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PubMed1990

Polypoid Menetrier's disease associated with acromegaly.

There are two forms of Menetrier's disease. The common form involves thickened gastric rugae, while the rare form involves discrete gastric polyps. The clinical literature suggests an association between Menetrier's disease and acromegaly, as well as other neuroendocrine neoplasms; the radiological literature has not addressed the issue. We describe a patient with acromegaly who developed the rare polypoidal form of Menetrier's disease.

Acromegaly↗
PubMed1999

A rare case of acromegaly associated with pachydermoperiostosis.

Pachydermoperiostosis (PDP) is a rare syndrome manifested clinically by finger clubbing, extremity enlargement, hypertrophic skin changes, and periosteal bone formation. The pathogenesis of the disorder has not been clarified and few endocrine abnormalities were apparent. We report here a 58-year-old man with acromegaly associated with PDP, the features of clubbed fingers, coarse skin, and cutis verticis gyrata. Acromegaly due to GH-producing pituitary adenoma was confirmed in endocrinological and pathological studies.

Acromegaly↗
PubMed2000

Short-term pre-surgical treatment with somatostatin analogues, octreotide and lanreotide, in acromegaly.

Eighteen patients with symptoms of active acromegaly were treated with somatostatin analogues for 4 weeks before surgery. Both before and after the treatment, levels of growth hormone (GH), prolactin (PRL), insulin growth factor -I (IGF-I), luteotropin (LH), folliculostimulin (FSH) and subunit alpha of glycoprotein hormones were estimated. Glucose tolerance test, magnetic resonance imaging (MRI) examination, sight acuity and field of vision tests were also performed. The same tests were performed on ten control patients with clinically and biochemically active acromegaly, subjected to surgery but not treated with somatostatin analogues. In six patients treated with somatostatin analogues GH levels decreased significantly to less than 5 ng/ml and in two patients remained elevated while in 10 patients GH level decreased and ranged from 6.1 to 42.9 ng/ml. In 13 patients we observed a decrease in IGF-I to normal levels (<400 ng/dl) and in 3 patients we noted a decrease to levels slightly higher than normal. There was also a slight decrease in alpha subunit concentration. In the glucose inhibition test 4 patients demonstrated normalized GH levels. In patients with elevated PRL and TSH levels, treatment with somatostatin analogues induced their decrease. No changes were observed in levels of LH and FSH. After therapy MRI examination disclosed a decrease in tumor volume in two patients (by 20 and 25%, respectively) and no changes in tumor size in 16 patients. The two patients with a decreased tumor volume also showed normalized glucose tolerance tests. All patients manifested an improved clinical condition. Neurosurgeons disclosed a decreased tumor consistency which greatly facilitated surgical procedure. Our studies documented favourable effects of somatostatin analogues on the assayed hormone levels, and on the general condition of the patients as well as on the course of the surgical procedure itself.

Acromegaly↗
PubMed2001

GH/IGF-I normalization and tumor shrinkage during long-term treatment of acromegaly by lanreotide.

