International Journal of Pediatric Endocrinology最新文献

Background: Gonadotropin releasing hormone agonists (GnRHa) are well established as a standard of care for the treatment of central precocious puberty (CPP) worldwide. While numerous delivery systems and routes of administration exist, depot intramuscular injections or sustained-release preparations have been most widely used. Leuprolide acetate is well tolerated among children though some can develop some complications.

Case presentation: We present a case report of a 6.5 year old girl with central precocious puberty who developed signs of pseudotumor cerebri after 2 doses of leuprolide acetate 3.75 mg given monthly. Systemic exam and other tests to look for the cause did not yield anything. However, fundoscopy showed marked papilloedema with blurred disc margins. After six weeks' treatment with acetazolamide and withdrawal of the GRNHa the papilloedema resolved.

Conclusions: If a patient presents with complaints such as headache, nausea, vomiting, and double vision in pediatric patients treated with GnRH analogue one should highly consider the presence of pseudotumor cerebri and fundus examination be performed.

Background: Fanconi-Bickel syndrome (FBS) is a rare condition of carbohydrate metabolism, caused by a recessive defect in the facilitative glucose transporter GLUT2 encoded by the SLC2A2 gene and characterized by a wide spectrum of phenotypical features. There is a paucity of reported data on FBS from Sub-Saharan Africa. Here, we describe the clinical, biochemical and genetic characteristics of our patients with FBS from Sudan, a country with a high consanguinity rate.

Patients & methods: Eleven patients from ten unrelated Sudanese families were included. Clinical & biochemical data were documented and imaging studies done including bone survey and abdominal ultrasound. Liver biopsy was done to confirm the pathological diagnosis in 45% of cases and molecular genetics was performed through contribution with the Exeter genomics laboratory for ten patients.

Results: Reported consanguinity was 70% among our patients. Growth was significantly impaired at presentation with mean weights of (-5.3 ± 1.8) SD and heights (-5.4 ± 2.5) SD. Severe chest deformity was present in (27%) and all patients showed features of rickets at presentation. Three patients had neonatal diabetes requiring insulin therapy of which one has been reported before. Six families lost undiagnosed siblings with similar clinical presentations. We identified a total of four homozygous pathogenic SLC2A2 variants in our patients, one of whom had a novel mutation.

Conclusions: FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals' awareness. This is the first series to describe this condition from Sub-Saharan Africa.

Background: Growth hormone (GH) deficiency is common in patients with Prader-Willi syndrome (PWS) and leads to short adult stature. The current study assessed clinical outcomes based on real-world observational data in pediatric patients with PWS who were treated with GH.

Methods: Data from patients previously naïve to treatment with GH who began therapy with somatropin were collected from 2006 to 2016 in the observational American Norditropin® Studies: Web-Enabled Research (ANSWER) Program® and NordiNet® International Outcome Study. Variables affecting change from baseline in height standard deviation scores (HSDS; n = 129) and body mass index standard deviation scores (BMI SDS; n = 98) were determined.

Results: Patients included in both HSDS and BMI SDS analyses were treated with a mean GH dose of 0.03 mg/kg/d (SD, 0.01 mg/kg/d). Results from the HSDS analysis revealed that baseline age and years on treatment had a significant impact on the change in HSDS. In the BMI SDS analysis, longer GH treatment time led to a greater change in BMI SDS from baseline, and patients with a higher BMI at the start of treatment had a greater decrease in BMI over time.

Conclusions: GH is effective in the management of children with PWS. Earlier treatment resulted in a greater gain in height, and a longer treatment period resulted in better outcomes for both height and BMI.

Trial registration: This study was registered with ClinicalTrials.gov ( NCT01009905 ) on November 9, 2009.

Background: Xq duplication is a rare condition with a very variable phenotype, which could mimic other genetic syndromes involving the long arm of chromosome X. Sometimes short stature and diminished ovarian reserve (DOR) may be present. Treatments with rGH (Recombinant growth Hormon) or with fertility preservation strategies have not been previously described.

Case presentation: We present the case of a female with a novel de novo Xq partial duplication (karyotype: 46,Xder(X)(qter→q21.31::pter→qter) confirmed by array-CGH analysis. She presented with short stature, Nonverbal Learning Disability, developmental delay during childhood, severe scoliosis, spontaneous onset of menarche and irregular menstrual cycles. AMH (Anti-Müllerian Hormone) allowed detection of a preserved but severely diminished ovarian reserve with a POI (Premature Ovarian insufficiency) onset risk. She was effectively subjected to fertility preservation strategies and rGH therapy. We also reviewed other published cases with Xq duplication, reporting the main clinics characteristics and any adopted treatment.

