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PubMed1981

No effect of bromocriptine in acromegaly: a controlled trial.

Although bromocriptine, a dopamine receptor agonist, is now widely used in the treatment of acromegaly, there have been no controlled trials of its biochemical or clinical effects on this disorder. We assessed its effects in a double-blind, crossover study. Eighteen patients with acromegaly were given bromocriptine and placebo alternately for three months per medication. Their responses to oral glucose-tolerance tests during the two regimens did not differ significantly. The number of patients noting amelioration of clinical symptoms during treatment with bromocriptine was almost identical to the number with clinical improvement during placebo. We conclude that it remains doubtful whether bromocriptine has a beneficial effect in acromegaly.

Acromegaly↗
PubMed2002

Elevated intraocular levels of insulin-like growth factor I in a diabetic patient with acromegaly.

Growth factors have become increasingly associated with various events of vitreoretinal disease. In the presence of proliferative retinopathy, elevated levels of insulin growth factor I (IGF-I) have been demonstrated in the vitreous. IGF-I expression itself is regulated by growth hormone, a hormone that is involved in the pathogenesis of acromegaly. In the present paper we report on the detection of very high IGF-levels in the subretinal fluid of a patient with acromegaly who was operated for retinal detachment. With a very sensitive RIA assay we found a four-fold elevation of the serum levels of IGF-I (604 ng/ml) and a high level of IGF-1 in the subretinal fluid (13 ng/ml). It is concluded that acromegaly may lead to an overexpression of IGF-I not only seen as increased concentrations in serum and vitreous, but in the subretinal space as well. This study emphasizes the need for further investigation of growth factor presence in pathological cavities, such as the subretinal space during retinal detachments.

Acromegaly↗
PubMed2001

Evaluation of surgery for acromegaly: role of intraoperative growth hormone measurement?

OBJECTIVE: Intraoperative growth hormone (GH ) measurement has earlier been tried to improve surgery for acromegaly. We calculated GH half-life after adenomectomy and evaluated the possible role of this variable in predicting the final outcome of pituitary surgery in 28 consecutive patients with acromegaly. The sensitivity, specificity and predictive values were determined in relation to the results from GH suppression during an oral glucose load and IGF-1 3 months postoperatively. The GH half-life data were also compared to the corresponding results obtained from GH measurements between 60 min and 180 min after adenomectomy, and early, within 1 week, postoperatively. RESULTS: GH half-life < or =31 min was recorded in 8/13 cured patients but also in 2/15 unsuccessful cases. A mean GH concentration < or =4.4 mU/L between 60 min and 120 min after adenomectomy was found in 11/13 cured subjects but also in 3/15 not cured patients. A mean GH < or =4.0 mU/L between 90 min and 180 min was found in 11/13 cured and in 4/15 not cured patients. A mean early postoperative GH concentration < or =2.6 mU/L was noted in all 13 cured patients, but also in 2/13 unsuccessful cases. The specificity of early postoperative GH < or = 2.6 mU/L was 100% compared to 62% for a GH half-life < or =31 min (p<0.05) and 85% for the GH mean values between 60 min and 120 min and 90 min and 180 min, respectively. The sensitivity for persistent disease of values above the four cut-off limits used was between 73% and 87%. The positive predictive value for a mean early postoperative GH value >2.6 mU/L was 100%, and 72% for a GH half-life >31 min (n.s.). CONCLUSION: Although intraoperative GH half-life might be useful in some cases, it was not a reliable tool for predicting outcome of pituitary surgery in acromegaly. In cases with a 51% decrease of a basal GH concentration >5.5 mU/L, mean GH values < or =4 to < or =4.4 mU/L late intraoperatively were more informative but not as good as those obtained from the mean of a series of GH values drawn on one occasion within 1 week postoperatively, offering a 100% specificity for cure if < or =2.6 mU/L. Intraoperative GH half-life measurements should therefore be used with caution. The predictive values of the cut-off limits used in this study should be further evaluated before general application.

Acromegaly↗
PubMed2004

Bilateral testicular enlargement and seminoma in a patient with acromegaly.