New depot somatostatin analogs such as lanreotide-slow release (LAN) represent a significant improvement in the medical treatment of acromegaly. Seventy-three consecutive acromegalic patients, treated by LAN, were evaluated in a retrospective monocentric study. Sixteen were excluded from further evaluation due to combined treatment with dopamine agonist drugs, early LAN withdrawal for persistence of headache, or gastrointestinal side-effects. Fifty-seven patients (aged 20-82 years, 16 males) were thus evaluated. Thirty-two patients had been previously treated by neurosurgery (Tx) and/or radiotherapy (Rx). After washout, LAN (30 mg) was administered im at 10-14-day intervals. Time intervals between injections were then individually tailored to normalize IGF-I levels. LAN was administered for 12 (6-36) [median (range)] months. GH and IGF-I levels decreased from 13 (7-20) [median (interquartile)] microg/l to 3.2 (1.7-6.2) microg/l (p<0.0001) and from 780 (596-1000) microg/l to 264 (180-530) microg/l (p<0.000001), respectively. Seven patients were resistant to treatment. Among the 50 sensitive patients, GH levels fell below 2.5 microg/l in 52% (and below 1 microg/l in 18%), IGF-I levels normalized in 72% and both results were obtained in 46%. IGF-I values normalized in 87% of patients treated every 14 days, in 100% every 21-28 days, in 69% every 10 days and in 22% every 7 days. No different control of GH/IGF-I hypersecretion was evidenced between patients previously treated or not by Tx and/or Rx. Patients with the lowest basal hormonal levels and those over 55 years showed greater responsiveness (both p<0.05). The maintenance of LAN schedule up to 18 months determined a further suppression (p=0.04 for IGF-I). A reduction of tumor size was shown in 60% of evaluated patients (6/10). HbA1c slightly increased in 42% of patients and gallstones were observed in 16%. LAN is a very effective tool in the treatment of acromegaly: its chronic administration normalizes GH/IGF-I levels in most patients, shrinks the tumor in a high percentage of patients and seems to control hormonal hypersecretion as primary treatment as well as neurosurgery.

Acromegaly↗
PubMed2006

Myocardial systolic strain abnormalities in patients with acromegaly: a prospective color Doppler imaging study.

BACKGROUND: Heart abnormalities are frequent findings in patients with acromegaly: systolic abnormalities are considered to be secondary to diastolic changes. AIM: The aim of the study was to evaluate whether early systolic abnormalities might be revealed in acromegalic patients using the high sensitive color Doppler myocardial imaging (CDMI) technique. PATIENTS AND METHODS: Twenty-two consecutive acromegalic patients with active untreated disease (ACROUNTR) were evaluated at baseline and after a 6-month course with SS analogs (SSa) (ACROSSa); 25 healthy subjects served as controls. All subjects underwent conventional 2D-color Doppler echocardiography, pulse wave tissue Doppler imaging (PW-TDI) and CDMI. RESULTS: Mean left ventricular (LV) ejection fraction did not differ in ACROUNTR and in controls; at variance, ACROUNTR patients had reduced mean LV diastolic function (E/A ratio: 0.96+/-0.3 vs controls: 1.6+/-0.3; p<0.002). Impairment of global LV diastolic function was confirmed by PW-TDI in ACROUNTR patients having a normal systolic function. Regional myocardial systolic strain (epsilon) and strain rate (SR) values, indices of regional systolic heart deformation, were lower in ACROUNTR [epsilonsys (S) -19.8+/-2.9 and epsilonsys (L): -17.7+/-2.2] than in controls [epsilonsys (S): -27.9+/-3.8; p<0.001 and epsilonsys (L): -25.3+/-2.6; p<0.001]. In addition, the early phase of diastolic function, evaluated using SR parameters, was impaired in acromegalic patients (p<0.005 vs controls). Strain and SR values were related to serum GH and IGF-I levels (p<0.02) and greatly improved after a 6-month course with SSa [epsilonsys (S) improved to -23.8+/-3.8 (p<0.05) and epsilonsys (L) improved to -24.7+/-2.4 (p<0.03)]. CONCLUSIONS: Our study confirms that ACROUNTR patients have impaired diastolic function. More important, our study clearly shows that ACROUNTR patients have an impairment of regional myocardial systolic function, which is not secondary to diastolic changes. These intramyocardial functional abnormalities improved during medical treatment of acromegaly. It is conceivable that GH-IGF-I excess has detrimental effects either on the diastolic or the systolic phases of heart function.

Acromegaly↗
PubMed2003

Three-hour spontaneous GH secretion profile is as reliable as oral glucose tolerance test for the diagnosis of acromegaly.

