Which parameters predict the beneficial effect of GnRHa treatment on height in girls with central precocious puberty?

OBJECTIVE: Data about GnRHa on adult height in girls with central precocious puberty (CPP) have shown variable results, ranging from improvement of growth prognosis to lack of any benefit. This study was designed to delineate the criteria to decide which girls with idiopathic CPP (iCPP) will have a height benefit from GnRHa treatment. DESIGN: Retrospective PATIENTS: 102 girls with iCPP who had reached final height (FH) were included. MEASUREMENTS: Auxological, hormonal and radiological findings at treatment onset, and FHs were extracted from records. RESULTS: Most important factor affecting height gain was chronological age (CA) at treatment onset. All the girls treated ≤6.4 years of age achieved a height gain of ≥1SDS, while none of the girls treated ≥8.3 years of age made the target. 75.6% of patients who started GnRHa between the ages of 6.4 and 8.3 years had a height gain of ≥1SDS. Most important factors affecting height gain in those treated 6.4-8.3 years were advanced bone age (BA), basal estradiol (E2 ) and pubertal stage (r2 : 0.906; P < .001). All individuals with BA advancement of ≥2.6 years or E2 of ≥32.6 pg/ml or pubertal stage of ≥3 had significant height gain, and none of the cases with BA advancement of <2 years or E2 of <21.5 pg/ml or pubertal stage of <2 had a height gain of ≥1SDS. CONCLUSIONS: Treatment with GnRHa is unquestionably beneficial to improve FH in girls with iCPP when initiated ≤6.4 years of age. GnRHa treatment after 8.3 years of age may not improve FH. Girls between the ages of 6.4 and 8.3 years at presentation can have a better height gain if BA (≥2.6 years over CA) and pubertal findings (pubertal stage ≥3 or E2 ≥32.6 pg/ml) are well-advanced.

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency.

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11ß-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11ß-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11ß-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11ß-hydroxylase deficiency CAH.

Further expanding the mutational spectrum and investigation of genotype-phenotype correlation in 3M syndrome.

3M syndrome is characterized by severe pre- and postnatal growth retardation, typical facial features, and normal intelligence. Homozygous or compound heterozygous mutations in either CUL7, OBSL1, or CCDC8 have been identified in the etiology so far. Clinical and molecular features of 24 patients (23 patients and a fetus) from 19 unrelated families with a clinical diagnosis of 3M syndrome were evaluated and genotype-phenotype correlations were investigated with the use of DNA sequencing, chromosomal microarray, and whole exome sequencing accordingly. A genetic etiology could be established in 20 patients (n = 20/24, 83%). Eleven distinct CUL7 or OBSL1 mutations, among which eight was novel, were identified in 18 patients (n = 18/24, 75%). Ten patients had CUL7 (n = 10/18, 56%) while eight had OBSL1 (n = 8/18, 44%) mutations. Birth weight and height standard deviation scores at admission were significantly (p < 0.05) lower in patients with CUL7 mutation compared to that of patients with OBSL1 mutation. Two patients with a similar phenotype had a de novo 20p13p deletion involving BMP2. No genetic etiology could be established in four patients (n = 4/28, 17%). This study yet represents the largest cohort of 3M syndrome patients from a single center in Turkey. Microdeletions involving BMP2 may cause a phenotype similar to 3M syndrome with some distinctive features. Larger cohort of patients are required to establish genotype-phenotype correlations in 3M syndrome.

Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.

Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.

Biochemical markers of glucose metabolism may be used to estimate the degree and progression of iron overload in the liver and pancreas of patients with ß-thalassemia major.

The use of cardiac and hepatic T2* MRI measurements to predict the amount of iron accumulation in these organs has been studied extensively and was suggested to be used reliably. However, it may not be practical to screen other organs with MRI related to economical issues and also the prolonged imaging durations. Herein, we aimed to test the use of fasting glucose, fasting, and postprandial insulin, homeostasis model assessment-insulin resistance (HOMA-IR) (calculated as insulin (µIU/ml) × glucose (mg/dl)/22.5), and homeostasis model assessment B score (HOMA-B) (calculated as insulin (µIU/ml) × 20/glucose (mg/dl) - 3.5) to estimate the tissue iron measured with MRI. A total of 37 patients with ß-thalassemia major (BTM), age 20.8 ± 6.3 years (7.1-36.8), were enrolled. MRI measurements were done concomitantly to the biochemical tests for glucose metabolism. A positive correlation between HOMA-IR and hepatic iron loading and a negative correlation between pancreatic T2* and fasting blood glucose were found. A positive correlation was found between fasting insulin levels and pancreatic R2* measures. Additionally, a correlation was detected between cardiac and pancreatic iron accumulations. In centers where T2*/R2* MRI facilities are unavailable, fasting insulin, fasting glucose, and HOMA-IR measurements may be used to predict iron overload and may urge the physician for MRI assessment in case of a deterioration in these biochemical tests. Since hepatic iron loading correlated with insulin resistance development, the insulin resistance among patients with BTM may partially be explained with decreased hepatic insulin clearance from heavily iron-loaded liver.

