Roger Abs

Publications (35)130.82 Total impact

• Article: Prevalence of Diabetes Mellitus in 6050 Hypopituitary Patients with Adult-Onset Growth Hormone (GH) Deficiency before GH Replacement - a KIMS Analysis.

  Roger Abs, Anders F Mattsson, Maria Thunander, Johan Verhelst, Miklós I Góth, Patrick Wilton, Maria Koltowska-Haggstrom, Anton Luger
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  ABSTRACT: OBJECTIVE: Growth hormone (GH) deficiency (GHD) in adults is characterized by a tendency towards obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed over expected prevalence proportions (SPR) of diabetes according to IDF (International Diabetes Federation) criteria in a large cohort of GH-untreated adult-onset GHD patients. DESIGN AND METHODS: Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the non-diabetes patients were done with covariance analysis. P-values <0.05 were considered statistically significant. RESULTS: PP was 9.3% compared to the expected 8.2%. SPR was 1.13 (95% CI, 1.04-1.23), significantly increased in females (1.23; 95% CI, 1.09-1.38), not in males (SPR 1.04; 95% CI, 0.92-1.17). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference and IGF-I SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of non-diabetes patients and were associated with higher BMI and waist. CONCLUSIONS: GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge to early initiation of lifestyle modification measures.
  European Journal of Endocrinology 12/2012; · 3.42 Impact Factor
• Article: Active acromegaly is associated with decreased hs-CRP and NT-proBNP serum levels : Insights from the Belgian registry of acromegaly.

  Johan Verhelst, Brigitte Velkeniers, Dominique Maiter, Patrick Haentjens, Guy T'sjoen, Ernst Rietzschel, Bernard Corvilain, Pascale Abrams, Frank Nobels, Roger Abs, Mieke Bex
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  ABSTRACT: OBJECTIVE:PATIENTS WITH ACTIVE ACROMEGALY HAVE AN INCREASED PREVALENCE OF CARDIOMYOPATHY AND HEART FAILURE BUT A LESS THAN EXPECTED RISK OF CORONARY ARTERY DISEASE, CONSIDERING THE FREQUENT ASSOCIATION OF DIABETES MELLITUS AND HYPERTENSION. WE EXAMINED WHETHER CHANGES IN HIGH-SENSITIVE C-REACTIVE PROTEIN (HS-CRP) AND N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE (NT-PROBNP) MIGHT CONTRIBUTE TO THIS PHENOMENON.DESIGN AND METHODS:TWO HUNDRED PATIENTS OF THE BELGIAN ACROMEGALY REGISTRY (ACROBEL) WERE DIVIDED IN TWO GROUPS: active disease (IGF-I z-score >2; n=95) and controlled disease (IGF-I z-score ≤ 2; n=105). Serum levels of hs-CRP and NT-proBNP were measured and correlated with BMI, blood pressure, fasting lipids, fasting glucose and insulin, HbA1c, IGF1, interleukin-6 (IL-6), adiponectin and sE-selectin. In a subset of acromegaly patients, hs-CRP, IL-6 and NT-proBNP levels were also compared with those/the values of an age-, gender- and BMI-matched reference group. RESULTS:PATIENTS WITH ACTIVE ACROMEGALY HAD SIGNIFICANTLY LOWER LEVELS OF HS-CRP (MEDIAN [INTERQUARTILE RANGE] : 0.5 mg/L [0.1, 0.9] vs. 1.3 mg/L [0.5, 4.1]; p<0.001) and NT-proBNP (47.0 ng/L [26.0, 86.0] vs. 71.0 ng/L [43.0, 184.0]; p<0.001) compared to patients with controlled acromegaly. COMPARED WITH THE REFERENCE POPULATION, HS-CRP WAS NOT DIFFERENT IN CONTROLLED ACROMEGALY, BUT SIGNIFICANTLY LOWER IN ACTIVE ACROMEGALY (MEDIAN: 0.4 mg/L [0.1, 0.8] vs. 1.4 mg/L [0.8, 2.9]; p<0.001), while NT-proBNP was similar in active acromegaly but significantly higher in controlled acromegaly (66.5 ng/L [40.0, 119.5] vs. 50.8 ng/L [26.5, 79.7]; p<0.001).CONCLUSIONS:Patients with active acromegaly have significantly lower values of NT-proBNP and hs-CRP compared to patients with controlled disease and even lower values of hs-CRP compared to control subjects.
  European Journal of Endocrinology 11/2012; · 3.42 Impact Factor
• Source

  Available from: Ulla Feldt-Rasmussen

  Article: Overall and cause-specific mortality in GH-deficient adults on GH replacement.