The diagnosis of acromegaly, in an appropriate clinical context, usually relies on lack of GH suppression below 1 microg/l during OGTT coupled with elevated IGF-I levels. On the other hand, in normal subjects glucose-induced inhibition of GH secretory bursts without any further decrease of interpulse GH levels had already been shown. Based on the foregoing, we aimed to compare the diagnostic reliability of OGTT-induced GH nadir with that recorded during 3-h spontaneous GH secretion. In 59 acromegalic patients (17 male and 42 female, age, mean +/- SE 51.5 +/- 1.9, range 21-76 yr) and in 82 normal subjects (43 male and 39 female, age, mean +/- SE 35.7 +/- 1.5, range 15-72 yr) GH secretion was evaluated every 30 min from 0 to 180 min during slow saline infusion or OGTT (75 g at 0 min). A nadir GH concentration below 1 microg/l was recorded in all normal subjects either during OGTT or saline infusion if GH secretion was evaluated over 180 min. In contrast in acromegalic patients a nadir GH concentration below 1 microg/l never occurred in both conditions. This study shows that a 3-h spontaneous GH profile is as reliable as OGTT in the diagnosis of active acromegaly.

Acromegaly↗
PubMed2005

Pituitary tumor disappearance in a patient with newly diagnosed acromegaly primarily treated with octreotide LAR.

We describe the case of an acromegalic patient primarily treated with octreotide LAR in whom the pituitary tumor disappeared after 18 months of treatment. A 68-yr-old woman, with clinical suspicion of acromegaly, was admitted to our Unit with the ultrasonographical evidence of cardiac hypertrophy, arrhythmias, right branch block and interatrial septum aneurism. She referred hands and feet enlargement since the age of 30 and facial disfigurements since the age of 50. At the age of 45 she underwent surgery for carpal tunnel syndrome and at the age of 61 an euthyroid nodular goiter was diagnosed. Hormonal evaluation showed elevated circulating GH levels (25+/-3.2 ng/ml), not suppressible after oral glucose load, and elevated IGF-I levels (646 ng/ml), whereas the remaining pituitary function was normal. Visual perimetry was normal, whereas magnetic resonance imaging (MRI) showed an intrasellar pituitary adenoma with maximal diameter of 9 mm. In order to improve cardiovascular function before surgery, the patient started octreotide LAR 20 mg every 4 weeks for 3 months. Then based on IGF-I values, the dose was adjusted to 30 mg. After 6 months a second MRI showed significant tumor reduction (>50% of baseline maximal diameter), GH and IGF-I were within the normal range and the patient continued the treatment. After one-year therapy, an improvement of cardiac alterations was recorded and the patient was referred to the neurosurgeon. However, she refused the operation. At 18-month follow-up, MRI showed the complete disappearance of direct and indirect signs of pituitary adenoma. To our knowledge, this is the first case of complete radiological remission of pituitary tumor during octreotide LAR treatment in acromegaly.

Acromegaly↗
PubMed1999

Twenty-four hour profile of blood pressure in patients with acromegaly. Correlation with demographic, clinical and hormonal features.

Cardiovascular events are frequently reported in patients with acromegaly and they are usually related to arterial hypertension. Aim of the present study was to assess the 24-hour profile of blood pressure (BP) and heart rate (HR) in patients with active acromegaly and to correlate them with clinical and hormonal data. Sixteen patients and 16 healthy, age and sex matched subjects underwent ambulatory blood pressure monitoring by means of a portable automatic device (SpaceLabs monitor 90207, Kontron) with measurements every 20 minutes for 24 hours. The presence of the nocturnal fall was assessed by the calculation of the night-day systolic and diastolic ratio. The mean 24-hour diastolic BP was significantly higher in acromegalic patients than in controls (79.1+/-11.5 mmHg vs 70.8+/-5.3 mmHg, p<0.05) and the circadian diastolic profile was flatten. In fact, 10/16 patients were defined as nondippers while this figure was 2/16 in the control group (62% vs 12%, p<0.01). Also the mean 24-hour systolic BP was higher in acromegalic patients than in controls (124.8+/-17.2 mmHg vs 114.1+/-8.6 mmHg, p<0.05). The circadian systolic profile paralleled that of diastolic and was flatten, without a significant nocturnal fall. Ten out of 16 patients were nondippers compared to 2/16 controls (62 vs 12%, p<0.01). No significant correlation was found between mean 24-hour BP, either diastolic or systolic, and demographic or hormonal characteristics of the patients. HR patterns did not differ between patients and controls and were characterized by a prominent nocturnal fall.

