Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACROMEGALY”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources
PubMed1996

Biochemical cure of recurrent acromegaly by resection of cervical spinal canal metastases.

Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight cases of malignant, growth hormone-secreting tumours, all metastatic within the central nervous system have been previously described. Complete surgical resection was not possible and the patients died within 4 years of presentation with distant spread. Here we describe the first case of an apparent surgical cure of a somatotroph carcinoma metastatic to the cervical spine, documented by biochemical assessment and magnetic resonance and radioligand imaging. The possibility that intrathecal metastasis of somatotroph tumours may be responsible for some cases of treatment resistant acromegaly is discussed.

Acromegaly↗
PubMed1998

The outcome of surgery for acromegaly: the need for a specialist pituitary surgeon for all types of growth hormone (GH) secreting adenoma.

OBJECTIVE: Acromegaly is associated with reduced life expectancy, while therapeutic 'cure' (defined by achievement of GH levels < 5 mU/l) is associated with normalization of life expectancy. Surgery remains the treatment of choice but in those in whom operative 'cure' is not achieved, radiotherapy and/or medical treatment are valuable treatment modalities. The chance of subsequent 'cure' with radiotherapy or somatostatin analogue therapy is increased if the post-operative GH level is reduced below 30 mU/l. Using strict criteria for cure and a single dedicated pituitary surgeon, two large European studies reported 'cure' rates of 42% and 56%. In the Manchester region, surgery for these patients has been performed by a number of neurosurgeons, with no specific designated pituitary surgeon dominating the picture. We wished to examine the impact of this surgical strategy on cure rates and the incidence of a post-operative GH level below 30 mU/l. DESIGN: We reviewed the GH results between 1974 and 1997 for every acromegalic who had been referred to the endocrine departments of the two Manchester hospitals responsible for the majority of pituitary disease referrals in Manchester and who had been subsequently referred for pituitary surgery. PATIENTS AND MEASUREMENTS: Seventy-three (33 male) patients had had GH status assessed before and after surgery by an OGTT or GH profile. The patients were aged between 19 and 70 (mean 43) years at surgery. Seventy-one underwent transsphenoidal and 2 transfrontal surgery. Nine surgeons performed operations. RESULTS: Eighteen (24.7%) had microadenomas and 51 (69.9%) macroadenomas. In 4 patients (5.5%) insufficient data were available to size the adenoma. 17.8% of patients were cured by surgery, 38.8% with microadenomas and 11.8% with macroadenomas. In addition, of 52 patients whose GH levels were > 30 mU/l before surgery, only 27 (51.9%) had GH levels below 30 mU/l post-operatively (81.8% of microadenomas, 43.2% of macroadenomas). CONCLUSION: In comparison with other series, the cure rate in this study is significantly lower. The success in reducing GH levels below 30 mU/l post-operatively is difficult to compare with previously published studies, as few groups have analysed their data in this manner. Nonetheless, of our acromegalic patients with a pretreatment GH level in excess of 30 mU/l, nearly 50% have similar GH status postoperatively, thereby rendering them less amenable to cure by alternative therapeutic modalities. This highlights the importance of a specialist pituitary surgeon, not only for GH secreting microadenomas but also for GH secreting macroadenomas. If these patients are not 'cured', the cost of continuing therapy becomes a significant burden on health-care costs. In addition, if the postoperative GH levels remain above 30 mU/l the chances of achieving adequate control of GH levels are greatly reduced, thereby increasing mortality rates as well as morbidity in these patients.

Acromegaly↗
PubMed1999

Recent primary transnasal surgical outcomes associated with intraoperative growth hormone measurement in acromegaly.

