Lamesch C, Neumann S, Pfäffle R, Kiess W, Paschke R
III. Medical Department, University of Leipzig, Germany.
Pituitary. 2002;5(3):163-8. doi: 10.1023/a:1023356915458.
Combined pituitary hormone deficiency (CPHD) can be caused by mutation of the pituitary transcription factors POU1F1 or PROP1. More recently mutations in the HESX1, the LHX3 and LHX4 transcription factor genes have also been described as a cause in patients with CPHD. In most patients the disorder is characterized by an impaired production of GH, TSH, PRL and gonadotropins. In some cases of CPHD adrenocorticotropin deficiency is also present. We report the progressive CPHD and its molecular etiology in a woman with CPHD presenting with first symptoms of ACTH/cortisol deficiency at the age of 48 years. The 49 year old patient's initial symptoms were growth retardation at the age of 2 years and symptoms of hypothyroidism at the age of 5 years. The patient never entered puberty spontaneously. No familial history of delayed puberty, growth retardation or other symptoms of CPHD were present. At the age of 48 years the patient presented with the first symptoms of hypocortisolism such as recurring hypoglycaemias and hyponatriaemia with coma. Cortisol, ACTH, TSH, fT3, fT4 and GH as well as LH, FSH and PRL were measured in basal conditions. GH, cortisol and ACTH were also measured in response to an Insulin Tolerance Test. Molecular analysis was performed by PCR amplification and sequencing of exon 1-3 of the PROP1 gene. The patient had insufficiencies of TSH, LH, FSH and GH. PRL was normal. Serum cortisol was low and basal ACTH was normal. However, there were no responses of cortisol, ACTH and GH to hypoglycaemia. Magnetic resonance imaging showed a hypoplastic anterior pituitary lobe. Direct sequencing revealed a homozygous 2 base-pair deletion 301-302delAG in exon 2 of the PROP1 gene. This case suggests that in patients with CPHD ACTH producing cells may be involved at a rather late age.
联合垂体激素缺乏症（CPHD）可由垂体转录因子POU1F1或PROP1的突变引起。最近，HESX1、LHX3和LHX4转录因子基因的突变也被描述为CPHD患者的病因。在大多数患者中，该疾病的特征是生长激素（GH）、促甲状腺激素（TSH）、催乳素（PRL）和促性腺激素的分泌受损。在某些CPHD病例中，也存在促肾上腺皮质激素缺乏。我们报告了一名48岁出现促肾上腺皮质激素/皮质醇缺乏首发症状的CPHD女性患者的进行性CPHD及其分子病因。这位49岁患者的初始症状是2岁时生长发育迟缓以及5岁时出现甲状腺功能减退症状。患者从未自然进入青春期。不存在青春期延迟、生长发育迟缓或其他CPHD症状的家族史。48岁时，患者出现了低皮质醇血症的首发症状，如反复低血糖和低钠血症伴昏迷。在基础状态下测量了皮质醇、促肾上腺皮质激素、促甲状腺激素、游离三碘甲状腺原氨酸（fT3）、游离甲状腺素（fT4）和生长激素，以及促黄体生成素（LH）、促卵泡生成素（FSH）和催乳素。还在胰岛素耐量试验后测量了生长激素、皮质醇和促肾上腺皮质激素。通过对PROP1基因外显子1 - 3进行PCR扩增和测序进行分子分析。该患者存在促甲状腺激素、促黄体生成素、促卵泡生成素和生长激素不足。催乳素正常。血清皮质醇低，基础促肾上腺皮质激素正常。然而，皮质醇、促肾上腺皮质激素和生长激素对低血糖无反应。磁共振成像显示垂体前叶发育不全。直接测序显示PROP1基因外显子2存在纯合的2个碱基对缺失（301 - 302delAG）。该病例表明，在CPHD患者中，促肾上腺皮质激素分泌细胞可能在相当晚的年龄才受到影响。
