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PubMed1994

[Treatment of acromegaly with a new slow release somatostatin analog, lanreotide].

Treatment of Acromegaly has been improved by the development of the somatostatin analogs characterized by an increased specificity and longer duration of action. One of these analogs-Lanreotide- (Somatuline) is supplied under a slow release formulation and does not require several daily injections like other analogs presently available. The clinical pharmacodynamic studies that have been conducted in healthy and acromegalic patients show that the i.m. injection of a single dose of this slow-release formulation leads to a significant decrease of the plasma GH and IGF-1 levels. This effect lasts at least 14 days. The Lanreotide slow-release formulation has been used to treat 123 acromegalic patients who presented with a still evolutive disease after conventional therapy. The product was given at a 30 mg-dose every 10 or 14 days during a 3-to 24-month period. This treatment led to a reduction of the symptoms and to a decrease of GH hypersecretion. GH and IGF-1 levels have been normalized respectively in 46% and 32% of the patients. The observed results allow to conclude to an immediate efficacy of the treatment (without escape sign). The adverse drug events are minor and transitory. The antitumor effects are modest and inconstant. The slow release formulation seems to provide the patients with a better quality of life, as compared to the several daily injections.

Acromegaly↗
PubMed1994

Magnetic resonance imaging of radiation necrosis after radiotherapy for acromegaly: report of a case.

A total 5,600 cGy in 28 fractions in 44 days was delivered to a 53-year-old woman with acromegaly after transsphenoid removal of a pituitary adenoma. Sixteen months later, she suffered a progressive loss of vision. Radiation optic neuropathy was diagnosed. A T1-weighted imaging showed gadolinium-enhanced lesions in the optic chiasm, pituitary stalk and hypothalamus. Magnetic resonance imaging is uniquely suited to detect radiation injury to the sellar region. The complications of radiation therapy for benign tumor can be severe even by current standard procedures.

Acromegaly↗
PubMed1993

[Response of growth hormone to sandostatin and bromocriptine and prognostic value of prolactin levels in serum and thyroliberin test in patients with active acromegaly].

Usefulness of determination of blood serum prolactin concentration and the result of thyroliberin (TRH) stimulation test for predicting the magnitude of growth hormone (GH) response to the administration of sandostatin and bromocriptine has been evaluated in 14 patients with active acromegaly. No relation was found between the occurrence of hyperprolactinemia and the response of GH to the administration of sandostatin and bromocriptine. Analysis of GH secretion after TRH administration made possible the selection of a group of acromegalic patients with paradoxical increase in GH secretion in response to TRH in whom the administration of sandostatin caused a significant decrease in blood serum concentration of GH following the administration of sandostatin. TRH stimulation test had, however, no value in predicting the effect of bromocriptine on GH secretion.

Acromegaly↗
PubMed1993

[Reevaluation of the I-dopa test in acromegaly: anatomo-clinical and prognostic correlations].

It is known that in acromegalic patients the GH secretion exhibits a pattern of response to various stimuli that differs from that observed in normal subjects. We have evaluated the paradoxical GH response to 1-Dopa in acromegaly, in order to clarify the relationships between this datum and the tumour size, the basal GH secretion, the GH response to TRH and the long-term prognosis. MATERIALS AND METHODS. 34 acromegalic patients, 12 men and 22 women, aged 35-70 yr, participated in this study. They were divided in 4 classes, according to Hardy's classification of pituitary neoplasias: (1) intrasellar microadenomas, < 10 mm (n = 8); (2) intrasellar macroadenomas, > 10 mm (n = 14); 3) adenomas with local expansion (n = 9); (4) adenomas with extrasellar expansion (n = 3). All patients underwent a 1-Dopa-test; 18 of them underwent a TRH-test. Basal postoperative GH and basal pre- and postoperative PRL levels were also determined. RESULTS. The basal preoperative GH values in all patients ranged between 16 and 278 ng/ml. 22 patients showed a paradoxical response to 1-Dopa, 12 were non-responders. The following results were observed in the different classes: [table: see text] Moreover, 10 subjects (56%) were TRH-responders (9 of them were also 1-Dopa-responders, 1 was non-responder) and 8 were TRH non responders (6 were 1-Dopa non-responders, 2 were 1-Dopa responders). Basal postoperative GH values were > 5 in 17 1-Dopa responders and in 9 non responders. Basal preoperative PRL levels were > 25 ng/ml in 7 1-Dopa responders and in 2 non responders. After surgery, basal PRL became normal in 5 responder patients. DISCUSSION. In a previous work we have correlated the paradoxical GH response to TRH with tumour size and GH levels, observing a higher percentage of paradoxical response in patients in class I and II and, postoperatively, lower GH levels in preoperative TRH responders. So, we have underlined the good prognostic feature of a preoperative paradoxical response. In this paper we have evaluated the paradoxical GH response to 1-Dopa in the different Hardy's classes and compared it with the GH levels and the GH response to TRH. The results show that a paradoxical response can be observed more frequently in small (class I) adenomas than in greater size ones, and in presence of lower GH basal levels. Moreover, a concordance between 1-Dopa and TRH tests can be observed. CONCLUSIONS. The results clearly indicate that the responses to dynamic GH tests should be evaluated considering the anatomic characteristics of the neoplasias. It could be suggested that the paradoxical response can be expressed only when hypothalamus-pituitary interactions are intact.

