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PubMed1978

Cure of acromegaly by operative removal of an islet cell tumor of the pancreas.

We studied a 30 year old woman in whom acromegaly was cured by operative removal of a large cystic beta cell adenoma of the pancreas. We detected substantial amounts of immunoreactive human growth hormone (hGH)-like activity in a tumor tissue extract. Extracts of the tumor and a normal human pituitary gland eluted from a Sephadex G-75 column in two identical peaks. Serial dilutions of the tumor extract displaced radioactive 125I hGH parallel to a standard curve. Surprisingly, an extract of a normal human pancreas contained large amounts of hGH-like activity and gave results similar to those of the tumor extract on gel chromatography and on serial dilution displacement in the growth hormone immunoassay. Paper electrophoretic studies of 125I hGH after incubation with normal pancreatic and tumor extracts with and without enzyme inhibitors suggested that pancreatic proteolytic enzymes damaged the 125I hGH used in growth hormone radioimmunoassay and produced a false detection of hGH.

Acromegaly↗
PubMed1983

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

Acromegaly↗
PubMed1990

Acromegaly first diagnosed in pregnancy: the role of bromocriptine therapy.

We report a case of acromegaly diagnosed in the second trimester of pregnancy. Bromocriptine (7.5 mg per day) corrected visual field defects and suppressed prolactin secretion but did not reduce fasting growth hormone levels. We propose that suppression of physiologic lactotroph hyperplasia by bromocriptine may permit noninvasive management of pituitary adenomas during pregnancy.

Acromegaly↗
PubMed1977

Bromocriptine treatment of acromegaly.

Bromocriptine at a dose of 7.5-30 mg/day was given to 12 acromegalics for 6 mo. Mean serum growth hormone (GH) levels during a glucose tolerance test (GTT) were significantly lowered by the drug. In four patients the serum GH response during a GTT was suppressed to normal (i.e. less than or equal to 5 mlU/liter). If bromocriptine had not brought the serum GH response to a GTT to normal at a dose of 20 mg/day, this effect was not achieved by raising the dose to 30 mg/day. Bromocriptine was effective for the duration of treatment. On discontinuing therapy there was an increase in serum GH levels. No obvious clinical changes in the acromegalic features were noted. One patient with impaired glucose tolerance and one with established diabetes had normal glucose tolerance while on bromocriptine and another two patients with impaired glucose tolerance showed no obvious changes while on the drug. Side effects were minor. X-rays of the pituitary fossa before starting and at the end of treatment showed no significant change. We conclude that although bromocriptine is the most promising form of medical treatment for acromegaly to date, it is fully effective only in a minority of patients.

Acromegaly↗
PubMed1992

The role of Sandostatin in acromegaly.

Long-acting somatostatin analogues are extensively used for the treatment of acromegalic patients who have not been cured by surgery or for whom surgery is contraindicated or hazardous. Such an analogue, Sandostatin, has been approved for this indication in various countries and to date an overall review is feasible. From the literature and our experience, clinical response of acromegaly is attained in 60% to 70%, with mainly a reduction in headaches, arthralgias, and acral growth. Hormonal response, evaluated on plasma growth hormone (GH) levels, is observed in more than 80% of the patients. In 36% to 45% of the patients, plasma GH levels are reduced to near-normal values, and in 50% of the patients, the percentage of reduction is greater than 50% of pretreatment values. The major source of concern is the occurrence of gallstones during the treatment; its frequency is evaluated differently. From the largest well-documented series, we retain a percentage of 12.5% of newly occurring cholelithiasis and in most cases they remain asymptomatic. Tumor shrinkage is minor in most cases.

Acromegaly↗
PubMed1992

Proceedings of the workshop, "Practical approaches to the diagnosis and treatment of acromegaly".

Practical approaches to the management of acromegaly are discussed. The roles of surgery, radiotherapy, and medical treatment with oral dopamine agonists such as bromocriptine or the long-acting somatostatin analogue octreotide given subcutaneously are reviewed. Most cases need surgery, but cure is rare in patients with macroadenomas, although common with microadenomas. Radiotherapy should be considered in surgical failures, but takes several years to be effective. Medical treatment with octreotide is effective in the majority, for whom it represents a major advance, but it needs to be administered subcutaneously and the development of gallstones and gastritis in long-term treatment are problems. Bromocriptine is usually less effective, but occasionally still plays a role in the therapeutic program. Combinations of the different modalities are usually required in the management of acromegalic patients.

Acromegaly↗
PubMed1995

Dynamic changes of growth hormone-binding protein concentrations in normal men and patients with acromegaly: effects of short-term fasting.

