Changes in plasma GH levels and clinical activity during bromocriptine therapy in acromegaly. The value of predictive tests

1984 ◽  
Vol 106 (2) ◽  
pp. 175-183 ◽  
Author(s):  
J. W. R. Nortier ◽  
R. J. M. Croughs ◽  
G. H. Donker ◽  
J. H. H. Thijssen ◽  
F. Schwarz
Keyword(s):  
Single Dose ◽  
Previous Treatment ◽  
High Specificity ◽  
Clinical Activity ◽  
List Type ◽  
Plasma Prolactin ◽  
Basal Plasma ◽  
Active Acromegaly ◽  
Pre Treatment ◽  
Plasma Gh

Abstract. Twenty-seven patients with active acromegaly despite previous treatment by surgery and/or radiotherapy received bromocriptine in a dose of 10–20 mg daily for a period of 6–9 months. The results of chronic bromocriptine treatment were evaluated by measurement of plasma growth hormone (GH) levels during the day and by subjective and objective criteria of clinical activity. The results of chronic bromocriptine treatment were also compared with four biochemical criteria obtained before treatment e.g. basal plasma prolactin (Prl) levels and the plasma GH response to oral administration of 2.5 mg bromocriptine respectively iv administration of 200 μg TRH and 500 μg somatostatin. The main observations may be summarized as follows: 1) The mean pre-treatment GH levels during the day ranged from 6–207 mU/l. Hyperprolactinaemia was present in 6 patients. 2) During bromocriptine treatment mean plasma GH levels decreased to less than 50% in 11 patients (GH responders) whereas in 19 patients changes of mean plasma GH and of subjective criteria of clinical activity were concordant. 3) Glucose tolerance improved significantly (P < 0.01) in 10 GH-responders and the urinary hydroxyproline/creatinine ratio decreased significantly (P < 0.05) in 8 GH-responders. 4) Five out of 6 patients with hyperprolactinaemia belonged to the group of GHresponders. 5) A single dose of 2.5 mg bromocriptine induced a more than 50% decrease of plasma GH in 8 of 11 GH-responders and in 5 of 16 GH non-responders. 6) The iv injection of 200 μg TRH was followed by a rise of plasma GH of more than 100% in 9 of 11 GHresponders and in 6 of 16 non-responders. 7) Responsiveness to both a single dose of bromocriptine and TRH was found in 8 of 11 GH-responders and in 3 of 16 GH non-responders. Conclusions Bromocriptine is effective as adjunctive therapy when active acromegaly persists after treatment with surgery and/or radiotherapy. In general, a good correlation is found between GH responsiveness and subjective and objective criteria of clinical activity during bromocriptine treatment. Hyperprolactinaemia predicts GH responsiveness to chronic bromocriptine treatment with high specificity. The combination of a bromocriptine test and a TRH test are of best predictive value with respect to the results of chronic bromocriptine therapy in normoprolactinaemic acromegalics.

Growth hormone and somatostatin gene expression in pituitary adenomas with active acromegaly and minimal plasma growth hormone elevation

1990 ◽  
Vol 122 (6) ◽  
pp. 745-752 ◽  
Author(s):  
Patrick Pagesy ◽  
Jacques Y. Li ◽  
Françoise Rentier-Delrue ◽  
Olivier Delalande ◽  
Yves Le Bouc ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Northern Blot Analysis ◽  
Secretory Activity ◽  
Ultrastructural Level ◽  
Wide Range ◽  
Igf I ◽  
Gh Gene ◽  
Basal Plasma ◽  
Active Acromegaly ◽  
Plasma Gh

Abstract. Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level < 4 μg/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 ± 16.1 μg/l, mean ± sem). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1± 0.37 vs 51.5± 34.1 μg · (10−6 cells) · min−1, p< 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6. In conclusion, because of the variability of the biosynthetic and secretory potential of the somatotropic adenomas, patients harbouring this type of pituitary tumours can exhibit a wide range of plasma GH levels. In acromegaly with minimal elevation of plasma GH, the synthesis of SRIH by the adenoma cells themselves could play a role in the inhibition of GH expression.