Evaluation of hypothalamic-pituitary function in children following acute bacterial meningitis.

BACKGROUND: Previous studies in adults and case reports in children have shown increased frequency of hypothalamo-pituitary dysfunction after infectious diseases of the central nervous system. The aim of this study was to evaluate the function of hypothalamo-pituitary axis in children with a history of bacterial meningitis. METHODS: Patients diagnosed with bacterial meningitis between April 2000 and June 2011 was included. Baseline and stimulated hormonal tests were performed as required for hormonal evaluations following a diagnosis of meningitis. RESULTS: Pituitary function was assessed following a period of 8-135 months (mean 53 months) after bacterial meningitis. Thirty-seven cases (27 male, 15 pubertal) with mean age of 11.1 ± 4.4 years were included. Mean height SDS was 0.01 ± 1.07 and mean BMI SDS was 0.54 ± 1.15 all patients had a SDS above -2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal functions in all patients. Gonadotropin deficiency was not detected in any of the pubertal cases. Four cases (10.8%) had low IGF1 and IGFBP3 z-scores (<-2 SD) according to age, sex and Tanner stage, but peak GH response in clonidin test was >10 ng/ml in three of them suggesting neurosecretary dysfunction of GH in these cases. The fourth case has died before the test. No one had TSH deficiency and diabetes insipidus, only one case had mild hyperprolactinemia. CONCLUSIONS: Our findings suggest that hypothalamo-pituitary dysfunction is not as common in childhood as in adulthood. The most remarkable finding was neurosecretary dysfunction of GH in some cases.

Epidemiology of type 1 diabetes mellitus in children and adolescents: A 50-year, single-center experience.

BACKGROUND: Global variations in epidemiology of type 1 diabetes mellitus (T1DM) exist. This study is designed to examine demographic and clinical features of T1DM over the past 3 decades as well as evolving trends in epidemiology over last 50 years. METHODS: Clinical characteristics of 925 patients with T1DM over last 30 years (1990-2019) were evaluated and compared to previously published data of 477 patients diagnosed between 1969 and 1990 from one of the major referral centers for diabetes in Turkey. RESULTS: Mean age at diagnosis decreased from 9.5 ± 4.0 to 7.1 ± 3.6 years within the past 50 years (p < .001). Age at diagnosis peaked at 12-14 years between 1969 and 1990, then fell to 10-11.9 years between 1990 and 1999, and to 4-5.9 years between 2000-2009 and 2010-2019 (p = .005). Although the percentage of patients diagnosed <6 years of age is gradually increasing, the percentage between the ages of 6 and 11.9 years is decreasing, and the percentage diagnosed ≥12 years remained stable. A total of 47.5% of patients had ketoacidosis, 38.2% had ketosis, and 14.3% had only hyperglycemia. 23% of patients had severe diabetic ketoacidosis (DKA), whereas 42% had moderate. Over last 3 decades, there has been no change in frequency of ketoacidosis at presentation, but there has been significant decline in severity (p = .865, and p < .001, respectively). Although the frequency of patients with mild DKA increased over time, frequency of patients with moderate DKA decreased; however, no significant difference was observed among patients with severe ketoacidosis. DKA was more frequent and severe in patients <6 years of age (p = .005, and p < .001, respectively). CONCLUSION: Age at diagnosis shifted to younger ages in T1DM in the past 50 years. Half of patients had ketoacidosis at diagnosis and frequency of presentation with DKA did not decrease, but severity decreased slightly. Increase in prevalence of T1DM in the younger age group and the fact that half of patients present with DKA indicate that awareness should be increased in terms of early diagnosis and treatment.

DOCK8 deficiency with hypereosinophilia and the syndrome of inappropriate antidiuretic hormone secretion during herpes infection.

