Objective: Arthropathy is an invalidating complication of acromegaly. Although acromegalic arthropathy shares features with primary osteoarthritis, joint spaces are widened rather than narrowed in... Show moreObjective: Arthropathy is an invalidating complication of acromegaly. Although acromegalic arthropathy shares features with primary osteoarthritis, joint spaces are widened rather than narrowed in patients with long term cure of acromegaly. The late effects of acromegaly on hand joints have not been characterized. Therefore the objective of the current study was to assess joint space widths of hand joints in patients with long-term control of acromegaly and to identify factors associated with joint space width.Design: Cross-sectional studyMethods: Cross-sectional study in 89 patients(age 58±12yr, 49% women) with long-term controlled acromegaly and 471 controls without hand symptoms(age 46±12yr, 42% women). Radiological joint space widths of individual hand joints were measured by automated image analysis.Results: Patients had wider mean joint spaces than controls: MCP-joints were ~24%, PIP-joints ~21%, and DIP-joints ~20% wider (patients vs controls; p<0.001 for all joints). Mean joint space width exceeded the 95th percentile of the values obtained in controls in 64% of patients. Higher IGF-1 and GH concentrations at diagnosis were associated with larger joint space widths (adjusted ß for pretreatment GH in tertiles:0.09(95%CI 0.03-1.84) and for IGF-1 in tertiles 0.14(95%CI 0.05-0.23) at the MCP-joints in acromegalic patients. In male, but not in female, patients increased joint space widths were associated with more self-reported pain(p=0.02).Conclusions: Using a new semi-automated image analysis of hand radiographs, acromegalic patients with long-term disease control appeared to have increased joint spaces of all hand joints. Joint space widths were positively related to disease activity at diagnosis, but not to duration of follow-up, suggesting irreversible cartilage hypertrophy. Irreversible cartilage hypertrophy may partly explain persisting hand complaints, despite long-term disease control. Show less
OBJECTIVE To investigate the validity of joint space width (JSW) measurements in millimeters (mm) in hand osteoarthritis (OA) patients by comparison to controls, grading of joint space narrowing ... Show moreOBJECTIVE To investigate the validity of joint space width (JSW) measurements in millimeters (mm) in hand osteoarthritis (OA) patients by comparison to controls, grading of joint space narrowing (JSN), and clinical features. METHODS Hand radiographs of 235 hand OA patients (mean age 65 years, 83% women) and 471 controls were used. JSW was measured with semi-automated image analysis software in the distal, proximal interphalangeal and metacarpal joints (DIPJs, PIPJs and MCPJs). JSN (grade 0-3) was assessed using the osteoarthritis research society international (OARSI) atlas. Associations between the two methods and clinical determinants (presence of pain, nodes and/or erosions, decreased mobility) were assessed using Generalized Estimating Equations with adjustments for age, sex, body mass index (BMI) and mean width of proximal phalanx. RESULTS JSW was measured in 5631 joints with a mean JSW of 0.98 mm (standard deviation (SD) 0.21), being the smallest for DIPJs (0.70 (SD 0.25)) and largest for MCPJs (1.40 (SD 0.25)). The JSN=0 group had a mean JSW of 1.28 mm (SD 0.34), the JSN=3 group 0.17 mm (SD 0.23). Controls had larger JSW than hand OA patients (P-value<0.001). In hand OA, females had smaller JSW than men (β -0.08, (95% confidence interval (95% CI) -0.15 to -0.01)) and lower JSW was associated with the presence of pain, nodes, erosions and decreased mobility (adjusted β -0.21 (95% CI -0.27, -0.16), -0.37 (-0.40, -0.34), -0.61 (-0.68, -0.54) and -0.46 (-0.68, -0.24) respectively). These associations were similar for JSN in grades. CONCLUSION In hand OA the quantitative JSW measurement is a valid method to measure joint space and shows a good relation with clinical features. Show less