Growth hormone (GH) excess has been associated with soft tissue changes and an increase in the incidence of colonic polyps and gastrointestinal cancer. We describe a patient with endogenous GH excess caused by a pituitary tumour, resulting in acromegaly. The patient had bilateral testicular enlargement, with tumour of the right testicle. Pituitary MRI revealed a macroadenoma. After resection of the pituitary tumour, GH levels fell below 0.5 ng/ml, with acromegaly resolution. Testicular resection revealed seminoma. Following acromegaly resolution, the enlarged remaining testicle decreased in size. The implications of the testicular enlargement and seminoma in the presence of a GH-secreting tumour are discussed.

Acromegaly↗
PubMed2005

Is there an association between acromegaly and thyroid carcinoma? A critical review of the literature.

Patients with acromegaly may have higher rates of cancer, possibly due to increased plasma levels of IGF-I, which is known to promote cellular growth. While simple and multinodular goiters are more common among acromegalics, reports of thyroid carcinoma are rare, and its true incidence is unclear. Here, we review the relevant literature in the context of a case of a patient with acromegaly with persistently elevated IGF-I levels who was subsequently diagnosed with thyroid carcinoma. The incidence and potential pathophysiologic mechanisms of benign and malignant thyroid disease in acromegaly are discussed. We conclude that in acromegalic patients with persistently elevated IGF-I levels, one should ensure careful monitoring of goiter and thyroid nodules, including fine-needle aspiration of nodules that are 1 cm or larger.

Acromegaly↗
PubMed1999

Clinical characteristics of acromegaly in Hong Kong.

This study analyses the clinical characteristics of acromegalic patients in Hong Kong. All patients with acromegaly under follow up in Prince of Wales Hospital, Hong Kong between January 1984 and December 1992 were reviewed retrospectively. Detailed hospital notes were available for review in 28 out of 34. Of the 28 patients with full records available, 27 were Chinese and 1 was Nepalese. There were 8 (28.6%) males and 20 (71.4%) females. The mean age (+/- SD) at presentation was 51.2+/-16.8 years (range: 28 to 84 years) (male, 49.9+/-13.9 years [range: 28-66]; female, 51.7+/-18.1 years [range: 31-84]; p-value: NS). The commonest mode of presentation (n=22, 78.6%) was clinical suspicion by medical staff during consultation for other conditions, acromegaly being later confirmed. The estimated duration of symptoms, before diagnosis, was 14 years (range: 1 to 30 years). CT scan imaging of the pituitary gland showed that 12 patients (42.9%) had pituitary macro-adenomas (> or =1 cm), 3 (10.7%) had micro-adenomas (<1 cm), 6 (21.4%) had normal imaging, 1 (3.6%) had an empty sella and 6 (21.4%) had suspicious but inconclusive lesions in the pituitary gland. Surgery was offered as initial treatment to all patients. 4 to 6 weeks after surgery, if the maximal growth hormone response following glucose loading exceeded 10 microg/L, radiotherapy was offered. Of the 28 patients, 13 received surgery and radiotherapy, 2 surgery only, 4 radiotherapy only, 4 no treatment and 5 defaulted. At presentation, 50% had some abnormality of glucose tolerance. The mean early morning fasting baseline growth hormone was 52.8+/-37.0 microg/L (mean +/- SD, median: 48.1 microg/L) and the maximal growth hormone response during an extended oral glucose tolerance test was 63.2+/-34.9 microg/L (median: 61.3 microg/L). Forty five percents of patients had a maximal growth hormone response exceeding 60 microg/L. Of the 19 patients who underwent surgery and/or radiotherapy, 15 had their pituitary function reassessed 6 months after intervention. Their early morning fasting growth hormone and maximal growth hormone response in an extended oral glucose tolerance test were 21.3+/-25.8 and 35.4+/-37.5 microg/L, respectively. In conclusion, acromegaly in Hong Kong has an estimated annual incidence of 3.8 per million. There is a female preponderance, tendency to late presentation (>10 years) and low number of large tumors. Up to 80% were referred following observer suspicion.

Acromegaly↗
PubMed2005

Reduced nitric oxide levels in acromegaly: cardiovascular implications.

