| 1. |
- Arlien-Soborg, Mai C., et al.
(författare)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 2. |
- Arlien-Søborg, Mai C., et al.
(författare)
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Acromegaly management in the nordic countries : a Delphi consensus survey
- 2024
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 3. |
- Casar-Borota, Olivera, et al.
(författare)
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Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in Somatotroph Adenomas Assessed by Monoclonal Antibodies Was Reduced by Octreotide and Correlated With the Acute and Long-Term Effects of Octreotide
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:11, s. E1730-E1739
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Tidskriftsartikel (refereegranskat)abstract
- Context: Reduced expression of somatostatin receptors (SSTRs) in somatotroph adenomas and their potential down-regulation after medical treatment may explain the unsatisfactory response to octreotide in particular acromegalic patients. The expression of SSTRs other than SSTR2a has not been studied in large, unselected cohorts using novel rabbit monoclonal antibodies. Objective: We aimed to determine the expression of SSTRs 1, 2a, 3, and 5 in somatotroph adenomas, to correlate expression with clinical characteristics and the response to octreotide, and to ascertain whether preoperative octreotide treatment affected SSTR expression. Design, Setting, Patients: The study included 78 adenomas from patients operated on consecutively during 2000 to 2010. After exclusion of 13 patients, immunohistochemical analysis with rabbit monoclonal antibodies against SSTRs 1, 2a, 3, and 5 (clones UMB-7, -1, -5, and -4) was performed on 65 adenomas. Intervention: Twenty-eight patients received preoperative octreotide, and 37 patients were operated on without pretreatment. Twenty-six patients were randomized to direct surgery (n = 13) or to octreotide pretreatment (n = 13). Main Outcome Measure: SSTR expression was evaluated using a 12-grade scoring system. The responses to the octreotide test dose (GH reduction) and to 6 months of octreotide (IGF-I reduction) were measured. Results: The majority of adenomas showed membranous expression of SSTRs 2a and 5. SSTR2a expression was reduced in the pretreated group and correlated with the acute octreotide test results and the effect of octreotide treatment. In a linear regression model with SSTR2 a expression as the determinant, the correlation with the acute test response improved after adjustment for medical pretreatment. Conclusion: Rabbit monoclonal antibodies are reliable markers of SSTRs in somatotroph adenomas. SSTR2a expression correlated with the response to octreotide and was reduced after octreotide treatment, indicating the need for adjustment when SSTR2a expression is correlated with baseline characteristics. Evaluation of SSTR subtypes may be an important aspect of improving the medical treatment for acromegaly.
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| 4. |
- Fougner, Stine Lyngvi, et al.
(författare)
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Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly
- 2012
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Ingår i: Clinical Endocrinology. - Malden : Wiley. - 0300-0664 .- 1365-2265. ; 76:1, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT:Somatotroph adenomas have been classified into densely granulated (DG) and sparsely granulated (SG) tumours with a transitional, intermediate group. Gsp oncogenes are activating mutations in the Gsα subunit gene, found in approximately 40% of somatotroph adenomas.OBJECTIVES:To explore granulation pattern and presence of gsp oncogene in acromegaly with correlations to clinical and biochemical variables and to the effect of treatment with somatostatin analogues (SA), as well as to describe granulation pattern in adenomas with and without SA pretreatment.DESIGN/SETTINGS/PATIENTS:Seventy-eight patients with active acromegaly were included. Long-term SA efficacy was evaluated in 29 patients treated preoperatively and in ten treated postoperatively. Granulation pattern was examined, as were immunohistochemical analyses for E-cadherin and SSTR2a. Protein levels of E-cadherin and SSTR2a were measured (Western blot). Gsp mutation analysis was available for 74 adenomas.RESULTS:DG adenomas and the transitional group had higher serum levels of IGF-1 per tumour volume than SG (P = 0·009; P = 0·005). Acute and long-term SA responses were lower in SG (P = 0·001; P = 0·043). No correlation between gsp mutation and granulation was found, and no difference in granulation pattern according to preoperative SA treatment was demonstrated. A significant correlation between granulation and E-cadherin was found, where SG had lowest immunohistochemical expression, substantiated by protein levels, and a highly significant gradient was observed from DG, through the transitional group, to SG.CONCLUSIONS:Densely granulated adenomas were highly responsive to somatostatin analogues in contrast to SG adenomas. The transitional group behaved clinically more like DG adenomas. However, based on E-cadherin, a marker of dedifferentiation, the transitional group seemed to be a true intermediate.
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| 5. |
- Godang, Kristin, et al.
(författare)
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The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism
- 2018
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Ingår i: Endocrine connections. - 2049-3614. ; 7:8, s. 941-948
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Tidskriftsartikel (refereegranskat)abstract
- Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors.To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism.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.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.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.
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| 6. |
- Heck, Ansgar, et al.
