scholarly journals Direct Postoperative and Follow-Up Results of Transsphenoidal Surgery in 19 Acromegalic Patients Pretreated with Octreotide Compared to Those in Untreated Matched Controls

1999 ◽  
Vol 84 (10) ◽  
pp. 3551-3555 ◽  
Author(s):  
N. R. Biermasz ◽  
H. van Dulken ◽  
F. Roelfsema
Keyword(s):  
Growth Factor ◽  
Adjuvant Therapy ◽  
Transsphenoidal Surgery ◽  
Normal Serum ◽  
Factor I ◽  
Preoperative Serum ◽  
Igf I ◽  
Pretreated Patients ◽  
Serum Gh

Abstract In this study 19 patients were preoperatively treated with octreotide for 1–17 months (mean, 5 months), with doses from 150–1500 μg daily, and those patients were matched to 19 untreated patients with comparable tumor classification and preoperative serum GH concentrations. Octreotide was started at 300 μg daily by sc injections or continuous sc infusion using a pump in increasing doses, depending on the responses of the serum GH and insulin-like growth factor I (IGF-I) concentrations. During pretreatment, seven patients achieved a serum GH concentration below 5 mU/L, whereas six patients normalized their serum IGF-I. Postoperatively, a serum GH concentration below 5 mU/L was achieved in 15 pretreated and 14 untreated patients, a normal serum IGF-I level (<2 sd) was achieved in 10 pretreated and 15 untreated patients, and normal serum GH suppression during GTT was reached in 12 treated and 14 control patients. No differences were found in complication rate or incidence of hypopituitarism caused by surgery. Adjuvant therapy was required in 7 treated and 5 untreated patients. At follow-up examination, 5.7 and 4 yr postoperatively, 10 pretreated and 12 control patients could be considered cured by surgery only, according to our criteria for remission (serum GH, <5 mU/L; normal GH suppression and normal serum IGF-Ι). In summary, we found no difference in direct postoperative and follow-up results of transsphenoidal surgery between pretreated patients and untreated patients. This finding is in discordance with other studies, which have claimed a beneficial effect of octreotide pretreatment.

Effects of elevated blood insulin-like growth factor-I (IGF-I) concentration upon IGF-I in bovine mammary secretions during the colostrum phase

1993 ◽  
Vol 137 (2) ◽  
pp. 223-230 ◽  
Author(s):  
D. L. Hadsell ◽  
C. R. Baumrucker ◽  
R. S. Kensinger
Keyword(s):  
Growth Factor ◽  
Nutrient Restriction ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Dry Period ◽  
Entire Treatment Period ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Serum Gh

ABSTRACT The objectives of these studies were to determine if the concentration of insulin-like growth factor-I (IGF-I) in mammary colostrum secretions could be altered through manipulation of IGF-I concentrations in blood and to compare the temporal changes of IGF-I in mammary secretions to those occurring for IgG1. Milking of 15 pregnant Holstein cows was stopped at 8 weeks prepartum and they were randomly assigned to one of three treatments. A control (C) treatment consisted of feeding the animals 100% of NRC requirements for protein and energy. A second group of cows was fed as the control group and injected with 1·8 μmol bovine GH/day. The third group was fed at 70% of NRC requirements for protein and energy to cause a moderate nutrient restriction (NR). Body weight was measured weekly. Blood was collected by tail venepuncture at 4 h intervals for 24 h. Mammary secretions were collected and pooled among contralateral front and rear quarters (diagonal) for measurement of volume, IGF-I and IgG1 concentrations. Samples were collected at −7, −5, −2, 0 and 1 week postpartum. Cows on the NR treatment failed to gain weight during the dry period compared with C cows (P < 0·05). Blood GH and IGF-I concentrations (P > 0·1) were unaffected by NR treatment. Cows treated with GH had higher (P < 0·01) serum GH and IGF-I levels throughout the entire treatment period, and higher serum IgG1 at 5 and 2 weeks prepartum (P < 0·01). Total mass of IGF-I secreted per diagonal averaged 3·6-fold greater for GH-treated cows during the prepartum period than C and NR cows (P < 0·01). The concentration of IGF-I in mammary secretions was not affected by treatment during the prepartum period, but was 40% greater (P < 0·05) in GH-treated cows than C and NR cows at parturition. Analysis of a selective index comparing IGF-I secretion with that of IgG1 suggested that IGF-I does not enter mammary secretions by passive diffusion from blood. Journal of Endocrinology (1993) 137, 223–230

