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PubMed1992

Pituitary imaging using a labelled somatostatin analogue in acromegaly.

OBJECTIVE: A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We have looked at the use of an 123I-labelled Tyr3-octreotide analogue of somatostatin in the visualization and functional characterization of growth hormone-secreting pituitary adenomas. PATIENTS: Fifteen patients with biochemically-proven acromegaly were scanned using this agent. In eight of these we also assessed acute GH responses to octreotide in order to correlate these responses with tumour uptake characteristics. MEASURES: Planar and single-photon-emission computerized tomographic (SPECT) images of the head were obtained using a gamma-camera at 10 minutes, and 4 and 24 hours, after injection of the radiopharmaceutical. Blood for serum GH was sampled for 12 hours after administration of a single dose of 100 micrograms octreotide. RESULTS: Twelve of the acromegalic subjects showed significant uptake of the radiopharmaceutical in the pituitary fossa. Of the eight patients in whom we assessed acute GH responses, five demonstrated a significant fall in GH in response to octreotide. These subjects also showed positive uptake in the pituitary on scanning. The three patients who had no fall in GH had no uptake on scanning. CONCLUSIONS: Uptake of 123I-labelled Tyr3-octreotide in the pituitary fossa appears to correlate closely with the presence of a therapeutic response to octreotide.

Acromegaly↗
PubMed1995

Assessment of GH status in acromegaly using serum growth hormone, serum insulin-like growth factor-1 and urinary growth hormone excretion.

OBJECTIVE: It is still not clear what is the most suitable method for monitoring progress of acromegaly. The aim of this study was to assess the relative merits of serum GH, serum IGF-I and urinary GH (uGH) excretion in the follow-up of acromegalic subjects. SUBJECTS AND METHODS: Thirty-six acromegalic patients each had a GH day series performed consisting of five serum GH measurements, together with an estimate of serum IGF-I and uGH. The first sample taken for serum GH was fasting (basal) whilst the third (1430h) was arbitrarily chosen as a random value. uGH was measured from two overnight collections and the mean value used for subsequent data analysis. MEASUREMENTS: Serum GH and IGF-I were measured by radioimmunoassay whilst uGH was estimated by an immunoradiometric assay using commercially available reagents. RESULTS: There is a highly significant linear correlation between serum GH and IGF-I following log transformation of these two variables (r = 0.85; P < 0.0001). Analysis of the raw data shows that the relation is in fact curvilinear rendering IGF-I less useful as a surrogate for integrated GH secretion at high levels of serum GH. There is a strong linear correlation between both a singleton basal serum GH and uGH (r = 0.78; P < 0.001) and the mean of five measurements (day series) and uGH (r = 0.81; P < 0.0001). Both uGH and IGF-I are excellent predictors of those patients with persistent elevation of serum GH, identifying 95 and 96% respectively with serum GH > 5mU/l. We have identified a number of patients, however, with persistent elevation of IGF-I in the presence of serum GH < 5mU/l and normal uGH. Until the significance of these findings with respect to long-term outcome is known, serum GH should continue to be used in the follow-up of these patients. An alternative, which reflects integrated overnight GH secretion, is uGH which is convenient and easy to collect as an outpatient and correlates strongly with serum GH. CONCLUSION: Acromegalic patients can be conveniently followed on an outpatient basis using a combination of uGH and serum IGF-I. Measurements of serum GH can be reserved for those with discrepant results.

Acromegaly↗
PubMed2004

Efficacy of Sandostatin LAR (long-acting somatostatin analogue) is similar in patients with untreated acromegaly and in those previously treated with surgery and/or radiotherapy.