Acromegaly↗
PubMed1993

Medical management of acromegaly--what and when?

GH and IGF-I levels are elevated in patients with acromegaly. At the time of diagnosis patients present with macroadenomas with a high surgical failure rate or microadenomas. Administration of octreotide (100 micrograms, three times daily) suppressed GH secretion during 8 h to < 5 micrograms/l in 47% and to < 2 micrograms/l in 26% of acromegalic patients after two weeks. IGF-I levels were normalized in up to 70% of patients. Increasing the dose of octreotide to 250 micrograms three times daily did not further improve results. Tumour shrinkage occurred in 37% after six months of treatment, while symptoms improved in 70%. Transient diarrhoea and nausea were noted in 88%, but after six months only 10% reported these symptoms. Gallbladder sludge and gallstones were noted in 19% of patients. IGF-I levels were normalized in 82% of patients with microadenoma and in 50% with macroadenoma. Well-defined pituitary adenomas are usually surgically removed. Invasive tumours are difficult to remove surgically but preoperative octreotide may shrink adenomas and improve response. Octreotide therapy, unlike surgery and irradiation, does not compromise pituitary function. This study suggests that octreotide therapy could be a viable primary management of small discreet adenomas. Where surgery and octreotide fail, other treatments of adenoma include bromocriptine and radiotherapy.

Acromegaly↗
PubMed1993

[Dilated cardiomyopathy in acromegaly worsening under octreotide treatment. Apropos of a case].

Dilated cardiomyopathy associated with acromegaly is rare, but may improve with octreotide, a somatostatin analogue. The authors give the first description here of paradoxical worsening in cardiac function during such treatment, with the onset of episodes of acute decompensation following each attempt at starting treatment. Thus worsening was confirmed objectively by a challenge test with octreotide: increased dyspnea, fall in shortening fraction and in echocardiographic cardiac output (of 17 to 14% and 4 to 3 l/min respectively), a decrease in isotopic ejection fraction from 15 to 6% and this in parallel with efficacy regarding hormone levels of GH and IGF1 and a reduction in tumour size by CT scan. No further episode of decompensation occurred after treatment was stopped permanently. The patient underwent a transplant 3 months later. Suppression of the positive inotropic effect of GH by octreotide, associated with an increase in peripheral resistance is suggested. A negative inotropic effect of this hormonal analogue on too advanced a case of heart disease is also a possibility.

Acromegaly↗
PubMed1995

Sumatriptan does not stimulate PRL and GH secretion in acromegaly.

