Objective: We studied the efficacy of octreotide treatment on hypoglycaemia in patients with insulinoma and its relationships with Octreoscan scintigraphy and the presence of tumoral somatostatin receptors sst2A and sst5. Design and methods: 17 patients with insulinoma were evaluated using (i) evaluation of blood glucose, insulin and C-peptide during a short 100 mg octreotide test in fasting patients and/or treatment over 8 days-8 months with octreotide, (ii) Octreoscan scintigraphy and (iii) immunostaining of the tumor with anti-sst2A and anti-sst5. Results: Octreotide was effective on hypoglycaemia in 10/17 patients. Octreoscan scintigraphy detected 4/17 insulinomas. sst2A receptor was detected in 7/17 insulinomas and sst5 in 15/17 insulinomas. Octreotide was effective on hypoglycaemia in those seven patients with sst2A receptorexpressing insulinoma, and in three patients with undetectable sst2A receptor and detectable sst5; it was ineffective in six patients whose tumor expressed the sst5 receptor with undetectable sst2A and in one patient with undetectable sst2A and sst5 receptor. Conclusions: Octreotide is an effective treatment of hypoglycaemia in more than 50% of patients with insulinoma. Detection of responsive patients was better based on a positive short test with subcutaneous octreotide than on the results of Octreoscan scintigraphy. Positive anti-sst2 receptor immunostaining is associated with efficacy of octreotide treatment, but does not account for all cases of responsiveness to octreotide. Expression of sst5 receptor does not appear to explain per se the efficacy of octreotide on sst2A-negative insulinomas.European Journal of Endocrinology 152 757-767
Objective: We evaluated the respective value of insulin, C-peptide and proinsulin levels in 33 patients with endogenous hyperinsulinism and in 67 controls to determine the best parameters and thresholds to make or to rule out the diagnosis of endogenous hyperinsulinism. Results: When blood glucose levels were below 2.5 mmol/l, insulin was !21 pmol/l in 8-35% of the patients and in all controls; C-peptide was O0.2 nmol/l in all insulinomas but not in the nesidioblastosis or in the controls; proinsulin was O5 pmol/l in all patients but not in the controls. When fasting blood glucose levels reached 2.5-3.3 mmol/l, proinsulin was !22 pmol/l in all the controls and O22 pmol/l in 74% of the patients. Proinsulin after an overnight fast was below 22 pmol/l in all non-obese controls and above 22 pmol/l in 73% of non-obese patients. Conclusion: Proinsulin levels above 5 pmol/l with blood glucose levels below 2.5 mmol/l during a 72 h fast test represent the best criterion for the diagnosis of endogenous hyperinsulinism, reaching 100% diagnostic specificity and sensitivity. Concomitant C-peptide levels above 0.2 nmol/l also make the diagnosis of all our insulinoma patients, not the diagnosis of nesidioblastosis, while insulin levels have much less diagnostic accuracy. Whether proinsulin levels above 22 pmol/l could also make the diagnosis of endogenous hyperinsulinism in part of the patients at the time of fasting blood glucose levels between 2.5 and 3.3 mmol/l or after an overnight fast in non-obese subjects needs further study. European Journal of Endocrinology 157 75-83
SummaryContext The role of somatostatin analogues (SSTa) in the treatment of acromegaly. Objective To evaluate the antihormonal and antitumour efficacy of long-term (up to 18 years) primary treatment with SSTa in patients with GH-secreting pituitary adenoma responsive to SSTa. Design An open, prospective, single-centre, clinical study. Patients Thirty-six acromegalic patients, aged 17-75 years (postoral glucose tolerance test GH > 1 µ g/l, increased IGF-1 for age and sex), were monitored in a single centre and treated with SSTa as firstline therapy. The mean pretreatment GH level was 13·5 ± 3·1 µ g/l, and IGF-1 (as a percentage of the value over the normal range) was 302 ± 26%. The patients had macroadenoma ( n = 25), microadenoma ( n = 8) or empty sella turcica ( n = 3). The mean duration of treatment was 8 years (range 3-18 years). Hormonal and morphological monitoring was undertaken after 6 months, and then the patients were followed annually. Results After 1 year, the mean GH and IGF-1 levels had reduced considerably (GH: 2·4 ± 0·3 µ g/l; IGF-1; 174 ± 14%, P < 0·01), and they continued to decrease over 10 years, with a mean GH level of 1·6 ± 0·1 µ g/l and IGF-1 of 123 ± 18% ( P = 0·02). GH < 2 µ g/l, normal IGF-1, or both were observed in 25 (70%), 24 (67%) and 21 (58%) patients, respectively. The mean reduction in tumour volume was 43% (range 13-97%) and shrinkage > 20% was obtained in 21 patients (72%). SSTa treatment was well tolerated with few digestive or metabolic side-effects. Conclusion Long-term (up to 18 years) treatment with SSTa used as first-line therapy is effective from both an antihormonal and antitumour perspective, and is well tolerated in acromegalic patients.
Introduction: Acromegaly, a chronic disease caused by GH/IGF-I excess, has a major impact on quality of life (QoL). Objective: To evaluate QoL of acromegalic patients in relation to control status of the disease. Design and methods: Single center observational study including 93 patients with acromegaly recruited to complete QoL questionnaire (AcroQol). QoL was evaluated at least 3 months after surgery and/or medical treatment. Patients were divided into two groups: controlled (I) and uncontrolled (II) according to the latest consensus acromegaly 'control' criteria and further subdivided into four subgroups according to the previous pituitary adenoma surgery (Ib and IIb) or without surgery (Ia and IIa). Results: Mean GH (0.81G0.47 ng/ml) and IGF-I (195G71 ng/ml) values in group I were significantly lower than in group II (GH, 7.01G12.05 ng/ml and IGF-I, 513G316 ng/ml; P!0.001). There was no difference in total AcroQol score, physical, or psychological scales between groups I and II. However, when adjusted to age and disease duration since diagnosis, patients of group I (63G20%) showed an improved psychological subscale appearance than those of group II (58G17%; PZ0.035). In group II, IGF-I level was lower after surgery (IIaZ588G353, IIbZ410G225 ng/ml; P!0.038), and psychological subscale appearance was significantly better in subgroup IIb (64.9G18.1%) than in subgroup IIa who had medical treatment (53.9G14.3%; PZ0.009). Conclusion: QoL is severely impaired in acromegalic patients. Control of GH/IGF-I excess by surgery or medical treatment seems to have a positive impact on psychological subscale appearance.
The 5% prevalence of heterozygous mutations discovered in our series is higher than initially thought and encourages GR mutation screening in patients with adrenal incidentalomas to unambiguously differentiate from Cushing's states and to optimize personalized follow-up.
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