OBJECTIVE: Since 1983, we have measured GH intraoperatively to improve the surgical outcome for acromegalic patients with GH secreting pituitary adenomas. Here, we present the recent results of primary surgery in patients with acromegaly to examine the effect of improved surgical techniques and experience. PATIENTS AND MEASUREMENT: Intraoperative GH concentrations were measured in 78 consecutive acromegalic patients who had not previously undergone surgery between May 1992 and April 1994 (45 females and 33 males, age range, 21-70 years, mean, 47.1 +/- 1.3). All patients were followed for at least 3 years. Direct transnasal tumour extirpation was performed. Intraoperative GH measurements were assayed 0, 20 and 60 min after tumour removal. A plasma GH level < or = 4.5 micrograms/l at 60 min after initial tumour removal was used as a criterion of radical tumour removal. In cases with intraoperative plasma GH concentrations > or = 40 micrograms/l prior to tumour resection, the half-life of the GH concentration at 20 min was used to assess completeness of tumour removal. In these cases, it was defined as having achieved a 50% reduction in plasma GH at 20 min compared to 0 min after tumour resection. To obtain intraoperative GH measurements, mild anaesthesia was continued for an average of 82 +/- 23 min. RESULTS: Radical tumour removal was determined intraoperatively in 51 patients and subsequently confirmed in 50 patients (98.0%). In 18 of 27 patients with incomplete tumour removal, immediate reoperation was performed under continous anaesthesia. In 11 of these 18 patients, endocrinological remission was achieved (14.1%; 11/78). None of the remaining nine patients who did not undergo secondary surgery achieved remission. Secondary surgery improved the remission rate from 85.7% (12/14) to 92.9% (13/14) in microadenomas and from 70.1% (38/54) to 88.9% (48/54) in non-invasive macroadenomas. Remission was not observed in patients with imageproven extrasellar extension. CONCLUSIONS: Secondary surgery based on intraoperative GH measurement improves the outcome of tumour resection in patients with non-invasive GH secreting macroadenomas.

Acromegaly↗
PubMed2000

Postoperative radiotherapy in acromegaly is effective in reducing GH concentration to safe levels.

OBJECTIVE: Several studies have established that in treated acromegaly mortality is only normalized in patients achieving a serum GH concentration below 5 mU/l. Few studies however, have addressed results of radiotherapy using this strict criterion. The aim of our study was to assess the efficacy of postoperative radiotherapy in reducing serum GH concentration below 5 mU/l. PATIENTS AND METHODS: Forty acromegalic patients who underwent radiotherapy for postoperative persistent disease after transsphenoidal surgery were studied. Mean time of follow-up after radiotherapy was 123+/-11.1 months. A serum GH concentration of <5 mU/l was used to define remission. RESULTS: Following surgery mean GH concentration decreased from 120.8+/-21 mU/l to 24.4+/-5.2 mU/l and mean GH concentration prior to radiotherapy, administered after a mean of 8.2+/-2.7 (0.5-96) months postoperatively was 26.0+/-5.1 mU/l. Using individual regression plots, GH was reduced to 50% by radiotherapy after a mean of 27+/-5 months (range 3-105 months). The observed mean GH concentration as measured at follow-up visits was reduced by 55% (-36-95%) after the first year, by 65% (-29-97.3%) after 2 years and by 78% (-29-99%) after 5 years. We could not demonstrate a significant correlation between a normalized GH concentration on the one hand and tumour size, preradiotherapy GH concentration or duration of follow-up on the other hand. During follow-up, GH-suppressive medical therapy was used in 11 patients, five of whom were still using medication at the end of follow-up. Eight patients had a follow-up of less than 5 years and three of them had a serum GH concentration of <5 mU/l at their latest follow-up visit (38%). At 5 years of follow-up after radiotherapy, 24 out of 32 patients had a GH level of <5 mU/l without medication (75%). At 10 years following irradiation, 16 of 21 patients (76%) had a GH level of <5 mU/l without medical treatment. At 15 years follow-up, a serum GH concentration of <5 mU/l was observed in 13 out of 15 patients (87%) without GH suppressive medication. At the latest follow-up visit, serum GH concentration below 5 mU/l was present in 75% of patients (30 out of 40) without medical therapy after a mean of 10.4+/-0.9 years, but five patients required octreotide up to the end of follow-up. Twenty-seven out of 37 patients with available IGF-I data had normal IGF-I at the end of follow-up (73%). Fifty percent of patients needed substitution therapy for (partial) hypopituitarism after 10 years and 75% after 15 years of radiotherapy. CONCLUSION: In our group of patients who were incompletely cured by surgery, but had a significant postoperative decrease of serum GH concentrations, radiotherapy was able to achieve 'safe' serum GH concentrations in the majority in the long term.