Conclusions: rGH treatment and cryopreservation in a multidisciplinary approach are good therapeutic strategies for Xq duplication syndrome with short stature and premature ovarian failure.

Background: Congenital Hyperinsulinism (CHI) is an important cause of severe hypoglycaemia in infancy due to excessive, dysregulated insulin secretion. In focal CHI, a localised lesion within the pancreas hypersecretes insulin and, importantly, hypoglycaemia resolution is possible through limited surgical resection of the lesion. Diagnosis of focal CHI is based on a crucial combination of compatible genetics and specialised imaging. Specifically, a focal lesion arises due to a paternal mutation in one of the ATP-sensitive potassium channel genes, KCNJ11 or ABCC8, in combination with post-zygotic loss of maternal heterozygosity within the affected pancreatic tissue. 6-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (¹⁸F-DOPA) positron emission tomography (PET)/computed tomography (CT) imaging is used to detect and localise the lesion prior to surgery. However, its accuracy is imperfect and needs recognition in individual case management.

Case presentation: We report the case of an infant with hypoglycaemia due to CHI and a paternally inherited KCNJ11 mutation, c.286G > A (p.Ala96Thr), leading to a high probability of focal CHI. However,¹⁸F-DOPA PET/CT scanning demonstrated diffuse uptake and failed to conclusively identify a focal lesion. Due to unresponsiveness to medical therapy and ongoing significant hypoglycaemia, surgery was undertaken and a small 4.9 × 1.7 mm focal lesion was discovered at the pancreatic neck. This is the second case where this particular KCNJ11 mutation has been incorrectly associated with diffuse ¹⁸F-DOPA uptake, in contrast to the correct diagnosis of focal CHI confirmed by pancreatic biopsy.

Conclusions: Identifying discrepancies between genetic and imaging investigations is crucial as this may negatively impact upon the diagnosis and surgical treatment of focal CHI. This case highlights the need for pancreatic biopsy when a strong suspicion of focal CHI is present even if ¹⁸F-DOPA imaging fails to demonstrate a discrete lesion.

Case presentation: We report for the first time a synchronous papillary and follicular thyroid carcinoma in a 12-year-old girl presenting with a large (5 cm diameter) left thyroid nodule, an increased left and right upper pole technetium tracer uptake at scintigraphy and hyperthyroidism. The uptake at the right lobe was explained by the crossing of the left nodule to the right site of the neck at Computed Tomography (CT) scanning.

Background: Although thyroid nodules are less common in children than in adults, there is more vigilance required in children because of the higher risk of malignancy. According to literature, about 5% of the thyroid nodules in adults are malignant versus 20-26% in children. The characteristics of 9 other pediatric cases with a differentiated thyroid carcinoma presenting with a toxic nodule, which have been reported during the last 20 years, are summarized. A nodular size of more than 3.5 cm and female predominance was a common finding.

Conclusions: The presence of hyperthyroidism in association with a hyperfunctioning thyroid nodule does not rule out thyroid cancer and warrants careful evaluation, even in the absence of cervical lymph node invasion.

Background: Antifungals act on fungal sterols structurally similar to human cholesterol. Ketoconazole reversibly suppresses steroidogenesis by inhibiting cytochrome P450 enzymes and interferes with dihydrotestosterone (DHT) activity by binding to the androgen receptor. Hypospadias was reported in infants exposed to nystatin in utero.

Case presentation: A male infant exposed to antepartum nystatin presented with severe under-undervirilization and transient adrenal corticosteroid abnormalities. He was born in USA at 31 weeks gestation to a mother treated with vaginal Polygynax capsules (nystatin-100,000 international units, neomycin sulphate-35,000 international units and polymyxin B-35,000 international units) for vaginal discharge in the Ivory Coast. She used approximately 60 capsules between the first trimester until delivery. The infant was born with micropenis, chordee, perineo-scrotal hypospadias and bifid scrotum with bilaterally palpable gonads. The karyotype was 46,XY. No Mullerian structures were seen on ultrasound. Serum 17-hydroxyprogesterone (17 OHP) on newborn screening was high (304 ng/ml, normal < 35). Cortisol response to cosyntropin on the 3rd day of life (DOL) was 10 mcg/ml; the subnormal cortisol response may have resulted from prematurity and the predelivery treatment with betamethasone. The elevation of several adrenal corticosteroids was not consistent with any specific enzymatic defect. Hydrocortisone and fludrocortisone were initiated at another hospital for suspected mild glucocorticoid and mineralocorticoid deficiencies. Genetic screening for adrenal and gonadal developmental defects performed when transferred to our care were normal. All medications were gradually discontinued over 5-8 months. Adrenal and testicular responses to cosyntropin and human chorionic gonadotropin (hCG) were normal at 8 months.

