Defining Inadequate Control and Clinical Candidacy for PTH Replacement in Chronic Hypoparathyroidism: A Focused Systematic Review

Abstract Background Chronic hypoparathyroidism is conventionally treated with calcium and activated vitamin D, but a subset of patients remains insufficiently controlled despite therapy. Definitions of inadequate control and criteria for considering parathyroid hormone (PTH) replacement vary across guidelines, consensus documents, and clinical studies. This review aimed to characterize these criteria and summarize the evidence relevant to PTH replacement in adults with chronic hypoparathyroidism. Methods We conducted a focused systematic review with structured narrative synthesis of normative, secondary, and primary clinical evidence. PubMed/MEDLINE and Embase were searched from inception through July 2026, supplemented by backward citation searching. Technology-assisted screening and extraction were performed within a human-in-the-loop workflow. Definitions, operational criteria, quantitative thresholds, clinical candidacy for PTH replacement, trial eligibility criteria, and treatment outcomes were extracted and synthesized descriptively. No meta-analysis, formal risk-of-bias assessment, or GRADE certainty rating was performed. Results Of 1,618 records identified, 164 reports were included. Inadequate control with conventional therapy was addressed in 108 reports, but only 24 provided an explicit textual definition. The most frequently represented domains were biochemical control (96/108, 88.9%), clinical manifestations (67/108, 62.0%), renal risk or complications (55/108, 50.9%), treatment burden (44/108, 40.7%), and patient-reported outcomes or quality of life (34/108, 31.5%). Quantitative thresholds were reported in 45 reports and persistence or repeated-occurrence requirements in 29, with substantial variability across sources. Fourteen reports directly addressed clinical candidacy for PTH replacement and were organized into 12 framework or guideline-version groupings. Recurrent candidacy domains included symptomatic or unstable calcium control, phosphate abnormalities, renal complications, high treatment requirements, impaired quality of life, malabsorption, and treatment intolerance. Sixty-seven primary reports evaluated PTH-based treatment outcomes. Across study programs, PTH replacement reduced conventional calcium and active vitamin D requirements and showed favorable biochemical, renal, and patient-reported outcomes in selected populations, although long-term comparative evidence and head-to-head data across formulations remained limited. Conclusions Inadequate control of chronic hypoparathyroidism is consistently represented as a multidimensional construct, but no single definition, threshold set, persistence requirement, or eligibility algorithm is universally accepted. This review provides an evidence framework to inform subsequent structured expert deliberation for a Colombian position statement, while preserving areas of uncertainty for explicit panel judgment.