Gordon Holmes spinocerebellar ataxia: a gonadotrophin deficiency syndrome resistant to treatment with pulsatile gonadotrophin-releasing hormone
Gordon Holmes spinocerebellar ataxia: a gonadotrophin deficiency syndrome resistant to treatment with pulsatile gonadotrophin-releasing hormone
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DOI：
10.1046/j.1365-2265.1999.00859.x
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发表时间：
1999-10-01
影响因子：
3.2
通讯作者：
Bouloux, PMG
中科院分区：
文献类型：
--
作者：
Quinton, R;Barnett, P;Bouloux, PMG
Gordon Holmes脊髓小脑共济失调综合征（GHS）与特发性促性腺功能减退症（IHH）有关，关于原发性神经内分泌缺陷是下丘脑GnRH分泌（与IHH的大多数原因一样）还是垂体对GnRH作用的抵抗，文献中有相互矛盾的报道。由于垂体门静脉循环在解剖学上的不可达性，在人类受试者中直接测量GnRH水平是不可能的。以前的研究人员试图通过使用GnRH刺激测试来解开这个问题，这种方法的局限性可以解释所获得的不同结果。我们采用更生理的方法治疗男性GHS患者四周，GnRH， 7-10 μ g/脉冲，通过便携式微型泵以90分钟的频率皮下输送。这种疗法没有引起血浆促性腺激素和睾酮浓度的升高。相比之下，外源性促性腺激素治疗8周，维持生理血浆睾酮浓度，诱导睾丸增大，诱导精子发生。这些数据表明GHS的原发性内分泌病变是垂体促性腺激素分泌，而不是下丘脑GnRH，并且患者没有GnRH受体基因突变。两项临床观察与促性腺功能进行性退化相一致，而不是先天性促性腺激素缺乏症，首先，患者的发育在最初表现时在青春期中期早期被阻止，其次，在促性腺激素治疗期间，有效的精子发生被极快地诱导，这表明睾丸先前暴露于FSH。因此，脊髓小脑共济失调和垂体功能障碍可能在儿童期晚期就开始进化了。
The Gordon Holmes spinocerebellar ataxia syndrome (GHS) is associated with idiopathic hypogonadotrophic hypogonadism (IHH), There are conflicting reports in the literature as to whether the primary neuroendocrine defect is of hypothalamic GnRH secretion, as with most causes of IHH, or of pituitary resistance to GnRH action. Because of the anatomical inaccessibility of the hypophyseal portal circulation, direct measurement of GnRH levels in human subjects is not possible. Previous investigators have attempted to unravel this problem through the use of GnRH stimulation tests and the limitations of this approach may explain the differing results obtained. We used the more physiological approach of treating a male GHS patient for four weeks with GnRH, 7-10 mu g/pulse, delivered subcutaneously at 90 minute frequency via a portable minipump. This therapy failed to induce any rise in plasma gonadotrophin and testosterone concentrations. By contrast, eight weeks treatment with exogenous gonadotrophins maintained physiological plasma testosterone concentrations and induced testicular enlargement with induction of spermatogenesis. The data indicate that the primary endocrinopathy in GHS is of pituitary gonadotrophin secretion and not of hypothalamic GnRH, Moreover, the patient did not harbour any mutation of the GnRH receptor gene. Two clinical observations are consistent with progressive involution of gonadotrophic function, rather than a congenital gonadotrophin deficiency, First, the patient's development was arrested at early mid-puberty at the time of original presentation and, second, effective spermatogenesis was induced extremely rapidly during gonadotrophin treatment, suggesting prior exposure of the testes to FSH, Both spinocerebellar ataxia and pituitary dysfunction might thus have been in evolution since late childhood.