Humans; Age determination by skeleton; Hypopituitarism; Dehydroepiandrosterone; Gonadotropin-releasing hormone; Estradiol; Testosterone; Gonadotropins
Abstract :
[en] Fifty-five hypopituitary patients (43 boys and 12 girls) treated with human GH were studied longitudinally before and during puberty, occuring either spontaneously or induced with testosterone enanthate (100 mg/month, im) in boys and ethinylestradiol (10 μg/day, orally) in girls. In addition, 53 boys with idiopathic delayed puberty (IDP) were studied. Gonadotropin integrated responses (IRs) during 90 min after the iv injection of 25 μg/m2 LRH, bone ages (BA), and plasma levels of dehydroepiandrosterone sulfate and testosterone were determined at least yearly. Prepubertal hypopituitary patients with gonadotropin deficiency were characterized by:1) a lowered FSH IR to LRH in most boys and in all girls; 2) a low LH IR for BA; 3) adrenarche either absent or delayed for BA; 4) height age close to BA; and 5) the presence of several pituitary deficiencies. In contrast, most prepubertal hypopituitary patients without gonadotropin deficiency showed: 1) a normal FSH IR to LRH; 2) a normal or intermediate (≥75 mIU/ml-90 min) LH IR for BA; 3) a normal adrenarche for BA; 4) a height age below BA; and 5) isolated GH or GH plus TSH deficiencies. A significant linear correlation was found between LH IR and the logarithm of plasma testosterone. The slopes and levels were similar in controls and hypopituitary boys without gonadotropin deficiency. In IDP, the level was significantly higher. All data obtained in these patients show that the increase in plasma testosterone and the clinical onset of puberty are delayed for the observed pubertal pattern of LH responsiveness. It is concluded that the study of several clinical and biological features, especiallythe gonadotropin IR to LRH, are of predictive value for the diagnosis of normal or deficient gonadotropic function in prepubertal patients with IDP and hypopituitarism.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Bourguignon, Jean-Pierre ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Vanderschueren-Lodeweyckx, M.
Wolter, R.
Malvaux, P.
Craen, M.
Du Caju, M. V. L.
Ernould, Christian ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie
Franchimont, Paul
Language :
English
Title :
Hypopituitarism and idiopathic delayed puberty: a longitudinal study in an attempt to diagnose gonadotropin deficiency before puberty
Publication date :
1982
Journal title :
Journal of Clinical Endocrinology and Metabolism
ISSN :
0021-972X
eISSN :
1945-7197
Publisher :
Oxford University Press, New York, United States - New York
Volume :
54
Issue :
4
Pages :
733-744
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FRSM - Fonds de la Recherche Scientifique Médicale
Frasier SD 1973 Growth hormone stimulation tests in children. In: Raiti S (ed) Advances in Human Growth Hormone Research. DHEW Publications no. 74, NIH, Bethesda, p 162
Illig R, Krawzynska H, Torresani T, Prader A 1975 Elevated plasma TSH and hypothyroidism in children with hypothalamic hypopituitarism. J Clin Endocrinol Metab 41:722
Job JC, Sizonenko PC, Balage M 1971 Interprétation statistique des épreuves de stimulation de la sécrétion d’hormone de croissance par l’insuline et l’arginine. Arch Franc Pediatr 28:505
Milner RDG, Russell-Fraser T, Brook CGD, Cotes PM, Farquhar JW, Parkin JM, Preece MA, Snodgrass GJAI, Stuart-Mason A, Tanner JM, Vince FP 1979 Experience with human growth hormone in Great Britain: the report of the MRC working party. Clin Endocrinol (Oxf) 11:15
Root AW, Snyder PJ, Rezvani I, Digeorge AM, Utiger RD 1973 Inhibition of thyrotropin-releasing hormone-mediated secretion of thyrotropin by human growth hormone. J Clin Endocrinol Metab 36:103
Winter JSD 1976 Analysis of clinical studies with LHRH in children and adolescents. Am J Dis Child 130:590
Tanner JM 1962 Growth at Adolescence, ed 2. Blackwell, Oxford