OBJECTIVE: To evaluate the association between radiographic osteoarthritis (OA) and either serum insulin-like growth factor-1 (IGF-1) levels or IGF-1 gene polymorphisms in patients with primary OA.... Show moreOBJECTIVE: To evaluate the association between radiographic osteoarthritis (OA) and either serum insulin-like growth factor-1 (IGF-1) levels or IGF-1 gene polymorphisms in patients with primary OA. METHODS: We conducted a systematic review of reported associations between circulating IGF-1 and/or IGF-1 gene polymorphisms and radiographic OA. Studies were eligible when: (1) investigating serum IGF-1 and/or IGF-1 gene polymorphisms in relation to prevalent or incident radiographic OA; (2) written in English; (3) full-text article or abstract; (4) patients had primary OA in knee, hip, hand or spine; (5) longitudinal, case-control or cross-sectional design. Quality assessment was done using a standardized criteria set. Best-evidence synthesis was performed based on guidelines on systematic review from the Cochrane Collaboration Back Review Group, using five evidence levels: strong, moderate, limited, conflicting and no evidence. RESULTS: We included 11 studies with more than 3000 primary OA cases. Data on the relationship between serum IGF-1 and radiographic OA were inconsistent. Adjustment for body mass index (BMI) was often omitted. Of four high-quality studies, three studies reported no association, one study found significantly higher IGF-1 levels in OA patients compared to controls. Patients with IGF-1 gene promoter polymorphisms and a genetic variation at the IGF-1R locus had an increased OA prevalence compared to controls. CONCLUSIONS: Observational data showed no association between serum IGF-1 and occurrence of radiographic OA (moderate level of evidence), and a positive relationship between IGF-1 gene polymorphisms and radiographic OA (moderate level of evidence); however the confounding effect of BMI was insufficiently addressed. Future well-designed prospective studies should further elaborate the role of the complex GH/IGF-1 system in primary OA. Show less
CONTEXT Cranial radiotherapy is an important cause of hypopituitarism. The prevalence of hypopituitarism varies considerably between studies. OBJECTIVE We conducted a systematic review and meta... Show moreCONTEXT Cranial radiotherapy is an important cause of hypopituitarism. The prevalence of hypopituitarism varies considerably between studies. OBJECTIVE We conducted a systematic review and meta-analysis of reported prevalences of hypopituitarism in adults radiated for nonpituitary tumors. DATA SOURCES We searched PubMed, EMBASE, Web of Science, and the Cochrane Library to identify potentially relevant studies. STUDY SELECTION Studies were eligible for inclusion with the following criteria: 1) cranial radiotherapy for nonpituitary tumors and/or total body irradiation for hematological malignancies; 2) adult population (>18 yr old); and 3) report on endocrine evaluation. DATA EXTRACTION Data review was done by two independent reviewers. Besides extraction of baseline and treatment characteristics, also endocrine tests, definitions, and cutoff values used to define pituitary insufficiency were extracted. RESULTS Eighteen studies with a total of 813 patients were included. These included 608 patients treated for nasopharyngeal cancer (75%) and 205 for intracerebral tumors. The total radiation dose ranged from 14 to 83 and 40 to 97 Gy for nasopharyngeal and intracerebral tumors, respectively. The point prevalence of any degree of hypopituitarism was 0.66 [95% confidence interval (CI), 0.55-0.76]. The prevalence of GH deficiency was 0.45 (95% CI, 0.33-0.57); of LH and FSH, 0.3 (95% CI, 0.23-0.37); of TSH, 0.25 (95% CI, 0.16-0.37); and of ACTH, 0.22 (95% CI, 0.15-0.3), respectively. The prevalence of hyperprolactinemia was 0.34 (95% CI, 0.15-0.6). There were no differences between the effects of radiotherapy for nasopharyngeal vs. for intracerebral tumors. CONCLUSION Hypopituitarism is prevalent in adult patients after cranial radiotherapy for nonpituitary tumors. Therefore, all patients treated by cranial radiotherapy should have structured periodical assessment of pituitary functions. Show less
