Long-term bromocriptine treatment and somatostatin in acromegaly

9 active acromegalic patients were treated for 12 months with bromocriptine (Parlodel, Sandoz) in a daily dose of 10 mg, and at the end of this treatment a somatostatin infusion was administered. The glucose tolerance and the serum hGH level were determined, and the changes in the clinical symptoms were evaluated. 7 patients (responder group) reacted favourably to the treatment; the other 2 proved to be non-responders, the hGH increasing as a consequence of bromocriptine treatment. The non-responders were among those patients who reacted to hyperglycaemia with a hGH increase (paradox glucose response). The somatostatin infusion employed in the drug treatment caused a very drastic decrease in the hGH level. The biochemical and clinical changes were not synchronous. The results permit the conclusions that (1) a relatively small dose of bromocriptine has a very good effect in the large majority of acromegalic patients; (2) the behaviour of the glucose response is an important point in the differentiation of the non-responders; (3) with somatostatin infusion during bromocriptine treatment a further considerable hGH decrease may be induced (a role is presumably played in the effect by the substitution of the hypothalamically drug-inhibited somatostatin release by exogenous material); (4) there is not a close parallel between the hGH decrease on bromocriptine treatment and the clinical improvement, which indicates the significance of the peripheral effects of the drug.     

Long-term treatment of acromegaly with bromocriptine.

Seventy-three patients with active acromegaly were treated for three to 25 months with bromocriptine 10-60 mg/day. Seventy-one patients showed symptomatic and objective clinical improvement. This included reduction in excessive sweating, hand and foot size, and the number of headaches; improved facial appearance; and increased energy and libido. Abnormal visual fields became normal in two patients, one of whom had concomitant radiotherapy. Mean circulating growth hormone levels, obtained by averaging serial samples through the day, fell by more than 7 microng/l or became undetectable in 58 patients (79%) but did not reach normal values: only 15 patients had mean levels on treatment of 5 microng/l or less. Twenty-three patients were diabetic before treatment, and glucose tolerance became normal in 15 and improved in a further five. Provided the drug was started slowly side effects were minor when compared with the considerable clinical benefit obtained.     

The combination therapy with bromocriptine and cyproheptadine in patients with acromegaly

The therapeutic efficacy of the combination of cyproheptadine and bromocriptine was studied in 15 patients with active acromegaly showing incomplete GH suppression in response to bromocriptine therapy alone. The mean basal plasma GH was 31.3 +/- 5.5 micrograms/L, and it decreased to 19.0 +/- 3.9 micrograms/L during the single bromocriptine therapy (10 to 20 mg for 2 to 21 months). When cyproheptadine (12 to 16 mg for 8 to 52 months) was added to bromocriptine therapy, plasma GH decreased further (9.4 +/- 3.0 micrograms/L: vs pretreatment, P less than 0.001; vs bromocriptine treatment, P less than 0.005), and GH normalization was obtained in 8 patients. The plasma somatomedin-C levels in these 8 patients (0.3-1.8 U/ml) were within the normal range during the combination therapy. Plasma GH responses to TRH or GHRH were markedly suppressed in 6 patients during the combination therapy compared to pretreatment or during bromocriptine treatment. In addition, a clear reduction in the tumor size was observed in 4 of 7 previously untreated patients during the combination therapy. In conclusion, cyproheptadine has therapeutic efficacy in acromegalic patients who showed incomplete GH suppression in response to treatment with bromocriptine alone. Following the cyproheptadine and bromocriptine combination therapy tumor shrinkage was observed in some patients.     

Long-term management of acromegaly with sandostatin

The present report illustrates the effectiveness of a long-acting somatostatin analog, SMS 201-995 (Sandostatin), in the chronic treatment of acromegaly. Daily doses of 50-300 micrograms were administered subcutaneously to 37 patients. Gradual dose increments induced a progressive GH decrease accompanied by a parallel reduction in plasma somatomedin C concentrations. There was a concomitant amelioration of clinical signs and symptoms throughout the investigational period. No escape phenomenon or tachyphylaxis was observed. It is concluded that chronic therapy with SMS 201-995 represents a promising medical alternative for the treatment of active acromegaly.     

Gel filtration studies of serum growth hormone in acromegaly following bromocriptine administration.

Sera of 7 patients with active acromegaly were fractionated by Sephadex G-100 chromatography and the effects of bromocriptine on the concentrations of total growth hormone (hGH) and its different molecular forms studied. Three immunoreactive peaks were observed, corresponding to molecular weights of about 20,000 ('little hGH'), 40,000 ('big hGH'), and more than 100,000 ('big big hGH') Following bromocriptine administration, there was significantly more reduction of 'little hGH' than of 'big big hGH'. Careful interpretation of these changes is required in view of the possible influences of sample storage and handling on hGH heterogeneity. We suggest that either bromocriptine acts differentially on the release of 'little' and 'big big hGH', or that these components differ in their metabolic half-life. However, even the suppression of 'little hGH' is insufficient to explain the clinical response of the disease to bromocriptine.     

Effects of pirenzepine, bromocriptine and their association on basal and GHRH- and TRH-induced GH secretion in acromegaly.

In order to ascertain if pirenzepine (Pz), an antimuscarinic drug, could inhibit GH secretion in acromegaly, 8 patients were submitted to 3 successive treatment courses of 9 days each: Pz, bromocriptine (BRC) and Pz plus BRC. No change in basal levels of GH after Pz administration was seen, but its reduction (p less than 0.05) by BRC was observed. Pz plus BRC did not improve this response. None of these drugs abolished the paradoxical GH response to TRH. In 7 normal controls, Pz suppressed the GH responsiveness to GHRH (p less than 0.001), but not in acromegalic patients. BRC, instead, blunted this response. In conclusion, cholinergic control of GH secretion is altered in acromegaly. Pz, either when administered alone or associated with BRC, is not useful for the treatment of this disease.     

The importance of presurgical somatostatin analogue therapy in acromegaly

Different types of treatment, including surgery, medical therapy and radiotherapy, are possible in achieving control of acromegaly. Of the medical therapies available, somatostatin analogues are effective in the majority of patients and can induce pituitary tumour shrinkage. The rationale and outcome of somatostatin analogue treatment before surgery in patients with acromegaly is briefly presented. In summary, the benefits of somatostatin analogues given preoperatively should be considered carefully as optimisation of cardiovascular, respiratory and metabolic functions is clinically relevant for perioperative morbidity. Somatostatin analogues also induce significant shrinkage of GH-secreting pituitary tumours, although this does not seem to be helpful in terms of improved surgical outcome.     

Comparison of TRF, propranolol-glucagon, insulin and glucose stimulation tests in acromegaly.

In 7 acromegalic patients growth hormone responses were studied following administration of synthetic TRF, propranolol-glucagon, insulin, and glucose p.o. Except for the glucose tolerance test, a good reproducibility of the STH response was observed. In 5 out of the 7 patients, there was a distinct rise in the plasma STH level after TRF. All patients with a positive insulin tolerance test responded to TRF, as did the two late responders to glucagon; the early responder to the latter test did not respond to TRF. It has been suggested (Liuzzi et al. 1974a) that TRF might be used as a screening test for detecting hypothalamic dependency of the acromegaly. This study suggests that further study is required before accepting this hypothesis and that a response to a combination of tests (TRF, glucagon, insulin) might be a better screening method.     

Research needs for predictive multispecies tests in aquatic toxicology

Aquatic multispecies tests are increasingly used to assess the fateand effects of pesticides in Europe. The rationale for their use,although originally based upon ecological arguments, is now morelikely to be based upon uncertainties surrounding the true exposure of organisms in natural ecosystems. This shift inrationale promotes the design of more focused studies, but does notovercome difficulties associated with the extrapolation of mesocosmand microcosm results to natural systems. Priorities for furtherresearch into these systems should be the extent to which resultscan be repeated and reproduced, and the level of precision andaccuracy of predictions from microcosms and mesocosms to naturalecosystems.     

A case of large prolactinoma supposed to be cured by bromocriptine therapy

The authors reported a patient with a large prolactinoma (PRL 1,716 ng/ml) who was treated with bromocriptine for two years and followed up for a subsequent 36 months. After the start of the therapy, the tumor size was dramatically reduced, and finally the disappearance of the tumor was confirmed by high resolution coronal CT. The serum prolactin level and pituitary function were normalized. The tumor has not regrown and the blood prolactin level has remained normal for 36 months since the discontinuation of bromocriptine administration. This is a very rare case report on the eradicative effect of bromocriptine on such a large prolactinoma. Another characteristic of this case was that the prolactin reserve was maintained not only before the therapy but also during the early stage of the therapy.     

N-acetyl-beta-glucosaminidase and albuminuria in acromegaly

Significantly increased albuminuria and N-acetyl-beta-glucosaminidase activity in serum and urine have been observed in acromegalic patients in comparison with healthy persons (P less than 0.001). No relationship between these biochemical variables and serum growth hormone or insulin concentration was found in our group of patients. Significant correlation was determined between urinary NAG activity and albuminuria of acromegalic patients (r = 0.84).     

Long-term growth hormone therapy in mitochondrial cytopathy

OBJECTIVE: To describe in a 5-year-old Caucasian male with mitochondrial cytopathy, a biochemical growth hormone (GH) deficiency associated with normal GH biological activity as evaluated by Nb2 cell bioassay and normal serum IGF-I and IGFBP3 values increasing slightly after GH administration. METHOD: Serum GH concentrations were measured with a commercial immunofluorometric assay and with a biological assay, which uses the Nb2 cell line. Serum IGF-I and IGFBP3 concentrations were measured with RIA. RESULTS: The GH-supplementary therapy was initially effective in terms of growth gain, but no therapeutic benefit was observed over a long period of time. CONCLUSION: In patients suffering from mitochondrial cytopathy, short stature seems to be attributed more to a disease-related inadequate protein substrate than to the non-classical GH deficiency.