Search PubMed⌕ Search

Biomedical subjects

R Bouillon

Publications and source records attributed to R Bouillon.

At least 145 records · Page 8Linked to original sources
PubMed1997

Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones.

Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use.

Adult↗
PubMed1997

Comparison of 6-s-cis- and 6-s-trans-locked analogs of 1alpha,25-dihydroxyvitamin D3 indicates that the 6-s-cis conformation is preferred for rapid nongenomic biological responses and that neither 6-s-cis- nor 6-s-trans-locked analogs are preferred for genomic biological responses.

The hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] generates biological responses via both genomic and rapid, nongenomic mechanisms. The genomic responses utilize signal transduction pathways linked to a nuclear receptor (VDRnuc) for 1alpha,25(OH)2D3, while the rapid responses are believed to utilize other signal transduction pathways that may be linked to a putative membrane receptor for 1alpha,25(OH)2D3. The natural seco steroid is capable of facile rotation about its 6,7 single carbon bond, which permits generation of a continuum of potential ligand shapes extending from the 6-s-cis (steroid like) to the 6-s-trans (extended). To identify the shape of conformer(s) that can serve as agonists for the genomic and rapid biological responses, we measured multiple known agonist activities of two families of chemically synthesized analogs that were either locked in the 6-s-cis (6C) or 6-s-trans (6T) conformation. We found that 6T locked analogs were inactive or significantly less active than 1alpha,25(OH)2D3 in both rapid responses (transcaltachia in perfused chick intestine, 45Ca2+ influx in ROS 17/2.8 cells) and genomic (osteocalcin induction in MG-63 cells, differentiation of HL-60 cells, growth arrest of MCF-7 cells, promoter transfection in COS-7 cells) assays. In genomic assays, 6C locked analogs bound poorly to the VDRnuc and were significantly less effective than 1alpha,25(OH)2D3 in the same series of assays designed to measure genomic responses. In contrast, the 6C locked analogs were potent agonists of both rapid response pathways and had activities equivalent to the conformationally flexibile 1alpha,25(OH)2D3; this represents the first demonstration that 6-s-cis locked analogs can function as agonists for vitamin D responses.

Animals↗
PubMed1997

Age-related (type II) femoral neck osteoporosis in men: biochemical evidence for both hypovitaminosis D- and androgen deficiency-induced bone resorption.

The problem of osteoporosis in men has recently been recognized as an important public health issue. To test the hypothesis that endocrine deficiency-mediated alterations in bone metabolism might contribute to osteoporotic fracture risk in elderly men, serum levels of 25-hydroxycholecalciferol (25(OH)D), 1,25-dihydroxycholecalciferol (1,25(OH)2D), intact parathyroid hormone (PTH), testosterone, and estradiol were measured in 40 males (mean age 73 years) who were consecutively recruited within 18 h following a fracture of the proximal femur, and in an equal number of community-living older men (mean age 72 years) who served as controls. In addition, circulating osteocalcin and urinary excretion of (deoxy)pyridinoline were determined as markers of bone formation and resorption, respectively. No differences were observed between the mean serum concentrations of osteocalcin and estradiol. Serum levels of 25(OH)D, 1,25(OH)2D, and testosterone, however, were decreased in hip fracture patients. When correcting for differences in vitamin D binding protein, differences in 1,25(OH)2D did not persist, whereas serum 25(OH)D was still significantly lower in patients than in controls (6.1 +/- 4.3 vs. 7.6 +/- 2.8, p = 0.01). Similarly, a highly significant deficit was observed in the free testosterone index, calculated from total testosterone and the level of sex hormone binding globulin (2.6 +/- 1.3 vs. 8.2 +/- 2.9, p < 0.001). Serum PTH and urinary pyridinium cross-links, however, were markedly increased in the fracture group. Moreover, in fracture patients, free 25(OH)D and free testosterone were both significant and mutually independent negative predictors of (deoxy)pyridinoline excretion. Although limited by its cross-sectional design, the present study suggests that both hypovitaminosis D and androgen deficiency may predispose to bone resorption in elderly men and in turn to remodeling imbalance and fracture risk.

