Parathyroidectomy for renal hyperparathyroidism in children and adolescents.

BACKGROUND: Renal hyperparathyroidism (rHPT) almost inevitably develops in pediatric patients with end-stage chronic kidney disease (CKD) and may require parathyroidectomy (PTX) despite intensified conservative therapy. Long-term duration of uncontrolled rHPT may result in disabling osteodystrophy and vascular calcifications. Only a few reports on children undergoing PTX for rHPT are available and mainly consist of case reports with short follow-up periods. To study this entity, we analyzed the course of 23 pediatic patients who underwent PTX for rHPT. METHODS: Twenty-three patients with a mean age of 15 years and who underwent PTX for rHPT between 1986 and 2006 were evaluated. Surgical indications and techniques, specific postoperative management, and follow-up courses are described. RESULTS: Preoperative mean serum (s-) calcium was 2.7+/-0.05 mmol/L (normal range=2.2-2.7 mmol/L); s-phosphate was 1.8+/-0.1 mmol/L (normal range=0.8-1.6 mmol/L), and mean intact parathyroid hormone (PTH) level was 1240.1+/-160.1 pg/ml (normal range=11-65 pg/ml). Twenty-one patients underwent initial PTX and two patients underwent reoperative PTX. Total PTX with parathyroid autotransplantation (AT) was performed in 18 patients. In three patients less than four parathyroid glands were identified and no AT was performed consecutively. Postoperatively, no complications with respect to bleeding or vocal cord damage were recorded. The postoperative values of s-calcium, s-phosphate, and PTH decreased to or below normal range (s-calcium=2.0+/-0.1 mmol/L, s-phosphate=1.2+/-0.1 mmol/L, PTH=50.1+/-11.2 pg/ml). All 15 children below the age of 15 years required calcium intravenously. Follow-up was obtained in all patients 69.6+/-11.4 months after PTX. Bone pain resolved in all previously symptomatic patients. S-calcium was 2.2+/-0.2 mmol/L, s-phosphate was 1.4 +/- 0.3 mmol/L, and PTH was 90.2+/-21.5 pg/ml. No patient required repeated parathyroid autografting, and only one underwent an explantation of his AT six years after initial PTX. CONCLUSION: Total PTX with AT in pediatric patients with rHPT is a safe and effective procedure. It should be considered if rHPT is refractory to conservative treatment, in view of the risk of potentially lethal vascular calcifications developing in the majority of adults with childhood onset of CKD.

Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis.

The weakness in myasthenia gravis (MG) is mediated by T helper cell (Th)-dependent autoantibodies against neuromuscular epitopes. So far, analyzing Th phenotypes or antigen specificities has yielded very few clues to pathogenesis. Here we adopt an alternative antigen-independent approach, analyzing T cell receptor (TCR) Vbeta usage/expansions in blood from 118 MG patients. We found major expansions (>or= five standard deviations above the mean of 118 healthy, individually age- and sex-matched controls) in diverse Vbeta in 21 patients (17.6%, p<0.001) among CD4+ T cells, and in 45 patients (38.1%, p<0.001) among CD8+ T cells. In informative probands, the expanded CD4+ cells consistently showed a Th cell phenotype (CD57+CXCR5+) and expressed Th1 cytokines. Furthermore, their expression of markers for activation, lymphocyte trafficking and B cell-activating ability persisted for >or=3 years. Surprisingly, we noted a selective decline in the expansions/their CD57 positivity while the probands' MG was improving. CDR3 spectratyping suggested mono- or oligoclonal origins, which were confirmed by the prevalent TCR Vbeta CDR3 sequences of Th cells cloned from repeat bleeds. Thus, our data provide evidence for persistent clonally expanded CD4+ B helper T cell populations in the blood of MG patients. These unexpected CD4+ expansions might hold valuable clues to MG immunopathogenesis.