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PubMedDate not supplied

[Sudden cardiac death in acromegaly. Anatomopathological observation of a case].

Involvement of the cardiovascular system in patients affected by acromegaly is an important factor in morbidity and mortality. The diagnosis in these subjects is acromegalic cardiomyopathy with cardiac decompensation, arrhythmias and sudden death. The pathologic substrate has rarely been described. The present study reports the findings in a case of sudden death in a 54-year-old man, affected by acromegaly. Subsequent diagnostic investigation revealed the characteristic aspects of acromegalic cardiomyopathy in the common myocardium and the presence of hyperacute myocardial infarct of the antero-septal wall of the left ventricle. Examination of conduction tissue revealed slight fibrolipomatosis and dispersion of the atrio-ventricular node (AVN), which extended to the His bundle and bifurcation. The right branch was prematurely intramural with sclerosis and lipomatosis. This location in atrio-ventricular conduction system has seldom been reported in the literature and if so, with different lesions from those found in the case we investigated. The results of microscopic examination convalidate the hypothesis of electrical instability in the heart, as confirmed by the subject's history of ventricular extrasystoles, left branch block and attacks of angina after effort. Death was correlated to hyperacute myocardial infarction of the anteroseptal wall of the left ventricle, in a subject with history of angina, affected by acromegalic cardiomegaly and electric instability. In this case, sudden death could also be considered arrhythmogenic in relation to the additional workload by persistent hormonal stimulation.

Acromegaly↗
PubMed1998

Somatuline LA: a new treatment for acromegaly.

Somatostatin analogues have become well established as treatment for acromegaly. However, to ensure growth hormone (GH) levels are sufficiently suppressed, thrice daily subcutaneous injections are required. The introduction of Somatuline LA, a long acting formulation which controls plasma GH levels for up to 14 days and improves acromegaly symptoms, is likely to improve patient compliance and quality of life.

Acromegaly↗
PubMed1998

Effectiveness of slow-release lanreotide, a long-acting somatostatin analogue, in the treatment of acromegaly.

We evaluated the effectiveness of slow-release lanreotide, a long-acting somatostatin analogue, in the treatment of acromegaly. Eleven patients with acromegaly were recruited, six of whom had received long-term treatment with octreotide. Lanreotide 30 mg was administered by intramuscular injection every other week for 24 weeks. The frequency of injection was adjusted as clinically needed after 2 weeks. Clinical effects were evaluated, and symptoms were recorded and scored. Finger circumferences and hand volumes were measured. Serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations were determined, and an oral glucose test was done at baseline and after treatment. Symptom scores, circumferences of the fingers, hand volumes, and serum GH and IGF-1 concentrations significantly decreased during treatment. Serum GH concentrations returned to normal in five (46%) of the 11 patients, while serum IGF-1 concentrations returned to normal in three (27%). Glucose intolerance was not significantly improved at the end of treatment. Although the mean serum GH concentration was significantly decreased after treatment, it was still not suppressed by glucose. In conclusion, slow-release lanreotide, given either twice or three times a month, is effective in controlling acromegalic symptoms as well as GH and IGF-1 hypersecretion. The treatment is well tolerated and convenient for patients.

Acromegaly↗
PubMed2005

Surgical removal of growth hormone-secreting pituitary adenomas with intensive microsurgical pseudocapsule resection results in complete remission of acromegaly.

Although some investigators recommended surgical removal of the borders between pituitary adenoma and the surrounding normal pituitary gland, there is so far little documentation of how intensive dissection of the border zone affects the actual clinical remission rate of pituitary adenomas. We investigated the precise histological characteristics of the boundary, using surgical specimens from patients who underwent intensive resection of "microsurgical pseudocapsule" of growth hormone (GH)-secreting pituitary adenomas. Furthermore, we compared the remission rate of acromegaly between subjects with (Group 1) and without (Group 2) intensive resection of microsurgical pseudocapsule in order to correlate the histological complete resection and endocrinological remission. Histologically, most adenomas were in direct contact with normal pituitary gland that formed an increased fibrous component facing the adenoma, without a true histological pseudocapsule. It was impossible to dissect the tumor at exactly the tumor--normal pituitary interface for the whole extent of the pituitary adenoma during surgery, and complete removal of the tumor inevitably included a portion of normal tissue (microsurgical pseudocapsule). The biochemical remission rate was significantly higher in Group 1 than in Group 2 (90.0 vs 61.1%), and Group 1 showed no additional postoperative pituitary hypofunction. The present results suggested that intensive resection of the microsurgical pseudocapsule is essential to accomplish histological and endocrinological total resection of the GH-secreting pituitary adenomas for remission of acromegaly.

