{
  "abstract": "Objective: The gonadotropin-releasing hormone (GnRH) stimulation test, the reference standard for confirming hypothalamic-pituitary-gonadal axis (HPGA) activation, is invasive and costly. Pituitary volume (PV) on MRI has been proposed as a non-invasive surrogate, yet whether PV constitutes a permissive morphological threshold or is redundant with clinical parameters remains undefined. We evaluated PV as a morphological threshold of HPGA activation and quantified its relative importance, unique information content, and clinical utility.\n\nMethods: We retrospectively enrolled 896 children who underwent pituitary MRI and GnRH stimulation testing. PV was measured using the ellipsoid approximation. Out-of-fold cross-validated AUC was the primary performance metric. Predictor importance was quantified by Shapley value decomposition, permutation importance, and Lindeman–Merenda–Gold (LMG) variance partitioning. Morphological-threshold analyses examined HPGA activation across PV deciles. Statistical mediation tested whether insulin-like growth factor 1 (IGF-1) mediated the PV–HPGA association, with formal power analysis for incremental AUC detection.\n\nResults: PV exhibited a threshold pattern: HPGA activation was 28.9% (95% CI 20.5–39.0) in the lowest PV decile (≤115 mm³) versus 92.2% (95% CI 84.8–96.2) in the highest (≥335 mm³; OR 4.38, 95% CI 2.60–7.36; per-IQR OR 2.04, 95% CI 1.59–2.62). PV ranked second by Shapley decomposition (+0.065 AUC, 22.2%), carrying unique information (LMG 20.4% of pseudo-R²). At the 203.9 mm³ cutpoint, the diagnostic odds ratio was 4.78, positive likelihood ratio 2.44, and number needed to screen 2.73. PV tertile AUC was 0.693; combined with IGF-1, AUC rose to 0.748. IGF-1 statistically mediated 37.4% of the PV–HPGA association. The full model OOF AUC was 0.801 (95% CI 0.772–0.828) versus 0.798 for the clinical model (ΔAUC +0.003); power was ~5% at N = 896, requiring N ≈ 25360 for 80% power. The age-sex-adjusted PV z-score AUC was 0.592 (95% CI 0.554–0.630).\n\nConclusion: PV serves as a permissive morphological threshold for HPGA activation; while it’s not a strictly necessary condition, HPGA activation is physiologically improbable below a critical PV. Although PV is not a standalone predictive tool and its incremental value over clinical parameters is minimal, it functions as a complementary morphological checkpoint that contextualizes hormonal interpretation when pituitary MRI has been conducted to exclude intracranial lesions as per guidelines.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology",
    "Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology",
    "MR Research, GE Healthcare",
    "Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jianjian Cai"
    },
    {
      "affs": [
        1
      ],
      "name": "Ling Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Weiyin Vivian Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Qin Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Jun Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Dong Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/axh2s2cyc3302.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1981603",
  "fulltext_url": null,
  "id": "axh2s2cyc3302",
  "issns": [
    "1664-2392"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1981603/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2743|Hypothalamic control of reproductive hormones"
    ]
  ],
  "openalex": "W7223181488",
  "pdf_url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1981603/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/axh2s2cyc3302.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.3389/fendo.2026.1981603",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1981603/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2743|Hypothalamic control of reproductive hormones",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Pituitary volume as a permissive morphological threshold for hypothalamic-pituitary-gonadal axis activation in children: a comprehensive diagnostic prediction study with relative importance decomposition",
  "title_text": "Pituitary volume as a permissive morphological threshold for hypothalamic-pituitary-gonadal axis activation in children: a comprehensive diagnostic prediction study with relative importance decomposition",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:20Z",
  "url": "https://research.draconitic.com/paper/axh2s2cyc3302",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}