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M Gourmelen

Publications and source records attributed to M Gourmelen.

At least 19 recordsLinked to original sources
PubMed1992

[Creutzfeldt-Jakob disease in 4 children treated with growth hormone].

Creutzfeldt-Jakob disease was diagnosed in four growth hormone recipients at the age of 10, 11, 18 and 19 years. To our knowledge, the two first cases are the first instances of Creutzfeldt-Jakob disease recorded in children. Three of them were still being treated with synthetic hormone at the onset of the disease. Neurological disorders: ataxia and diplopia, appeared first, dementia and myoclonus appeared later. Eighteen cases of Creutzfeldt-Jakob disease in growth hormone recipients are now recorded, and the present risk of Creutzfeldt-Jakob disease in pituitary growth recipients is estimated to be 1/300. Because of the long incubation period, new cases are to be feared. Other causes of iatrogenic Creutzfeldt-Jakob disease are reviewed. These facts incite to consider carefully using products of human origin in human therapy. The interactions between growth hormone, prion and host's genomic make-up are still not clear.

Adolescent↗
PubMed1991

Effects of exogenous insulin-like growth factor I on insulin-like growth factor binding proteins in a case of growth hormone insensitivity (Laron-type).

The electrophoretic profiles of serum insulin-like growth factor binding proteins (IGFBPs) from an 18-year-old patient with growth hormone (GH) insensitivity were analysed by Western ligand blotting before and after administration of recombinant human insulin-like growth factor I (IGF-I). Under basal conditions, the profile was the same as that observed in all cases of GH deficiency or insensitivity, that is, low IGFBP-3 (seen as two bands of 41.5 and 38.5 kDa) and enhanced IGFBP-2 and, to a lesser extent, IGFBP-1. Subcutaneous injection of IGF-I, 40 micrograms/kg, provoked an increase in serum IGF-I levels to close to the lower limits of the normal range and a small increase in IGFBP-3, suggesting that IGF-I has a direct effect on the synthesis of this GH/IGF-I-dependent IGFBP. Moderate increases were also observed in IGFBP-2 and IGFBP-4. Repeated doses of IGF-I over 7 days had no further effect on these changes, which persisted for a few days after the last injection.

Adolescent↗
PubMed1991

Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism.

In addition to its classical effects on growth, growth hormone (GH) has been shown to have a number of other actions, all of which are initiated by an interaction with specific high affinity receptors present in a variety of tissues. Purification of a rabbit liver protein via its ability to bind GH has allowed the isolation of a cDNA encoding a putative human growth hormone receptor that belongs to a new class of transmembrane receptors. We have previously shown that this putative growth hormone receptor gene is genetically linked to Laron dwarfism, a rare autosomal recessive syndrome caused by target resistance to GH. Nevertheless, the inability to express the corresponding full-length coding sequence and the lack of a test for growth-promoting function have hampered a direct confirmation of its role in growth. We have now identified three nonsense mutations within this growth hormone receptor gene, lying at positions corresponding to the amino terminal extremity and causing a truncation of the molecule, thereby deleting a large portion of both the GH binding domain and the full transmembrane and intracellular domains. Three independent patients with Laron dwarfism born of consanguineous parents were homozygous for these defects. Two defects were identical and consisted of a CG to TG transition. Not only do these results confirm the growth-promoting activity of this receptor but they also suggest that CpG doublets may represent hot spots for mutations in the growth hormone receptor gene that are responsible for hereditary dwarfism.

Dwarfism↗
PubMed1990

Insulin-like growth factor-I gene analysis in subjects with constitutionally variant stature.

The IGF-I gene from leukocyte DNA of a control population of normal stature was studied using Southern blotting. Restriction fragment lengths for 21 enzymes were determined and three restriction fragment length polymorphisms (RFLP) were found (EcoRV, HindIII, and PvuII). In addition, the IGF-I gene of 64 constitutionally short subjects, five Pygmies, and 10 constitutionally tall subjects was analyzed. No IGF-I gene alterations were detectable by Southern blot in any of these conditions. Linkage analysis using genetic markers (RFLP) yielded results that were uninformative for five constitutionally short families investigated, owing to the limited number of RFLP and their low incidence (17% for the 5.2-kb HindIII, 5-kb PvuII RFLP alleles, and 13% for the 13-kb EcoRV RFLP allele). The EcoRV RFLP was found to map near Exon 1. The incidence of the 13-kb polymorphic allele with EcoRV proved to be lower (4%) in the group with constitutionally short stature than in controls. These results could suggest that modifications in the region of the IGF-I gene may be involved in constitutionally short subjects.

