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PubMed2000

Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.

BACKGROUND: Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone. METHODS: We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. RESULTS: The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups. CONCLUSIONS: On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

Acromegaly↗
PubMed1993

Effects of metoclopramide on the paradoxical growth hormone response to galanin in acromegaly.

Galanin is able to enhance growth hormone (GH)-releasing hormone stimulated GH secretion in normal man. In acromegaly circulating GH levels are elevated and the GH response to GHRH may be exaggerated. Galanin has been recently shown to decrease circulating GH levels in acromegaly. Dopaminergic drugs were the only previously known agents able to cause a paradoxical GH fall in acromegaly. Aim of our study was to investigate the effects of a potent central dopaminergic receptor blocker, metoclopramide (MCP), on the galanin-induced paradoxical GH secretion in acromegalic subjects. Two male and three female patients with active acromegaly (age range 44-66 years, body mass index range 24.6-28 Kg/m2) were studied after 45 min i.v. infusion of porcine galanin (0.5 mg in 100 ml of saline) from 0 to 45 min combined with a 60 min i.v. infusion of a) saline (100 ml) or b) MCP (10 mg in 100 ml of saline) from -15 to 45 min. After galanin, GH values fell from baseline (27.5 +/- 10 micrograms/L) to a mean nadir of 16.4 +/- 6.1 micrograms/L; after galanin + MCP, circulating GH levels were also decreased (mean nadir 17.3 +/- 8.1 micrograms/L) in all the patients with respect to baseline (23.6 +/- 9.7 micrograms/L). No significant differences were found in absolute or percent of baseline GH levels after galanin+saline vs galanin + MCP. Our results suggest that the paradoxical GH fall after galanin in acromegalic patients is not mediated through dopaminergic receptor. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by GH-secreting adenomatous cells.

Acromegaly↗
PubMed1999

Goiter associated with acromegaly: sonographic and scintigraphic findings of the thyroid gland.

Elevation in serum human growth hormone (GH) level is known to be a factor that causes goiter development. The present study was designed to analyze sonographic and scintigraphic appearances of the thyroid in patients with acromegaly. The records of 48 consecutive patients with acromegaly were examined. Two patients had a history of operation for thyroid cancer. One had an atrophic thyroid gland after 131I treatment for Graves' disease. Goiter was palpable in 39 of the remaining 45 patients. Neither ultrasonography (US) nor scintigraphy was performed in 17 patients, including 6 with no palpable goiter and 11 with small diffuse goiter (group 1). Of the remaining 28 patients who underwent US, 14 had a moderately or markedly enlarged diffuse goiter (group 2), 13 were diagnosed as having adenomatous goiter (group 3), and 1 had a solitary cystic nodule. Among 11 patients in group 3 who underwent 123I or 99mTc thyroid scintigraphy, 6 showed uneven uptake, and 2 with undetectably reduced levels of thyrotropin (TSH) showed localized functioning areas. The mean serum TSH concentration in group 3 was significantly lower than that in group 1 or 2 (p<0.01). The duration of illness as acromegaly was significantly longer in group 2 and 3 as compared with group 1 (p<0.05). These results suggest that long-term stimulation by GH and insulin-like growth factor-I of thyroid follicular cells might be responsible for thyroid enlargement, presence of functioning lesions, slight overactivity of the thyroid, and the subsequent formation of multiple nodules in acromegalic patients. In conclusion, excluding two patients with thyroid cancer and one with Graves' disease, goiter was palpable in 39 of the 45 patients with acromegaly, among whom 14 (13 adenomatous goiters and 1 solitary cystic nodule) showed nodular enlargement.

Acromegaly↗
PubMed1999

Outcome of surgery for acromegaly--the experience of a dedicated pituitary surgeon.