BACKGROUND: Hyperimmunoglobulin E syndrome (HIES) due to dedicator of cytokinesis8 (DOCK8) deficiency may present in infancy and childhood with different clinical features involving recurrent infections, allergic dysregulation, and autoimmunity. CASE: In this report, we describe a patient who first presented with severe hypereosinophilia and went on to develop the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in the context of a severe herpes infection. Investigation revealed the presence of underlying DOCK8 deficiency presenting with atypical clinical features. CONCLUSIONS: Distinct inflammatory features associated with infections may be seen in the course of primary immunodeficiency diseases, and early functional and molecular genetic tests will aid the proper management.

Challenges During the Coronavirus Disease 2019 Pandemic: Diabetes Control and Psychosocial Issues in Children with Type 1 Diabetes Mellitus and Their Mothers.

OBJECTIVE: Governments have enforced restrictions to prevent the spread of coronavirus dis- ease 2019, which has affected lifestyle and psychosocial well-being. The aim of this study is to examine the psychosocial dimensions of children with type 1 diabetes mellitus and lifestyle changes in the face of the pandemic. MATERIALS AND METHODS: Sixty school-aged children with type 1 diabetes mellitus were included to evaluate socioeconomic status, lifestyle changes, and psychological state after a 3-month school closure, using a questionnaire as well as scales in children and mothers [Depression-Anx iety-Stress Scale (short-form), Revised Child Anxiety-Depression Scale (parent-version), The Perceived Stress Scale in Children] via a Google® Form. The effect of pre-pandemic glycemic control on lifestyle and factors affecting HbA1c change were also investigated. RESULTS: The percentage of mothers having scale scores above the cutoff in terms of stress, anxiety, and depression were 18.3%, 23.3%, and 33.3%, respectively. Mother's and children's anxiety, depression, and stress scores were positively correlated. Employed mothers had higher depression scores. Paternal unemployment increased the anxiety of the mothers. Seventy-eight percent (n = 46) of the mothers thought that diabetes in their children increased the risk of coro- navirus disease 2019 infection, and children of these mothers had higher depression, anxiety, and stress scores(P = .01, P < .01, P < .01). The majority of participants were adversely affected by coronavirus disease 2019 in terms of daily routines and dietary compliance. Patients with poor-controlled type 1 diabetes mellitus deteriorated more in terms of diet compliance (P = .01). CONCLUSION: Coronavirus disease 2019 affects the psychosocial dimensions in the family of chil- dren with type 1 diabetes mellitus. The psychosocial impact is reflected within the family and may affect diabetic control. Thus, it should be handled within the context of family. The provi- sion of proper information and guidance to parents may be crucial to alleviate the psychosocial burden on the family during the pandemic.

Assessment of gonadotrophin suppression in girls treated with GnRH analogue for central precocious puberty; validity of single luteinizing hormone measurement after leuprolide acetate injection.

OBJECTIVE: Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of hypothalamic-pituitary-gonadal axis in the diagnosis of central precocious puberty (CPP) and in the assessment of pubertal suppression. However, this test is time-consuming, costly and uncomfortable for the patients. We aimed to analyse the validity of single LH sample 90 min after GnRH analogue (GnRHa) administration in the evaluation of gonadotrophin suppression during CPP therapy and to determine a cut-off level for LH indicating adequate suppression. DESIGN: Prospective study. PATIENTS AND METHODS: One hundred and forty-two patients with CPP were included in this study. Peak LH level during iv GnRH stimulation test after the third dose of GnRHa was compared with LH level 90 min after injection of the 3rd dose of GnRHa. RESULTS: There was a positive correlation between LH level following a GnRHa injection and peak LH during standard iv GnRH stimulation test (r = 0·83; P < 0·0001). A LH value of 2·5 mIU/ml or less 90 min after GnRHa injection was considered to be the cut-off for the determination of pubertal suppression (sensitivity and specificity was 100% and 88%, respectively). In 117 patients, gonadotrophin suppression was existed according to both GnRHa and iv GnRH tests. In 25 patients, gonadotrophin suppression was not found in the GnRHa test. However, 16 of them were suppressed according to the iv GnRH test. CONCLUSION: Single LH determination 90 min after GnRHa administration using a cut-off level of 2·5 mIU/ml reflects pubertal suppression with a high sensitivity and specificity. However, this test may fail to show pubertal suppression in some cases. Those patients who appear to be inadequately suppressed should be reassessed using standard iv GnRH stimulation test for optimal dose adjustment.

