We present a Caucasian male patient who was diagnosed with Kallmann syndrome (KS) at age 15 years. Testosterone treatment was started. At age 26 the patient presented with mild headache. MRI revealed two separate pituitary adenomas along with the absence of the olfactory bulbs. Given the presence of marked hyperprolactinemia (17x upper limit of the reference range) the diagnosis prolactinoma was made and treatment with cabergoline was started which resulted in a complete biochemical response and in marked reduction of both adenomas in size. Hypogonadism persisted and testosterone replacement therapy was continued. Genetic testing of genes associated with pituitary tumors, Kallmann syndrome and idiopathic hypogonadotropic hypogonadism was negative. Mild concomitant hypercalcemia in accordance with familial hypocalciuric hypercalcemia (FHH) prompted mutation analysis of the calcium receptor (CASR) gene which yielded a pathogenic inactivating variant.
The presence of two separate prolactinomas in a patient with KS has not yet been reported in the literature. The effect of sex hormone treatment of KS patients on the possible development of prolactinoma is unknown at present. The occurance of multiple prolactinomas in our patient suggests increased susceptibility. Although CaSR is expressed in GnRH neurons in mouse brain and CaSR deficient mice have a reduced hypothalamic GnRH neuronal population, the relevance of the CASR gene variant in our patient for the KS phenotype is unclear at present.
■我们介绍了一名白人男性患者,他在15岁时被诊断患有Kallmann综合征(KS)。开始睾酮治疗。患者26岁时出现轻度头痛。MRI显示两个单独的垂体腺瘤,并且没有嗅球。鉴于存在明显的高催乳素血症(参考范围的17倍上限),可以诊断为催乳素瘤,并开始使用卡麦角林进行治疗,从而导致完全的生化反应,并且两个腺瘤的大小均显着减少。性腺功能减退持续存在,睾酮替代疗法继续进行。与垂体瘤相关基因的基因检测,Kallmann综合征和特发性低促性腺激素性性腺功能减退症阴性。根据家族性低钙血症高钙血症(FHH),轻度伴随高钙血症提示钙受体(CASR)基因的突变分析,产生致病性失活变体。
■在患有KS的患者中存在两个独立的泌乳素瘤尚未在文献中报道。目前尚不清楚KS患者性激素治疗对泌乳素瘤可能发展的影响。我们患者的多发性泌乳素瘤的发生表明易感性增加。尽管CaSR在小鼠大脑的GnRH神经元中表达,但CaSR缺陷小鼠的下丘脑GnRH神经元数量减少,目前尚不清楚我们患者的CASR基因变异与KS表型的相关性.