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.

Long-term Survival in a Child with Malignant Insulinoma After Liver Transplantation.

Insulinoma belongs to pancreatic neuroendocrine tumors and is immensely rare in children. The tumor leads to severe consequences of hypoglycemia caused by excessive insulin release. We report a pediatric patient with malignant insulinoma linked with liver transplantation due to metastases to this organ. A 13-year-old girl presented with symptoms of hypoglycemia due to hyperinsulinism. In computed tomography (CT), a polycyclic lesion in the head of the pancreas and enlarged lymph nodes were revealed. Modified Whipple's operation was performed, and histological examination confirmed pancreatic neuroendocrine tumor. CT of the body showed an enlarged liver with numerous metastases. Allogeneic liver transplantation was carried out successfully. Positron emission tomography-computed tomography (PET/CT) using 68Ga-DOTA-labeled somatostatin analogs at the age of 22 confirmed the complete metabolic remission. The patient currently remains under immunosuppressive and antiproliferative treatment. Multiple surgical interventions, liver transplantation combined with somatostatin analogs, and immunosuppressive medication could be effective in malignant insulinoma.

Pituitary Stalk Thickening: Causes and Consequences. The Children's Memorial Health Institute Experience and Literature Review.

Background: Pituitary stalk thickening (PST) is a rare abnormality in the pediatric population. Its etiology is heterogeneous. The aim of the study was to identify important clinical, radiological and endocrinological manifestations of patients with PST and follow the course of the disease. Materials and Methods: It is a study conducted in 23 patients (13 boys) with PST with/without central diabetes insipidus (CDI) diagnosed between 1990 and 2020 at Children's Memorial Health Institute (CMHI) in Warsaw, Poland. We analyzed demographic data, clinical signs and symptoms, radiological findings, tumor markers, hormonal results, treatment protocols and outcomes. Results: The median age at the diagnosis of PST was 9.68 years (IQR: 7.21-12.33). The median time from the onset of the symptoms to the diagnosis was 2.17 years (IQR: 1.12-3.54). The most common initially reported manifestations were polydipsia, polyuria and nocturia (82.6%); most of the patients (56.5%) also presented decreased growth velocity. Hormonal evaluation at the onset of PST revealed: CDI (91.3%), growth hormone deficiency (GHD) (56.5%), hyperprolactinemia (39%), central hypothyroidism (34.8%), adrenal insufficiency (9%), precocious puberty (8.7%). The majority of the patients were diagnosed with germinoma (seventeen patients - 73.9%, one of them with teratoma and germinoma). Langerhans cell histiocytosis (LCH) was identified in three patients (multisystem LCH in two patients, and unifocal LCH in one patient). A single case of atypical teratoid rhabdoid tumor, suspected low-grade glioma (LGG) and lymphocytic infundibuloneurohypophysitis (LINH). The overall survival rate during the observational period was 87.0%. Conclusions: The pituitary infundibulum presents a diagnostic imaging challenge because of its small size and protean spectrum of disease processes. Germinoma should be suspected in all children with PST, especially with CDI, even when neurological and ophthalmological symptoms are absent.

Pituitary stalk thickening in patients under 18 years of age - the most common causes and diagnostic procedures.

INTRODUCTION: Pituitary stalk thickening (PST) is a rare abnormality in children, and it may be challenging due to its diverse clinical picture. AIM OF THE STUDY: The aim of the study is to summarize the data on the causes and diagnostic procedures of PST. MATERIAL AND METHODS: Papers were searched in the PubMed database identifying published randomized clinical trials, reviews, systematic reviews, meta-analyses, and case reports. RESULTS: The most common causes of a thickened pituitary stalk in children are germ cell tumours (GCTs), Langerhans cell histiocytosis (LCH), and lymphocytic infundibulo-neurohypophysitis (LINH). Neurosarcoidosis, pituitary tuberculosis, granulomatosis, or specific inflammations were only reported in the paediatric population as case studies. PST mainly affects teenagers and is often detected with brain magnetic resonance imaging (MRI) in patients with central diabetes insipidus (CDI). It is not possible to differentiate the causes of PST with the use of the MRI image alone. Although various biochemical and oncological markers and other imaging tests are used, the diagnosis of PST remains a significant diagnostic challenge for clinicians. The final diagnosis is made based on histopathological examination. The indications for a biopsy are not uniform. Most experts, including the authors of the 2021 British consensus, recommend biopsy in the case of PST with a stalk lesion diameter ≥ 6.5-7 mm. CONCLUSIONS: The differential diagnosis of PST is a challenge. The diagnostic and treatment strategy should be individually adapted. Patients should be diagnosed in large clinical centres with experience in this field.