(författare)
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Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly
- 2012
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 77:1, s. 72-78
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Tidskriftsartikel (refereegranskat)abstract
- 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):155180 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 (2.34.9), 2.9 (2.63.8) and 1.9 (1.32.6), respectively (P = 0.006 for difference between groups). Median GH values (mu g/l) of a 3- to 5-point profile were 17.5 (6.135), 9.3 (6.032.5) and 4.1 (1.58.3), (P = 0.025). Median IGF-1 reduction (% of baseline) after first-line SA treatment was 51 (4970), 36 (1974) and 13 (542) (P = 0.03); median reduction in GH (% of baseline) was 86 (7294), 78 (6285) and 46 (170) (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.
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| 7. |
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| 8. |
- Heck, Ansgar, et al.
(författare)
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Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly
- 2016
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 52:2, s. 333-343
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Tidskriftsartikel (refereegranskat)abstract
- In growth hormone (GH)-producing adenomas, T2-weighted MRI signal intensity is a marker for granulation pattern and response to somatostatin analogs (SSA). Prediction of treatment response is necessary for individualized treatment, and T2 intensity assessment might improve preoperative classification of somatotropinomas. The objectives of this study are (I) to explore the feasibility of quantitative T2-weighted MRI histogram analyses in newly diagnosed somatotroph adenomas and their relation to clinical and histological parameters and (II) to compare the quantitative method to conventional, visual assessment of T2 intensity. The study was a retrospective cohort study of 58 newly diagnosed patients. In 34 of these, response to primary SSA treatment after median 6 months was evaluated. Parameters from the T2 histogram analyses (T2 intensity ratio and T2 homogeneity ratio) were correlated to visually assessed T2 intensity (hypo-, iso-, hyperintense), baseline characteristics, response to SSA treatment, and histological granulation pattern (anti-Cam5.2). T2 intensity ratio was lowest in the hypointense tumors and highest in the hyperintense tumors (0.66 ± 0.10 vs. 1.07 ± 0.11; p < 0.001). T2 intensity at baseline correlated with reduction in GH (r = -0.67; p < 0.001) and IGF-1 (r = -0.36; p = 0.037) after primary SSA treatment (n = 34). The T2 homogeneity ratio correlated with adenoma size reduction (r = -0.45; p = 0.008). Sparsely granulated adenomas had a higher T2 intensity than densely or intermediately granulated adenomas. T2 histogram analyses are an applicable tool to assess T2 intensity in somatotroph adenomas. Quantitatively assessed T2 intensity ratio in GH-producing adenomas correlates with conventional assessment of T2 intensity, baseline characteristics, response to SSA treatment, and histological granulation pattern.
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| 9. |
- Kolnes, Anders Jensen, et al.
(författare)
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TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours
- 2023
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Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 26:2, s. 227-236
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data.Methods 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSH beta and LH beta was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells.Results TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LH beta (median 2 [IQR 0-3] in TGFBR3L negative and median 6 [IQR 3-9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSH beta (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9-9.6] and median 3.0 [IQR 1.8-5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L.Conclusion TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LH beta staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.
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| 10. |
- Lekva, Tove, et al.
(författare)
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Epithelial Splicing Regulator Protein 1 and Alternative Splicing in Somatotroph Adenomas
- 2013
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 154:9, s. 3331-3343
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Tidskriftsartikel (refereegranskat)abstract
- Somatotroph adenomas secrete supraphysiological amounts of GH, causing acromegaly. We have previously hypothesized that epithelial mesenchymal transition (EMT) may play a central role in the progression of these adenomas and that epithelial splicing regulator 1 (ESRP1) may function prominently as a master regulator of the EMT process in pituitary adenomas causing acromegaly. To further elucidate the role of ESRP1 in somatotroph adenomas and in EMT progression, we used RNA sequencing (RNAseq) to sequence somatotroph adenomas characterized by high and low ESRP1 levels. Transcripts identified by RNAseq were analyzed in 65 somatotroph adenomas and in GH-producing pituitary rat cells with a specific knockdown of Esrp1. The clinical importance of the transcripts was further investigated by correlating mRNA expression levels with clinical indices of disease activity and treatment response. Many of the transcripts and isoforms identified by RNAseq and verified by quantitative PCR were involved in vesicle transport and calcium signaling and were associated with clinical outcomes. Silencing Esrp1 in GH3 cells resulted in changes of gene expression overlapping the data observed in human somatotroph adenomas and revealed a decreased granulation pattern and attenuated GH release. We observed an alternative splicing pattern for F-box and leucine-rich repeat protein 20, depending on the ESPR1 levels and on changes in circulating IGF-I levels after somatostatin analog treatment. Our study indicates that ESRP1 in somatotroph adenomas regulates transcripts that may be essential in the EMT progression and in the response to somatostatin analog treatment.
