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PubMed1985

Human pancreatic growth hormone-releasing factor (hpGRF-44) in acromegaly before and after adenomectomy. Modifications induced by somatostatin (GHRIH) infusion.

The influence of human pancreatic growth hormone-releasing factor (hpGRF-44) on GH secretion was investigated in 15 patients with active acromegaly. Following the administration of hpGRF-44 (1 microgram/kg, iv) mean (+/- SE) serum GH level increased from 22.4 +/- 6.3 ng/ml to 42.9 +/- 8.2. ng/ml (peak, p less than 0.01). The pattern and the magnitude of the GH rises were widely variable and it was possible to identify three types of responses: in fact in 2 cases a very large serum GH rise, eight folds over baseline, was observed, in 7 patients a clear GH stimulation, two-three fold over baseline was noticed and in 6 patients no significant GH modifications were seen. No correlation was found between the response to hpGRF-44 and the existence of abnormal GH responses to dopamine infusion, TRH and dopamine-sulpiride test. In 5 acromegalic patients hpGRF-44 was injected again after transsphenoidal adenomectomy. The magnitude of serum GH response decreased in one hyperresponsive patient, increased in 2 previously unresponsive cases and did not change in the remaining cases. In 6 GH responsive patients hpGRF-44 was injected at 120 min during a 4 hour infusion of somatostatin (GHRIH, 3.33 micrograms/min). GHRIH infusion significantly suppressed GH levels in all the patients and blunted the hpGRF-44 stimulated GH increase. The different patterns of GH response to hpGRF-44 in acromegalic patients suggest a different sensitivity of the adenomatous somatotrophs and a possible contribution by normal GH-secreting cells to hpGRF-44 induced GH response.

Acromegaly↗
PubMed1992

Plasma growth hormone (GH) responses to corticotropin-releasing hormone in patients with acromegaly--the effect of dexamethasone pretreatment and the comparison with GH responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and GH-releasing hormone.

It has been reported that paradoxical GH responses to corticotropin-releasing hormone (CRH) occur in only few patients with acromegaly. However, we have observed such responses in 7 of 14 active acromegalic patients. Therefore, we have studied the GH responses to thyrotropin-releasing hormone (TRH) (500 micrograms, iv), gonadotropin-releasing hormone (LHRH) (100 micrograms, iv) and GH-releasing hormone (GHRH) (100 micrograms, iv) in these patients to examine the relationships between the GH responses to CRH and the responses to these hypothalamic hormones. Further, these patients received human CRH (1-41) NH2 (100 micrograms, iv) with or without dexamethasone (Dex) pretreatment (1 mg/100 ml saline, iv, from -30 to +30 min) to study the mechanism of CRH-induced GH secretion, and a perifusion experiment was performed using adenoma tissue obtained at surgery from one patient (10(-7) M CRH and TRH were added) to elucidate whether CRH acts directly at the pituitary level. Aberrant GH responses induced by CRH were found in 7 of 14 (50%) acromegalic patients (TRH responders: 10/13, 77%; LHRH responders: 2/9, 22%; GHRH responders: 10/12, 83%). In these patients, percent GH increment induced by CRH ranged from 81 to 144% (Mean +/- SE, 118 +/- 8%), and the GH peak (19 +/- 3 min) appeared as early as after TRH (23 +/- 4 min, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1994

The evaluation of hypothalamic somatostatin tone using pyridostigmine and thyrotropin releasing hormone in patients with acromegaly.

To indirectly evaluate the hypothalamic somatostatin (SS) tone in patients with acromegaly, the effects of pyridostigmine (PD), a cholinesterase inhibitor which can inhibit hypothalamic SS secretion, on TRH-induced TSH secretion and the effects of SMS 201-995 on TSH or GH secretion were studied in acromegalic patients (31-69 yr, n = 10), normal young (21-24 yr, n = 7) and normal old male subjects (62-71 yr, n = 7). After pretreatment with PD (60 mg po, -30 min), normal young subjects showed significantly enhanced TSH responses to TRH (500 micrograms i.v., 0 min) compared to single administration of TRH, whereas normal old and acromegalic patients did not show such enhancement. Plasma TSH response to a single administration of TRH in acromegalic patients was significantly lower than that of normal young and old subjects. Although normal young and old subjects showed significantly enhanced GH responses to GHRH (100 micrograms i.v. at 0 min) after the pretreatment with PD (60 mg, -30 min), no such enhancement was observed in acromegalic patients. In contrast, the decrement in plasma TSH after SMS 201-995 administration was similar between normal subjects (5 young 5 old) and 7 acromegalic patients. Further, the maximal plasma GH decrement after administration was significantly greater in acromegalic patients than in the 5 normal young and 5 old subjects p < 0.01). In conclusion, hypothalamic SS tone does not appear to be elevated in acromegalic patients compared to normal young and probably old subjects.

