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PubMed1996

Self-organized segmentation of time series: separating growth hormone secretion in acromegaly from normal controls.

The pulsatile pattern of growth hormone (GH) secretion was assessed by sampling blood every 10 min over 24 h in healthy subjects (n = 10) under normal food intake and under fasting conditions (n = 6) and in patients with a GH-producing tumor (acromegaly, n = 6), before and after treatment with the somatostatin analog octreotide. Using autocorrelation, we found no consistent separation in the temporal dynamics of GH secretion in healthy controls and acromegalic patients. Time series prediction based on a single neural network has recently been demonstrated to separate the secretory dynamics of parathyroid hormone in healthy controls from osteoporotic patients. To better distinguish the differences in GH dynamics in healthy subjects and patients, we tested time series predictions based on a single neural network and a more refined system of multiple neural networks acting in parallel (adaptive mixtures of local experts). Both approaches significantly separated GH dynamics under the various conditions. By performing a self-organized segmentation of the alternating phases of secretory bursts and quiescence of GH, we significantly improved the performance of the multiple network system over that of the single network. It thus may represent a potential tool for characterizing alterations of the dynamic regulation associated with diseased states.

Acromegaly↗
PubMed2003

The evaluation of lipid peroxidation and acute effect of octreotide on lipid peroxidation in patients with active acromegaly.

BACKGROUND: Although lipid peroxidation has been suggested to play a role in the etiology of many diseases, there is no report about its role in acromegaly in the literature. In the present study, we analyzed the basal levels of lipid peroxides (LPO) in newly diagnosed acromegalic patients, and to evaluate whether octreotide (OCT) has any effect on lipid peroxidation in these patients. METHODS: Plasma lipid peroxide levels before and after acute OCT administration were measured in 12 newly diagnosed acromegalic patients. Blood samples were drawn at basal and 4, 8, and 24 h after octreotide injection (100 microg s.c.). Plasma concentrations of lipid peroxides were estimated from measurement of thiobarbituric acid reactive substance (TBARS), using 1,1,3,3-tetra-ethoxypropane as a standard. RESULTS: This study shows that acromegalic patients have significantly higher basal plasma lipid peroxides levels compared to hours after OCT injection (p<0.001). Although a significant decrease was observed after 8 and 24 h in comparison to basal level (p<0.001), the lipid peroxide levels tended to increase at 24 h though still low when compared to basal level. CONCLUSION: Acromegalic patients have high basal lipid peroxide levels, which was significantly decreased after OCT administration.

Acromegaly↗
PubMed1994

Marginally elevated prolactin levels require magnetic resonance imaging and evaluation for acromegaly.

Marginal elevations in serum PRL concentration represent a particularly difficult diagnostic dilemma. In most cases, mild hyperprolactinemia is not associated with organic disease. Patients with menstrual disturbances, galactorrhea, and confirmed elevations in serum PRL should have a screening TSH to rule out primary hypothyroidism (5). In cases where there is no clear etiology of hyperprolactinemia, an MRI should be performed. Magnetic resonance imaging with gadolinium is more sensitive and specific than CT scanning in detecting all types of pituitary tumors and is the study of choice (4). Further, a serum IGF-1 level (or OGTT) should be obtained when clinical symptoms and/or a pituitary mass suggest the possibility of acromegaly. An individual with abnormal GH screening tests but an unremarkable MRI would be subjected to an especially careful follow-up, including IGF-1 and PRL levels every 6 to 12 months. In this way, early tumor growth may be detected making a surgical cure more likely (Fig. 1). Although we have stressed the importance of GH-producing tumors as a cause of hyperprolactinemia, other tumor types of the pituitary may do so as well. Most of these will be detected by MRI.

Acromegaly↗
PubMed1996

Acromegaly.

