Jens Otto Lunde Jørgensen

Long-acting growth hormone (LAGH) preparations have moved from development to routine clinical use over the past decade. Several products are now approved for paediatric growth hormone deficiency (GHD), selected non-GHD short-stature indications, and, in some regions, for adult GHD. The Growth Hormone Research Society convened an international workshop in October 2025 to reappraise the evidence base and refine clinical recommendations. Currently, data are available for up to 7 years of LAGH treatment in over 8000 individuals. This remains substantially shorter and smaller than for daily GH. Across preparations, short- to mid-term efficacy appears comparable to daily somatropin, provided dosing is individualized and monitored appropriately. Approvals and pivotal trials include both treatment initiation and switching from daily GH, depending on product and regional label. No new major safety signals have been identified in trials and real-world reports, although data on BMI trajectories require further evaluation. Injection-site reactions remain the most frequent adverse event and vary by formulation. Anti-drug antibodies have been observed, yet evidence suggests they have limited clinical impact. Effects on glucose metabolism resemble those of daily therapy, but metabolically, high-risk groups are under-represented in studies. Among cancer survivors, data on tumour recurrence and second neoplasms with LAGH are not yet available. Recommendations and practice points emphasized careful patient selection and counselling, product-specific dosing, and insulin-like growth factor-I (IGF-I) monitoring. Urgent knowledge gaps include transition care, long-term efficacy, adherence, and safety in cancer survivors. Well-resourced registries are essential for addressing these gaps and supporting safe, effective, and patient-centred use of LAGH.

Cancer risk in acromegaly remains debated, with studies showing both increased and similar risk compared to the background population. We conducted a nationwide cohort study examining the risk of cancer and benign colorectal lesions in acromegaly patients. The study included acromegaly patients diagnosed in Denmark (1977-2021, n = 809, median follow-up 12.2 [IQR: 5.6-21.7] years (range: 0.04-44.0) and controls matched on sex and birth year (n = 80,900). All diagnoses of acromegaly were biochemically validated. We investigated the occurrence of cancer diagnoses, benign colorectal lesions, performance of colonoscopies and mortality with time-to-event statistics and logistic regression. Overall cancer risk was not clearly increased (IRR: 1.10 [0.93;1.30], p = 0.27), but patients with acromegaly had an increased risk of colorectal cancer (IRR: 1.78 [1.22;2.60], p < 0.01) and thyroid cancer (IRR: 3.68 [1.16;11.66], p = 0.03). Colorectal cancers were more often localized (IRR: 2.00 [1.21;3.30], p = 0.007) as compared to controls, and the use of endoscopic colorectal procedures was increased (IRR: 2.85 [2.54;3.19], p < 0.01). The incidence of benign colorectal lesions was elevated in acromegaly patients (IRR: 2.32 [1.96;2.76], p < 0.01) and dominated by tubular adenomas (43.6%) and hyperplastic polyps (33.2%). Fecal immunochemical test (FIT) screening and clinical suspicion guided the use of colonoscopies, rather than systematic colonoscopy screening.All-cause mortality was elevated in acromegaly (IRR: 1.18 [1.02; 1.36], p = 0.03), but cancer-specific mortality was not (IRR: 0.95 [0.72;1.25], p = 0.72). Acromegaly carries an increased risk of colorectal cancer, but neither overall cancer risk, nor cancer-specific mortality are increased.

Introduction Patients on low-dose prednisolone may develop adrenal insufficiency causing reduced health-related quality of life (HRQoL) and increased risk of adrenal crisis. This study examines whether supplemental hydrocortisone during mild to moderate stress improves HRQoL in patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) with adrenal insufficiency on low-dose prednisolone. Methods and analysis A multicentre, randomised, double-blinded, placebo-controlled, clinical trial including patients with PMR/GCA receiving ongoing prednisolone ≤5 mg/day. Eligible patients undergo an adrenocorticotropic hormone (ACTH) test, and 250 patients with a stimulated cortisolEthics and dissemination The study is approved by the Ethics Committee of the Capital Region of Denmark and the Danish Medicines Agency. Recruitment began June 2022. The last patient’s last visit is expected in 2026. Results will be disseminated via peer-reviewed publication and conference presentations. Trial registration numbers EudraCT:2021-002528-18, CTIS:2024-518272-30-00, NCT05435781.

