ABSTRACT
A 15-year-old boy had hypercalcemia in association with malignant retroperitoneal paraganglioma. He had suppressed circulating levels of intact parathyroid hormone, whereas parathyroid hormone-related protein (PTHrP) immunoreactivity was elevated in plasma. Both the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were normal. Preoperatively the patient required control of hypercalcemia with intravenous pamidronate therapy. His circulating calcium and PTHrP concentrations became normal after a successful surgical resection of the primary retroperitoneal tumor. To our knowledge, this is the first reported case of elevated PtHrP levels in a patient with paraganglioma which resolved postoperatively.
Subject(s)
Hypercalcemia/etiology , Paraganglioma/complications , Proteins/metabolism , Retroperitoneal Neoplasms/complications , Adolescent , Diphosphonates/therapeutic use , Humans , Hypercalcemia/therapy , Male , Pamidronate , Paraganglioma/blood , Paraganglioma/surgery , Parathyroid Hormone-Related Protein , Retroperitoneal Neoplasms/blood , Retroperitoneal Neoplasms/surgery , Tomography, X-Ray ComputedABSTRACT
To investigate IGF-I resistance in African Efe Pygmies, we examined clonal responsiveness to IGF-I in Epstein-Barr virus-transformed B-lymphocytes from three Efe Pygmies and three American control subjects. The Efe B-lymphoblasts did not increase clonal responsiveness when incubated with IGF-I (as high as 250 micrograms/liter) in contrast to the control B-lymphoblasts which showed a bimodal dose-response with a maximal stimulation of 50% above baseline. The proliferative response of Efe B-lymphoblasts was similar to that of control B-lymphoblasts when incubated with another growth factor, phorbol 12-myristate 13-acetate, which does not activate the IGF-I receptor. These findings indicate that Efe Pygmy B-lymphoblasts are resistant to IGF-I as measured by in vitro clonal proliferation assays. Coupled with our previous report of IGF-I unresponsiveness in Efe Pygmy HTLV-II-transformed T-lymphocytes, these data suggest that IGF-I resistance is generalized and may play a central role in the etiology of short stature in this population.
Subject(s)
B-Lymphocytes/virology , Black People , Insulin-Like Growth Factor I/metabolism , Receptor, IGF Type 1/metabolism , Adult , B-Lymphocytes/metabolism , Body Height , Body Weight , Democratic Republic of the Congo/ethnology , Human Growth Hormone/metabolism , Humans , In Vitro Techniques , Insulin-Like Growth Factor Binding Protein 3/metabolism , Insulin-Like Growth Factor II/metabolism , Male , Middle Aged , Thyrotropin/metabolismABSTRACT
We used an in vitro T-lymphoblast clonal proliferation assay to quantify human IGF-I (hIGF-I)-, human PTH (hPTH)-, human ACTH (hACTH)-, and human TSH (hTSH)-stimulated growth of human T-cell leukemia virus-II-transformed T-lymphoblast cell lines from normal individuals and to elucidate the role of IGF-I as the mediator of hPTH-, hACTH-, and hTSH-induced T-cell growth. Normal T-lymphoblast cell lines respond to hIGF-I in a bimodal fashion. The mean first peak response was 143 +/- 9.8% above baseline (defined as 100%) occurring at 8 micrograms/L, and the mean second peak response was 154 +/- 14.4% occurring at 100 micrograms/L. Both responses were completely blocked after incubation with alpha IR-3, an MAb to the IGF-I receptor (by analysis of variance, p = 0.015 between full response curves). After stimulation with hPTH, the mean peak clonal response of normal T-lymphoblast cell lines was 189 +/- 7.0%; after incubation with alpha IR-3, the mean peak clonal response was 108 +/- 7.9% (p = 0.0015 between full response curves). The mean peak clonal response of normal T-lymphoblast cell lines after hACTH stimulation was 192 +/- 8.6%; preincubation with alpha IR-3 reduced the mean peak clonal response to 94 +/- 1.2% (p < 0.0001 between full response curves). With hTSH stimulation, the mean peak clonal response of normal T-lymphoblast cell lines was 167 +/- 7.0%; after incubation with alpha IR-3, the mean peak clonal response was 94 +/- 8.2% (p = 0.003 between full response curves).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Adrenocorticotropic Hormone/pharmacology , Insulin-Like Growth Factor I/physiology , Parathyroid Hormone/pharmacology , T-Lymphocytes/drug effects , Thyrotropin/pharmacology , Adult , Black People , Body Height/physiology , Cell Division/physiology , Cell Line, Transformed , Cell Transformation, Viral , Human T-lymphotropic virus 2 , Humans , Reference Values , Reproducibility of Results , Stimulation, ChemicalABSTRACT
A 17-year-old boy with Kallmann syndrome had complex congenital heart disease that included double-outlet right ventricle, d-mal-position of the great arteries, right aortic arch, and hypoplastic main pulmonary artery. He had neurosensory hearing loss and mental retardation. The 7 previously reported patients with Kallmann syndrome and cardiac abnormalities were short with height > or = 2 standard deviations below the mean for age (5/7), lacked a family history of Kallmann syndrome (6/6), and were mentally retarded (4/4). Patients presenting with Kallmann syndrome and congenital heart defects appear to represent a distinct subgroup of patients with Kallmann syndrome. The cause of this association is unclear, but may involve either autosomal recessive inheritance, sporadic dominant mutation, or a shared teratogenic event during the first trimester of gestation.
