Purpose
Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was to ...obtain updated epidemiological data from Norway in a clinically well-defined cohort with complete register-based follow-up.
Methods
Patients diagnosed with acromegaly from South-Eastern Norway between 1999–2019 (
n
= 262) and age and sex matched population controls (1:100) were included (
n
= 26,200). Mortality and cancer data were obtained from the Norwegian Cause of Death and Cancer Registry. Mortality and cancer incidence were compared by Kaplan–Meier analyses and Cox regression; we report hazard ratios (HRs) with 95% confidence intervals (95% CI).
Results
Median age at diagnosis was 48.0 years (interquartile range (IQR): 37.6–58.0). Mean annual acromegaly incidence rate was 4.7 (95% CI 4.2–5.3) cases/10
6
person-years, and the point prevalence (2019) was 83 (95% CI 72.6–93.5) cases/10
6
persons. Overall mortality was not increased in acromegaly, HR 0.8 (95% CI 0.5–1.4), cancer-specific and cardiovascular-specific mortality was also not increased (HR: 0.7 (95% CI 0.3–1.8) and 0.8 (95% CI: 0.3–2.5) respectively). The HR for all cancers was 1.45 (1.0–2.1;
p
= 0.052).
Conclusion
In this large cohort study, covering the period 1999–2019, patients were treated with individualized multimodal management. Mortality was not increased compared to the general population and comparable with recent registry studies from the Nordic countries and Europe. Overall cancer risk was slightly, but not significantly increased in the patients.
Summary
Background Primary, preoperative medical treatment is an option in selected patients with acromegaly, but a subset of patients respond poorly. Valid prediction of response to somatostatin ...analogues (SA) might thus alter treatment stratification. The aims of this study were to assess whether T2 signal intensity could determine long‐term response to first‐line SA treatment and to assess clinical and biochemical baseline characteristics, as well as histological subtype in relation to the magnetic resonance imaging (MRI) appearances.
Methods In 45 newly diagnosed patients, T2‐weighted signal intensity of the tumour was classified into hypo‐, iso‐ or hyperintense. Biochemical and clinical baseline variables for the three groups were compared. In 25 patients primarily treated with long‐acting SA for a median of 6 months interquartile range (IQR):155–180 days, GH and IGF‐1 reduction was assessed, and in 34 cases, immunohistochemical granulation pattern was evaluated.
Results The results showed that 12 (27%) adenomas were hypointense, 15 (33%) isointense and 18 (40%) hyperintense. Median IGF‐1 ratio IGF‐1/ULN; (upper limit of normal) was 3·5 (2·3–4·9), 2·9 (2·6–3·8) and 1·9 (1·3–2·6), respectively (P = 0·006 for difference between groups). Median GH values (μg/l) of a 3‐ to 5‐point profile were 17·5 (6·1–35), 9·3 (6·0–32·5) and 4·1 (1·5–8·3), (P = 0·025).
Median IGF‐1 reduction (% of baseline) after first‐line SA treatment was 51 (49–70), 36 (19–74) and 13 (5–42) (P = 0·03); median reduction in GH (% of baseline) was 86 (72–94), 78 (62–85) and 46 (1–70) (P = 0·02).
T2 hyperintensity was associated with sparse granulation pattern on immunohistochemistry.
Conclusion In patients with acromegaly, T2 signal intensity at diagnosis correlates with histological features and predicts biochemical outcome of first‐line SA treatment.
