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PubMed2000

Exercise-induced microalbuminuria in patients with active acromegaly: acute effects of slow-release lanreotide, a long-acting somatostatin analog.

Recent clinical studies have demonstrated an increase of urinary albumin excretion (UAE) at rest in acromegalic patients and, on the other hand, a reduced UAE in patients with growth hormone (GH) deficiency. Physical exercise is known to induce abnormal UAE in patients with diabetes, probably unmasking early glomerular alterations. The effect of exercise on UAE in acromegaly is not known. Moreover, the effect of acute but sustained GH inhibition in acromegaly on UAE at rest and after exercise has never been studied. The aim of our study was to evaluate the acute short-term effects of slow-release lanreotide (SR-L), a long-acting somatostatin analog, on UAE and alpha1-microglobulinuria (A-1-M), a marker of renal tubular damage, at rest and after exercise in 7 normotensive patients with active acromegaly and normal renal function (4 males and 3 females; mean age, 53 +/- 3.1 years; body mass index [BMI], 27.3 +/- 1.1 kg/m2) at baseline and 7 and 14 days after SR-L injection (30 mg). Two of the acromegalic patients were microalbuminuric at rest, and in other 3 cases, UAE was in the borderline range (10 to 20 microg/min). At baseline in the acromegalic subjects, we found a significant increase in UAE at rest with respect to 7 normal subjects considered as a control group. GH and insulin-like growth factor-1 (IGF-1) were also reduced compared with baseline 7 and 14 days after SR-L injection (GH, 13.4 +/- 7.3 and 13.61 +/- 7 v 18.5 +/- 9.3 microg/L, P < .05; IGF-1, 230 +/- 53 and 255 +/- 54 v 275 +/- 64 microg/L). Concomitantly, we observed a significant decrease of UAE at rest and after exercise and 7 and 14 days after SR-L injection as compared with baseline values (27.3 +/- 20.5 and 18.2 +/- 13.7 v 35.3 +/- 12.8 microg/min, P < .05; exercise, 48.5 +/- 24.1 and 18.6 +/- 6.8 v68.3 +/- 39.7 microg/min, P < .05). A-1-M always remained in the normal range (< 12 mg/L) both at rest and after exercise. We can thus conclude that in acromegaly, submaximal exercise induces abnormal increases in microalbuminuria. We hypothesize that this phenomenon may be due to the functional glomeruler involvement. SR-L can significantly reduce UAE at rest and after exercise in the short-term in acromegaly, probably via a decrease in circulating GH levels.

Acromegaly↗
PubMed2003

Cephalometric assessment of cranial abnormalities in patients with acromegaly.

OBJECTIVE AND PATIENTS: Patients with acromegaly (12 women, 26 men) and a control group (36 women, 50 men) were chosen for cephalometry to assess the size, shape and positional characteristics of the craniofacial bones and the upper airways. RESULTS: When compared with the controls, patients of both sexes with acromegaly were found to have significant anomalies in the orofacial skeleton: increased facial height, elongated ascending ramus mandibulae and greater basion-supramentale distance, a negative difference between maxillary and mandibular protrusions, enlarged lower part of the gonion angle and of the angle of inclination of the maxilla, as well as alterations in the neurocranium: enlargement of sella turcica and of sinus frontalis and protrusion of the supraorbital ridges. As for the soft tissues, patients with acromegaly exhibited an elongated soft palate and a diminished angle between the uvular axis and the palatal plane. A comparison between the cephalometric parameters of patients with active acromegaly and those without active disease revealed no significant differences in either sex. CONCLUSION: Patients with acromegaly exhibited an enlargement of all parts of the neurocranium and orofacial bones except the maxilla. The greatest anomaly was seen in the mandible, with greater enlargement of the ascending ramus than of the body of the mandible. The shape of this bone was also altered.

Acromegaly↗
PubMed1999

Familial acromegaly: case report and review of the literature.