  Rolf C Gaillard, Anders F Mattsson, Ann-Charlotte Akerblad, Bengt-Åke Bengtsson, José Cara, Ulla Feldt-Rasmussen, Maria Koltowska-Häggström, John P Monson, Bernhard Saller, Patrick Wilton, Roger Abs
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  ABSTRACT: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available. This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05. All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044). GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.
  European Journal of Endocrinology 03/2012; 166(6):1069-77. · 3.42 Impact Factor
• Article: Prevalence and characteristics of the metabolic syndrome in 2479 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis.

  Johan Verhelst, Anders F Mattsson, Anton Luger, Maria Thunander, Miklós I Góth, Maria Koltowska-Häggström, Roger Abs
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  ABSTRACT: An increased risk of cardiovascular morbidity and mortality in adult GH deficiency (GHD) may be related to hypopituitarism but also to the presence of the metabolic syndrome (MetS). Our objective was to investigate the characteristics and prevalence of MetS as well as its comorbidities in adult GHD. Design In KIMS (Pfizer International Metabolic Database) 2479 patients with severe adult-onset GHD, naïve to GH replacement, with complete information on all MetS components were found. MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP) and the International Diabetes Foundation (IDF). The prevalence of MetS was calculated and compared with previously published data from the normal population. Associations were assessed between background variables, baseline variables, comorbidities, and MetS. MetS was present in 43.1% (NCEP) and in 49.1% (IDF) of patients, clearly higher than data from the normal population (20-30%). MetS prevalence was related to age, GHD duration, and body mass index (BMI), but not to GHD severity, extent of hypopituitarism, or etiology of pituitary disease. Adjusted for age, gender, and BMI, patients with MetS had a higher prevalence ratio for diabetes mellitus: 4.65 (95% confidence interval (CI): 3.29-6.58), for cardiovascular morbidity: 1.91 (95% CI: 1.33-2.75), and for cerebrovascular morbidity: 1.77 (95% CI: 1.09-2.87) than patients without MetS. MetS is highly prevalent in GHD and is associated with a higher prevalence ratio for comorbidities. The presence of MetS in GHD may therefore contribute to the increased risk of cardiovascular morbidity and mortality found in these patients.
  European Journal of Endocrinology 12/2011; 165(6):881-9. · 3.42 Impact Factor
• Article: Incidence of diabetes mellitus and evolution of glucose parameters in growth hormone-deficient subjects during growth hormone replacement therapy: a long-term observational study.

  Anton Luger, Anders F Mattsson, Maria Koltowska-Häggström, Maria Thunander, Miklos Góth, Johan Verhelst, Roger Abs
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  ABSTRACT: Growth hormone (GH) deficiency is associated with insulin resistance and diabetes. The aim of the current study was to determine incidence of diabetes during GH replacement therapy (GHRT) and the effect of GHRT on fasting plasma glucose concentrations and HbA(1c) in adult patients with GH deficiency. A total of 5,143 GH-deficient patients (male 49.9%; mean age ± SD, 49 ± 13 years; BMI 29.1 ± 5.9 kg/m(2)) were analyzed. Mean observation period was 3.9 years (range 0.01-13). Total number of patient-years was 20,106. Observed number of cases (O) was compared with expected number of cases (E). Reference rates were from Sweden, three additional European regions, and one U.S. region. Patients who developed diabetes (n = 523) were older; had higher BMI, waist circumference, triglyceride concentrations, and blood pressure; and had lower HDL-cholesterol concentrations (P < 0.0001) than those who did not develop diabetes. Diabetes incidence was 2.6 per 100 patient-years, equal in both sexes, and significantly increased compared with the Swedish reference (O/E = 6.02; P < 0.0001) as well as with the four other populations (O/E = 2.11-5.22). O/E increased with BMI and decreased with duration of GHRT (P < 0.0001). There was no significant association with GH dose (P = 0.74) or IGF-I SDS (P = 0.47). In subjects not developing diabetes, plasma glucose concentrations increased from 84.4 ± 0.9 mg/dL to 89.5 ± 0.8 mg/dL (0.70 mg/dL/year) and HbA(1c) increased from 4.74 ± 0.04% to 5.09 ± 0.13% (0.036%/year) after 6 years of GHRT. Diabetes incidence appears to be increased in GH-deficient patients receiving GHRT and exhibiting an adverse risk profile at baseline. Therefore, glucose homeostasis parameters should be monitored carefully in these patients.
  Diabetes care 11/2011; 35(1):57-62. · 8.09 Impact Factor
• Article: Lessons learned from 15 years of KIMS and 5 years of ACROSTUDY.

