Comprehensive Insights Into Pediatric Craniopharyngioma: Endocrine and Metabolic Profiles, Treatment Challenges, and Long-term Outcomes from a Multicenter Study

Objective: Craniopharyngiomas (CPG) have complex treatment challenges due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. The aim of this study was to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. A further aim was to highlight the difficulties associated with CPG management. Methods: Sixteen centers entered CPG patients into the ÇEDD NET data system. The clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features were evaluated. Results: Of the 152 evaluated patients, 64 (42.1%) were female. At presentation, the mean age was 9.1±3.67, ranging from 1.46 to 16.92, years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), and nausea and vomiting (7%). The surgical procedures were gross total resection (GTR) in 97 (63.8%) and subtotal resection in 55 (36.2%). Radiotherapy (RT) was initiated in 11.8% of the patients. Histopathological examination reported 92% were adamantinamatous type and 8% were papillary type. Postoperatively, hormone abnormalities consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated in 27 (17.8%). The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median (range) time of relapse was 1.82 (0.13-10.35) years. Relapse was related to longer followups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 (17.1%), neurological deficits in 13 (8.5%) and diabetes mellitus in 5 (3.3%) patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative RT. Challenges emerged for multidisciplinary regular follow ups. It is suggested that early interventions, such as dietary restrictions and increased exercise to prevent obesity, be implemented.

Adherence to Growth Hormone Treatment in Children During the COVID-19 Pandemic

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Methods: This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence). Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 µg/kg, the annual growth rate was 1.15 standard deviation score (minimum -2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased. Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

Clinical and therapeutic outcomes of pediatric pituitary adenomas: a single pituitary center experience.

PURPOSE: Pediatric pituitary adenomas (PPA) are rare. Although PPAs are mostly benign, they can be challenging to manage. Most studies evaluating PPA are based on surgical series. We aimed to present the clinical features, hormonal status and treatment outcomes of children with PPA managed in a joint neuroendocrine setting. METHODS: In this single-center study, demographic, clinical and endocrinological data of patients under 19 years old who were followed up with the diagnosis of PPA between 2002-2022 were retrospectively reviewed. A total of 21 studies published in the past 20 years were also systematically reviewed. RESULTS: There were 79 patients (52 girls, 27 boys) with a median age of 15.8 years. Median follow-up time was 30 months. The most common adenoma subtype was non-functioning adenoma (NFA) (35.5%), followed by prolactinoma (29.1%), corticotropinoma (21.5%), and somatotropinoma (13.9%), respectively. The frequency of micro and macroadenomas was almost equal while 38% of all adenomas were invasive. Headache, visual impairment and menstrual irregularity were the most common complaints, while the most common hormonal deficiency at diagnosis was central hypothyroidism (31.6%), followed by hypogonadotropic hypogonadism (22.7%), growth hormone deficiency (15.2%) and central adrenal insufficiency (11.4%), respectively. Fifty patients (63.2%) underwent endoscopic endonasal transsphenoidal surgery (EETS). Following the surgery, impaired endocrine functions recovered at a rate of 62% while permanent central diabetes insipidus was observed in 6%, and new onset hypopituitarism developed in 4%. CONCLUSION: NFA was more common in this cohort than in previous reports, which is one of the largest PPA series in the literature. Hormonal disorders, which were common at the time of diagnosis, were largely resolved with appropriate endocrinological and surgical approaches, while the rate of pituitary hormonal deficiencies after EETS was relatively low. Therefore, we recommend that children with PPA be managed in the setting of a high-volume pituitary center to provide long-term low morbidity.

Successful Management of Severe Hypercalcemia with Zoledronic Acid: A Report of Two Pediatric Cases.

Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with Zoledronic acid in the treatment of pediatric severe hypercalcemia. Here, we present two pediatric cases of severe hypercalcemia, one due to vitamin D intoxication and the second to malignancy, in which Zoledronic acid was used as the first-line bisphosphonate in the treatment. While both cases responded well to a single dose of Zoledronic acid, the second case experienced hypocalcemia requiring calcium treatment after Zoledronic acid infusion. Our report shows that Zoledronic acid may be an effective option in the treatment of severe pediatric hypercalcemia, although patients should be followed closely after infusion due to the risk of hypocalcemia. We provide additional published evidence for the effectiveness of Zoledronic acid in correcting severe pediatric hypercalcemia and hope this will encourage future studies with larger numbers of patients.