Aged↗
PubMed1997

Microgravity reduces the differentiation of human osteoblastic MG-63 cells.

Spaceflight leads to osteopenia in both humans and animals, principally as a result of decreased bone formation, which might be the consequence of impaired osteoblast differentiation. The effect of microgravity on osteoblast differentiation in vitro was investigated using the human osteosarcoma cell line MG-63. Genes related to matrix formation and maturation were quantified both at the protein and mRNA level in untreated and hormone-treated (dihydroxyvitamin D3 [1,25(OH)2D3], 10(-7) M; transforming growth factor beta2 (TGF-beta2), 10 ng/ml) cells cultured for 9 days under microgravity conditions aboard the Foton 10 satellite and compared with ground and inflight unit-gravity cultures. The expression of alkaline phosphatase (ALP) activity following treatment at microgravity increased only by a factor of 1.8 compared with the 3.8-fold increase at unit-gravity (p < 0.01), whereas no alteration was detected in the production of collagen type I between unit- and microgravity. In addition, gene expression for collagen Ialpha1, ALP, and osteocalcin following treatment at microgravity was reduced to 51, 62, and 19%, respectively, of unit-gravity levels (p < 0.02). The lack of correlation between collagen type I gene and protein expression induced by microgravity is most likely related to the different kinetics of gene and protein expression observed at unit-gravity: following treatment with 1,25(OH)2D3 and TGF-beta2, collagen Ialpha1 mRNA increased gradually during 72 h, but collagen type I production was already maximal after treatment for 48 h. In conclusion, microgravity decreases the activity of osteoblasts in vitro; in particular the differentiation of osteoblasts in response to systemic hormones and growth factors is reduced by microgravity.

Alkaline Phosphatase↗
PubMed1997

Measurement of vitamin D and its metabolites (calcidiol and calcitriol) and their clinical significance.

The serum concentration of vitamin D will only give information about the recent exposure to either nutritional vitamin D or to recent vitamin D production in the skin. Within hours vitamin D is removed from the circulation and reappears again a few hours later as 25(OH)D. Measurements of vitamin D therefore are not useful to judge the vitamin D status of man. Plasma concentrations of 25-hydroxyvitamin D (25(OH)D) are the best markers of imminent or existing vitamin D deficiency. Suboptimal vitamin D supply (or 25(OH)D plasma concentrations) are observed in most European countries and North America from November to April. Vitamin D substitution is recommended to persons with a serum concentration of 25(OH)D below 50 nmol/L (20 micrograms/L). Plasma concentrations of 1,25(OH)2D3 (calcitriol) depend mainly on renal function, concentrations of intact PTH and the supply of the organism with calcium and phosphate. High PTH, low calcium and low phosphate supply are the main stimulators of the production of calcitriol. Vitamin D substitution, or if necessary, therapy with active vitamin D metabolites or analogs, e.g. calcitriol or alfacalcidol, are often necessary in hypercalcemic persons with low serum concentrations of calcitriol, e.g. in patients with renal failure. Disorders with low or high vitamin D metabolite concentrations in serum are described in this paper.

Biomarkers↗
PubMed1997

Fluoride kinetics of the axial skeleton measured in vivo with fluorine-18-fluoride PET.

