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PubMed1985

Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995.

We treated four patients with acromegaly for 8 to 24 weeks with SMS 201-995, the long-acting somatostatin analogue, in dosages of 100 to 300 micrograms a day given subcutaneously. A rapid amelioration of the clinical signs and symptoms and near normalization of laboratory test results occurred in all patients. Mean plasma growth hormone concentrations (+/- S.E.M.), as measured over 24 hours, fell from an initial value of 57 +/- 18 micrograms per liter to 7.5 +/- 2 micrograms per liter at the end of the investigational period. Likewise, levels of plasma somatomedin-C, which were originally elevated in all patients, dropped to the normal or nearly normal range. The suppression of insulin secretion and the resulting hyperglycemia that were observed at the beginning of treatment became less marked as therapy progressed. There was evidence of slight tumor shrinkage in three of the subjects. No side effects were recorded throughout the treatment period. These preliminary results suggest that SMS 201-995 represents an additional option for the management of acromegaly, especially in patients who do not benefit sufficiently from surgery or radiotherapy and do not respond well to treatment with dopaminergic drugs.

Acromegaly↗
PubMed1995

Hexarelin, a novel GHRP-6 analog, counteracts the inhibitory effect of hydrocortisone on growth hormone secretion in acromegaly.

Hexarelin (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a GHRP-6 analog with the substitution of D-tryptophan with its 2-methyl derivative. The aim of our study was to ascertain whether hexarelin was able to counteract the glucocorticoid-mediated increase in hypothalamic somatostatin tone and consequent inhibition on serum GH levels in acromegalic patients. Ten patients (5 males, 5 females; age range 27-71 years; BMI range 23.3-35 kg/m2) with active acromegaly underwent: 1) hydrocortisone alone: a bolus iv injection of 100 mg hydrocortisone succinate in 2 mL saline, at time -60 followed by a 120 min iv infusion of 250 mg hydrocortisone succinate in 250 mL saline, from -60 to 60 min; 2) hexarelin+hydrocortisone: a bolus iv injection of hexarelin 100 micrograms, 60 min after initiation of a 2-hour hydrocortisone infusion; 3) hexarelin alone: a bolus iv injection of hexarelin at time 0, 60 min after initiation of a 2-hour saline infusion. The mean GH peak, expressed as percent change with respect to baseline level (mean of -75 and -60 minute samples), after hexarelin (1750 +/- 1157%) did not differ significantly with respect to that observed after hexarelin+hydrocortisone (1120 +/- 770%). After hydrocortisone alone the patients showed a mean decrease in GH levels as compared to baseline levels, of 47 +/- 7%. Our data show that the GH response to hexarelin in acromegaly is resistant to the inhibitor action of an acute and sustained elevation of serum cortisol levels. That hexarelin counteracts the glucocorticoid-mediated inhibition of GH secretion supports the hypothesis of an hexarelin-induced decrease in endogenous somatostatin tone.

Acromegaly↗
PubMed2006

A case of acromegaly in pregnancy: concomitant transsphenoidal adenomectomy and cesarean section.

The case of a 32-year-old woman at 29 weeks gestational age with acromegaly initially diagnosed in pregnancy is presented. During follow-up at 34 weeks of gestation, concomitant emergency cesarean section and transsphenoidal surgery were performed because of advancing vision loss. In tertiary centers, success in pregnancy can be made possible for a patient with acromegaly under the constant supervision of an obstetrician and neurosurgeon.

Acromegaly↗
PubMed1998

The effect of thyrotropin-releasing hormone on gonadotropin and free alpha-subunit secretion in patients with acromegaly and functionless pituitary tumors.

UNLABELLED: Paradoxical response of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and alpha-subunits (alpha-SU) to thyrotropin-releasing hormone (TRH) have previously been reported in individuals with clinically nonfunctioning pituitary tumors (NFT). In the present study, we assessed the in vivo responses of LH, FSH, alpha-SU to TRH in 34 patients with NFT and 29 patients with agromegaly. Twenty-three clinically NFT were postoperatively analyzed by immunocytochemistry and 21 stained positive for beta-FSH and/or beta-LH. Two patients with NFT had elevated basal circulating levels of FSH (41.5 IU/L) and thus were characterized as FSH-secreting adenomas. TRH in these patients increased LH from basal 1.6 IU/L to 32.6 IU/L. In other patients with NFT, circulating levels of glycoprotein peptides were not elevated. TRH induced significant rise of LH in 8 (23.5%), FSH in 5 (14.7%), and alpha-SU in 10 (29.4%) patients with NFT. Thus, a bolus dose of TRH elicited a notable increment in FSH, LH or alpha-SU in 23 of 34 patients with NFT. Among 29 patients with acromegaly, LH rose in 6 (20.7%), FSH in 5 (17.2%), and alpha-SU in 3 (10.3%) patients. IN CONCLUSION: (1) We confirm that most NFTs are capable of synthesizing gonadotropin hormones and subunits (beta-FSH, beta-LH). (2) Most patients in our study responded by either FSH, LH or alpha-SU secretion after TRH, independent of basal hormone levels. Furthermore, recent studies show that by measurement of TRH stimulated beta-FSH and beta-LH one might further improve the diagnostic tools. (3) Gonadotropin response and possibly alpha-SU to TRH are also found in some patients with acromegaly. This could be a marker of a plurihormonal pituitary tumor.