Acromegaly↗
PubMed1988

Spontaneous remission of acromegaly after pituitary apoplexy following head trauma.

A 34-year-old man with acromegaly was observed, and the clinical course and various endocrinological deficiencies occurring before, during and after the development of pituitary apoplexy were evaluated. Following the attack, the patient experienced acute reductions in growth hormone (GH) and other pituitary hormones, adrenohypophyseal insufficiency and transient diabetes insipidus which appeared subsequent to glucocorticoid therapy. The level of growth hormone in serum and cerebrospinal fluid (CSF) was measured synchronously, and the respective regressions of GH levels in serum and CSF were observed. The results demonstrated the utility of measuring hormonal levels in CSF in the clinical evaluation of pituitary apoplexy in a patient with a functioning pituitary tumor.

Acromegaly↗
PubMedDate not supplied

Plasma renin activity and urinary aldosterone in acromegaly.

The behaviour of the renin-angiotensin-aldosterone system was evaluated in 16 acromegalic patients, of whom 7 were hypertensive. The patients were studied in basal conditions, after suppression with 9alpha-fluorohydrocortisone, and after stimulation with furosemide. Baseline and after furosemide PRA were significantly lower in acromegalic hypertensive patients than in the normotensive group. Mean urinary aldosterone excretion was found at the upper limits of the normal range; it was occasionally elevated, but the values were not satistically different in the two groups. There was a suppression after 9 alpha fluorohydrocortisone in both groups, though it did not reached the 50%. These data show that there is a disorder of the renin-angiotensin-aldosterone system in acromegalic subjects. This defective regulation is sometimes similar to that present in primary aldosteronism. In fact in two patients a typical phlebographic and scintigraphic picture of primary aldosteronism has been found; surgery, performed in both patients, revealed a large cortical adenoma in one case and a macronodular hyperplasia in the second case. However, the relationship between this adrenal abnormalities and hypertension in acromegaly are not yet completely clarified.

Acromegaly↗
PubMed1990

Acromegaly, multinodular goiter and silent polyostotic fibrous dysplasia. A variant of the McCune-Albright syndrome.

A 36-year-old woman is reported with a possible variant of the McCune-Albright syndrome. The triad was incomplete because of the absence of skin pigmentation and since the sexual precocity was not evident. The presence of a pituitary mass and the secretory dynamics of growth hormone and prolactin were suggestive of a mammosomatotroph cell adenoma. A toxic multinodular goiter was also associated, but unique was the spontaneous normalization of the thyroid function. Unusual was the silent evolution of the polyostotic fibrous dysplasia, which was only fortuitously discovered during magnetic resonance imaging of the pituitary region. Treatment of the acromegaly with the long-acting somatostatin analogue octreotide resulted in an important inhibition of the GH secretion and in a reduction of the volume of the pituitary adenoma.

Acromegaly↗
PubMed1990

Resistance to a long-acting somatostatin analog (SMS 201-995) reversed by surgery in acromegaly.

