Disease relevance of Acromegaly

• Some clinical observations implicate GH in human mammary growth, for example, gynecomastia occurs in some children treated with GH (ref. 6), and tall stature and acromegaly are associated with an increased incidence of breast cancer [1].
• A 64-year-old woman with active acromegaly of 33 years' duration, severe carpal tunnel syndrome, and subclinical heart disease was treated with bromocriptine mesylate [2].
• GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states, such as acromegaly, anorexia nervosa, and hyperthyroidism [3].
• Serum levels of immunoreactive insulinlike growth factors (IGF) I and II were determined by a modified IGF I and a new IGF II radioimmunoassay in normal children and adults, and in patients with acromegaly, isolated growth hormone deficiency, and extrapancreatic tumor hypoglycemia [4].
• CONCLUSIONS: Improvement in indices of sleep apnea severity occurs in association with octreotide treatment in patients with sleep apnea and acromegaly [5].

High impact information on Acromegaly

• Successful pregnancy in a previously infertile woman treated with SMS-201-995 for acromegaly [6].
• We measured the ability of plasma extracts from patients with acromegaly to inhibit the binding of ouabain to the sodium pump in normal red cells and to inhibit the enzymatic activity (sodium-potassium-ATPase) of the sodium pump in membrane preparations from normal kidneys [7].
• Although bromocriptine, a dopamine receptor agonist, is now widely used in the treatment of acromegaly, there have been no controlled trials of its biochemical or clinical effects on this disorder [8].
• Measurement of somatomedin-C appears to provide a reliable means for confirming the diagnosis of acromegaly and of clinical disease activity than measurement of growth hormone concentrations [9].
• Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly [10].

Chemical compound and disease context of Acromegaly

• After glucose ingestion, the resistance to insulin in acromegaly is further enhanced and antilipolysis is also impaired [11].
• The primary structures of three polypeptides, possessing high intrinsic growth hormone-releasing activity and derived from a human pancreatic carcinoma which had caused acromegaly, were established by sequence analyses of the intact peptides and their cyanogen bromide digestion fragments with a gas-phase sequenator [12].
• BACKGROUND: Treatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones [13].
• Estradiol treatment of acromegaly. Reduction of immunoreactive somatomedin-C and improvement in metabolic status [14].
• In conclusion, these data confirm the efficacy and the tolerance of the long-term SR lanreotide administration (30 mg im every 10-14 days) in the control of acromegaly [15].
• Acromegaly subjects were insulin resistant [16].

Biological context of Acromegaly

• To assess the effect of chronically elevated plasma growth hormone (GH) levels on bone metabolism and bone mineral density (BMD), 16 patients (10 females and 6 males) with a mean age of 49.1 +/- 13.2 years (range 33-68) with active acromegaly were studied and compared to a control group of 16 sex- and age-matched subjects [17].
• This study was conducted to determine whether administration of a GH receptor antagonist to patients with acromegaly and insulin resistance would result in improvement in insulin sensitivity and whether IGF-I had any additional insulin-sensitizing effects over and above those induced by its ability to suppress GH secretion [18].
• Blood pressure response to an angiotensin II antagonist in patients with acromegaly [19].
• Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes [20].
• Pharmacokinetics and efficacy of a long-acting formulation of the new somatostatin analog BIM 23014 in patients with acromegaly [21].

Anatomical context of Acromegaly

• Growth hormone-releasing factors (GRF's) from two human pancreatic tumors (hpGRF's) that caused acromegaly and from the rat hypothalamus ( rhGRF ) were recently isolated and characterized [22].
• Thyroid volume and serum thyroglobulin levels in patients with acromegaly: correlation with plasma insulin-like growth factor I levels [23].
• In this investigation, the pituitary glands of eight patients with CNC and acromegaly [age, 22.9+/-11.6 yr (mean +/- SD)] were studied histologically [24].
• This study examined the effects of acromegaly treatment on adipose tissue LPL [25].
• Our data demonstrate that patients with long-term acromegaly have normal sympathetic activity in the skeletal muscle in the basal, postabsorptive state and normal increments in NE spillover in response to the sympatho-excitatory effect of insulin [26].

Gene context of Acromegaly

• Somatostatin (SRIF) analogs provide safe and effective therapy for acromegaly [27].
• SMS 201-995 can lower plasma concentrations of growth hormone and somatomedin-C in patients with pituitary acromegaly, but no controlled trials to assess symptomatic response or change in tumor size have been done [28].
• Growth hormone and prolactin secretion in acromegaly: correlations between hormonal dynamics and immunocytochemical findings [29].
• Octreotide suppresses both growth hormone (GH) and GH-releasing hormone (GHRH) in acromegaly due to ectopic GHRH secretion [30].
• Considering the ALS/IGFBP-3 molar ratio, almost 55% of ALS circulated in a free form in active acromegaly [31].

Analytical, diagnostic and therapeutic context of Acromegaly

• These preliminary results suggest that SMS 201-995 represents an additional option for the management of acromegaly, especially in patients who do not benefit sufficiently from surgery or radiotherapy and do not respond well to treatment with dopaminergic drugs [32].
• Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed [10].
• 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 [33].
• We assessed serum growth hormone (GH) levels in ten patients with acromegaly during a 24-hour profile and a 75-g oral glucose tolerance test (GTT) [34].
• SMS 201-995 is, therefore, a useful new palliative treatment for acromegaly [35].

References