The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Oct 2002
Multicenter Study Clinical TrialPrimary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size.
Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. ⋯ Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 microg/liter).
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J. Clin. Endocrinol. Metab. · Oct 2002
Case ReportsA 21-year-old woman with consumptive hypothyroidism due to a vascular tumor expressing type 3 iodothyronine deiodinase.
We present a 21-yr-old female with a large hepatic vascular tumor and subclinical hypothyroidism. A high level of the thyroid hormone inactivating enzyme type 3 iodothyronine deiodinase (D3) was detected in her tumor, and the TSH of 26.2 mU/liter returned to normal after surgical resection of the mass. This indicates that the vascular tumor caused this adult's hypothyroidism as has now been documented in nine infants with this syndrome. This first example of consumptive hypothyroidism in an adult indicates that the inactivation rate of thyroid hormone by D3 in a vascular tumor can stress the secretory capacity even of the TSH-stimulated normal adult thyroid gland.
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J. Clin. Endocrinol. Metab. · Oct 2002
Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence.
Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. ⋯ Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an up-regulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation.
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J. Clin. Endocrinol. Metab. · Sep 2002
Case ReportsFamilial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene.
Approximately 10% of catecholamine-secreting tumors are malignant, and 10% are familial. These tumors have been associated with several hereditary syndromes, including multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and familial paraganglioma. Mutations in succinate dehydrogenase (SDH) subunit genes have been identified in some kindreds with catecholamine-secreting tumors. ⋯ Sequencing of the SDHB gene in the tumors did not reveal any somatic mutations or loss of heterozygosity of the remaining allele. Thirty years after the initial diagnosis, the father is one of the longest living survivors of malignant catecholamine-secreting paraganglioma. Our findings indicate that mutations in SDHB may be associated with metastatic, yet clinically indolent, abdominal paraganglioma in some families.
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J. Clin. Endocrinol. Metab. · Jul 2002
Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors.
Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. ⋯ GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the cytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.