17beta-hydroxysteroid dehydrogenase type 3 deficiency as a result of a homozygous 7 base pair deletion in 17betaHSD3 gene.

17-beta-Hydroxysteroid dehydrogenase type 3 (17betaHSD-3) converts delta4 androstenedione (A) to testosterone (T) in the testes. This enzyme plays a key role in androgen synthesis and it is essential for normal fetal development of male genitalia. 17betaHSD-3 deficiency is a rare cause of 46,XY disorders of sexual development. Here, we report a 16-year-old 46,XY patient with 17betaHSD-3 deficiency raised as a female and significantly virilized in puberty. A homozygous 7 base pair deletion on exon 10 was determined in HSD17B3 gene (c.777-783del_GATAACC). Our patient had one of the very rare mutations, which was previously unencountered in Turkish patients with 17betaHSD type 3, and she is the second reported case with this deletion.

Feminizing Adrenocortical Tumors as a Rare Etiology of Isosexual/Contrasexual Pseudopuberty

Objective: Estrogen-secreting adrenocortical tumors (ACTs) are quite rare with feminizing adrenocortical tumors (FATs) accounting for 0.37-2% of all ACTs. The aim was to evaluate clinical and hormonal characteristics of FATS as well as treatment options and follow-up in the pediatric age group. Methods: Medical records of children with ACTs presenting to a single center in the last two decades were reviewed. Literature review within Pubmed revealed 34 pediatric patients (22 boys) with FAT among 192 articles. Results: Among the 25 children presenting with ACTs in the last two decades, two new pediatric cases of FAT were identified, one benign and the other malignant, in two genders with different clinical presentations. Literature review showed that FATs are extremely rare tumors that are most commonly seen in men and boys presenting with gynecomastia. FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. While boys present with contrasexual pseudopuberty signs, girls present with isosexual pseudopuberty. A high estrogen level strongly supports diagnosis, while elevations in other adrenal hormones may be seen. FATs are usually malignant in adults and prognosis is generally very poor. However, in children approximately half are benign although assessment of malignant potential depends on clinical behavior of the tumor. FATs are very unpredictable so even after surgery long-term follow-up is required. FATs presenting in childhood may have a better prognosis than adult presentation tumors as most FATs in children are followed without recurrence of tumor. Conclusion: FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. FATs in childhood may have a better prognosis than in adult males.

Apparent mineralocorticoid excess: A diagnosis beyond classical causes of severe hypertension in a child.

A genetic defect of 11 ß-hydroxysteroid dehydrogenase causes apparent mineralocorticoid excess syndrome. Since 50 days of life, our patient was hospitalized several times for various reasons including hypokalemia. At the age of 3.3 years, she was diagnosed with severe hypertension (160/120 mmHg). She also had left ventricular hypertrophy and hypertensive retinopathy and referred to our center. Her renal function and electrolytes were normal except for hypokalemia. She was on captopril treatment; nifedipine and propranolol were added. Plasma renin and aldosterone concentrations were 1.13 pg/ml (1-8.2 pg/ml) and 12.2 ng/dl (35-300 ng/dl), respectively. Severe hypertension, hypokalemia, low renin and aldosterone levels pointed to the diagnosis of apparent mineralocorticoid excess syndrome. Strict salt-restricted diet and potassium citrate were ordered. Genetic analysis of the HSD11B2 gene showed c.623G>A (p.Arg208His). Spironolactone was initiated. On follow-up, amiloride was added and her blood pressure was controlled. In patients with severe HSD11B2 mutation, combination therapy of spironolactone with amiloride could be effective in controlling blood pressure.

Hyperinsulinism May Be Underreported in Hypoglycemic Patients with Phosphomannomutase 2 Deficiency