Repeat Transsphenoidal Surgery for the Treatment of Remaining or Recurring Pituitary Tumors in Acromegaly

Neurosurgery ◽  
2010 ◽  
Vol 67 (4) ◽  
pp. 949-956 ◽  
Author(s):  
Shozo Yamada ◽  
Noriaki Fukuhara ◽  
Kenichi Oyama ◽  
Akira Takeshita ◽  
Yasuharu Takeuchi
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Adjuvant Therapy ◽  
Surgical Outcome ◽  
Transsphenoidal Surgery ◽  
Hazard Ratio ◽  
Insulin Like Growth Factor ◽  
Cure Rate ◽  
Factor I

Abstract BACKGROUND: Acromegaly is a disorder characterized by hypersecretion of growth hormone caused by a growth hormone–secreting pituitary adenoma. OBJECTIVE: To evaluate the long-term efficacy and safety of repeat transsphenoidal surgery for persistent or recurrent acromegaly. METHODS: We retrospectively reviewed records for 53 acromegalic patients who underwent repeat transsphenoidal surgery for persistent or progressive acromegaly at Toranomon Hospital between 1987 and 2006. Multivariate logistic regression was performed to evaluate preoperative factors influencing the surgical outcome. RESULTS: Thirty-one patients (58.5%) met the criteria for cure on long-term follow-up endocrine findings. Furthermore, 17 patients were well controlled with normal insulin-like growth factor I levels without (2 patients) or with medication (15 patients), whereas insulin-like growth factor I levels were still above normal in 5 patients after postoperative adjuvant therapy. Only 1 patient was undergoing additional hormonal replacement after surgery, although transient cerebrospinal fluid leak, transient abducens nerve palsy, severe nasal bleeding, and pituitary abscess occurred in each patient, respectively. Multivariate analysis clarified that a favorable surgical outcome was achieved in patients without cavernous sinus invasion (hazard ratio 12.56), tumor segmentation (hazard ratio 5.82), or in those older than 40 years old (hazard ratio 3.21). CONCLUSION: Repeat surgery can be performed safely with an approximately 60% long-term cure rate in this series. Reoperation should therefore be considered for persistent or recurrent disease in acromegalic patients in whom adjuvant therapy is not effective enough or cannot be accepted. The careful study of initial or preoperative magnetic resonance imaging and the use of micro-Doppler, endoscope, and eye movement monitoring device during surgery can help increase cure rate with a lower complication rate.

scholarly journals Recovery of Growth Hormone Release from Suppression by Exogenous Insulin-Like Growth Factor I (IGF-I): Evidence for a Suppressive Action of Free Rather Than Bound IGF-I1

1998 ◽  
Vol 83 (8) ◽  
pp. 2836-2842
Author(s):  
Ian M. Chapman ◽  
Mark L. Hartman ◽  
Karen S. Pieper ◽  
Emily H. Skiles ◽  
Suzan S. Pezzoli ◽  
...  
Keyword(s):  
Growth Factor ◽  
Time Course ◽  
Temporal Association ◽  
Saline Control ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Rebound Increase ◽  
Serum Gh

abstract To determine the time course of recovery of GH release from insulin-like growth factor I (IGF-I) suppression, 11 healthy adults (18–29 yr) received, in randomized order, 4-h iv infusions of recombinant human IGF-I (rhIGF-I; 3 μg/kg·h) or saline (control) from 25.5–29.5 h of a 47.5-h fast. Serum GH was maximally suppressed within 2 h and remained suppressed for 2 h after the rhIGF-I infusion; during this 4-h period, GH concentrations were approximately 25% of control day levels [median (interquartile range), 1.2 (0.4–4.0) vs. 4.8 (2.8–7.9) μg/L; P &lt; 0.05]. A rebound increase in GH concentrations occurred 5–7 h after the end of rhIGF-I infusion [7.6 (4.6–11.7) vs. 4.3 (2.5–6.0) μg/L; P &lt; 0.05]. Thereafter, serum GH concentrations were similar on both days. Total IGF-I concentrations peaked at the end of the rhIGF-I infusion (432 ± 43 vs. 263 ± 44 μg/L; P &lt; 0.0001) and remained elevated 18 h after the rhIGF-I infusion (360 ± 36 vs. 202 ± 23 μg/L; P = 0.001). Free IGF-I concentrations were approximately 140% above control day values at the end of the infusion (2.1 ± 0.4 vs. 0.88 ± 0.3 μg/L; P = 0.001), but declined to baseline within 2 h after the infusion. The close temporal association between the resolution of GH suppression and the fall of free IGF-I concentrations, and the lack of any association with total IGF-I concentrations suggest that unbound (free), not protein-bound, IGF-I is the major IGF-I component responsible for this suppression. The rebound increase in GH concentrations after the end of rhIGF-I infusion is consistent with cessation of an inhibitory effect of free IGF-I on GH release.