OBJECTIVE: Serotoninergic receptors are involved in the regulation of PRL and GH secretion. We studied the effects of sumatriptan, a new 5-HT1D receptor agonist, on PRL and GH secretion in active acromegaly. EXPERIMENTAL DESIGN: After their informed consent, all subjects were submitted to sumatriptan or placebo administration in single blind and in a random order. The time interval between the tests was of 7 days. ENVIRONMENT: We examined all patients in the morning, after 12 hours of fasting. All subjects were in recumbent position during the tests. Pulse rate and blood pressure were monitored during the test. SUBJECTS: Eight acromegalics (42-65 years) and 10 age-matched (33-63 years) normal subjects. PROTOCOL: Blood samples were taken after needle insertion kept patent by slow saline solution infusion. PRL and GH secretion were evaluated after sumatriptan (6 mg sc) and placebo. Blood samples were taken before (45, 15 and 0 minutes) and every 15 minutes for 2 hours after sumatriptan or placebo administration. RESULTS: No significant changes in PRL secretion were observed after sumatriptan in both groups of subjects. A significant increase in GH levels after sumatriptan was observed in controls but not in acromegalics. An age-related negative trend in GH response to sumatriptan was observed in controls. CONCLUSIONS: Our study indicated that 5-HT1D receptors are not involved in PRL and GH secretion in middle-aged acromegalics.

Acromegaly↗
PubMed1995

[Sarcoidosis-lymphoma syndrome in a woman with acromegaly].

The occurrence of lymphoid malignancy tissue, most often Hodgkin or non-Hodgkin lymphoma, after several years of the diagnosis of sarcoidosis has been named sarcoidosis-lymphoma syndrome. The pathogenesis of this syndrome is probably connected with dysregulation of T lymphocytes. A woman with acromegaly with non-Hodgkin lymphoma diagnosed six years after sarcoidosis is presented in this paper. The CVP chemotherapy helped to establish 9-years, lasting remission still.

Acromegaly↗
PubMedDate not supplied

Systolic and diastolic cardiac function in acromegaly. An echocardiographic study.

The aim of this study was to establish the existence of primary acromegalic cardiomyopathy different from the cardiovascular complications often associated with acromegaly. Thirty-four acromegalic patients, referred to our non-invasive laboratory and divided into two groups on the basis of the presence of hypertension, underwent echocardiographic studies. A control group of 34 subjects individually matched with the patients for age, sex, and blood pressure values was also studied. To evaluate cardiac function during exercise, the normotensive acromegalics, the control group, and a group of 9 athletes with left ventricular mass comparable to that of the acromegalic subjects underwent a handgrip test. Cardiac mass was increased in all patients; hypertensive patients had a greater increase than normotensive patients (144.9 +/- 38 vs 120.9 +/- 20.8 g/m, p < 0.02). Systolic wall stress and percent fractional shortening, although similar to the values confirmed in controls, were modified in the hypertensive patients (wall stress 77.5 +/- 9.3 vs 60.8 +/- 9.4 dyne/cm2, p < 0.01). In all patients, diastolic function at rest was similar to that in controls, although the hypertensive patients had deteriorated diastolic function (E peak 56.9 +/- 12.4 vs 71 +/- 15 cm/s, p < 0.01; A peak 70.4 +/- 21.1 vs 52.3 +/- 16.4 cm/s, p < 0.03; E/A ratio 0.89 +/- 0.37 vs 1.38 +/- 0.35, p < 0.02). During handgrip testing, wall stress in both the normotensive acromegalics and the control subjects increased but remained unchanged in the athlete group; percent fractional shortening decreased in all patients and controls but increased slightly in the athlete group. In conclusion, cardiac hypertrophy caused by GH hyperincretion does not improve acromegalic heart activity: diastolic function, although normal at rest, appears deficient during isometric exercise.

Acromegaly↗
PubMed1977

Growth hormone levels in acromegaly after external radiotherapy.

A 56-year-old acromegalic patient was treated with conventional radiotherapy. One year after treatment, the patient's growth hormone level was normal and remained so for a full year. Subsequently, the growth hormone level returned to the pretreatment, acromegalic range. The attainment of a normal growth hormone level after treatment of acromegaly is no assurance that the level will remain normal. Repeated growth hormone level determinations are necessary before cure can be considered permanent.

Acromegaly↗
PubMed1995

The magnitude of growth hormone elevation is related with the proportion of monomeric form in acromegaly.

