Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy

1989 ◽  
Vol 120 (2) ◽  
pp. 187-194 ◽  
Author(s):  
S. L. Hyer ◽  
P. S. Sharp ◽  
R. A. Brooks ◽  
J. M. Burrin ◽  
E. M. Kohner
Keyword(s):  
Normal Subjects ◽  
High Plasma ◽  
Prolonged Treatment ◽  
Somatostatin Analogue ◽  
Clinical Value ◽  
Gh Secretion ◽  
Treatment Regimens ◽  
Igf I ◽  
Before And After ◽  
Long Acting

Abstract. The response to GH releasing hormone (GHRH 1–29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 μg by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 μg/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU · l−1 · h−1;h 209 ± 81 vs 121 ± 82; P=0.01). Mean ± sd IGF-I levels (μg/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2–16) pump administration (203 ± 62 vs 60 ± 25; P= 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.

scholarly journals Octreotide long-acting repeatable and lanreotide Autogel are equally effective in controlling growth hormone secretion in acromegalic patients

2004 ◽  
pp. 489-495 ◽  
Author(s):  
SW van Thiel ◽  
JA Romijn ◽  
NR Biermasz ◽  
BE Ballieux ◽  
M Frolich ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Binding Affinity ◽  
Receptor Subtype ◽  
Somatostatin Analogue ◽  
Deconvolution Analysis ◽  
Octreotide Lar ◽  
Gh Secretion ◽  
Igf I ◽  
Long Acting ◽  
Lanreotide Autogel

OBJECTIVE: Recently a new depot preparation of the long-acting somatostatin analogue, lanreotide Autogel was introduced for the treatment of acromegaly. Like octreotide long-acting repeatable (LAR), it has high binding affinity for the somatostatin receptor subtype SSTR 2 and less binding affinity for SSTR 5. We hypothesized that the ability to suppress growth hormone (GH) secretion in patients with acromegaly would be similar for these depot preparations. PATIENTS AND STUDY DESIGN: Seven patients (mean age+/-S.E.M. 48.4+/-7 years) on long-term octreotide LAR treatment at a monthly injection interval for a mean of 2.8 years were enrolled in the study. They underwent a GH secretory profile study with 10 min sampling for 24 h, 28 days after an injection. At 2, 4 and 6 weeks after the next injection fasting GH profiles (every 30 min for 3.5 h) and serum IGF-I measurements were measured. These investigations were repeated 12 months later, when the patients were on an individually titrated stable dose of lanreotide Autogel. RESULTS: Secretory characteristics and total 24 h GH secretion, estimated by deconvolution analysis of the 10 min 24 h plasma GH concentrations, did not show differences between these two long-acting somatostatin analogues. Both drugs were equally effective in GH and IGF-I suppression as measured at 2, 4 and also at 6 weeks following an injection. CONCLUSION: The efficacy of lanreotide Autogel and octreotide LAR was equal, notwithstanding that these drugs are administered in a different way and have different pharmacokinetics.

Influence of chronic naltrexone treatment on growth hormone secretion in normal subjects

1997 ◽  
pp. 631-634 ◽  
Author(s):  
P Villa ◽  
D Valle ◽  
L De Marinis ◽  
A Mancini ◽  
A Bianchi ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Subjects ◽  
Molar Ratio ◽  
Normal Female ◽  
Gh Secretion ◽  
Igf I ◽  
Before And After ◽  
Ghrh Test ◽  
Igfbp 3

OBJECTIVE: To verify if a chronic opioid blockade could affect the GH/IGF-I axis. DESIGN: We have investigated the effects of naltrexone (NTX) treatment on GH response to GHRH in normal women. METHODS: GHRH test (50 micrograms i.v.) performed in seven normal female volunteers (age 25-38 years, with a body mass index ranging from 19.8 to 23.1 kg/m2) before and after 4-weeks NTX treatment (50 mg p.o. daily). RESULTS: Basal GH, IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3) plasma levels and the IGF-I/IGFBP-3 molar ratio remained unaffected by NTX. NTX significantly reduced the GH peak values (15.52 +/- 3.59 vs 4.78 +/- 0.49 micrograms/l; P < 0.01), and GH area under curve (918.93 +/- 253.96 vs 401.09 +/- 79.63 micrograms/l; P < 0.01). CONCLUSIONS: This finding suggests that the long-term opioid receptor blockade has an inhibitory role on GHRH-induced GH secretion. A central influence on neurotransmitter control of GH might be hypothesised. The inhibition of stimulated GH release, without interference with the basal level, could indicate an enhanced somatostatin secretion and/or activity. Opioids could be involved only in the regulation of GH dynamics and not in basal secretion. Nevertheless, a direct involvement of opioids at the pituitary level, which could be modified by NTX, cannot be excluded.

Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli

1991 ◽  
Vol 125 (4) ◽  
pp. 366-371 ◽  
Author(s):  
Michael Glikson ◽  
Irit Gil-Ad ◽  
Eithan Galun ◽  
Rivka Dresner ◽  
Shalom Zilberman ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Carcinoid Tumour ◽  
Hormone Secretion ◽  
High Plasma ◽  
Somatostatin Analogue ◽  
Bronchial Carcinoid ◽  
Mixed Meal ◽  
Gh Secretion ◽  
Before And After ◽  
Plasma Gh

Abstract. Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (>500 to 42 ng/l and 15.4 μg/l to 0.8 μg/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.

Effect of gonadectomy on growth hormone, IGF-I and sex steroids in children with complete and incomplete androgen insensitivity

1989 ◽  
Vol 121 (6) ◽  
pp. 777-783 ◽  
Author(s):  
Alessandro Cicognani ◽  
Emanuele Cacciari ◽  
Moreno Tacconi ◽  
Maria G. Pascucci ◽  
Susanna Tonioli ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Arginine Test ◽  
Mean Values ◽  
Androgen Insensitivity ◽  
Gh Secretion ◽  
Number Of Patients ◽  
Igf I ◽  
Before And After ◽  
Estradiol Levels ◽  
Normal Controls

Abstract. IGF-I, testosterone and estradiol levels were evaluated in 8 girls with androgen insensitivity immediately before and from 1 to 3 months after bilateral gonadectomy. In 6 patients GH secretion was evaluated before and after gonadectomy by means of an arginine test and in 3 a sleep test was also performed. Mean IGF-I level before surgery was significantly higher than that of normal controls (2850 ± 1230 vs 1680 ± 1040 U/l, p < 0.025). After gonadectomy a significant decrease was evident for testosterone, estradiol and IGF-I levels. A positive correlation between IGF-I and estradiol levels was present before surgery (p < 0.005). The presence of a correlation with estradiol, but not with testosterone, and the knowledge that this syndrome is due to an insensitivity to androgens, but not to estradiol, support the hypothesis that the estradiol level is the major determinant for the control of IGF-I values in these patients. After gonadectomy, a substantial decrease of the 12-h nocturnal GH secretion was evident. Comparison of the nocturnal GH levels before surgery of the 3 patients with those of normal subjects of the same age showed hormonal values higher than 1 sd over the mean values of control subjects. Even if the number of patients studied is too small to draw any definitive conclusion, these data may suggest that sex hormones play a role in the control of IGF-I levels, a function which seems to be mediated through GH secretion.

scholarly journals Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl

2005 ◽  
Vol 153 (2) ◽  
pp. 195-201 ◽  
Author(s):  
M Rix ◽  
P Laurberg ◽  
A S Hoejberg ◽  
B Brock-Jacobsen
Keyword(s):  
Well Being ◽  
Lymphocytic Infiltration ◽  
High Serum ◽  
Serum Prolactin ◽  
Great Promise ◽  
Oral Glucose ◽  
Somatostatin Analogue ◽  
Tall Stature ◽  
Gh Secretion ◽  
Igf I

Objective: The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour. Design: To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism. Methods: Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age. Results: A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being. Conclusions: We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

Cholinergic modulation of GH secretion in acromegalic patients before and after pituitary surgery

1992 ◽  
Vol 127 (6) ◽  
pp. 489-493 ◽  
Author(s):  
Leon Fiszlejder ◽  
Olga Penacini ◽  
Susana Ratz ◽  
Adriana Oneto ◽  
Maria Storani ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Pituitary Surgery ◽  
Normal Subjects ◽  
Physiological Control ◽  
Gh Secretion ◽  
Pathophysiological Role ◽  
Before And After ◽  
Transsphenoidal Adenomectomy ◽  
Ghrh Test

