Medical Treatment Of Acromegaly Research Articles

Clinical results of long-term slow-release lanreotide treatment of acromegaly.

Medical therapy is frequently needed to normalize growth hormone/insulin-like growth factor I secretion in acromegaly. The aim of this study was to determine the long-term effects of the slow-release (SR) somatostatin analogue lanreotide in 57 acromegalic patients. SR lanreotide (30 mg) was given every 14 days for 12 months. In 33% of patients, the drug dosage was raised to 60 mg and/or the time interval was shortened to 10 days. Two months of clinical evaluation followed drug discontinuation in 47 out of 48 (84%) patients who completed the 12-month period. A drug-related decrease in GH/IGF-I levels was observed. Basal GH/IGF-I levels were significantly (P < 0.001) reduced at 12 months, IGF-I was normalized in 35% of patients and GH levels were < 5 micrograms L-1 in 54%. There was a clinical improvement in patients complaining of joint pain, rachialgias, headache, digital paraesthesias and hyperhidrosis. Soft-tissue changes were documented by significant (P < 0.001) decreases in finger size. In 52 (91%) patients without overt diabetes, a slight but significant increase in integrated glycaemia (P < 0.001) was noted, while integrated insulin levels were reduced (P < 0.001). Of 33 (58%) patients with normal basal ultrasound examination of the gall bladder, three (9%) had developed asymptomatic gall stones or biliary sludge after 12 months. Adverse events were generally mild. They frequently (52%) occurred after the first SR lanreotide administration; only 28% were recurrent and 20% appeared for the first time during therapy. SR lanreotide is an effective treatment in most unselected acromegalic patients. Tolerance towards the drug is high. Subjective benefits seem to override the simple biochemical control of the disease. Glucose homeostasis more than the incidence of gall stones seems to require monitoring on therapy. SR lanreotide is clearly advantageous in improving patient compliance with medical treatment for acromegaly.

Predicting the effects of long-term medical treatment in acromegaly. At what cost? For what benefits?

Predicting the effects of long-term medical treatment in acromegaly. At what cost? For what benefits?

Effect of different dopaminergic agents in the treatment of acromegaly.

Medical treatment of acromegaly with dopamine agonists possesses 2 main advantages: the oral administration and the low costs. In this study, we reported on the results of chronic treatments with quinagolide (CV 205-502), cabergoline (CAB) and long-acting depot preparation of bromocriptine (BRC-LAR) in 34 acromegalics. Patients were divided into three groups on the basis of different treatment: CV 205-502 given to 16 patients at the dose of 0.3-0.6 mg/day for 6 months; CAB given to 11 patients at the dose of 1.0-2.0 mg weekly for 6 months; and BRC-LAR injected into 7 patients at the dose of 100 mg/month for 6-12 months. Basal and oral glucose tolerance test-stimulated serum GH levels, basal and TRH-stimulated PRL levels, plasma insulin-like growth factor I (IGF-I) levels, computed tomography scan, and/or magnetic resonance imaging were assessed before and quarterly during treatments. The chronic administration of CV 205-502, CAB, and BRC-LAR caused a significant decrease of circulating GH, IGF-I, and PRL levels (P < 0.005). Normalization of circulating GH and IGF-I levels was obtained in 7 of 16 (43.8%) patients treated with CV 205-502. Serum GH response to oral glucose tolerance test (oGTT) significantly improved (P < 0.005), and PRL levels were significantly suppressed during treatments. No correlation was found between basal and TRH-stimulated PRL levels and GH suppression during different therapies. Immunohistochemical staining revealed 19 GH-positive and 10 GH + PRL-positive adenomas. A significant association was found between GH/PRL staining and responsiveness to chronic treatments (chi 2 = 7.985, P < 0.005). Three patients had significant adenoma shrinkage. Slight nausea and hypotension which spontaneously disappeared within therapy progression, were referred by 5/16 patients during CV 205-502 and 2/7 during BRC-LAR. The results of this study indicate that CAB and BRC-LAR cannot be considered as useful medical approaches for acromegalics, whereas CV 205-502 normalized circulating GH and IGF-I levels in 47.8% of patients.

Effect of Different Dopaminergic Agents in the Treatment of Acromegaly

Medical treatment of acromegaly with dopamine agonists possesses 2 main advantages: the oral administration and the low costs. In this study, we reported on the results of chronic treatments with quinagolide (CV 205–502), cabergoline (CAB) and long-acting depot preparation of bromocriptine (BRC-LAR) in 34 acromegalics. Patients were divided into three groups on the basis of different treatment: CV 205–502 given to 16 patients at the dose of 0.3–0.6 mg/day for 6 months; CAB given to 11 patients at the dose of 1.0–2.0 mg weekly for 6 months; and BRC-LAR injected into 7 patients at the dose of 100 mg/month for 6–12 months. Basal and oral glucose tolerance test-stimulated serum GH levels, basal and TRH-stimulated PRL levels, plasma insulin-like growth factor I (IGF-I) levels, computed tomography scan, and/or magnetic resonance imaging were assessed before and quarterly during treatments. The chronic administration of CV 205–502, CAB, and BRC-LAR caused a significant decrease of circulating GH, IGF-I, and PRL levels (P < 0.005). Normalization of circulating GH and IGF-I levels was obtained in 7 of 16 (43.8%) patients treated with CV 205–502. Serum GH response to oral glucose tolerance test (oGTT) significantly improved (P < 0.005), and PRL levels were significantly suppressed during treatments. No correlation was found between basal and TRH-stimulated PRL levels and GH suppression during different therapies. Immunohistochemical staining revealed 19 GH-positive and 10 GH+PRL-positive adenomas. A significant association was found between GH/PRL staining and responsiveness to chronic treatments (χ2 = 7.985, P < 0.005). Three patients had significant adenoma shrinkage. Slight nausea and hypotension, which spontaneously disappeared within therapy progression, were referred by 5/16 patients during CV 205–502 and 2/7 during BRC-LAR. The results of this study indicate that CAB and BRC-LAR cannot be considered as useful medical approaches for acromegalics, whereas CV 205–502 normalized circulating GH and IGF-I levels in 47.8% of patients.

Advances in medical therapy for pituitary disease: treating patients with growth hormone excess and deficiency.

Two recent developments in the medical treatment of patients with pituitary disease are discussed. Conventional treatment for patients with acromegaly has been surgery and/or radiotherapy. Dopamine agonist therapy may be useful. Somatostatin is a naturally occurring neuropeptide that inhibits growth hormone (GH) secretion. The development of long-acting preparations has resulted in a considerable advance in the medical treatment of acromegaly, though some caution remains about the long-term side-effects of such therapy (e.g. cholelithiasis) and its cost/benefit analysis. Although further epidemiological studies are required, hypopituitarism appears to be associated with an increased mortality rate, and this has largely been attributed to GH deficiency. With the widespread availability of recombinant GH (thereby circumventing any risks from cadaveric GH) many adult GH-deficient patients are now being treated. Beneficial effects on body composition, nitrogen and calcium balance and bone mass have already emerged, although studies on 'well being' have been conflicting. The debate continues concerning the minimum effective dose and who exactly should be treated, in view of the costs incurred. The endocrinologists' use of long-acting somatostatin analogues and recombinant GH will undoubtedly increase over the next few years. Whilst it is clear that many patients with both acromegaly and hypopituitarism will benefit, long-term controlled trials are still required to establish firmly the benefit in terms of major morbidity.

EFFECTIVE AND LASTING GROWTH-HORMONE SUPPRESSION IN ACTIVE ACROMEGALY WITH ORAL ADMINISTRATION OF SOMATOSTATIN ANALOGUE SMS 201-995

Oral administration of the long-acting somatostatin analogue, SMS 201-995 (Sandoz), was assessed in five patients with active acromegaly, four of whom had not responded to pituitary irradiation. Doses of 4-8 mg three times daily lowered mean 24 h growth-hormone concentrations by over 50% in every case, with suppression to below 10 mU/1 for several hours after the morning dose. Despite effective suppression of serum insulin levels, deterioration in glucose tolerance was very slight, and the drug had no side-effects. Orally administered SMS 201-995 avoids the need for multiple daily injections and is potentially valuable in the medical treatment of acromegaly.

Medical Treatment of Acromegaly

ade­ noma of the pituitary gland, causes morbidity and mortality in affected patients by both local and peripheral physical changes (1-7). First, GR-secreting ade­ nomas, like other tumors of the pituitary, cause compression of surrounding neural and bony structures, among which are the normal pituitary tissues, the sphenoid and cavernous sinuses, optic nerves, and third ventricle. Second, the excess secretion of GR in acromegaly can lead to changes in the peripheral tissues, which result in gross disfigurement of the face, hands, and other parts of the body; crippling arthritis; carpal tunnel syndromes; heart disease; hyper­ tension; lung disease; a number of dermal changes; and carbohydrate and lipid abnormalities. Obviously, patients with acromegaly require therapeutic

Effect of ergot alkaloids on growth hormone and prolactin secretion in humans.

The effects of ergot alkaloids (mainly bromocriptine) on the secretion of GH and PRL in normal subjects and in pathological conditions (i.e. acromegaly and hyperprolactinemic states) are discussed. In the normal subjects, bromocriptine releases GH whereas in about 50% of acromegalics it causes a marked and long-lasting inhibition of the hormone secretion. PRL release is reduced by the drug both in normal subjects and in hyperprolactinemic states. Physiopathological studies in the humans indicate that, according to the experimental data, bromocriptine inhibits GH release in acromegaly and PRL secretion through a dopaminergic mechanism of action playing at the pituitary level. Data are reported on the effectiveness of bromocriptine in the medical treatment of acromegaly and of hyperprolactinemic states.

Effect of fenfluramine on human growth hormone release.

In order to investigate the effect of fenfluramine on hormonal and metabolic changes with exercise, five normal volunteers have been studied during and after 20 minutes of steady exercise on a bicycle ergometer after injection of fenfluramine (20 mg intravenously). Fenfluramine abolished the rise of plasma human growth hormone (HGH) which occurred in control investigations. Fenfluramine also affected plasma insulin, blood glucose, and ketone body levels.The acute effect of fenfluramine on the release of growth hormone was examined further by studying its effect in patients with acromegaly. A marked depression of growth hormone occurred both at rest and with exercise. These observations indicate that fenfluramine has a direct effect on pathways controlling growth hormone release. We also suggest that this action may have practical use in the medical treatment of acromegaly.