Subcellular mechanisms support the notion of an intrinsic pituitary defect in acromegaly, with elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels that affect the cardiovascular and respiratory system, as well as neoplastic cell proliferative activity. Surgery, even with external-beam irradiation adjuvant therapy, is only successful in less than 60% of patients, and there are side effects. Normalization of GH levels may improve survival rates. Octreotide has revolutionized patient management, normalizing GH and IGF-1 levels in up to 60%, ameliorating soft-tissue abnormalities and reducing tumor size in up to 50%, and attenuating GH levels in more than 90% of patients. Issues concerning the role of octreotide, as well as clarifying precise outcome measures, still need to be resolved.

Acromegaly↗
PubMed1996

Relationships between pathological diagnosis and clinical parameters in acromegaly.

From our series of 185 somatotropic adenomas with acromegaly, we found that sparsely granulated adenomas were more frequent (56%) than densely granulated ones. Immunocytochemistry detected growth hormone (GH) plurihormonal adenomas in 68% of patients. GH-alpha-subunit (alpha SU) and GH-alpha SU-prolactin (PRL) were more frequent (38%) than GH monohormonal adenomas (32%). The colocalization of GH and alpha SU in the same cell was obvious in many tumors. In contrast, colocalization of GH and PRL was demonstrated in only 25% of GH-PRL adenomas. The relationships between age, sex, tumor size, GH and PRL plasma levels, granularity, and percentage of GH-, alpha SU-, and PRL-immunoreactive cells were established in 105 acromegalic patients by three statistical methods, mainly by a principal component analysis. Correlations were found between the percentage of alpha SU- and GH-immunoreactive cells, and between densely granulated character and the percentage of GH-immunoreactive cells. Tumor size was not correlated with alpha SU, but was positively correlated with PRL plasma levels. Patients' age and percentage of GH-immunoreactive cells were inversely related to tumor size. Plurisecretion and sparsely granulated aspect are not related to age and tumor size.

Acromegaly↗
PubMed1996

Assessment of functional liver mass and plasma flow in acromegaly before and after long-term treatment with octreotide.

Functional liver mass and functional liver plasma flow (FLPF) were assessed in 11 patients with clinical features of acromegaly by determining galactose elimination capacity (GEC) and extrarenal clearance of sorbitol, before and 5 to 7 months after treatment with the long-acting somatostatin analog, octreotide (150 to 600 micrograms/d in three subcutaneous injections). Growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, as well as liver size by ultrasound, were also recorded. Baseline GEC was increased in every patient but one, for a mean of 0.78 +/- 0.10 g/min (normal, 0.53 +/- 0.07; P < .01). At reevaluation after 5 to 7 months of octreotide treatment, a significant reduction of GEC was observed (0.62 +/- 0.08 g/min, P < .001). Changes of GEC paralleled those of GH (38.6 +/- 34.4 v 11.7 +/- 15.2 micrograms/L, P < .01) and IGF-I (5.0 +/- 1.7 v 2.7 +/- 2.2 U/ml, P < .001). Significant correlations were found between GEC and GH (r = .50, P < .05) and between GEC and IGF-I (r = .55, P < .01). FLPF, assessed by extrarenal clearance of sorbitol, was within the normal limit in all cases (0.98 +/- 0.19 v 0.97 +/- 0.12 L/min, NS) and remained normal after 5 to 7 months of octreotide treatment (0.99 +/- 0.11 L/min). Hepatic structure determined with ultrasonic scanning and conventional liver-function tests were basally normal in all patients, with a slight increase of liver volume in three cases. No change of biochemical and/or morphological features occurred during follow-up evaluation. The results support the hypothesis that GH and especially IGF-I enhance liver metabolic capacity; conversely, functional liver perfusion is largely independent of their actions. Our data also suggest that octreotide is unable to produce well-structured changes of liver circulation when administered long-term.

Acromegaly↗
PubMed1997

Comparative study of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) level and IGF-I/IGFBP-3 ratio measurements and their relationship with an index of clinical activity in the management of patients with acromegaly.

