Mineralocorticoid deficiency in post-operative cerebral salt wasting.

Acute hyponatremia, following neurosurgery, results from inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting (CSW). CSW is due to abnormally high atrial or brain natriuretic peptides (ANP, BNP), which block all stimulators of zona glomerulosa steroidogenesis, resulting in mineralocorticoid deficiency. A 3 year-old girl presented CSW at day 4, after resection of craniopharyngioma and hypophysectomy. Hyponatremia, hyperkalemia and high natriuresis occurred on day 8, with low renin and aldosterone and elevated BNP 120.3 ng/ml (undetectable before surgery). Fludrocortisone 100 microg/day controlled natriuresis and restored electrolytes within 24 hours. A 5 year-old boy presented CSW at day 6 after partial resection of optic glioma. Fludocortisone 100 microg/day restored electrolytes within 8 hours. ANP was elevated, 60.6 ng/l, aldosterone and renin were low. Fludrocortisone supplementation should be considered in CSW, as excessive natriuresis is controlled, and electrolytes are easily restored, avoiding life-threatening complications of this complex disorder.

Very early prophylactic thyroid surgery for infants with a mutation of the RET proto-oncogene at codon 634: evaluation of the implementation of international guidelines for MEN type 2 in a single centre.

OBJECTIVE: Genetic diagnosis available since 1993 established germinal mutations of the RET proto-oncogene at codon 634 as the main cause of inherited medullary thyroid carcinoma (MTC). International guidelines established in 1999 recommend that children with such mutations undergo a total thyroidectomy before age 5, with unspecified cervical neck dissection. Since 1993, only 41 of 275 thyroidectomies reported in RET 634 children were performed before age 5 (15%). The aim of this study was to evaluate the implementation of these guidelines in a single centre. DESIGN AND PATIENTS: Genetic diagnosis was proposed to the parents of all eight children born after 1992 from two RET 634 families. Total thyroidectomy was proposed before age 5 if the child carried a mutation. RESULTS: Genetic diagnosis was performed in all the children (aged 1-3) and thyroidectomy in the five who carried a mutation (aged 2-5). Cervical lymph node dissection varied from lymphadenectomy of central and lateral compartments in the eldest child to pickings in the youngest. There was no permanent hypoparathyroidism or recurrent nerve paralysis. C-cell hyperplasia, medullary thyroid carcinoma and lymph node metastasis were present in 5/5, 3/5 and 0/5, respectively. Undetectable pentagastrin-stimulated CT levels were achieved and maintained postoperatively in all five children (average follow-up 3.6 years). CONCLUSIONS: MEN 2 guidelines on thyroidectomy can be efficiently and safely implemented by a multidisciplinary team operating in a single centre. The lack of guidelines on cervical neck dissection remains a problem; this could be solved by determining an age under which this procedure would be deemed unnecessary.

Pulse transit time improves detection of sleep respiratory events and microarousals in children.

OBJECTIVES: To evaluate the additional information provided by pulse transit time (PTT), a noninvasive tool, when using during polysomnography for the diagnosis of sleep breathing disorders in a pediatric population. MAIN FINDINGS: Respiratory and microarousals events were scored twice. The first scoring was performed using nasal pressure, thermistors, thoracic and abdominal movements, and oxygen saturation. The second scoring, blinded to the first scoring, was performed using PTT in combination with all the other signals. Microarousals were scored once visually on the EEG trace (cortical arousals [CAs]) and once using the PTT signal (autonomic arousals [AAs]) blinded to EEG. For the whole group of 16 children studied (mean age, 9.5 years), there was no significant difference between the respiratory disturbance index (RDI) with or without PTT analysis (22.4 +/- 13.5/h vs 20.4 +/- 14.3/h; not significant [mean +/- SD]). Among the children exhibiting a "without PTT" RDI < 30/h, 5 of 12 children (41.66%) showed a clinically significant >/= 5/h increase in RDI when using PTT. AAs detected by PTT were significantly more frequent than CAs during rapid eye movement (REM) sleep (7.4 +/- 3.9/h vs 3.2 +/- 2.3/h; p < 0.001) and slow wave sleep (SWS) [6.0 +/- 4.3/h vs 0.6 +/- 0.5/h; p < 0.0001]. CONCLUSIONS: The quantification of respiratory effort using PTT improves the detection of respiratory events in children. The detection of microarousals is improved particularly in REM and SWS.

Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type.