UNLABELLED: The aim of this study was to quantify regional bone blood flow and influx rate with PET and [18F]fluoride in patients with metabolic bone disorders. METHODS: Dynamic imaging of the spine or pelvis was performed after administration of 300-370 MBq of 18F-. Plasma clearance of 18F- was determined in blood sampled from the radial artery. A three-compartment model was used to estimate the regional flow and fluoride influx rate. RESULTS: In this preliminary study, fluoride flux (in micromol/min/liter) could be measured regionally. The flux was consistent with the pathophysiology of the studied metabolic disorders and allowed the various disease states to be distinguished. Bone blood flow and influx rate were low in osteoporosis (in the "normal-appearing" bone) and high in Paget's disease. CONCLUSION: With PET and [18F]fluoride, local bone blood flow and fluoride influx rate can be quantified in patients in vivo. Metabolically active zones have an increased influx rate and an accordingly increased flow. In principle, this technique permits classification of bone disorders and has potential for the monitoring of therapy response in metabolic bone disease.

Adult↗
PubMed1996

Syndrome of lipoatrophic diabetes, vitamin D resistant rickets, and persistent Müllerian ducts in a Turkish boy born to consanguineous parents.

Congenital lipodystrophy (MIM 269700), persistent Müllerian ducts (MIM 261550), and vitamin D resistant rickets (MIM 277440) were observed in an 8 1/2-year-old boy born to consanguineous parents. Measurements of hormone sensitive lipase activity from a sample of the suprapubic fat depot were normal. Although the insulin receptor appeared normal (including autophosphorylation), insulin action, assessed by induction of total mRNA, was decreased. The vitamin D receptor was normal in size and amount, with a slight decrease in affinity for 1,25(OH)2D3. Induction of 24-hydroxylase, used as a measure of responsiveness to 1,25(OH)2D3, was only mildly defective. Assessment of anti-Müllerian hormone (AMH) failed to show any abnormalities explaining the persistent Müllerian ducts. We speculate that a defect in general hormone action common to 1,25(OH)2D3, insulin, and AMH may exist in this patient although we can not exclude the unlikely possibility that he is homozygous for two or three individually rare mutations.

Adult↗
PubMed1996

Effects of recombinant human growth hormone and insulin-like growth factor-I, with or without 17 beta-estradiol, on bone and mineral homeostasis of aged ovariectomized rats.

This study aimed to evaluate whether recombinant human growth hormone (rhGH) or insulin-like growth factor-I (rhIGF-I) can reverse or prevent further bone loss in aged osteopenic ovariectomized (OVX) rats and to compare their effects with those of 17 beta-estradiol (E2). Twelve-month-old rats were OVX, remained untreated for 8 weeks, and subsequently received daily subcutaneous (SC) injections of rhGH (75 micrograms/day), rhIGF-I (250 micrograms/day), E2 (1.5 micrograms/day), and their respective combinations during 8 weeks, and were then compared with sham-operated, pretreatment OVX, and saline-treated OVX rats. A single sc injection of rhGH resulted in peak hGH concentrations after 90 minutes, with a half-life of 124 minutes; the highest plasma IGF-I concentrations were reached 45 minutes after rhIGF-I injection (+57% vs. baseline) with a gradual decline thereafter. Measurements included: biochemical parameters of bone remodeling (plasma osteocalcin and urinary pyridinolines); histomorphometry of proximal tibial metaphysis; DXA of femur; biomechanical analysis of femur and fifth lumbar vertebra (L5); plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and calbindin-D9K in duodenal mucosa. Whereas all E2-treated OVX rats had much suppressed bone remodeling, rhGH or rhIGF-I had no effect on any biochemical or histomorphometrical parameter of remodeling. The bone mineral density (BMD) at the distal femoral metaphysis as well as parameters of strength at L5 were maintained at pretreatment values in OVX rats treated with E2, GH, or IGF-I, but not in saline-treated OVX rats; their effects were not additive, however. Trabecular bone volume in the tibial metaphysis was also higher in rats treated with these agents than in saline-treated rats, but this was more apparent at the primary than at the secondary spongiosa, suggesting that their mechanism of action is on primary spongiosa formation or breakdown. E2 alone was ineffective to augment the BMD at the femoral diaphysis; however, the diaphyseal BMD was 12-14% higher (p < 0.01) after 8 weeks of GH treatment than in pretreatment or saline-treated OVX rats and sham-operated rats, while IGF-I was less effective than GH, GH or IGF-I treatment had no effect on plasma 1,25(OH)2D3 or duodenal calbindin-D9K concentrations, but the combination of GH or IGF-I with E2 potentiated the effect of E2 to stimulate calbindin-D9K concentrations and urinary calcium excretion, indicating "hyperabsorption hypercalciuria." In conclusion, the administration of rhGH and rhIGF-I, like that of E2, into aged OVX rats prevents further loss of bone mass and strength at sites containing trabecular bone. In addition, rhGH increases cortical bone mass above pretreatment values.