Familial acromegaly is an exceptional clinical entity when not associated with features of multiple endocrine neoplasia type 1 (MEN1). We report here 3 pedigrees in each of which 2 patients have been shown to develop acromegaly. In 4 patients, clinical follow-up, and biological screening allowed to confidently exclude MEN1. Absence of mutation in the MEN1 gene after direct DNA analysis in 2 pedigrees reinforces the conviction that the families do not have MEN1. In families 1 and 2, diagnosis was made at a very early age and voluminous adenomas with suprasellar expansion were already present at the time of diagnosis. We review the 20 previous reports of familial acromegaly, some of them questionable. Our 3 families, combined with some other published pedigrees, allow the delineation of a familial form of acromegaly, distinct from MEN1. Dominant inheritance with reduced, age-dependant penetrance is the most parsimonious model to explain the recurrences. Gs protein pathway could be the site of action of the gene responsible of familial acromegaly, but no data have been published to sustain or reject this hypothesis.

Acromegaly↗
PubMed2001

Cardiovascular complications in acromegaly: methods of assessment.

Cardiac involvement is common in acromegaly. Evidence for cardiac hypertrophy, dilation and diastolic filling abnormalities has been widely reported in literature. Generally, ventricular hypertrophy is revealed by echocardiography but early data referred increased cardiac size by standard X-ray. Besides, echocardiography investigates cardiac function and value disease. There are new technologic advances in ultrasonic imaging. Pulsed Tissue Doppler is a new non-invasive ultrasound tool which extends Doppler applications beyond the analysis of intra-cardiac flow velocities until the quantitative assessment of the regional myocardial left ventricular wall motion, measuring directly velocities and time intervals of myocardium. The radionuclide techniques permit to study better the cardiac performance. In fact, diastolic as well as systolic function can be assessed at rest and at peak exercise by equilibrium radionuclide angiography. This method has a main advantage of providing direct evaluation of ventricular function, being operator independent. Coronary artery disease has been poorly studied mainly because of the necessity to perform invasive procedures. Only a few cases have been reported with heart failure study by coronarography and having alterations of perfusion which ameliorated after somatostatin analog treatment. More recently, a few data have been presented using perfusional scintigraphy in acromegaly, even if coronary artery disease does not seem very frequent in acromegaly. Doppler analysis of carotid arteries can be also performed to investigate atherosclerosis: however, patients with active acromegaly have endothelial dysfunction more than clear-cut atherosclerotic plaques. In conclusion, careful assessments of cardiac function, morphology and activity need in patients with acromegaly.

Acromegaly↗
PubMed1999

Obstructive sleep apnoea in acromegaly: the role of craniofacial changes.

Obstructive sleep apnoea (OSA) is due to craniofacial changes and acromegaly. The question addressed by this study was whether growth hormone (GH) induced craniofacial changes might explain persisting OSA despite endocrine inactivity in acromegaly. Nineteen patients treated for acromegaly were examined cephalometrically for craniofacial changes and polysomnographically for OSA. Twelve patients proved to have OSA with an apnoea/hypopnoea index >15; seven patients showed no evidence of OSA at all. With respect to the endocrinological parameters, there were no differences between the two groups that would explain the presence or absence of OSA. Neither group differed with respect to sex, age, or body mass index. Craniofacial changes were predominantly found in the mandible. The group with OSA proved to have increased vertical, dolichofacial growth compared to those without OSA. Consecutively, in the OSA group the posterior airway space was narrowed, and the hyoid was displaced more caudally. Thus, it seems that craniofacial structures of patients with acromegaly and persisting obstructive sleep apnoea are different from those without obstructive sleep apnoea. Surgical corrections of pertaining acromegaly-induced craniofacial changes should be performed with an awareness of the individual craniofacial condition so as not to enhance obstructive sleep apnoea.

Acromegaly↗
PubMed1996

Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure.

OBJECTIVE: Previous studies of surgical treatment for acromegaly have used varied criteria for 'cure', but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN: We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew's Hospital between 1985 and 1993. PATIENTS: One hundred consecutive patients (53 male, mean age 46 years, range 18-68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5-8 years) after operation. MEASUREMENTS: GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900 h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS: Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5 mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission post-operatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5-8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS: The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.

Acromegaly↗
PubMed1997

Acromegaly, colonic polyps and carcinoma.