Cholinergic neurotransmission exerts a physiological control on GH secretion. Pirenzepine (Pz), an antagonist of muscarinic receptors, by enhancing hypothalamic somatostatin release, inhibits stimulated GH secretion in normal subjects but not in acromegalic patients. To address the hypothesis that a feedback effect of GH hypersecretion can be involved in this condition, GH responses to GHRH 1–29, 1 μg/kg iv, with and without administration of Pz, 40mg iv before tests, were investigated in eight acromegalic patients, before and 20–30 days after transsphenoidal adenomectomy. Pz diminished (p<0.001) the incremental area under the curve (AUC) of GH responses to GHRH in seven normal controls. In contrast, GHRH responsiveness in untreated acromegalic patients was not affected by Pz. Postoperative basal GH levels decreased by 62.4±14.9% (p<0.01). Pz inhibited GH responses to GHRH (p<0.01). Furthermore, a direct relationship (r = 0.73, p<0.01) between basal concentrations and the AUC of GH responses following Pz plus GHRH-test was found. The finding that muscarinic receptor activity recovered after the reduction of serum GH basal levels by pituitary surgery lends support to the proposed pathophysiological role of GH excess as a possible determinant factor in cholinergicsomatostatinergic dysfunction in acromegaly.

The effect of somatostatin analogue on chiasmal dysfunction from pituitary macroadenomas

1989 ◽  
Vol 71 (5) ◽  
pp. 687-690 ◽  
Author(s):  
André Warnet ◽  
José Timsit ◽  
Philippe Chanson ◽  
Pierre-Jean Guillausseau ◽  
Françoise Zamfirescu ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Visual Fields ◽  
Somatostatin Analogue ◽  
Tumor Shrinkage ◽  
Content Type ◽  
Gh Secretion ◽  
Visual Improvement ◽  
Long Acting ◽  
Pituitary Macroadenomas

✓ The long-acting somatostatin analogue SMS 201-995 has been shown to be efficient in the treatment of somatotropic and thyrotropic adenomas. In some cases, it can suppress adenoma secretion and lead to tumor shrinkage. Pituitary macroadenomas are often associated with a vision-threatening chiasmal syndrome. In this series, SMS 201-995 was administered subcutaneously to eight patients with pituitary macroadenomas of various types responsible for severe long-lasting visual defects. An obvious improvement of both visual fields and acuity occurred in six patients, in two of these during the first 4 to 6 hours of treatment; in two patients, gonadotropic adenomas were unresponsive. Maximal improvement (normalization of visual fields in three cases) occurred within 6 to 45 days and was sustained during the 1- to 12-month follow-up period. This effect seems independent of the type of adenoma since the adenomas secreting growth hormone (GH) and thyroidstimulating hormone and silent corticotropic-secreting adenomas responded as well as did two of the non-functioning adenomas. In one acromegalic patient visual improvement was obtained while the abnormal GH secretion remained unaltered. In all cases but one, no tumor shrinkage could be demonstrated. These data demonstrate that SMS 201-995 can rapidly improve the chiasmal syndrome due to pituitary macroadenoma, and suggest that this effect might be independent of a reduction in tumor volume.

Plasma dehydroepiandrosterone sulfate levels in patients with hyperfunctioning and non-hyperfunctioning adrenal tumors before and after adrenal surgery

1997 ◽  
Vol 136 (3) ◽  
pp. 290-295 ◽  
Author(s):  
Miklós Tóth ◽  
Károly Rácz ◽  
Ibolya Varga ◽  
Vilmos Adleff ◽  
Csilla Jakab ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Dehydroepiandrosterone Sulfate ◽  
High Plasma ◽  
Adrenal Tumors ◽  
Adrenal Surgery ◽  
Adrenocortical Tumors ◽  
Adrenocortical Adenomas ◽  
Before And After ◽  
Adrenocortical Carcinomas ◽  
Glucocorticoid Production