Acromegaly↗
PubMed1997

Twenty-four hour melatonin pattern in acromegaly: effect of acute octreotide administration.

We investigated the melatonin (MT) circadian rhythm before and after somatostatin (octreotide) acute administration in ten subjects (4 M, 6 F. 23-52 yr old) with active acromegaly due to pituitary microadenoma. Blood samples were drawn every 2 hours over a 48-h span; after 24-h basal blood collection, octreotide (Sandostatin, Sandoz) 100 micrograms sc/8 h was administered. As control, 7 healthy adult subjects (3M, 4F; 26-50 yr old) were studied in basal condition over a 24-h span. Plasma MT and GH levels were measured by RIA in each sample, IGF-1 levels were measured by immunoradiometric assay in basal and after octreotide morning samples. The comparisons were made by Mann-U-Withney and Wilcoxon test as appropriate; the existence of a MT circadian rhythm was validated by cosinor analysis; GH and MT values were correlated by Pearson's correlation coefficient. All of 7 control subjects and 2 of 10 acromegalics had significant 24-h MT rhythm. The area under curve (AUC), mesor and amplitude of the MT rhythms in acromegalics were significantly lower than in the controls (p < 0.001, 0.002 and 0.0006, respectively), with an earlier acrophase (median value: 22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH concentrations were significantly increased in acromegalics in comparison with the control group. Octreotide administration significantly reduced GH, restoring a circadian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC not different from controls. Mean amplitude still remained lower than controls (p < 0.0006), with an earlier acrophase (median 00:01 h). No significant correlation was found between individual GH and MT levels. Our data indicate a reduction of MT circadian secretion in acromegaly, due especially to a blunted nocturnal increase with earlier MT peak; moreover, acute octreotide administration increase MT levels without modifying amplitude and phase of night-time secretion significantly. These findings suggest a negative interrelationship between GH and MT secretions or a facilitatory influence of somatostatin on daytime MT release only. This partial recovery of pineal secretion after octreotide in acromegalics could be a clinically significant contribution to improve their quality of life, considering that MT is involved in the regulation of several important functions.

Acromegaly↗
PubMed2004

Cerebral aneurysm and acromegaly: a case report.

Few cases are reported concerning the association between cerebral aneurysms and acromegaly, and this is the first case report documenting an increase in diameter of a cerebral aneurysm in persistent acromegaly. Persistently elevated GH plasma levels might promote an increase in diameter of cerebral aneurysms. An accurate follow-up in acromegalic patients is important, especially concerning the cerebrovascular system. Establishing the effectiveness and usefulness of this strategy will require future prospective studies.

Acromegaly↗
PubMed1995

A prospective multicenter octreotide dose response study in the treatment of acromegaly.

The somatostatin analog octreotide has proven to be an effective form of treatment for various hypersecretory states including acromegaly. This report describes the effects of escalating doses of octreotide on the growth hormone (GH) profiles, insulin-like growth factor-1 (IGF-1), prolactin (PRL), and adverse effects in 99 patients with acromegaly. Treatment with octreotide was initiated at 50 micrograms sc every 8 h and the dose gradually titrated to a maximum of 1500 micrograms/d if more than 75% of GH determinations in a 12-h day profile were above detection limits. This dose was maintained for the duration of 6 months. Seventy-three percent of patients did not reach the GH reduction criterion at the 300 micrograms dose. Mean GH levels decreased from 33 +/- 4 micrograms/l to 10 +/- 1 microgram/l (p < 0.001) while receiving the 300 micrograms/d dose. The percentage decrease in mean GH levels, however, was dose-independent reaching 50 +/- 5% of baseline with 300 micrograms/d, 55 +/- 5% with 600 micrograms/d, 57 +/- 6% with 900 micrograms/d, and 56 +/- 5% with 1500 micrograms/d. Maximal GH suppression, however, was achieved in 40%, 17%, 7%, and 16% of subjects by the 300 micrograms, 600 mg, 900 micrograms, and 1500 micrograms doses respectively. GH suppression was independent of duration of treatment. While there was a tendency for a greater degree of IGF-1 reduction with the higher doses, the rate of normalization (30-37%) was not influenced by the dose of octreotide administered. Elevated PRL levels also declined with the use of higher doses of octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Coexisting acromegaly and a unilateral cortisol-producing adrenal adenoma: a possible variant of multiple endocrine neoplasia type I.