Adult↗
PubMedDate not supplied

Pegvisomant: a new treatment modality for acromegaly.

Acromegaly, a multisystemic disease resulting from excessive growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels in adults, is associated with a two-to-threefold increase in mortality. The available treatment options (surgery, radiotherapy and medical treatment with somatostatin analogues or dopamine agonists) fail to achieve the currently accepted goals of therapy in a substantial number of patients. Pegvisomant, a newly developed GH receptor antagonist, represents a novel treatment modality for this disease. It binds with the GH receptor and induces internalization, but blocks receptor signaling events, thereby reducing IGF-I production. The two main published studies suggest that it is the most potent medical therapy with greater specificity, without being dependent on the tumour characteristics. However, apart from its high cost and the dilemmas raised concerning the appropriateness of using serum IGF-I concentrations as a marker of disease activity, it may also occasionally be associated with elevations in liver enzyme levels. Further studies are required to confirm its high success rates as well as to investigate the possibility of inducing an increase in the pituitary tumour size. Currently, pegvisomant is a second line treatment for acromegaly with an adjuvant role and possibly of greater value in cases of resistance to other therapeutic options.

Journal Article↗
PubMed1975

Acromegaly. Treatment by transsphenoidal microsurgery.

Serum growth hormone levels, thyroid function, and adrenal function were measured before and after surgery in 16 of 17 acromegalic patients undergoing undergoing transnasal transsphenoidal microsurgery of the pituitary. Thirteen patients have been followed up for 12 to 24 months; three patients have been followed up for three to six months. Serum growth hormone levels decreased to less than 5 ng/ml in seven of nine previously untreated patients; thyroid and adrenal function were preserved in eight of these nine patients. In seven patients treated previously by other modes of therapy, growth hormone levels after transsphenoidal surgery decreased to less than 5 ng/ml in three, to between 5 and 10 ng/ml in three, and from 98 to 41 ng/ml in one. Preoperative adrenal function was normal in six of these seven patients and was preserved in four; thyroid function was normal in five patients preoperatively and was preserved in three. Transsphenoidal microsurgery appears to offer an effective means of lowering growth hormone levels and a possiblity of preserving any remaining normal pituitary function. It may be considered for initial treatment in selected patients in whom more rapid arrest of acromegaly is indicated.

Acromegaly↗
PubMed1984

Multihormonal carcinoid tumor of the pancreas. Secreting growth hormone-releasing factor as a cause of acromegaly.

This report describes the histologic, immunocytochemical, and ultrastructural study of a multihormonal carcinoid tumor of the pancreas, secreting a growth hormone releasing factor (GRF) which provoked acromegaly. The patient presented a nonfamilial multiple endocrine neoplasia, type 1. The absence of radiologic signs of a pituitary adenoma in conjunction with elevated plasma levels of pancreatic polypeptide, glucagon, somatostatin, as well as growth hormone (GH), led to the discovery of the tumor. Its surgical excision produced a rapid disappearance of most of the clinical and biologic disorders. No immunoreactive GH was found in the tumor using radioimmunoassay and immunocytochemistry. In contrast, three peptides with GH-releasing activity were extracted and characterized. Immunocytochemistry showed that the GRF-reactive cells, together with rare somatostatin-storing cells, made up areas which demonstrated a medullary pattern of growth with extracellular amyloid deposits. Under electron microscopic examination, actively secreting cells were observed which carried endocrine granules of 100 to 150 nm in diameter. The other regions of the tumor presented a different type of growth and were composed of pancreatic polypeptide-, glucagon-, or somatostatin-reacting cells. Cells immunostained with antisera raised against beta-endorphin were also noted. These data suggest that GRF may be a new biologic marker for pancreatic endocrine tumors.