Acromegaly is characterized by major cardiovascular alterations. Although the underlying mechanisms of these vascular modifications have not been elucidated, recent studies have focused on endothelial dysfunction. Nitric oxide (NO) may contribute to increased vascular resistance, reduced platelet aggregation, inhibition of smooth muscle cell proliferation, and reduction of lipoxygenase activity. At present, no data on NO production in acromegalics are available. The aim of this study was to evaluate the effect of high levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) present in acromegaly on NO pathway to investigate the role played by this molecule in the cardiovascular changes experienced by these patients. We studied 13 acromegalics and 12 sex- and age-matched normotensive controls. Platelet NO levels were measured in the supernatant of lysed platelets. Endothelial NO synthase (eNOS) was determined by Western blot analysis of platelets. NO concentrations were significantly reduced in patients (p<0.0001). There were no differences between male and female patients, nor were platelet NO levels and the presence/absence of hypertension related in acromegalics; by contrast, NO concentrations inversely correlated with GH (p=0.03) and IGF-1 (p=0.04) levels, and with disease duration (p=0.04). eNOS protein concentrations were significantly reduced in the platelets of patients compared with controls (p<0.0001). This study demonstrates for the first time a strong reduction in platelet NO concentrations in acromegalic patients due to reduced eNOS expression. Moreover the inverse correlation of NO levels with GH, IGF-1 and disease duration suggests that reduced levels of platelet NO linked to GH excess may contribute to the vascular alterations affecting patients with acromegaly.

Acromegaly↗
PubMed1998

Uterine leiomyomata--a feature of acromegaly.

In order to assess the prevalence of leiomyomata in patients diagnosed with acromegaly, files of all women so diagnosed were obtained (n = 25). Eight of these patients had undergone hysterectomy. In eight of the remaining patients, assessment of the uterus was performed by gynaecological examination and transvaginal ultrasound. The prevalence of leiomyomata was 81% (13/16) in patients who had undergone hysterectomy (8/8) or who underwent gynaecological examination (5/8). In conclusion, the very high prevalence of leiomyomata in patients diagnosed with acromegaly warrants the inclusion of growth hormone excess as a cause of leiomyomata. Leiomyomata are a feature of the organomegalic syndrome associated with acromegaly.

Acromegaly↗
PubMed2000

Anaesthetic complications of acromegaly.

The anaesthetic risks of acromegaly include difficulties in airway management, hypertension, and cardiac, gastrointestinal and renal problems. To estimate the incidence of major complications in this rare group of patients, we reviewed 28 patients with acromegaly who had pituitary tumour excision over a 10-yr period. Each patient was matched for age, weight and sex to a non-acromegalic patient undergoing transsphenoidal pituitary surgery. Acromegalic patients received significantly more fentanyl and midazolam and less thiopental and succinylcholine than controls (all P < 0.05). Mean arterial pressure (baseline, minimal and maximal values) was higher in acromegalic patients than in controls. There was no difference between groups in the use of vasoactive drugs. PaO2, FIO2 and PaCO2 were similar in both groups. Arterial pH was significantly lower (P = 0.015), blood glucose was higher (P < 0.001) and fluid intake minus output was higher (P = 0.04) in acromegalic patients than in controls. Airway difficulty and tongue enlargement were encountered more often in acromegalic patients (P = 0.002 and P = 0.001, respectively). Our data confirm that in acromegalic patients: airway difficulties occurred more frequently; severe haemodynamic instability did not typically occur during surgery for acromegaly; pulmonary gas exchange was not altered during operation; glucose intolerance may be an intraoperative problem; and fluid regulation may be altered.

Acromegaly↗
PubMedDate not supplied

Aldosterone in acromegaly.

Ten patients with acromegaly, six with active acromegaly and four with inactive acromegaly were studied with regard to the possible relationship between aldosterone metabolism and hypertension. It was noted that tetrahydroaldosterone-3-glucuronide levels were highest in those cases which exhibited the highest prolactin levels. It was in these cases that hypertension was present and they were active as judged by clinical and biochemical parameters. On administration of bromocryptine there was a reduction of tetrahydroaldosterone-3-glucuronide, prolactin and also a significant reduction of blood pressure. The significance of these results is discussed.

Acromegaly↗
PubMed1988

Relief of sleep apnea in acromegaly by bromocriptine.