Previous large series of outcome following pituitary surgery for acromegaly, including our own, have demonstrated poor results, with cure, defined as GH <5 mU/l, achieved in only 33-42% of patients. In our previous series, surgery was performed by one of eight different surgeons. Largely based on the disappointing results of this previous audit of outcome, our practice since 1990 has been, whenever possible, to refer all patients with acromegaly to a dedicated pituitary surgeon (APJ). The objective of the current study was to re-analyse the outcome of surgical treatment for acromegaly since instituting this change. Tumour size and extension was determined on CT/MRI scanning. Biochemical cure was defined as a basal GH <5 mU/l or a nadir GH of <2 mU/l across an OGTT following initial pituitary surgery. Surgery was performed on 66 patients and 42 (64%) were cured, compared with 26/78 (33%) in our previous study (p<0.0005, chi (2) test). The cure rate for microadenomas (n=22) was 86%, and for macroadenomas 52%, compared with 54% (p<0.05, chi (2) test) and 30% (p<0.05, chi (2) test) respectively, in our previous study. We conclude that surgical outcome for acromegaly is enhanced if patients are operated on by a single experienced surgeon.

Acromegaly↗
PubMed1988

A hyperkinetic heart in uncomplicated active acromegaly. Explanation of hypertension in acromegalic patients?

Cardiac function was studied by echocardiography in 12 patients with active acromegaly and in 12 age- and sex-matched healthy control subjects. None of the patients had cardiovascular diseases or other endocrine diseases than acromegaly. The patients had a mean age of 39 +/- 5 years and were short-term acromegalic with a mean duration of disease of 6 +/- 3 years. Mean left ventricular mass was 163 +/- 43 g/m2 in the acromegalic group versus 120 +/- 24 g/m2 in the control group. Preload (the diastolic diameter of the left ventricle) was within normal limits, while afterload (end-systolic meridional wall stress) was significantly decreased in the acromegalic group. Myocardial contractility assessed as fractional shortening of the left ventricle was 39.9 +/- 3.6% in the acromegalic group versus 32.9 +/- 5.1% in the control group, and cardiac output was increased by 52% in the acromegalic group because of increased heart rate and stroke volume. We suggest that augmented peripheral blood flow is responsible for the condition of cardiac hyperkinesia in short-term acromegaly and involved in the development of hypertension, which is a frequent complication of long-term acromegaly.

Acromegaly↗
PubMed1979

Immunoreactive somatomedin B in acromegaly and in Turner's syndrome.

Serum somatomedin B was measured by radioimmunoassay in forty-seven normal subjects, twenty-nine patients with acromegaly before and twenty-four after treatment, and eighteen patients with Turner's syndrome. Somatomedin B levels were significantly elevated in untreated acromegaly and in Turner's syndrome compared with the control group; they decreased following treatment of acromegaly. Because of the overlap between the groups, little information could be obtained from single somatomedin B estimations, which could, therefore, not replace dynamic tests of growth hormone secretion. No correlation between growth hormone and somatomedin B in acromegaly was detected; however, somatomedin B appeared to be related to the insulin response during the oral glucose tolerance test. In Turner's syndrome, no relationship between somatomedin B and insulin production, urinary oestrogen excretion, growth hormone secretion, gonadotrophin levels, age or height was found. The reason for the raised somatomedin B levels in Turner's syndrome remains at present unknown.

Acromegaly↗
PubMed1980

Epidemiology of acromegaly in the Newcastle region.

In an attempt to derive estimates of the incidence and prevalence of acromegaly a survey of the population in the area served by the former Newcastle Regional Hospital Board has been conducted to detect cases of acromegaly alive after 1 January 1960 and diagnosed before 31 December 1971. Cases were detected by means of letters to general practitioners, hospital physicians, neurosurgeons and to hospital records officers, as well as from death certificates. From the population of 3.1 millions a firm diagnosis of acromegaly was made in 164 patients, in eighty-one on clinical grounds alone and in eighty-three with confirmation by assay of human growth hormone (hGH). The annual incidence of acromegaly appears to be close to three cases per million and the prevalence of diagnosed cases up to forty cases per million. In male acromegalics there was a significant increase in the risk of death from cardiovascular, cerebrovascular respiratory and malignant diseases but in females from cerebrovascular disease only.

Acromegaly↗
PubMed1983

Skin thickness in patients with acromegaly and Cushing's syndrome and response to treatment.