  Anton Luger, Ulla Feldt-Rasmussen, Roger Abs, Rolf C Gaillard, Michael Buchfelder, Peter Trainer, Thierry Brue
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  ABSTRACT: BACKGROUND: Pharmacoepidemiological surveys provide a valuable contribution to the continued monitoring of drug-related effects in patients with rare disorders. One of the earliest examples of this type of survey is KIGS (Pfizer International Growth Study Database), which has monitored the safety and effectiveness of growth hormone (GH) therapy in GH-deficient children since its inception in 1987. Following closely in the footsteps of KIGS is KIMS (Pfizer International Metabolic Database). As of 2009, KIMS has been collecting data on the long-term safety and clinical outcomes of GH replacement in GH-deficient adults for 15 years. Approximately 5 years ago, the ACROSTUDY database was established to monitor the long-term safety and effectiveness of pegvisomant in patients with acromegaly. CONCLUSIONS: By collecting data on the treatment of relatively rare conditions in routine clinical practice, pharmacoepidemiological surveys such as KIMS and ACROSTUDY provide valuable information on the safety and effectiveness of treatment with GH replacement and pegvisomant in the real world.
  Hormone Research in Paediatrics 01/2011; 76 Suppl 1:33-8.
• Article: Discontinuation of growth hormone (GH) treatment during the transition phase is an important factor determining the phenotype of young adults with nonidiopathic childhood-onset GH deficiency.

  Maria Kołtowska-Häggström, Mitchell E Geffner, Peter Jönsson, John P Monson, Roger Abs, Václav Hána, Charlotte Höybye, Hartmut A Wollmann
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  ABSTRACT: Little is known about the impact of childhood-onset GH deficiency (GHD), in particular the duration of GH cessation during the transition phase, on adult phenotype. We investigated the association between the manifestations and management of GHD during childhood/adolescence and the clinical features of GHD in adulthood. DESIGN/SETTING/PATIENTS/INTERVENTION: Patients with reconfirmed childhood-onset GHD who resumed GH treatment as adults were identified from two sequential databases (n = 313). The cohort was followed up longitudinally from GH start in childhood to reinitiation of treatment in adulthood and 1 yr beyond. Analyses were performed in the total cohort and in subgroups of patients with idiopathic GHD (IGHD) and non-IGHD. The cohorts were stratified based on duration of GH cessation (short, < or = 2 yr; long, > 2 yr). Regimen of pediatric GH administration, duration of GH interruption, IGF-I sd score, lipid concentrations, and quality of life were measured. Mean duration of GH interruption was 4.4 yr. IGF-I sd score in adulthood was related to severity of childhood GHD. In non-IGHD patients, a longer duration of GH interruption was associated with a worse lipid profile (P < 0.0001). Non-IGHD patients who gained more height during childhood GH treatment reported better quality of life than those who gained less height (P < 0.05). Pediatricians should tailor GH treatment, not only for its beneficial effect on growth but also for future health in adulthood. In adults with reconfirmed GHD, particularly those with non-IGHD, early recommencement of GH should be considered.
  The Journal of clinical endocrinology and metabolism 03/2010; 95(6):2646-54. · 6.50 Impact Factor
• Article: Cardiovascular risk factors in hypopituitary GH-deficient adults.