The effect of photoperiod on plasma hormone concentrations in wether lambs with genetic differences in body composition

1997 ◽  
Vol 65 (3) ◽  
pp. 441-450 ◽  
Author(s):  
S. M. Francis ◽  
B. A. Veenvliet ◽  
S. K. Stuart ◽  
R. P. Littlejohn ◽  
J. M. Suttie
Keyword(s):  
Body Composition ◽  
Food Intake ◽  
Major Effect ◽  
Carcass Composition ◽  
Short Photoperiod ◽  
Plasma Prolactin ◽  
Basal Plasma ◽  
Plasma Hormone ◽  
Plasma Gh ◽  
Long Photoperiod

AbstractThe aim of this study was to determine whether the decrease in plasma growth hormone (GH) levels during a lamb's first autumn is a function of photoperiodic or developmental changes. Wether lambs (no. = 30) from Coopworth sheep selected for low (lean) or high (fat) backfat plus a randomly selected line (control) were subjected to long (16 h light: 8 h dark) or short (8 h light: 16 h dark) photoperiod over a 5-month period after the summer solstice. The animals were regularly blood sampled to determine plasma hormone concentrations. Daily food intake and weekly live weights were measured and the animals were slaughtered at the end of the trial to determine body composition.Food intake and growth rate were greater for sheep on long than on short photoperiod but photoperiod had no major effect on carcass composition. Mean and basal plasma GH, as well as the number and amplitude of pulses, were not affected by photoperiod, however GH secretion decreased from January to May. Plasma levels ofprolactin, insulin-like growth factor 1 (IGF-1), insulin and glucose were greater in animals under long than short photoperiod, while non-esterified fatty acids (NEFA) were unaffected by photoperiod.Lean animals had greater mean and basal plasma GH and increased number and amplitude of pulses compared with fat animals. Prolactin concentrations were also greater in the lean than in the fat sheep, while there were no differences in insulin, glucose and NEFA levels. IGF-1 levels were higher in lean than in fat sheep under long photoperiod but lower under short photoperiod.These results suggest that the decline in plasma GH with increasing age is not affected by photoperiod. While long photoperiod stimulates plasma prolactin and IGF-1 levels as well as intake and growth, the relationship between these parameters is unknown. Hormonal differences between lean and fat genotype sheep are found within the GH axis and prolactin but not within the gonadotropin or insulin axes.

Plasma growth hormone and prolactin responses to TRH and arginine given before and during bromocriptine therapy to patients with acromegaly

1980 ◽  
Vol 95 (3) ◽  
pp. 298-307 ◽  
Author(s):  
Kunihiko Hanew ◽  
Atsushi Sasaki ◽  
Toraichi Mouri ◽  
Kaoru Yoshinaga
Keyword(s):  
Peak Plasma ◽  
Chronic Administration ◽  
Acute Administration ◽  
Plasma Prolactin ◽  
Response Patterns ◽  
Close Relationship ◽  
Basal Plasma ◽  
Plasma Gh ◽  
Sites Of Action ◽  
Marked Suppression