BACKGROUND AND OBJECTIVES: Somatostatin analogues have been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly for over 15 years, but debate surrounds their use as primary therapy. Newman suggested that octreotide was equally effective as primary or adjuvant therapy, but the effects of previous surgery/radiotherapy may have led to a preselection bias. In an attempt to eliminate this bias, the efficacy of the depot somatostatin analogue Sandostatin LAR as primary and adjuvant therapy has been assessed using GH and IGF-I levels at diagnosis as baseline values. DESIGN: We retrospectively analysed the GH and IGF-I data from a large multicentre study in which patients' biochemical response to treatment with the depot somatostatin analogue Sandostatin LAR as primary and adjuvant therapy was assessed. We used GH and IGF-I levels at diagnosis as baseline values to eliminate any preselection bias. PATIENTS AND RESULTS: In 91 patients (42 male) studied, mean serum GH fell from 36.2 +/- 3.3 micro g/l (SEM) at diagnosis to 2.2 +/- 0.2 micro g/l after 48 weeks of treatment (P < 0.0001). In the primary (n = 34) and adjuvant (n = 57) therapy groups, mean GH fell from 30.7 +/- 5.7 to 2.6 +/- 0.4 micro g/l (P < 0.0001) and from 39.5 +/- 4.1 to 2.0 +/- 0.2 micro g/l (P < 0.0001), respectively. Sixty-two percent of patients in the primary therapy group and 70% in the adjuvant therapy group achieved GH < 2 micro g/l. Serum IGF-I levels were available in 67 patients (34 male). In the primary therapy group (n = 25) mean IGF-I fell from 764 +/- 68 to 414 +/- 31 micro g/l (P < 0.0001) at 48 weeks. In the adjuvant therapy group (n = 42) mean IGF-I was 666 +/- 50 micro g/l, falling to 384 +/- 30 micro g/l (P < 0.0001) at 48 weeks. 72% of patients achieved normal age-related IGF-I-values. There were no statistically significant differences in GH or IGF-I levels between the primary and adjuvant therapy groups at diagnosis, pre Sandostatin LAR or after 48 weeks of treatment. CONCLUSION: This retrospective study demonstrates that in a group of patients with similar diagnostic GH and IGF-I levels, Sandostatin LAR was equally effective as primary therapy in acromegalic patients as in patients previously treated with surgery and/or radiotherapy.

Acromegaly↗
PubMed2005

Treatment of acromegaly with octreotide-LAR: extensive experience in a Brazilian institution.

OBJECTIVE: Somatostatin analogues have become the mainstay of the medical treatment of acromegaly. The aim of our study was to evaluate the efficacy and tolerability of octreotide-LAR (OCT-LAR) treatment in acromegalic patients. DESIGN: Prospective open trial. PATIENTS AND METHODS: Eighty acromegalic patients (46 women; 18-80 years) were treated with OCT-LAR. Mean +/- SD duration of follow-up was 16.6 +/- 6.6 months (6-24 months). Twenty-eight patients received OCT-LAR as primary treatment. The target was to achieve normal IGF-I levels. Clinical activity was evaluated by symptom score and fasting samples for GH and IGF-I serum concentrations, obtained under basal conditions as well as during treatment. Pituitary tumour volume was assessed by magnetic resonance imaging of the sella. A tumour volume reduction of at least 25% was considered significant. RESULTS: Clinical improvement was attained in most patients. Fifty-nine (74%) of them attained mean GH < 2.5 ng/ml and 33 (41%) achieved normal IGF-I by the 24th month of treatment. GH and IGF-I control increased throughout treatment. Regarding the 46 patients treated for at least 12 months there was a significant decrease of GH and IGF-I levels by the third month compared to basal levels, persisting with no subsequently variation. In the patient group that achieved normal serum IGF-1 during treatment (controlled group: n = 43) 20 patients maintained normal levels up to the latest follow-up, whereas 23 of them once again showed altered serum IGF-1-values of some measurements during follow-up, despite dose maintenance or elevation. Baseline percentage of the upper limit of IGF-I normal range, GH levels by the third month and length of treatment were predictive factors of IGF-I normalization. Tumour shrinkage occurred in 76% of primary patients. Among 21 diabetic patients, four worsened and five improved glycaemic control, based on glycated haemoglobin. One previously intolerant patient progressed to overt diabetes. Nine patients developed gall bladder sludge, other nine patients acquired microlithiasis and one patient developed gallstone pancreatitis. CONCLUSION: OCT-LAR is an effective agent in alleviating symptoms, suppressing GH, normalizing IGF-I and inducing tumour shrinkage in many acromegalic patients. Overall, OCT-LAR is well tolerated and should be recommended for nonsurgically cured acromegalics, and also be considered as primary therapy for selected cases, mainly for those with a low probability of surgical cure.

Acromegaly↗
PubMed1977

Metabolic and clinical studies on patients with acromegaly treated with bromocriptine over 22 months.