Context: Cranial radiotherapy is an important cause of hypopituitarism. The prevalence of hypopituitarism varies considerably between studies. Objective: We conducted a systematic review and meta... Show moreContext: Cranial radiotherapy is an important cause of hypopituitarism. The prevalence of hypopituitarism varies considerably between studies. Objective: We conducted a systematic review and meta-analysis of reported prevalences of hypopituitarism in adults radiated for nonpituitary tumors. Data Sources: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library to identify potentially relevant studies. Study Selection: Studies were eligible for inclusion with the following criteria: 1) cranial radiotherapy for nonpituitary tumors and/or total body irradiation for hematological malignancies; 2) adult population (>18 yr old); and 3) report on endocrine evaluation. Data Extraction: Data review was done by two independent reviewers. Besides extraction of base-line and treatment characteristics, also endocrine tests, definitions, and cutoff values used to define pituitary insufficiency were extracted. Results: Eighteen studies with a total of 813 patients were included. These included 608 patients treated for nasopharyngeal cancer (75%) and 205 for intracerebral tumors. The total radiation dose ranged from 14 to 83 and 40 to 97 Gy for nasopharyngeal and intracerebral tumors, respectively. The point prevalence of any degree of hypopituitarism was 0.66 [95% confidence interval (CI), 0.55-0.76]. The prevalence of GH deficiency was 0.45 (95% CI, 0.33-0.57); of LH and FSH, 0.3 (95% CI, 0.23-0.37); of TSH, 0.25 (95% CI, 0.16-0.37); and of ACTH, 0.22 (95% CI, 0.15-0.3), respectively. The prevalence of hyperprolactinemia was 0.34 (95% CI, 0.15-0.6). There were no differences between the effects of radiotherapy for nasopharyngeal vs. for intracerebral tumors. Conclusion: Hypopituitarism is prevalent in adult patients after cranial radiotherapy for nonpituitary tumors. Therefore, all patients treated by cranial radiotherapy should have structured periodical assessment of pituitary functions. (J Clin Endocrinol Metab 96: 2330-2340, 2011) Show less
Objective: To establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture... Show moreObjective: To establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk. Design: Case-control study. Patients and measurements: Eighty-nine patients (46% male, mean age: 58 years) were included. We studied VFs and non-VFs, bone mineral density (BMD), and markers of bone turnover. In 48 patients, BMD assessment was also obtained 7 years prior to the current study. To compare VF prevalence, data from a sample of the Dutch population (n=3469) were used. Results: VF prevalence was 59% (men 64% and women 54%), significantly increased when compared with controls (odds ratio up to 6.5), and independent of the duration of disease control, BMD, markers of bone turnover, and acromegalic disease characteristics. Mean number of VFs per patient was 3.4 +/- 0.3 (range 1-8). There was no relationship between the number and severity of fractures, parameters of bone turnover, and follow-up BMD measurements. BMD did not change during prolongation of follow-up by 7 years of controlled acromegaly. Conclusion: There is a very high prevalence of VFs in acromegaly patients with long-term controlled disease, independently of BMD. In view of the significant morbidity and mortality associated with VFs in general and the inability of BMD to predict fracture risk in acromegalic patients, we propose to include VF assessment, for example by lateral conventional radiographs of the spine in the screening of patients with acromegaly, both at diagnosis and during follow-up after establishment of disease control. Show less
Objective To compare the distribution of osteophytes and joint space narrowing (JSN) between patients with acromegaly and primary generalised osteoarthritis to gain insight into the... Show moreObjective To compare the distribution of osteophytes and joint space narrowing (JSN) between patients with acromegaly and primary generalised osteoarthritis to gain insight into the pathophysiological process of growth hormone (GH) and insulin-like growth factor type I (IGF-I)-mediated osteoarthritis. Methods We utilised radiographs of the knee and hip joints of 84 patients with controlled acromegaly for a mean of 14.0 years with 189 patients with primary generalised osteoarthritis. Hips and knees with with doubtful or definite osteoarthritis (Kellgren-Lawrence score of >= 1) were compared in the current study. For a semiquantitative assessment of radiological osteoarthritis (range 0-3) osteophytes and JSN of the medial and lateral tibiofemoral and hip joints were scored according to the Osteoarthritis Research Society International atlas. Logistic regression analysis was performed with adjustment for age, sex, body mass index and intrapatient effect. Results Knee and hip osteoarthritis in patients with cured acromegaly was characterised by more osteophytosis (OR 4.1-9.9), but less JSN (OR 0.3-0.5) in comparison with patients with primary osteoarthritis. Patients with acromegaly and osteoarthritis had significantly less self-reported functional disability than patients with primary osteoarthritis (p < 0.001). Self reported functional disability was associated with JSN rather than with osteophytosis. Conclusion Arthropathy caused by GH oversecretion results in osteophytosis and to a lesser extent in JSN. This observation suggests that the GH-IGF-I system is mainly involved in bone formation resulting in osteophytosis, but may possibly protect against cartilage loss. Show less
