Endocrine dysfunction in children with Shwachman-Diamond syndrome

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by pancreatic exocrine insufficiency, immune deficiency, bone marrow failure, and bone malformations. Systematic data concerning endocrine function in SDS are limited. We studied patients diagnosed in The Children's Memorial Health Institute in Warsaw, Poland, to assess the prevalence of various endocrinopathies.

In the pilot study, retrospective data were collected for 5 patients with SDS. Subsequently, patients with SDS aged 3-16 years were recruited prospectively. In total, 19 patients with mutations in the SBDS gene were studied. Data were collected on anthropometric measurements, systemic screening tests of pituitary, thyroid, adrenal, pancreatic, and gonadal function, as well as bone mineral density. Descriptive statistics were tabulated and group differences assessed.

Twelve patients (63%) had ≥ 1 endocrine disorder, including growth hormone dysfunction (10 patients, 53%), hypothyroidism (2 patients, 10%), congenital hypopituitarism (1 patient, 5%), and/or type 1 diabetes mellitus (T1DM) (1 patient, 5%). The group of boys presented with a significantly lower height (-2.1 SD, p < 0.0001) and BMI (-1.0 SD, p < 0.00001). The group of girls also showed significantly lower height (-2.6 SD, p < 0.00001) and BMI (-0.7 SD, p < 0.0001). All patients had significantly lower height than their mid-parental height. Delayed bone age was found in 15 patients (84%) and osteopaenia in 12 of 15 patients (80%).

Endocrine dysfunctions are common in SDS, especially growth hormone (GH) deficiency. Children with poor growth can benefit from an endocrinological evaluation and tests for GH deficiency. Bone mineral density measurements should be a part of a routine screening. Longitudinal studies are needed to better understand the aetiology and true prevalence of these disorders.