Occurrence of Hypopituitarism in Tunisian Turner Syndrome patients: familial versus sporadic cases

Abstract

Objective

To explore unusual association between Turner Syndrome (TS) and Hypopituitarism in a Tunisian cohort.

Methods

We reported 6 patients with TS associated to Hypopituitarism, including three familial cases except the fourth sister who showed only a TS phenotype. Biochemical analysis, resonance magnetic imaging and cytogenetic analyses were performed.

Results

The average age of our patients was 17.2 years (11–31 years). They were all referred for short stature and pubertal delay, except for the fourth sister who presented spontaneous puberty with the integrity of the pituitary axis and the presence of an X ring chromosome. Karyotype analysis showed monosomy in 3 cases and a mosaic TS in the 3 remaining cases, including one patient with abnormal X chromosome structure. Somatotropic and corticotropic deficiencies were confirmed in 2 sporadic cases while the gonadotropic and thyrotropic axes were spared. In contrast; familial cases were consistently affected by the integrity of the corticotropic axis. MRI showed pituitary hypoplasia in all familial cases and pituitary stalk interruption syndrome in only one sporadic case. No correlation was found between the chromosome formula and the anterior pituitary involvement.

Conclusion

Co-segregation of congenital Hypopituitarism with pituitary hypoplasia and X chromosome aberrations could imply a molecular anomaly of transcription factors responsible for the differentiation and development of pituitary cells such as PROP1, POUF1, Hesx1, Lhx3, Lhx4. The etiopathogenic link between X chromosome abnormalities and the occurrence of Hypopituitarism remains unclear; however, the progress of molecular biology may clarify the interrelation between transcription factors and sex chromosome segregation abnormalities.

突尼斯特纳综合征患者垂体功能减退症的发生：家族性与散发病例对照 摘要

目的：在突尼斯队列中探索特纳综合征 (TS) 与垂体功能减退症之间非同寻常的关联。

方法：我们报告了 6 例与垂体功能减退症相关的特纳综合征患者, 包括 3 例家族性病例, 除了第四位妹妹仅显示 TS 表型。并对她们进行了生化分析、共振磁成像和细胞遗传学分析。

结果：我们患者的平均年龄为 17.2 岁（11-31 岁）。他们都因身材矮小和青春期发育延迟而被转诊, 除了第四个妹妹出现自发性青春期, 垂体轴完整且存在 X 环染色体。核型分析显示 3 例为单体性, 其余 3 例为嵌入型特纳综合征, 其中 1 例患者 X 染色体结构异常。

在 2 例散发性病例中证实了促生长素和促肾上腺皮质素缺乏, 而促性腺激素和促甲状腺素轴却没有受到影响。相比之下；家族性病例始终受到促皮质轴完整性的影响。 MRI显示所有家族性病例均有垂体发育不全, 仅有1例散发性垂体柄中断综合征。未发现染色体公式与垂体前叶受累之间存在相关性。

结论：先天性垂体功能减退与垂体发育不全和 X 染色体突变的共同分离可能意味着负责垂体细胞分化和发育的转录因子的分子异常, 如 PROP1、POUF1、Hesx1、Lhx3、Lhx4。

X 染色体异常与垂体功能减退发生之间的病因联系尚不清楚；然而, 随着分子生物学的进步可能会阐明转录因子与性染色体分离异常之间的相互关系。

Keywords:

• Familial Hypopituitarism
• Familial Turner Syndrome
•  factors
•  correlation

Acknowledgments

We are indebted to the patients who participated in the study and their corresponding family members for invaluable cooperation. This work was supported by the Tunisian Ministry of Public Health. We thank Mr. Kamel Maaloul for his critical reading of this paper.

Disclosure statement

No potential conflict of interest was reported by the author(s).