[Management of erectile dysfunction by general practitioners and endocrinologists in diabetes: a survey of 130 patients]. / Attitudes des médecins généralistes et endocrinologues face à la dysfonction érectile du patient diabétique: enquête auprès de 130 patients.

OBJECTIVES: To assess the prevalence, the severity and expectations regarding erectile dysfunction (ED) in diabetic patients, then to investigate how general practitioners (GP) and endocrinologists manage this disorder. PATIENTS AND METHODS: A questionnaire was given during 5 weeks to every diabetic patient addressed to the endocrinology department in order to assess erectile function (IIEF5), patient's bother and expectations to be treated, and the management of ED by GP and endocrinologists and differences in management between male and female doctors. RESULTS: One hundred and thirty questionnaires were available. Mean age was 57.5 and the mean IIEF5 score was 13.6. Twenty-two patients (16.9%) reported an IIEF5 score less than 5 and 75 patients (57,6%) reported an IIEF5 between 5 and 20. Eighty-six patients declared ED (66.2%). In these patients, 76 (88.4%) sought for a medical treatment and 11 (12.8%) received a treatment for ED. Endocrinologists were more active than GP in the screening of ED (59.5% vs 19.4%, P=0.001) but prescribed a treatment less often (14.3% vs 45.2%, P=0.008). Female doctors seemed less active in ED management (29.3% vs 13.3%, NS). CONCLUSIONS: This study highlighted the lack of ED management by GT and endocrinologists in diabetic patients in spite of ED's frequency and patients' expectations.

Somatostatin receptor scintigraphy in pituitary adenomas: a somatostatin receptor density index can predict hormonal and tumoral efficacy of octreotide in vivo.

UNLABELLED: Previous studies have failed to predict somatostatin analog response with somatostatin receptor scintigraphy in pituitary adenomas. In vitro studies have shown that the density of somatostatin receptors in pituitary tumors might be critical for octreotide response. METHODS: The density of somatostatin receptors was calculated in vivo combining the uptake index obtained from somatostatin receptor scintigraphy and the tumor volume obtained by MRI. The ratio of these two values, called density index (DI), was established in 32 of 37 consecutive patients with pituitary adenomas (11 had growth hormone-secreting adenomas, 4 thyroid-stimulating hormone-secreting and 17 nonfunctioning). It was compared with hormonal response, assessed in 15 secreting adenomas on growth hormone or thyroid stimulating hormone suppression (which was considered significant when it reached at least 50% of basal level), and with tumor shrinkage (which was considered significant when > or =20% of pretherapeutic value) in 12 secreting and 14 nonfunctioning adenomas. RESULTS: In agreement with previous reports, uptake index is not predictive of octreotide response. In contrast, DI predicts both hormonal suppression and tumor shrinkage (P = 0.009 and P = 0.0002, respectively) obtained with octreotide therapy. DI sensitivity, specificity and accuracy were 92% each, and a positive correlation was found between DI and the percentage of tumor shrinkage (r = 0.54, P = 0.004). CONCLUSION: The combination of scintigraphic and MRI data allows the computation of a DI for somatostatin receptors that points out patients who can profit from somatostatin analog treatment.

A new quantitative D-dimer assay appropriate in emergency: reliability of the assay for pulmonary embolism exclusion diagnosis.

Plasma D-dimers, degradation products of cross-linked fibrin, are elevated in several thrombotic diseases. In the last decade, their measurement has been performed with specific monoclonal antibody based ELISA assay, with a high negative predictive value of such pathologies. However these methods have a low clinical impact since they cannot be used in emergency because they are time consuming and require series. Recently, rapid tests have been proposed with similar accuracy and are feasible for use in emergency conditions. The aim of our study was to evaluate the potential value of a new quantitative rapid assay, based on agglutination of latex microparticles coated with two monoclonal antibodies specific for D-dimers (Liatest D-Di, Diagnostica Stago), in the exclusion diagnosis of pulmonary embolism (PE). Eighty-five consecutive suspected PE patients were included in the study. D-dimer determination was performed with both standard ELISA and Liatest D-Di just before pulmonary scintigraphy. Sixty-nine patients were free of PE and 16 had PE. Our results confirm the excellent sensitivity and negative predictive values of the conventional D-dimer ELISA. Using a cut-off value of 500 ng/ml, the sensitivity and the negative predictive values of Liatest D-Di were 94% and 96%, respectively. Only one case of PE had a D-dimer value at 480 ng/ml, close to the cut-off value. This study demonstrates that the Liatest D-Di assay is sensitive enough to be used as the first step in the assessment of PE. However, the best cut-off value has to be determined to get an exclusion diagnosis with certainty.