Abstract. The chronic effects of bromocriptine (CB-154) administration on pituitary somatotrophs and lactotrophs were investigated in 9 patients with acromegaly. Following therapy with CB-154 for 3 to 20 weeks, 6 of 9 cases showed a normalization of plasma GH (below 5 ng/ml) and a clinical improvement. These cases were termed 'CB-154-responders'. Plasma GH responses to TRH were observed in all cases of'CB-154-responders' before the therapy and were significantly suppressed during CB-154 therapy, although the response patterns expressed in logarithms were retained. When TRH was administered in 3 cases of acromegaly after acute administration of CB-154 and before chronic CB-154 therapy, the peak plasma GH responses were between those responses seen before and during CB-154 therapy. After iv infusion of arginine, 5 cases of 'CB-154-responders' showed an increase in plasma GH levels. These responses were also significantly suppressed during CB-154 therapy, while the response patterns were also preserved. In these same patients, basal plasma prolactin was consistently suppressed to low levels (mean ± sem: 3.4 ± 0.9 ng/ml) in all 9 cases during CB-154 therapy and plasma prolactin responses to TRH almost disappeared after either acute or chronic administration of CB-154. These findings demonstrate: 1) chronic CB-154 therapy in acromegalic patients gradually reduces the activity of the somatotrophs to synthesize and to release GH while it causes a rapid and marked suppression of lactotrophs; 2) the sites of action to CB-154 on the somatotrophs may be different from those to TRH and arginine (possibly GH-RF),while CB-154 and TRH appear to have a close relationship in regard to sites of action on the lactotrophs

Long-term follow-up of five untreated acromegalic patients

1984 ◽  
Vol 106 (4) ◽  
pp. 437-442 ◽  
Author(s):  
J.W. R. Nortier ◽  
R.J. M. Croughs ◽  
J. H. H. Thijssen ◽  
F. Schwarz
Keyword(s):  
Tolerance Test ◽  
Clinical Activity ◽  
Oral Glucose ◽  
List Type ◽  
Treatment Protocols ◽  
Gh Secretion ◽  
Spontaneous Course ◽  
Long Term Follow Up ◽  
Plasma Gh

Abstract. The present study describes the clinical, biochemical and radiological follow-up of 5 patients with acromegaly, selected from a group of 53 patients, who did not receive treatment during a follow-up period of 5–16 years. The characteristics of these patients included: 1) older age (4 cases), 2) a long history of mild symptoms and signs (4 cases), 3) absence of diabetes mellitus (5 cases), 4) relatively low plasma GH levels (3 cases). The following observations were made during follow-up: clinical activity remained constant in 3 patients and lessonned in 2 patients, the lateral fossa area as calculated from a plain lateral X-ray of the skull remained constant and plasma GH levels measured during an oral glucose tolerance test remained constant in 3 cases, decreased substantially in one case and reached low levels in another case. In this last patient a reproducible increase of plasma GH was found after oral administration of a single dose of 2.5 mg bromocriptine, suggesting complete normality of GH secretion. It is concluded that acromegaly not necessarily progresses in all patients. The results re-emphasize the importance of taking the spontaneous course of pituitary adenomas into account when assessing the effect of various treatment protocols.

Bromocriptine treatment of prolactin secreting macroadenomas: a radiological, ophthalmological and endocrinological study

1986 ◽  
Vol 112 (4) ◽  
pp. 487-493 ◽  
Author(s):  
Johanna W. van 't Verlaat ◽  
Ronald J. M. Croughs ◽  
Martin J. Hendriks ◽  
Nicolaas J. Bosma ◽  
Johan W. R. Nortier ◽  
...  
Keyword(s):  
Tumour Size ◽  
Empty Sella ◽  
List Type ◽  
Plasma Prolactin ◽  
Oculomotor Palsy ◽  
Normal Range ◽  
Plasma Prolactin Level ◽  
Basal Plasma ◽  
Bitemporal Hemianopia ◽  
Tumour Reduction

Abstract. Twelve patients, six women and six men, with macroprolactinomas characterized by extrasellar extension and basal plasma prolactin levels >6 U/l were treated with 10–20 mg bromocriptine daily in four divided doses for a mean period of 2.4 years (range 0.5–3.5 years). The following observations were made: Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in 10 patients. Tumour size was reduced by more than 75% in 11 patients and by 50–75% in one patient. Tumour-reduction was associated with the development of a partial empty sella in eight cases. In four cases the pituitary became visible. Diminished visual acuity (three patients), bitemporal hemianopia (three patients), unilateral or bilateral central scotomas (three patients) and oculomotor palsy (two patients) restored to normal. Hypogonadism (all patients), hypothyroidism (six patients) and hypocorticism (three patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10–20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumour size.

