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Treating hypercortisolism in patients with Cushing’s disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing’s disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was −82.6% (−89.0, −41.9) and −81.8% (−89.8, −67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. This represents the longest prospective trial of a medical therapy for Cushing’s disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing’s disease.

OBJECTIVE: Cross-sectional studies report a high prevalence of hypopituitarism after traumatic brain injury (TBI); however, no longitudinal studies on time of manifestation and reversibility exist. This study was conducted to assess hypopituitarism 3 and 12 months after TBI. DESIGN: This was a prospective, longitudinal, diagnostic study. METHODS: Seventy-eight patients (52 men, 26 women, mean age 36.0 years) with TBI grades I–III and 38 healthy subjects (25 men, 13 women, mean age 36.4 years) as a control group for the GHRH + arginine test were studied. The prevalence ofhypopituitarism was assessed 3 and 12 months after TBI by GHRH + arginine test, short adrenocorticotropic hormone (ACTH) test, and basal hormone measurements in patients. RESULTS: After 3 months, 56% of all patients had impairments of at least one pituitary axis with axes being affected as follows: gonadotropic 32%, corticotropic 19%, somatotropic 9% and thyrotropic 8%. After 12 months, fewer patients were affected, but in some cases new impairments occurred; 36% still had impairments. The axes were affected as follows after 12 months: gonadotropic 21%, somatotropic 10%, corticotropic 9% and thyrotropic 3%. CONCLUSIONS: Hypopituitarism occurs often in the post-acute phase after TBI and may normalize later, but may also develop after the post-acute phase of TBI.

Objective: Cross-sectional studies report a high prevalence of hypopituitarism after traumatic brain injury (TBI); however, no longitudinal studies on time of manifestation and reversibility exist. This study was conducted to assess hypopituitarism 3 and 12 months after TBI.Design: This was a prospective, longitudinal, diagnostic study.Methods: Seventy-eight patients (52 men, 26 women, mean age 36.0 years) with TBI grades I–III and 38 healthy subjects (25 men, 13 women, mean age 36.4 years) as a control group for the GHRH + arginine test were studied. The prevalence ofhypopituitarism was assessed 3 and 12 months after TBI by GHRH + arginine test, short adrenocorticotropic hormone (ACTH) test, and basal hormone measurements in patients.Results: After 3 months, 56% of all patients had impairments of at least one pituitary axis with axes being affected as follows: gonadotropic 32%, corticotropic 19%, somatotropic 9% and thyrotropic 8%. After 12 months, fewer patients were affected, but in some cases new impairments occurred; 36% still had impairments. The axes were affected as follows after 12 months: gonadotropic 21%, somatotropic 10%, corticotropic 9% and thyrotropic 3%.Conclusions: Hypopituitarism occurs often in the post-acute phase after TBI and may normalize later, but may also develop after the post-acute phase of TBI.

Patient registries are valuable tools to study long-term morbidity and mortality of rare diseases. Acromegaly is rare (incidence 3-4/mill/year, prevalence 40-70/mill; approx. 300 new patients/yr and up to 5700 patients in Germany). Diagnostic and therapeutic possibilities have considerably improved, but treatment results remain often unsatisfactory. The main cause is residual disease activity after surgery, most importantly due to invasive macroadenomas. The German Acromegaly Registry is an initiative of the Pituitary Study Group of the German Endocrine Society (DGE). Formally established in January 2003 by the Board of the DGE, long-term financial support is guaranteed by an unrestricted grant from Novartis Pharma GmbH to the DGE. The registry cooperates closely with the United Kingdom and the Austrian registries. The aim of the German Acromegaly Registry is to establish a database of sufficient epidemiological strength in order to (1) document co-morbidity and mortality, (2) provide data on diagnostic and therapeutic procedures/effectiveness, (3) enable comparison of procedures in different national centres, (4) provide information for patient support groups/interaction with health care providers, (5) enable comparison with other national registries within Europe. The registry has at present 82 participating centres, and 42 have included patients (20 university clinics, 8 non-university hospitals, 14 centres in private practice). The database aims to include all acromegalic patients in Germany who are cared for and treated at present. Up to December 2005 1543 patients have been entered in a retrospective manner. Data collection is by external monitoring by highly trained study nurses who visit the individual centres. Inclusion is planned to continue at a rate of 500 per year. Starting in 2005 centres are revisited every 3 years at a rate of 500 per year (prospective phase of the registry). Quality of the data has been validated by an independent monitoring team which demonstrated high data concordance. Conclusions: Initial results of the German Acromegaly Registry show that it was possible to include a large number of patients within 3 years into the registry. Data quality has been validated and shown to be satisfactory. Therefore, the registry will be a useful tool to study long-term morbidity and mortality in a large series of patients.