To evaluate the utility of measuring the serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) level and the IGF-I/IGFBP-3 ratio in the management of acromegalic patients, we comparatively studied the basal concentration of the aforementioned parameters with determination of plasma IGF-I levels and an index of clinical activity of acromegaly in 16 newly diagnosed acromegalic patients (aged 34 to 64 years) before and after hypophysectomy. After adenomectomy, 10 patients remained with "active" disease and six were "cured." Twenty-nine healthy sex- and age-matched volunteers were also studied. Comparison of individual values between untreated acromegalic patients and control subjects showed that none of the patients had overlapping values for IGF-I, whereas five of 16 and three of 16 patients had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3 ratio, respectively. When we compared the study parameters between the patients who remained with active disease after adenomectomy and the controls, two of 10 had overlapping values for IGF-I, but six of 10 and five of 10 had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3 ratio, respectively. Moreover, comparison of these parameters between cured and active patients after hypophysectomy showed that none had overlapping values for IGF-I, whereas three of six and one of six had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3 ratio, respectively. All biochemical variables studied showed significant relationships with an index of clinical activity of disease. In conclusion, our results seem to indicate that among determinations of plasma IGF-I, serum IGFBP-3, and the ratio IGF-I/IGFBP-3 in the evaluation of acromegalic patients, measurement of the plasma IGF-I level has the most discriminative value in the management of these patients.

Acromegaly↗
PubMed1975

Bromocriptine therapy in acromegaly.

Bromocriptine (CB-154, Sandoz) has been given to 21 acromegalic patients (11 female, 10 male) for a period of 6-10 months. The mean serum growth-hormone (G.H.) levels ranged from 10 mug/1 to 512 mug/1 before therapy. Bromocriptine suppressed G.H. values to 5 mug/1 or less in 4 patients and to less than 10 mug/1 in a further 8 patients, but in 2 patients G.H. levels did not show any significant reduction. Bromocriptine did not block stress-induced G.H. secretion. It did not distrub pituitary function other than secretion of prolactin and had negligible side-effects. Its effect on tumour size is uncertain and it is therefore unsuitable for patients with suprasellar extension of the tumour. Otherwise it seems reasonable to offer a trial of bromocriptine to all patients with acromegaly where therapy is deemed necessary. In those who show a full response of G.H. levels with a dose of 20-40 mg of bromocriptine per day, external radiation to the pituitary can be used to prevent tumour expansion and bromocriptine withdrawn at intervals to assess the effect of the radiation. In patients with a partial response to bromocriptine, the decision to offer alternative therapy depends on the extent of the response and on the age and medical condition of the patient. In patients who fail to respond to bromocriptine, particularly those younger patients with active disease, more definitive local treatment (e.g., trans-sphenoidal removal of the tumour or yttrium-90 implantation) would be indicated. Bromocriptine may also be used with benefit in the large number of patients who have shown a partial response to other forms of therapy.

11-Hydroxycorticosteroids↗
PubMed1984

Long-acting and selective suppression of growth hormone secretion by somatostatin analogue SMS 201-995 in acromegaly.

In 6 of 7 acromegalic patients a single subcutaneous injection of 50 micrograms of a new octapeptide somatostatin analogue (SMS 201-995) reduced serum growth hormone (GH) from 30 +/- 12 ng/ml to 1.4 +/- 0.4 (mean +/- SEM). Serum GH remained below basal concentration for 9 h. In the remaining patient who had very high basal preprandial serum GH, SMS 201-995 produced a reduction in serum GH of only 20%. Plasma glucose concentrations were increased to the upper limits of the normal range when a high-carbohydrate meal was consumed 2 h after injection. In non-diabetic patients plasma glucose did not exceed 129 mg/dl. The 40% decrease in plasma glucagon, which lasted for 7 h after SMS 201-995 injection, was not statistically significant. No side-effects and no rebound phenomenon were observed. These results suggest that SMS 201-995 may be the first somatostatin analogue suitable for the clinical management of acromegaly.

Acromegaly↗
PubMed1989

Continuous infusion of octreotide in acromegaly.