Absorptiometry, Photon↗
PubMed1996

Lack of in vitro evidence for storage of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 1,25(OH)2D3 binding protein in skeletal matrix.

A few studies have reported on the measurement of 1, 25-dihydroxycholecalciferol (1,25(OH)2D3) in bone, using chloroform/methanol extraction and radioreceptor assay. As the significance of bone 1,25(OH)2D3 content was not defined in any of these reports, the objective of the current investigation was to determine whether 1,25(OH)2D3 may be stored in skeletal matrix. Bone powder samples from the iliac crest were extracted in ethylacetate/cyclohexane and 1,25(OH)2D3 isolated from the extract by means of Sephadex LH-20 and high pressure liquid chromatographic separation and subsequently measured by radioimmunoassay (RIA). Within the detection range of the RIA, no 1,25(OH)2D3 could be measured, suggesting that 1,25(OH)2D3 is not stored in skeletal matrix. Vitamin D bone concentrations previously measured may therefore have reflected plasma contamination. Consistent with this hypothesis, only traces of skeletal 1,25(OH)2D3 binding protein were measured when compared with serum values. Although 1,25(OH)2D3 may act as a potential local determinant of bone remodeling, there is no evidence supporting a delayed paracrine function by matrix-derived 1, 25(OH)2D3.

Adult↗
PubMed1996

Aromatization of androgens is important for skeletal maintenance of aged male rats.

A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6-10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9-14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance.

Absorptiometry, Photon↗
PubMed1996

Ascorbate increases the 1,25 dihydroxyvitamin D3-induced monocytic differentiation of HL-60 cells.

1,25 Dihydroxyvitamin D3 (calcitriol) induces differentiation of HL-60 leukemia cells. We studied the in vitro effect of a physiological concentration of ascorbate as potentiator of 1,25 dihydroxyvitamin D3 [(OH)2D3] activity by determining different markers of differentiation: nitroblue tetrazolium reduction, nonspecific esterase activity, and the expression of CD11b and CD14 surface antigens. Nitroblue tetrazolium reduction and nonspecific esterase activity increased up to 50% in the presence of both 1,25 (OH)2D3 plus 0.2 mM ascorbate (ASC), compared with (OH)2D3 as a unique agent. ASC also increased the expression of specific surface antigens (CD11b and CD14) during differentiation induced by 1,25 (OH)2D3, the effect being more pronounced after 48 hours of treatment with 10(-8) M 1,25 (OH)2D3. Furthermore, 1,25 (OH)2D3 alone increased intracellular cAMP level during differentiation, and the addition of ASC increased its concentration from 60 to 100% above the level reached with 1,25 (OH)2D3 as unique agent. ASC did not enhance the antiproliferative effect of calcitriol, suggesting that it only affects the ability of 1,25 (OH)2D3 to promote differentiation of HL-60 cells.

Ascorbic Acid↗
PubMed1996

Lymphocytic infundibulohypophysitis presenting in the postpartum period: case report.

