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S. L. Hyer, P. S. Sharp, R. A. Brooks, J. M. Burrin and E. M. Kohner

Abstract. Complete suppression of GH secretion may halt the development of retinal new vessels in patients with diabetic proliferative retinopathy. We have investigated the effectiveness of two cholinergic antagonists, atropine and propanthelene given orally for 2 weeks, in suppressing 24-h GH and IGF-I levels. Seven insulin-dependent diabetics (3 males, 4 females; aged 22–34 years) with active proliferative retinopathy and 6 matched non-diabetic normal subjects were studied in random order with at least 2 weeks between treatments. Suppression of GHRH-induced GH release was demonstrated in both groups of subjects. Twenty-four hour GH secretion was not, however, suppressed in either the patient group (mean area under the GH curve mU·1−1·h−1 ± sd; baseline: 251 ± 108.7; after atropine: 174 ± 106.9; after propanthelene: 180 ± 72.4; P > 0.05) or in the control group (baseline: 103 ± 53.1; after atropine: 73 ± 83.6; after propanthelene: 122 ± 71.6; P >0.05). GH release at times of hypoglycemia was not suppressed. Mean IGF-I concentration was not significantly reduced. Two subjects (one patient and one control) could not tolerate atropine for more than one week. We conclude that repeated doses of atropine and propanthelene do not achieve complete 24-h GH suppression and are associated with a high incidence of unpleasant adverse reactions.

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S. L. Hyer, P. S. Sharp, R. A. Brooks, J. M. Burrin and E. M. Kohner

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.