Radiological assessment of skin thickness (ST) was assessed in 22 patients with acromegaly and 17 patients with Cushing's syndrome. The age ranges of the patients studied and the 55 individuals in the control group were comparable. The skin thickness in males was significantly greater than in females (P less than 0.01). Mean skin thickness in patients with acromegaly and Cushing's syndrome was significantly greater and less respectively than the mean skin thickness of the normal controls (P less than 0.02). Following successful treatment of acromegaly (growth hormone less than 5 micrograms/l) there was a significant reduction in skin thickness (P less than 0.02 males: P less than 0.01 females). The skin thickness declined at approximately 0.3 mm/year for the first two years and more slowly thereafter. A highly significant correlation was observed between the logarithm of the pre and post treatment plasma GH concentrations and ST values. With one exception, all patients with growth hormone (GH) levels greater than 5 micrograms/l had ST values above the normal range. At an average of 4.5 years after successful treatment of Cushing's syndrome the average increase in ST was 0.23 mm (P less than 0.01). It is concluded that the measurement of skin thickness is a useful screening test for both acromegaly and Cushing's syndrome and provides an objective assessment of the clinical response to treatment.

Acromegaly↗
PubMed1985

Growth hormone releasing factor-test in acromegaly: comparison with other dynamic tests.

Human pancreatic growth hormone releasing factor (hpGRF1-44) was given intravenously as a 100 micrograms bolus to 20 patients with active acromegaly. The GH-responses were variable, ranging from an increase of 8 to 2813% from the basal level (mean +/- SE, 428 +/- 136%). Sixteen GRF-responders (delta% greater than or equal to 100%) were arbitrarily distinguished from four GRF non-responders, whose GH-levels increased less than 100% from basal level after GRF-administration. The outcome of the GRF-test did not correlate with the results of other dynamic tests of GH-secretion in acromegaly (oral glucose tolerance test, insulin hypoglycaemia, TRH-, LHRH-, CRF-stimulation). In 10 patients who had not been treated before, the GH-increments after GRF were higher than those in seven patients who had previously been subjected to transsphenoidal surgery, though they still had clinically and biochemically active acromegaly. Ten acromegalics, who were tested with GRF, were later treated surgically by the transsphenoidal route and were reevaluated with GRF-stimulation 2 months after surgery. Eight patients appeared clinically cured of whom four had complete normalization and four had significantly lower basal and conventionally stimulated GH-levels postoperatively. These patients also had normal postoperative GH-responses to GRF, which had been significantly higher before surgery compared with normal controls. It is concluded that the GRF-test in acromegaly does not help in establishing the diagnosis. The normalization of the GH-response to GRF after transsphenoidal surgery seems to represent additional evidence for normalization of GH-secretion, though the latter is not proven by the normal outcome of this test.

Acromegaly↗
PubMed1990

Overnight urinary growth hormone measurement in the diagnosis of acromegaly.

Several studies report higher urinary GH excretion in acromegalic patients compared to control subjects. We investigated the diagnostic potential of overnight urinary GH excretion in acromegaly, using a recently developed enzyme-linked immunosorbent assay. Overnight urine samples were obtained from 117 control subjects and nine patients with untreated acromegaly. GH excretion was higher in acromegalic patients compared to control subjects, with geometric mean total overnight values of 46.35 and 5.73 microU respectively. The range for total overnight urinary GH in control subjects was 0.75-21.75 microU and two of the nine patients with untreated acromegaly had GH measurements within this range. Urinary GH measurements were corrected using predictive clinical variables but this resulted in minimal improvement in discrimination between control subjects and acromegalic patients. Lack of complete discrimination between control subjects and acromegalic patients limits the usefulness of a single overnight urinary GH measurement as a screening test for acromegaly.

Acromegaly↗
PubMed1991

Inter-relations between growth hormone, insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1) and sex hormone-binding globulin in acromegaly.

Acromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF-I, an important mediator of its actions. IGF-I itself is intimately related to insulin both in structure and function. IGF-I circulates associated with specific binding proteins which appear to have important effects on its activity. We have examined the inter-relations between GH, prolactin, insulin, IGF-I and one of the binding proteins, IGFBP-1, in 62 patients with acromegaly of varying activity. Serum IGF-I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P less than 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF-I. IGF-I concentrations were independent of prolactin. Fasting insulin levels were high and unrelated to mean GH levels but correlated with those of IGF-I (r = 0.542; n = 57; P less than 0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP-1 (r = 0.684; n = 57; P less than 0.001). Even in subjects whose acromegaly was well controlled or cured, as indicated by GH levels of less than 1 mU/l or IGF-I levels of less than 2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP-1 levels were low and unrelated to mean GH but were inversely related to fasting insulin levels (r = -0.593; n = 57; P less than 0.001). We propose that a cascade of events occurs in acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

High affinity growth hormone binding protein in plasma of patients with acromegaly and the effect of octreotide treatment.