  Johan Verhelst, Roger Abs
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  ABSTRACT: Design Data on lipids, body composition, and blood pressure (BP) from all published KIMS papers are summarized and compared with a literature review. Results KIMS data confirm and extend previous research showing that adults with GH deficiency (GHD) have an adverse cardiovascular risk profile. GHD patients have high levels of dyslipidemia, elevated body mass index, unfavorable waist-to-hip ratio and body composition, and a high risk of hypertension. These abnormalities are likely to explain the increased cardiovascular mortality observed in patients with hypopituitarism. When given GH replacement therapy, an improvement is seen in KIMS as well as earlier studies for lipid profile, body composition, and BP. The added value of the different KIMS papers over previous research is that KIMS involves a much larger number of patients, that lipid concentrations and IGF1 are measured in a single central laboratory, and that the effects of GH replacement therapy can be followed longer than the duration of earlier trials. By the large number of patients, KIMS gives insight into the effects of GH in different patients' subgroups such as elderly patients, patients with idiopathic GHD, patients with craniopharyngioma, patients after irradiation, and so on. In addition, KIMS has made it possible to calculate more exactly the influence of baseline parameters on these cardiovascular risk parameters and their response to GH. Conclusions Taken together, data from KIMS confirm earlier knowledge about the important benefits of GH replacement therapy, but also on the use of GH in specific subgroups such as isolated GHD, patients above 65 years, and patients after irradiation. No subgroup yet has been identified as not responding well to GH.
  European Journal of Endocrinology 09/2009; 161 Suppl 1:S41-9. · 3.42 Impact Factor
• Article: From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum - a KIMS analysis.

  M Klose, B Jonsson, R Abs, V Popovic, M Koltowska-Häggström, B Saller, U Feldt-Rasmussen, I Kourides
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  ABSTRACT: To describe baseline clinical presentation, treatment effects and evolution of isolated GH deficiency (IGHD) to multiple pituitary hormone deficiency (MPHD) in adult-onset (AO) GHD. Observational prospective study. Baseline characteristics were recorded in 4110 patients with organic AO-GHD, who were GH naïve prior to entry into the Pfizer International Metabolic Database (KIMS; 283 (7%) IGHD, 3827 MPHD). The effect of GH replacement after 2 years was assessed in those with available follow-up data (133 IGHD, 2207 MPHD), and development of new deficiencies in those with available data on concomitant medication (165 IGHD, 3006 MPHD). IGHD and MPHD patients had similar baseline clinical presentation, and both groups responded similarly to 2 years of GH therapy, with favourable changes in lipid profile and improved quality of life. New deficiencies were observed in 35% of IGHD patients, which was similar to MPHD patients with one additional deficit other than GH. New deficiencies most often presented within the first year but were observed up to 6 years after GH commencement. Conversion of IGHD into MPHD was not predicted by aetiology, baseline characteristics, surgery or radiotherapy, whereas in MPHD additional deficits were predicted by age (P<0.001) and pituitary disease duration (P<0.01). Both AO-IGHD and -MPHD patients have similar baseline clinical presentation and respond equally well to 2 years of GH replacement. Hypopituitarism in adults seems to be a dynamic condition where new deficiencies can appear years after the initial diagnosis, and careful endocrine follow-up of all hypopituitary patients, including those with IGHD, is warranted.
  European Journal of Endocrinology 09/2009; 161 Suppl 1:S75-83. · 3.42 Impact Factor
• Article: Lipoatrophy in GH deficient patients treated with a long-acting pegylated GH.

  Philippe Touraine, Gwyn A D'Souza, Ione Kourides, Roger Abs, Paul Barclay, Rujia Xie, Antonio Pico, Elena Torres-Vela, Bertil Ekman
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  ABSTRACT: Changes observed during adult GH deficiency (GHD) are most often reversed with the administration of recombinant human GH (rhGH). To avoid daily injections, a long-acting GH molecule has been obtained by covalent binding of polyethylene glycol (PEG) with rhGH (PEG-GH), allowing weekly s.c. injections. This study was designed to assess its efficacy and safety, in adult GHD subjects. This was a randomized, double-blind, placebo-controlled, multiple-dose, parallel group study. Subjects were recruited from 34 centers. A total of 105 subjects with GHD were assigned a treatment. They received 6 weekly injections of either PEG-GH or placebo. Subjects were randomized into one out of four treatment groups (Groups A-D) or placebo (Group E). Groups A, B, and C received 1, 3, and 4 mg PEG-GH respectively, for the first 3 weeks followed by 2, 6, and 8 mg PEG-GH respectively, for the remaining 3 weeks. Group D received 4 mg PEG-GH for 6 weeks. Group E received placebo. The study was suspended because of the development of lipoatrophy in certain subjects and restarted with an injection rotation plan, before being terminated due to further subjects developing lipoatrophy. A total of 13 cases of injection-site lipoatrophy were reported, of which ten were in females and three occurred after the first injection; all cases were independent of PEG-GH dose or IGF1 levels, either basal or under treatment. The unpredictable occurrence of injection-site lipoatrophy with weekly long-acting pegylated GH molecules may be a limiting factor for their development.
  European Journal of Endocrinology 09/2009; 161(4):533-40. · 3.42 Impact Factor
• Article: Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients.