scholarly journals Time-to-Treatment in Oral Cancer: Causes and Implications for Survival

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1321
Author(s):  
Constanza Saka-Herrán ◽  
Enric Jané-Salas ◽  
Antoni Mari-Roig ◽  
Albert Estrugo-Devesa ◽  
José López-López
Keyword(s):  
Oral Cancer ◽  
Previous Treatment ◽  
Diagnostic Procedures ◽  
Original Data ◽  
Primary Treatment ◽  
Medical Attention ◽  
Time Interval ◽  
Pre Treatment ◽  
The Impact ◽  
Lack Of Knowledge

The purpose of this review was to identify and describe the causes that influence the time-intervals in the pathway of diagnosis and treatment of oral cancer and to assess its impact on prognosis and survival. The review was structured according to the recommendations of the Aarhus statement, considering original data from individual studies and systematic reviews that reported outcomes related to the patient, diagnostic and pre-treatment intervals. The patient interval is the major contributor to the total time-interval. Unawareness of signs and/or symptoms, denial and lack of knowledge about oral cancer are the major contributors to the process of seeking medical attention. The diagnostic interval is influenced by tumor factors, delays in referral due to higher number of consultations and previous treatment with different medicines or dental procedures and by professional factors such as experience and lack of knowledge related to the disease and diagnostic procedures. Patients with advanced stage disease, primary treatment with radiotherapy, treatment at an academic facility and transitions in care are associated with prolonged pre-treatment intervals. An emerging body of evidence supports the impact of prolonged pre-treatment and treatment intervals with poorer survival from oral cancer.

395 A first-in-human study of FS118, a tetravalent bispecific antibody targeting LAG-3 and PD-L1, in patients with advanced cancer and resistance to PD-(L)1 therapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A420-A420
Author(s):  
Timothy Yap ◽  
Deborah Wong ◽  
Siwen Hu-Lieskovan ◽  
Kyriakos Papadopoulos ◽  
Michelle Morrow ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Advanced Cancer ◽  
Bispecific Antibody ◽  
Acquired Resistance ◽  
Human Study ◽  
Clinical Activity ◽  
List Type ◽  
Link Type ◽  
Antibody Targeting