Chronic diarrhoea and diabetes mellitus: prevalence of small intestinal bacterial overgrowth.

The mechanisms of chronic diarrhoea, a frequent symptom in diabetes mellitus, are multifactorial and complex, although small intestinal bacterial overgrowth and autonomic neuropathy seem to play a major role. This study evaluated the prevalence of small intestinal bacterial overgrowth and the effects of antibiotic treatment in a population of diabetic patients with chronic diarrhoea (defined as > 3 stools/24 h, weight > 200 g/24 h, duration > 3 weeks). Small intestinal bacterial overgrowth syndrome was diagnosed by glucose-hydrogen breath testing (sensitivity: 78%, specificity: 89%). The characteristics of diarrhoea (duration, number of stools per day, and gastrointestinal symptoms) were noted. Autonomic neuropathy was assessed by cardiac parasympathetic tests. A total of 35 patients were included, 15 with small intestinal bacterial overgrowth syndrome (43%, group 1) and 20 with no bacterial overgrowth (group 2). Age (52.9 +/- 13.5 vs. 53.9 +/- 11.8 years, NS), duration of diabetes (13.8 +/- 9.1 vs. 10.6 +/- 7.8 years, NS), and HbA1c level (10 +/- 2.9 vs. 10.9 +/- 2.4%, NS) were not different between the two groups. In group 1, duration of diarrhoea was longer (18.1 +/- 18.5 vs. 7.75 +/- 4.02 months, P = 0.05), the number of stools higher (7.1 +/- 5.7 vs. 4.6 +/- 2.6/24 h, P < 0.05), and gastrointestinal symptoms more frequent (13 vs. 10, P < 0.05). The prevalence of small intestinal bacterial overgrowth syndrome and gastrointestinal symptoms was not different in patients with and without autonomic neuropathy (9 vs. 8 and 12 vs. 11 respectively, NS). Eight patients with bacterial overgrowth received antibiotics (amoxicillin-clavulanic acid, 1.5 g/24 h for 10 days). Dramatic clinical improvement was observed in 6 out of 8 of these patients. It is concluded that small intestinal bacterial overgrowth should be considered in case of chronic diabetic diarrhoea because of its frequency (43%), facility of diagnosis, and often successful treatment with antibiotics.

Whole-body (201)Tl scintigraphy can detect exercise lower limb perfusion abnormalities in asymptomatic diabetic patients with normal Doppler pressure indices.

Significant lower limb arterial obstruction is usually detected by Doppler ankle-brachial pressure index (ABPI) measurement. However, ABPI is non-contributory in cases of diabetic medial sclerosis or calcifications and is unsuitable for the detection of small vessel involvement. Thallium-201, a perfusion agent, is frequently used for the investigation of coronary artery disease, and whole-body (201)Tl scintigraphy (WBS) has also been reported to be useful in the assessment of peripheral artery disease (PAD). Thus, we evaluated the clinical feasibility of simultaneous myocardial and lower limb perfusion assessment. WBS was performed after treadmill exercise and myocardial scintigraphy, and again 4 h later. Calf (201)Tl fractional activities (percentage of whole-body (201)Tl uptake) were calculated. We determined a threshold value of normal post-exercise calf (201)Tl uptake (mean of the (201)Tl fractional uptakes minus 2 SD) in a control group of nine healthy volunteers. We checked its accuracy in a pilot group of 25 diabetic patients with proven PAD. This method permitted the detection of lower limb perfusion abnormalities in 38% of 47 asymptomatic diabetic patients with no evidence of PAD. In conclusion, for asymptomatic diabetic patients, whole-body (201)Tl scintigraphy after a treadmill test seems an efficient method of showing lower limb perfusion abnormalities not detected by ABPI measurement. It allows the evaluation of vascular status with no additional inconvenience for patients when performed after myocardial scintigraphy.

[Hypophyseal adenomas: functional and tumor evaluation and therapeutic approaches]. / Adénomes hypophysaires: bilan tumoral et fonctionnel et abords thérapeutiques. therapeutic approaches]

Patients with pituitary adenomas present with hypersecretion syndrome(s), and/or pituitary failure(s), and/or signs of mass effect, or incidentally. Pituitary function evaluation, visual acuity and field check-up, and MRI or at least CAT are compulsory for diagnosis, and for therapeutic approach; surgery for Cushing's disease, dopamine agonists for prolactinomas, somatostatin analogs or surgery for thyrotroph adenomas, surgery and/or somatostatin analogs and/or radiotherapy in acromegaly, surgery with additional irradiation in most adenomas of other types, or even expectation in some instances.