Acromegaly↗
PubMed2001

Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS) and IGFBP-3 levels in acromegaly.

OBJECTIVE: Radiotherapy (RT) has been used for many years in order to complete the cure of unsuccessfully operated acromegalic patients. Several studies have shown its efficacy in normalizing GH levels, while reports about IGF-I normalization are conflicting. Moreover, data regarding other markers of disease activity, such as IGFBP-3 and acid-labile subunit (ALS), i.e. the other two components of the circulating 150 kDa complex, are lacking. DESIGN: Retrospective study. PATIENTS AND MEASUREMENTS: Sixty-seven acromegalic patients (20 males and 47 females, aged 40 +/- 6 years) who underwent postoperative RT (in fractionated doses for a total of 40-75 Gy) were followed-up for 11 +/- 6 years (range: 1-26 years, median: 10 years). Serum GH and IGF-I levels off medical therapy were measured in all patients; ALS and IGFBP-3 were measured in 11 patients with normalization of IGF-I concentrations. Computed tomography or nuclear magnetic resonance imaging periodically assessed possible development of pituitary deficiency along with imaging of the hypothalamic-pituitary region. RESULTS: Forty-one out of 67 patients (58%) achieved GH levels < 2.5 microg/l by 1-15 years after RT (mean 8 +/- 6) and 37/67 patients (55%) had normal or low IGF-I levels 1-26 years after RT (mean: 12 +/- 6), a normalization of both parameters being seen in 37 patients. GH < 2.5 microg/l and normal IGF-I levels were achieved in 17/26 (65%) patients followed-up for at least 15 years. ALS and IGFBP-3 concentrations paralleled IGF-I levels in all patients studied. With respect to secondary pituitary insufficiency, acquired ACTH deficiency was found in 25 patients, TSH deficiency in 20, gonadotropin deficiency in 23 and GH deficiency in seven. In total, two cases of meningioma and one pineal tumour, possibly related to RT, were seen 9-22 years after RT. CONCLUSIONS: RT is an effective, although slow-acting, therapeutic tool for acromegaly, with 'safe' GH levels and normal IGF-I concentrations being achieved in 65% of patients after 15 years. IGF-I levels normalize more slowly than GH levels. Radiotherapy is able to normalize the concentration of all three components of the circulating 150 kDa complex. Checks for loss of pituitary function and appearance of second brain tumours must be carried out life-long.

Acromegaly↗
PubMed2002

Submandibular salivary gland volume is increased in patients with acromegaly.

OBJECTIVE: Acromegaly is characterized by an enlargement of various organs. The aim of the present study was to evaluate whether acromegalic patients have an increased volume of submandibular salivary glands. DESIGN AND SUBJECTS: Prospective study on 40 consecutive acromegalic patients (18 male, 22 female; mean age +/- SD, 50 +/- 13 years, range 22-74 years) submitted to submandibular salivary gland ultrasound. Among acromegalic patients, 15 had active and untreated disease (Acro-U), 13 were under long-acting somatostatin analogue therapy (Acro-SA), 12 were in remission after surgery (Acro-R). Two hundred subjects (90 male, 110 female, mean age +/- SD, 50 +/- 11 years, range 23-74 years) matched for age, sex and body mass index served as controls. MEASUREMENTS: Submandibular salivary gland volume was measured in all acromegalic patients and normal subjects by ultrasound and calculated by the ellipsoid model. Serum GH and IGF-I concentrations were measured in all subjects. RESULTS: Acro-U patients had higher serum IGF-I levels (691 +/- 235 microg/l) than Acro-R (174 +/- 74 microg/l), Acro-SA (436 +/- 239 microg/l) or controls (151 +/- 66 microg/l) (P < 0.0001, P = 0.008, P < 0.0001, respectively). The mean submandibular salivary gland volume was higher in acromegalic patients than in controls: Acro-U 18.1 +/- 3.3 ml, Acro-SA 16.2 +/- 3.3 ml, Acro-R 15.7 +/- 3.0 ml and controls 8.2 +/- 2.4 ml (P < 0.0001). Differences among subgroups of Acro patients were not significant. Enlargement of the submandibular salivary glands was present in 35/40 (87.5%) acromegalic patients. A positive correlation between serum IGF-I (P < 0.0001), GH (P < 0.0001) and submandibular salivary gland volume was found. CONCLUSIONS: Acromegalic patients have an increased volume of submandibular salivary glands, independently of the activity of disease.

