Faculty Opinions recommendation of Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: a randomized multicentre study.

2020 ◽  
Author(s):  
Maria Fleseriu
Keyword(s):  
Multicentre Study ◽  
Somatostatin Analogue ◽  
Igf I

scholarly journals Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: a randomized multicentre study

2018 ◽  
Vol 178 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Jakob Dal ◽  
Marianne Klose ◽  
Ansgar Heck ◽  
Marianne Andersen ◽  
Caroline Kistorp ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multicentre Study ◽  
Somatostatin Analogue ◽  
Dose Increase ◽  
Biochemical Control ◽  
Igf I ◽  
Biochemical Assessment ◽  
Assessment Of Disease Activity ◽  
Disease Specific

Context Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. Objective To evaluate the effects of targeting either IGF-I or GH during somatostatin analogue (SA) treatment. Patients and Methods 84 patients with controlled acromegaly after surgery (n = 23) or SA (n = 61) underwent a GH profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n = 33) or GHnadir (n = 28). SA dose escalation was allowed at baseline and 6 months. Main outcome measures GHnadir and IGF-I at baseline and 12 months, and disease-specific Quality of Life (QoL). Results IGF-I and fasting GH levels were comparable between the surgery and the SA group, whereas GHnadir (µg/L) was lower in the surgery group (GHnadir 0.7 ± 0.1 vs 0.3 ± 0.1, P < 0.01). SA dose increase was performed in 20 patients in the GH group and in 8 patients in the IGF-I group (P = 0.02), which increased the number of concordantly controlled patients (P = 0.01). QoL was only mildly affected at baseline in all groups and did not changed consistently during the study. Conclusion (1) Discordant values in terms of high GH levels are prevalent in SA patients and more so if applying glucose-suppressed GHnadir; (2) targeting discordant levels of either GH or IGF-I translates into SA dose increase and improved biochemical control; (3) even though QoL was not improved in this study, we suggest biochemical assessment of disease activity to include glucose-suppressed GHnadir also in SA patients.

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.

Effect of octreotide on experimental diabetic renal and glomerular growth: importance of early intervention

1995 ◽  
Vol 147 (1) ◽  
pp. 95-102 ◽  
Author(s):  
H Grønbæk ◽  
B Nielsen ◽  
J Frystyk ◽  
H Ørskov ◽  
A Flyvbjerg
Keyword(s):  
Early Intervention ◽  
Volume Fraction ◽  
Diabetic Rats ◽  
Somatostatin Analogue ◽  
Protein Accumulation ◽  
Renal Hypertrophy ◽  
Renal Growth ◽  
Glomerular Volume ◽  
Igf I ◽  
Octreotide Treatment

Abstract IGF-I acts as a renotropic factor in early streptozotocin-induced diabetes. Somatostatin analogue (octreotide) treatment initiated at the onset of diabetes prevents kidney IGF-I accumulation and renal growth. Seven days of octreotide treatment initiated after 3, 5, 7 or 9 days of untreated diabetes was investigated. Diabetic renal hypertrophy was followed by renal hyperplasia. Compared with placebo-treated diabetic rats, the earliest octreotide intervention was followed by a greater reduction in renal growth compared with intervention later on (days 3 to 10, 12%; days 5 to 12, 10%; days 7 to 14, 9%; days 9 to 16, 6%; P<0·05). Octreotide treatment was unable to reduce protein accumulation and kidney DNA increase consistently. No difference in glomerular volume fraction or total glomerular volume was observed between placebo- and octreotide-treated diabetic rats. Octreotide treatment was followed by reduced kidney and serum IGF-I especially following early intervention, while no effect over that of diabetes was observed in the later intervention periods. The results confirm the notion that initial renal IGF-I accumulation is a prerequisite for early diabetic kidney hypertrophy in rats and show that delayed octreotide treatment cannot reverse renal and glomerular growth which is already manifest. Journal of Endocrinology (1995) 147, 95–102

scholarly journals Occurrence and effects of octreotide antibodies during nasal, subcutaneous and slow release intramuscular treatment

2000 ◽  
pp. 353-361 ◽  
Author(s):  
A Kaal ◽  
H Orskov ◽  
S Nielsen ◽  
AM Pedroncelli ◽  
I Lancranjan ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Exposure Time ◽  
Antibody Formation ◽  
Carcinoid Syndrome ◽  
Drug Exposure ◽  
Slow Release ◽  
Somatostatin Analogue ◽  
Igf I ◽  
Large Populations ◽  
Local Reactions

OBJECTIVE: Previous studies have indicated that antibody formation against octreotide is extremely rare. We examined the occurrence of octreotide antibody formation after treatment with three administration forms in large populations of patients with acromegaly or carcinoid syndrome. DESIGN: (i) Nasally administered octreotide: 70 previously untreated patients and 81 previously s.c. octreotide-treated patients participated. (ii) Subcutaneously administered octreotide: 172 acromegalic patients and 59 patients with carcinoid syndrome treated for up to 12 years participated. (iii) Intramuscularly administered depot octreotide (Sandostatin LAR): 62 acromegalic patients participated. METHODS: Presence of antibodies is defined as increased precipitation by polyethylene glycol of (125)I-octreotide after incubation with serum; this was also used for screening of cross-reaction with somatostatin and lanreotide (Somatuline). RESULTS: In patients who received nasal octreotide for at least 9 and up to 12 months (n=42), the occurrence of octreotide antibodies was 77% and 81% for previously untreated and treated patients respectively. In subcutaneously treated patients it was 63/231 (27%) after a mean exposure of 3 years. In patients treated for more than 5 years (n=53) it was 57% and after 8 years (n=18) 72%. In contrast, no patient could with certainty be identified to be antibody-positive after a mean of 2.5 years intramuscular Sandostatin LAR treatment (n=47). In all populations, the antibody-positive patients were as well controlled as the antibody-negative patients. Octreotide antibodies did not cross-react with native somatostatin (n=141), while about 25% of the antibody-positive sera did cross-react with the somatostatin analogue, lanreotide (Somatuline, Ipstyl, Angiopeptin). CONCLUSIONS: Antibody formation against octreotide is much more frequent than previously believed. It depends primarily on drug exposure time and route of administration. It does not alter the GH/IGF-I status in treated acromegalic patients and induces only mild local reactions in some patients.