  Etienne Delgrange, Tania Daems, Johan Verhelst, Roger Abs, Dominique Maiter
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  ABSTRACT: Macroprolactinomas poorly responsive to dopamine-agonists are often more aggressive and are usually termed 'resistant' but this clinical concept has always been defined empirically. To define resistance to cabergoline (CAB) on the basis of a dose-response relationship established in a large series of macroprolactinoma patients and to assess the influence of gender and tumor invasiveness on the response to treatment. Retrospective study. One hundred and twenty-two patients (72 women and 50 men) primarily treated with CAB for at least 1 year were included. Main outcome measures were serum prolactin (PRL) and tumor size. Normalization of PRL was obtained in 115 out of the 122 patients (94%). The majority of patients (96/115, 83%) were controlled with a CAB dose < or =1.5 mg/week. Most of the other patients (19/26) had only a partial resistance, responding to a further increase of the CAB dose. Beyond the dose of 3.5 mg/week, there was no clear advantage in further increasing the dose instead of continuing the treatment at the same dose. Most tumors (98/119 assessable cases, 82%) showed a significant shrinkage during CAB treatment. It was more likely to occur in cases of PRL normalization. Both cavernous sinus invasion and male gender were significantly and independently associated with partial or complete resistance to treatment. Most macroprolactinomas primarily treated with CAB are adequately controlled with doses < or =1.5 mg/week. About 20% of patients, mainly men and/or those with invasive tumors will require a higher dose of CAB. We suggest defining such patients as resistant to CAB.
  European Journal of Endocrinology 02/2009; 160(5):747-52. · 3.42 Impact Factor
• Article: GH replacement in hypopituitarism improves lipid profile and quality of life independently of changes in obesity variables.

  Pascale Abrams, Hugo Boquete, Hugo Fideleff, Ulla Feldt-Rasmussen, Peter J Jönsson, Maria Koltowska-Häggström, Patrick Wilton, Roger Abs
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  ABSTRACT: GH deficiency (GHD) in adults is characterized by elevated body mass index (BMI), increased waist girth (WG) and increased fat mass (FM). Information about how these indicators of obesity affect the lipid profile and quality of life (QoL) of GHD subjects is scarce. It is also unclear how changes in these indicators brought about by GH replacement influence lipids and QoL. Adult GHD subjects from the Pfizer International Metabolic Database were grouped according to BMI (n=291 with BMI <25 kg/m(2), n=372 with BMI 25-30 kg/m(2), n=279 with BMI >30 kg/m(2)), WG (n=508 with normal WG, n=434 with increased WG) and FM (n=357) and according to changes in these variables after 1 year of GH replacement. Serum IGF-I concentrations, lipid concentrations and QoL using the QoL Assessment of GHD in Adults questionnaire were assessed at baseline and after 1 year of treatment. At baseline, total and low-density lipoprotein (LDL) cholesterol were similarly elevated in the BMI and WG groups, but high-density lipoprotein (HDL) cholesterol decreased and triglycerides increased with increasing BMI and WG. QoL was progressively poorer with increasing BMI and WG. After 1 year of GH replacement, total and LDL cholesterol and QoL improved in all BMI, WG and FM groups. Variables of obesity adversely affect the already unfavourable lipid profile in GHD subjects by decreasing HDL cholesterol, but do not counteract the positive effect of GH replacement on LDL cholesterol. Similarly, QoL is influenced by obesity, but responds equally well to GH treatment independent of BMI, WG and FM.
  European Journal of Endocrinology 09/2008; 159(6):825-32. · 3.42 Impact Factor
• Article: Follow-up of pituitary tumor volume in patients with acromegaly treated with pegvisomant in clinical trials.