Acromegaly↗
PubMed2003

Primary medical therapy for acromegaly.

There is now considerable evidence that the clinical outcome in patients with acromegaly can be improved very substantially by means of better surgical expertise and effective medical therapies used in a flexible and innovative manner. Medical therapy alone in patients who have not undergone surgery or radiotherapy (primary medical therapy) offers the prospect of near normalisation of GH/IGF-I levels together with substantial tumour shrinkage in a significant number of patients.

Acromegaly↗
PubMed2003

Bone mineral density in acromegaly: the effect of gender, disease activity and gonadal status.

OBJECTIVE: Data on bone mineral density (BMD) in acromegaly are conflicting as most previous studies collectively evaluated eugonadal and hypogonadal patients of both sexes, with or without active disease. We have evaluated BMD in 152 acromegalic patients of both sexes with varying disease activity and gonadal status. DESIGN: Cross-sectional, retrospective. PATIENTS: We studied 152 acromegalic patients (99 women aged 26-72 years, and 53 men aged 21-75 years), 107 with active and 45 with controlled disease. Eighty-five patients had normal gonadal status and 67 were hypogonadal. MEASUREMENTS: In all patients we measured serum GH levels by immunoenzimometric assay, and serum IGF-I levels by radioimmunoassay. BMD was assessed at spine L2-L4 (LS) and at femoral neck (FN) by dual energy X-ray absorptiometry; results are expressed as Z-values. RESULTS: We evaluated the effect of GH excess on bone at different sites in relation to gonadal status, disease activity and gender. At LS, in respect to the reference population, BMD (mean +/- SE) values were higher in eugonadal patients (active: 0.71 +/- 0.29, P < 0.02; controlled: 0.65 +/- 0.28, P < 0.05) and lower in hypogonadal ones (active: -0.64 +/- 0.35, 0.1 < P < 0.05; controlled: -1.05 +/- 0.36, P < 0.01), regardless of disease activity. On the contrary, at FN, BMD was higher than in the reference population, both in eugonadal (1.01 +/- 0.22, P < 0.001) and hypogonadal (0.63 +/- 0.17, P < 0.001) patients only in subjects with active disease, but not in those in which the disease was controlled (eugonadal: 0.31 +/- 0.23, P = ns; hypogonadal 0.04 +/- 0.28, P = ns). We did not observe any difference in BMD values according to gender both at LS (males vs. females -0.02 +/- 0.30 vs. 0.01 +/- 0.24, P = ns) or at FN (0.77 +/- 0.19 vs. 0.63 +/- 0.15, P = ns). CONCLUSIONS: The anabolic effect of GH excess on bone in acromegalic patients is: (i) gender-independent; (ii) evident at the spine only in eugonadal regardless of disease activity; (iii) evident at femoral neck only in the presence of active disease regardless of gonadal status.

Absorptiometry, Photon↗
PubMed2003

Perturbations in adiponectin, leptin and resistin levels in acromegaly: lack of correlation with insulin resistance.

BACKGROUND: Insulin resistance, impaired glucose tolerance and type 2 diabetes are common in acromegalic subjects. The mechanism underlying this insulin resistance is unclear. DESIGN: We investigated the levels of the adipocytokines, resistin, adiponectin and leptin in a group of 18 acromegalic subjects and 18 control subjects matched for age, gender and body mass index. RESULTS: Here we demonstrate for the first time significant elevation in adiponectin levels in acromegalic subjects compared to control subjects 12.5 +/- 1.2 vs. 8.97 +/- 1.1 mg/l, P = 0.029. The resistin levels were similar in acromegalic subjects and controls; 20.65 +/- 2.99 vs. 19.03 +/- 4.72 micro g/l. No evidence of a correlation between adiponectin and insulin resistance as calculated from HOMA-R was found. No correlation was observed either between adiponectin or resistin levels and GH levels, total IGF-I or free IGF-I levels. Leptin levels were significantly reduced in acromegalic subjects, 8.22 +/- 2.26 vs. 18.3 +/- 4.1 micro g/l, P = 0.004. In control subjects, significant correlations between leptin levels and HOMA-R and between resistin levels and HOMA-R were observed. These relationships were not apparent in acromegalic subjects. CONCLUSION: From these data we conclude that changes in resistin and adiponectin levels are unlikely to account for the insulin resistance of acromegaly.