OBJECTIVE: It has been suggested that patients with acromegaly may be at risk of developing colorectal carcinoma. In order to clarify this issue, we have evaluated the prevalence of carcinoma, premalignant tubulovillous adenomas and hyperplastic colonic polyps in a large cohort of patients with acromegaly. DESIGN: Prospective colonoscopic examination by a single operator. PATIENTS: One hundred and twenty-nine patients with biochemically proven acromegaly. RESULTS: At least one lesion was visualized in 63 patients. Adenocarcinoma was present in six patients (5%), but only two had symptoms; all lesions were endoscopically obvious. Compared with a normal group, the odds ratio of colorectal cancer is increased at 13.5 (95% confidence intervals (c.i.) 3.1-75). One or more tubulovillous adenoma was found in 34 patients (26%) and this prevalence was age-dependent, occurring in 39% of patients aged 70 years or over. Comparing the prevalence of left-sided colonic adenomas with that in a normal group, there is a higher prevalence among patients over 49 years with an odds ratio of 4.2 (95% c.i. 2.5-6.8). Patients with acromegaly who had an adenoma were significantly older than unaffected patients (61.9 vs 54.1 years; P < 0.001) but had similar GH and IGF-1 levels and duration of disease. CONCLUSIONS: Patients with acromegaly have an increased risk of developing colorectal cancer and a significantly higher prevalence of tubulovillous adenomas compared with normal subjects. Routine surveillance colonoscopy is indicated in this group of patients.

Acromegaly↗
PubMed1997

Ocular naevus and melanoma in acromegaly.

Acromegaly favours the development of extrapituitary neoplasms presumably promoted through increased GH and IGF-I levels. We describe here two patients which acromegaly and benign and malignant melanocytic tumours of the eye choroid. The first patient had a 15 year history of progressive acromegaly despite trans-sphenoidal surgery, radiation and bromocriptine therapy when she presented with melanoma of the eye and a contralateral benign melanocytic tumour. The second patient was referred with typical acromegaly. The initial fundal examination revealed a right sided benign melanocytic tumour of the choroid. Subsequent follow up of the naevi has not shown any change in the tumours after one and three years respectively. The occurrence of melanoma has not been reported in acromegaly. Increased growth of benign naevi might be expected as GH and IGF-I receptors have been described on melanocytes. As naevi may degenerate into melanomas in normal subjects and radiation therapy could trigger their transformation, we suggest that prior to irradiation, acromegalic subjects should undergo a careful ocular examination in order to assess the presence of ocular naevi.

Acromegaly↗
PubMed1997

Cabergoline treatment of acromegaly: a preliminary dose finding study.

OBJECTIVES: Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long-acting and well-tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GH DESIGN AND MEASUREMENTS: Patients with active acromegaly (defined as most recent random GH > 5 mU/l) were identified from the departmental clinical information system. After informed consent was obtained, basal GH levels were estimated during a 5 point day curve at least 2 months after withdrawal of any existing medical therapy for acromegaly. The cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5 point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the intermediate dose increment stages. Serum IGF-1 and prolactin were estimated on each occasion. Biochemical remission was defined as serum GH < 5 mU/l. PATIENTS: Eleven acromegalics were investigated. Previous treatment included surgery (7), radiotherapy (5) and bromocriptine (5). Three patients had not received any previous treatment. All had random GH persistently > 5 mU/l prior to the study. RESULTS: Ten patients completed the study. Of these, 7 showed a fall in the GH to < or = 33% and IGF-1 to < or = 67% of the basal value but only 2 achieved biochemical remission. All subjects showed maximum GH response at a dose of 0.5 mg daily of cabergoline. Four patients were unable to tolerate the maximum dose of 1 mg daily (nausea in one and nonspecific symptoms in three). The patient excluded from the analysis discontinued cabergoline and underwent surgery after 1 month because of worsening visual field defects. CONCLUSIONS: Cabergoline may be a useful adjunct to the currently available treatment for acromegaly, but rarely achieves the goal of mean GH < 5 mU/l. The maximum suppression of GH is achieved within the dose range 1 mg twice weekly to 0.5 mg daily.

Acromegaly↗
PubMed1998

Long-term therapy with long-acting octreotide (Sandostatin-LAR) for the management of acromegaly.