Acromegaly↗
PubMed1992

Persistent or recurrent acromegaly. Long-term endocrinologic efficacy and neurologic safety of postsurgical radiation therapy.

As in other clinics, pituitary surgery was definitive treatment in less than 50% of cases of acromegaly treated at one institution over several decades. From 1965 to 1989, 24 acromegalic patients who had noncurative pituitary surgery received radiation therapy at the National Institutes of Health, with a basal human growth hormone level of greater than 5 ng/ml as the criterion for active disease. Using megavoltage irradiation, more than 60% of these patients stabilized at a normal hormonal range, and the overwhelming majority had decreasing growth hormone levels with time. No major side effects of irradiation were encountered except panhypopituitarism of varying degrees. The authors evolved a policy of surgery as the first option, followed by irradiation for patients with postoperative growth hormone levels more than 5 ng/ml.

Acromegaly↗
PubMed1980

Roentgen cephalometric studies on skull development in rats. III. Gigantism versus acromegaly: age differences in response to prolonged growth hormone administration.

Experimental conditions simulating the induction of clinical pituitary gigantism and acromegaly were established by prolonged administration of growth hormone in high dosage to adult male rats starting at two different ages: 6 months (growth still active) and 14 1/2 months (growth virtually arrested). Treatment continued for 14 1/2 months, control receiving saline injections. Each group numbered eight at onset. Standardized x-rays of skull were made in ventro-dorsal and lateral planes, at onset, mid-period, and end of the study. Representative dimensions of cranial and facial segments were measured, including lengths, widths, palate dimensions, gnathic and interzygomatic angles, and incisor curvature. Some related indices were calculated. Means and standard errors were computed, usually on five to eight rats (oldest controls: three only). The response pattern of overall skull length was most illustrative. Younger adult controls grew actively until 14 months of age (5%) while injected rats grew still faster (8%); thereafter, controls grew negligibly (1%) and injected rats only slightly (2%). Older controls showed negligible skull elongation from 14 1/2 to 29 months of age, and growth hormone stimulated no gain. In the younger group, skull length gains were almost entirely in the facial region; cranium gained no length and widened only slightly. Cranial index increased slightly with the hormone. Facial (bizygomatic) width increased in both injected groups--proportionately in younger rats(to giganntism) and disproportionately in older rats. Palatal and dental growth followed facial patterns in both groups. Cranial vault bones thickened and, in older rats, developed surface irregularities, giving them a more massive, acromegaloid structure.

Acromegaly↗
PubMed1990

"Paradoxical" growth hormone secretion in acromegaly: an avian model?

Acromegaly is a pathological human condition resulting from an excess of growth hormone (GH) secretion in adults. The regulation of GH secretion in acromegalics is characterised by "paradoxical" GH responses to dynamic tests of pituitary GH function. Many of these "paradoxical" responses appear to be normal, physiological GH responses in aves. Comparative studies on the control of GH secretion in immature birds may therefore provide an experimental model for testing the effects of therapeutic agents of GH secretion.

Acromegaly↗
PubMed1989

A simple method for assessment of glomerular size and its use in the study of kidneys in acromegaly and compensatory renal enlargement.

As measurement of absolute glomerular size is difficult we developed a method of assessing glomerular size that was simple and practical and could be used to compare the kidneys in different groups of patients. Using a semi-automatic image analyser, the cross-sectional area of 100 randomly-selected glomeruli, outlined by Bowman's capsule, was measured on sections of kidneys taken at necropsy. The mean of the logarithms of the largest 25 areas was calculated. The method was applied to compare control kidneys (53) with the kidneys in acromegalics (20), in patients with one kidney (10) and in patients with asymmetrical kidneys (12). Kidneys were heavier in the three test groups than in controls. Glomerular sizes were similar in controls and in acromegalics but were larger in single and disparate kidneys. There was a relationship between glomerular size and kidney weight within the control group and across the four groups taken together. This only partly accounted for the observed differences in glomerular size between the groups. Histological comparison of the acromegalic and single kidneys showed more global glomerulosclerosis in single kidneys and also segmental lesions, mainly at the glomerular hilum, only in the single kidneys. These findings show that renal enlargement occurs in acromegaly and in single and disparate kidneys but is accompanied by markedly different glomerular features. This implies different mechanisms for the renal enlargement. The method of assessing glomerular size is useful in the study of these and other conditions affecting the kidney.