Acromegaly↗
PubMed1999

Growth hormone receptor antagonists therapy for acromegaly.

Knowledge of the interaction between growth hormone (GH) and the growth hormone receptor (GHR) has led to the rational design of a GHR antagonist. An analogue of GH able to block the action of GH at the cellular level offers greater specificity of effect compared with current medical therapies and is not dependent on tumour characteristics. This chapter reviews the interaction between GH and the GHR, and discusses the outstanding issues regarding GHR antagonist therapy in acromegaly.

Acromegaly↗
PubMed2002

Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: a retrospective evaluation of 50 patients.

The objective of this study was to investigate the relationship between growth hormone (GH) dynamic tests (thyrotropin-releasing hormone [TRH] test and oral glucose tolerance test [OGTT]), insulin-like growth factor-I (IGF-I) plasma values, tumor size, and clinical outcome in patients with GH-secreting pituitary adenomas. Furthermore, we investigated the potential prognostic utility of the above biochemical parameters in the follow-up of patients with acromegaly. We studied 50 acromegalic patients (18 males and 32 females; mean age, 40 years; range, 16 to 69) who underwent trans-sphenoidal removal of a GH-secreting pituitary adenoma from 1990 to 1994. Preoperatively, we evaluated (1) GH plasmatic levels after an oral glucose load (OGTT) (blood samples were drawn at -15, 0, 30, 60, 90, 120, 150, and 180 minutes after oral administration of 0.75 g/kg body weight [BW] of glucose), (2) GH plasma levels after a TRH test (200 microg as an intravenous [IV] bolus), and (3) basal IGF-I plasma levels after an overnight fast. From 3 to 12 months after surgery we evaluated (1) GH plasma values after an OGTT, and (2) basal plasma IGF-I, free triiodothyronine (FT(3)), free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and urinary free cortisol. The same tests were performed every year for 5 years. All of the patients were classified into 4 subgroups according to the system of Hardy and Vezina. Preoperatively, "controlled" patients (n = 29) had a GH paradoxical response to TRH (n = 28) and an unresponsiveness to OGTT (n = 29); 23 of them belonged to the I and II classes. Only 5 poorly controlled patients (n = 21) showed a preoperative paradoxical response to TRH and 9 had a preoperative GH partial inhibition after OGTT; 19 of them belonged to the III and IV classes. Our data suggest that in the preoperative period in acromegalic patients the simultaneous presence of a GH paradoxical response to TRH and lack of GH inhibition after OGTT is inversely related to the tumor size and therefore more likely to be restored to normal by surgical treatment.

Acromegaly↗
PubMed1977

Comparison of TRF, propranolol-glucagon, insulin and glucose stimulation tests in acromegaly.

In 7 acromegalic patients growth hormone responses were studied following administration of synthetic TRF, propranolol-glucagon, insulin, and glucose p.o. Except for the glucose tolerance test, a good reproducibility of the STH response was observed. In 5 out of the 7 patients, there was a distinct rise in the plasma STH level after TRF. All patients with a positive insulin tolerance test responded to TRF, as did the two late responders to glucagon; the early responder to the latter test did not respond to TRF. It has been suggested (Liuzzi et al. 1974a) that TRF might be used as a screening test for detecting hypothalamic dependency of the acromegaly. This study suggests that further study is required before accepting this hypothesis and that a response to a combination of tests (TRF, glucagon, insulin) might be a better screening method.

Acromegaly↗
PubMed2004

Acromegaly and heart failure: revisions of the growth hormone/insulin-like growth factor axis and its relation to the cardiovascular system.