OBJECTIVES: To evaluate the efficacy and safety of a long-acting preparation of the somatostatin analogue octreotide, Sandostatin-LAR (SMS-LAR) for the treatment of acromegaly. DESIGN AND PATIENTS: Thirteen patients with acromegaly received intramuscular injections of SMS-LAR 20-40 mg at 4-6 week intervals for a period of up to 3 years. MEASUREMENTS: Serial measurement of serum GH and IGF concentrations were obtained. Symptoms related to acromegaly were scored by patients at baseline and following each injection. Serial gallbladder ultrasound and pituitary imaging was performed throughout the study. RESULTS: One patient was withdrawn from the study after 6 months because of continued gastrointestinal side effects; 4 patients were treated with monthly injections for 12 months and 8 patients with injections at either 1 month or 6-week intervals for 36 months; hence data is presented for n = 12 for up to 12 months; and thereafter n = 8. SMS-LAR significantly reduced serum GH and IGF-1 values: for the whole group GH concentrations fell from 24.8 +/- 4.2 mU/l (mean +/- SE) at baseline to 5.2 +/- 0.8 mU/l at 12 months (P < 0.01, n = 12). In the 8 patients treated for 3 years GH fell from 27.8 +/- 6.1 mU/l at baseline to 4.2 +/- 0.8 mU/l at the end of 3 years (P < 0.01, n = 8). GH fell to < 10 mU/l in all subjects and was < 5 mU/l in 50% after both 1 and 3 years. IGF-1 concentrations fell from 95 +/- 13 nmol/l at baseline to 63 +/- 13 nmol/l after 1 year (P < 0.01, n = 12; reference range < 65 nmol/l). In the 8 patients treated for 3 years IGF-1 concentrations fell from 119 +/- 14 nmol/l at baseline to 60 +/- 13 nmol/l after 3 years (P < 0.001, n = 8). IGF-1 was < 65 nmol/l in 60% of patients after 1 year and 75% after 3 years. Treatment resulted in trends towards improvement in symptoms of acromegaly and statistically significant improvement in sweating. There was no evidence of tachyphylaxis or evidence to suggest development of glucose intolerance. Only 2 patients (15%) developed gallbladder sludge which was asymptomatic; no patient developed gallstones. CONCLUSIONS: We conclude that SMS-LAR is a safe, effective and well tolerated treatment, making it an important therapeutic option in the management of acromegaly.

Acromegaly↗
PubMed1999

Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience.

BACKGROUND: A number of surgical series have been reported on the treatment of acromegaly and their results vary widely. The acceptable definition of remission has changed in recent years and it is known, though in a small series, that growth hormone levels of > 5 mU/l are still associated with an increased mortality from the condition. We have analysed data at this centre and examined the outcome of transphenoidal surgery for acromegaly, compared our results with recently published series from other centres and also assessed factors which might effect outcome including whether there is any demonstrable effect of the experience of the surgeon on outcome. PATIENTS AND METHODS: We have analysed data from all of our 139 patients in whom follow up data are available who have undergone initial transphenoidal surgery for acromegaly by one surgeon at this centre, between 1974 and 1995. Follow up was for a median of 5 years (range 1 month to 17 years). RESULTS: 67% of patients achieved the criterion for remission (mean GH < 5 mU/l). Success was related to tumour size and preoperative growth hormone values. Thus 91% of patients with microadenomas were in remission postoperatively compared to 46% of patients with macroadenomas. Analysis of the results according to the year of operation showed an improvement in success rates with time. More than 15 years ago, the success rate according to the growth hormone criteria set was 48% and the failure rate 52%. In contrast in the last 5 years analysed, the overall success rate was 74% with a failure rate of 26% (P < 0.04). The success rate for microadenomas was 50% initially, then remained 100%. The case mix was analysed and no change was found. We have also demonstrated an improvement in pituitary function (including normalization of preoperative elevated prolactin) with time so that pre 1981 16% of patients' pituitary function improved perioperatively but 10 years later this figure had risen to 34% (P < 0.03). There was no change over time in the development of pituitary hypofunction, complication rate or recurrence rate. CONCLUSION: Surgical treatment is a safe and effective treatment for acromegaly and remains the first choice of treatment for most acromegalic patients. The results of this centre compare favourably with series from other centres. We have demonstrated improved results, both in terms of post operative growth hormone values and pituitary function tests with time and increasing neurosurgical experience. We conclude that outcome for the surgical treatment for acromegaly is best achieved with one surgeon specialising in pituitary surgery. Improved operative outcome thus achieved has major cost implications and avoids the necessity for consideration of postoperative radiotherapy and the use of expensive growth hormone suppressing drugs in the postoperative period.

