The sequential administration of growth hormone-releasing hormone followed 120 minutes later by hexarelin, as an effective test to assess the pituitary GH reserve in man.


OBJECTIVE:GH deficiency, either in children or in adults, is a clinically relevant problem. The diagnosis is based on dynamic tests of GH secretion, which are clear cut on a group basis but highly problematic for individual diagnosis. The controversy surrounding the diagnosis of GH deficiency reflects the absence of a gold standard dynamic test. The synthetic hexapeptide hexarelin and GHRH stimulate GH secretion using different mechanisms. A sequential test has been devised using the administration of GHRH as first stimulus followed 120 minutes later by hexarelin. The two aims of the study were (a) to evaluate the interaction of GHRH and hexarelin, and (b) to devise a sequential test of GH reserve. DESIGN:The GH stimuli used were GHRH (1 microgram/kg i.v.) as a pituitary stimulus, and hexarelin (1 microgram/kg i.v.) as a GH stimulus whose main action is hypothalamic. Each subject was tested twice in order to serve as his own control. Three different studies, each with two duplicate tests, were performed on separate groups of individuals: (a) GHRH followed 120 minutes later by hexarelin and on the second day hexarelin followed 120 minutes later by GHRH; (b) GHRH followed 120 minutes later by GHRH and on the other day hexarelin followed 120 minutes later by hexarelin; (c) GH 0.5 IU i.v. followed 120 minutes later by GHRH and on the other day, the same dose of GH followed 120 minutes later by hexarelin. PATIENTS:Eighteen normal volunteers (12 women, 6 men) after giving informed consent. MEASUREMENTS:Plasma GH levels were measured by time-resolved fluoroimmunoassay; each value shown is the mean +/- SEM of n = 6. RESULTS:GHRH followed 120 minutes later by hexarelin induced two episodes of GH secretion (expressed as mean GH peak, mU/l). The GHRH-mediated GH release showed a mean GH peak of 38.2 +/- 13.6 mU/l and after hexarelin 120 minutes later of 56.7 +/- 18.0 mU/l. The contrary sequence blocked the second stimulus, i.e. the hexarelin-stimulated GH mean peak was 54.7 +/- 18.4, and the GH release 120 minutes later after GHRH was 4.8 +/- 1.9 (P < 0.05 vs GHRH used as first stimulus). In the two sequential tests using the same stimulus, the second GH peak was reduced. In fact, GHRH induced a GH mean peak of 63.8 +/- 21.1 mU/l as first stimulus, greater (P < 0.05) than when GHRH was administered again 120 minutes later (22.0 +/- 5.9 mU/l). Similar results were obtained with hexarelin, with a first mean peak of 70.6 +/- 10.3 mU/l, and a second one 120 minutes later of 13.4 +/- 4.6 mU/l (P < 0.05). The blockade of the second stimulus was not due to the feed-back action of the GH released by the first stimulus. In fact, the i.v. administration of exogenous GH induced a mean GH peak of 168.0 +/- 89.7 and reduced the action of GHRH administered 120 minutes later (26.1 +/- 8.1). The previous administration of GH (mean peak 115.5 +/- 42.0) did not alter the action of hexarelin injected 120 minutes later, showing a mean peak of 71.9 +/- 11.2. The large variability in the stimulatory action of GHRH contrasted vividly with the reproducibility of hexarelin. Furthermore, individually analysed, only one of the 12 subjects tested first with hexarelin, compared to 4 out of 12 tested with GHRH as first stimulus, presented a blunted response (< 13 mU/l). After the sequential stimulus there were no false negatives. CONCLUSION:The sequential administration of GHRH in normal subjects and of hexarelin 120 minutes later provides separate information regarding pituitary GH reserve, of both secretagogues without mutual interference. There were not false negative results to the combined test. This sequentially delayed test may be of some value in the clinical setting for assessing pituitary GH reserve.