OBJECTIVE: To assess the efficacy of etanercept in patients with juvenile idiopathic arthritis (JIA), and to assess the tolerance of these patients to etanercept. METHODS: All JIA patients with active chronic polyarthritis, who were first treated with etanercept between November 1999 and June 2001 in 18 French centers because of poor response or intolerance to methotrexate, were included in this open-label, prospective, multicenter study. A standardized questionnaire was sent to the treating physicians. We assessed the validated international core-set score for JIA activity every 3 months and performed an intent-to-treat analysis. We also compared the risk of treatment failure in patients defined as having systemic-onset, oligoarticular-onset, or polyarticular-onset JIA. RESULTS: Sixty-one patients were enrolled and were followed up for a median of 13 months. Treatment had to be stopped in 1 patient who became pregnant and in 12 patients due to severe side effects, including neurologic or psychiatric disorders, retrobulbar optic neuropathy, major weight gain, severe infection, cutaneous vasculitis with systemic symptoms, hemorrhagic diarrhea, uveitis flare, and pancytopenia. All of these side effects disappeared after discontinuation of etanercept. Crohn's disease was subsequently diagnosed in 1 child. Scores improved by > or =30% in 73% of patients after 3 months, but this proportion decreased to 39% after 12 months. The response rate was significantly lower in patients with systemic-onset JIA than in those with oligoarticular- or polyarticular-onset JIA. CONCLUSION: Treatment of JIA with etanercept may be associated with a wide spectrum of severe side effects. Although most patients initially respond to etanercept, this initial response is not always followed by sustained improvement over longer periods of time. In addition, the higher rate of treatment failure in the group with systemic-onset JIA indicates that these patients in particular may require alternative treatments.

Validation of the French version of the Childhood Health Assessment Questionnaire (CHAQ) in juvenile idiopathic arthritis.

OBJECTIVES: To translate, cross-culturally adapt, and validate the functional disability tool Childhood Health Assessment Questionnaire (CHAQ), a variant of the Health Assessment Questionnaire (HAQ), in children with juvenile idiopathic arthritis (JIA). CHILDREN AND METHODS: The disability index is the mean of the scores on the eight domains of the CHAQ and can range from 0 (no disability) to 3 (maximum disability). The CHAQ was first translated into French and adapted, then validated in a multicenter cross-sectional study in 306 children with JIA (systemic onset, 23%; polyarticular onset, 22%; extended oligoarticular subtype, 25%; and persistent oligoarticular subtype, 30%). RESULTS: Overall CHAQ scores discriminated between the four JIA subtypes (systemic: 1.1 +/- 0.9; polyarticular: 0.8 +/- 0.7, extended oligoarticular 0.8 +/- 0.7, and persistent oligoarticular: 0.4 +/- 0.5 [P < 0.0001]). Reproducibility evaluated by test-retest at a 7-day interval was excellent (intraclass coefficient, 0.91), as was agreement between the Parent's and Children's versions of the questionnaire (intraclass coefficient, 0.89). Significant correlations were found between the overall CHAO score and variables reflecting disease severity (joint counts, physician's and parent's global assessments, and erythrocyte sedimentation rate), indicating excellent convergent validity of the tool. CONCLUSION: The French version of the CHAQ displays good psychometric characteristics, although its sensitivity to change remains to be established. The French version of the CHAO should prove useful in international studies and can be expected to be helpful for monitoring individual patients with JIA.

A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate.

Thyroid dysgenesis is the most common cause of congenital hypothyroidism (CH) and its genetic basis is largely unknown. Here, we describe the second homozygous missense mutation in TTF-2 (or FOXE1), a transcription factor that has been implicated in thyroid development. Two male siblings, born to consanguineous parents, presented with CH, athyreosis and cleft palate and were found to be homozygous for a mutation corresponding to a serine to asparagine substitution at codon 57 (S57N) in the forkhead DNA binding domain of TTF-2. Their heterozygous parents were unaffected and this mutation was not found in 31 unrelated cases of athyreosis or normal controls. Consistent with its location, the S57N TTF-2 mutant protein showed impaired DNA binding and partial loss of transcriptional function. Such incomplete loss of TTF-2 function may account for the absence of choanal atresia and bifid epiglottis in our patients, anomalies which were present together with CH and cleft palate in two other individuals with the only other, more deleterious, TTF-2 mutation (A65V) described previously. Our observations support the role of TTF-2 in both thyroid and palate development but suggest phenotypic heterogeneity of this syndromic form of CH.