Adolescent↗
PubMed1989

[21-deoxycortisol. A new marker of virilizing adrenal hyperplasia caused by 21-hydroxylase deficiency].

21-deoxycortisol is a steroid produced mainly by the adrenal gland. Its normal plasma baseline concentrations (0.03 to 0.30 n/ml) and its concentrations after tetracosactide injection (0.15 to 0.76 ng/ml) do not significantly vary with age, sex and phases of the menstrual cycle. 21-deoxycortisol was assayed in plasma by a specific radioimmunological method and its values were compared with those of 17-OH progesterone in heterozygous subjects with the classical and non-classical forms of 21-hydroxylase deficiency, and in the amniotic fluid of foetuses with this deficiency. Baseline concentrations of 21-deoxycortisol in the classical forms of 21-hydroxylase deficiency (n = 12; 55.36 to 186.6 ng/ml) and post-tetracosactide concentrations in non-classical late onset forms (n = 31; 4.04 to 47 ng/ml) were much higher than in normal subjects, thus making this steroid as sensitive as, or even more sensitive than 17-OH progesterone in diagnosing 21-hydroxylase deficiency. Post-tetracosactide assays of 21-deoxycortisol in 84 heterozygous subjects with 21-hydroxylase deficiency (0.70 to 5.40 ng/ml) enabled these subjects to be detected with a more than 90 percent sensitivity, which cannot be obtained with 17-OH progesterone assays. 21-deoxycortisol concentrations in the amniotic fluid of foetuses with 21-hydroxylase deficiency (n = 11; 0.391 to 0.930 ng/ml) were constantly superior to those observed in normal foetuses (n = 38; 0.034 to 0.221 ng/ml), so that the deficiency can be diagnosed with the steroid as easily as with 17-OH progesterone.

17-Hydroxycorticosteroids↗
PubMed1989

Molecular forms of serum insulin-like growth factor (IGF)-binding proteins in man: relationships with growth hormone and IGFs and physiological significance.

Insulin-like growth factor-I (IGF-I) and IGF-II are associated in the blood with specific binding proteins (BPs), forming complexes that elute in gel filtration with estimated mol wt around 40 and 150 kD. The latter appears to be under GH control. Five molecular forms of BP (41.5, 38.5, 34, 30, and 24 kD) have been identified by Western blotting using 125I-labeled IGF. All five forms are present in the smaller complexes, but only the 41.5- and 38.5-kD forms are found in the larger complexes. In this study immunoblotting showed that the 41.5- and 38.5-kD forms were recognized by antibodies directed against the GH-dependent BP purified from human plasma, and the 30-kD form was recognized by antibodies directed against the BP purified from amniotic fluid. The 34- and 24-kD forms proved to be immunologically unrelated to the other three. In sera with large quantities of the 41.5- and 38.5-kD forms, an additional band was often observed immediately ahead of the migration front of the 30 kD band. This was recognized by the anti-GH-dependent BP antibody and probably corresponds to a degradation product of the 41.5- and 38.5-kD BPs. Serum 41.5- and 38.5-kD BPs have been found to be elevated in acromegaly, where GH hypersecretion causes increased IGF-I levels, and diminished in cases of genetic or idiopathic GH deficiency and defects of the GH receptor (Laron's syndrome), where both IGF-I and IGF-II are decreased, as well as in Pygmy adults and children who have isolated IGF-I deficiency. In all of these conditions, the proportions of the 34- and 30-kD forms were inversely related to those of the 41.5- and 38.5-forms. Under treatment, the BP profiles tended to return to normal. In cases of GH deficiency caused by a tumor, the BP profiles resembled those of hypopituitary or normal serum, depending on whether IGF levels were diminished or normal. It, therefore, seems that BP synthesis is coordinated with IGF-I synthesis and may not be directly GH dependent. The results of neutral pH gel filtration analysis of hypopituitary (idiopathic and tumoral) and normal sera point to a relationship between the levels of circulating IGFs and those of the 150-kD IGF-BP complex whose binding units are the 41.5- and 38.5-kD BPs. It, therefore, seems that the 150-kD complex controls the bioavailability of IGF-I and IGF-II.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed1986

Somatomedin (insulin-like growth factors)-binding proteins. Molecular forms and regulation.