OBJECTIVE: Plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio is an established screening test for primary hyperaldosteronism. Due to the increased recognition of adrenal incidentalomas, reliable parameters are required. Determination of active renin concentration (ARC) in contrast to PRA offers advantages with regard to processing and standardization. The present study compared PRA and ARC under random conditions to establish thresholds for the diagnosis of primary hyperaldosteronism. DESIGN AND METHODS: Fifty patients with various adrenal tumors, including ten patients with aldosterone-secreting adrenal adenomas, as well as ten hypertensive patients and 23 normotensive volunteers were studied. PAC and PRA were measured by radioimmunoassay. ARC was determined by an immunoluminometric assay. RESULTS: Receiver operating curve (ROC) analysis suggested a PAC to ARC ratio threshold of 90 ((ng/l)/(ng/l)) (sensitivity 100%, specificity 98.6%) and a ratio threshold of 62 by additional consideration of PAC > or =200 ng/l (sensitivity 100%, specificity 100%) for the diagnosis of aldosterone-secreting adrenal adenomas. CONCLUSIONS: A PAC to ARC ratio of > or =62 in patients with PAC levels > or =200 ng/l is a reliable screening method for primary hyperaldosteronism in patients with an aldosterone-producing adenoma under random conditions. Because of its advantages with regard to probe processing and its independence from endogenous angiotensinogen levels, ARC may be preferred to PRA.

OBJECTIVE: Plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio is an established screening test for primary hyperaldosteronism. Due to the increased recognition of adrenal incidentalomas, reliable parameters are required. Determination of active renin concentration (ARC) in contrast to PRA offers advantages with regard to processing and standardization. The present study compared PRA and ARC under random conditions to establish thresholds for the diagnosis of primary hyperaldosteronism. DESIGN AND METHODS: Fifty patients with various adrenal tumors, including ten patients with aldosterone-secreting adrenal adenomas, as well as ten hypertensive patients and 23 normotensive volunteers were studied. PAC and PRA were measured by radioimmunoassay. ARC was determined by an immunoluminometric assay. RESULTS: Receiver operating curve (ROC) analysis suggested a PAC to ARC ratio threshold of 90 ((ng/l)/(ng/l)) (sensitivity 100%, specificity 98.6%) and a ratio threshold of 62 by additional consideration of PAC > or =200 ng/l (sensitivity 100%, specificity 100%) for the diagnosis of aldosterone-secreting adrenal adenomas. CONCLUSIONS: A PAC to ARC ratio of > or =62 in patients with PAC levels > or =200 ng/l is a reliable screening method for primary hyperaldosteronism in patients with an aldosterone-producing adenoma under random conditions. Because of its advantages with regard to probe processing and its independence from endogenous angiotensinogen levels, ARC may be preferred to PRA.

OBJECTIVE: The diagnosis of GH deficiency in adults should be made using provocative testing of GH secretion. The insulin tolerance test (ITT) is recommended as the gold standard investigation. Because of the risk of serious complications, patients with epilepsy or known ischemic heart disease should not undergo this test. GHRP-6 is a synthetic hexapeptide that releases GH by binding to specific hypothalamic and pituitary receptors. We assessed the diagnostic capability of GH stimulation by GHRP-6 alone or in combination with GHRH in comparison to the results of an ITT. DESIGN: Twenty patients underwent an ITT for suspected pituitary or adrenal disease. Either GHRP-6 (1 microg/kg) alone, or GHRP-6 in combination with GHRH (1 microg/kg) were administered on different days. Blood samples were obtained during a subsequent 90-min period for measurement of GH. RESULTS: Ten patients had a GH peak response of less than 3 microg/l during ITT and were considered growth hormone deficient (GHD). The GH mean peak (+/-S.E.M., range) in this group was 0.7 microg/l (+/-0.3, 0.1-2.9) compared with 14.5 microg/l (+/-3.5, 3.8-40.8) in the group of patients with a GH peak response of more than 3 microg/l (growth hormone sufficient (GS)). For the GHRP-6 test, the GH mean peak was 1.3 microg/l (+/-0.6, 0.1-6.7) in the GHD group versus 25.7 microg/l (+/-5.5, 7.7-54.2) in the GS group. After GHRP-6+GHRH, the GH mean peaks were 4.0 microg/l (+/-1.3, 0.2-11.9) versus 54.7 microg/l (+/-11.1, 13.9-136.0) respectively. During administration of GHRP-6, the only side effects observed were flush symptoms. CONCLUSIONS: Peak GH levels below 7 microg/l for the GHRP-6 test and below 13 microg/l for the combined GHRP-6+GHRH test identified all patients with GH deficiency correctly as defined by ITT. The results suggest that testing with GHRP-6 or GHRP-6+GHRH is as sensitive and specific as an ITT for the diagnosis of adult GH deficiency.

