Endocrine Abstracts

Objective: To identify a range of IGF-I values representative of growth hormone deficiency (GHD), which could be utilised to reduce the risk of 'functional' GHD in Pegvisomant treated acromegaly.Method: We analysed centrally measured IGF-I data from the KIMS European GHD database. We stratified this cohort into six gender based, age ranges and assessed IGF-I and IGF-I standard deviation scores (SDS).Results: Baseline measurements f...

We report the efficacy, safety, and effects on glucose homeostasis of converting patients with acromegaly from slow release octreotide (OT, treated for >3 months) to pegvisomant (Peg), a GH receptor antagonist. 52 patients (median age 49, range 23-81, 13 with diabetes) who had previously participated in a Peg clinical trial and subsequently treated with OT were enrolled in a 32-week, open-label, multicentre study. Peg 10 mg/d was started 4 weeks after the last dose of OT (w...

Serum IGF-I is increasingly used, and IGFBP-3 has been proposed, as a marker of treatment efficacy in patients with acromegaly. IGF-I bioactivity and half-life are dependent on the degree of IGF-I incorporation into 150kDa ternary complexes with IGFBP-3 and ALS. When serum GH is lowered in patients with acromegaly all three ternary complex components decline, but effects on ternary complex formation have not been described. We investigated GH action on ternary complex formatio...

In many centres a test dose (TD) of octreotide is administered prior to commencing LAR. The value of the TD as a predictor of subsequent response to therapy remains uncertain. We have studied the relationship of the GH response to a TD to the subsequent response to LAR in 26 patients (median age 59 years, range 20- 84). After baseline GH sampling, 50mcg subcutaneous octreotide was administered and sampling continued for six hours. Results of the TD were compared to the lowest ...

Tumoural GH secretion in acromegaly is characterised by increased non-pulsatile (basal) release, pulse amplitude and pulse frequency. We have studied the effect of primary therapy with Sandostatin LAR on GH pulsatility in 9 patients with acromegaly who achieved disease control (mean serum GH<2ug/L) on therapy (7 males; median (range) age 67 (43-75). Data obtained were compared with 16 healthy subjects (10 males, age 50 (30-75)). Spontaneous 24-h GH secretion (20 minute samp...

Carpal tunnel syndrome (CTS) in acromegaly is caused, in part, by median nerve (MN) swelling. Pegvisomant (Peg), a growth hormone receptor (GHR) antagonist, lowers serum insulin-like growth factor-I (IGF-I) concentrations in patients with acromegaly, but serum GH levels rise and Peg is detected by most GH assays. Demonstrating that normalisation of serum IGF-I by Peg is associated with improvement/reversal of the consequences of GH excess is desirable. We documented changes in...

Pegvisomant is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Insulin resistance is an important factor in the increased cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to compare insulin sensitivity (IS) in a group of 7 patients with acromegaly (3 male, mean age 59+/-13 years, SD), treated first with a stable dose of depot octreotide (OT) (median dose 20mg four weekly, range 10-20) for at least t...

Vascular endothelial growth factor (VEGF) is involved in the activation of the matrix metalloproteinase system (MMP) which in turn degrades the extracellular matrix involved in development, morphogenesis and tissue remodelling. Increased activity of MMPs has been implicated in atherosclerosis and cardiovascular disease. This study assessed plasma MMP and VEGF levels in patients with active acromegaly (IGF-I >130%ULN), and on treatment with pegvisomant.<p class="abstext"...

Patients with acromegaly treated with medical therapy intermittently discontinue therapy to allow assessment of underlying disease activity. This is particularly so in patients treated with pituitary irradiation. Typical 'washout' times include 5 weeks for bromocriptine and 2 weeks for short-acting sc octreotide; longer periods are required for cabergoline and slow-release somatostatin analogues. Pegvisomant is a novel medical therapy for acromegaly that functions as a GH rece...

It has been suggested that primary medical treatment of patients with acromegaly using somatostatin analogues (SSA) is as effective at controlling GH levels as post-operative SSA therapy.We have carried out a prospective study in patients harbouring GH secreting macroadenomas to see, in a within-patient comparison, whether debulking pituitary surgery improved GH control on lanreotide compared with that obtained pre-operatively. Local Ethical Committee ap...