BackgroundUpregulation of immune checkpoints, such as LAG-3, plays an important role in promoting resistance to anti-PD-(L)1 therapy. Targeting PD-L1 and LAG-3 using a bispecific antibody may overcome resistance to PD-(L)1 blockade.1 We report initial data from a first-in-human study evaluating FS118 in patients with advanced cancer and resistance to PD-(L)1 therapy.MethodsThe ongoing Phase I FIH study (NCT03440437) is being conducted to evaluate safety, tolerability, immunogenicity, PK/PD and clinical activity of FS118 administered IV weekly to heavily pre-treated patients who had previously received anti-PD-(L)1 therapy for a minimum of 12 weeks. Adverse events were assessed using CTCAEv4.03 and tumor responses assessed using RECISTv1.1 and iRECIST. Single subject dose escalation cohorts were followed by a 3+3 ascending dose design. Three cohorts (3, 10, 20 mg/kg) were expanded to evaluate PK, PD and clinical activity. Pharmacodynamic studies examined soluble LAG-3 production and peripheral T-cell expansion.ResultsForty-three patients (median 6 lines of prior therapy, including ICB) with solid tumors received FS118 at doses from 0.8 mg up to 20 mg/kg across 8 dose levels. Weekly administration of FS118 was well tolerated and did not result in dose- or treatment-limiting toxicities. An MTD was not reached. No safety signals unexpected for the drug class of immune-checkpoint inhibitors were identified in the early study population. The majority (95%) of treatment-emergent adverse events (TEAE) considered by the Safety Review Committee (SRC) to be treatment-related were Grade 1 and 2. Grade 3 TEAEs toxicities (elevated liver enzymes) were observed in 2 patients (5%). No SAEs or deaths were attributed to FS118 treatment. Anti-drug antibodies, observed in half of patients, were typically transient in nature. The pharmacokinetic profile confirmed preclinical predictions and PD parameters included a dose-dependent increase in serum soluble LAG-3 and expansion of peripheral T cells. Long-lasting disease stabilisation (>6 months) was observed in a subset of patients with acquired resistance (defined as a CR, PR or SD ≥3 months on previous PD-(L)1 treatment), but not in patients with primary resistance. Two patients remain on FS118 treatment as of 2 Jul 2020 (duration 10 and 16 months). Retrospective IHC analysis of PD-L1 and LAG-3 co-expression in the tumor was assessed as a potential biomarker associated with clinical outcome.ConclusionsWeekly treatment with FS118 was well tolerated up to 20 mg/kg and was associated with pharmacodynamic markers of FS118 activity. Encouraging signs of clinical activity were observed in highly pre-treated patients who had acquired resistance to prior PD-(L)1 therapy.Trial RegistrationRegistered at www.clinicaltrials.gov, NCT03440437ReferenceKraman M, Faroudi M, Allen N, Kmiecik K, Gliddon D, Seal C, Koers A, Wydro M, Winnewisser J, Young L, Tuna M, Doody J, Morrow M, Brewis N. FS118, a bispecific antibody targeting LAG-3 and PD-L1, Enhances T-Cell activation resulting in potent antitumor activity. Clin Cancer Res 2020; 26:3333–3344.

Regomune: A phase II study of regorafenib + avelumab in solid tumors—Results of the biliary tract cancer (BTC) cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4096-4096
Author(s):  
Sophie Cousin ◽  
Carine A. Bellera ◽  
Jean Philippe Guégan ◽  
Thibault Mazard ◽  
Carlos A. Gomez-Roca ◽  
...  
Keyword(s):  
Phase Ii ◽  
Adaptive Design ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Clinical Activity ◽  
Open Label

4096 Background: Regorafenib (R) has shown promising efficacy in patients (pts) with BTC refractory to standard chemotherapy. Anti-PD1/PD-L1 antibodies have only limited clinical activity. Synergy between R and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical solid tumor models. Methods: This is a single-arm open-label multicentric phase II trial (Bayesian adaptive design) assessing the efficacy and safety of R (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in BTC pts. The primary endpoint was the objective response rate under treatment, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Nov. 2018 and Nov. 2019, 34 BTC pts were enrolled in 4 centers. Median age was 63 (range 36 – 80). Median follow-up was 9.8 months. Median number of previous treatment lines for metastatic or locally advanced disease was: 2 (range 1 – 4). Twenty-nine (85.3%) pts experienced at least 1 dose modification or treatment interruption of R or A due to an adverse event (AE) related to the treatment. The most common grade 3/4 AEs were : Hypertension (17.6%), Fatigue (14.7%), and maculo-papular rash (11.8%). No death was related to the treatment. Among the 29 pts with at least one imaging tumor assessment, 4 (13.8%) achieved a partial response, and 11 (37.9%) demonstrated stable disease including 10 (34.5%) pts with tumor shrinkage. Fourteen pts (48.3%) had progressive disease. The median PFS and OS were 2.5 months (95%CI 1.9 – 5.5) and 11.9 months (95%CI 6.2 – NA) respectively. Baseline tumor samples were available for 27 pts. High IDO and PD-L1 expression at baseline was associated with better outcome. Conclusions: The R+A combination is associated with significant anti-tumor activity with promising survival rates in this heavily pre-treated population. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

scholarly journals Performance evaluation of the Simtomax® CoronaCheck rapid diagnostic test