scholarly journals A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly

2008 ◽  
Vol 159 (2) ◽  
pp. 89-95 ◽  
Author(s):  
I M Holdaway ◽  
M J Bolland ◽  
G D Gamble
Keyword(s):  
Meta Analysis ◽  
Serum Levels ◽  
Somatostatin Analogues ◽  
Normal Serum ◽  
Mortality Data ◽  
Standardized Mortality Ratio ◽  
Endocrine Society ◽  
Igf I ◽  
Serum Gh

ObjectiveFormal studies of acromegaly have found increased mortality associated with the disorder, although reduction of serum levels of GH and IGF-I by treatment appears to improve survival. A meta-analysis of mortality studies in acromegaly has thus been performed to assess the effect of lowering serum GH and IGF-I on survival.Design and methodsMedline was searched for studies under ‘acromegaly’, ‘mortality’ and ‘cause of death’ (1965–2008), and abstracts of recent meetings of the US Endocrine Society were hand searched. Studies were restricted to those presenting mortality data according to serum GH and IGF-I at last follow-up, and with mortality expressed as a standardized mortality ratio (SMR).ResultsPatients with random serum GH <2.5 μg/l following treatment, mostly measured by standard RIA, had mortality close to expected levels (SMR 1.1, 95% confidence interval (CI) 0.9–1.4) compared with an SMR of 1.9 (95% CI 1.5–2.4) for those with final GH >2.5 μg/l. Similarly, a normal serum IGF-I for age and sex at last follow-up after treatment was associated with an SMR of 1.1 (95% CI 0.9–1.4) compared with an SMR of 2.5 (95% CI 1.6–4.0) for those with continued IGF-I elevation. There was a significant trend for reduced mortality in series reporting frequent use of somatostatin analogues and in studies reporting high (>70%) rates of biochemical remission after treatment.ConclusionsClinicians treating acromegalic patients should aim for random serum GH <2.5 μg/l measured by RIA (probably <1 μg/l measured by modern sensitive immunoassay) and normal serum IGF-I values, to restore the elevated mortality of the condition to normal levels.

scholarly journals Insulin-like growth factor-I: marker for diagnosis of acromegaly and monitoring the efficacy of treatment

2003 ◽  
pp. S15-S20 ◽  
Author(s):  
G Brabant
Keyword(s):  
Growth Factor ◽  
Disease Activity ◽  
Insulin Like Growth Factor ◽  
Metabolic Markers ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Serum Gh ◽  
Persistent Elevation ◽  
Important Marker

Acromegaly is caused by chronic excess secretion of growth hormone (GH) and resultant persistent elevation in concentrations of insulin-like growth factor-I (IGF-I), also called somatomedin-C. A number of diagnostic tests are available to support the diagnosis of acromegaly, but those that rely on measurement of serum GH concentrations have important limitations. Concentrations of serum IGF-I, which is produced principally in the liver and mediates the actions of GH, have been shown to correlate with clinical and metabolic markers of disease activity. Additionally, normalisation of IGF-I levels in acromegaly is associated with the resolution of symptoms and normal life expectancy. Thus, serum IGF-I is an important marker of disease activity and a sensitive, practical, and reliable measure of integrated GH concentrations in patients with acromegaly.

Transsphenoidal Surgery for Acromegaly: Endocrinological Follow-up of 98 Patients

Neurosurgery ◽  
2001 ◽  
Vol 48 (6) ◽  
pp. 1239-1245 ◽  
Author(s):  
Ilan Shimon ◽  
Zvi R. Cohen ◽  
Zvi Ram ◽  
Moshe Hadani
Keyword(s):  
Growth Factor ◽  
Transsphenoidal Surgery ◽  
Remission Rate ◽  
Insulin Like Growth Factor ◽  
Postoperative Evaluation ◽  
Factor I ◽  
Surgical Failure ◽  
Growth Factor I ◽  
First Time