  Camilo Jimenez, Pia Burman, Roger Abs, David R Clemmons, William M Drake, Kent R Hutson, Michael Messig, Michael O Thorner, Peter J Trainer, Robert F Gagel
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  ABSTRACT: We examined pituitary tumor volumes in patients treated with pegvisomant for 18 months or longer, and in whom the tumors were monitored for at least 3 years. We present details on 9 of 304 patients in clinical trials with pegvisomant who experienced tumor growth within the first year of treatment. Magnetic resonance images prior to start of pegvisomant and at last follow-up were examined in 43 patients (14% of participating patients). Twenty-nine had received prior radiation therapy (18% of irradiated patients) and all but five received somatostatin analogs between periods of pegvisomant treatment. At follow-up, the median tumor volume was 0.6 cc (range 0.0-19.7 cc), in comparison with 1.6 cc (0.0-19.7 cc) at baseline (P<0.001). Twenty-five patients, of which 23 received radiation therapy, had tumor volume reduction. Seventeen patients had no significant change. One patient, who had not received radiation therapy, had an increase in tumor volume from 1.61 to 1.93 cc. Of the nine patients with tumor growth, six had progressive growth before initiating pegvisomant. Two patients with stable tumors while on octreotide experienced enlargement after octreotide discontinuation but remained stable on long-term pegvisomant therapy. The present data indicate that pegvisomant does not promote tumor growth and suggest that the nine observed cases of tumor progression, which occurred within 8 months after commencing pegvisomant, are likely rebound expansions after discontinuation of somatostatin analogs and/or the natural history of aggressively growing pituitary tumors. Continued long-term surveillance of tumor volume, particularly in non-irradiated patients, is recommended.
  European Journal of Endocrinology 08/2008; 159(5):517-23. · 3.42 Impact Factor
• Article: Divergence between growth hormone and insulin-like growth factor-i concentrations in the follow-up of acromegaly.

  Orsalia Alexopoulou, Marie Bex, Roger Abs, Guy T'Sjoen, Brigitte Velkeniers, Dominique Maiter
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  ABSTRACT: Divergence between GH and IGF-I values is regularly observed in treated acromegalic patients, and its significance is unclear. The objective of the study was to explore the frequency and identify potential determinants of discordant serum GH and IGF-I concentrations in noncured acromegalic patients. Two hundred twenty-nine noncured acromegalic patients of the Belgian acromegaly registry (AcroBel) were grouped according to their mean GH level (< or = or > 2 microg/liter) and IGF-I z-score (< or = 2 or > 2). Clinical and metabolic parameters were compared between groups with active disease (high GH and IGF-I; n=81),high GH (with normal IGF-I; n=25), high IGF-I (with normal GH; n=55), and controlled disease (GH and IGF-I normal; n=68). Compared with the high IGF-I group, the high GH group was characterized by younger age (52 vs. 58 yr, P < 0.05), female predominance (72 vs. 36%, P < 0.01), and lower body mass index (25 vs. 31 kg/m(2); P < 0.001), fasting glucose (91 vs. 99 mg/dl; P < 0.05), and glycated hemoglobin levels (5.7 vs. 6.1%; P < 0.01). There was no difference among the groups regarding baseline characteristics of pituitary adenoma, current medical treatment, or symptom score. Thirty-five percent of noncured acromegalic patients exhibit a discordant GH and IGF-I pattern. The high GH phenotype was found predominantly in younger estrogen-sufficient females, implying a possible role for age, gender, and estrogens in this biochemical divergence. The high IGF-I phenotype was associated with a worse metabolic profile, suggesting that high IGF-I, rather than high GH, is indicative of persistently active disease.
  Journal of Clinical Endocrinology &amp Metabolism 05/2008; 93(4):1324-30. · 6.50 Impact Factor
• Article: Modification of hormonal secretion in clinically silent pituitary adenomas.

  Tania Daems, Johan Verhelst, Alex Michotte, Pascale Abrams, Dirk De Ridder, Roger Abs
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  ABSTRACT: Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.
  Pituitary 04/2008; 12(1):80-6. · 1.83 Impact Factor
• Article: Remission of acromegaly following long-term therapy with cabergoline: report of two cases.

