Endocrine Abstracts

Introduction: Congenital hypopituitarism is a rare disease induced by mutations in transcription factors involved in the pituitary development or ubiquitous transcription factors. It can be associated with a malformative syndrome. We herein describe clinical and hormonal features of congenital hypopituitarism in two Tunisian families.

Observation 1: We report the case of three sisters, born at term to healthy consanguineous parents. The index case was referred at the age of 20 years for delayed growth. Physical examination showed a short stature with a height of 125 cm (< – 4 s.d.), an immature appearance, a high-arched palate, low blood pressure and female external genital organs with Tanner stage 1. Her bone age was seven years. On hormonal investigations, she had a combined pituitary hormone deficiency. The pituitary magnetic resonance imaging (MRI) found a pituitary hypoplasia. Her two sisters had the same clinical presentation. Molecular analysis of PROP1 concluded to a homozygous mutation in three sisters.

Observation 2: We report the case of two sisters, born at term to healthy consanguineous parents. The index case was referred at the age of 14 years for delayed growth. Physical examination showed a short stature with a height of 131 cm (between –3 and – 4 s.d.), a microcephaly, a saddle nose, a high-arched palate and female external genital organs with Tanner stage 1. Her bone age was eleven years. Hormonal investigations revealed a partial growth hormone deficiency, a corticotropin and gonadotropin deficiency. The pituitary MRI was normal. Her 8-year-old sister had an intellectual disability, and a delayed growth. She was 131 cm (< – 4 s.d.) and had a digital agenesis. Hormonal investigations only showed a corticotropin deficiency. The pituitary MRI was normal. Molecular analysis is still ongoing.

Conclusion: These two cases highlight the disparities of the phenotype presentation, sharing only the consanguinity and short stature in the siblings, motivating the investigations and leading to the diagnosis of congenital hypopituitarism. Molecular analysis is recommended for the genotypic diagnosis and guides the familial investigations and genetic counseling.