Acromegaly↗
PubMed1993

Evidence for biventricular involvement in acromegaly: a Doppler echocardiographic study.

To investigate left and right ventricular involvement in acromegaly, 20 patients were studied by Doppler echocardiography. Nine of them had systemic hypertension. Right ventricular free wall thickness was significantly increased in acromegalic patients (8 +/- 2 vs 4 +/- 1 mm; P < 0.001). Left ventricular mass index was augmented both in the whole group and in the subgroup of normotensive acromegalics, as compared with normals (134 +/- 33 and 115 +/- 20 vs 80 +/- 18 g.m-2; P < 0.01). Ejection phase indices were normal in the patient group, while impaired left and right ventricular diastolic filling was found. In fact isovolumic relaxation time was prolonged (118 +/- 21 vs 78 +/- 12 ms; P < 0.001), ratio of early to late mitral (0.9 +/- 0.3 vs 1.8 +/- 0.5; P < 0.001) and tricuspid (1.0 +/- 0.2 vs 1.4 +/- 0.3; P < 0.001) flow velocities were significantly decreased as compared with controls. Superior vena cava flowmetry was also abnormal showing a marked decrease of diastolic filling wave and, consequently, of the ratio between peak diastolic and peak systolic flow velocity. No significant differences were observed between normotensive and hypertensive acromegalics, except for left ventricular mass index (115 +/- 20 vs 156 +/- 31 g.m-2; P < 0.01). These findings indicate that abnormal diastolic filling patterns of transmitral, transtricuspid, and superior vena cava flowmetry suggesting 'impaired relaxation' associated with increased left and right ventricular mass, frequently occur in acromegaly.

Acromegaly↗
PubMed1992

Arrhythmia profile in acromegaly.

In a controlled study, the cardiac involvement and arrhythmia profile of 32 patients with acromegaly were correlated with endocrine parameters (somatomedine C, growth hormone), clinical score and duration of the disease. Data were compared with those of 50 controls free of cardiac disease. Stress ECG, 24 h Holter monitoring and echocardiography were performed. Supraventricular premature complexes occurred no more often in acromegalics than in controls. Both prevalence and severity of ventricular arrhythmia, however, were significantly higher in patients compared to controls (P less than 0.01). 15/32 (48%) acromegalic patients had complex ventricular arrhythmias (Lown III-IV) as compared with 6/50 (12%) normal subjects (P less than 0.01). Repetitive ventricular arrhythmias (Lown IV a/b) occurred in 10/32 (31%) patients, but only in 4/50 (8%) controls (P less than 0.01). Furthermore, the frequency of ventricular premature complexes increased with duration of acromegaly (P less than 0.01). No correlation was found between the severity of ventricular arrhythmia and hormone levels. Left ventricular muscle mass was significantly increased (285 +/- 139 g, P less than 0.02) due to concentric hypertrophy. Severity of ventricular arrhythmias correlated with left ventricular mass and with clinical activity score (P less than 0.01). Thus, compared to controls, acromegalic patients show more frequent and complex ventricular arrhythmias and left ventricular hypertrophy. Duration of the disease rather than hormone levels seems to be relevant for these pathological changes.

Acromegaly↗
PubMed1992

Case report: acromegaly and Cushing's disease in a patient with synchronous pituitary adenomas.