OBJECTIVE: The objective of this study was to investigate the effect of plasma GH-levels on the high affinity growth hormone binding protein (GHBP). PATIENTS: We studied plasma samples of eight patients with acromegaly and eight age and sex matched healthy subjects. DESIGN: Patients with acromegaly were treated with octreotide administered by continuous subcutaneous infusion. Levels of growth hormone binding protein (GHBP) were measured in plasma samples before therapy and 3, 6 and 12 months after starting treatment. During this period, octreotide was administered in doses of 300-800 micrograms/day. The mean dose per patient over the study period ranged from 300 to 575 micrograms/24 h. The GHBP levels of patients with acromegaly were compared with those in the healthy subjects. MEASUREMENTS: Bound and free 125I-GH in plasma were measured using FPLC gel chromatography on a Superose 12 column, after an overnight incubation period. The binding data were used for a Scatchard plot analysis. Wilcoxon's signed rank test was used for statistical analysis. RESULTS: We found lower GHBP levels in acromegalic patients (P = 0.01) than in the control subjects. Octreotide treatment resulted in IGF-I levels < 300 micrograms/l in four patients. In these patients GHBP levels increased. CONCLUSIONS: We conclude that growth hormone binding protein levels are down regulated in acromegaly, indicating an important role for GH in the regulation of this protein.

Acromegaly↗
PubMed1992

Insulin secretion and insulin-like growth factor-I levels in active and controlled acromegaly.

OBJECTIVE: We examined the contributions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) to insulin sensitivity and beta-cell function in acromegaly. DESIGN: A cross-sectional study was used with continuous infusion of glucose with model assessment to determine insulin sensitivity and beta-cell function. PATIENTS: Ten patients with active acromegaly, seven with controlled disease and 22 normal individuals were studied. MEASUREMENTS: Glucose and insulin levels were measured fasting and at the end of the one-hour glucose infusion to calculate insulin sensitivity and beta-cell function. Random GH and IGF-I were recorded. Most patients had values of GH taken after a 100-g oral glucose tolerance test and K values from intravenous glucose tolerance tests. RESULTS Patients with active acromegaly had significantly decreased insulin sensitivity compared to the normal population (P less than 0.001), while those with controlled disease did not. There was a significant negative correlation between IGF-I and insulin sensitivity in those with active disease (P less than 0.05). Beta-cell function in both active and controlled patient groups was elevated compared to the normal population (P less than 0.05, P less than 0.01 respectively) and this was significantly related to IGF-I in the active group (P less than 0.05). GH levels did not correlate with fasting insulin, glucose, insulin sensitivity or beta-cell function in either group. CONCLUSIONS: Patients with active acromegaly have decreased insulin sensitivity and increased beta-cell function that are significantly related to IGF-I but not GH levels. When the disease is controlled, beta-cell function remains elevated but insulin sensitivity improves.

Acromegaly↗
PubMed1994

Serum lipoproteins in acromegaly before and 6-15 months after transsphenoidal adenomectomy.

OBJECTIVES: Acromegaly is a rare disorder characterized by over-secretion of GH, most often because of a pituitary adenoma. The disease is associated with disturbances in lipoprotein metabolism and an increased cardiovascular mortality. The aim of the present study was to investigate whether treatment of acromegaly results in changes in serum concentrations of lipids and apolipoproteins, including lipoprotein(a) (Lp(a)). DESIGN: Fourteen patients with clinical features of acromegaly and increased GH secretion were studied 1-10 months before and 6-15 months after transsphenoidal adenomectomy in an open study. PATIENTS: Three patients had diabetes mellitus before surgery and two of these patients had normalized serum glucose levels post-operatively. Mean and baseline plasma GH levels were determined from 24-hour GH profiles. Serum samples were taken in the morning after an overnight fast. All patients were normocholesterolaemic, and four patients were hypertriglyceridaemic before treatment. RESULTS: Mean plasma GH levels decreased from 34.5 +/- 7.4 to 2.1 +/- 0.4 mU/l (mean +/- SEM). Serum IGF-I, insulin and free T3 levels decreased and serum SHBG concentrations increased post-operatively. There was no effect of treatment on serum cholesterol concentrations, but serum triglyceride concentrations decreased. Serum apolipoprotein (apo) B and apoE levels were unaffected by treatment. Serum apoA-I levels increased and Lp(a) levels decreased post-operatively. CONCLUSIONS: Successful treatment of acromegaly, resulting in normal mean GH values (< 5 mU/l) and/or normal responsiveness to TRH, have beneficial effects on serum lipoproteins with increased serum apoA-I levels and decreased serum levels of triglycerides and Lp(a). These effects seem to be independent of improvement in glucose tolerance, since patients with diabetes mellitus before surgery and normal fasting blood glucose levels post-operatively had similar lipoprotein responses to treatment as those with normal fasting blood glucose levels before surgery.

