Familial cortisol resistance: differential diagnostic and therapeutic aspects.
Familial cortisol resistance: differential diagnostic and therapeutic aspects.
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家族性皮质醇抵抗：鉴别诊断和治疗方面。
DOI：
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发表时间：
1986
影响因子：
5.8
通讯作者：
F. de Jong
中科院分区：
文献类型：
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作者：
S. Lamberts;D. Poldermans;M. Zweens;F. de Jong
一名26岁女性，表现为多毛、男性型头皮秃发（“地头病”）和月经不规律。她没有高血压或其他库欣综合征的体征和症状。血浆皮质醇水平在地塞米松作用下明显升高，正常情况下不受抑制。皮质醇与转质结合正常。血浆雄烯二酮和睾酮水平升高，但17-羟孕酮和醛固酮水平正常。进一步的研究显示，胰岛素诱导的低血糖会导致皮质醇生成速率增加、24小时尿皮质醇排泄增加、血浆ACTH水平增加、皮质醇升高的正常昼夜节律以及血浆ACTH、皮质醇、GH和PRL的正常增量。父亲和两个兄弟的血浆皮质醇水平也有所升高，这在地塞米松的正常作用下是不会被抑制的。慢性地塞米松治疗（最初1毫克，后来0.5毫克，每天3次）超过30周，导致多毛症减少，头皮头发和月经周期正常化，血浆睾酮和雄烯二酮水平正常。没有出现库欣综合征的体征或症状，ACTH、皮质醇、GH和PRL（胰岛素试验、昼夜节律）分泌的中枢调节在较低的设定点保持定性正常。我们的结论是，该患者患有常染色体显性遗传的遗传性（部分）皮质醇不敏感，导致肾上腺皮质皮质醇和雄激素分泌增加。后者并未导致三名患病男性家庭成员出现临床症状，但在提议中出现了。结果还表明胰岛素测试在区分这种疾病和库欣病方面的潜在用处。
A 26-yr-old woman presented with hirsutism, male pattern scalp baldness ("geheimratsecken"), and menstrual irregularities. She had no hypertension or other signs and symptoms of Cushing's syndrome. Plasma cortisol levels were greatly elevated and did not suppress normally in response to dexamethasone. Cortisol binding to transcortin was normal. Plasma androstenedione and testosterone levels were also increased, but 17-hydroxyprogesterone and aldosterone levels were normal. Further studies revealed an increased cortisol production rate, increased 24-h urinary cortisol excretion, increased plasma ACTH levels, a normal diurnal rhythm of cortisol at an elevated level, and normal increments of plasma ACTH, cortisol, GH, and PRL in response to insulin-induced hypoglycemia. The father and two brothers also had increased plasma cortisol levels, which did not suppress normally in response to dexamethasone. Chronic therapy with dexamethasone (at first 1 and later 0.5 mg, three times daily) for more than 30 weeks resulted in decreased hirsutism, normalization of scalp hair and menstrual cyclicity, and normal plasma testosterone and androstenedione levels. No signs or symptoms of Cushing's syndrome developed, and the central regulation of secretion of ACTH, cortisol, GH, and PRL (insulin test, diurnal rhythm) remained qualitatively normal at a lower set-point. We conclude that this patient had autosomal dominantly inherited hereditary (partial) cortisol insensitivity, which had resulted in increased adrenocortical cortisol and androgen secretion. The latter had not resulted in clinical symptoms in the three afflicted male members of the family, but had in the propositus. The results also indicate the potential usefulness of the insulin test in distinguishing this disorder from Cushing's disease.