Clin Endocrinol (Oxf)


Clinical endocrinology


Micic D,Popovic V,Kendereski A,Peino R,Dieguez C,Casanueva FF




Has Abstract


1996-11-01 00:00:00












  • Relationships between emerging cardiovascular risk factors, z-BMI, waist circumference and body adiposity index (BAI) on adolescents.

    abstract:OBJECTIVE:The body adiposity index (BAI) has been recently proposed as an alternative index to body mass index (BMI) and waist circumference (WC) to evaluate adiposity in adults, with special focus on its ability to discriminate gender specificities on adiposity. Endothelial dysfunction, circulating endothelial cells (...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Dias IB,Panazzolo DG,Marques MF,Paredes BD,Souza MG,Manhanini DP,Morandi V,Farinatti PT,Bouskela E,Kraemer-Aguiar LG

    更新日期:2013-11-01 00:00:00

  • Studies in constitutionally tall adolescents: somatostatin decrease associated with growth hormone increase after TRH injection.

    abstract::The paradoxical GH response to TRH observed in certain adolescents with constitutional tall stature is associated with a 60% fall in plasma levels of somatostatin. Conversely, those tall subjects who do not show a GH increase after TRH, or during a saline control infusion maintain steady levels of somatostatin in plas...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Garcia Blanco M,Evain Brion D

    更新日期:1984-10-01 00:00:00

  • Which testosterone replacement therapy?

    abstract::Three different forms of testosterone (T) replacement therapy were compared; they were the intramuscular injection of mixed testosterone esters 250 mg; the subcutaneous implantation of 6 X 100 mg pellets of fused testosterone; and the oral administration of testosterone undecanoate (TU) 80 mg twice daily. Six hypogona...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Cantrill JA,Dewis P,Large DM,Newman M,Anderson DC

    更新日期:1984-08-01 00:00:00

  • Cytotoxic T lymphocyte antigen 4 gene polymorphism confers susceptibility to type 1 diabetes in Japanese children: analysis of association with HLA genotypes and autoantibodies.

    abstract:OBJECTIVE:Although the polymorphisms of the cytotoxic T lymphocyte antigen 4 (CTLA4) gene have been shown to be associated with Type 1 diabetes in Caucasians, some conflicting results have been reported among subjects of different ethnic backgrounds. We examined a CTLA4 polymorphism and its relationship to human leucoc...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Kikuoka N,Sugihara S,Yanagawa T,Ikezaki A,Kim HS,Matsuoka H,Kobayashi Y,Wataki K,Konda S,Sato H,Miyamoto S,Sasaki N,Sakamaki T,Niimi H,Murata M

    更新日期:2001-11-01 00:00:00

  • PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency.

    abstract:OBJECTIVE:Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND MEASUREMENTS:A mul...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,多中心研究


    authors: Lemos MC,Gomes L,Bastos M,Leite V,Limbert E,Carvalho D,Bacelar C,Monteiro M,Fonseca F,Agapito A,Castro JJ,Regateiro FJ,Carvalheiro M

    更新日期:2006-10-01 00:00:00

  • A ten-year clinical update of a large RET p.Gly533Cys kindred with medullary thyroid carcinoma emphasizes the need for an individualized assessment of affected relatives.

    abstract:OBJECTIVE:Reviewing the clinical outcomes of a large kindred with a RET p.Gly533Cys mutation, 10 years after the first description of this kindred, has provided an important set of clinical data for healthcare decision-making. DESIGN AND PATIENTS:We identified 728 RET533 Brazilian relatives, spread out over 7 generati...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Signorini PS,França MI,Camacho CP,Lindsey SC,Valente FO,Kasamatsu TS,Machado AL,Salim CP,Delcelo R,Hoff AO,Cerutti JM,Dias-da-Silva MR,Maciel RM

    更新日期:2014-02-01 00:00:00

  • Acromegaly surgery in Manchester revisited--the impact of reducing surgeon numbers and the 2010 consensus guidelines for disease remission.

    abstract:INTRODUCTION:  Surgical remission rates for acromegaly vary and are dependent on the tumour morphology, biochemical definition of disease remission and surgical expertise. A previous report from the Manchester region in 1998 reported an overall surgical remission rate of 27% using accepted criteria for biochemical remi...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Wang YY,Higham C,Kearney T,Davis JR,Trainer P,Gnanalingham KK