A patient with longstanding acromegaly complicated by sleep apnea was treated with bromocriptine prior to surgery. In addition to a significant reduction of the plasma growth hormone concentration and measurable decrease in acral overgrowth, a dramatic improvement of the sleep apnea was observed. After three months of therapy, the amount of sleep time occupied by apneic episodes fell from 48 to 12%. The response indicates: (a) that the sequelae sleep apnea in acromegaly can be improved even when ablative therapy of the pituitary is impossible and (b) bromocriptine may prevent perioperative complications caused by clinically significant airway obstruction in patients with acromegaly.

Acromegaly↗
PubMed2004

Enlarged extraocular muscles as the presenting feature of acromegaly.

: The authors report the case of a 32-year-old woman who presented with bilateral lower eyelid swelling and extraocular muscle enlargement as the initial manifestation of acromegaly. The acromegaly, however, was not diagnosed until 6 years after her symptoms began. Acromegaly should be entertained in the differential diagnosis of any patient who presents with bilateral, symmetrical extraocular muscle enlargement on computed tomographic scan, especially in the patient with normal thyroid hormone levels and no clinical findings associated with thyroid orbitopathy.

Acromegaly↗
PubMed1982

Changes in circulating somatomedin-C levels in bromocriptine-treated acromegaly.

To determine whether the improvement in clinical status of patients with active acromegaly correlates with a reduction of circulating somatomedin-C, serum immunoreactive somatomedin-C was measured in twenty-seven patients before and during bromocriptine therapy. The patients were assessed using a clinical and metabolic score which included both subjective criteria of improved sweating and facial features, and objective criteria of a reduction in ring circumference and the area under the glucose tolerance curve. Using this, together with the change in GH levels before and during bromocriptine therapy, the patients could be divided into three groups. In one group, there was no clinical improvement, a less than 30% decline in somatomedin-C, and in four of six patients no significant decline in GH. In both the other groups there was clinical improvement and a greater than 30% decrease in somatomedin-C. In one of these two groups, however GH did not decline, while in the other it was reduced significantly. The results suggest that during bromocriptine treatment of acromegaly, serum somatomedin-C concentrations correlate better with clinical status that does serum GH. Since some patients have no significant fall in GH but show both clinical improvement and a reduction in somatomedin-C, it seems likely that in some patients bromocriptine may improve acromegaly by a mechanism other than a simple decrease in total immunoreactive GH secretion.

Acromegaly↗
PubMed1984

Familial acromegaly.

An uncle and nephew with acromegaly are described. Two other families with acromegaly have been reported by others and three other possible cases are reviewed. Our patients are unlikely to form part of the multiple endocrine neoplasia (MEN) type 1 syndrome because of the absence of other endocrine disease at an advanced age. A family history of acromegaly should be considered in those presenting with the disease.

Acromegaly↗
PubMed1984

Plasma growth hormone suppressive effect of bromocriptine in acromegaly. Evaluation by plasma GH day profiles and plasma GH concentrations during oral glucose tolerance tests.

In most studies reporting favourable results of chronic bromocriptine treatment in acromegaly, plasma GH levels are measured at fixed intervals during the day. Negative results are reported in one major study measuring plasma GH levels during oral glucose tolerance tests (Lindholm et al., 1981). This study does not mention the time interval between the last dose of bromocriptine and the performance of an OGTT, but due to the short duration of action of bromocriptine this may be critical. Therefore, in the present report the plasma GH suppressive effect of bromocriptine in acromegaly is studied using plasma GH day-profiles as well as OGTT's during continued bromocriptine administration and OGTT's at two different time intervals after the last dose of bromocriptine. Twelve patients with clinically active acromegaly were treated with 10-20 mg bromocriptine for 6-9 months. After 6-9 months during continued bromocriptine administration the plasma GH suppressive effect of bromocriptine was evaluated by the mean of four plasma GH determinations during the day and by the mean of seven plasma determinations during oral glucose tolerance tests (OGTT's) performed 1 h, 10 h and 34 h after the last dose. The percentage decrease of the mean plasma GH level during the day induced by chronic bromocriptine treatment showed a good correlation (r = 0.86, P less than 0.001) with the percentage decrease of the mean plasma GH level during OGTT, if the post-treatment test was carried out one hour after the last dose of bromocriptine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1985

The effect of a new ergoline derivative, CU 32-085, in the treatment of acromegaly. A controlled study.