In acromegalic patients monomeric GH form constitutes the larger proportion of circulating GH; however, no data are available concerning the relation between total GH elevation and the predominance of GH forms. Therefore, we studied the relationship between the degree of GH elevation and the proportion of GH isoforms. Sera from 11 patients with active acromegaly were subjected to gel chromatography on Sephadex G-100 column and fractions were collected for RIA to measure GH. The monomeric form of GH was predominant and exhibited a lineal correlation (r = 0.76, p < 0.01) with the circulating GH, thus the higher elevation of GH, the major proportion of monomeric GH. IGF-1 changes correlate with changes in monomeric GH but no better than for total GH. There was a correlation observed (r = 0.65) between the proportion of low GH forms and the presence of hyperglycemia, although the physiological role of the lower molecular GH forms is still unknown. In conclusion, it was demonstrated that the relative proportion of GH molecular forms changes according to the magnitude of the elevation of total GH.

Acromegaly↗
PubMed1996

[Acromegaly].

The diagnosis of acromegaly, in more than 95% linked to a pituitary adenoma, is essentially a clinical dysmorphic syndrome. Because of its low evolution, the illness is too often diagnosed when complications (cardio-respiratory, diabetes...) occur. The biological diagnosis is based on high insulin growth factor 1 (IGF1) and growth hormone (GH) levels which are not suppressed under an oral glucose load. The treatment is mainly surgical (transsphenoidal selective adenomectomy) at first intention. Irradiation and medical treatment (dopaminergic or somatostatinergic drugs) are used in case of surgical failure.

Acromegaly↗
PubMed1996

[Early diagnosis of impaired glomerular and renal tubule function in patients with acromegaly].

BACKGROUND: Albuminuria (A), increased urinary excretion of glycosaminoglycans (GAG) and increased activity of N-acetyl-beta-glucosaminidase (NAG) in urine are early markers of glomerular and tubular changes in various pathological conditions at a time when renal functions do not yet display impaired function and when the changes are still reversible. The objective of the presented study was to assess to what extent these early changes may play a part in acromegaly. METHODS AND RESULTS: In a group of 24 acromegalic patients and in 18 healthy controls the authors examined the microalbuminuria (RIA Immunotech Prague), urinary excretion of glycosaminoglycans (spectrophotometrically by the carbazole method) and they assessed the NAG activity in urine (spectrophotometrically). In acromegalic patients before surgical and pharmacological treatment the authors found, as compared with healthy controls, increased urinary excretion of GAG [4.4 (0.9-22.7) g/mol creat. vs. 2.1 (0.8-5.5) g/mol creat, p < or = 0.001], elevated albuminuria [3.6 (0.3-37.4) g/mol creat. vs. 0.5 (0.1-2.2) g/mol creat, p < or = 0.001 and an enhanced NAG activity [1005 (345-2935) U/l vs. 470 (195-1135) U/l, p < or = 0.001]. The parameters of albuminuria and urinary GAG excretion characterize rather glomerular renal function, they correlate mutually (r = 0.64 p < or = 0.001), while the urinary NAG activity, depending on tubular function, does not correlate with them. No correlation of these parameters with the IGI concentration (for A: 0.3, for GAG: -0.04 and for NAG: -0.02 according to Pearson was found. CONCLUSIONS: In hormonally active acromegalic patients without apparent altered renal functions (normal serum creatinine, Albustix negative) the authors detected early changes of glomerular and tubular functions. They found a significant correction between albuminuria and GAG excretion.

Acetylglucosaminidase↗
PubMed1997

[Prediction of pharmacological effect of octreotide in acromegaly by means of 111In-pentetreotide scintigraphy and calculation of a pituitary uptake index].

AIM: The aim of our prospective study was to optimize the determination of the pituitary somatostatin receptor status by means of 111-In-pentetreotide scintigraphy and to compare it intraindividually with the pharmacological effect of octreotide in active acromegaly. METHODS: In n = 22 patients with growth hormone (GH) secreting pituitary adenoma, 111-In-pentetreotide scintigraphy was performed, and the specific radionuclide accumulation in the pituitary area (evaluation visually as well as semiquantitatively by means of ROI technique and calculation of various uptake indices) was correlated with the acute drop of GH after administration of 100 micrograms octreotide s. c. (octreotide acute test). RESULTS: The uptake index we propose (cts/pixel-ratio circular pituitary ROI: irregular cerebrum ROI after background correction in the sagittal SPECT slice with maximum pituitary uptake 24 h p.i.) correlates best with the pharmacological effect (acute decrease of GH levels) of octreotide; its upper normal limit amounts of 3.5. CONCLUSION: As often the normal pituitary gland can be visualized scintigraphically, the purely visual differentiation between a normal and a pathological receptor status sometimes is equivocal. A pituitary uptake index, calculated by means of a standardized ROI technique, facilitates this discrimination and so contributes to select possible responders for a treatment with octreotide.