In twenty-two patients with active acromegaly who were untreated or unsuccessfully operated or irradiated (mean growth hormone (GH) values greater than 4 ng/ml) the following investigations were performed: routine laboratory tests, tomography of pituitary fossa, oral glucose tolerance tests, TRH and other pituitary function tests and GH profiles over 5-10 h before and during bromocriptine treatment with daily doses between 7.5 and 50 mg. In seventeen patients GH was suppressed to less than 50% by bromocriptine, in thirteen of them it was normalized on at least one occasion. A TRH induced GH release was observed in all but two responders to bromocriptine before therapy. This effect of TRH was not blunted during treatment with bromocriptine and also in the two patients with negative tests before therapy a significant GH increase was observed. In no non-responder to bromocriptine was a significant increase of GH after TRH observed. One patient showed a secondary resistance to bromocriptine during a period of treatment with griseofulvin. In the remaining sixteen patients the GH suppression has been consistent for between 3 and 22 months. A single dose of pimozide abolished the bromocriptine effect on GH totally in one patient; in others a slight or no significant effect was observed. Tissue swelling and sweating decreased in all bromocriptine responders and glucose tolerance improved in five patients. In four diabetic patients a partial or full remission of diabetes occurred. Apart from postural hypotension after the first administration in two patients no other severe side effects have been observed. Sella size and the other pituitary functions did not change during the time of the study. It seems that a high percentage of acromegalics may be successfully treated with bromocriptine.

Acromegaly↗
PubMed1986

Enzymatic determination of urinary chondroitin sulphate: applications in renal stone disease and acromegaly.

A method was developed for the determination of urinary chondroitin sulphate (CS), including dermatan sulphate and chondroitin 4 and 6-sulphates, using an enzymatic degradation with chondroitinase-ABC followed by precipitation with Alcian blue, whereby CS was determined as the difference between undigested and chondroitinase digested material. The method was linear in the range 0-100 mg l-1 with a detection limit of 1 mg l-1 and allowed determinations on small urine volumes without pretreatment of the urine. It could be demonstrated that males excreted more CS than females, and growing children had the highest urinary content of CS. Renal calcium stone formers did not differ from healthy controls in urinary CS. Patients with acromegaly had a higher excretion of CS compared with controls. There was also, in these patients, a positive correlation between the serum growth hormone levels and the urinary CS, indicating that CS-excretion may be an estimate of the activity of the pituitary disorder.

Acromegaly↗
PubMed1987

Relationship between growth hormone and somatomedin-C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with sandostatin (SMS 201-995).

Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin-C (SM-C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post-prandial and mean 24-h) plasma GH and SM-C concentrations in twenty-two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 micrograms 1(-1) were considered (n = 18 patients, P less than 0.01). The distribution of molecular forms of GH ('little', 'big' and 'big-big') did not differ between the four patients with GH levels above 100 micrograms 1(-1) and in four patients with levels between 40 micrograms 1(-1) and 80 micrograms 1(-1). Therefore, it is suggested that GH levels of 80-100 micrograms 1(-1) maximally activate Somatomedin-C production in man and that further increases in GH in general will not result in a further increase in SM-C generation. There was a significant correlation between GH and SM-C levels in forty-nine acromegalic patients after surgery and/or radiotherapy (P less than 0.001). In twenty-three of thirty-one patients with elevated SM-C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM-C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1993

Adipose tissue and muscle volume determination by computed tomography in acromegaly, before and 1 year after adenomectomy.

The adipose tissue volume, skeletal muscle and skin volume and visceral organ volume were determined using the multiscan CT (computed tomography) technique in 15 patients with acromegaly. The examinations were performed before treatment and 1 year after transsphenoidal adenectomy. The mean body weight did not change significantly after treatment; 91.3 kg and 92.3 kg pre and postoperatively in men and 66.7 kg and 65.9 kg in women respectively. The total adipose tissue volume increased by 7.11 (59.2%, P < 0.01) in the male group and 3.9 1 (20.3%, P < 0.05) in the female group. Muscle and skin mass and visceral organ mass decreased significantly after treatment. The muscle and skin mass decreased by 3.6 1 (-7.4%, P < 0.01) in males and by 3.2 1 in females (-11.5%, P < 0.02). The corresponding decrease in visceral organ mass was 1.5 1 (-17.0%, P < 0.01) in males and 1.0 1 (15.4%, P < 0.05) in females respectively. On average, the fractions of adipose tissue in the subcutaneous trunk and the intra-abdominal depots increased after treatment, while the fractions of adipose tissue in the limbs and the head and neck region decreased. The change in adipose tissue distribution pattern reached significance (P < 0.005) in men only.

Acromegaly↗
PubMed1994

Improvement of sleep apnoea due to acromegaly during short-term treatment with octreotide.