    更新日期:2012-03-01 00:00:00

  • Problems in diagnosing atypical Gitelman's syndrome presenting with normomagnesaemia.

    abstract:OBJECTIVE:Gitelman's syndrome, recognized as a variant of Bartter's syndrome, is characterized by hypokalaemic metabolic alkalosis in combination with hypomagnesaemia and hypocalciuria. Overlapping biochemical features in Gitelman's syndrome and Bartter's syndrome has been observed. Here, we investigated the clinical, ...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Nakamura A,Shimizu C,Nagai S,Yoshida M,Aoki K,Kondo T,Miyoshi H,Wada N,Tajima T,Terauchi Y,Yoshioka N,Koike T

    更新日期:2010-02-01 00:00:00

  • 17 beta-oestradiol counteracts the formation of the more acidic isoforms of follicle-stimulating hormone and luteinizing hormone after menopause.

    abstract:OBJECTIVE:When the gonadotrophin levels increase at midcycle, more basic isoforms of FSH and LH appear in the circulation. However, when these gonadotrophins increase at menopause more acidic forms appear. The present study was done to see whether chronic 17 beta-oestradiol (E2) administration to post-menopausal women ...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Wide L,Naessén T

    更新日期:1994-06-01 00:00:00

  • Cranial radiotherapy of childhood brain tumours: growth hormone deficiency and its relation to the biological effective dose of irradiation in a large population based study.

    abstract:OBJECTIVE:The study was to determine the incidence of GH deficiency (GHD) following cranial radiotherapy (RT) for a childhood brain tumour in a large population based study and analyse the biological effective dose (BED) to the hypothalamus/pituitary (HP) region as a risk factor. DESIGN:BED was assessed by use of the ...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Schmiegelow M,Lassen S,Poulsen HS,Feldt-Rasmussen U,Schmiegelow K,Hertz H,Müller J

    更新日期:2000-08-01 00:00:00

  • Normal prolactin response following thyrotrophin releasing hormone in patients with autonomously functioning euthyroid multinodular goitre.

    abstract::Twelve female patients (mean age 60 years, range 41--74) with euthyroid multinodular goitre and a flat TRH test (median delta TSH 0.9 muIU/ml, range 0--3.5) had normal prolactin responses to TRH (median data prolactin 48 ng/ml, range 6--115). The results are comparable with those in euthyroid patients receiving full s...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Elte JW,Wiarda KS,Frölich M,Haak A

    更新日期:1978-11-01 00:00:00

  • The basal plasma glucose: a simple relevant index of maturity-onset diabetes.

    abstract::The 'basal' plasma glucose, defined as the stable overnight concentration, has been assessed as an index of diabetes control by comparison with plasma glucose measurements during 24-h profiles in diet-treated maturity-onset diabetic patients and normal subjects. The basal plasma glucose correlated with the total (r=0....

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Holman RR,Turner RC

    更新日期:1981-03-01 00:00:00

  • Use of Tag single nucleotide polymorphisms (SNPs) to screen PTPN21: no association with Graves' disease.

    abstract:OBJECTIVE:The protein-tyrosine-phosphate nonreceptor 22 gene (PTPN22) has recently been identified as a susceptibility locus for a number of autoimmune diseases including Graves' disease (GD). PTPN21 is another member of the PTPN family and its gene PTPN21 maps to the first reported region of genetic linkage to GD, GD-...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Zeitlin AA,Heward JM,Brand OJ,Newby PR,Franklyn JA,Gough SC,Simmonds MJ

    更新日期:2006-09-01 00:00:00

  • Serum testosterone bioassay evaluation in a large male cohort.

    abstract:OBJECTIVE:To assess if a cell-based readout of androgen action in serum demonstrates a closer association with recognized classical parameters of androgen action in men than current measures of serum testosterone (T). DESIGN:To develop, validate and utilize a mammalian cell-based assay to measure specifically bioactiv...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Need EF,O'Loughlin PD,Armstrong DT,Haren MT,Martin SA,Tilley WD,Florey Adelaide Male Aging Study.,Wittert GA,Buchanan G

    更新日期:2010-01-01 00:00:00

  • Serum thyroglobulin concentrations and 131I whole body scans in the diagnosis of metastases from differentiated thyroid carcinoma (after thyroidectomy).