The effect of a new dopamine agonist, CU 32-085 (8 alpha-amino-ergoline), on pituitary function in acromegaly was evaluated by a controlled, single blind study of 12 acromegalics. The study included a single dose placebo/drug (0.5 mg CU 32-085) trial and a long-term crossover trial with 3 month periods (placebo/CU 32-085 8 mg daily). The patients were evaluated clinically and biochemically (oral glucose tolerance (OGTT), TRH- and LHRH-tests) before and after each 3 month period. Nine patients completed this long-term trial; one died from myocardial infarction during the placebo period, and two dropped out because of side effects. The release of GH, judged from more than 9 h suppression of serum GH following the single dose, and from the response to OGTT after the long-term treatment, was significantly inhibited by CU 32-085. Serum GH reached normal values in 4 of 9 patients. Serum PRL was also markedly suppressed, to subnormal values after the 3 months in all but one hyperprolactinemic patient. Serum TSH, cortisol, FSH and LH were generally unaffected. Glucose tolerance was not significantly altered, although an improvement was found in six of nine patients. A semiquantitative evaluation of subjective symptoms showed a significant improvement following the long-term treatment, while objective signs of acromegaly were unaffected. The blood pressure was slightly lowered, both after a single dose and after 3 months' treatment. Seven patients experienced nausea and dizziness, two of them with vomiting, after a single dose of the drug. Four of these had similar symptoms initially during the long-term treatment, which forced two to interrupt the trial. We conclude that CU 32-085 caused a marked suppression of the release of GH and PRL and an improvement of the major symptoms of acromegaly, a therapeutic effect that is comparable to the previous experience with bromocriptine.

Acromegaly↗
PubMed1987

Leucocyte sodium transport in acromegaly.

The leucocyte sodium pump was studied in patients with active and treated acromegaly. The ouabain-sensitive 22Na+ efflux rate constant was significantly raised in active acromegaly (median 2.71 [range 2.33-3.20] vs 2.32 [1.55-3.67] h-1, P less than 0.008) and was lowered into the normal range with successful treatment. Plasma GH and insulin levels and skin fold thickness on the dorsum of the hand were positively correlated with this efflux rate constant (rs = 0.06 P less than 0.02; rs = 0.57, P less than 0.02; rs = 0.57 P less than 0.04, respectively). GH, in vitro, stimulated ouabain-sensitive efflux in leucocytes at a concentration of 25 mU/l. We propose that this action of GH may explain the sodium retaining and calorigenic effects and possibly the stimulation of amino acid uptake by the hormone. The activity of the leucocyte sodium pump in acromegaly may be associated with other indices of disease activity.

Acromegaly↗
PubMed1987

Investigation of the criteria for assessing the outcome of treatment in acromegaly.

The outcome of treatment in acromegaly is usually assessed by measuring plasma concentrations of growth hormone (GH)--either basal spontaneous levels or during hyperglycaemia. There is no consensus on how cure should be defined. Many studies have considered basal plasma growth hormone concentrations below 20 mU/l (10 ng/ml) as proof of cure, although some recent studies have applied lower values. At present a limit of 10 mU/l (5 ng/ml) seems to be accepted as evidence of cure. We have studied 28 acromegalic patients after transsphenoidal adenomectomy. Plasma GH concentrations (basal and during hyperglycaemia) as well as plasma somatomedin C (SMC) concentrations were measured and compared to the clinical symptoms. There was a close correlation between plasma GH and SMC concentrations (except when plasma GH levels were low) and between the clinical assessment and SMC concentrations. Very low plasma GH levels (less than 1 mU/l or 0.5 ng/ml) were associated with normal SMC values and clinical cure, high GH levels (greater than 10 mU/l or 5 ng/ml) with elevated SMC levels and persisting acromegaly. Moderately elevated plasma GH concentrations (1.9-9.6 mU/l) did not allow any conclusions on the outcome of treatment as assessed from SMC determinations and clinical evaluation. It is concluded that the usual criteria for cure in acromegaly may not be sufficiently strict.

Acromegaly↗