Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma - case series and literature review.

INTRODUCTION: Adrenocortical carcinoma (ACC) is rare and an aggressive tumour. Mitotane is the mainstay adjuvant drug in treating ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological complications during mitotane therapy. MATERIAL AND METHODS: This retrospective study enrolled 4 patients with ACC treated with mitotane therapy complicated by PP. We analysed clinical manifestations, radiological, histopathological findings, and hormonal results. RESULTS: The median age at the diagnosis of ACC was 1.5 years. All patients were treated with surgery and mitotane, accompanied by chemotherapy regimens in 2 cases. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, and hormonal and imaging tests. In one patient, incomplete peripheral PP was followed by central PP. The median time from the therapy initiation to the first manifestations of PP was 4 months. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In 2 patients, hypothyroidism was diagnosed. All patients presented neurological symptoms of varying expression, which were more severe in younger children. CONCLUSIONS: The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be highlighted. Some patients require levothyroxine replacement therapy. The neurotoxicity of mitotane is a significant clinical problem.

Growth hormone improves short stature in children with Shwachman-Diamond syndrome.

INTRODUCTION: Shwachman-Diamond syndrome (SDS) is a rare, autosomal recessive multisystemic disorder characterized by pancreatic insufficiency and bone marrow failure. Short stature is a recognized feature of SDS syndrome; however, systemic data concerning recombinant human growth hormone (rGH) treatment are limited. Aim of the study: To assess the effect of rGH treatment in patients with SDS. MATERIAL AND METHODS: Retrospective data were collected from patients with SDS and growth hormone deficiency (GHD) treated with rGH in the Children's Memorial Health Institute in Warsaw. The annual growth velocity (GV) and height standard deviation score (SD) were compared for up to 2 years of rGH treatment. RESULTS: Six SDS patients (M : F = 1 : 5) treated with rGH were identified. The median age of starting rGH therapy was 7.5 years, with a mean baseline height SD of -4.06 (range: -6.3 to -2.3 SD). The height SD significantly improved to -3.3 (p = 0.002) and then -3.03 (p = 0.002), following 1 and 2 years of treatment, respectively. The average GV for the patients prior to starting treatment was 4.9 cm/year (range: 3.1-6.5 cm/year), which significantly improved to 7.6 cm/year (range: 5.7-9.6 cm/year) after 1 year of rGH treatment (p = 0.020) and to 6.7 cm/year at the end of 2 years. CONCLUSIONS: Our study has shown that rGH treatment significantly improves the height SDS and GV of patients with SDS and GHD without any side effects. Further research is required to analyse the long-term effect of rGH therapy in patients with SDS.

Endocrine dysfunction in children with Shwachman-Diamond syndrome.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Somatic development in children with Shwachman-Diamond syndrome.

BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare genetic, multi-systemic disease characterized by exocrine pancreatic insufficiency, immune deficiency, bone marrow failure and skeletal abnormalities. Most patients present with failure in somatic development and short stature, but systematic data concerning those features are limited. The aim of the study was to assess the prevalence of failure in somatic development in the children with SDS. METHODS: An analysis of anthropometric measurements of 21 patients (14 girls and 7 boys),aged 2 to 17 years (mean age 6.3 years) with SDS diagnosed in The Children's Memorial Health Institute in Warsaw, Poland was performed. The patients were measured using a Holtain Limited stadiometer, an electronic scale, a Harpenden anthropometer, a metric tape and a spreading caliper. The assessed anthropometric parameters were expressed as standard deviation scores in relation to the reference values in Poland, suitable for sex as well as calendar and growth age. RESULTS: A total of 66 measurements was collected and analyzed with a median number of 3 observations per patient. The group of boys presented with a significantly lower height (- 3.0 SD, p < 0.0001) and BMI (- 1.4 SD, p < 0.00001), and in the relation to the growth age a lower weight (- 1.0 SD, p < 0.001) as well as a smaller chest width (- 0.9 SD, p < 0.05), hip width (- 0,5 SD, p < 0,05) and lower limb length (- 0,5 SD, p < 0,05). The group of girls also showed significantly lower height (- 2.6 SD, p < 0.00001) and BMI (- 0.8 SD, p < 0.00001), and in relation to the growth age, lower weight (- 0.5 SD, p < 0.001) as well as decreased width of the chest (- 1.7 SD, p < 0.0001) and shoulder (- 1.0 SD, p < 0.001) were observed. Boys and girls were also characterized by significantly decreased circumference and width of head, additionally, girls had also smaller head length. CONCLUSIONS: Patients with SDS have abnormal somatic development. Both boys and girls are characterized by short stature, decreased weight, BMI, leg length, chest width as well as circumference and width of head. Anthropometric measurements provide important data on the process of growth and body proportions in children with SDS.

Ki67 as a prognostic factor of craniopharyngioma's recurrence in paediatric population.

PURPOSE: Craniopharyngioma is one of the most frequent benign tumours of the central nervous system in the paediatric population. Although it is a benign tumour according to the WHO classification, it significantly deteriorates the patient's quality of life. The aim of this study is to assess if proliferation index Ki67 can be a useful marker of the risk of craniopharyngioma's recurrence. METHODS: Expression of Ki67 was examined in 85 specimens of primary craniopharyngioma and in 11 specimens of the recurring tumour. In all the cases, adamantinomatous type of craniopharyngioma was diagnosed. Values of Ki67 expression were compared between patients with and without recurrence, between patients with progression and relapse and between primary and recurrent tumours. RESULTS: No statistically significant differences were found between proliferation index Ki67 values in tumours with recurrence and without (median values 2.5% and 3%, respectively, p = 0.69). The median value of proliferation index Ki67 in progression group was 1% and in the relapse group 4%; no statistical significance between those groups was found (p = 0.067). The median value of proliferation index Ki67 in primary tumours was 3% (0-20%) and in recurrent tumours it was 5% (0-14%). Despite the lack of statistical significance (p = 0.61), a tendency towards higher values of Ki67 in recurring tumours in comparison with primary tumours was shown. CONCLUSIONS: Proliferation index Ki67 is not a reliable prognostic factor of craniopharyngioma's recurrence.