Abstract To investigate the clinical significance of plasma dehydroepiandrosterone sulfate (DHEAS) measurements, 175 patients with histologically confirmed adrenal tumors, 10 cortisol-producing adenomas, 59 aldosterone-producing adenomas, 56 non-hyperfunctioning adenomas, 13 adrenocortical carcinomas, 13 adrenal cysts, and 24 adrenomedullary tumors were studied. Plasma DHEAS levels were expressed as percentage of the mean of sex- and age-matched groups of healthy, normal subjects (DHEAS %). We found that before adrenal surgery, DHEAS % values were significantly reduced in patients with cortisol-producing (mean, 15·2% of control; 95% confidence interval (CI), 9·4–24·7%), non-hyperfunctioning (28·4%; 22·4–36·0% as well as aldosterone-producing adrenocortical adenomas (55·4%; 47·1–65·1%) compared with controls, while values were normal in patients with adrenal cysts and in those with adrenomedullary tumors. Plasma DHEAS % values exhibited a great variability in adrenocortical carcinomas (mean, 84·0%; 95% CI, 33·2–212·5%). Death from adrenocortical carcinoma was more frequent in patients with high plasma DHEAS % values compared with those with low DHEAS %. During long-term postoperative monitoring, we found that plasma DHEAS levels of patients with aldosterone-producing and non-hyperfunctioning adenomas returned to normal in the second and fourth postoperative year respectively. In patients with cortisol-producing adenomas, plasma DHEAS remained suppressed for as long as 8 years after the operation. These findings show that except in adrenocortical carcinomas and cysts, plasma DHEAS levels are significantly decreased in all groups of adrenocortical tumors, including non-hyperfunctioning and aldosteroneproducing tumors. The extent of this decrease and the postoperative persistence of suppressed plasma DHEAS levels may be related to the glucocorticoid production of adrenocortical tumors. European Journal of Endocrinology 136 290–295

Real-time monitoring of circulating stromal cells in the blood to predict responsiveness of new-line therapies in metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14048-e14048
Author(s):  
Daniel Adams ◽  
R Katherine Alpaugh ◽  
Stuart S Martin ◽  
Rena G. Lapidus ◽  
Saranya Chumsri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Univariate Analysis ◽  
Metastatic Breast ◽  
Prognostic Indicator ◽  
Ct Scans ◽  
Clinical Value ◽  
Size Change ◽  
Treatment Regimens ◽  
Before And After

e14048 Background: Cancer associated macrophage like cells (CAMLs), a circulating stromal cell subtype, has been shown as an independent prognostic indicator of survival in late stage metastatic breast cancer when cells enlarge to ≥50µm. However, no study has evaluated the clinical relationship between changes in CAML size and their ability to predict treatment response. While CAMLs are prognostic for progression, we hypothesized that monitoring changes in CAMLs after initiation of therapy may be predictive for responsiveness of new treatment regimens. Methods: A prospective 12 months blind multi-institutional pilot study was undertaken to evaluate CAMLs before, and after, induction of a new line of investigational therapy based on CT scans. Patients with progressive metastatic breast cancer (n = 29) who had failed at least 2 prior therapies were recruited. A baseline (BL) blood sample was taken prior to induction of a new therapy and a 2nd sample (T1) taken after initiation (~30 days). Blood was filtered by CellSieve filtration.The quantities and sizes of CAMLs were analyzed based on PFS hazard ratios (HRs) by censored univariate analysis. Results: CAMLs were found in 97% of BL samples and 93% of T1 samples. At first CT scan, after the assigned dose of investigational treatment, 17 of 29 patients had clinical progression with 14/17 (82%) patients having an increased CAML size and 3/17 (18%) having a decreased CAML size. The remaining 12 of 29 patients saw clinically stable, or regression, of disease with 10/12 (83%) having decreased CAML size and 2/12 (17%) having increased CAML size. Overall CAML size change after therapy induction was 83% accurate at predicting response or progression based on CT scans. Further, patients with increasing CAML size at T1 had a 4 month mPFS vs 10 month mPFS for decreasing CAMLs, with a lower 12 month PFS HR = 3.7 (95%CI = 1.5-10.1, p = 0.020). Conclusions: Our data suggests that in metastatic breast cancer, monitoring CAMLs changes over the first 30 days of treatment accurately predicts responsiveness of disease to new treatments. Further, we suggests using blood sampling may increase the clinical value of blood based diagnostics by rapidly predicting the benefit of subsequent therapies.

Sign in / Sign up

Export Citation Format

Share Document