The insulin-like growth factor (IGF)-binding proteins present in the human serum and various biological media have been characterized by several methods: gel filtration, sucrose gradient sedimentation, polyacrylamide gel electrophoresis and chromatofocusing. Several forms have been identified with molecular weights of approximately 42,000, 39,000, 34,000, 30,000 and 24,000 daltons. Results of competitive binding studies suggest that the different forms of binding proteins have different affinities for IGF-I and IGF-II. The influence of various hormones and pathophysiological conditions on the biosynthesis of the binding proteins has been investigated.

Adult↗
PubMed1986

Specific assay for insulin-like growth factor (IGF) II using the IGF binding proteins extracted from human cerebrospinal fluid.

A protein-binding assay for insulin-like growth factor II (IGF II) is described. The assay uses IGF binding proteins extracted from human cerebrospinal fluid which have selective affinity for IGF II. IGF I was 9 times less potent than IGF II in displacing [125I]IGF II, and when mixtures of the IGFs were assayed at IGF I/IGF II ratios of 2, 5, and 10, interference from IGF I in the assay was 0%, 5%, and 9%, respectively. Given the serum concentrations of IGF I and IGF II estimated by RIA and by this protein-binding assay, IGF I can be said to have had no cross-reaction when IGF II was assayed in human serum and at most 5% cross-reaction in the case of rat serum. After separation of IGFs from their binding proteins by acidic gel filtration, serum IGF II levels (mean +/- SE) measured by this method were 1322 +/- 66 ng/ml in normal adults, 500 +/- 65 ng/ml in patients with total GH deficiency, 1327 +/- 69 ng/ml in untreated acromegalic patients, and 1817 +/- 145 ng/ml in uremic patients undergoing chronic hemodialysis. In postpubertal young rats, the mean serum IGF II level was 43 +/- 2.6 ng/ml and after hypophysectomy it was 16 +/- 2.4 ng/ml. Although the IGF II levels in man and in the rat were different, they appeared to be similarly GH dependent, although less so than IGF I. In view of the sensitivity (0.03 ng IGF II) and the specificity of this assay, the small quantities of cerebrospinal fluid required (1 mu leq/assay tube) and its applicability for IGF II measurement in several species, the use of this assay for measuring IGF II in a variety of biological media can be envisaged.

Adolescent↗
PubMed1986

Serum levels of insulin-like growth factor (IGF) and IGF-binding protein in constitutionally short children and adolescents.

Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF-bp) levels were studied in 92 constitutionally short children and adolescents (height less than mean for age -2 SD) and in 13 subjects after completion of growth. IGF levels increased with age in a manner similar to that in normal subjects, but at lower levels (P less than 0.001). The values were 0.41 +/- 0.03 SEM U/ml in 1 to 5 year old children, 0.72 +/- 0.03 U/ml in 6- to 16 year old prepubescent children and 0.95 +/- 0.05 U/ml during puberty. IGF-bp levels developed in a similar way, the values being 0.45 +/- 0.06, 0.61 +/- 0.04 and 0.85 +/- 0.06 U/ml, respectively, for the three periods considered. Both IGF and IGF-bp levels in each of the three groups were significantly lower than those in normal subjects at the same stage of development. After fusion of the epiphyses, IGF and IGF-bp levels were within the normal range. A longitudinal study was undertaken in 15 subjects, showing increases in height corresponding with increases in IGF levels. For all the subjects studied during their growth period, there was a correlation between height age and IGF levels (r = 0.64, P less than 0.001). All the subjects exhibited a normal rise in GH levels following stimulation. Although the possibility of quantitative or qualitative disorders of GH biosynthesis cannot be excluded in some of the cases, our data are compatible with the hypothesis that the growth retardation observed in constitutionally short children results, at least in part, from insufficient IGF production during post-natal growth.

Adolescent↗
PubMed1979

Transient partial hGH deficiency in prepubertal children with delay of growth.

UNLABELLED: The hGH response to an ornithin or an insulin test was measured in 105 children from 11-18 yr old with delay of growth more than 2 SD. Besides 74 subjects with normal values and 7 with complete lack of response, 24 subjects exhibited a partial rise of GH. Most of the latter had decreasing growth rate and no sign of puberty. Out of 15 assessed for GH function after onset of puberty, 14 showed a normal response accompanying a markedly increased growth velocity. Four other subjects with partial response who were receiving sexual hormones for 48 hr before the second test showed a normal response also. An exogenous hGH treatment administered in two of these patients resulted in a marked and sustained growth increase far before entering puberty. SPECULATION: The findings that plasma GH responses to stimulation tests is reduced in some children with decreasing growth rate before puberty and return to normal after onset of sexual development, would suggest a transient and functional defect in growth hormone secretion and the physiologic role of sexual hormones on GH release mechanism at that period of life.

