Showing papers by "Susan M. Webb published in 2008"

Evaluation of health-related quality of life in patients with Cushing's syndrome with a new questionnaire

Abstract: Chronic exposure to hypercortisolism has significant impact on patient’s health and health-related quality of life (HRQoL), as demonstrated with generic questionnaires. We have developed a diseasegenerated questionnaire to evaluate HRQoL in patients with Cushing’s syndrome (CS; CushingQoL). Objective: Validate the CushingQoL questionnaire in patients with CS in clinical practice conditions. Design: Observational, international, cross-sectional study. Methods: A total of 125 patients were recruited by 14 investigators from Spain, France, Germany, The Netherlands, and Italy over a 2-month period. Clinical and hormonal data were collected and correlated with results of the generic short form 36 (SF-36) questionnaire, a question on self-perceived general health status and the CushingQoL score. Results: A total of 107 patients were pituitary-dependent and 18 adrenal-dependent CS; 104 (83%) were females,meanage45years(range20‐73years);39(31%)werecurrentlyhypercortisolemic;and47(38%) adrenalinsufficient.Inclinicalpractice,CushingQoLwasfeasible(117;94%ofpatientsfullyrespondedtothe questionnaire in a mean time of 4 min), reliable (Crohnbach’s aZ0.87), and valid (factorial analysis demonstrated unidimensionality and Rasch analysis lead to a final version with 12 items). A significant (P!0.001) correlation was observed between CushingQoL score and patients self-perceived general health status and dimensions of SF-36 (Pearson’s correlation coefficient R0.597). Patients with current hypercortisolism scored worse (lower) than those without (44G22 vs 56G21, PZ0.004). Linear regression analysis identified female gender and hypercortisolism as significant predictors for worse QoL. Conclusion: CushingQoL is useful to evaluate HRQoL in patients with CS and correlates with clinical parameters.

Quality of Life in Acromegalic Patients during Long-Term Somatostatin Analog Treatment with and without Pegvisomant

Abstract: Objective: The objective of the study was to assess whether weekly administration of 40 mg pegvisomant (PEG-V) improves quality of life (QoL) and metabolic parameters in acromegalic patients with normal age-adjusted IGF-I concentrations during long-acting somatostatin analog (SSA) treatment. Design: This was a prospective, investigator-initiated, double blind, placebo-controlled, crossover study. Twenty acromegalic subjects received either PEG-V or placebo for two consecutive treatment periods of 16 wk, separated by a washout period of 4 wk. Efficacy was assessed as change between baseline and end of each treatment period. QoL was assessed by the Acromegaly Quality of Life Questionnaire (AcroQoL) and the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ). Results: The AcroQoL (P 0.008) and AcroQoL physical (P 0.002) improved significantly after PEG-V was added. The addition of PEG-V also significantly improved the PASQ (P 0.038) and the single PASQ questions, perspiration (P 0.024), soft tissue swelling (P 0.036), and overall health status(P0.035).NosignificantchangeinZ-scoreofIGF-I(P0.34)wasobservedduringaddition of PEG-V. Transient liver enzyme elevations were observed in five subjects (25%). Conclusion: Improvement in quality of life was observed without significant change in IGF-I after the addition of 40 mg pegvisomant weekly to monthly SSA therapy in acromegalic patients who had normalized IGF-I on SSA monotherapy. These data question the current recommendations in how to assess disease activity in acromegaly. Moreover, the findings question the validity of the current approach of medical treatment in which pegvisomant is used only when SSA therapy has failed to normalize IGF-I. (J Clin Endocrinol Metab 93: 3853–3859, 2008)

Rab18 is reduced in pituitary tumors causing acromegaly and its overexpression reverts growth hormone hypersecretion.

Abstract: Context: Rab proteins regulate the sequential steps of intracellular membrane transport. Alterations of these GTPases and their associated proteins are emerging as the underlying cause for several human diseases involving dysregulated secretory activities. Objective: Herein we investigated the role of Rab18, which negatively regulates hormone secretion by interacting with secretory granules, in relation to the altered functioning of tumoral pituitary somatotropes causing acromegaly. Patients: A total of 18 patients diagnosed with pituitary tumors causing acromegaly (nine patients) or nonfunctioning adenomas (nine patients) underwent endoscopic transsphenoidal surgery. Adenomas were subsequently processed to evaluate Rab18 production in relation to GH secretion. Results: We found that somatotropinoma cells are characterized by a high secretory activity concomitantly with a remarkably reduced Rab18 expression (15%) and protein content levels (30%), as compared with cells from nonfunctioning pituitary adenom...

Gender dimorphism in body composition abnormalities in acromegaly: males are more affected than females

Abstract: Background: Acromegaly changes body composition (BC), but long-term gender differences have not been reported. Objective: To evaluate BC in active and controlled acromegalic patients. Design and methods: Clinical and biochemical variables and BC (by dual-energy X-ray absorptiometry) were evaluated in 60 acromegalic patients (19 active, 41 controlled) and 105 controls, matched for age and gender. Results: Acromegalic males (nZ24) had more total mass (89G13 vs 76.5G15.3 kg, P!0.001), lean body mass (LBM; 64.6G8.7 vs 56.4G5.8 kg, P!0.001), and bone mineral content (BMC; 2.9G0.5 vs 2.6G0.3 kg, P!0.05) than controls (nZ33). Controlled male patients (nZ14) had more total mass (89G14.7 vs 76.5G15.3 kg, P!0.05) and a trend to have more LBM (61.8G9.4 vs 56.4G5.8 kg, PZ0.065) than controls. Only in active disease was a decrease in fat mass (FM) observed, compared with controlled patients and controls (males: 19.5G5.3 vs 27G6.2 and 25.9G4%, P!0.001; females: 30.3G 6.7 vs 37.1G5.8 and 36.5G6.6%, P!0.01). In females, no further differences were observed. No differences in BMC were found between eugonadal and hypogonadal acromegalic patients, but in hypogonadal females, acromegaly appeared to prevent the BMC loss seen in hypogonadal postmenopausal controls. GH and IGF1 levels were negatively correlated with FM (males, P!0.05; females, P!0.001), but in the regression analysis GH was a predictor of FM only in women. Conclusions: Control of acromegaly reverts decreased FM in both genders; only in males more total mass and a trend for more LBM persist. The anabolic effect of GH on bone reverted in cured males, but persisted in females and appeared to override the bone loss of menopause.