Acromegaly↗
PubMed1989

Fibrous dysplasia of the skull with acromegaly and sarcomatous transformation. Two cases with a review of the literature.

Two cases of fibrous dysplasia of the skull are reported. Both patients were young women with acromegaly and were treated with radiotherapy. Progressive pareses of cranial nerves, pain, and a malignant course of the disease were characteristic in both patients, and the diagnosis of osteogenous sarcoma proved in one of them by histological examination. The clinical picture of fibrous dysplasia of the skull and the role of radiotherapy with the risk of development of malignancy is discussed.

Acromegaly↗
PubMed1993

Serum levels of bone Gla protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegaly: effects of long-term octreotide treatment.

We measured serum concentrations of bone Gla-protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150-450 micrograms/day for 6-33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2 +/- 4.2 micrograms/liter versus 8.0 +/- 3.3 micrograms/liter, P < 0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r = 0.67, P < 0.001). Also IGF-I concentrations were positively correlated with BGP (r = 0.66, P < 0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146 +/- 46 micrograms/liter versus 127 +/- 44 micrograms/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.

Acromegaly↗
PubMed1980

Morphological and biochemical relationships in 31 human pituitary adenomas with acromegaly.

In 22 pure GH cell adenomas and 9 mixed GH cell-prolactin cell adenomas with acromegaly, we compare the morphological and functional data (secretory activity and granular appearance) with GH levels (radioimmunoassays) in the blood and in the tumor. According to morphological criteria, the secretory activity is marked in 13 cases (Group I), mild in 9 cases (Group II), and weak in 9 others (Group III). The mean values of the plasma GH levels in the 3 groups (80 ng/ml plus or minus 22; 26.5 ng/ml plus or minus 2; and 16.89 ng/ml plus or minus 2 respectively) are significantly different. In 17 densely granulated adenomas and 14 sparsely granulated adenomas, the plasma GH values were very variable. The mean levels of these 2 groups (49.76 ng/ml plus or minus 22 and 41.8 ng/ml plus or minus 7.8 respectively) are not significantly different. The GH concentrations in the tumor were also very variable (358 to 78,900 ng/mg). Their highly significant relationship with the granular appearance is an indirect proof of the granular localisation of GH. We distinguish between 4 functional aspects of the GH cell adenoma which define the different levels of synthesis, storage, and excretion. The secretory activity of the GH adenomatous cell varies with the adenomas and differs from that of the normal cell.

Acromegaly↗
PubMed1993

Serum bone Gla protein as a marker of bone turnover in acromegaly.

Serum bone Gla protein, a sensitive and specific marker of bone turnover, was measured in 35 acromegalic patients (14 untreated, 8 clinically active, and 13 cured) and 21 controls. We also examined 10 acromegalic patients before and after transsphenoidal surgery. Untreated and clinically active acromegalic patients had significantly higher serum bone Gla protein concentrations than the control subjects. Other nonspecific biochemical markers of bone metabolism, such as urinary hydroxyproline and urinary calcium, were also present in significantly greater amounts in active acromegalic patients. After treatment, a significant decrease in levels was observed, with return to control levels. In acromegalic patients, positive correlations were found among serum bone Gla protein and serum growth hormone and serum insulin-like growth factor I levels, as well as among levels of insulin-like growth factor I and serum phosphorus, serum alkaline phosphatase, and urinary hydroxyproline. These results suggest that serum bone Gla protein is a sensitive marker of the action of growth hormone in bone metabolism in acromegaly, a role that is probably mediated by insulin-like growth factor I.