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| 11. |
- Lundstam, Karolina, et al.
(författare)
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Effect of Surgery Versus Observation : Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study)
- 2017
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 32:9, s. 1907-1914
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Tidskriftsartikel (refereegranskat)abstract
- Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm(2) and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p<0.001) and CTX-1 (p<0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm(2)) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p<0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p<0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm(2)) for all compartments (FN, p<0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p<0.001) with the exception of the LS, whereBMDwas stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT.
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| 12. |
- Lundstam, Karolina, et al.
(författare)
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Effects of parathyroidectomy versus observation on the development of vertebral fractures in mild primary hyperparathyroidism
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:4, s. 1359-1367
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Tidskriftsartikel (refereegranskat)abstract
- Context: Mild primary hyperparathyroidism (PHPT) is a common disease especially in middle-aged and elderly women. The diagnosis is frequently made incidentally and treatment strategies are widely discussed. Objective: To study the effect of parathyroidectomy (PTX) compared with observation (OBS) on biochemistry, safety, bone mineral density (BMD), and new fractures. Design: Prospective, randomized controlled study (SIPH study), 5-year follow-up. Setting: Multicenter, tertiary referral centers. Patients: Of 191 randomized patients with mild PHPT, biochemical data were available for 145 patients after 5 years, mean age at inclusion 62.8 years (OBS group, 9 males) and 62.1 years (PTX group, 10 males). Intervention: Parathyroidectomy vs observation. Main outcome measures: Biochemistry, BMD and new radiographic vertebral fractures. Results: Serum-calcium and PTH-levels normalized after surgery and did not deteriorate by observation. BMD Z-scores were normal at inclusion in the lumbar spine (LS) and femoral neck (FN). For LS, BMD Z-scores were stable for 5 years with observation, but decreased in FN (P<0.02). After surgery, BMD Z-scores increased significantly in both compartments (P<0.02 for both), with a highly significant treatment effect of surgery compared to observation (P<0.001). During follow-up, 5 new clinically unrecognized vertebral fractures were found in 5 females, all in the OBS group (P=0.058). Conclusion: Even though new vertebral fractures occurred only in the observation group, the frequency was not significantly different from the surgery group. Longer follow-up is needed before firm conclusions can be drawn about the long-term safety of observation, as opposed to surgery.
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| 13. |
- Lundstam, Karolina, et al.
(författare)
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The Influence of Dxa Hardware, Software, Reference Population and Software Analysis Settings on the Bone Mineral Density and T-Score Relationship
- 2021
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Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950 .- 1559-0747. ; 25:1, s. 24-33
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Tidskriftsartikel (refereegranskat)abstract
- Different dual-energy x-ray absorptiometry (DXA) hardware can affect bone mineral density (BMD) measurements and different reference populations can affect t-scores. Long-term analyses describing differences in the relationship between BMD and t-scores are lacking. BMD-values were plotted against t-scores for 241 Lunar DXA scans on females obtained over 18 years from several centers in Sweden and Norway. The result of the plot was compared to hardware/software versions, reference populations and different software analysis settings (Basic vs Enhanced analysis for total body and Single Photon Absorptiometry (SPA) vs Lunar calibration for forearm). For the forearm compartments, we found different BMD-t-score relationships depending on the use of SPA or Lunar calibration (p<0.001). With Lunar calibration, BMD-values were 24% higher, but there was no effect on t-scores. Total body measurements with iDXA scanners and Enhanced analysis for Prodigy scanners (software version 14.10) resulted in a different BMD-t-score relationship compared to the other hardware/software versions (p<0.001), with the largest discrepancy for lower BMD-values. Switching from Basic to Enhanced analysis generally decreased BMD-values and often changed t-scores (both increased and decreased). For the femoral neck, there were two different BMD-t-score relationships caused by different reference populations (p<0.001). In contrast to total body, the difference for femoral neck was more pronounced for higher values, with little impact in the clinical decision-making area. Hardware, software, reference populations and software analysis settings can affect the BMD-t-score relationship, but do so differently for different compartments. The BMD-t-score-plot is a simple and effective tool to discover systematic differences. Longitudinal analyses of DXA scans should be performed based on raw data analyzed in “one run” with the same software version and settings, in order to avoid systematic differences.
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| 14. |
- Pretorius, Mikkel, et al.
(författare)
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Mortality and Morbidity in Mild Primary Hyperparathyroidism : Results From a 10-Year Prospective Randomized Controlled Trial of Versus Observation
- 2022
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 175:6, s. 812-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. Objective: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). Design: Prospective randomized controlled trial. (ClinicalTrials. gov: NCT00522028) Setting: Eight Scandinavian referral centers. Patients: From 1998 to 2005, 191 patients with mild PHPT were included. Intervention: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). Measurements: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. Results: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). Limitation: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. Conclusion: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. Primary Funding Source: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority
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