Acromegaly↗
PubMed1997

Is growth hormone bad for your heart? Cardiovascular impact of GH deficiency and of acromegaly.

At present, there is growing evidence implicating GH and/or IGF-I in the intricate cascade of events connected with the regulation of heart development and hypertrophy. Moreover, GH excess and/or deficiency have been shown to include in their advanced clinical manifestations almost always an impaired cardiac function, which may reduce life expectancy. This finding is related both to a primitive impairment of heart structure and function and to metabolic changes such as hyperlipidemia, increase of body fat and premature atherosclerosis. Patients with childhood or adulthood-onset GH deficiency have a reduced left ventricular mass and ejection fraction and the indexes of left ventricular systolic function remain markedly depressed during exercise. Conversely, in acromegaly the cardiac enlargement, which is disproportionate to the increase in size of other internal body organs, has been a rather uniform finding. The severity of the acromegalic cardiomyopathy was reported to be correlated better with the disease duration than with circulating GH and/or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often results in concentric hypertrophy of both ventricles. The treatment of GH deficiency and excess improved cardiac function. Interestingly, based on the evidence that GH increases cardiac mass, recombinant GH was administered to patients with idiopathic dilated cardiomyopathy. It increased the myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement of hemodynamics, myocardial energy metabolism and clinical status. These promising results open new perspectives for the use of GH in heart failure.

Acromegaly↗
PubMed1976

[Paranoid-hallucinatory psychoses in acromegaly].

Paranoid halluzinatory psychoses associated with acromegaly occur rarely. This paper presents three own observations and at the same time gives a revue of cases reported in the literature. Based on these observations it is attempted to characterize structure and cause of these psychoses and to correlate the psychopathology with the development and severity of the somatic disease. The discussion of the psychopathology includes the problem of differentiation between somatic determined psychoses and endogenous disorders, i.e. schizophrenic and manic depressive illness. It also considers factors such as personality structure and situation of life.

Acromegaly↗
PubMed1998

Novel somatostatin analogs for the treatment of acromegaly and cancer exhibit improved in vivo stability and distribution.

The biodistribution of several radiolabeled somatostatin (SRIF) analogs was determined in the rat. Newly developed analogs BIM-23190 and BIM-23197 attained higher plasma levels and much greater target tissue concentrations than the clinically used BIM-23014 analog. Highest tissue concentrations of BIM-23190 and BIM-23197 were found in adrenal, kidney, pituitary and pancreas, tissues that are known to be abundant in mRNA for the somatostatin subtype 2 receptor. BIM-23190 and BIM-23197 associated radioactivity in these tissues was prolonged compared with that of BIM-23014, especially in the SRIF-receptor-rich pituitary. BIM-23190 and BIM-23197 were more stable in vivo and much less subject to biliary excretion than BIM-23014. These properties account for the elevated plasma and target tissue concentrations of these new SRIF analogs. Based on higher plasma levels, greater distribution to target tissues and longer in vivo stability, BIM-23190 and BIM-23197 may prove to be superior to BIM-23014 for the treatment of acromegaly and some types of cancer.

Acromegaly↗
PubMed1997

[Disappearance of the sleep apnea syndrome in a female patient after surgery of a hypophyseal adenoma with acromegaly].

The association of the syndrome of sleep apnoea and acromegaly was described in the literature. However, so far no satisfactory explanation was given of the more frequent concomitant incidence of these diseases. The authors describe the disappearance of the sleep apnoea syndrome in a female patient after removal of an intrasellar microadenoma of the pituitary with overproduction of growth hormone.

Acromegaly↗