A 42-year-old woman had acromegaly and a large macroadenoma with supra- and parasellar extension. Her GH levels (median 85 ng/ml, range 63-170 ng/ml) were not responsive to TRH (200 micrograms iv), GHRH (100 micrograms iv) and bromocriptine (Br 2.5 mg po) acute tests; Sm-C level was 8 U/ml. She was treated with octreotide (SMS) (up to 1500 micrograms daily) for 3 months. No changes of clinical, biochemical and radiological findings were seen, therefore she underwent transsphenoidal surgery. After surgery, hypopituitarism and diabetes insipidus appeared: GH levels remained high (median 45 ng/ml; range 37-56 ng/ml), but became responsive to Br acute test. The patient was given SMS again, and this resulted in clinical improvement, marked reduction of GH and Sm-C levels and slight shrinkage of the residual tumor. Speculative hypotheses about this previously unreported phenomenon might be either an excess of both GHRH and somatostatin, caused by a primary increase of dopaminergic tone, or a primary excess only of GHRH; in both cases the surgical lesion of the hypothalamic-pituitary region might have impaired the neurohormones inflow to the residual pituitary and so let SMS and Br exert their inhibitory actions on GH secretion.

Acromegaly↗
PubMed1990

Acromegaly and thymic hyperplasia: a case report.

Growth hormone overproduction is characterized by increased size of visceral organs as well as growth of bone and soft tissues. We describe a case of a 23-year-old female acromegalic patient, who had been previously unsuccessfully operated upon by transsphenoidal pituitary surgery and then irradiated. In November 1987 a routine X-ray chest examination revealed a mediastinal mass, subsequently confirmed by CT scan. The patient underwent surgical removal of the mass: macroscopical aspect, histological sections and immunocytochemistry showed typical thymic structures without any evidence of neurosecretory activity. No GH-positive cells were found and only small amounts of immunoreactive GHRH like material (9.2 ng/g wet wg) were detected in the tumor extract. Before surgery plasma GHRH levels were not elevated (26 pg/ml); serum GH and IGF-I levels were 27.4 +/- 4.9 micrograms/l and 191 nmol/l, respectively, and remained unchanged after surgery. These data ruled out a GHRH and/or GH ectopic production, confirming the primitive pituitary origin of acromegaly in this patient. It is likely that thymic hyperplasia may be explained by longstanding overproduction of GH and the young age of the patient.

Acromegaly↗
PubMed1995

Circadian profile of serum melatonin in patients with Cushing's syndrome or acromegaly.

We evaluated the 24-h profile of serum melatonin (MT) in 16 patients with Cushing's syndrome (11 pituitary- and 5 adrenal-dependent) aged 38.1 +/- 13.8 years and in 19 patients with acromegaly due to GH-secreting pituitary adenoma aged 52 +/- 11.9 years. Thirty-three healthy subjects aged 30 +/- 7 years and 26 healthy subjects aged 59 +/- 12 years served as age-matched controls for the two groups of patients, respectively. All the patients had active disease and were off treatment; none had overt hypopituitarism. Blood drawings were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00 and 06:00 h in controls and patients. Serum MT, cortisol, GH and IGF-I were measured by specific RIA kits and ACTH by IRMA. Cosinor rhythmometry was employed for chronobiological analysis. The acromegalic patients displayed, as a whole group, higher 24-h mean MT levels with respect to age-matched controls (M +/- SD: 52.9 +/- 14.6 vs 32.9 +/- 8.0 pg/ml, p < 0.01) with normally synchronized MT profiles in 11/19 patients. No correlation was apparent between MT and either GH (24-h mean) or IGF-I. In the patients with Cushing's syndrome the circadian profile of serum MT was maintained in 10/16 cases; serum MT levels were comparable to those of controls (48.8 +/- 14.0 vs 50.0 +/- 16.0 pg/ml, NS) without any difference between pituitary- and adrenal-dependent forms. No correlation was found between MT and either ACTH or cortisol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1989

Insulin resistance in acromegaly: evaluation by studies of insulin binding to erythrocytes.

Insulin binding to erythrocytes (RBC) was evaluated in 10 acromegalic patients (6 females and 4 males) in comparison to 22 normal subjects (12 females and 10 males) in an attempt to study the insulin resistance of acromegaly. Basal glucose from all acromegalic patients were within the normal range but incremental glucose and insulin curves, respectively, on oGTT were significantly increased in the acromegalic patients suggesting an insulin resistant state. Basal growth hormone concentrations were elevated in all acromegalic patients, but no correlation was observed between insulin and GH levels. The insulin binding studies in the acromegalic patients showed a decreased binding due to a reduction in the receptor number per cell but with no alterations in the affinity state. Correction of data for creatine, as a procedure of normalization of binding data for a standardized RBC cell age, enhanced the reduction of insulin binding of the acromegalic patients in comparison to controls in consequence to the younger population of acromegalic RBC as indicated by their increased creatine concentrations. In conclusion, the insulin resistant state in acromegalics observed in our study is accompanied by a decrease in the insulin binding to the RBC receptor due to a reduction of the receptor concentration as mediated by the compensatory hyperinsulinemia.