Adolescent↗
PubMed1979

17-Hydroxyprogesterone in the cosyntropin test: results in normal and hirsute women and in mild congenital adrenal hyperplasia.

The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗
PubMed1978

Early paradoxical decrease in serum somatomedin activity following injection of growth hormone.

The early effects have been investigated of an intra-muscular growth hormone injection (6 mg/m2) on serum somatomedin activity in 21 children with growth hormone deficiency and in 5 children with constitutional short stature. In cases of hGH total deficiency, there was an early and significant decrease in SM activity, which reached a minimum level 2 hours after the injection (-34% p less than 0.01). After 24 hours, SM activity increased to +64% above basal levels. In cases of hGH partial deficiency and in short, non-hGH deficient children, no similar early changes were observed. Neither was any correlation found between the variations in SM activity and those in hGH or free fatty acid levels. The unexpected early decrease in SM activity following hGH administration seems to be related to GH deficiency.

Child↗
PubMed1978

Pituitary-adrenal axis activity in treated congenital adrenal hyperplasia: static and dynamic studies.

The pituitary-adrenal axis activity was evaluated in 43 patients, treated for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, by measuring plasma ACTH, 17-hydroxyprogesterone (17-OHP), testosterone, and aldosterone. Dynamic studies were performed by injecting 250 micrograms synthetic ACTH im and collecting blood samples 1 h later for steroid analysis. Twelve to fourteen hours after the last hydrocortisone dose given the evening before, plasma ACTH fluctuated widely from less than 10-475 pg/ml, 17-OHP exceeded normal values and varied from 1-275 ng/ml, while testosterone ranged from 3-151 ng/100 ml. The correlations between ACTH and 17-OHP (n equal 61, r equal 0.665, P less than 0.001) and between 17-OHP and testosterone (n = 43, r = 0.761, P less than 0.001) were good, while that between 17-OHP and aldosterone (n = 64, r = 0.512, P less than 0.001) was rather poor. One hour after ACTH injection, the mean level of 17-OHP was significantly increased as compared to the mean basal level [96.8 ng/ml +/- 10.6 (SE) as compared to 67.0 ng/ml +/- 8.1 (SE)]. However, only 12 out of the 48 tests showed a positive response equal to or greater than 100%, and the majority of these responses (10 out of 12) occurred when basal levels of 17-OHP were between 10-70 ng/ml. This suggests that when basal levels fall outside these values, the pituitary-adrenal axis is either too inhibited or too stimulated to react to exogenous ACTH. Of the 48 tests where 17-OHP was measured, 23 had basal level values within these limits, the mean being 40.3 ng/ml. The corresponding mean ACTH level was 99 pg/ml with a wide range (1-230 pg/ml). On the other hand, in prepubertal children who exhibited 17-OHP concentrations between 10-70 ng/ml, testosterone varied from 3-30 ng/100 ml, with a mean of 16.0 ng/100 ml +/- 1.9 (SE) which is not different from the mean level found in normal children [14.0 ng/100 ml +/- 1.3 (SE)]. Thus, under the influence of endogenous ACTH which is moderately increased, 17-OHP concentrations far exceed normal values, whereas plasma testosterone seems to be unaffected.

17-alpha-Hydroxyprogesterone↗
PubMed1976

Plasma aldosterone concentrations related to 17alpha-hydroxyprogesterone in congenital adrenal hyperplasia.

Plasma aldosterone and 17alpha-hydroxyprogesterone (17-OHP) concentrations were measured in 35 patients with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. Ten patients had never been treated and among them were 4 salt-losing infants. Both aldosterone and 17-OHP were high in the 6 untreated non salt-losers. The values ranged respectively from 110 to 376 pg/ml and from 150 to 292 ng/ml. Results were variable in the 4 salt-losers. Three out of 5 untreated non salt-losers who were submitted to a low sodium diet, responded by doubling their aldosterone levels. When plasma 17-OHP concentrations were less than 30 ng/ml, the mean aldosterone level in the treated non salt-losers (n=6) was 15.3 pg/ml +/- 4.3 (SE). This value was not different from the mean level found in the control children (n=7), 18.8 pg/ml +/- 3.2. In the treated salt-losers (n=9), the measured aldosterone levels were less than or equal to 10 pg/ml 7 times out of 9. When the treated patients exhibited plasma 17-OHP concentrations greater than 30 ng/ml, the salt-losers (n=11) were distinguished from the non salt-losers (n=8) in that they showed as significantly lower aldosterone mean level, 24.6 pg/ml +/- 4.3 against 69 pg/ml +/- 13.4 found in the non salt-losers. The salt-losers displayed no aldosterone increases to synthetic ACTH stimulation under treatment or at the withdrawal of treatment, while positive aldosterone responses were often observed in the non salt-losers. In the latter group, studied under different conditions (with and without therapy, on low sodium diet, after ACTH test) a significant correlation was found between aldosterone and 17-OHP levels expressed in log. values, (n=38, r=0.80, P less than 0.001). The relationship could also be established with the values obtained from all the salt-losers, but it was less significant, (n=35, r=0.46, P less than 0.02).