Summary This study compared the pharmacokinetics of orally administered isosorbide-5-mononitrate (20 mg) in patients with and without signs of ischemic heart failure after acute myocardial infarction. The central venous pressure was used as a parameter of global myocardial function and to separate 17 patients into two groups with normal (group I: CVP<6 cmH2O; Killip class I;n=9) and elevated (group II: CVP>-6 cmH2O; Killip class II–III;n=8) pressure. As compared to subjects with normal CVP patients with hemodynamic impairment showed a markedly lower peak concentration of isosorbide-5-mononitrate levels (475±32 vs 663±38 ngml-1;p<0.01; mean±SEM) which occurred delayed (32±6 vs 55±9 s;p<0.05). Reduced cardiac function also resulted in a prolonged elimination of isosorbide-5-mononitrate as was suggested by the diminished elimination rate constant (0.14±0.01 vs 0.18±0.01 h-1;p<0.05). Thus, in patients with ischemic heart failure cardiac performance influences both the absorption and apparent elimination phase of oral isosorbide-5-mononitrate.

We report the first case of a male patient with iodine-induced hyperthyroidism and unstable angina pectoris in whom a diagnostic cardiac catheterization with gadolinium as contrast agent was chosen. The patient was hospitalized with an iodine-induced hyperthyroidism after angioplasty using an iodinated contrast agent. He presented with a continuous arrhythmia and unstable angina pectoris. A repeated cardiac catheterization using iodinated contrast agent was contraindicated. This case report shows that gadolinium is a useful alternative contrast agent for cardiac intervention in patients with iodine-induced hyperthyroidism.

Nous présentons les résultats d’une étude de phase III évaluant efficacité et tolérance du pasiréotide à libération prolongée (LP) administré en injection intramusculaire mensuelle chez des patients avec MC.

Un traitement primaire par lanréotide 120mg entraîne une diminution du volume adénomateux et des concentrations de GH/IGF-1 chez les patients acromégales.

PREMESSE: La malattia di Cushing è una patologia ad alta morbidità e mortalità per la quale oggi non vi è una terapia medica di provata efficacia. Il pasireotide, un ligando multirecettoriale per i recettori per la somatostatina (SS), ha dimostrato di possedere nell’animale in vitroe in vivoun significativo effetto inibitorio sulla funzione corticotropa con conseguente riduzione della secrezione glucocorticoide in tumori ACTH-secernenti. SCOPO:Valutare l’efficacia di un trattamento a breve termine con pasireotide in pazienti affetti da malattia di Cushing. METODI: È stato valutato l’effetto del trattamento per 15 giorni con pasireotide (600 mg/bid) in 39 pazienti con malattia di Cushing, de novo, persistente o recidivata dopo trattamento neurochirurgico. RISULTATI: Dei 29 pazienti in cui si è potuta eseguire l’analisi di efficacia, il 76% (N=22) ha dimostrato una significativa riduzione dei livelli di cortisoluria, con normalizzazione nel 17% (N=5), in associazione a una riduzione dei livelli di ACTH e cortisolo, più pronunciata nei soggetti responder. I livelli plasmatici steady statedi pasireotide sono stati ottenuti entro 5 giorni dall’inizio del trattamento. I pazienti responderhanno dimostrato livelli plasmatici di pasireotide più elevati rispetto ai non responder. CONCLUSIONI: Il trattamento a breve termine con pasireotide ha dimostrato un significativo effetto inibitorio sui livelli di cortisoluria nella maggior parte dei pazienti studiati con malattia di Cushing, associato a una riduzione della secrezione corticotropa, suggerendo una potenziale nuova prospettiva terapeutica in tale patologia.

Les anomalies métaboliques sont fréquentes chez les patients atteints d’acromégalie, et l’équilibre glycémique peut s’aggraver au cours du traitement par certains analogues de la somatostatine.

Chez les patients acromégales, le traitement primaire par lanreotide Autogel diminue le volume adénomateux et contrôle l’hypersécrétion somatotrope, mais les données sur la qualité de vie (QdV) sont limitées. Nous rapportons les résultats sur la QdV au cours de l’étude PRIMARYS.

L’acromégalie est une maladie rare, due à une production excessive d’hormone de croissance (GH) et d’IGF-1. L’objectif de l’étude SAGIT était d’évaluer l’acceptabilité par les endocrinologues d’un nouvel outil destiné à la pratique clinique.