Daily Endocrinology Research Analysis
Analyzed 98 papers and selected 3 impactful papers.
Summary
Analyzed 98 papers and selected 3 impactful articles.
Selected Articles
1. Somapacitan in children born small for gestational age: a randomized controlled phase 3 trial.
In a 52-week, multicenter phase 3 RCT in short children born SGA (n=142), once-weekly somapacitan achieved height velocity of 11.0 cm/year and met noninferiority versus daily GH (0.035 or 0.067 mg/kg/day), with superiority over the lower daily dose. Safety profiles were similar, and once-weekly dosing reduced treatment burden.
Impact: This trial provides high-level evidence that once-weekly GH can maintain efficacy with lower burden in SGA, addressing adherence and quality-of-life barriers inherent to daily injections.
Clinical Implications: Once-weekly somapacitan is a viable alternative to daily GH for SGA-related short stature, potentially improving adherence and outcomes; protocols may adopt somapacitan particularly where injection burden limits daily therapy.
Key Findings
- Somapacitan achieved 11.0 cm/year height velocity at week 52.
- Noninferiority to daily GH (0.035 and 0.067 mg/kg/day) was confirmed; superiority over 0.035 mg/kg/day was demonstrated.
- Safety profiles were similar across groups; once-weekly dosing reduced treatment burden.
Methodological Strengths
- Multinational, multicenter randomized active-comparator phase 3 design
- Pre-registered (NCT05330325) with clear primary endpoint and basket structure
Limitations
- Open-label design may introduce performance/assessment bias
- 52-week main phase limits long-term efficacy and safety inferences (e.g., adult height, metabolic effects)
Future Directions: Assess long-term growth outcomes (adult height), adherence, metabolic/cardiometabolic effects, and head-to-head comparisons among long-acting GH agents.
OBJECTIVE: Short stature in children born small for gestational age (SGA) is treated with daily injections of recombinant growth hormone (GH), a significant treatment burden. The objective of this study is to demonstrate the efficacy and safety of once-weekly somapacitan, a long-acting GH, in short children born SGA. DESIGN: REAL8 (NCT05330325) is a multinational, multicenter, randomized, open-labeled, active comparator, phase 3 basket study including four non-GH deficiency indications comprising a 52-week main phase and 104-week extension. Here, we present 52-week results from the SGA sub-study. METHODS: 142 prepubertal, treatm
2. Who can safely discontinue lifelong follow-up among patients with sporadic pheochromocytoma and paraganglioma?
In a cohort of 703 nonmetastatic, nonhereditary, completely resected PPGLs, age >40 years, tumor size <6 cm, and PASS <4 or GAPP <3 independently predicted lower recurrence. No recurrences were observed among patients meeting all three criteria in both internal and NIH external validation sets.
Impact: Defines and validates a very low-risk sporadic pheochromocytoma subgroup that may safely forgo lifelong surveillance, potentially changing follow-up guidelines.
Clinical Implications: For sporadic PCC patients >40 years with tumors <6 cm and low PASS/GAPP, clinicians may consider de-escalating to time-limited follow-up rather than lifelong monitoring, reducing patient burden and healthcare resource use.
Key Findings
- Age >40 years (HR 0.36), tumor size <6 cm (HR 0.43), and PASS <4 or GAPP <3 (HR 0.37) independently associated with lower recurrence risk.
- Cutoffs derived via ROC analysis (37 years, 5.7 cm) and rounded to pragmatic thresholds (>40 years, <6 cm).
- No recurrences among patients meeting all criteria in internal (n=114) and external NIH validation (n=13) sets.
Methodological Strengths
- Large single-disease cohort with internal and external validation
- Use of standardized pathology scores (PASS/GAPP) and time-to-event modeling
Limitations
- Retrospective design with potential selection and information bias
- External validation very-low-risk set was small (n=13), and criteria may not generalize to paragangliomas or hereditary/metastatic cases
Future Directions: Prospective validation across diverse centers including paragangliomas; cost-effectiveness analyses of de-escalated surveillance; integration with biochemical/genetic risk markers.