Adolescent↗
PubMed1975

Studies of ACTH secretion control in 116 cases of Cushing's syndrome.

Plasma ACTH (normal value: 0.16 plus or minus mU/100 ml) was measured in 116 patients with Cushing's syndrome, using a bioassay including dynamic tests and sequential determinations. In 10 patients with adrenal tumors ACTH levels were nondetectable (ND) or low, and usually nonstimulatable. In 10 patients with ectopic ACTH secretion high levels (0.42 plus or minus 0.07 mU/100 ml) were measured. The extracts of 6 tumors yielded an ACTH-like substance. Forty-three patients with Cushing's disease (without pituitary tumor) had, before treatment, a mean ACTH level of 0.18 plus or minus 0.01 mU/100 ml, accompanied by high levels of plasma cortisol (32.1 plus or minus 1.9 mug/100 ml). Irregular nycthemeral variations occurred. ACTH rose to 0.30 mU/100 ml after incomplete adrenalectomy (20 patients) and to 1.14 mU/100 ml after total adrenalectomy (21 patients). Dexamethasone (8 mg per day) suppressed ACTH levels. Metyrapone induced a normal ACTH rise, but at abnormal times. Lysine-vasopressin (LVP) induced an ACTH mean relative increase of 120% before, and of 140% after adrenalectomy (i.e., within the normal range). Six nonadrenalectomized patients with pituitary tumors showed similar abnormalities of ACTH regulation. However, the ACTH rise after LVP was above 500%. When pituitary tumors occurred after adrenalectomy (12 patients) the mean basal ACTH level was 18 mU/100 ml. Dexamethasone induced a 90% decrease, and LVP a 416% increase in ACTH levels. In 6 patients with nodular adrenal hyperplasia, ACTH was undetectable before treatment. After adrenalectomy, ACTH rose to 0.4 mU/100 ml (11 patients) and the increase after LVP was 90%. Five additional patients developed pituitary tumors. These data confirm the abnormalities of ACTH feedback regulation in Cushing's disease. However, even when pituitary tumors occur, ACTH levels can be altered by metyrapone, dexamethasone and LVP. This last test is of particular interest for the detection of pituitary tumors. The follow-up pattern of treated nodular adrenal hyperplasia appears to be very similar to that of Cushing's disease.

Adrenal Gland Diseases↗
PubMed1975

Organ culture of human somatotrophic pituitary adenomas: ultrastructure and growth hormone production.

Ten somatotrophic adenomas removed from acromegalic patients and fragments of the non-tumoural surrounding pituitary were submitted to organ culture for periods of up to one month. Electron microscopic observation shows that these tumours retain their histological differentiation throughout the culture period. The cell morphology of the cultured tumours remains essentially unchanged and in particular the secretory granules keep their initial size (150 and 130 nm). However, the granules disappear gradually so that most of the cells look chromophobic by the 4th week of culture, and numerous lysosomes as well as autophagic figures appear at the same time. The hGH concentration in the culture medium has been measured of 4 adenomas. It is very high (10-fold greater than that from non-tumoural pituitary medium) during the first week (range 200-300 mug/ml). It still remains very high in the same experiments until the second week of culture in one experiment (200 mug/ml). After incubation of cultures with 3-H-leucine 3 H-hGH is obtained in the medium giving evidence of hormone synthesis by adenoma cells in culture. 3-H-hGH represents 40 percent of 3-H-proteins in the culture medium and gives the same elution pattern as standard hGH on Sephadex G 100 chromatography. A certain degree of correlation is observed between morphological and biological results: the greatest hGH production is obtained from explants which maintain the best histological appearance.

Acromegaly↗