Vanderschueren-Lodeweyckx M, Wolter R, Malvaux P, Eggermont E, Eeckels R 1974 The glucagon stimulation test. Effect on plasma GH, insulin, cortisol and glucose in children. J Pediatr 85:182
Ernould C, Bourguignon JP, Franchimont P 1979 Usefulness and limits of GnRH test in boys with lack of sexual maturation. Acta Paediatr Belg 32:105
Tanner JM, Whitehouse RH, Takaishi M 1966 Standards from birth to maturity for height, weight, height velocity and weight velocity: British children, 1965. Arch Dis Child 41:454
Zachmann M, Prader A, Kind HP, Hafliger H, Budliger H 1974 Testicular volume during adolescence. Cross-sectional and longitudinal studies. Helv Paediatr Acta 39:61
Greulich WW, Pyle SI 1959 Radiographic Atlas of the Skeletal Development of Hand and Wrist, ed 2. Stanford University Press, Stanford
Franchimont P 1968 Radioimmunoassay of gonadotrophic hormones. In: Margoulies M (ed) Protein and Polypeptide Hormones, part 1. Excerpta Medica, Amsterdam, p 99
Reuter AM, Hendrick JC, Franchimont P 1973 Mise au point d’un dosage radioimmunologique rapide des gonadotrophines. Ann Biol Clin 31:479
Franchimont P, Becker H, Ernould C, Thys C, Demoulin A, Bourguignon JP, Legros JJ, Valcke JC 1974 The effect of hypothalamic luteinizing hormone releasing hormone (LH-RH) on plasma gonadotrophin levels in normal subjects. Clin Endocrinol (Oxf) 3:27
Bell J, Spitz I, Slonim A, Perlman A, Segal S, Palti Z, Rabinowitz D 1973 Heterogeneity of gonadotropin response to LHRH in hy-pogonadotropic hypogonadism. J Clin Endocrinol Metab 36:791
Coscia AM, Fleischer N, Besch PK, Brown LP, Desiderio P 1974 The effect of synthetic luteinizing hormone-releasing factor on plasma LH levels in pituitary disease. J Clin Endocrinol Metab 38: 83
Bremner WJ, Fernando NN, Paulsen CA 1977 The effect of luteinizing hormone-releasing hormone in hypogonadotrophic eunuchoidism. Acta Endocrinol (Copenh) 86:1
Santner SJ, Kulin HE, Santen RJ 1977 Usefulness of urinary gonadotropin measurements to assess luteinizing hormone releasing factor (LRF) responsiveness in hypogonadotropic states. J Clin Endocrinol Metab 44:313
Snoep MC, De Lange WE, Sluiter WJ, Doorenbos H 1977 Differential response of serum LH in hypogonadotropic hypogonadism and delayed puberty to LHRH stimulation before and after clomi-phene citrate administration. J Clin Endocrinol Metab 44:603
Grumbach MM, Roth JC, Kaplan SL, Kelch RP 1974 Hypothalamic putuitary regulation of puberty in man: evidence and concepts derived from clinical research. In: Grumbach MM, Grave GD, Mayer FE (eds) The Control of the Onset of Puberty. Wiley, New York, p 115
Chaussain JL, Garnier PE, Binet E, Vassal J, Scholler R, Job JC 1974 Effect of synthetic leuteinizing hormone-releasing hormone (LH-RH) on the release of gonadotropins in hypophyso-gonadal disorders of children and adolescents. III. Hypopituitarism. J Clin Endocrinol Metab 38:58
Kelch RP, Markovs M, Huss J 1976 LH and FSH responsiveness to intravenous gonadotropin-releasing hormone (GnRH) in children with hypothalamic or pituitary disorders: lack of effect of replacement therapy with human growth hormone. J Clin Endocrinol Metab 42:1104
Kelch RP, Hopwood NJ, Marshall JC 1980 Diagnosis of gonadotropin deficiency in adolescents. Limited usefulness of a standard gonadotropin-releasing hormone test in obese boys. J Pediatr 97: 820
Bourguignon JP, Vanderschueren-Lodeweyckx M, Wolter R, Malvaux P, Du Caju M, Craen M, Ernould C, Franchimont P 1981 Assessment of gonadotrophin deficiency in pituitary dwarfism. Pediatr. Res 15:83 (Abstract)
Job JC, Chaussain JL, Garnier PE, Toublanc JE 1976 Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotropin in hypophysogonadal disorders of children and adolescents. VII. Constitutional delay of puberty in males. J Pediatr 88:494
Sizonenko PC, Paunier L 1975 Hormonal changes in puberty. III. Correlation of plasma dehydroepiandrosterone, testoterone, FSH and LH with stages of puberty and bone age in normal boys and girls and in patients with Addison’s disease or hypogonadism or premature or late adrenarche. J Clin Endocrinol Metab 41:894