Acromegaly↗
PubMed2001

Effect of Sandostatin LAR on sleep apnoea in acromegaly: correlation with computerized tomographic cephalometry and hormonal activity.

OBJECTIVES: Sleep apnoea has been reported to occur in subjects with acromegaly. This study evaluates the relationship among biochemical activity, sleep apnoeic activity and upper airway anatomic profile in acromegaly, and the effect of Sandostatin LAR, a long-acting somatostatin analogue, on these parameters. PATIENTS: Fourteen subjects with acromegaly were recruited. MEASUREMENTS: Subjects were assessed at baseline and those with apnoea-hypopnoea index (AHI) > or = 5 were reassessed after 6 months of treatment with Sandostatin LAR 20-30 mg IMI 4-weekly. Biochemical activity was assessed with levels of GH and IGF-1. Sleep disordered breathing was assessed with overnight polysomnography. Upper airway anatomic profile was defined with computerized tomographic cephalometry. RESULTS: Of 14 subjects (age 42.0 +/- 8.1 years, mean +/- SD; 11 men) at baseline, there was a positive correlation between GH and tongue length (VT; P = 0.004), and between AHI and cephalometric indices: length of soft palate (PMU; P = 0.002); mandibular plane-hyoid bone distance (MPH; P = 0.017), maximum thickness of soft palate (Max-SP; P = 0.018) and VT (P = 0.027). Eight patients had sleep disordered breathing (AHI > or = 5) which was predominantly obstructive in nature (AHI = 29.4 +/- 22.6). After treatment, there were significant improvements in hormonal profile: GH, mU/l (before, 51.5 +/- 27.8; after, 8.0 +/- 7.4; P = 0.017) and IGF-1, nmol/l (before, 95.5 +/- 23.4; after, 35.0 +/- 12.4; P = 0.012); sleep-disordered breathing: AHI (before, 29.4 +/- 22.6; after, 13.4 +/- 11.12; P = 0.025), snoring episodes (before, 486 +/- 240; after, 165 +/- 170; P = 0.05); cephalometric indices, mm: MPH (before, 18.8 +/- 12.1; after, 14.8 +/- 8.4; P = 0.018), VT (before, 72.3 +/- 4.4; after, 69.7 +/- 4.3; P = 0.05). There was a positive correlation between the reduction in GH and AHI (r = 0.738, P = 0.037). CONCLUSIONS: The findings demonstrated that there was correlation between sleep apnoea severity and soft tissue overgrowth at the upper airway region in acromegaly. They also suggest that Sandostatin LAR improved obstructive sleep apnoea in acromegaly, and the effect might be partly mediated via a reduction in upper airway soft tissue, in particular that of the tongue, concomitant with a reduction in GH levels.

Acromegaly↗
PubMed1987

Evidence of an endogenous digitalis-like factor in the plasma of patients with acromegaly.

Evidence suggests that plasma-volume expansion leads to the release of a digitalis-like factor, which is thought to act on the renal tubular cells and cause natriuresis. We postulated that this factor might be present in patients with acromegaly (in whom plasma volume is elevated) and might return to normal levels when the disease was treated successfully. 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. In 21 patients with active acromegaly, the mean (+/- SE) level of ouabain-binding inhibition (1.56 +/- 0.38) was higher (P less than 0.01) than that in either 11 successfully treated patients (0.18 +/- 0.05) or in 27 normal controls (0.19 +/- 0.03). The inhibition of sodium-potassium-ATPase activity by plasma was also greater in patients with active acromegaly (38.1 +/- 6.8 percent) than in successfully treated patients (18.4 +/- 5.6 percent, P less than 0.05) or controls (21.1 +/- 2.7 percent, P less than 0.05). Significant correlations were found between plasma volume and ouabain-binding inhibition in 23 patients (r = 0.72, P less than 0.01) and sodium-potassium-ATPase inhibition in 19 patients (r = 0.62, P less than 0.01). Pituitary adenomectomy decreased plasma volume and the inhibition by plasma of ouabain binding. We conclude that an endogenous digitalis-like factor is present in the plasma of patients with chronic volume expansion due to acromegaly. These results are consistent with the hypothesis that this natriuretic factor may have a physiologic role in water and sodium homeostasis.

Acromegaly↗
PubMed2002

Treatment of acromegaly improves myocardial abnormalities.