Acromegaly↗
PubMed1995

Nocturnal breathing abnormalities in acromegaly after adenomectomy.

OBJECTIVE: The incidence of sleep apnoea is increased in acromegaly. The aim of the study was to determine the occurrence of nocturnal breathing abnormalities and upper airway morphology in acromegalic patients some years after adenomectomy. DESIGN: A case-control study. PATIENTS: Eleven patients with treated acromegaly and two control groups: (1) sleep studies: 197 subjects randomly selected from the population, (2) cephalometry: 27 healthy subjects and 17 patients with obstructive sleep apnoea. MEASUREMENTS: Nocturnal breathing was monitored with a static charge-sensitive bed. The upper airway soft tissues and bone morphology were assessed by cephalometric X-ray photography. The upper airway collapsibility was investigated with dynamic nasopharyngoscopy. Endocrinological investigations were also performed. RESULTS: Nocturnal breathing abnormalities were present in all but one acromegalic patient (91%), which was far more frequent than in the general population (29.4%, P < 0.0001). Treated acromegaly was the most powerful predictor of breathing abnormalities, independent of the other significant predictors, age and body mass index. The predominant breathing abnormality was periodic breathing with symmetrically waxing and waning respiratory effort without a major body movement component. Episodes of complete obstruction with repetitive arousals were rare. Except for the longer soft palate, the cephalometric findings were similar to normal. In comparison to obstructive sleep apnoea, the treated acromegalic patients had rather prognathic than retrognathic mandibles. Fibreoptic endoscopy in the acromegalic patients revealed collapsible upper airways at the level of the soft palate, whereas at the base of the tongue little, if any, dynamic narrowing was observed. CONCLUSION: Our study confirms that nocturnal breathing abnormalities are common in treated acromegaly, and may persist years after the removal of the GH secreting tumour. The breathing abnormalities and the upper airway morphology in acromegalic patients after adenomectomy are different from those observed in primary obstructive sleep apnoea, suggesting a different pathophysiology of the airway obstruction.

Acromegaly↗
PubMed1995

The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly.

BACKGROUND: Reduction of GH concentrations in acromegalic subjects may improve the increased mortality associated with the condition. Audit of the biochemical outcome of the management of acromegaly is, therefore, important. OBJECTIVES: (1) To audit the biochemical 'cure' rate of acromegalic patients treated by surgery and/or radiotherapy under the care of the South Birmingham Endocrine Clinic. (2) To assess the correlation between random or basal GH with IGF-I and nadir GH during an oral glucose tolerance test. DESIGN AND MEASUREMENTS: Ascertainment of acromegalic patients from a pituitary database. Mode of therapy, pretreatment GH, pretreatment tumour size, post-treatment GH, post-treatment IGF-I and post-treatment nadir GH were recorded. Biochemical cure was defined as a most recent random or basal GH < 5 mU/l. Cure rates were determined. PATIENTS: Eighty-nine acromegalic patients were identified as having received surgery and/or radiotherapy. In 35/89 (39%) the most recent GH was < 5 mU/l. The cure rate following surgery was 26/78 (33%). This was not significantly associated with tumour size, but was associated with pretreatment GH concentration (chi 2 = 7.1, 2d.f., P < 0.05). Random/basal GH showed a log-linear association with IGF-I, r = 0.72, and a linear association with nadir GH, r = 0.93. CONCLUSIONS: Biochemical cure of acromegaly was more strongly associated with pretreatment GH than with tumour size. Random/basal GH measurements are useful and convenient for the audit of treatment outcome in acromegaly. Ways of improving the biochemical outcome of acromegaly should be sought.

