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Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG)syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101. We studied XLAG syndrome patients (n = 18)to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2 ratio (LR)compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8% These characteristics were repli

Anhand von 24 retrospektiv analysierten Fällen mit hypophysärem Riesenwuchs aus 14 verschiedenen Kliniken innerhalb der letzten 3,5 Jahrzehnte werden die klinische Symptomatik, die endokrinologische und bildgebende Diagnostik und die gewählten Therapieansätze mit ihren Langzeitverläufen verglichen und diskutiert. Gegenwärtige Therapie der Wahl ist die selektive operative Resektion des Wachstumshormon-produzierenden Hypophysenadenomes, gegebenenfalls ergänzt durch eine medikamentöse Behandlung mit Somatostatin-Analoga und/oder Dopamin-Agonisten sowie durch eine Strahlentherapie. Für die größten Fortschritte im Verlauf der Studie, verbunden mit verbesserten Prognosen, ist in erster Linie die weiterentwickelte Operationstechnik verantwortlich, in geringerem Maße auch die Pharmako- und Radiotherapie., This retrospective multicenter analysis of 24 patients with pituitary gigantism over a period of 3.5 decades compares and discusses the clinical manifestations, the biochemical and radiologic diagnosis and the treatment with its long-term outcome and sequelae. Patient characteristics: 16 male, 8 female patients with an estimated duration of excessive growth before diagnosis of 1-11 (mean 3,9) years, age at diagnosis between 3 and 21 years, height of +2.4 to 9.4 SD. Macrocephaly was present in 8 of 13, obesity in 10 of 24, visual field defects in 4, neurologic signs and symptoms in 3, and orthopedic signs and symptoms in 8 patients, bone age identical to chronologic age or mildly advanced. Maximum basal GH levels ranged between 14 and 400 ng/ml (mean 88,4), non-suppressible by oral glucose in 21 of 21 patients, IGF-1 elevated in 13 of 14, IGFBP-3 elevated in 8 of 8, impaired glucose tolerance in 5 of 17, hyperprolactinemia in 8 of 18, and normal pituitary function (other than GH and PRL) in 17 of 20 cases. Treatment: Transsphenoidal (17) or transcranial (3) operation or both consecutively (4) revealed GH-secreting pituitary micro- (7) or macroadenomas (17) which were acidophilic (21), partly (2) or exclusively (1) chromophobic or chromophobic on reoperation (1). Long-term cure was achieved by surgery alone in 7 patients, 5 of whom had microadenomas. Among the 17 patients with unsatisfactory surgical results, dopamine agonists were almost ineffective in all 10 patients, somatostatin analogues were effective in 4, incompletely effective in 4 and ineffective in 1 of 9 patients, conventional radiotherapy was effective in 2 patients and insufficiently effective in 1, stereotactic radiosurgery was effective in 1 of 2 patients, and iridium implantation was ineffective in 1 patient. Side effects included panhypopituitarism after surgery (5) and conventional radiotherapy (3), diabetes insipidus (6), bilateral hemianopsia (1), transient CSF leakage (2), hygroma (1) and hyperph

Anhand von 24 retrospektiv analysierten Fällen mit hypophysärem Riesenwuchs aus 14 verschiedenen Kliniken innerhalb der letzten 3,5 Jahrzehnte werden die klinische Symptomatik, die endokrinologische und bildgebende Diagnostik und die gewählten Therapieansätze mit ihren Langzeitverläufen verglichen und diskutiert. Gegenwärtige Therapie der Wahl ist die selektive operative Resektion des Wachstumshormon-produzierenden Hypophysenadenomes, gegebenenfalls ergänzt durch eine medikamentöse Behandlung mit Somatostatin-Analoga und/oder Dopamin-Agonisten sowie durch eine Strahlentherapie. Für die größten Fortschritte im Verlauf der Studie, verbunden mit verbesserten Prognosen, ist in erster Linie die weiterentwickelte Operationstechnik verantwortlich, in geringerem Maße auch die Pharmako- und Radiotherapie., This retrospective multicenter analysis of 24 patients with pituitary gigantism over a period of 3.5 decades compares and discusses the clinical manifestations, the biochemical and radiologic diagnosis and the treatment with its long-term outcome and sequelae. Patient characteristics: 16 male, 8 female patients with an estimated duration of excessive growth before diagnosis of 1-11 (mean 3,9) years, age at diagnosis between 3 and 21 years, height of +2.4 to 9.4 SD. Macrocephaly was present in 8 of 13, obesity in 10 of 24, visual field defects in 4, neurologic signs and symptoms in 3, and orthopedic signs and symptoms in 8 patients, bone age identical to chronologic age or mildly advanced. Maximum basal GH levels ranged between 14 and 400 ng/ml (mean 88,4), non-suppressible by oral glucose in 21 of 21 patients, IGF-1 elevated in 13 of 14, IGFBP-3 elevated in 8 of 8, impaired glucose tolerance in 5 of 17, hyperprolactinemia in 8 of 18, and normal pituitary function (other than GH and PRL) in 17 of 20 cases. Treatment: Transsphenoidal (17) or transcranial (3) operation or both consecutively (4) revealed GH-secreting pituitary micro- (7) or macroadenomas (17) which were acidophilic (21), partly (2) or exclusively (1) chromophobic or chromophobic on reoperation (1). Long-term cure was achieved by surgery alone in 7 patients, 5 of whom had microadenomas. Among the 17 patients with unsatisfactory surgical results, dopamine agonists were almost ineffective in all 10 patients, somatostatin analogues were effective in 4, incompletely effective in 4 and ineffective in 1 of 9 patients, conventional radiotherapy was effective in 2 patients and insufficiently effective in 1, stereotactic radiosurgery was effective in 1 of 2 patients, and iridium implantation was ineffective in 1 patient. Side effects included panhypopituitarism after surgery (5) and conventional radiotherapy (3), diabetes insipidus (6), bilateral hemianopsia (1), transient CSF leakage (2), hygroma (1) and hyperph