BACKGROUND: Lymphocytic adenohypophysitis is a well-known autoimmune disorder affecting the anterior pituitary gland. Posterior pituitary gland function can be impaired by a similar autoimmune disorder called lymphocytic infundibulohypophysitis. Only very few cases have been reported. CLINICAL PRESENTATION: We present a patient with central diabetes insipidus in the postpartum period. On radiologic and endocrine evidence lymphocytic involvement of the pituitary stalk and infundibulum was suspected. INTERVENTION: A diagnostic pterional craniotomy was performed. The diagnosis of lymphocytic infundibulohypophysitis was confirmed by biopsy. CONCLUSION: We present a case of lymphocytic infundibulohypophysitis. In view of its autoimmune pathophysiology the occurrence of this disorder in the postpartum period is not surprising, even though it has not been reported before. This rare disorder should be distinguished from the more common lymphocytic adenohypophysitis.

Adult↗
PubMed1996

Differing shapes of 1 alpha,25-dihydroxyvitamin D3 function as ligands for the D-binding protein, nuclear receptor and membrane receptor: a status report.

1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] is the principal mediator of a wide array of biological responses through the far reaching network of the vitamin D endocine system (VDE). The steroid hormone 1 alpha,25(OH)2D3 is delivered to the various target organs of the VDE via a specific plasma transport protein, the vitamin D binding protein (DBP). Also 1 alpha,25(OH)2D3 is known to initiate biological responses through a nuclear receptor, the nVDR (50 kDa) which regulates selected gene transcription and, in addition in some target tissues, through a second receptor located in the cell membrane, the mVDR (approximately 60 kDa), which is linked to protein kinase C and/or voltage-gated Ca2+ channels so as to generate biological responses very rapidly. 1 alpha,25(OH)2D3 as a ligand is unusually conformationally flexible due to the eight carbon side chain, the seco B-ring which permits rotation about the 6-7 single carbon bond, and the A-ring which undergoes chair-chair conformational interconversion characteristic of cyclohexane rings. This paper reviews the evidence that different shapes of the 1 alpha,25(OH)2D3 satisfy the optimal requirements of the ligand binding domains of the DBP, nVDR and mVDR. The presence of a relatively rigid side chain (composed by the presence of an aromatic ring) enhances ligand interaction 2-3 fold with the DBP, but diminishes ligand affinity for the nVDR by 100 fold. The mVDR responds effectively to analogs of 1 alpha,25(OH)2D3 which are 6-s-cis locked [e.g. 1 alpha,25(OH)2-previtamin D3 or 1 alpha,25(OH)2-provitamin D3], but these same analogs have only 1-2% of the activity of 1 alpha,25(OH)2D3 in regulating gene transcription. Finally the 6-s-trans analog, 1 alpha,25(OH)2-tachysterol3, had <0.1% of the activity of 1 alpha,25(OH)2D3 in regulating gene transcription.

Animals↗
PubMed1996

Enhancement of antiproliferative activity of 1alpha,25-dihydroxyvitamin D3 (analogs) by cytochrome P450 enzyme inhibitors is compound- and cell-type specific.

Ketoconazole (keto) or liarozole (liaro), inhibitors of the cytochrome P450 enzymes that mediate vitamin D and A hydroxylations, could potentiate the antiproliferative effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and its analogs. Proliferation of MCF-7 and T47-D human breast cancer cells, MG-63 human osteosarcoma cells and HL-60 human promyeloid leukemia cells was concentration dependently inhibited by 1alpha,25(OH)2D3. The vitamin D analogs KH 1060 [20-epi-22-oxa-24,26,27-trihomo-1alpha,25(OH)2D3], RO 23-6010 [16-ene-23-yne-26-trifluoro-1,25(OH)2D2D3], ZXY 835 [20-epi-23-yne-25,26-epoxy-1alpha(OH)D3], and CD 99 [11alpha-methyl-1alpha,25(OH)2D3] were 150-,58-,16- and 7-fold more potent than 1alpha,25(OH)2D3 in inhibiting the proliferation of MCF-7 cells, respectively. A similar rank order of potency was observed in other cell lines. The antiproliferative effects of the vitamin D hormone and analogs was enhanced in MCF-7 cells when coincubated with 1 microM keto (7-, 10-, 5-, 25- and 1.3-fold more potent than in the absence of keto), respectively. The antiproliferative effect was less enhanced when 1alpha,25(OH)2D3 or its analogs KH 1060, ZXY 835 and RO 23-6010 were combined with liaro (3-, 7-, 2- and 3-fold, respectively). Keto and liaro did not markedly potentiate the activity of 1alpha,25(OH)2D3 or its analogs in MG-63 or HL-60 cells. These results suggest that differences in cellular metabolism can at least partially explain the different potency of vitamin D analogs. Moreover, the metabolism of vitamin D analogs is cell-type specific.