A 40-year-old white woman presented with hirsutism, amenorrhea, generalized fatigue, diffuse weight gain, acral changes, and coarsened facial features. Physical examination revealed mild diastolic hypertension, acromegalic features, hirsutism, and seborrhea. The growth hormone concentration was elevated and did not suppress after glucose administration. Urinary free cortisol excretion was increased and was not suppressed during a 2 mg low-dose dexamethasone suppression test. Magnetic resonance imaging of the sella demonstrated a 1.3 x 1.2 x 0.8 cm pituitary adenoma. Trans-sphenoidal resection was performed, and portions of the resected tumor were analyzed by routine pathologic methods. Histopathologic and immunohistochemical findings indicated discrete growth hormone- and adrenocorticotropic hormone-producing pituitary adenomas. Coexisting acromegaly and Cushing's syndrome due to pituitary neoplasia was previously reported in two patients. However, to the authors' knowledge, this represents the first description of a patient with acromegaly and Cushing's disease resulting from discrete synchronous adenomas of the pituitary gland as defined by modern histopathologic techniques.

17-Ketosteroids↗
PubMed1996

Nocturnal monitoring of growth hormone, insulin, C-peptide, and glucose in patients with acromegaly.

Circulating growth hormone, insulin, C-peptide, and glucose levels were compared during the sleep state in adults with acromegaly and healthy control subjects. Growth hormone secretion was episodic in both groups, with the sleep-related growth hormone peak noticeably absent in the acromegalic subjects. The mean nocturnal plasma insulin concentration was greater in the acromegalics. There was no significant difference in the C-peptide between the two groups. Insulin and glucose levels did not show an early morning rise in either acromegalics or healthy subjects. The authors conclude that there is a marked difference in the circulating levels of growth hormone and insulin between the acromegalic and the healthy groups during the sleep state, and there is no sleep-related nocturnal growth hormone peak in the acromegalic subjects. The hyperinsulinism of patients with acromegaly cannot be attributed to excess secretion of insulin.

Acromegaly↗
PubMed2002

A multihormonal pituitary adenoma with growth hormone and adrenocorticotropic hormone production, causing acromegaly and Cushing disease.

Pituitary adenoma with growth hormone (GH) and corticotropin (ACTH) production causing apparent acromegaly and Cushing disease is extremely rare. A 45-year-old woman had a pituitary macroadenoma and severe insulin resistance. Physical examination showed a fully developed acromegaly associated with mild Cushingoid features. Serum GH, insulin-like growth factor-I, ACTH, and cortisol levels were all elevated. Hormonal loading tests resulted in GH levels increasing paradoxically in response to thyrotropin-releasing hormone (TRH), but not corticotropin-releasing hormone (CRH). A similar unexpected increase in ACTH and cortisol levels occurred in response to TRH and GH-releasing hormone. After trans-sphenoidal resection of the pituitary macroadenoma immunohistochemistry revealed the presence of either diffuse but faintly GH-positive cells or sparse but distinct ACTH-stained cells. A marked amelioration of insulin resistance was observed postoperatively. The elevated ACTH and cortisol levels should therefore be investigated by CRH and dexamethasone suppression tests for the coexistence of Cushing disease to exclude the possibility of underlying ACTH-producing tumors.

Acromegaly↗
PubMed1978

Surgical correction of the facial deformities of acromegaly.

The neurosurgical treatment of acromegaly is well established, but little has been written about correction of the facial deformities of this disease. Although hypertrophy of the skin and subcutaneous tissues may decrease after successful treatment of the pituitary tumor, there is no reversal of the bony changes. An acromegalic patient is presented whose facial deformities were repaired in stages by mandibular osteotomy and soft tissue excision. The history and pathology of acromegaly are reviewed.

Acromegaly↗
PubMed1994

The external rhinoplasty approach for the treatment of acromegaly.

Acromegaly produces a syndrome of physiological and physical derangements. Patients afflicted with this disease are often as concerned with the changes in their appearance as with the pituitary tumor. The external rhinoplasty approach to transphenoid hypophysectomy has recently been shown to improve visualization and to have fewer complications compared with the sublabial approach devised initially by Cushing. Three patients are presented in whom this approach was used to simultaneously treat the physiological derangement of acromegaly and to correct the nasal deformity.

Acromegaly↗
PubMed1997

Intrasellar pituitary gangliocyto-adenoma presenting with acromegaly: case report.

OBJECTIVE AND IMPORTANCE: A gangliocytoma in the sellar region is extremely rare. We describe a rare case of intraseller gangliocytoma coexisting with a growth hormone-producing pituitary adenoma, which presented with acromegaly. CLINICAL PRESENTATION AND INTERVENTION: A 64-year-old woman was admitted to our hospital with headache and acromegaly. Endocrinological studies revealed an elevated serum level of growth hormone (GH). Magnetic resonance imaging showed a tumor at the intrasellar and suprasellar regions. The tumor was totally removed via a transsphenoidal approach. RESULTS: A histological examination of the resected specimen showed areas of ganglionic cells and adenomatous cells. Immunohistochemical examination demonstrated GH-releasing hormone-positive ganglionic cells and GH-positive pituitary adenoma. CONCLUSION: Based on these immunohistochemical findings, we hypothesized that the intrasellar gangliocytoma promoted the growth of the pituitary adenoma, which had been transformed from a region of pituitary hyperplasia by chronic overstimulation from excess GH-releasing hormone produced by the intrasellar gangliocytoma.