BACKGROUND: Current guidelines recommend at least 10 years of follow-up for all pheochromocytoma and paraganglioma (PPGL) patients and lifelong monitoring for high-risk individuals. Nonetheless, data identifying patients who may not require routine lifelong follow-up are scarce. METHODS: Among 999 patients with PPGL, 703 who were non-metastatic, non-hereditary, and had undergone complete resection were included. Variables that significantly differed between the recurrence (n = 50) and non-recurrence groups over 10 years (n = 83) were identified, and cutoff values were determined using receiver-operating characteristic curve analysis. These very low-risk criteria were validated in an internal cohort and an external dataset from the National Institutes of Health. RESULTS: The non-recurrence group was older and had smaller pheochromocytomas (PCCs) than the recurrence group, with cutoffs of 37 years and 5.7 cm, respectively. The non-recurrence group had a higher percentage of patients with pheochromocytoma of the adrenal gland scaled score (PASS) <4 or grading system for adrenal pheochromocytoma and paraganglioma (GAPP) score <3 (p = 0.027). Age >40 years (hazard ratio [HR] [95% confidence intervals] of 0.36 [0.17-0.76]), PCC size <6 cm (HR = 0.43 [0.19-0.98]), and PASS <4 or GAPP score <3 (HR = 0.37 [0.16-0.89]) were associated with lower recurrence risk. None of the patients meeting all these criteria in the internal (n = 114) and external (n = 13) validation sets experienced recurrence. CONCLUSION: This study suggests that routine lifelong follow-up may be unnecessary for patients with sporadic PCC aged >40 years, size <6 cm, and PASS <4 or GAPP score <3.
3. Pseudohypoxia and Family History Are Key Predictors of Severe Outcomes in Hereditary Pheochromocytoma and Paraganglioma Syndromes.
In a prospective multicenter cohort (n=221), machine learning integrating clinical features and germline variants showed that age <41 years with positive family history predicted PPGL pathogenic variants with 100% PPV, while >40 years with solitary PPGL had 86% NPV. Pseudohypoxia-related variants and elevated catecholamine metabolites identified high risk for multifocal/metastatic disease (PPV ~80%).
Impact: Provides actionable, validated predictors integrating genotype, biochemistry, and family history to personalize genetic testing and surveillance intensity in hereditary PPGL.
Clinical Implications: Early, intensive surveillance is warranted for PH-related variant carriers and those with elevated catecholamine metabolites, while older patients with solitary PPGL may undergo de-escalated genetic testing/surveillance.
Key Findings
- Age <41 years with positive family history had 100% PPV for carrying PPGL pathogenic variants; >40 years with solitary PPGL had 86% NPV.
- Pseudohypoxia-related variants conferred younger age at diagnosis and higher risk of multifocal/metastatic disease.
- Elevated catecholamine metabolites plus PH-related variants yielded ~80% PPV for multifocal/metastatic PPGL; negative family history with non-PH genes had high NPV (91–100%).
Methodological Strengths
- Prospective, multicenter design with integrated clinical, biochemical, and germline data
- Application of machine learning with explicit PPV/NPV metrics for clinically relevant endpoints
Limitations
- Moderate sample size and potential spectrum bias across referral centers
- External validation scope is limited; applicability to all ethnicities and healthcare settings requires confirmation
Future Directions: Broader external validation and integration into decision-support tools; testing cost-effectiveness of stratified surveillance based on PH-variant and metabolite profiles.
OBJECTIVE: Pheochromocytoma and paraganglioma (PPGL) have high genetic predisposition rates. In this multicenter study, we aimed to identify risk-modulating factors for disease development and aggressiveness in patients carrying pathogenic variants (PPGLgPV) related to PPGL genes. METHODS: Observational prospective study including patients with PPGL, family history of PPGL or suspected PPGL-related hereditary syndrome. Patients underwent clinical and germline PPGLgPV evaluation. Machine learning analyses were conducted to predict a patient's risk of carrying PPGLgPV, developing PPGL, and developing metastatic or multifocal disease. RESULTS: Of 221 patients (age 33.5±19.9 years, 45.2% males), 143 (64.7%) patients harbored PPGLgPV and 91 (41.2%) developed PPGL (46 pheochromocytoma, 45 paraganglioma/both, 29 multifocal/metastatic PPGL). Age at diagnosis of <41 years with a positive family history showed a 100% positive predictive value (PPV) for carrying PPGLgPV, compared to an 86% negative predictive value (NPV) when diagnosed at age >40 years with a solitary PPGL. Pseudohypoxia (PH)-related PPGLgPV carriers were younger at PPGL diagnosis and had an increased risk of multifocal/metastatic disease. Elevated catecholamine metabolites and PH-related PPGLgPV had 80% PPV for metastatic/multifocal disease, vs. high NPV for non-elevated catecholamine metabolites with negative family history (100%) or non-PH gene alterations (91%). Patients with PV found incidentally had a lower PPGL risk compared with carriers screened due to a family member with PPGL (p=0.026). CONCLUSIONS: Machine learning identified combined clinical and genetic characteristics for predicting hereditary PPGL syndromes, and multifocal/metastatic PPGL. This enables personalized risk stratification to guide genetic testing and surveillance in patients with PPGL and their relatives.