挑战已知的：肢端肥大症和亚临床库欣综合征的罕见病例报告

摘要(中文译文)

垂体神经内分泌肿瘤（PitNETs）通常以激素分泌谱为特征，其与谱系特异性转录因子的表达相对应。生长激素（GH）和催乳素（PRL）的分泌受垂体特异性转录因子-1（Pit-1）调控，而促肾上腺皮质激素（ACTH）的生成经典上依赖于T-box转录因子19（T-pit）。因此，单一垂体腺瘤同时分泌GH和ACTH极为罕见。一名41岁男性表现为典型的肢端肥大症特征及严重代谢异常，包括控制不佳的糖尿病，但无库欣综合征的明显临床表现。内分泌评估显示GH和胰岛素样生长因子-1水平显著升高，口服葡萄糖耐量试验中GH不能被抑制，并有ACTH依赖性皮质醇增多症的生化证据，符合亚临床库欣病。垂体磁共振成像显示一侵袭性大腺瘤延伸至蝶窦。患者接受了经蝶窦肿瘤切除术。组织病理学检查显示GH和PRL呈弥漫性强免疫反应性，ACTH呈局灶性稀疏阳性。免疫组化显示Pit-1强表达，而T-pit染色完全阴性，表明为生长催乳素细胞型PitNET伴异常ACTH表达，而非真正的促肾上腺皮质激素细胞谱系分化。术后，ACTH和皮质醇水平显著下降，皮质醇可抑制性恢复，下丘脑-垂体-肾上腺轴功能保持完整，证实皮质醇增多症缓解。相比之下，肢端肥大症的生化缓解不完全，需要继续随访。本例描述了一例罕见的Pit-1谱系垂体大腺瘤，与肢端肥大症和亚临床库欣病相关。ACTH过度分泌与T-pit表达缺失之间的不一致突出了多激素PitNETs中非典型的激素调控，并强调了当前基于谱系的分类的局限性。

Abstract

Pituitary neuroendocrine tumors (PitNETs) are usually characterized by hormone secretion profiles that correspond to lineage-specific transcription factor expression. Growth hormone (GH) and prolactin (PRL) secretion is regulated by pituitary-specific transcription factor-1 (Pit-1), whereas adrenocorticotropic hormone (ACTH) production is classically dependent on T-box transcription factor 19 (T-pit). Accordingly, the concomitant secretion of GH and ACTH from a single pituitary adenoma is exceedingly rare. A 41-year-old man presented with typical acromegalic features and severe metabolic abnormalities, including poorly controlled diabetes mellitus, but without overt clinical manifestations of Cushing's syndrome. Endocrine evaluation demonstrated markedly elevated GH and insulin-like growth factor-1 levels, failure of GH suppression during oral glucose tolerance testing, and biochemical evidence of ACTH-dependent hypercortisolism, consistent with subclinical Cushing's disease. Pituitary magnetic resonance imaging revealed an invasive macroadenoma extending into the sphenoid sinus. The patient underwent transsphenoidal resection of the tumor. Histopathological examination showed diffuse and strong immunoreactivity for GH and PRL, with focal and sparse ACTH positivity. Immunohistochemistry revealed robust Pit-1 expression, while T-pit staining was entirely negative, indicating a mammosomatotroph PitNET with aberrant ACTH expression rather than true corticotroph lineage differentiation. Postoperatively, ACTH and cortisol levels declined substantially, cortisol suppressibility was restored, and hypothalamic-pituitary-adrenal axis function remained intact, confirming remission of hypercortisolism. In contrast, biochemical remission of acromegaly was incomplete, requiring continued follow-up. This case describes a rare Pit-1 lineage pituitary macroadenoma associated with acromegaly and subclinical Cushing's disease. The discordance between ACTH hypersecretion and absent T-pit expression highlights atypical hormone regulation in plurihormonal PitNETs and underscores the limitations of current lineage-based classifications.

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