Acromegaly↗
PubMed1998

Pituitary apoplexy in acromegaly, a long-term follow-up study in two patients.

Pituitary apoplexy is a serious complication in about 3% of patients with a pituitary adenoma. Very often, the diagnosis of a functioning or non-functioning adenoma is made in retrospect. In this report, we describe two patients in whom the diagnosis of acromegaly was made before the apoplexy. In one patient, surgical intervention was necessary because of remaining clinical and biochemical activity; in the other patient conservative follow-up was pursued. Seven and nine years after apoplexy, respectively, the patients were clinically and biochemically in remission. During the follow-up, three and five years after apoplexy, respectively, the patients underwent a 10-min venous sampling procedure for 24 hours, and the GH secretory profile was investigated with multiparameter deconvolution analysis and by approximate entropy (ApEn), a scale- and model-independent regularity measure. The deconvolution analysis revealed an increased basal (nonpulsatile) GH secretion rate, while the total 24 h secretion rate was normal compared with 13 healthy male control subjects. ApEn was much larger for each patient than for any control subject value, indicating markedly more irregular GH secretion. We hypothesize that these subtle abnormalities are caused by non-specific damage as a result of vascular insult, leading to abnormal vascular supply, or abnormal autocrine and paracrine GH regulation within the remaining gland.

Acromegaly↗
PubMed1985

Effect of the new ergot derivative terguride on plasma PRL and GH levels in patients with pathological hyperprolactinemia or acromegaly.

Terguride, a derivative of lisuride, has been shown to possess a mixed dopaminergic-antidopaminergic activity in experimental models. We have studied the effects on PRL and GH levels of 0.2 mg po of terguride in 8 normal subjects, in 15 patients with pathological hyperprolactinemia (PHP) and in 17 patients with active acromegaly. In PHP, PRL levels were significantly reduced up to 300 min after terguride with a nadir (45 +/- 4.0% SE) significantly lower (p less than 0.05) than the one observed in the 8 normal subjects (72 +/- 3.5%). There was no significant difference in plasma PRL levels after 0.2 mg terguride or lisuride in 7 out of 15 patients tested with both drugs. Terguride did not significantly modify GH levels in PHP and in normals but when considering basal and peak (occurring between 60 and 150 min) GH values, a significant difference was found (p less than 0.01). Mean peak of GH did not differ significantly between PHP (5.0 +/- 1.1 ng/ml) and normals (6.8 +/- 1.7 ng/ml). Plasma GH levels of 17 acromegalics were not modified by 0.2 mg of terguride but were significantly reduced by 2.5 mg of bromocriptine. Terguride and bromocriptine reduced PRL levels in acromegalics (p less than 0.01) without any significant difference between the two drug. 0.2 mg terguride bid given for 15 days to 7 healthy volunteers significantly reduced both basal and sulpiride (25 mg im)-stimulated PRL levels. Side effects were observed only in 4 out of 47 subjects tested with terguride and in 8 out of 34 tested with bromocriptine.

Acromegaly↗
PubMed1989

Does SMS 201-995 normalize growth hormone secretion in acromegaly? GH day profiles and GH concentrations after oral glucose loading.

GH secretion in acromegaly was studied in 8 patients before and during treatment with SMS 201-995, a somatostatin analogue, 100 micrograms twice daily, by evaluating GH day profiles and GH suppressibility after oral glucose tolerance tests (OGTT). Normalization of GH secretion, estimated by OGTT, was only observed in the three patients who had a decrease in plasma GH to less than 2 micrograms/l after SMS 201-995 injection, and who had the lowest mean plasma GH levels during the day and the largest percent decline of mean plasma GH levels. We conclude that real normalization of GH secretion during SMS 201-995 therapy only occurs in a subset of patients. The data illustrate that the applicability of the generally held cut-off value of 5 micrograms/l, between normal and abnormal plasma GH, has to be reconsidered in the case of chronic intermittent subcutaneous therapy with SMS 201-995.