Objective: Phosphomannomutase 2 deficiency (PMM2-CDG) is a disorder of protein N-glycosylation with a wide clinical spectrum. Hypoglycemia is rarely reported in PMM2-CDG. In this study, we evaluated cause, treatment options and outcomes in cases with hypoglycemia in the course of PMM2-CDG. Methods: Clinical records of patients followed with PMM2-CDG within the last two decades were reviewed. Medical data of patients with hypoglycemia were evaluated in more detail. Demographic and clinical findings, organ involvement and laboratory investigations at time of hypoglycemia were recorded. Time of first attack of hypoglycemia, cause, treatment modalities, duration of hypoglycemia (permanent/transient), and duration of treatment, as well as outcome were also recorded. Other published cases with PMM2-CDG and hypoglycemia are also reviewed in order to elucidate characteristics as well as pathophysiology of hypoglycemia. Results: Nine patients with PMM2-CDG were reviewed, and hypoglycemia was present in three cases. All three had hyperinsulinism as the cause of hypoglycemia. In the first two cases reported here, serum insulin level concurrent with hypoglycemic episodes was elevated, and glucose response was exaggerated during glucagon test, favoring hyperinsulinism. However, in the third case, the serum insulin level at time of hypoglycemia was not so high but hypoglycemia responded well to diazoxide. Hyperinsulinism was permanent in two of these three cases. No genotype-phenotype correlation was observed with respect to hyperinsulinism. Conclusion: The main cause of hypoglycemia in PMM2-CDG appears to be hyperinsulinism. Although insulin levels at the time of hypoglycemia may not be very high, hypoglycemia in patients with PMM2 responds well to diazoxide.

Persistent hypoglycemia caused by umbilical arterial catheterization.

Hypoglycemia as an umbilical artery catheter (UAC) complication is rare. We present a neonate with hyperinsulinemic hypoglycemia due to a high-positioned UAC used inadvertently for parenteral nutrition. The aim of this report is to increase physicians' awareness of the possibility of this rare complication.

Two pediatric patients with Von Hippel-Lindau disease type 2b: from patient to screening, from screening to patient.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease characterized by the development of hemangioblastomas of the brain, spinal cord and retina; pheochromocytomas and renal cell carcinoma. The disease is caused by mutations in the VHL tumor suppressor gene located on chromosome 3p26-p25. In this paper, we present two patients with VHL disease type 2B confirmed by genetic analysis. Diagnosis in the first patient was based on demonstration of retinal hemangioblastoma in association with bilateral pheochromocytoma. Family screening revealed renal cell carcinoma in her father and uncle. The second patient was discovered during family screening of another index case in adult age. VHL disease should be clinically suspected in any individual with a pheochromocytoma especially when there is bilateral and/or multifocal disease or family history. Screening of patients and at-risk family members for VHL-associated tumors should be essential in management of VHL.

Alpha-Melanocyte-Stimulating Hormone is Elevated in Hypothalamic Obesity Associated with Childhood Craniopharyngioma.

OBJECTIVE: The purpose of this study was to investigate the peripheral concentrations of leptin and neuropeptides taking part in the melanocortin pathway in hypothalamic obesity (HO) associated with craniopharyngioma (CP) and to find a peripheral marker for diagnosis. METHODS: Thirty-one patients (52% girls; median age 16 years) with CP were enrolled in the study group. They were grouped as CP with obesity (CPobesity , n = 17) and CP without obesity (CPnonobesity , n = 14). Two control groups without CP consisted of 27 children with obesity (OC) (55% girls; median age 13.8 years) and 25 children without obesity (normal control [NC]) (72% girls; median age 14.5 years). Obesity was defined as BMI percentile ≥ 95%. Fasting serum concentrations of leptin, brain-derived neurotrophic factor (BDNF), and alpha-melanocyte-stimulating hormone (α-MSH) were measured in the groups. RESULTS: Leptin and BDNF concentrations were correlated with BMI SD score (SDS) in controls (OC + NC) and CP. However, there was no correlation between α-MSH and BMI-SDS in CP or control groups. After adjusting for age, sex, and BMI-SDS, α-MSH was found to be significantly higher in CPobesity than in other groups, whereas leptin and BDNF were comparable among the four groups. CONCLUSIONS: Serum BDNF, just like leptin, increased with BMI, regardless of hypothalamic damage. On the contrary, α-MSH concentration was significantly high in HO, designating a potential biomarker for HO in CP.

Approach to pheochromocytoma and paraganglioma in children and adolescents: A retrospective clinical study from a tertiary care center.