Two acromegalic patients suffering from severe obstructive sleep apnoea syndrome were treated with the long-acting somatostatin analogue octreotide. Daytime sleepiness and fatigue improved within a few days. Repeat sleep studies performed after octreotide treatment revealed more confluent sleep with a shorter duration of sleep apnoea. Nocturnal hypoxaemia improved in one patient. Octreotide might be an effective noninvasive treatment for sleep apnoea of acromegaly.

Acromegaly↗
PubMed1975

Regression of acromegaly following pituitary apoplexy.

A case of acromegaly complicated by pituitary apoplexy is described. The pituitary apoplexy occurred while the patient was under investigation in a metabolic ward permitting full assessment of pituitary function both before and immediately after the event. This demonstrated a remarkably selective reduction in the plasma growth hormone concentration with preservation of other pituitary function excluding mild diabetes insipidus. The plasma growth hormone fell from values greater than 120 ng/ml to less than 4 ng/ml. The brisk inappropriate release of growth hormone observed on stimulation with thyrotrophic hormone releasing hormone, associated with a severe headache and the onset of pituitary apoplexy two days later raised the possibility of provocative tests of pituitary function precipitating pituitary apoplexy.

Acromegaly↗
PubMed1979

Treatment of acromegaly with bromocryptine.

Twelve acromegalic patients with clinical and biochemical evidence of active disease were studied whilst on bromocryptine (Sandoz) at a maximum dosage of 10--60 mg. The patients were followed for a period of 9--23 months. Clinically, ten patients showed a reduction or disappearance of sweating and seven patients had a reduction in soft tissue mass. Of the five patients who had diabetes prior to treatment, three reverted to normal glucose tolerance during treatment. Biochemically, there was no difference between mean plasma levels of growth hormone (hGH) before and on maximum therapy with bromocryptine. There was a significant difference between fasting plasma hGH before treatment with bromocryptine and following treatment for 9--23 months in five individual patients. Side effects were not disabling in this series except for a reversible paranoid psychosis in one patient. The overall results are disappointing; although some clinical features improved, plasma hGH levels returned to normal in only three patients. Bromocryptine has a limited place in the management of acromegaly for those patients in whom conventional therapy has been ineffective or is contraindicated.

Acromegaly↗
PubMed1979

Treatment of acromegaly with bromocriptine.

Five men and three women with active acromegaly were treated with bromocriptine. After three months' therapy (30 mg/day) mean GH during the day decreased by 50% in six out of eight subjects. In the remaining two subjects (non-responders) GH was persistently over 100 micrograms/l. Mean GH during glucose tolerance test were not significantly decreased in three out of the eight subjects, of whom two were the nonresponders. The minimum dose of bromocriptine required to achieve maximum GH suppression ranged from 7.5 to 20 mg/day. In contrast, serum prolactin (PRL) throughout the day suppressed significantly in all subjects after 5 mg/day bromocriptine. Decreases in clinical symptoms, hand volume, urinary hydroxyproline and calcium excretion were seen in about half of the subjects. Three of the four subjects with diabetes mellitus showed improvement in glucose tolerance. Although minor side effects were uncommon, one patient died because of massive gastrointestinal haemorrhage from a duodenal ulcer.

Acromegaly↗
PubMed1987

Resolution of acromegaly after removal of a bronchial carcinoid shown to secrete growth hormone releasing factor.

A 29 year old woman with an enlarged pituitary fossa and classical acromegaly, possibly present for ten years, had biochemical and partial somatic resolution of the disorder after removal of a bronchial carcinoid tumour. In addition, galactorrhea stopped, menstruation returned after two years, and amenorrhea and elevated prolactin levels fell towards normal. Immunocytochemistry showed numerous growth hormone releasing factor (GRF) staining cells in the tumour. The tumour cells, when cultured, produced a supernatant selectivity stimulating human pituitary somatotrophic cell cultures to produce growth hormone (GH). The bronchial carcinoid did not secrete detectable GH, but extracts of it, and preoperative serum contained GRF immunoreactivity which coeluted with synthetic human pancreatic GRF.

Acromegaly↗
PubMed1989

Inferior petrosal sinus sampling in acromegaly.

