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ObjectiveIt is established that external pituitary irradiation (EPI) effectively reduces serum GH levels in acromegaly. However, its effect in normalising serum IGF1 has been disputed. We looked at the number of our patients who achieved persistently normal IGF1 levels whilst free of adjunctive treatment for at least 1 year after EPI.Patients and designWe identified 63 acromegalic patients between 1964 and 2004 who received EPI. Six were excluded: three had surgery after EPI, two had no medical records available, and one had a pituitary Yttrium implant.MeasurementsPatients received 4500–5000 cGy in fractionated doses. IGF1 levels were correlated with their respective age-related reference ranges.ResultsAfter EPI, the number of patients with normal IGF1 and free of adjunctive medical treatment for at least 1 year were four patients by 3 years, nine patients by 5 years and seventeen by 10 years, with the current number of 25/57 (44%). Concordance between IGF1 levels and random GH dropped from 90% at the time of EPI to 65% at 3 years, 66% at 5 years and 71% at 10 years.ConclusionsWe have demonstrated that, with time, EPI achieves a normal IGF1 in significant numbers of patients with acromegaly, thus obviating the need for life-long expensive medical therapy. For each patient this benefit has to be weighed against the possibility of new hypopituitarism as a result of the treatment. Any decision to use EPI is easier in the context of pre-existent hypopituitarism.

The pathogenesis of hypertension associated with Cushing's syndrome is incompletely understood. We have studied basal and saline-stimulated levels of plasma atrial natriuretic hormone in 10 subjects with active Cushing's syndrome (8 F: 2 M), aged 43±4 years (mean±sem). Ten age- and sex-matched normal control subjects were also studied. Subjects fasted from 22.00 h, rose at 07.45 h, and remained ambulant until 09.45 h when blood was taken for plasma ANH, plasma renin activity and serum aldosterone. Subjects then rested supine until 10.00 h when blood was again taken, and blood pressure recorded. Then, while subjects remained supine, 2 1 of 0.9% NaCl were infused between 10.00 and 14.00 h. Blood was taken hourly. Basal plasma ANH was 8.0±0.9 pmol/l in Cushing's subjects and 6.9±2.5 pmol/l in controls. Levels increased in response to saline in both groups, and became significantly higher in the group of patients with Cushing's syndrome (14.00 h level 21.3±3.9 vs 10.4± 1.9 pmol/l; p

The results of treating 10 acromegalic patients with octreotide are compared with those of bromocriptine. Bromocriptine (5 mg 4 times daily for 5 weeks) reduced mean growth hormone (GH) concentrations from 60 to 35 mU/1 in 8 patients; a further 2 patients were unable to tolerate this dose. Ten patients (8 unresponsive to bromocriptine) received octreotide 100 µg 3 times daily, rising to 500 µg 3 times daily according to monthly 24-hour GH profiles. Two patients were withdrawn from octreotide therapy; in the remaining 8, mean GH fell from 36 to 11 mU/1 after 6 months’ therapy (a reduction to 22% of basal concentrations, compared to a reduction to 58% on bromocriptine). Asymptomatic changes of glucose tolerance and the development of gallstones were noted; further information on the latter is urgently required. In summary, the smallest effective dose of octreotide should be used and each patient should be monitored biochemically.action than the native hormone [9]. We have studied the effects of octreotide in a group of treatment-resistant acromegalic subjects. GH was assessed by 24-hour profiles, and side effects of octreotide were also investigated. For comparison, the results of a previously published trial [ 10] from our group, which studied the effect of bromocriptine in a similar group of patients, are presented.

McKnight JA, McCance, DR, Sheridan B, Atkinson AB. Four years' treatment of resistant acromegaly with octreotide. Eur J Endocrinol 1995;132:429–32. ISSN 0804–4643 This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21–62 years) with persistent growth hormone (GH) elevation (duration 1–15 years) despite previous therapy were studied. Octreotide was given subcutaneously in increasing doses for the first year to a maximum of 500 μg three times daily. The dose then was reduced to 200 μg three times daily for the next 3 years. At annual assessments, 24-h GH profiles, insulin-like growth factor I (IGF-I) and a side-effect profile including gall-bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were performed basally and after 6 months and 3 years of therapy. Haemoglobin A1 (HbA1) was also assessed. Side effects were recorded. Mean GH (± sem) was 36.0 ± 9 mU/l basally and was reduced significantly at all subsequent assessments on therapy (4-year mean, 9.4 ± 2.1 mU/l). The IGF-I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3–9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4–15.7 mmol/l); p < 0.05). Five patients developed gallstones and in three these had disappeared following 1 year of bile salt dissolution therapy. Octreotide continues to suppress serum GH and IGF-I long term without attenuation of effect. Gallstone formation is a major side effect. Two hours after glucose load the plasma glucose level was elevated but HbA1 did not change long term. Further similar studies of long duration are required to establish the long-term safety profile of the drug. AB Atkinson, Sir George E Clark Metabolic Unit, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland

There is little information available concerning the presence or absence of a normal variation in the circulating concentration of atrial natriuretic homone throughout a 24 h period. We have examined this in 8 normal subjects (aged 23–35 years) on a fixed 120 mmol Na+ diet. Circulating levels of ANH, plasma renin activity, serum aldosterone and serum cortisol were determined two-hourly during 24 h in a supine position. There was a significant change in the concentration of each of these four hormones during the study period (P< 0.05). ANH: peak 8.5 (22.00 h), nadir 4.0 (12.00 h) (pmol/l); PRA: peak 1.7 (04.00 h), nadir 0.8 (22.00 h) (μg · l−1 · h−1); aldosterone: peak 350 (14.00 h), nadir 143 (22.00 h) (pmol/l); cortisol: peak 346 (08.00 h), nadir 51 (22.00 h) (nmol/l). Peak plasma ANH occurred at 22.00 h and with the exception of times 20.00 h and 10.00 h this value was significantly higher than all the other time means (P< 0.05). The only other significant differences were between plasma ANH at 20.00 h and 06.00 h, 08.00 h, 12.00 h and 14.00 h, respectively (P< 0.05). From midnight until 18.00 h, there was no significant difference between any of the time means. There was a peak in PRA at 04.00 h, while peak serum aldosterone and serum cortisol occurred at 14.00 h and 08.00 h, respectively. This study suggests that ANH may display a diurnal rhythm. Our findings provide further physiological evidence that plasma ANH and PRA may have a reciprocal relationship.