Abstract OBJECTIVE Transsphenoidal surgery is the preferred treatment modality for growth hormone (GH)-secreting pituitary adenomas. In many series, the reported postoperative remission is based mainly on achievement of GH levels less than 2 ng/ml. Strict criteria for insulin-like growth factor I normalization and even lower GH levels (&lt;1 ng/ml) are now suggested to define cure of acromegaly, but the evidence does not yet support such low GH levels in epidemiological follow-up. We analyzed our postoperative results in a large cohort of patients with acromegaly. METHODS Ninety-eight patients harboring GH-secreting adenomas (46 microadenomas and 52 macroadenomas) underwent transsphenoidal surgery between 1990 and 1999. Ninety-one patients were operated for the first time, and 12 patients underwent reoperations because of previous surgical failure (7 had undergone surgery elsewhere previously). Biochemical remission was defined as a repeated fasting or glucose-suppressed GH level of 2 ng/ml or less, and a normal insulin-like growth factor I level. RESULTS Remission was achieved in 74% of all patients after one operation, including 84% of patients with microadenomas and 64% of patients with macroadenomas. Seventy-three percent of patients with macroadenomas 11 to 20 mm in size achieved remission, as compared with a 20% remission rate for patients with adenomas larger than 20 mm. Patients with preoperative random GH levels lower than 50 ng/ml had a better outcome (85% remission), whereas GH greater than 50 ng/ml was associated with remission in 30% of the patients. Only one of the patients (8%) with postoperative active disease who underwent a second operation achieved remission. Recurrence was rare (one patient), and all failed surgical attempts could be detected during the immediate postoperative evaluation. CONCLUSION On the basis of strict postoperative GH and insulin-like growth factor I criteria to define remission, our series demonstrates the efficacy of transsphenoidal surgery for acromegalic patients with microadenomas and noninvasive macroadenomas. However, patients with large adenomas (&gt;20 mm) and preoperative GH greater than 50 ng/ml have a poor prognosis and require adjunctive medical or radiation therapy to control GH hypersecretion.

scholarly journals Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) on GH and Insulin-Like Growth Factor I Levels in Transgenic Mice Overexpressing the Human GHRH Gene, an Animal Model of Acromegaly*

Endocrinology ◽  
1997 ◽  
Vol 138 (11) ◽  
pp. 4536-4542 ◽  
Author(s):  
Magdolna Kovacs ◽  
Rhonda D. Kineman ◽  
Andrew V. Schally ◽  
Marta Zarandi ◽  
Kate Groot ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Messenger Rna ◽  
Pituitary Cells ◽  
Releasing Hormone ◽  
Factor I ◽  
Igf I ◽  
Ghrh Antagonists ◽  
Serum Gh

Abstract Transgenic mice overexpressing the human GH-releasing hormone (hGHRH) gene, an animal model of acromegaly, were used to investigate the effects of potent GHRH antagonists MZ-4–71 and MZ-5–156 on the excessive GH and insulin-like growth factor I (IGF-I) secretion caused by overproduction of hGHRH. Because metallothionein (MT)-GHRH mice express the hGHRH transgene in various tissues, including the pituitary and hypothalamus, initial experiments focused on the effectiveness of the GHRH antagonists in blocking basal and stimulated GH secretion from pituitary cells in vitro. Both MZ-4–71 and MZ-5–156 suppressed basal release of GH from superfused MT-GHRH pituitary cells, apparently by blocking the action of endogenously produced hGHRH. In addition, these antagonists effectively eliminated the response to stimulatory action of exogenous hGHRH(1–29)NH2 (30 and 100 nm). To ascertain whether MZ-4–71 and MZ-5–156 could antagonize the effect of hGHRH hyperstimulation in vivo, each antagonist was administered to MT-GHRH transgenic mice in a single iv dose of 10–200 μg. Both compounds decreased serum GH levels in transgenic mice by 39–72% at 1 h after injection. The inhibitory effect of 50 μg MZ-5–156 was maintained for 5 h. Twice daily ip administration of 100 μg MZ-5–156 for 3 days suppressed the highly elevated serum GH and IGF-I concentrations in transgenic mice by 56.8% and 39.0%, respectively. This treatment also reduced IGF-I messenger RNA levels in the liver by 21.8% but did not affect the level of GH messenger RNA in the pituitary. Our results demonstrate that GHRH antagonists MZ-4–71 and MZ-5–156 can inhibit elevated GH levels caused by overproduction of hGHRH. The suppression of circulating GH concentrations induced by the antagonists seems to be physiologically relevant, because both IGF-I secretion and synthesis also were reduced. Our findings, showing the suppression of GH and IGF-I secretion with GHRH antagonists, suggest that this class of analogs could be used for the diagnosis and therapy of disorders characterized by excessive GHRH secretion.

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