BACKGROUND: Treatment for acromegaly decreases left ventricular (LV) mass, but it is not clear whether diastolic dysfunction is also reversible. With Doppler echocardiography, before and after effective therapy, we assessed the LV morphology and function of patients with acromegaly who were free of complications. METHODS: In 15 patients with active acromegaly (age range, 33.4 +/- 9.3 years), we compared LV Doppler echocardiographic indices, before and after transsphenoidal surgery or radiotherapy or before and after both procedures, noting a significant drop in plasma levels of growth hormone (<2.0 ng/mL after oral glucose tolerance testing). Patients did not have arterial hypertension, diabetes mellitus, thyroid dysfunction, or coronary artery disease. Occasionally, in this series, patients had no symptoms of heart failure, and patients who underwent treatment with somatostatin analog drugs were not included because they did not have a significant hormonal drop. The follow-up period after hormonal control was 2.7 +/- 1.7 years. We also studied 15 healthy control subjects matched for age, sex, and body surface area. RESULTS: Patients with acromegaly compared with healthy control subjects had increased LV mass index, relative wall thickness, and deteriorated diastolic function. After therapy, most of the abnormalities improved: LV mass index (104 +/- 21 g/m(2) x 87 +/- 21 g/m(2); P <.01), LV relative wall thickness (0.40 +/- 0.06 x 0.35 +/- 0.04; P <.01), proto/telediastolic transmitral peak flow velocity ratio (1.17 +/- 0.33 x 1.49 +/- 0.34; P <.001), and isovolumetric relaxation period (126 +/- 18 ms x 113 +/- 13 ms; P <.05). CONCLUSION: Treatment of acromegaly in patients without clinical heart failure improves both LV morphology and diastolic function. Avoidance of progression to more advanced forms of acromegalic cardiomyopathy should be possible.

Acromegaly↗
PubMed2002

Impact of disease activity on left ventricular performance in patients with acromegaly.

BACKGROUND: In patients with acromegaly, abnormalities of systolic and diastolic left ventricular (LV) performance, mostly associated with hypertension or LV hypertrophy, have been reported. We used 2-dimensional/Doppler echocardiographic methods and tissue Doppler imaging (TDI) to elucidate the impact of disease activity on LV function in patients with acromegaly. METHODS: In a prospective study design, 15 patients with active acromegaly (AA group; mean age-adjusted serum insuline-like growth factor-I [IGF-I] level, 420 +/- 170 ng/mL, mean growth hormone nadir during 75-g oral glucose load, 12.3 +/- 30.1 microg/L), 18 patients with cured (n = 14, mean IGF-I level 205 +/- 115 ng/mL, mean growth hormone nadir during glucose load 0.72 +/- 0.34 microg/L) or well-controlled (n = 4, normal age-adjusted ranges of IGF-I levels with medication with somatostatin analogues 354 +/- 88 ng/mL) acromegaly (CA group), and 24 control subjects (control group) underwent 2-dimensional/Doppler echocardiographic measurements, including assessment of the Tei index (isovolumic contraction time and isovolumic relaxation time divided by ejection time). Systolic and diastolic mitral annular velocities (peak systolic velocity, peak early diastolic velocity [E'], peak late diastolic velocity [A'], E'/A' ratio) were derived from pulsed TDI. RESULTS: No significant differences between study groups were observed with respect to muscle mass and systolic parameters, such as ejection fraction, fractional shortening, and peak systolic velocity. In patients with AA, E' and the E'/A' ratio were lower than in control and CA subjects (AA 6.8 +/- 1.7 cm/s, control 10.0 +/- 1.7 cm/s, CA 9.1+/- 3.0 cm/s, P <.01 AA vs control, P <.05 AA versus CA, AA 0.68 +/- 0.22, control 0.98 +/- 0.16, CA 0.89 +/- 0.37, P <.01 AA vs control and CA, respectively). In comparison with control subjects and patients with CA, patients with AA had a reduced mitral peak velocity of early/late filling ratio (AA 0.78 +/- 0.22 m/s, control 1.12 +/- 0.33 m/s, CA 1.11 +/- 0.36 m/s, P <.05 AA vs control and CA) and a prolonged deceleration time (AA 223 +/- 41 ms, control 188 +/- 26 ms, CA 185 +/- 25 ms, P <.05 AA vs control and CA). The Tei index was significantly elevated in patients with AA in comparison with control subjects and patients with CA (AA 0.54 +/- 0.13, control 0.40 +/- 0.09, CA 0.44 +/- 0.10, P <.05 AA vs control and CA). No significant differences were observed between control subjects and patients with CA with respect to mitral flow-derived variables, TDI parameters, and the Tei index. CONCLUSION: Disease activity has a significant impact on LV performance in patients with acromegaly. In subjects with active disease, diastolic dysfunction and beginning impairment of overall LV performance are present. In patients with cured/well-controlled disease, systolic and diastolic function appear normal.