Acromegaly↗
PubMed2004

Prevalence and determinants of left ventricular hypertrophy in acromegaly: impact of different methods of indexing left ventricular mass.

BACKGROUND: Left ventricular hypertrophy (LVH) is the most common cardiac abnormality in acromegaly. Left ventricular mass (LVM) is an important parameter measured to detect LVH, but the relationship with body size should be considered by correcting LVM to body surface area (BSA), height or height2.7. All trials concerning acromegaly have detected LVH on the basis of LVM indexed for BSA, but have been criticized for disregarding the effects of obesity. PATIENTS AND MEASUREMENTS: 97 patients with active acromegaly and a control group of 97 nonacromegalic subjects, were compared for the prevalence of LVH, calculated with different corrections of LVM for BSA, height and height2.7. In addition, we evaluated determinants of LVH in acromegalic group. RESULTS: In controls, the prevalence of LVH, determined by correcting LVM for BSA (10.3%) was significantly lower than correcting by LVM/height (21.6%, P = 0.05) and LVM/height2.7 (33%, P < 0.0001). Similarly, in the acromegalic population the prevalence of LVH was significantly higher when measured by LVM/height (86.6%) or LVM/height2.7 (89.7%), than by LVM/BSA (67%) (P = 0.002 and P < 0.0001, respectively). A lower prevalence of LVH detected by LVM/BSA than LVM/height and LVM/height2.7 has been observed in an acromegalic overweight group, while in patients with normal weight there was no significant differences using different corrections. In acromegalic patients with disease duration of 10 years. By separate multiple regression analyses systolic blood pressure was the only independent determinant of LVM/BSA or LVM/height, while systolic blood pressure and GH levels were both predictors of LVM/height2.7. CONCLUSIONS: LVM indexed for height2.7 appears to be the most appropriate method to identify LVH in acromegaly, particularly in overweight patients and those with shorter disease duration.

Acromegaly↗
PubMed2004

Systematic dose-extension of octreotide LAR: the importance of individual tailoring of treatment in patients with acromegaly.

OBJECTIVE: The depot long-acting somatostatin analogue octreotide LAR (LAR) provides effective and well-tolerated treatment for acromegaly. Despite a 4-weekly recommended injection frequency, prolonged duration of GH suppression has been observed in some patients following treatment with long-acting somatostatin analogues. The aim of our study was to perform a prospective systematic study to determine whether extending the interval between doses of LAR allows maintenance of 'safe' GH in selected patients with acromegaly. PATIENTS AND METHODS: Twenty-two patients (15 men, seven women), mean age 58.9 years (35-81 years) with active acromegaly (mGH > 5 mU/l), requiring treatment were selected to receive treatment with LAR. Eleven patients had received previous treatment with both transsphenoidal surgery and radiotherapy, while six had received surgery alone. All patients were commenced on treatment with 20 mg LAR intramuscularly (i.m.) every 4 weeks. Mean GH (mGH) was measured after three consecutive injections immediately prior to the fourth injection. The dose frequency was systematically reduced after every four injections if mGH < 5 mU/l. Once mGH > 5 mU/l, the dose frequency was increased and mGH reassessed. RESULTS: The dosing interval was successfully increased to greater than 4 weeks in 20/22 patients (90.9%). Six of 22 (27.3%) were receiving injections every 8 weeks and 3/22 (13.6%) every 12 weeks. GH and IGF-I were lower on treatment compared with baseline (P < 0.01). There was no difference in individual mGH and IGF-I between the values on 4-weekly dosing and those at final dose frequency. There was no relationship between final dose frequency and either mean GH or IGF-I prior to LAR, patient age, or previous treatment. The percentage suppression following 100 micro g octreotide subcutaneously did not predict subsequent dose frequency of LAR. The drug cost if patients had continued at 4-weekly intervals would be UK pound 187 850, compared with UK pound 101 065 for the individually titrated dose frequency (P < 0.01). This represents a final cost of 53.8% of the 4-weekly injection price. CONCLUSION: Individual tailoring of LAR administration maintains control of acromegaly, with reduced injection frequency and improved cost-effectiveness.

Acromegaly↗