An unusual case of coexisting acromegaly and Cushing's syndrome is reported in a 34-yr-old female. There was no biochemical or morphological evidence to suggest the presence of other endocrinopathies. She did not have any family history to suggest a hereditary tendency to endocrine disorders. Her acromegaly and Cushing's syndrome were proven to be due to a pituitary somatotroph adenoma and a cortisol-producing adenoma in the right adrenocortex, respectively. Surgical removal of both tumors led to a marked biochemical improvement of the two endocrinopathies. To account for the simultaneous occurrence of the two endocrine tumors, at least two endocrine syndromes may be considered. One of them is Carney's complex. However, Cushing's syndrome in this complex is unexceptionally due to primary pigmented nodular adrenocortical disease, differing from the adrenal pathology of our patient. In addition, a lack in this case of any other characteristic suggestive of this syndrome appears to speak against this possibility. A second possibility is multiple endocrine neoplasia type 1. The absence of a parathyroid or pancreatic islet cell tumor does not strongly support this possibility, but adrenocortical lesions are not rare in this syndrome although they are only rarely functional. However, existence of similar case reports, although very few, in the literature leaves the possibility that she represents another rare variant of sporadic multiple endocrine neoplasia type I syndrome.

Acromegaly↗
PubMed2006

Resistance to somatostatin analogs in acromegaly: an evolving concept?

The aim of acromegaly treatment is to control the disease by suppressing GH hyperactivity and reducing the size or impeding the growth of the pituitary GH secreting mass. Over recent years, many studies have emphasized the role of SS analogs in the treatment of acromegaly. In fact, SS analogs have been demonstrated to be an effective tool not only in the control of GH hypersecretion but also more recently in the control of tumor growth, in a relevant number of acromegalic patients both as primary or adjunctive treatment. In this context, the therapeutic failure of medical treatment with SS analogs needs to be accurately defined particularly when they are used as primary treatment but also when they are given to patients previously operated upon, since other effective therapeutic options are nowadays available. Current definition of resistance to SS analogs is based on their efficacy to control GH and IGF-I. However, due to the emerging significance of the shrinkage effect of SS analogs on pituitary adenomas as well as to the apparent dissociation between this effect and the biochemical effects of treatment with these analogs, an evolution in the concept of SS resistance is likely to be occurring. In this review, we will discuss the biological basis of the discordance between biochemical and volumetric effects of SS analogs, and we will address the intriguing clinical and therapeutic aspects related to a possible redefinition of the resistance to SS analogs.

Acromegaly↗
PubMedDate not supplied

Hypoproteinemia in acromegaly.

Although it is well known that growth hormone may influence protein metabolism, few investigations have been undertaken on serum protein levels in acromegaly; recently hypoglobulinemia has been observed in this endocrine disorder. In 28 acromegalic patients and 56 control subjects sera have been analyzed for total protein determination and for electrophoretic protein separation. The results have shown that in acromegalic there is a slight but statistically highly significant decrease of serum total protein (mean +/- SE 6.66 +/- 0.07 g/100 ml vs 7.10 +/- 0.07 g/100 ml), albumin, alpha 1 and alpha 2-globulins. Since growth hormone stimulates protein synthesis, the pathophysiological significance of hypoproteinemia of acromegaly is at present obscure.

Acromegaly↗
PubMed1988

Criteria for the cure of acromegaly: comparison between basal growth hormone and somatomedin C plasma concentrations in active and non-active acromegalic patients.