    abstract::Measurements of circulating thyroglobulin (hTg) and 131I whole body scan were performed in 101 patients with differentiated thyroid carcinoma who had been subjected to surgical thyroidectomy and 131I ablation of remaining thyroid tissue. All 45 patients with positive scans (i.e. functioning metastases) had elevated hT...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Pacini F,Pinchera A,Giani C,Grasso L,Baschieri L

    更新日期:1980-07-01 00:00:00

  • Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome.

    abstract:OBJECTIVE:To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome. DESIGN:An evaluation of the standard clinical practice at one institution. PATIENTS:Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adr...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Verhelst JA,Trainer PJ,Howlett TA,Perry L,Rees LH,Grossman AB,Wass JA,Besser GM

    更新日期:1991-08-01 00:00:00

  • Incidence of abnormal liver biochemical tests in hyperthyroidism.

    abstract:OBJECTIVE:Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen the severity of the abnormal serum liver biochemistries. There is a wide range of the incidence of these abnormalities in the published literature...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Lin TY,Shekar AO,Li N,Yeh MW,Saab S,Wilson M,Leung AM

    更新日期:2017-05-01 00:00:00

  • The level of endothelin-like immunoreactivity in seminal fluid correlates positively with semen volume and negatively with plasma gonadotrophin levels.

    abstract:OBJECTIVE:The newly discovered vasoactive peptides, endothelin 1, 2 and 3, and their receptors are widely distributed in various non-vascular tissues. Recent studies have suggested the presence, as well as possible regulatory roles, of endothelins at several levels of the pituitary-gonadal axis. We determined the level...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Hammami MM,Haq A,AlSedairy S

    更新日期:1994-03-01 00:00:00

  • Radiofrequency ablation for the management of thyroid nodules: A critical appraisal of the literature.

    abstract::The majority of benign thyroid nodules are asymptomatic, remain stable in size and do not require treatment. However, a minority of patients with growing nodules may have local symptoms or cosmetic concerns, and thus demand surgical therapy. The timely use of ultrasound-guided, minimally invasive thermal therapies has...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,评审


    authors: Cesareo R,Palermo A,Pasqualini V,Cianni R,Gaspa G,Manfrini S,Pacella CM

    更新日期:2017-12-01 00:00:00

  • Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience.

    abstract:BACKGROUND:There has been a rapid shift from open to laparoscopic approaches in adrenal surgery, but the safety and efficacy of bilateral laparoscopic adrenalectomy (BLA) in patients with corticotrophin (ACTH)-dependent Cushing's syndrome continues to be defined. OBJECTIVE:Review outcomes in the largest series of pati...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Chow JT,Thompson GB,Grant CS,Farley DR,Richards ML,Young WF Jr

    更新日期:2008-04-01 00:00:00

  • Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients.

    abstract:INTRODUCTION:Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment enc...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Mormando M,Chiloiro S,Bianchi A,Giampietro A,Angelini F,Tartaglione L,Nasto L,Milardi D,Formenti AM,Giustina A,De Marinis L

    更新日期:2016-11-01 00:00:00

  • Diverse genetic aetiologies and clinical outcomes of paediatric hypoparathyroidism.

    abstract:CONTEXT:Hypoparathyroidism is characterized by hypocalcaemia, hyperphosphataemia, and low or inappropriately normal parathyroid hormone (PTH) levels. Idiopathic or genetic drivers are the predominant causes of hypoparathyroidism in paediatric-age patients. OBJECTIVE:This study investigated the aetiology and clinical c...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Kim JH,Shin YL,Yang S,Cheon CK,Cho JH,Lee BH,Kim GH,Lee JO,Seo EJ,Choi JH,Yoo HW

    更新日期:2015-12-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of growth hormone in patients on chronic haemodialysis compared with matched healthy subjects: an open, nonrandomized, parallel-group trial.

    abstract:BACKGROUND:GH may be beneficial in treating patients with end-stage renal disease (ESRD). However, the efficacy and safety of GH could be compromised by the potential for accumulation in the circulation. OBJECTIVE:The objective was to investigate the pharmacokinetics and safety of GH treatment in ESRD patients. DESIG...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Langbakke IH,Nielsen JN,Skettrup MP,Harper A,Klitgaard T,Weil A,Engelhardt E,Lange M