Acromegaly↗
PubMed2004

Familial acromegaly: a familial report and review of the literature.

Familial acromegaly without features of multiple endocrine neoplasie type 1 (MEN 1) is an exceptional clinical entity. We report in this article three cases of acromegaly due to pituitary macroadenomas without any other endocrinopathy in a family. A 31-year-old woman (subject A) and her 34-year-old sister (subject B) with elevated basal rolactin (PRL) levels, elevated growth hormone (GH) levels during the oral glucose tolerance test (OGTT) and a pituitary adenoma in Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) were diagnosed as acromegaly. Subject A was treated only with radiotherapy and Lysuride. Subject B underwent transsphenoidal microsurgical extirpation 15 years ago. 11 years later her 24-year-old son (subject C) also presented with typical signs of acromegaly, elevated basal PRL level and elevated GH levels during OGTT. A pituitary macroadenoma was identified by MRI and he also underwent transsphenoidal adenomectomy. Pathology reports confirmed the diagnosis of GH-secreting pituitary adenoma in subject B and C. Immunocytochemistry revealed that tumours of subject B (> 20% of tumour cells) and C (> 50% of tumour cells) were positive for GH. Tumours of subject B (> 10% of tumour cells) and C (> 50% of tumour cells) also exhibited immunoreactivity for PRL. On investigation of histocompatibility antigens, it was observed that the subject A, B, and C shared the same haplotypes [HLA A24(9), HLA B13(6), HLA B35, HLA DQ7(3), HLA DR13(6)] and so it is very possible that investigation of HLA antigens in patients with pituitary tumour, contributes to better identification of its familial nature and frequency. Here we describe an acromegaly family and the distributions of HLA antigens.

Acromegaly↗
PubMed1995

An association between acromegaly and thyroid carcinoma.

Acromegaly has been associated with goiter as well as with benign and malignant tumors. Three cases of thyroid carcinoma in patients with acromegaly had been reported in the literature. We previously reported two additional cases of thyroid carcinoma and now present a third from 100 patients with acromegaly, exceeding the expected prevalence. All three thyroid carcinomas were multifocal, suggesting a generalized promotion toward malignancy. These patients had elevated levels of growth hormone and somatomedin-C [insulin-like growth factor (IGF-1)] at the time of thyroid carcinoma diagnosis. We discuss the role of IGF-1 in both benign and malignant thyroid growth, including the presence of IGF-1 receptors on thyroid cells, stimulation of thyroid cell replication by IGF-1, and paracrine secretion of IGF-1 and its binding proteins by thyroid cells. We propose possible mechanisms for the development of thyroid carcinoma in patients with acromegaly and discuss implications for the physician treating patients with acromegaly.

Acromegaly↗
PubMed1997

Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia.

Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published cases. Tissue ELISA with Adnab-9 antibody, a putative colorectal cancer risk marker, from a patient with ZES and from seven patients with acromegaly was compared to 13 controls at average risk for colorectal neoplasia. The patient with ZES without detectable colonic neoplasia and seven patients with acromegaly had increased binding of Adnab-9 in the colonic mucosa by ELISA. The difference was significant for the acromegaly patients compared to the controls (p < 0.05). The accumulated 34 instances of colorectal neoplasia in ZES patients suggests that this association may not be rare. Adnab-9 expression, detectable in both ZES and acromegaly, may reflect predisposition to colorectal neoplasia in both hyper-secretory states. Therefore, while a basis for association of colorectal neoplasia and hypergastrinemia exists, the clinical data are not compelling enough to warrant surveillance of patients with ZES. To resolve this problem, more definitive case control studies should be conducted.

Acromegaly↗