Acromegaly↗
PubMed1998

Recent results of secondary transnasal surgery for residual or recurring acromegaly.

OBJECTIVE: The results of secondary surgery for either residual or recurring acromegaly have been reported to be unfavorable. To evaluate the effectiveness of recent techniques of secondary transnasal microsurgery, we analyzed the surgical results of remnant or recurring acromegaly in patients who underwent secondary transnasal surgery from 1990 to 1996. METHODS: Secondary transnasal explorations were performed in 28 acromegalic patients (mean age+/-standard error, 39+/-2.3 yr) who had been previously treated with microsurgery (patients at our institutions, n=5; patients at other institutions, n=23). For most of these patients, medical treatment after primary surgery was unsatisfactory. Magnetic resonance imaging demonstrated 18 transnasally resectable tumors (64.3%) and 10 nonresectable grossly invasive tumors (35.7%). Surgical indication was based on elevated plasma growth hormone (GH) levels and evidence of tumor revealed by magnetic resonance imaging. RESULTS: Intraoperative GH measurement was performed in all patients. In 13 of 18 patients with resectable tumors, the surgical assessment with sufficient GH decline intraoperatively was likewise judged as complete and was later proved. In three of five patients with inadequate GH decline, endocrinological remission was achieved by performing further surgery. Thus, an endocrinological remission was achieved in 16 of 18 patients (88.9%) with resectable tumors. In 10 patients with nonresectable tumors, the tumor mass was further reduced. Overall, the endocrinological remission rate was 57.1% (16 of 28 patients). There was no serious morbidity and there was no mortality in this series. CONCLUSION: We conclude that in patients with transnasally resectable tumor residuals or recurrences confirmed by magnetic resonance imaging, endocrinological remissions can be obtained with high probability, even in secondary surgery after an unsuccessful previous operation.

Acromegaly↗
PubMed2001

Transsphenoidal surgery for acromegaly: endocrinological follow-up of 98 patients.

OBJECTIVE: Transsphenoidal surgery is the preferred treatment modality for growth hormone (GH)-secreting pituitary adenomas. In many series, the reported postoperative remission is based mainly on achievement of GH levels less than 2 ng/ml. Strict criteria for insulin-like growth factor I normalization and even lower GH levels (<1 ng/ml) are now suggested to define cure of acromegaly, but the evidence does not yet support such low GH levels in epidemiological follow-up. We analyzed our postoperative results in a large cohort of patients with acromegaly. METHODS: Ninety-eight patients harboring GH-secreting adenomas (46 microadenomas and 52 macroadenomas) underwent transsphenoidal surgery between 1990 and 1999. Ninety-one patients were operated for the first time, and 12 patients underwent reoperations because of previous surgical failure (7 had undergone surgery elsewhere previously). Biochemical remission was defined as a repeated fasting or glucose-suppressed GH level of 2 ng/ml or less, and a normal insulin-like growth factor I level. RESULTS: Remission was achieved in 74% of all patients after one operation, including 84% of patients with microadenomas and 64% of patients with macroadenomas. Seventy-three percent of patients with macroadenomas 11 to 20 mm in size achieved remission, as compared with a 20% remission rate for patients with adenomas larger than 20 mm. Patients with preoperative random GH levels lower than 50 ng/ml had a better outcome (85% remission), whereas GH greater than 50 ng/ml was associated with remission in 30% of the patients. Only one of the patients (8%) with postoperative active disease who underwent a second operation achieved remission. Recurrence was rare (one patient), and all failed surgical attempts could be detected during the immediate postoperative evaluation. CONCLUSION: On the basis of strict postoperative GH and insulin-like growth factor I criteria to define remission, our series demonstrates the efficacy of transsphenoidal surgery for acromegalic patients with microadenomas and noninvasive macroadenomas. However, patients with large adenomas (>20 mm) and preoperative GH greater than 50 ng/ml have a poor prognosis and require adjunctive medical or radiation therapy to control GH hypersecretion.

Acromegaly↗
PubMed1994

Symptomatic Chiari-I malformation in a patient with acromegaly.

