior mediastinal mass. We present the different diagnoses and a review of the literature.

Acromegaly↗
PubMed2003

[Therapeutic strategies in somatotroph adenomas with extrasellar extension: role of the medical approach, a consensus study of the French Acromegaly Registry].

UNLABELLED: From the first 198 patient files included into the French Acromegaly Registry, we analyzed 68 patients harboring a somatotroph adenoma with extrasellar extension, after exclusion of those treated by stereotactic or conventional radiotherapy. In these patients (including 37 women), aged 21-77 yr. (45.7 +/- 13.3), GH concentrations ranged from 2-260 microg/L (38.6 +/- 44.3), and IGF I from 86-967% of age-matched upper limit of normal (303 +/- 164). Maximal diameter of the adenoma at MRI was 11-36.5 mm (20.4 +/- 6.5), with cavernous sinus involvement in 68% of cases. Three subgroups were defined: 20 patients treated by long-acting somatostatin analogs only (group M), for a mean duration of 3 yr. (extremes 1-7 yr.), 48 patients initially treated by transsphenoidal surgery (group C), of whom 21 were secondarily treated by long-acting somatostatin analogs (group CM) for a mean duration of 1.2 yr. (extremes 0.2-2 yr.). All 3 groups were not statistically different in terms of tumor mass and initial levels of GH and IGF-1. Patients from group M were significantly older than those of the other groups (p<0.05). RESULTS: 46% of patients from group C after surgery vs. 45% of patients from group M had a mean GH below 2.5 microg/L. Biochemical remission (GH<2.5 microg/L and normal IGF1 normal) was obtained in 31% of cases in group C, vs. 25% in group M. In this group, a decrease of the largest tumor diameter was observed in 10 patients (71.5%), ranging from 10-25% in 7 (50%) and exceeded 50% in 3 (21.5%). In group CM, the biochemical remission rate (42%) and final GH or IGF1 values were not significantly different from group M. In conclusion, these data suggest that surgery or long-acting somatostatin analogs have a comparable efficacy in terms of remission rates in somatotroph macroadenomas with extrasellar extensions.

Acromegaly↗
PubMed2002

Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly.

Lanreotide Autogel is a new long-acting aqueous preparation of lanreotide for the treatment of acromegaly and is administered by deep sc injection from a small volume, prefilled syringe. The aim of this study was to evaluate the efficacy and safety of this new long-acting formulation in a large population of acromegalic patients previously responsive to lanreotide 30 mg, im (sustained release microparticle formulation). Lanreotide Autogel was administered by deep sc injection every 28 d to 107 patients (54 males and 53 females; mean age, 54 +/- 1.2 yr). All patients had been treated with lanreotide (30 mg) for at least 3 months before study entry and had a mean GH level less than 10 ng/ml after at least 4 subsequent im injections every 14 d (48%), 10 d (32%), or 7 d (20%). Treatment was switched from lanreotide 30 mg injected every 14, 10, or 7 d to 60, 90, or 120 mg lanreotide Autogel, respectively, every 28 d. After three fixed dose injections of lanreotide Autogel, mean lanreotide levels were similar to those obtained at steady state with lanreotide 30 mg. During lanreotide Autogel treatment, the control of acromegalic symptoms was comparable with that previously achieved during lanreotide 30 mg treatment. After 3 injections of lanreotide Autogel, mean GH (2.87 +/- 0.22 ng/ml) and IGF-I (317 +/- 15 ng/ml) values were comparable with those recorded at the end of lanreotide 30 mg treatment (GH, 2.82 +/- 0.19 ng/ml; IGF-I, 323 +/- 16 ng/ml). GH levels below 2.5 ng/ml and age-/sex-normalized IGF-I were achieved in 33% and 39% of patients during lanreotide 30 mg and lanreotide Autogel treatment, respectively. Diarrhea, abdominal pain, and nausea were reported by 38%, 22%, and 18% of patients during lanreotide 30 mg treatment and by 29%, 17%, and 9% of patients, respectively, during lanreotide Autogel treatment. In conclusion, this clinical study shows that lanreotide Autogel is at least as efficacious and well tolerated as lanreotide 30 mg. This new long-acting lanreotide formulation, lanreotide Autogel, which is administered from a small volume, prefilled syringe by deep sc injection, is therefore likely to improve the acceptability of medical treatment for patients requiring long-term somatostatin analog therapy.

Acromegaly↗
PubMed2002

[Multihormonal bilateral petrosal sinus sampling in Cushing's disease: radiological, surgical and pathological correlations].

Multihormonal bilateral petrosal sinus sampling (BPSS) has been proposed to improve corticotroph microadenomas prediction of lateralisation. Few series have simultaneously compared data of pituitary MRI, surgical findings and multihormonal BPSS. Seven patients (6F/1M) with Cushing's disease, mean age at diagnosis of 35 years (range 24-55) were prospectively studied to compare radiological and multihormonal BPSS data with surgical and pathological findings. In untreated patients, simultaneous measures of ACTH, TSH and prolactine (PRL) were done at time 0, 7, 15, 22 minutes after CRH (500 microgram) and TRH (200 microgram) stimulation. An intersinus gradient of 1.4 was considered as a lateralisation. All microadenomas were identified during surgery, diameters ranged from 2 to 7 mm. All patients were in long-term surgical remission. Pathological studies confirmed a tumoral tissue with ACTH immunostaining in 6/7 cases and PRL in 3/7 cases. Pituitary MRI correctly identified tumors in 4 cases, the remaining tumors were not seen. Basal and stimulated intersinus gradients of ACTH, TSH and PRL were homolateral in 6/7 cases and were coincident with surgical findings in 4/7 cases. The other three cases were contralateral to MRI and surgical data. In conclusion, simultaneous gradient of ACTH, PRL and TSH did not improve lateralisation prediction in this series. Hormonal hypersecretion was homolateral in six cases whereas pathological studies demonstrated a mixed secretion in only three cases. A preferential pituitary draining could explain these discordances. Data from our series and from others (done with CRH stimulation and ACTH-PRL measures) strongly suggest a paracrine interaction between tumoral and normal pituitary tissue.

Adenoma↗
PubMed2002

[Differential diagnosis and medical treatment in Cushing's disease].

Cushing's disease remains a difficult diagnosis in spite of new technical procedures such as pituitary MRI, selective bilateral petrosal or cavernous sampling, (111)In pentreotide scan and 18 Flurodeoxyglucose pituitary PET scan. In this article, we review biological diagnostic procedures of Cushing's disease and corticotroph adenomas. According to our experience and the literature, we summarize the approach in medical treatment of Cushing's disease.

ACTH Syndrome, Ectopic↗