  Johan A Verhelst, Pascale J Abrams, Roger Abs
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  ABSTRACT: Dopamine agonists are effective in some patients with acromegaly and in this condition treatment is considered to be chronic. We describe two acromegalic patients who responded adequately to the long-acting dopamine agonist cabergoline, but surprisingly maintained normal GH and IGF-I levels once therapy was discontinued after 42 and 76 months because of possibly related side effects. A 32-year-old woman with mild acromegaly (IGF-I: 423 microg/l, GH after OGTT: 2.5 microg/l, adenoma 4 mm) was treated with cabergoline as primary therapy and reached safe GH levels (2 microg/l or less) and normal IGF-I levels with 3.5 mg cabergoline weekly. After 42 months of therapy the patient experienced a progressive decrease of libido, which she attributed to the intake of cabergoline. After stopping medication, serum levels of GH and IGF-I remained normal during the following 2.5 years. A 53-year-old man with moderate acromegaly (serum IGF-I: 547 microg/l, GH after OGTT: 5.9 microg/l, adenoma 7 mm) preferred cabergoline as primary therapy. Serum GH levels below 2 microg/l and normal levels of IGF-I were obtained with 3.5 mg cabergoline weekly. When the patient experienced severe stomach pains after 76 months of treatment, cabergoline was held responsible and discontinued. Serum GH and IGF-I did not increase again and stayed at the same level during a follow-up of 5.5 years. These two cases demonstrate that acromegalic patients with a good response to cabergoline may occasionally remain in remission after stopping therapy. This phenomenon has previously only been described in patients with a prolactinoma.
  Pituitary 02/2008; 11(1):103-7. · 1.83 Impact Factor
• Article: Pregnancy outcomes following cabergoline treatment: extended results from a 12-year observational study.

  Annamaria Colao, Roger Abs, David González Bárcena, Philippe Chanson, Wolfgang Paulus, David L Kleinberg
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  ABSTRACT: Cabergoline is a dopamine agonist used to treat hyperprolactinaemia. Because hyperprolactinaemia is a significant cause of infertility in women, cabergoline and other dopamine agonists are frequently prescribed to reduce prolactin levels and restore normal menses. They are usually discontinued shortly after the patient becomes pregnant. Although cabergoline has been used to treat hyperprolactinaemia since the mid-1990s, safety data related to maternal and foetal exposure to this agent are still limited. The current prospective, observational study reports on a total of 380 pregnancies. This extends by 154 pregnancies the results of a previously published interim report on the outcomes of 226 pregnancies in women treated with cabergoline up to 1994. Outcomes examined include the incidence of abortions and premature delivery and the number and types of foetal malformations or abnormalities. Follow-up data were available for 329 pregnancies, including 258 (78%) deliveries and 71 (22%) abortions. Of the 71 reported abortions, 31 (44%) were voluntary, 30 (42%) were spontaneous miscarriages, and nine (13%) were therapeutic. Of the 258 deliveries, 250 (97%) were live deliveries, four (2%) were stillbirths, and the status of delivery was unknown for the remaining four (2%). Of the 250 live deliveries, 193 (77%) were term deliveries (gestational period > 37 weeks), 45 (18%) were preterm deliveries (gestational period < or = 37 weeks), and 62% of the infants had normal birthweights (i.e. 3-4 kg). Neonatal abnormalities were recorded for 23 (9%) of the infants with no apparent pattern in type or severity. The results of this study suggest that foetal exposure to cabergoline through early pregnancy does not induce any increase in the risk of miscarriage or foetal malformation.
  Clinical Endocrinology 02/2008; 68(1):66-71. · 3.17 Impact Factor
• Article: Optimalization and cost management of lanreotide-Autogel therapy in acromegaly.

  Pascale Abrams, Orsalia Alexopoulou, Roger Abs, Dominique Maiter, Johan Verhelst
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  ABSTRACT: Lanreotide-Autogel is a depot formulation of the somatostatin analog lanreotide used in the treatment of acromegaly. We investigated whether prolonging or shortening the interval between injections would offer any benefit. The interval was prolonged from once every 4 weeks to once every 6 weeks when patients (n=9) had normal IGF-I and GH concentrations. When patients (n=12) had still elevated IGF-I or GH on the maximal dose of 120 mg every 4 weeks, the interval was shortened to once every 3 weeks. Serum IGF-I and GH were measured after 12 and 24 weeks to allow for dose adaptation. Symptoms and tumor volume were evaluated at baseline and after 36 weeks. In seven of the nine subjects with normal IGF-I and GH, the interval could be extended to 6 weeks without loosing efficacy on IGF-I (195 vs 213 microg/l; not significant, NS) and GH concentrations (1.4 vs 1.3 microg/l; NS). The weekly dose could significantly be reduced (from 23.3 to 17.8 mg; P=0.002). In only 1 of the 12 not-controlled patients, reducing the interval to once every 3 weeks induced normalization of IGF-I and GH. In subjects whose acromegaly is well controlled using lanreotide-Autogel, prolonging the time interval between injections can often be increased 4 to 6 weeks without loss of efficacy, thereby improving the subject's comfort and reducing the cost of treatment. On the other hand, in subjects whose acromegaly is not controlled on a dose of 120 mg every 4 weeks, reducing the interval to every 3 weeks is rarely beneficial.
  European Journal of Endocrinology 12/2007; 157(5):571-7. · 3.42 Impact Factor
• Article: Impact of the primary aetiology upon the clinical outcome of adults with childhood-onset GH deficiency.