Background: Adipose tissue (AT) fibrosis impairs tissue function and is linked to obesity and insulin resistance. Acromegaly, caused by growth hormone excess, promotes lipolysis-driven insulin resistance and profound stimulation of collagen synthesis. It is unknown if this translates into excessive tissue fibrosis Aim: Quantification of collagen turnover and fibrosis in fat and muscle in patients with acromegaly before and after treatment. Methods: Two patient cohorts were examined before and after treatment. In cohort 1 (n = 17), AT collagen content and fibrosis- and inflammation-related gene expression were analyzed. In cohort 2 (n = 15), skeletal muscle collagen content, and serum fibroblast activation protein (FAPα) activity and levels were analyzed. Collagen turnover serum biomarkers were analyzed in both cohorts. Results: AT collagen content (%) decreased from 4.6 ± 2.9 before to 2.1 ± 1.2 after disease control (P < .05). AT type I and III collagen gene expression decreased by 53% and 39%, respectively, and correlated closely with disease activity. Muscle collagen content (relative units) decreased from 0.020 ± 0.004 to 0.012 ± 0.008 after disease control (P = .0460). FAPα activity (RFU/min) and levels (µg/L) decreased following disease control (373 ± 111 [before] vs 248 ± 62 [after]; P < .0001, and 102 ± 35 [before] vs 63 ± 23 [after]; P < .001, respectively). In both cohorts, collagen turnover biomarkers declined after disease control. Inflammatory markers were unaffected. Conclusion: Our study reports for the first time that prolonged growth hormone excess induces reversible fibrosis in human adipose and muscle tissue. We hypothesize that fibrosis in acromegaly is mainly driven by a direct effect on collagen formation and likely not secondary to inflammation, which contrasts with obesity-driven AT fibrosis. Clinical trial registration number: NCT00647179; NCT03431727.

Introduction: Glucocorticoid therapy is prescribed for a variety of inflammatory conditions and is associated with severe adverse effects. A glucocorticoid withdrawal syndrome (GWS) may occur after prolonged glucocorticoid treatment—with or without biochemical glucocorticoid-induced adrenal insufficiency (GIAI). Previously, GWS was not considered an entity, probably due to the overlap between symptoms of GWS and GIAI. The Addison’s disease-specific quality of life questionnaire (AddiQoL-30) is a validated tool for quantifying symptoms of adrenal insufficiency resembling GWS. In the present study, we test the hypothesis that patients with a low AddiQoL-30 score and/or low cortisol response to a short Synacthen test (SST), after cessation of prednisolone treatment, may benefit from low-dose hydrocortisone therapy without increasing the risk of metabolic and cardiovascular disease during prolonged cortisol exposure. Methods and analysis: REPLACE is a multi-centre, double-blinded, placebo-controlled randomised controlled trial in patients with polymyalgia rheumatica or giant cell arteritis after cessation of prednisolone treatment. Criteria for randomisation are an AddiQoL-30 score ≤85 and/or plasma cortisol response to SST, 30-min p-cortisol >100 and 85; and (2) patients with a SST-stimulated cortisol ≤100 nmol/L. Ethics and dissemination: The study is conducted in accordance with the Declaration of Helsinki, registered at the Clinical Trials Information System (CTIS: 2024-513822-53-00) and Clinicaltrials.gov ( NCT05193396 ), and publications will be in accordance with the recommendations of the International Committee of Medical Journal Editors. The trial is monitored by local independent Good Clinical Practice units and overseen by the Danish Data Protection Agency (journal no. 21/27119), the Regional Committees on Health Research Ethics for Southern Denmark (project ID: S-20210076), the Danish Patient Safety Authority and the Danish Medicines Agency. Trial registration number: NCT05193396 .