2020 ◽  
Author(s):  
P. J. Ducrest ◽  
A. Freymond ◽  
J.-M. Segura
Keyword(s):  
Diagnostic Test ◽  
Rapid Diagnostic Test ◽  
Diagnostic Performance ◽  
High Sensitivity ◽  
High Specificity ◽  
Negative Control ◽  
List Type ◽  
Plasma Samples ◽  
Rt Pcr ◽  
Two Samples

AbstractThe aim of this study was to evaluate the diagnostic performance of Simtomax® CoronaCheck, a serology rapid diagnostic test (RDT) for the detection of IgG and IgM against SARS-CoV-2. 48 plasma samples positive for SARS-CoV-2 based on RT-PCR and 98 negative control samples were studied. Diagnostic performance of the IgG/IgM RDT was assessed against RT-PCR and the electro-chemiluminescence immunoassay (ECLIA) Elecsys® Anti-SARS-CoV-2 total Ig. Overall, the RDT sensitivity was 92% (95% confidence interval [95%CI]: 79-97), specificity 97% (95% CI: 91-99%), PPV 94% (95% CI: 81-98) and the NPV 96% (95% CI: 89-99). When considering only samples collected ≥ 15 days post-symptoms (DPS), the sensitivity increased to 98% (95%CI: 86-100) and the specificity was 97% (95% CI: 91-99%). Two samples with 180 DPS were still positive for IgG. Globally, this IgG/IgM RDT displayed a high diagnostic accuracy for SARS-CoV-2 IgG/IgM detection in plasma samples in high COVID-19 prevalence settings. It could be effectively used, in absence of facilities for routine diagnostic serology, for samples with a DPS between 15 and 180 days.Highlights–The rapid diagnostic test Simtomax CoronaCheck displays a high sensitivity of 98% and a high specificity of 97% for SARS-CoV-2 IgG/IgM detection in plasma samples after 15 days post-symptoms.–The rapid diagnostic test Simtomax CoronaCheck can detect SARS-CoV-2 antibodies in plasma up to 180 days after symptom onset.–The rapid diagnostic test Simtomax CoronaCheck could be effectively used as an alternative to serological analysis using laboratory facilities.

Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men

1991 ◽  
Vol 124 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Hiroshi Bando ◽  
Chenyu Zhang ◽  
Yukinobu Takada ◽  
Ryuichi Yamasaki ◽  
Shiro Saito
Keyword(s):  
Growth Hormone ◽  
Young Men ◽  
The Elderly ◽  
Elderly Group ◽  
Elderly Men ◽  
Age Related ◽  
Igf I ◽  
Basal Plasma ◽  
Plasma Gh ◽  
Ghrh Test

Abstract. The GHRH test and L-dopa test were performed in 12 normal young men (24.1 ± 1.1 years) and 12 normal elderly men (77.8±1.4 years) to investigate age-related changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and GH were not significantly different in young and elderly men, but the basal plasma level of IGF-I was higher in the young men (159.0± 11.7 vs 86.7± 11.6 μg/1). The area under the curve for plasma GH in the GHRH test was less in the elderly group (35.1 ±5.9 vs 11.2 ± 2.1 μg · h−1 · 1−1, p<0.001). The AUCs for the plasma GHRH and GH responses in the L-dopa test in young and elderly men were 32.0±2.7 vs 20.3±1.8 ng · h−1 · 1−1 (p<0.001), and 21.8±4.6 vs 5.4±1.1 μg · h−1 · 1 (p<0.01), respectively, indicating decreased releases of GHRH and GH in the elderly. Correlations between the AUCs for plasma GHRH and GH responses in L-dopa were found in both groups, but the ratio of the AUCs for GH/GHRH was lower in the elderly group. The elderly group showed a significant correlation between the basal plasma IGF-I level and the AUCs for plasma GH in the GHRH and L-dopa tests. These results suggest that elderly men have a decreased reserve of hypothalamic GHRH, resulting in secondarily impaired GH release, which may lead to a lower level of IGF-I than in young men.

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