Summary
It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0 ± 6.8 mg/day for 12 ± 3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 min after oral glucose load increased from 5.05 ± 0.61 to 5.77 ± 0.78 mmol/1 and from 5.61 ±2.05 to 7.55 ± 3.05 mmol/1, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin A1c was not observed. Bromocriptine led to a significant decrease in basal as well as glucose-stimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients. Similarly to the increased growth hormone secretion after drug withdrawal in 11 patients, a rise in glucose-stimulated insulin secretion was found in all patients; hereby, the mean insulin levels at 0 and 120 min during oral glucose load rose significantly from 7.5 ± 2.6 to 12.1 ± 5.1 mU/1 (P<0.01) and from 71.3±52.1 to 101.4±50.7 mU/1 (P<0.02), respectively. A direct relationship between disturbance in glucose homeostasis and degree of hypersomatotropism was not observed. Our data confirm that the beneficial effect of bromocriptine therapy on glucose homeostasis in selected patients with acromegaly is still present after dopaminergic treatment over a mean period of 12 years. Compared with the published rates on improved glucose homeostasis under octreotide, the effect of bromocriptine seems to be more favorable.
Similar content being viewed by others
Abbreviations
- AUC:
-
area under the curve
- GH:
-
growth hormone
- PRL:
-
prolactin
References
Althoff PH, Böttger B, Rosak C, Harz C, Jungmann E, Schöffling K (1982) Zur Bromocriptin-Langzeitbehandlung der Akromegalie. In: Pfeiffer EF (ed) Bromocriptin. Ein fachübergreifendes Therapieprinzip. Schattauer, Stuttgart, pp 149–173
Carlson HE, Levin SR, Braunstein GD, Spencer EM, Wilson SE, Hershman JM (1984) Effect of bromocriptine on serum hormones in acromegaly. Horm Res 19:142–152
Chiba T, Chihara K, Minamitani N, Goto S, Kadowaki S, Taminato T, Matsukura S, Fujita T (1982) Effect of longterm bromocriptine treatment on glucose intolerance in acromegaly. Horm Metab Res 14:57–61
Faglia G, Arosio M, Ambrosi B (1985) Recent advances in diagnosis and treatment of acromegaly. In: Imura H (ed) The pituitary gland. Raven, New York, pp 363–404
Feek CM, Bevan JS, Taylor S, Brown NS, Baird JD (1981) The effect of bromocriptine on insulin secretion and glucose tolerance in patients with acromegaly. Clin Endocrinol 15:473–478
Halse J, Harris AG, Kvistborg A, Kjartansson O, Hanssen E, Smiseth O, Djosland O, Hass G, Jervell J (1990) A randomized study of SMS 201–995 versus bromocriptine treatment in acromegaly: clinical and biochemical effects. J Clin Endocrinol Metab 70:1254–1261
Haslbeck M, Mehnert H (1984) Diagnose und Differentialdiagnose. In: Mehnert H, Schöffling K (eds) Diabetologie in Klinik und Praxis. Thieme, Stuttgart, pp 100–137
Johnston DG, Alberti KG, Nattrass M, Burin JM, Bleas-Malpica G, Hall K, Hall R (1980) Hyperinsulinaemia in hyperprolactinaemic women. Clin Endocrinol 13:361–368
Koenig RJ, Peterson CM, Kilo C, Cerami A, Williamson JR (1976) Hemoglobin A, as an indicator of the degree of glucose intolerance in diabetes. Diabetes 25:230–232
Landgraf R, Landgraf-Leurs MM, Weissmann A, Hörl R, von Werder K, Scriba PC (1977) Prolactin: a diabetogenic hormone. Diabetologia 13:99–104
Lerario AC, el-Andere W, Wajchenberg BL, Ohnuma LY, Rocha MH, Andriolo A (1989) Insulin resistance in acromegaly: evaluation by studies of insulin binding to erythrocytes. J Endocrinol Invest 12:155–161
Liuzzi A, Chiodini PG, Botalla L, Cremascoli G, Müller EE, Silvestrini F (1974) Decreased plasma growth hormone (GH) levels in acromegalics following CB 154 (2-Br-α-ergo-cryptine) administration. J Clin Endocrinol Metab 38:910–912
Luft R, Ikkos D, Gemzell CA, Olivecrona H (1958) Effect of human growth hormone in hypophysectomized diabetic subjects. Lancet I:721–722
McKnight JA, McCance CR, Sheridan B, McIlrath E, Hadden DR, Kennedy L, Atkinson AB (1991) A long-term dose-response study of somatostatin analogue (SMS 201–995, octreotide) in resistant acromegaly. Clin Endocrinol 34:119–125
Nathan DM, Singer DE, Hurxthal K, Goodson JD (1984) The clinical information value of the glycosylated hemoglobin assay. N Engl J Med 310:341–346
Rau H, Althoff PH, Schmidt K, Usadel KH (1992) Bromocriptine treatment over 12 years in acromegaly: effect on growth hormone and prolactin secretion. Acta Endocrinol 126:247–252
Sachs L (1984) Angewandte Statistik: Anwendung statistischer Methoden. Springer, Berlin Heidelberg New York, pp 244–246, 548–549
Sassolas G, Harris AG, James-Deidier A (1990) Long-term effect of incremental doses of the somatostatin analog SMS 201–995 in 58 acromegalic patients. French SMS 201–995 approximately equal to Acromegaly Study Group. J Clin Endocrinol Metab 71:391–397
Sönksen PH, Greenwood FC, Ellis JP, Lowy C, Rutherford A, Nabarro JD (1967) Changes in carbohydrate tolerance in acromegaly with progress of the disease and in response to treatment. J Clin Endocrinol Metab 27:1418–1430
Vance ML, Harris AG (1991) Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Results of the International Multicenter Acromegaly Study Group. Arch Intern Med 151:1573–1578
Von Werder K (1988) Bromocriptine treatment in acromegaly. In: Lamberts SW (ed) Sandostatin in the treatment of acromegaly. Springer, Berlin Heidelberg New York, pp 45–52
Wass JA, Cudworth AG, Bottazzo GF, Woodrow JC, Besser GM (1980) An assessment of glucose intolerance in acromegaly and its response to medical treatment. Clin Endocrinol 12:53–59
Wright AD, Hartog M, Palter H, Tevaarwerk G, Doyle FH, Arnot R, Joplin GF, Russel Fraser T (1970) The use of yttrium 90 implantation in the treatment of acromegaly. Proc R Soc Med 63:221–223
Author information
Authors and Affiliations
Additional information
Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday
Rights and permissions
About this article
Cite this article
Rau, H., Althoff, PH., Schmidt, K. et al. Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion. Clin Investig 71, 372–378 (1993). https://doi.org/10.1007/BF00186626
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00186626