Fasting plasma growth hormone (GH) and somatomedin C (SmC) levels were compared as criteria for the cure of acromegaly in 7 untreated and 16 treated acromegalic patients studied 1 to 16 yr after pituitary surgery and/or radiotherapy. The patients without active disease presented a significant correlation between GH and SmC. Only when basal GH was lower than 2.5 ng/ml were SmC values within the normal range. The subjects with active acromegaly (both treated and untreated) presenting GH higher than 5 ng/ml did not show any correlation between GH and SmC levels.

Acromegaly↗
PubMed1988

Effects of theophylline infusion on the growth hormone (GH) and prolactin response to GH-releasing hormone administration in acromegaly.

Since theophylline has been shown to blunt the GH response to growth hormone-releasing hormone (GHRH) in normal subjects, we investigated whether the same effect of theophylline administration could be reproduced in patients with active acromegaly. Ten acromegalic patients received on two different days 100 micrograms GHRH iv alone and the same GHRH dose during a constant infusion of theophylline (3.56 mg/min), beginning 2 h before GHRH administration. In the whole group theophylline did not affect basal GH secretion significantly (from a mean of 44.6 +/- 14.4 at 0 min to 41.8 +/- 13.5 ng/ml at 120 min). However, the amount of GH released after GHRH stimulation was lower when theophylline was concomitantly infused (7525 +/- 3709 ng min/ml vs. 12038 +/- 6337 ng min/ml; p less than 0.05). The inhibitory effect of theophylline was not homogeneous, since either marked or minimal reductions of the GHRH-stimulated GH secretion occurred. Serum PRL levels increased after GHRH administration in 6 patients and theophylline infusion had no influence upon this response. Peak GHRH levels were not different in both studies (14.9 +/- 1.7 and 17.1 +/- 4.0 ng/ml, respectively). Free fatty acid levels rose progressively during theophylline administration (from 0.66 +/- 0.10 at 0 min to 1.04 +/- 0.10 mEq/l at 240 min) and were significantly higher than after GHRH stimulation alone from 180 min up to the end of the test. Our results demonstrate that in active acromegaly theophylline blunts the GH response to GHRH, though this effect is not uniformly seen in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed2006

[Treatment of pituitary gland hyperfunction: from acromegaly to prolactinoma].

Evidence based drug therapy is currently available for the treatment of prolactinomas and growth hormone secreting adenomas (acromegaly). Dopamine agonists such as bromocriptine, quinagolide or cabergoline represent the standard therapy for the treatment of micro- and macro-prolaktinomas. In pregnancy, more differentiated, individual and patient-adapted therapeutic procedures have to be considered. Transsphenoidal adenomectomy is the treatment of choice for patients suffering from acromegaly. If biochemical cure (defined by normalized IGF-1 serum levels or by a GH nadir <1 microg/l during a 3-h oral glucose tolerance test) cannot be achieved, somatostatin analogues such as octreotide and lanreotide are effective. In some cases, dopamine agonists can be added. In therapy-resistant cases, growth hormone receptor antagonists can be used.

Acromegaly↗
PubMed1997

MRI of pituitary adenomas in acromegaly.

Adenomas causing acromegaly represent at least a quarter of pituitary adenomas. We studied 12 patients presenting with active acromegaly due to a pituitary adenoma with a 1.5 T superconductive MRI unit. All had T1-weighted sagittal and coronal sections before and after Gd-DTPA; six had coronal T2-weighted images. Surgical correlation was obtained in seven patients. Histologically, there were eight growth hormone (GH)-secreting and three mixed [GH and prolactin (PRL) secreting] adenomas, and one secreting GH, PRL and follicle-stimulating hormone. Macroadenomas (10) were more frequent than microadenomas (2). No correlation was found between serum GH and tumour size. There were nine adenomas in the lateral part of the pituitary gland; seven showed lateral or infrasellar invasion. Homogeneous, isointense signal on T1- and T2-weighted images was observed in six cases. Heterogeneous adenomas had cystic or necrotic components.

Acromegaly↗