15 patients with acromegaly were treated with continuous subcutaneous infusion of octreotide in increasing dose from 200 to 1600 micrograms per 24 h by 200 micrograms increments each week. Patients were studied during the initial 7 h of infusion, weekly at each dose level, then after 1 and 2 months at maximum dosage. 13 patients responded well, as judged by growth hormone (GH) suppression and return of insulin-like growth factor 1 to normal, although 1 patient withdrew due to adverse effects; 2 patients showed no significant reduction in GH. In the 12 responders GH level fell within the first 3 h of infusion at a mean plasma octreotide level of 0.76 (SE 0.26) micrograms/l, corresponding to 25 micrograms of infused drug. Optimum suppression of GH occurred at a dosage of 600 micrograms per 24 h, a plasma drug level of 3.5 (0.5) micrograms/l. A definite reduction in tumour size was seen on computerised tomographic scan in 2 patients. All responders noted subjective improvement in acromegalic symptoms. Adverse effects comprised gastrointestinal disturbances, which were transient and mild in 14 patients but severe in 1; biliary sludging occurred in 1 patient. No significant deterioration in carbohydrate tolerance was seen in the responders.

Acromegaly↗
PubMed2003

Radiation optic neuropathy after external beam radiation therapy for acromegaly: report of two cases.

For diagnosing radiation optic neuropathy (RON) ophthalmological and imaging data were evaluated from 63 acromegalic patients, irradiated between 1967 and 1998. Two patients developed RON: one patient in one optic nerve 10 years and another patient in both optic nerves 5 months after radiation therapy. RON is a rare complication after external beam radiation therapy for acromegaly, which can occur after a considerable latency period.

Acromegaly↗
PubMed1986

Correction of jaw deformities subsequent to treatment of acromegaly.

In acromegaly, growth of facial bones and changes of oral and laryngeal mucosa are well accepted facts. Orthognathic surgical procedures should in these cases be postponed until the acromegalic process is well controlled. 2 cases of mandibular osteotomies (patients aged 61 and 38 years) are reported. The surgical procedures and the postoperative course of these patients were uneventful and did not deviate from those of otherwise healthy patients.

Acromegaly↗
PubMed1986

Surgical correction of residual facial deformity following treatment of acromegaly.

The features and treatment of acromegaly are described and emphasis placed on the apparent failure of the bone deformities to regress. A method of one stage correction of such residual facial deformity is described and illustrated in a patient with deformities of the mandible, frontal, zygomatic and nasal bones, nine years after hypophysectomy.

Acromegaly↗
PubMed1993

Effects of octreotide on morphology of pituitary adenomas in acromegaly.

We studied the effects of the long-acting somatostatin analogue octreotide (SMS 201-995, Sandoz, Basel, Switzerland) on the morphology of pituitary adenomas in acromegaly. Of the 29 adenomas examined by light microscopy, 16 had been treated pre-operatively with octreotide. The treated adenomas were compared with the untreated adenomas. 14 adenomas were also studied by electron microscopy. In 23 cases we performed in-situ-hybridization for GH-mRNA. Under light microscopy, we found a decrease in amyloid deposits and a higher amount of cell necroses and fibroses after treatment, mainly in the tumors with shrinkage. Tumor shrinkage was diagnosed when the maximal diameter of the adenoma decreased for at least 1/3 during octreotide treatment in NMR examination. Immunohistochemical examinations showed that treated adenomas, especially those with tumor shrinkage, possessed more GH immunoreactive cells, and after in-situ-hybridization we found a higher content of GH-mRNA. On the ultrastructural level, rough endoplasmic reticulum appeared to be increased in treated adenomas. The increase of GH-mRNA and of rough endoplasmic reticulum suggests the likelihood of an increased secretory activity due to a rebound effect after short-term pre-operative omission of octreotide. Other findings are discussed.

Acromegaly↗
PubMed1983

Myopathy in acromegaly. A case study.

The muscle findings in a patient with acromegaly of 20 years duration are presented. The patient demonstrated mild muscular weakness and atrophy. Standard needle electromyography was normal and single fiber electromyography showed normal motor unit densities. Muscle biopsy revealed normal size type-I muscle fibers, but three populations of type-II fibers - hypertrophied, atrophied, and normal-sized fibers. Hypertrophy of type-II fibers may be the direct result of the excess growth hormone, while the atrophic fibers may result from the disturbance of other endocrine function.

Acromegaly↗