Ducharme JR, Forest MG, De Peretti E, Sempe M, Collu R, Bertrand J 1976 Plasma adrenal and gonadal sex steroids in human pubertal development. J Clin Endocrinol Metab 42:468
Apter D, Pakarinen A, Hammond GL, Vihko R 1979 Adrenocortical function in puberty. Acta Paediatr Scand 68:599
Reiter EO, Fuldauer VG, Root AW 1977 Secretion of the adrenal androgen, dehydroepiandrosterone sulfate during normal infancy, childhood and adolescence, in sick infants and in children with endocrine abnormalities. J Pediatr 90:766
Grumbach MM, Richards GE, Conte FA, Kaplan SL 1978 Clinical disorders of adrenal function and puberty: an assessment of the role of the adrenal cortex in normal and abnormal puberty in man and evidence for an ACTH-like pituitary adrenal androgen stimulation hormone. In: James VH, Serio M (eds) The Endocrine Function of the Human Adrenal Cortex. Academic Press, London, p 583
Parker LN, Odell WD 1979 Evidence for existence of cortical androgen-stimulating hormone. Am J Physiol 236:616
Forest MG, De Peretti E 1980 What is the human adrenarche? Static and dynamic hormonal patterns in normal and pathological conditions as indirect evidence for a specific regulation of adrenal androgenic secretions. Horm Res 12:183
Sklar CA, Kaplan SL, Grumbach MM 1980 Evidence for dissociation between adrenarche and gonadarche. Studies in patients with idiopathic precocious puberty, gonadal dysgenesis, isolated gonadotropin deficiency and constitutionally delayed growth and adolescence. J Clin Endocrinol Metab 51:548
Copeland KC, Paunier L, Sizonenko PC 1977 Secretion of adrenal androgens and growth patterns of patients with hypogonadotropic hypogonadism and idiopathic delayed puberty. J Pediatr 91:985
Vanderschueren-Lodeweyckx M, Ilondo MM, Pizarro E, Malvaux P, Eggermont E, Eeckels R 1978 Plasma levels of adrenal androgens before and throughout puberty. Pediatr Res 12:1090 (Abstract)
Rolland A, Roger M, Nahoul K, Canlorbe P, Job JC 1977 La dehydroépiandrosterone plasmatique chez les garçons normaux et dans les retards staturaux et pubertaires, l’obésité et le nanisme hypophysaire des garçons. Arch Franc Pediatr [Suppl 2] 34:133
Tanner JM, Whitehouse RH 1975 A note on the bone age at which patients with true isolated growth hormone deficiency enter puberty. J Clin Endocrinol Metab 41:788
Ernould C, Bourguignon JP, Lambrechts L, Craen M, Du Caju M, Malvaux P, Van Vliet G, Wolter R, Vanderschueren-Lodeweyckx M 1980 Effects of spontaneous and testosterone-induced puberty on height velocity, bone maturation and pubertal development in boys with hypopituitarism during human growth hormone therapy. In: Cacciari E, Prader A (eds) Pathophysiology of Puberty. Academic Press, London and New York, p 315
Illig R, Prader A 1970 Effect of testosterone on growth hormone secretion in patients with anorchia and delayed puberty. J Clin Endocrinol Metab 30:615
Frasier SD, Hilburn JM, Smith FG 1970 Effect of adolescence on the serum growth hormone response to hypoglycemia. J Pediatr 77:465
Blizzard RM, Thompson RG, Baghdassarian A, Kowarski A, Mig-eon CJ, Rodriguez A 1974 The interrelationship of steroids, growth hormone and other hormones on pubertal growth. In: Grumbach MM, Grave GD, Mayer FE (eds) The Control of the Onset of Puberty. Wiley, New York, p 342
Aynsley-Green A, Zachmann M, Prader A 1976 Interrelation of the therapeutic effects of growth hormone and testosterone on growth in hypopituitarism. J Pediatr 89:992
Tanner JM, Whitehouse RH, Hughes PC, Carter BS 1976 Relative importance of growth hormone and sex-steroids for the growth at puberty of trunk length, limb length and muscle width in growth hormone deficient children. J Pediatr 89:1000
Martin LG, Grossman MJ, Connor TB, Levitsky LL, Clark JW, Camitta FD 1979 Effect of androgen on growth hormone secretion and growth in boys with short stature. Acta Endocrinol (Copenh) 91:201