Cardiomyopathy is a major cause of death in overt acromegaly. Recent progress in research has increasingly revealed the molecular mechanisms concerning growth hormone and insulin-like growth factor in the development of heart failure. In this article, we propose mechanisms according to which heart failure occurs, and we aim to extrapolate this knowledge to more general processes involved in heart failure.

Acromegaly↗
PubMed1994

Neoplastic colonic polyps in acromegaly.

A high prevalence of neoplastic colorectal polyps has been described in acromegalic patients. The aim of the present report was to confirm the high prevalence of neoplastic colorectal polyps in acromegaly and the existence of special risk factors for this type of polyps among acromegalic patients. A fiberoptic colonoscopy was performed in 27 active acromegalic patients, followed by both polypectomy and biopsy when indicated. Several prognostic variables were analysed a potential risk factors, in all cases. The prevalence of neoplastic colorectal polyps found in our series (22.2%) was similar to that in previous studies, and did not show any apparent increment compared to that in the populations in which it is known. None of the prognostic variables studied were related to the presence of neoplastic colorectal polyps.

Acromegaly↗
PubMed1981

Conn's syndrome in a patient with acromegaly.

The renin-angiotensin-aldosterone system (RAAS) in a female patient suffering from acromegaly and severe hypertension was studied and a suppressed plasma renin activity could be found. A catheterisation of both adrenal veins, a bilateral adrenal gammagraphy and an abdominal CT scan confirmed the diagnosis of an aldosterone-producing right adrenal adenoma (Conn's Syndrome). We greatly emphasized the need of investigating the RAAS in acromegalic patients suffering from hypertension.

Acromegaly↗
PubMed1995

Do "so-called" normal growth hormone concentrations (2-5 micrograms/l) indicate cure in acromegaly?

The study was undertaken to determine whether acromegalic patients with mean growth hormone (GH) concentrations of 2-5 micrograms/l have biochemically active disease following pituitary surgery or radiotherapy. 22 patients with acromegaly, 22 post surgery, 19 post radiotherapy had GH concentrations estimated during: (i) an oral glucose tolerance test (OGTT), (ii) a standard TRH test and (iii) 20 minute sampling for 8 hours. IGF-1 concentrations were measured. 6 normal subjects were also studied. Patients were divided into 3 groups on the basis of their mean GH concentration during the 8 hour sampling, > 5 micrograms/l, 2-5 micrograms/l, < 2 micrograms/l. Patients with mean GH concentrations of 2-5 micrograms/l (n = 6) had biochemically active disease: all had inadequate suppression of GH after OGTT, 5 had elevated IGF-1 concentrations, 4 had a paradoxical response to TRH. Patients with mean GH concentrations > 5 micrograms/l (n = 6) all had inadequate suppression after OGTT, 5 of 6 had increased IGF-1 concentrations, and 5 had abnormal responses to TRH. Of patients with mean GH concentrations < 2 micrograms/l (n = 10), 2 had elevated IGF-1 levels, 5 had abnormal responses to TRH and 4 inadequate GH suppression after OGTT. GH pulse number was similar in the three groups and GH pulse amplitude was significantly higher in those with GH > 5 micrograms/l compared to the other groups. In conclusion patients with GH concentrations of 2-5 micrograms/l have biochemically active disease and should be considered for further therapy after hypophysectomy.

Acromegaly↗
PubMed1992

[Cardiac function and the skin microcirculation in acromegaly].

The microcirculation was measured by nail-fold capillary video microscopy in 21 patients (12 men, 9 women; mean age 54.7 [29-74] years) with acromegaly. Levels of growth hormone (12.0-71.7 microU/ml) and of somatomedin C (2.4-10.5 IU/ml) were elevated in 10 patients, despite preceding treatment. Eleven patients had an increase in myocardial thickness and nine had impairment of left ventricular function, although only slight in most. Left ventricular hypertrophy was demonstrable even in the absence of hypertension. No patient had evidence of coronary heart disease. Nail-fold capillary video microscopy (capillary density, torque index, reactive hyperaemia, epidermal blood flow) failed to distinguish between successfully treated patients and those with persistently elevated growth hormone concentrations or disease duration of over 5 years. There was no evidence of inadequate capillary blood flow as a cause of abnormal function in hypertrophied organs.

Acromegaly↗