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.

scholarly journals Inhibitory effects of octreotide on renal and glomerular growth in early experimental diabetes in mice

2002 ◽  
Vol 172 (3) ◽  
pp. 637-643 ◽  
Author(s):  
H Gronbaek ◽  
B Nielsen ◽  
B Schrijvers ◽  
I Vogel ◽  
R Rasch ◽  
...  
Keyword(s):  
Experimental Diabetes ◽  
Placebo Treatment ◽  
Diabetic Mouse ◽  
Somatostatin Analogue ◽  
Diabetes In Mice ◽  
Igf I ◽  
Octreotide Treatment ◽  
Human Type 1 Diabetes ◽  
Analogue Octreotide

It was recently discovered that the streptozotocin (STZ)-diabetic mouse model is characterised by GH hypersecretion in contrast to the STZ-diabetic rat, the former thus mimicking the changes in GH in human type 1 diabetes. Inhibition of circulating and renal IGF-I by long-acting somatostatin analogues reduces renal and glomerular growth and urinary albumin excretion in diabetic rats. The aim of the present study was to examine renal and glomerular growth in early experimental diabetes in mice along with changes in the GH/IGF-I axis following treatment with the somatostatin analogue octreotide. Balb/C(a) mice were randomised into non-diabetic controls, placebo-treated and octreotide-treated diabetic (50 microg/day) mice and examined 7 and 14 days after induction of diabetes. There was no effect of octreotide treatment on body weight, glycaemic control or food intake. However, octreotide treatment significantly inhibited renal and glomerular growth by the end of the study period when compared with placebo treatment. In addition, octreotide prevented an increase in kidney IGF-I by day 7. GH hypersecretion was observed in the diabetic groups but octreotide treatment reduced GH levels compared with placebo treatment by day 14. No significant differences in serum or kidney IGF-binding protein-3 levels were observed between placebo- and octreotide-treated diabetic mice. In conclusion, this new diabetic mouse model mimicking human type 1 diabetes is characterised by GH hypersecretion and the somatostatin analogue octreotide is able to prevent renal and glomerular growth, probably mediated through changes in circulating GH and local kidney IGF-I levels.

scholarly journals Soluble alpha klotho in acromegaly: Comparison to traditional markers of disease activity

2021 ◽  
Author(s):  
Júnia R O L Schweizer ◽  
Katharina Schilbach ◽  
Michael Haenelt ◽  
Alexandre V Giannetti ◽  
Mariana F Bizzi ◽  
...  
Keyword(s):  
Disease Activity ◽  
Dynamic Range ◽  
Close Association ◽  
Systematic Evaluation ◽  
Somatostatin Analogue ◽  
Igf I ◽  
Igf Binding ◽  
High Concentrations ◽  
Igf Binding Protein

Abstract Context Soluble alpha klotho (sαKL) has been linked to growth hormone (GH) action, but systematic evaluation and comparison to traditional biomarkers in acromegaly are lacking. Objective To evaluate the potential of sαKL to aid classification of disease activity. Design and setting Retrospective study at two academic centers. Patients Patients with acromegaly before surgery (A, n=29), after surgery controlled, discordant or uncontrolled without (B1, B2, B3, n=28, 11, 8) or with somatostatin analogue treatment (C1, C2, C3, n=17,11, 5), non-functioning pituitary adenomas (n=20) and healthy controls (n=31). Interventions sαKL was measured by immunoassay and compared to traditional biomarkers (random and nadir GH, insulin-like growth-factor I (IGF-I), IGF binding-protein 3. Associations with disease activity were assessed. Results sαKL was correlated to traditional biomarkers, but particularly to IGF-I (rs=0.80, p&lt;0.0001). High concentrations before treatment (A, median, IQR: 4.04 xULN (2.26-8.08)) dropped to normal after treatment in controlled, and in most discordant patients. A cut-off of 1548 pg/mL for sαKL discriminated controlled (B1, C1) and uncontrolled (B3, C3) patients with 97.8% (88.4-99.9) sensitivity and 100% (77.1-100) specificity. sαKL was below the cut-off in 84% of the discordant subjects. In the remaining 16%, sαKL and IGF-I persisted elevated, despite normal random GH. Sex, age, BMI and markers of bone and calcium metabolism did not significantly affect sαKL concentrations. Conclusions Our data support sαKL as a biomarker to assess disease activity in acromegaly. It exhibits close association with GH secretory status, large dynamic range and robustness towards biological confounders. Its measurement could be helpful particularly when GH and IGF-I provide discrepant information

Sign in / Sign up

Export Citation Format

Share Document