AIM: Pheochromocytoma (PCC) and paraganglioma (PGL) are rare tumors in childhood. They are catecholamine secreting tumors and present with signs or symptoms related to their excess. Most common signs and symptoms are hypertension, headache and diaphoresis. The management of children usually depend on experience of adulthood. This study is conducted to present the clinical characteristics, surgical management and outcome of childhood PCC and PGL in a tertiary care center. MATERIAL AND METHODS: We reviewed clinical records of all patients operated for PCC and PGL between 2000 and 2020 retrospectively. RESULTS: There were 18 children operated for PCC and PGL in the study period. The female to male ratio was 1:1. The median age at diagnosis was 13 (IQR, 9-15) years. The most common presenting symptoms were headache and diaphoresis. Hypertension was the most common sign. Three patients had von Hippel-Lindau (VHL). Tumors of two patients with VHL were detected during routine follow-up. Three patients had multifocal disease. Medical preparation for surgery was carried out in all patients. Antihypertensive treatments were administered preoperatively. Since the patients are at risk for postoperative hypotension due to chronic vasoconstriction and blood volume contraction, high salt diet was recommended. Intravenous normal saline at a rate of 3000 ml/m2 body surface area per day was started for intravascular volume expansion preoperatively. The mean duration for preoperative medication to achieve normal blood pressure was 22 days (range, 16-30). Twenty-five tumors were excised in eighteen patients. One patient who had bone metastases on diagnosis and is on I131MIBG therapy. The median follow-up time was 5.6 years (range, 1 months - 21 years). Five patients reached adulthood during the study period. Four of these had recurrent metastases (n = 2) and new tumors (pancreatic neuroendocrine tumor, n = 1 and pancreatic neuroendocrine tumor and renal cell carcinoma, n = 1) after the age of 18. CONCLUSION: Multidisciplinary approach is necessary to achieve safe surgical treatment and surveillance of PCC and PGL. Detection of associated familial cancer susceptibility syndromes and long-term follow-up is essential to detect late recurrences and new tumors.

Adrenocortical tumours in children: a review of surgical management at a tertiary care centre.

BACKGROUND: Adrenocortical tumours (ACT) are rare tumours of childhood usually presenting with endocrine dysfunction. This retrospective study is designed to review our institutional experience in surgical management. METHODS: Records of children treated for ACT between 1999 and 2019 were reviewed retrospectively. RESULTS: The median age of 24 children was 78 months. Fourteen patients had adrenocortical carcinoma, nine had adrenocortical adenoma and one had neuroendocrine differentiation of ACT. Endocrine dysfunction was noted in 79% of the patients. Five patients had preoperative chemotherapy but none had a decrease in tumour size. Transabdominal approach was used in all but two patients who had thoracoabdominal incision for excision of giant tumours and ipsilateral lung metastases. Two patients had visceral excision to achieve R0 resection. Five patients, four of whom had spillage and one with partial resection died of widespread disease. Two patients with stage 4 adrenocortical carcinoma are still on chemotherapy. All patients with stage I-III disease who had total excision without spillage (n = 17) are disease-free for 2-170 months. CONCLUSIONS: Our results show the importance of excision in ACT without spillage for survival. However, multicentre prospective studies should enhance the knowledge of children about ACT and develop alternative therapies for stage III and IV cases.

Growth hormone deficiency due to traumatic brain injury in a patient with X-linked congenital adrenal hypoplasia.

X-linked adrenal hypoplasia congenita (AHC) is characterized by primary adrenal insufficiency and is frequently associated with hypogonadotropic hypogonadism (HH). The production of other pituitary hormones (adrenocorticotropic hormone [ACTH], growth hormone [GH], thyroid-stimulating hormone [TSH], and prolactin [PRL]) is usually normal. Mutations of the DAX-1 gene have been reported in patients with AHC and HH. We present a 13-year-old male patient with AHC caused by a nonsense mutation in the DAX-1 gene who developed GH deficiency following head trauma. He showed signs of adrenal insufficiency at the age of 23 months, and glucocorticoid and mineralocorticoid treatment was started. His parents reported head trauma due to a traffic accident at the age of 21 months. Adrenal computed tomography revealed hypoplasia of the left and agenesis of the right adrenal gland. Decreased growth rate was noted at the age of 12.5 years while receiving hydrocortisone 15 mg/m2/day. His height was 139.9 cm (-1.46 SD), body weight was 54.9 kg, pubic hair was Tanner stage 1, and testis size was 3 ml. His bone age was 7 years. His gonadotropin (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and testosterone levels were prepubertal. The evaluation of GH/insulin-like growth factor-1 (IGF-1) secretion at the age of 13 years revealed GH deficiency. Pituitary magnetic resonance imaging demonstrated a hypoplastic hypophysis (< 2.5 mm) and a normal infundibulum. GH treatment (0.73 IU/kg/week) was started. This paper reports a patient with genetically confirmed AHC demonstrating GH deficiency possibly due to a previous head trauma. Complete pituitary evaluation should be performed in any child who has survived severe traumatic brain injury.