Acromegaly↗
PubMed1998

Bone mineral density and circulating cytokines in patients with acromegaly.

Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p < 0.01), but not at femoral neck level or at Ward's triangle level (0.92 + 0.15 g/cm2 vs 0.97 + 0.11 g/cm2, p = NS; and 0.74 +/- 0.16 g/cm2 vs 0.85 +/- 0.1 g/cm2, p = NS) when compared to controls. Baseline serum levels of TNF-alpha and IL-1 were in the normal range both in patients and controls. After acute octreotide administration, no differences in circulating TNF-alpha and IL-1 levels were found. In conclusion, acromegalic patients present a reduced BMD at lumbar spine but not at femoral neck level and Ward's triangle. Circulating cytokines such as TNF-alpha and IL-1 are in the normal range. These data suggest that cytokines are not involved in the pathogenesis of GH-excess induced osteoporosis. The possibility that the GH excess might affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.

Acromegaly↗
PubMed2004

Value of petrosal sinus sampling: coexisting acromegaly, empty sella and meningioma.

Simultaneous occurrence of an intracranial meningioma and a growth hormone (GH)-producing pituitary adenoma is exceedingly rare, as is coexistence of an empty sella and acromegaly. We report all these rare entities in the same patient. We evaluated the role of inferior petrosal sinus sampling for lateralisation of an adenoma in this patient.

Acromegaly↗
PubMed1999

Locking of metacarpophalangeal joints in a patient with acromegaly.

A 39-year-old man with acromegaly exhibited locking of metacarpophalangeal (MCP) joints of both index fingers. Large osteophytes were found at the metacarpal heads by radiography and computerized tomography (CT). Magnetic resonance (MR) images revealed hypertrophy of volar plates. We suggest that these characteristic acromegalic features caused locking of MCP joints. Surgery was required on one of the joints to release the locking.

Acromegaly↗
PubMed2002

Hepatocellular carcinoma in a patient with acromegaly and high serum levels of insulin-like growth factor I: report of a case.

A 64-year-old woman with high serum levels of growth hormone, insulin-like growth factor-I (IGF-I), and alpha-fetoprotein resulting from partially treated acromegaly was found to have a tumor under the left diaphragm. The patient also had a history of type C viral hepatitis. Laparotomy revealed that the tumor was fixed to the diaphragm and connected to the liver and spleen. The tumor was excised with partial resection of the diaphragm, liver, and spleen, and a diagnosis of left-sided pedunculated hepatocellular carcinoma (HCC) was made. Further examination showed a higher level of IGF-I receptor mRNA in the tumor than in the normal liver parenchyma. We believe it is likely that the high serum levels of IGF-I may have played a role in the development of the pedunculated HCC in this patient.

Acromegaly↗
PubMed1999

Sphenoidal sinus mucocele after transsphenoidal surgery for acromegaly.

This report concerns one case of a sphenoid sinus mucocele occurring 17 years after transsphenoidal surgery for acromegaly. In 1979, a 51-year-old man was successfully operated by the transnasal transsphenoidal approach for a growth hormone (GH) adenoma 1 cm in diameter. In 1996, the patient was hospitalized for headaches and diplopia. He presented a loss of right visual acuity with paralysis of the right oculomotor nerve. The basal GH level was normal with a satisfactory decrease after oral glucose ingestion. Pituitary sellar radiography showed a disappearance of the posterior clinoid while magnetic resonance imaging revealed the existence of a bilocular, circular, homogeneous lesion of the sphenoid sinus 3 cm in diameter with a posterior and lateral extension. The diagnosis of mucocele was confirmed by surgical treatment, allowing drainage of the mucocele through a transsphenoidal approach. The drained material was composed of sinus epithelium containing many polynuclear and resorptive cells. Postoperatively, the symptoms decreased dramatically, leading to full recovery of visual function and disappearance of the headaches. Apart from the tumor recurrence, the mucocele of the sphenoid sinus can be evoked as a possible long term complication of transsphenoidal surgery for pituitary adenoma.

Acromegaly↗