Bakula Trivedi

Reduced 125I-hGH binding by serum of dwarf pigs but not by serum of dwarfed poodles.

1. Normal and growth-deficient poodle and swine strains were characterized for serum growth hormone-binding protein (GH-BP) content as well as other growth-related hormones, and the relationship between these factors and body size was examined. 2. GH-BPs were found in all strains of pigs and poodles. Concentrations of GH-BPs (as expressed by specific bindings) did not vary among the poodle breeds, but did correlate with body size in pigs. 3. Insulin-like growth factors (IGFs) I and II were decreased 71 and 44% respectively in miniature compared to standard size poodles. 4. Only the Yucatan micro pig strain had reduced serum IGF-I concentrations compared to normal controls. 5. Growth hormone concentrations however were normal to elevated in all micro and miniature pig strains. 6. Serum triiodothyronine concentrations were reduced in Yucatan mini and micro pigs in spite of normal circulating levels of thyroxine. 7. Body size reductions in the swine and dog strains are probably attributable to different primary defects of various growth related hormones or hormone receptors. 8. Each species breed therefore could serve as a model for a different human growth-deficient condition.

Abnormal serum IGF-II transport in non-islet cell tumor hypoglycemia results from abnormalities of both IGF binding protein-3 and acid labile subunit and leads to elevation of serum free IGF-II.

The syndrome of non-islet cell tumor hypoglycemia (NICTH) is the result of hypersecretion of IGF-II by a tumor although serum IGF-II is seldom elevated. This is attributable to abnormalities of the IGF binding proteins (IGFBPs) present in NICTH which is characterized by a marked decrease in the fraction of IGFBP-3 present in the 150 kD complex with acid labile subunit (ALS) and a 2- to 4-fold increase in IGFBP-2. We studied the impact of these changes in IGFBPs on the concentration of free IGF-II using a neutral C-18 Sep-Pak extraction procedure. We found that free IGF-II was increased 8- to 20-fold in NICTH. Thus there is no limitation of free IGF-II for complex formation. Additional experiments were conducted to determfine whether ALS deficiency limits 150 kD complex formation. We observed that addition of purified ALS to NICTH sera only partially succeeded in converting smaller complexes containing IGFBP-3 to large 150 kD complexes. We conclude that both a functional deficiency of ALS and IGFBP-3 are present in NICTH sera. The increased free IGF-II in NICTH sera contributes greatly to bioactivity and largely explains the marked hypoglycemia of NICTH patients even when total serum IGF-II concentrations may remain within normal limits.

Non-islet cell tumour induced hypoglycaemia with acromegaloid facial and aral swelling

The syndrome of non‐islet cell tumour hypoglycaemia (NICTH) has been linked with the synthesis and secretion of ‘big’ IGF‐II. We report a patient with a large pelvic clear cell sarcoma who developed recurrent severe hypoglycaemia and In addition presented with severe soft tissue facial swelling, skin tags and nuchal hyperpigmentation. After resection of the tumour serum ‘big’ IGF‐II returned to normal and the acromegaloid skin changes remitted.

Whole Body Nitrogen Kinetics and Their Relationship to Growth in Short Children Treated with Recombinant Human Growth Hormone

ABSTRACT: We studied the effects of growth hormone on retention of 15N-labeled amino acids in 34 short, prepubertal, growth hormone-sufficient children and three growth hormone-deficient subjects. All 34 non-growth hormone-deficient children had apparently normal circulating growth hormone molecules and no mutations were detected in the growth hormone or IGF-I genes of any subjects. Fibroblasts from 34 children responded normally when challenged with recombinant human IGF-I. During the last 72 h of a 4-d challenges with recombinant human growth hormone (16 μg/kg body wt), retention of a mixed 15N-amino acid dose varied between 5.7 and 50.5%. Whole body protein synthesis, breakdown, and net anabolism calculated from the 15N kinetics were all increased by the acute growth hormone challenge. However, no routine clinical feature or laboratory determination correlated with the nitrogen retention response. After subsequent treatment (75 μg/kg three times a week) with recombinant human growth hormone for 1 y, there was a significant increase in height velocity. but this increase was not related significantly to pretreatment variables other than inversely to pretreatment height velocity. There was a significant (p = 0.03) correlation between the change in height velocity Z score and the degree of nitrogen retention to acute challenge with growth hormone, but this correlation was too weak (r = 0.37) to be of practical value in predicting the treatment growth response in an individual child.