    更新日期:2007-11-01 00:00:00

  • Is the management of thyroid nodules and differentiated thyroid cancer in accordance with recent consensus guidelines? - Results of a national survey.

    abstract:OBJECTIVE:To assess approaches to patients with a potentially malignant thyroid nodule and patients with differentiated thyroid carcinoma and compare them with the European Consensus and Guidelines by the American Thyroid Association. DESIGN:A survey of the 388 active members of the Belgian Thyroid Club. METHODS:A qu...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Van den Bruel A,Moreno-Reyes R,Bex M,Daumerie C,Glinoer D

    更新日期:2008-04-01 00:00:00

  • Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation.

    abstract:OBJECTIVE:This study was designed to investigate whether an elevated serum antithyroglobulin antibody (TgAb) reflects cancer recurrence in thyroglobulin (Tg)-undetectable patients with differentiated thyroid carcinoma (DTC) after thyroid ablation. DESIGN:We measured serum TgAb level and evaluated the disease status in...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Chung JK,Park YJ,Kim TY,So Y,Kim SK,Park DJ,Lee DS,Lee MC,Cho BY

    更新日期:2002-08-01 00:00:00

  • Effect of naloxone on neurohypophyseal peptide responses to breast feeding and breast stimulation in man.

    abstract::We have investigated the role of endogenous opioid peptides in the release of oxytocin (OT) in response to breast feeding and breast stimulation in humans. Five breast feeding women were studied on two separate occasions within 4 weeks of delivery. Saline or naloxone, 4 mg bolus and 6 mg/h, was administered intravenou...

    journal_title:Clinical endocrinology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Johnson MR,Andrews MA,Seckl JR,Lightman SL

    更新日期:1990-07-01 00:00:00

  • Serum free cortisol as an ancillary tool in the interpretation of the low-dose 1-μg ACTH test.

    abstract:OBJECTIVE:Serum free cortisol, rather than serum total cortisol (TC), determines glucocorticoid activity in vivo, but how the considerable inter-subject variation in ambient serum free cortisol affects the outcome of dynamic hypothalamic-pituitary-adrenal (HPA) assessment in noncritically ill subjects is unknown. DESI...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Limor R,Tordjman K,Marcus Y,Greenman Y,Osher E,Sofer Y,Stern N

    更新日期:2011-09-01 00:00:00

  • Sodium fluoride stimulates osteocalcin in normal subjects.

    abstract::To test whether the administration of sodium fluoride in vivo results in an increase in osteocalcin concentration, we administered sodium fluoride to seven healthy male subjects for a period of 3 weeks. Fasting calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone and osteocalcin were meas...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Dandona P,Coumar A,Gill DS,Bell J,Thomas M

    更新日期:1988-10-01 00:00:00

  • The effect of single-dose orlistat on postprandial serum glucose, insulin and glucagon-like peptide-1 levels in nondiabetic obese patients.

    abstract:OBJECTIVE:Glucagon-like peptide-1 is an insulin secretion-stimulating gut hormone that is produced in response to food intake. Orlistat (Xenical, F. Hoffman-La Roche, Basel, Switzerland), which decreases fat absorption and increases intestinal fat content, may therefore affect the secretion of glucagon-like peptide-1. ...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,随机对照试验


    authors: Sahin M,Tanaci N,Yucel M,Tutuncu NB,Guvener N

    更新日期:2007-09-01 00:00:00

  • Blockage of the positive feedback effect of oestradiol during prolonged administration of clomiphene citrate to normal women.

    abstract::The effect of clomiphene citrate on the occurrence and timing of the endogenous LH surge in superovulated cycles is unclear. To study further this event, five normally ovulating women were treated with clomiphene citrate 100 mg per day in two different cycles, that is, for 5 days in one cycle (days 2 to 6, CC-5) and f...

    journal_title:Clinical endocrinology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Messinis IE,Templeton A

    更新日期:1988-11-01 00:00:00