Conclusions: We report severe undervirilization in a 46,XY infant born to a mother treated with prolonged and high dose nystatin during pregnancy. This presentation suggests that prolonged antepartum use of high dose nystatin could lead to severe but transient defects in androgen synthesis and/or action possibly by acting as an endocrine disruptor. Further studies are warranted to confirm this finding. Thus, endocrine disruptors should be considered in male newborns with atypical genitalia not explained by common pathologies.

Background: Thyrotoxic periodic paralysis is a rare complication of hyperthyroidism and is associated with hypokalemia and muscle paralysis. This condition is most commonly seen in Asian men.

Case presentation: We report on a 14-year-old African American male with Graves' disease and intermittent asthma who presented with bilateral leg weakness. The patient demonstrated signs of thyrotoxicosis and laboratory evaluation revealed hypokalemia and hyperthyroidism. Following the administration of potassium supplementation clinical status improved and the patient was discharged home on a high dose of methimazole and propranolol. At a 6-month follow up visit, he was found to be clinically euthyroid and demonstrated no signs of hyperthyroidism or muscle weakness.

Conclusion: Children presenting with weakness and hypokalemia should be investigated for thyroid dysfunction. Correction of hypokalemia improves acute presentation, but the patient will remain at risk for paralysis until euthyroid state is achieved.

Background: Progressive Familial Intrahepatic Cholestasis Type 2 (PFIC2) is a rare congenital cholestatic liver disease that progresses to end stage liver disease. It is associated with fat soluble vitamin D deficiency rickets and severe dyslipidemia; however, treatment of these secondary effects remains a challenge.

Case presentation: One year old twin males born to a mother with intrahepatic cholestasis during pregnancy presented with jaundice, pruritus and failure to thrive. Lab evaluation revealed significant transaminitis, direct hyperbilirubinemia and normal gamma glutamyl transferase (GGT). Genetic studies confirmed PFIC2. Further evaluation for fat soluble vitamin deficiencies revealed severe vitamin D deficiency rickets. High dose vitamin D replacement therapy using Ergocalciferol (Vitamin D₂) 50,000 IU three times a week over 10 weeks led to the improvement of Vitamin D, 25-Hydroxy (25-OH) serum levels and resolution of rickets. Dyslipidemia with very low high density lipoprotein-cholesterol (HDL-C) and high triglycerides was more profound in our patients compared to what has been described in the literature thus far. The dyslipidemia improved 2 months after internal biliary diversion.

Conclusions: Higher doses of Vitamin D therapy are needed for treatment of rickets secondary to cholestasis. Extremely low HDL-C levels are characteristic of PFIC and improve with treatment of underlying cholestasis. Maternal intrahepatic cholestasis during pregnancy can be an early warning sign.

Background: Acrodyostosis type 1 (ACRDYS1) is a rare skeletal dysplasia, and sometimes it can be misdiagnosed as pseudohypoparathyroidism type 1A (PHP1A), a subtype of Albright hereditary osteodystrophy (AHO), due to overlapping features. Growth hormone releasing hormone (GHRH) resistance with severe short stature is common in both ACRDYS1 and PHP1A (Emily L. Germain-Lee, et al. J Clin Endocrinol Metab, 88:4059-4069, 2003). Whereas growth hormone (GH) treatment has been studied in patients with PHP1a, the same is not true for the rarer ACRDYS1. Here in we report an adverse orthopedic outcome in a patient with ACRDYS1 with severe short stature treated with growth hormone. Our experience could have implications for the treatment of other patients with this disorder.

Case presentation: We report a case of Legg-Calve-Perthes Disease (LCPD) in an 8-year old female with ACRDYS1 treated with GH. She initially presented with marked short stature (height Z-score - 3.46) with a low normal insulin like growth factor-1 (IGF1) level, and had biochemical evidence of thyrotropin and parathyroid hormone resistance. GH therapy was initiated at 0.35 mg/kg/week leading to increased growth velocity. After 7 months on GH, she developed right knee pain. Radiographic images revealed flattening of her right femoral head consistent with LCPD. GH was discontinued. Six weeks later, radiographs revealed further collapse of the entire femoral head. Her lesion stabilized after 8 months with conservative management and she never resumed GH. Her final adult height is 4'2″ (128 cm).

Conclusion: Patients with ACRDYS1 on GH therapy may be at increased risk of LCPD. This has not been reported in patients with PHP1A treated with GH. Clinicians and families need to be aware of this potential complication when counseling about GH treatment.