Calcitriol↗
PubMed1996

Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness.

OBJECTIVE: Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN: Critically ill adults (n = 40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n = 10), GHRH and GHRP-2 (n = 10), GHRP-2 and GHRH+GHRP-2 (n = 10), GHRH+GHRP-2 and GHRH+GHRP-2 + TRH (n = 10). The GHRH and GHRP-2 doses were 1 microgram/kg and the TRH dose was 200 micrograms. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS: Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS: Critically ill patients presented a striking GH response to GHRP-2 (mean +/- SEM peak GH 51 +/- 9 micrograms/l in older patients and 102 +/- 26 micrograms/l in younger patients; P = 0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P = 0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P = 0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P = 0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response > ninefold (P = 0.005), elicited a 60% rise in serum T3 (P = 0.01) and an 18% increase in T4 (P = 0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P = 0.007). GHRP-2 increased basal serum cortisol levels (531 +/- 29 nmol/l) by 35% (P = 0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P = 0.05). CONCLUSIONS: The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.

Adult↗
PubMed1996

Relationship between baseline insulin-like growth factor-I (IGF-I) and femoral bone density in women aged over 70 years: potential implications for the prevention of age-related bone loss.

OBJECTIVE: To test the hypothesis that the decline in femoral bone mass associated with healthy aging is partially accounted for by deficiency of the growth hormone-insulin-like growth factor-I (IGF-I) axis. DESIGN: Cross-sectional study. STUDY PARTICIPANTS: A sample of 245 community-dwelling healthy women aged 70 and older. Exclusion criteria were diseases or medications known to affect the musculoskeletal system or the somatotrophic axis. MEASUREMENTS: Serum levels of IGF-I, calcitriol, and osteocalcin were determined by radioimmunoassay; serum calcidiol was measured by competitive binding assay, and serum parathyroid hormone (PTH) was assessed immunochemically. Urinary pyridinium crosslinks were measured by fluorescent detection after high-pressure liquid chromatography. Isometric and isokinetic quadriceps strength was evaluated using an isokinetic dynamometer. Bone density (BMD) was assessed by dual-energy X-ray absorptiometry at the proximal femur. Multiple regression was used to adjust for potential confounders. RESULTS: At the proximal femur, BMD declined by 0.59-0.84% per year. In addition to body mass index and muscle strength, serum IGF-I was found to be an independent predictor of BMD at all femoral sites. CONCLUSION: The data support the hypothesis that circulating IGF-I not only reflects the integrated growth hormone secretion but also has a direct role in the endocrine regulation of bone remodeling. The present findings support the need for further studies to assess the potential of IGF-I in attenuating age-related femoral bone loss.

Age Factors↗
PubMed1996

Asymptomatic primary hyperparathyroidism.

The prevalence of hypercalcaemia in the adult population is probably between 0.6 and 1.1%, sufferers being predominantly women over 50 years of age. Most apparently asymptomatic hypercalcaemic patients are found to have primary hyperparathyroidism, and may in fact show some symptoms of the condition (lowered bone mineral density, cardiovascular disease and/or neuropsychiatric symptoms). The criteria for surgical intervention in these cases are discussed in the light of the high success rate of parathyroidectomy in experienced hands and the lack of effective alternative treatments.

Affective Symptoms↗