A case of adrenal insufficiency during multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a disease related to coronavirus disease 2019 (COVID-19). Although the effects of COVID-19 on many systems are known, there is limited data regarding its effects on the endocrine system. This study aimed to discuss the effect of COVID-19 on cortisol dynamics in a patient who developed adrenal insufficiency after COVID-19 infection. An 11-yr-old boy with polymerase chain reaction-proven COVID-19 one month previously was referred with a five-day history of fever, vomiting, and rash. On admission, he had hypotension, tachycardia, and severe hyponatremia. After the evaluation, he was diagnosed with MIS-C and glucocorticoid therapy was initiated. During follow-up, the patient experienced adrenal insufficiency, and hydrocortisone treatment was initiated at a crisis dose. Four months later, the adrenal axis function had not recovered. The adrenocortical response in COVID-19 patients may be significantly impaired, resulting in increased mortality or morbidity.

Ectopic parathyroid hormone as a rare aetiology of hypercalcemia with rhabdomyosarcoma: a new treatment strategy with zoledronic acid and Denosumab.

OBJECTIVES: Ectopic parathyroid hormone (PTH) secretion is rare in children with rhabdomyosarcoma, and only a few pediatric cases have been reported to date. Reports of the use of zoledronic acid (ZA) and Denosumab are limited for the treatment of hypercalcemia of malignancy (HCM) in the pediatric population. The aim of presenting this pediatric case of rhabdomyosarcoma accompanied by HCM, secondary to ectopic PTH secretion, was to highlight the benefits of ZA as a first-choice bisphosphonate in this situation with Denosumab as an alternative therapy. CASE PRESENTATION: The patient was diagnosed at 13 years with alveolar rhabdomyosarcoma. Multiple bone metastases first appeared at 15 years, but he remained normocalcemic until 17 years old when serum calcium was 15.1 mg/dL and PTH 249 pg/mL. While serum calcium responded well after ZA and Denosumab cycles, PTH remained elevated, reaching a peak value of 1851 pg/mL during treatment cycles. CONCLUSIONS: We report a patient with rhabdomyosarcoma accompanied by HCM, secondary to ectopic PTH, in whom the HCM was successfully managed with ZA and Denosumab. We believe that ZA should be the bisphosphonate of choice in pediatric HCM with rhabdomyosarcoma, while Denosumab may be another option in ZA-refractory cases.

Respiratory function in children with nephrotic syndrome: Comparative evaluation of impulse oscillometry and spirometry.

AIM: To evaluate the respiratory functions of children with nephrotic syndrome (NS) by impulse oscillometry (IOS) and its correlation with spirometry. METHODS: Fifty-five NS patients aged 3-18 years were included as the study group and 40 healthy children of the same age formed the control group. Patients were divided into nephrotic phase (first attack and relapse) and remission. Demographic, anthropometric, and laboratory data of the children were recorded. Respiratory functions were evaluated by IOS and spirometry. Children over 6-years old performed both IOS and spirometry while children under 6 years performed only IOS. RESULTS: The R (R5%, R10%, R5-20), AX and Z5% values of IOS in patients with nephrotic phase were higher than remission patients and control group while spirometry indices of PEF% and MEF25-75% were lower. Z scores of MEF25-75 were significantly negatively correlated with z scores of R5, R10, Z5, and Fres while they were significantly positively correlated with z scores of X values (5, 10, 15, and 20 Hz). Z scores of forced expiratory volume in 1 /forced vital capacity significantly negatively correlated with z scores of R values (R5, R10), Z5 and AX and positively correlated with z scores of X values (X5, X10, X15 Hz). CONCLUSION: Our study demonstrated that respiratory functions measured by IOS and spirometry were affected at the time of nephrotic phase in NS patients. IOS, a novel method easily applicable even in small children, is a potentially valuable tool to detect this condition; given its good correlation with spirometry.