  Charlotte Hoybye, Peter Jönsson, John P Monson, Maria Koltowska-Häggström, Václav Hána, Mitchell Geffner, Roger Abs
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  ABSTRACT: The impact of the aetiology of childhood-onset GH deficiency (CO-GHD) on the clinical presentation during adulthood and the response to GH replacement has been poorly defined. Our study aims to characterize CO-GHD in adults due to different aetiologies and evaluate the effect of 2 years of GH replacement therapy. Data from 353 adults with CO-GHD from Pfizer International Metabolic Database KIMS were retrospectively grouped according to GHD aetiology: non-organic disorder (n=147), organic pituitary disease (n=159), and brain tumour (n=47). Extent of pituitary dysfunction, IGF-I concentration, lipid concentrations and quality-of-life (QoL) were assessed at baseline and after 2 years of GH replacement. GHD was diagnosed at a later age in the organic pituitary group than in the other groups, resulting in a shorter duration of GH treatment during childhood. However, the final height was greater in the organic pituitary group. Panhypopituitarism was most common in the non-organic disorder and in the organic pituitary groups, while isolated GHD was more prominent in the brain tumour group. Serum IGF-I levels were the lowest in the non-organic group. QoL was the poorest in the brain tumour group. Lipid profile and QoL improved significantly during GH replacement. The adverse consequences of CO-GHD in adulthood vary between aetiologies, but improve similarly with GH treatment. It is, therefore, important to consider retesting all patients with CO-GHD in early adulthood and, if persistent severe GHD is confirmed, recommence GH replacement.
  European Journal of Endocrinology 12/2007; 157(5):589-96. · 3.42 Impact Factor
• Article: Health-related quality of life in acromegalic subjects: data from AcroBel, the Belgian registry on acromegaly.

  Guy T'Sjoen, Marie Bex, Dominique Maiter, Brigitte Velkeniers, Roger Abs
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  ABSTRACT: To assess the impairment of quality of life (QoL), evaluated by the acromegaly QoL (AcroQoL) questionnaire, in patients with controlled and uncontrolled acromegaly. Cross-sectional evaluation of AcroBel, a national observational registry of acromegalic patients newly diagnosed or in follow-up. Disease perception by the patients was evaluated by the disease-specific signs and symptoms score (SSS) and QoL was assessed by the AcroQoL questionnaire. Hormonal status was determined by central measurements of GH and IGF-I. Patients (n = 291) had a median GH of 1.43 mug/l (0.65-3.03; IQR), a median IGF-I of 231 mug/l (150-367), and a mean IGF-I z-score of +1.91 (s.d. 2.21). The AcroQoL total score in the whole group was 67.1 (51.1-78.4), with a score of 65.6 (43.8-78.1) for the physical dimension, 67.9 (53.6-80.4) for the psychological dimension, 78.6 (64.3-89.3) for personal relations and 57.1 (39.3-75) for appearance. The median SSS was 3 (1-5). There was a negative correlation between both questionnaires (r = -0.478; P < 0.001). There was no correlation between AcroQoL score and biochemical markers of disease activity. When subdividing patients into groups of biochemical control according to GH and IGF-I levels, no difference could be established for either SSS or AcroQoL scores. The AcroQoL results from the AcroBel registry confirm the marked impairment of the patients' QoL, especially in relation with appearance. A negative correlation between AcroQoL and SSS was confirmed. There was, however, no correlation between AcroQoL and biochemical markers of disease activity.
  European Journal of Endocrinology 10/2007; 157(4):411-7. · 3.42 Impact Factor