OBJECTIVE To compare the distribution of osteophytes and joint space narrowing (JSN) between patients with acromegaly and primary generalised osteoarthritis to gain insight into the... Show moreOBJECTIVE To compare the distribution of osteophytes and joint space narrowing (JSN) between patients with acromegaly and primary generalised osteoarthritis to gain insight into the pathophysiological process of growth hormone (GH) and insulin-like growth factor type I (IGF-I)-mediated osteoarthritis. METHODS We utilised radiographs of the knee and hip joints of 84 patients with controlled acromegaly for a mean of 14.0 years with 189 patients with primary generalised osteoarthritis. Hips and knees with with doubtful or definite osteoarthritis (Kellgren-Lawrence score of ≥ 1) were compared in the current study. For a semiquantitative assessment of radiological osteoarthritis (range 0-3) osteophytes and JSN of the medial and lateral tibiofemoral and hip joints were scored according to the Osteoarthritis Research Society International atlas. Logistic regression analysis was performed with adjustment for age, sex, body mass index and intrapatient effect. RESULTS Knee and hip osteoarthritis in patients with cured acromegaly was characterised by more osteophytosis (OR 4.1-9.9), but less JSN (OR 0.3-0.5) in comparison with patients with primary osteoarthritis. Patients with acromegaly and osteoarthritis had significantly less self-reported functional disability than patients with primary osteoarthritis (p < 0.001). Self reported functional disability was associated with JSN rather than with osteophytosis. CONCLUSION Arthropathy caused by GH oversecretion results in osteophytosis and to a lesser extent in JSN. This observation suggests that the GH-IGF-I system is mainly involved in bone formation resulting in osteophytosis, but may possibly protect against cartilage loss. Show less
Objective: To establish the prevalence of osteoporosis, vertebral, and non-vertebral fractures in acromegaly patients with long-term controlled disease and factors potentially influencing fracture... Show moreObjective: To establish the prevalence of osteoporosis, vertebral, and non-vertebral fractures in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk. Design: Case-control study Patients and measurements: Eighty-nine patients (46% male, mean age: 58 years) were included. We studied vertebral and non-vertebral fractures, bone mineral density (BMD), and markers of bone turnover. In 48 patients BMD assessment was also obtained 7 years prior to the current study. To compare vertebral fracture prevalence, data from a sample of the Dutch population (n=3469) was used. Results: Vertebral fracture prevalence was 59% (men 64%, women 54%), significantly increased when compared with controls (odds ratio up to 6.5), and independent of the duration of disease control, BMD, markers of bone turnover, and acromegalic disease characteristics. Mean number of vertebral fractures per patient was 3.4 ± 0.3 (range 1-8). There was no relationship between the number and severity of fractures, parameters of bone-turnover, and follow-up BMD measurements. BMD did not change during prolongation of follow-up by 7 years of controlled acromegaly. Conclusion: There is a very high prevalence of vertebral fractures in acromegaly patients with long-term controlled disease, independently of BMD. In view of the significant morbidity and mortality associated with vertebral fractures in general and the inability of BMD to predict fracture risk in acromegalic patients, we propose to include vertebral fracture assessment, for example by lateral conventional radiographs of the spine in the screening of patients with acromegaly, both at diagnosis and during follow-up after establishment of disease control. Show less