[Lymphoma of the pituitary stalk]. / Lymphome cérébral primitif de la tige pituitaire.

INTRODUCTION: Tumors of the pituitary stalk are rare and their diagnosis is sometimes difficult. CASE REPORT: We report a case of a primary lymphoma of the pituitary stalk in a 78-year-old patient. To our knowledge, only seven similar cases have been previously published: prominent symptoms were headache, fatigue and diplopia; biologically, anterior pituitary low secretion or hyperprolactinemia were found in the majority of cases; regarding the imaging, only three patients presented an initial and isolated lesion of the stalk; histological evidence was obtained by a trans-sphenoidal biopsy in case of hypothalamic or pituitary associated lesion or by a trans-cranial biopsy in the event of an isolated lesion. As an alternative, a lumbar puncture could be performed; although less invasive, its diagnostic performance is lower. CONCLUSION: Current treatment relies on chemotherapy with intravenous methotrexate associated with intrathecal methotrexate infusion if cerebrospinal showed abnormal cells. Unfortunately, the results remain poor with a median survival of 9 months.

Somatostatin receptor imaging in non-functioning pituitary adenomas: value of an uptake index.

Somatostatin receptor imaging (SRI) was performed in five patients with known non-functioning pituitary adenomas. To determine whether the pituitary uptake correlates with response to octreotide therapy, an uptake index (UI) was calculated. Pituitary adenomas were detected in all five patients. The UI was, respectively, 15.1, 3.7, 2.2, 2.2 and 2.2 (the UI calculated in 12 normal subjects was between 1 and 1.9). Only the patient with the highest UI (15.1) had a dramatic improvement in tumour volume and visual function in response to octreotide therapy. The UI might be a good predictive parameter of octreotide therapy efficacy in non-functioning adenomas.

The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site.

OBJECTIVE: Given the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours. DESIGN: We determined if GnRHR mRNA was expressed in gonadotroph tumours using RT-PCR and analysed the GnRHR gene for the presence of mutations in its coding region, using direct sequencing of PCR products. Results were analysed according to the pattern of expression of alpha, beta-FSH and beta-LH subunit (SU) genes. SUBJECTS: RNA was extracted from 20 gonadotroph tumours identified by immunohistochemistry (> 10% of stained cells): 9 adenomas were functioning (high serum gonadotrophin levels), 3 were associated with high alpha-SU levels and 8 were nonfunctioning. Genomic DNA was extracted from 64 normal subjects. RESULTS: We found GnRHR mRNA in 12 tumours (60%): 8/9 functioning (88%), 1/3 alpha-secreting (33%) and 3/8 nonfunctioning (37.5%) gonadotroph adenomas. There was a significant association between GnRHR expression and immunostaining for beta-FSH (P = 0.014). The nucleotide sequence of the amplified products was identical to that of human pituitary except for the presence, in 3 functioning adenomas, of a silent C to T transition at nucleotide 453 encoding for the serine residue situated in the second intracellular loop at position 151. Heterozygosity provided evidence that both alleles were transcribed in these tumours. This substitution creates a Mae III restriction site. Genomic DNA from normal subjects were then tested for the presence of this new polymorphism. The frequency of the heterozygosity (18.7%) was not significantly different from that found in gonadotroph tumours (25%) and this new Mae III polymorphism site cannot be used as a tumoural marker. CONCLUSION: The GnRHR gene is preferentially expressed in functioning rather than in nonfunctioning gonadotroph adenomas, but no mutations altering the coding region of the gene were found to further substantiate its role in the pathogenesis of gonadotroph tumours.

Somatostatin receptor imaging in somatotroph and non-functioning pituitary adenomas: correlation with hormonal and visual responses to octreotide.

OBJECTIVE: A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH-secreting and non-functioning pituitary adenomas. SUBJECTS AND METHODS: Somatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non-functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty-five patients were treated for 1 month with octreotide (300 micrograms daily). The therapeutic response was assessed on GH and IGF-I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied. RESULTS: From the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide-induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non-functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non-functioning pituitary adenomas with expression of sst2 only. CONCLUSION: In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non-functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.

Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly.

BACKGROUND AND OBJECTIVE: The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin LAR, Novartis Pharma AG) and lanreotide SR (Somatuline, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients. PATIENTS AND METHODS: A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3. RESULTS: The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values < or = 6.5 mU/l (2.5 microg/l) and < or = 2.6 mU/l (1.0 microg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated. CONCLUSION: Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly.