PubMed · 9284694
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A Colao, B Merola, D Ferone, G Lombardi. 1997. Acromegaly.. https://doi.org/10.1210/jcem.82.9.4257
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
This article focuses on developments in treatment options for pituitary adenomas. We review the literature on the advances in diagnosis and treatment modalities, including medical and surgical approaches. We also discuss conventional radiation and the recently proposed genetic treatments for pituitary tumors.
The aim of the study was to investigate the effects of 1-yr treatment with octreotide (OCT) on left ventricular diastolic and systolic function, assessed at rest and during physical exercise by gated blood pool cardiac scintigraphy, in 30 patients with active acromegaly. OCT was initially given at a dose of 0.05-0.1 mg, 3 times daily, and the dose was subsequently increased to achieve GH/insulin-like growth factor I (IGF-I) normalization. Hormone normalization after treatment was considered when basal and/or oral glucose test-suppressed GH values were below 2.5 and 1 microg/L, respectively, and IGF-I values were within the normal range for age. To evaluate the response to OCT treatment in terms of cardiac performance, the 30 patients were divided into 2 groups on the basis of normalized (in 13 patients) or nonnormalized (in 17 patients) circulating GH and IGF-I levels. At study entry, hypertension was found in 6 patients (20%), abnormal left ventricular diastolic filling was found in 12 patients (40%), and impaired left ventricular ejection fraction was found in 2 patients at rest (6.6%) and in 18 patients at peak exercise (60%). Before OCT treatment, exercise duration ranged from 6-10 min, and exercise workload ranged from 50-125 watts. After 1-yr treatment with OCT, a significant decrease in circulating GH and IGF-I levels was achieved in all patients, but normalization was obtained only in 13 of 30 patients. In patients achieving circulating GH and IGF-I normalization after OCT treatment but not in those with persistently elevated hormone levels, a significant decrease in heart rate, both at rest (from 75.7 +/- 3.3 to 66.5 +/- 2.9 beats/min; P < 0.01) and after exercise (from 137.5 +/- 4.9 to 123.7 +/- 4.1 beats/min; P < 0.01), and a significant increase in left ventricular ejection fraction, both at rest (from 56.5 +/- 1.8% to 66.5 +/- 2.2%; P < 0.01) and after exercise (from 52.6 +/- 2.4% to 67.1 +/- 1.7%; P < 0.01), were found. In the 17 patients who had persistently high circulating GH and IGF-I levels after 1 yr of OCT treatment, left ventricular ejection fraction was unchanged at rest but was significantly reduced after exercise compared to the basal value (from 64.9 +/- 2.4% to 57.2 +/- 2.6%, P < 0.01); systolic blood pressure at rest was significantly increased (from 128.5 +/- 4.9 to 141.2 +/- 5.4 mm Hg; P < 0.05). In these 17 patients, the ejection fraction response to exercise was significantly impaired, mostly in those less than 40 yr of age (from 11.6 +/- 3.2% to -0.3 +/- 5.6%; P < 0.05). In particular, among 9 patients who had a normal response to exercise at study entry, 6 developed an abnormal response after 1 yr. Left ventricular diastolic filling was unchanged by OCT treatment in all patients. Exercise duration (only in young patients from 7.5 +/- 0.5 to 9.3 +/- 0.7 min; P < 0.05) and exercise workload (in all 13 patients from 80.8 +/- 6.4 to 92.3 +/- 5.9 watts; P < 0.05) were significantly increased in the group of patients with normalized GH and IGF levels, but not in the remaining 17 (from 7.6 +/- 0.4 to 7.5 +/- 0.4 min and from 89.9 +/- 5.5 to 84.4 +/- 4.5 watts, respectively). In conclusion, the results of the present study indicate that suppression of basal or glucose-suppressed GH levels below 2.5 or 1 microg/L, respectively, together with normalization of plasma IGF-I levels for 1 yr are followed by a significant improvement, but not complete normalization, of left ventricular ejection fraction either at rest or at peak exercise without significant changes in diastolic filling. By contrast, the persistence for 1 yr of elevated hormone levels caused a significant increase in systolic blood pressure and impaired cardiac performance. These data suggest that prolonged suppression of circulating GH and IGF-I levels could normalize cardiac performance and probably reverse the poor prognosis for cardiovascular disease in acromegaly.
Familial acromegaly/gigantism occurring in the absence of multiple endocrine neoplasia type I (MEN-1) or the Carney complex has been reported in 18 families since the biochemical diagnosis of GH excess became available, and the genetic defect is unknown. In the present study we examined 2 unrelated families with isolated acromegaly/gigantism. In family A, 3 of 4 siblings were affected, with ages at diagnosis of 19, 21, and 23 yr. In family B, 5 of 13 siblings exhibited the phenotype and were diagnosed at 13, 15, 17, 17, and 24 yr of age. All 8 affected patients had elevated basal GH levels associated with high insulin-like growth factor I levels and/or nonsuppressible serum GH levels during an oral glucose tolerance test. GHRH levels were normal in affected members of family A. An invasive macroadenoma was found in 6 subjects, and a microadenoma was found in 1 subject from family B. The sequence of the GHRH receptor complementary DNA in 1 tumor from family A was normal. There was no history of consanguinity in either family, and the past medical history and laboratory results excluded MEN-1 and the Carney complex in all affected and unaffected screened subjects. Five of 8 subjects have undergone pituitary surgery to date, and paraffin-embedded pituitary blocks were available for analysis. Loss of heterozygosity on chromosome 11q13 was studied by comparing microsatellite polymorphisms of leukocyte and tumor DNA using PYGM (centromeric) and D11S527 (telomeric), markers closely linked to the MEN-1 tumor suppressor gene. All tumors exhibited a loss of heterozygosity at both markers. Sequencing of the MEN-1 gene revealed no germline mutations in either family, nor was a somatic mutation found in tumor DNA from one subject in family A. The integrity of the MEN-1 gene in this subject was further supported by demonstration of the presence of MEN-1 messenger ribonucleic acid, as assessed by RT-PCR. These data indicate that loss of heterozygosity in these affected family members appears independent of MEN-1 gene changes and suggest that a novel (tissue-specific?) tumor suppressor gene(s) linked to the PYGM marker and expressed in the pituitary is essential for regulation of somatotrope proliferation.