We describe, for the first time, a patient with both symptomatic acromegaly and Chiari-I malformation. These conditions could coexist by chance alone, but the probability of both presenting simultaneously in a previously healthy man seem quite remote. Alternatively, acromegaly through associated bony and soft tissue enlargement could lead to the development of symptoms from Chiari-I malformation in this patient.

Acromegaly↗
PubMed2006

Conductive hearing loss in patients with active acromegaly.

OBJECTIVE: There have been rare conflicting results reported concerning possible higher frequency of hearing loss in acromegalic patients. Our goal was to determine whether there is higher frequency of conductive hearing loss in acromegalics and what may cause it if there is any. STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Thirty previously untreated patients with acromegaly were compared with 20 age- and sex-matched healthy control subjects. INTERVENTIONS: In all subjects: Otomicroscopy, tuning fork tests, audiometry tympanometry, cochleostapedial reflex, otoacoustic emissions. In acromegalics: endocrinologic assessment, MRI and if necessary, epipharyngoscopy. MAIN OUTCOME MEASURES: We searched for: 1) Signs of ossicle fixation: absence of stapedial reflex in the presence of normal tympanogram, conductive hearing loss, and absence of or grossly disturbed OAE; 2) Disturbances of middle ear ventilation: excessive negative pressure (tympanogram type C), or middle ear effusion (tympanogram type B). RESULTS: The only statistically significant difference between untreated acromegalics and healthy subjects was the presence of middle ear ventilation problem: 7/30 acromegalics (23%) in comparison to none out of 20 healthy controls (0%), p = 0.033. The acromegalics with middle ear ventilation problem were significantly older, had longer duration of the disease, and lower mean growth hormone (GH) levels in comparison with acromegalics without this problem (51.6 +/- 1.7 vs. 44.4 +/- 2.5 years, 11.6 +/- 2.4 vs. 7.7 +/- 0.4 years, 21.68 +/- 4.89 vs. 49.98 +/- 12.54 microg/L respectively). CONCLUSION: Patients with active acromegaly have more frequent middle ear ventilation problem than normal population, especially those with longer duration of the disease. Possible causes are discussed.

Acoustic Impedance Tests↗
PubMed1975

Hypothalamic hormone interaction in acromegaly.

The growth hormone response to the administration of the currently available synthetic hypothalamic hormones was assessed in eleven patients with acromegaly. Eight of them showed a positive GH response to thyrotrophin releasing hormone and three showed no response. The GH response to TRH was shown to be unrelated to the thyrotrophin response to TRH. The GH response to TRH was inhibited by the administration of growth hormone release inhibiting hormone. Luteinizing hormone/follicle stimulating hormone releasing hormone (LHRH) caused a positive GH response in four patients, but this was trivial in three. The TRH mediated GH release in acromegaly is not mediated via TSH and appears to be attributable to loss of specificity of the receptor sites on the somatotroph to the hypothalamic hormones.

Acromegaly↗
PubMed1976

A comparison of the effect of levodopa and somatostatin on the plasma levels of growth hormone, insulin, glucagon and prolactin in acromegaly.

The acute suppressive effects of L-dopa and somatostatin (growth hormone release inhibiting hormone) on the elevated plasma GH concentrations of seven patients with acromegaly were compared. In addition the effects of the two agents on fasting concentrations of plasma glucose, insulin, glucagon and prolactin were studied. In six of the seven patients hourly samples for GH assay were taken from 08.00 to 20.00 hours on a control day. Synthetic cyclic somatostatin (100 mug) was infused intravenously in an albumin/saline solution over 75 min with a Harvard constant infusion pump. Levodopa 500 mg was given orally. Somatostatin infusion produced a reduction in plasma GH concentrations in six of seven patients (mean reduction 55%). L-Dopa produced a reduction in plasma GH concentrations in the same six patients (mean reduction 52%). The minimum GH concentrations achieved in the two tests were comparable and did not differ significantly from the minimum GH concentrations recorded during the 12 h control study. Mean plasma insulin and glucagon concentrations were also significantly reduced during the somatostatin infusion (P less than 0-025; P less than 0-05 respectively). Plasma glucose concentrations did not change. L-Dopa did not alter mean plasma glucose, insulin or glucagon values. Somatostatin did not alter prolactin values but L-Dopa suppressed basal values to less than 2 ng/ml in five patients. This study shows that the plasma GH change after the administration of L-dopa and somatostatin in acromegaly is comparable and confirms the pancreatic effects of somatostatin.

Acromegaly↗