Graphical The increased detection of adrenal incidentalomas and drug-induced adrenal insufficiency increases the demand for cortisol testing. While liquid chromatography–tandem mass spectrometry (LC-MS/MS) and dynamic testing remain the gold standard, more expedient tools are needed. We compared the Elecsys Cortisol II immunoassay (ElecsysCort II) with LC-MS/MS during dynamic testing and evaluated the diagnostic performance of baseline cortisol cutoffs (0 min cortisol during a short Synacthen test). The study included 547 overnight dexamethasone suppression tests (44% abnormal), mainly performed in adrenal incidentaloma patients (69%), and 519 Synacthen tests (32% abnormal). ElecsysCort II slightly underestimated cortisol compared with LC-MS/MS with a Passing–Bablok regression of −3.20 (95% CI: −3.66 to −2.83) + 0.96X (95% CI: 0.96–0.97) and a mean relative difference of −8.22% (95% CI: −8.99% to −7.45%) by Bland–Altman, which was within the limits of acceptable bias based on biological variation. Agreement was not affected by glucocorticoid or estradiol intake. Compared with LC-MS/MS, ElecsysCort II demonstrated a specificity of 100%, sensitivity of 84%, positive predictive value of 99%, and negative predictive value of 86% for an abnormal overnight dexamethasone suppression test (480 min cortisol ≥50 nmol/L). For an abnormal Synacthen test (30 min cortisol 300 nmol/L to rule out and 92%) and a positive predictive value (>87%). Our study supports the use of ElecsysCort II in general and baseline cortisol as a screening tool for adrenal insufficiency. The high proportion of abnormal overnight dexamethasone suppression tests among incidentaloma patients warrants further research.

Background: Growth hormone (GH) potently stimulates collagen turnover which underlies its anabolic effects on bone in children, whereas it may promote fibrosis in adults. Fibroblast activation protein-α (FAPα) is a serine protease which substrates include collagen and fibroblast growth factor 21 (FGF21). FAPα levels are reversibly elevated in active acromegaly. Aim: To measure circulating FAPα activity and levels, as well as FAPα substrates, in adult patients with GH-deficiency (GHD) before and after GH replacement therapy. Methods: FAPα activity and levels were analyzed in serum samples from two groups of GHD patients before and after 3-6 months GH replacement therapy as compared to non-GHD hypopituitary patients and a healthy reference group. Furthermore, collagen turnover biomarkers (PINP, PIIINP, CTx) and intact FGF21 were analyzed. Results: FAPα activity (RFU/min) significantly increased after GH replacement in both GHD groups [290.6 ± 47.8 (before) vs. 428.5 ± 66.4 (after) P < .05; 291.0 ± 37.4 (before) vs. 403.0 ± 52.9 (after); P < .05]. Likewise, FAPα levels significantly increased by 40% after GH replacement in both groups (P < .01) and correlated closely with FAPα activity. PINP, PIIINP and CTx significantly increased after 3 months of GH replacement. Intact FGF21 remained unchanged. Conclusions: (1) Our study documents for the first time that GH stimulates FAPα activity in vivo in human subjects. (2) The concomitant increase in collagen turnover and the lack of change in intact FGF21 suggest that GH-driven FAPα activity predominantly involves collagen breakdown, and (3) FAPα is a novel biomarker of GH/IGF-I activity and may be causally linked to GH-induced fibrosis.

Objective: To investigate adrenal function and the prevalence of glucocorticoid (GC) induced adrenal insufficiency (GIAI) in patients with polymyalgia rheumatica (PMR), the first 18 months after diagnosis. Methods: Newly diagnosed patients with PMR underwent short corticotropin tests before commencement of GC treatment and after 10 weeks, 6 months, and 12 months. Patients still on GC or with GIAI after 12 months were invited to a test after 18 months. GIAI was defined as a stimulated serum cortisol level <420 nmol/l. Results: : Sixty patients with PMR were enrolled. The mean (S.D.) stimulated cortisol levels declined significantly between baseline (678 ± 95) and month 6 (491 ± 114), followed by an increase at month 12 (549 ± 100). An inverse relationship was found between stimulated cortisol levels and current GC dose (P < 0.001). The proportion of GIAI peaked at month 6 (13/53, 25%) when all patients received GC. By 12 months, adrenal function had recovered in 12/13 (92%) of these patients. At month 12 and month 18, GIAI was present in 1/31 (3%) and 0/12 (0%), who were no longer receiving GC. Conclusion: Stimulated serum cortisol levels in patients with PMR did not reach pretreatment levels after cessation of GC treatment. GIAI was frequent but reversible during GC treatment for PMR, which supports the concept of increased GC dosing during stress in these patients. Implementation of routine use of the short corticotropin test for the diagnosis of GIAI after planned cessation of GC treatment in PMR is not justified by our data. Trial registration: Clinicaltrials.gov, http://clinicaltrials.gov, NCT04519580.