Somatostatin analogs (SA) have been established as the first line medical treatment for acromegaly, but following long-term treatment, SA normalizes GH and IGF-I levels in only 40-60% of patients. ...The epithelial marker E-cadherin plays a crucial role in the epithelial mesenchymal transition (EMT) and is associated with a poor response to SA treatment. We hypothesized that the characterization of transcripts regulated by SA in somatotroph adenomas with high and low E-cadherin expression may identify signaling pathways and mediators that can explain the poor response to SA treatment. We performed a microarray analysis of sixteen adenomas with different levels of E-cadherin and SA treatment to identify regulated transcripts. Candidate transcripts were further explored in vivo in sixty-five adenomas, and interactions between SA treatment and EMT progression on mRNA expression profiles and associations with clinical recovery were assessed. Finally, the effects of SA treatment on adenoma cells in vitro from acromegalic patients were determined. Microarray analysis of selected adenomas with differential E-cadherin expression, as a marker of EMT progression, identified 172 genes that displayed differential expression that was dependent on SA treatment. The validation of selected candidates in the entire cohort identified 9 transcripts that showed an interaction between E-cadherin expression and SA treatment. Further analysis of the impact of these genes suggests that attenuated RORC expression in somatotroph adenomas is associated with increased tumor size and a blunted clinical response. Our study indicates that attenuated RORC may be involved in the poor clinical response to SA treatment in patients with acromegaly.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors. Objective To assess the effect of parathyroidectomy on fat mass, ...glucose and lipid metabolism. Design, patients, interventions, main outcome measures 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization. Results In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected. Conclusion In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.
Context Bone turnover is increased in acromegaly. Despite normalization of bone turnover after treatment, the risk for vertebral fractures remains increased. Gonadal status, but not BMD, is ...correlated with vertebral fractures. Trabecular bone score (TBS) is related to bone microarchitecture. Objective The aim of this study is to assess the longitudinal change in TBS and BMD following treatment for acromegaly. Design, Setting, Patients, Interventions, and Main outcome measures This longitudinal study included 48 patients with acromegaly between 2005 and 2015. BMD, TBS, and markers for bone turnover (P1NP and CTX-1) were measured at baseline and following treatment. Results Following treatment, the mean TBS decreased by 3.0 (±7.0) %, whereas the BMD at the lumbar spine (LS) increased by 3.2 (±4.9) % (both P<0.01). The changes in BMD LS and TBS were not correlated (P=0.87). The TBS change was found to be −4.5 % (±6.7; P=0.003) in men and −0.3 % (±6.8; P=0.85) in women (P=0.063 for interaction men vs women). The mean BMD LS increased in men +4.2 g/cm2 (±4.3; P<0.001), but not in women +1.5 g/cm2 (±5.6; P=0.36); (P=0.073 for interaction). BMD increased in the ultradistal radius and total body (both P<0.01). The increase in BMD LS was associated with a decrease in P1NP and CTX-1 (P<0.001) and with lower P1NP and CTX-1 at the follow-up (P<0.02). Conclusion Treatment of acromegaly affects TBS and BMD at LS in different manners. The reduction of bone turnover markers predicts the increase in BMD but not the decrease in TBS. The DXA changes were more pronounced in men. Alterations in trabecular bone architecture may explain the persistent fracture risk despite the increase in BMD after disease control.
Parathyroid hormone independent hypercalcemia in adults Bollerslev, Jens; Pretorius, Mikkel; Heck, Ansgar
Baillière's best practice & research. Clinical endocrinology & metabolism,
October 2018, 2018-10-00, Letnik:
32, Številka:
5
Journal Article
Recenzirano
Parathyroid independent hypercalcemia is characterized by suppressed parathyroid hormone (PTH) in the presence of hypercalcemia.
Well known causes and mechanisms are redistribution of calcium from ...the skeleton, by malignant diseases; inadequately increased intestinal calcium uptake mediated by increased vitamin D activity, and reduced renal elimination due to medications. Frequent and infrequent causes are discussed, and more recent mechanistic models presented in this review.
Most hypercalcemic conditions are stable and in equilibrium between the different organs, whereas the utmost severe cases are characterized by rapid rising calcium levels and renal failure, resulting in a vicious circle where a disequilibrium state is developed. Management and treatment depends on the underlying condition and severity.
The aim of this review is to discuss non-parathyroid hypercalcemic conditions as seen in the modern clinic, with a focus on areas where recent gain of knowledge has been achieved.
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