In view of the diagnostic value of bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) in localising preoperatively the site of the microadenoma in pituitary dependent Cushing's disease, the clinical value of BSIPSS was evaluated in five acromegalic patients with equivocal or negative pituitary CT scans. Intersinus GH gradients were obtained for all patients (range 1.6-4.2) but in only one case was the gradient correctly localised to the side of the tumour. Gradients of several other pituitary hormones, particularly prolactin (range 1.6-4.0), also demonstrated gradients parallel to the GH intersinus gradients. Despite the paradoxical intersinus GH gradients, the surgeon was able to readily identify the tumour at the time of surgery. Thus BSIPSS is of little assistance to the surgeon for the preoperative radiological evaluation in acromegaly and these results caution against the universal adoption of the BSIPSS technique in the radiological assessment of all secretory pituitary microadenomas.

Acromegaly↗
PubMed1991

Carbohydrate tolerance and serum lipids in acromegaly before and during treatment with high dose octreotide.

Carbohydrate tolerance and serum lipids were studied in 14 patients with acromegaly before and in response to treatment with high dose somatostatin analogue (octreotide) over a 14-week period. Patients were assessed with respect to growth hormone (GH) profile, IGF1, HbA1, fasting lipids, and the GH, glucose, and insulin response to a standard 75 g oral glucose tolerance test (OGTT) before and during therapy. Prior to treatment mean fasting serum insulin levels were 11.7 +/- 2.8 (+/- SE) mU I-1 with a mean insulin response to OGTT of 49.8 +/- 10.8 mU I-1. Twelve of the 14 patients responded to octreotide with a reduction in mean 24-h serum GH (32.9 +/- 9.3 to 4.3 +/- 0.9 mU I-1), suppression of GH at 60 min during OGTT (3.0 +/- 0.8 mU I-1) and normalization of serum IGF1 (71 +/- 7 to 27 +/- 3 (normal 9-48 nmol I-1)). In this group the fasting insulin levels fell to 2.2 +/- 0.7 mU I-1 (p less than 0.01), and mean insulin response during OGTT was reduced (46.6 +/- 15.0 to 12.3 +/- 2.3 mU I-1) (p less than 0.01). Despite the reduction in insulin secretion there was no significant deterioration in fasting blood glucose (4.8 +/- 0.2 vs 4.6 +/- 0.4 mmol I-1), HbA1 (7.2 +/- 0.3 vs 6.8 +/- 0.3%) or mean blood glucose response to OGTT (7.9 +/- 0.7 vs 8.2 +/- 0.5 mmol I-1). Fasting triglycerides were reduced with treatment from 1.5 +/- 0.2 to 1.1 +/- 0.1 mmol I-1 (p = 0.04) in the responsive group, but serum cholesterol levels were not significantly altered (5.3 +/- 0.3 vs 5.2 +/- 0.3 mmol I-1).

Acromegaly↗
PubMed1987

Psychiatric morbidity in acromegaly.

Previous reports on psychiatric morbidity in acromegaly have been unsystematic. This study examined 51 acromegalic patients for psychiatric morbidity using the General Health Questionnaire and a standard psychiatric interview, the Present State Examination. Although psychiatric morbidity was higher in the female than the male acromegalics, the study showed no increase in psychiatric morbidity in general, nor an increased incidence of depression, in comparison with general population and patient samples. No relationship was found between growth hormone levels and psychiatric morbidity. The results raise the question whether acromegalic patients show lower psychiatric morbidity than expected from patients with such an illness. The data suggest that previous reports of depression in acromegalic patients examplify the simple coincidence of a likely and an unlikely condition.

Acromegaly↗
PubMed1999

Transient diabetes insipidus in a dog with acromegaly.

A nine-year-old female beagle with acromegaly and extreme polyuria and polydipsia during dioestrus is described. It was demonstrated that polyuria was related to an inadequate rise of arginine-vasopressin (AVP) levels after water deprivation and stimulation with hypertonic saline. Administration of AVP did not lead to a significant increase in urine osmolality or reduction of urine volume. Clinical signs, except for bony changes, completely disappeared following ovariohysterectomy.

Acromegaly↗
PubMed1982

Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly.

A 44 amino acid peptide with growth hormone-releasing activity has been isolated from a human tumor of the pancreas that had caused acromegaly. The primary structure of the tumor-derived peptide is H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala- Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly -Ala-Arg-Ala-Arg-Leu-NH2. The synthetic replicate has full biological activity in vitro and in vivo specifically to stimulate the secretion of immunoreactive growth hormone. The tumor-derived peptide is identical in biological activity and similar in physiochemical properties to the still uncharacterized growth hormone-releasing factor present in extracts of hypothalamic tissues.

Acromegaly↗