Acromegaly↗
PubMed1984

Mammosomatotroph hyperplasia associated with acromegaly and hyperprolactinemia in a patient with the McCune-Albright syndrome. A histologic, immunocytologic and ultrastructural study of the surgically-removed adenohypophysis.

An 11-year-old girl, with the McCune-Albright syndrome, exhibited fibrous dysplasia of several bones, skin pigmentation, precocious puberty, growth hormone hypersecretion, acromegaly and hyper-prolactinemia. Histologic, immunocytologic and ultrastructural investigation of the surgically-removed pituitary showed massive mammosomatotroph hyperplasia. Since no adenoma was found, the abundance of these bihormonal cells, capable of producing both growth hormone and prolactin, was implicated in the causation of growth hormone and prolactin excess. Somatoliberin overproduction and/or somatostatin and dopamine deficiency could not account for the hypophysial abnormality, since changes in secretory rates of these hypothalamic hormones would lead to proliferation of mature somatotrophs and lactotrophs, rather than mammosomatotrophs. In our patient, a congenital hypothalamic malfunction might have been accompanied by hypersecretion of an unidentified releasing factor, resulting in pathologic differentiation of the pituitary and mammosomatotroph hyperplasia. Alternatively, mammosomatotroph hyperplasia may have been due to an inherent genetic or embryonic defect affecting primarily the pituitary. According to this interpretation, the pituitary lesion represented yet another developmental error in the setting of the McCune-Albright syndrome.

Acromegaly↗
PubMed1997

Pituitary apoplexy with spontaneous cure of acromegaly and its possible relation to Gd-DTPA-administration.

A case of pituitary apoplexy occurring after Gd-DTPA-administration for contrast enhanced MRI in a patient with an hGH-producing macro-adenoma is presented. Within days the initially increased hGH level fell to the normal range, the oral glucose tolerance test (OGTT) showed a normal suppression of hGH and complete anterior pituitary insufficiency developed. At this time repeated MRI suggested a haemorrhagic infarction of the macro-adenoma. Fourteen months later re-examination confirmed spontaneous cure of the acromegaly, improvement of adenopituitary function and shrinkage of the sellar content. The causal linkage between the pituitary adenoma apoplexy and Gd-DTPA-administration is unclear. It might be due to contrast induced blood pressure and endothelial permeability changes, possibly promoted by pre-existing diabetes mellitus associated vasculopathy.

Acromegaly↗
PubMed1989

Cardiac function in endocrine diseases: I. Acromegaly.

The aim of our echocardiographic study was to characterize cardiac function and anatomy of 14 acromegalics (A: 9 women, 5 men; mean age: 42.4 yrs) more closely. The duration of acromegaly in 4 of these patients was between 3 and 12 years; the disease was diagnosed for the first time in the other patients. Double M-mode echocardiography was performed in all patients and the results compared with data obtained from a control group of 24 healthy volunteers (N: 22 men, 2 women; mean age: 23 yrs). The mean left ventricular diameter at end-diastole was greater in the acromegalics than in the controls (A: 55 +/- 6 mm, N: 50 +/- 4 mm; p less than 0.005, means +/- SD). After correction for age and body surface area, it, however, was outside the 95% confidence interval in 5 patients. Left ventricular hypertrophy was present in 3 patients, one of whom had coexistent arterial hypertension. A total of 3 patients were hypertensive. Significantly higher values for the maximal velocity of systolic wall thickening (A: 6.1 +/- 0.6 cm/s, N: 4.2 +/- 0.6 cm/s, p less than 0.001) and diameter change (A: 12.4 +/- 2.0 cm/s, N: 10.6 +/- 1.0 cm/s, p less than 0.005) indicate increased contractility with concurrently increased relaxation; fractional shortening did not differ significantly (A: 38 +/- 5%, N: 37 +/- 5%, ns). The isovolumetric relaxation period at diastole was slightly longer in the acromegalics (A: 70 +/- 17 ms, N: 61 +/- 13 ms, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