Melo Maria Edna, Marui Suemi, Carvalho Luciani Renata, Arnhold Ivo Jorge Prado, Leite Claudia Costa, Mendonça Berenice Bilharinho, Knoepfelmacher Mirta
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM 42, Disciplina de Endocrinologia - HCFMUSP, Brazil.
Clin Endocrinol (Oxf). 2007 Jan;66(1):95-102. doi: 10.1111/j.1365-2265.2006.02692.x.
LHX4 and HESX1 are important in early stages of pituitary development and their mutations can be associated with an ectopic posterior lobe (EPL) in the pituitary of patients with hypopituitarism. The EPL can be located at the median eminence or at the path of the pituitary stalk. The aim of this study was to analyse LHX4 and HESX1 and characterize the hormonal deficiency profiles, establishing relationships with magnetic resonance imaging (MRI) findings in these patients.
Sixty-two patients with hypopituitarism associated with EPL were submitted to evaluation of pituitary function, analysis of MRI with EPL location and molecular analysis of LHX4 and HESX1 using polymerase chain reaction (PCR), digestion with restriction enzyme and automatic sequencing.
Forty-two patients had a nonvisualized pituitary stalk (NPS), and 20 a visualized pituitary stalk (VPS). Most patients (95%) with NPS had combined pituitary hormone deficiency (CPHD), with ACTH deficiency in 85%. In patients with VPS, CPHD was found in 50% and ACTH deficiency occurred in only 20%. The frequency of the location of EPL was similar in patients with VPS and NPS: 35% at median eminence and 65% at the path of the stalk. No mutations in LHX4 and HESX1 were identified. Three new polymorphisms in LHX4 were found.
ACTH deficiency is frequent in patients with hypopituitarism and NPS (85%), the location of EPL at the median eminence was not predictive of the hormonal profile [isolated GH deficiency (IGHD) or CPHD], and LHX4 and HESX1 genes mutations remain rare causes of hypopituitarism associated with EPL.
LHX4和HESX1在垂体发育早期很重要，它们的突变可能与垂体功能减退患者垂体的异位后叶（EPL）有关。EPL可位于正中隆起或垂体柄走行处。本研究的目的是分析LHX4和HESX1，并描述激素缺乏谱，建立与这些患者磁共振成像（MRI）结果的关系。
62例伴有EPL的垂体功能减退患者接受了垂体功能评估、EPL定位的MRI分析以及使用聚合酶链反应（PCR）、限制性内切酶消化和自动测序对LHX4和HESX1进行分子分析。
42例患者垂体柄不可见（NPS），20例患者垂体柄可见（VPS）。大多数NPS患者（95%）有联合垂体激素缺乏（CPHD），其中85%有促肾上腺皮质激素（ACTH）缺乏。VPS患者中，CPHD发生率为50%，ACTH缺乏仅发生在20%。VPS和NPS患者中EPL的位置频率相似：35%位于正中隆起，65%位于垂体柄走行处。未发现LHX4和HESX1的突变。在LHX4中发现了3种新的多态性。
垂体功能减退和NPS患者中ACTH缺乏很常见（85%），EPL位于正中隆起并不能预测激素谱[孤立性生长激素缺乏（IGHD）或CPHD]，LHX4和HESX1基因突变仍然是与EPL相关的垂体功能减退的罕见原因。