Plasma concentrations of growth hormone (GH) and GH-binding protein (GHBP) were measured at hourly intervals in five healthy men and five patients with acromegaly during the fed state and after a 5-day fast. GHBP concentrations (both total and complexed with endogenous GH) were analyzed by the ligand-mediated immunofunctional assay (LIFA). Total GHBP was similar in both groups during the fed state (104.4 +/- 5.2 and 101.6 +/- 10.3 pmol/L), did not exhibit a diurnal rhythm, and was unchanged by fasting (91.9 +/- 5.4 and 109.9 +/- 10.5 pmol/L, respectively). However, the GHBP/GH complex concentration was significantly higher in acromegalics than in controls (41.0 +/- 2.8 v 18.0 +/- 2.2 pmol/L, respectively; P < .05), closely followed diurnal GH rhythm in normals, and was significantly correlated with mean 24-hour GH concentrations (r = .86, P < .01). We conclude that plasma concentrations of GHBP are stable throughout the day and are unchanged either by short-term calorie deprivation or by chronic exposure to high levels of endogenous GH. In contrast, GHBP/GH complex concentrations are altered both acutely and chronically by ambient GH.

Acromegaly↗
PubMed1984

Acromegaly with multiple secreting pituitary adenomas.

A case of acromegaly with two separate growth hormone-secreting pituitary adenomas is presented. The multiplicity was suspected on computerized tomographic scan and confirmed at transsphenoidal surgery. Possible occurrence of multiple adenomas is discussed.

Acromegaly↗
PubMed1985

Transsphenoidal surgery for acromegaly--long-term results in 100 patients.

A series of 100 patients with acromegaly who were operated on using the transsphenoidal microsurgical approach is presented along with a review of the literature. Emphasis is placed on long-term follow-up to assess the value of the technique. The authors caution against early normalization of growth hormone as a criterion for biologic cure in that cases of late recurrence are presented. It is proposed that 5 ng/mL baseline growth hormone values with normal dynamic testing is the most reliable way to ascertain biologic cure. Using these criteria, a cure rate of 78% for enclosed and 33% for invasive adenomata was obtained. No long-term recurrence was seen in patients considered cured along these lines.

Acromegaly↗
PubMed1991

Pseudomyxoma peritonei et ovarii associated with sequential ovarian and appendicular tumors and acromegaly.

Pseudomyxoma peritonei associated with highly differentiated mucinous, intestinal-type ovarian tumor is reported in a 46-year-old acromegalic patient. Five years after its discovery a second operation revealed a mucinous cystadenoma of the appendix. The coexistence of pseudomyxoma peritonei with ovarian and appendicular tumors is rare, raising questions about the primary was origin of the peritoneal tumor. In this case the primary was ovarian while the appendicular tumor occurred later. Since acromegaly is associated with a high risk for the development of colorectal tumors, it could also have elicited a similar response in the intestinal-type ovarian tumor and the appendicular neoplasm found in this patient. The role of appendectomy in the surgical treatment and staging of ovarian tumors is stressed.

Acromegaly↗
PubMed1995

A re-evaluation of the prolactin-releasing activity of growth hormone-releasing hormone in acromegaly in vivo.

In 1985, Losa et al reported that an i.v. bolus injection of GH-releasing hormone (GHRH) was able to paradoxically stimulate PRL secretion in more than half of their acromegalic patients. However, this observation was not generally accepted since several other investigators have concluded that such an anomalous PRL response to GHRH was an extremely rare phenomenon in acromegaly. Therefore, in this study we examined a large number (51 patients) of active acromegalics in order to obtain more reliable data on the incidence of the paradoxical PRL response to GHRH in this disorder. Each patient underwent i.v. bolus injections of GHRH (100 micrograms) and thyrotropin-releasing hormone (TRH, 500 micrograms) on separate days, and plasma levels of GH and PRL were measured. The plasma PRL response to GHRH was considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. We found that only 6 patients (12%) showed a positive PRL response to GHRH. These PRL-responders to GHRH had higher GH responses to this peptide than PRL-non-responders to GHRH. Although PRL-responders and non-responders to GHRH had a similar PRL responsiveness to TRH, the GH response to TRH was lower in PRL-responders to GHRH than PRL-non-responders to this peptide. In addition, PRL-non-responders to GHRH had lower basal GH and higher basal PRL levels than PRL-responders to GHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1990

Eruptive seborrheic keratoses in a young woman with acromegaly.

The sign of Leser-Trélat, or eruptive seborrheic keratoses, is purported to be a cutaneous marker for many underlying malignancies. Elevation in levels of growth factors has been postulated to be the stimulus for the sudden eruption of multiple new seborrheic keratoses. In support of this hypothesis we present a case of eruptive seborrheic keratoses in a young woman with acromegaly and elevated levels of growth hormone.

Acromegaly↗
PubMed1991

Analgesic effect of octreotide in headache associated with acromegaly is not mediated by opioid mechanisms. Case report.

We report a patient with acromegaly who had severe, intractable headache unrelated to tumor size which dramatically resolved with the somatostatin analog octreotide. The analgesic effects of octreotide were neither related to significant inhibition of growth hormone nor influenced by naloxone. Our data suggest that octreotide should be considered in patients with intractable headache associated with pituitary adenomas. Mechanisms other than tumor size or interaction with the opioid system, such as non-opioid algesic peptide secretion, may be the explanation for severe head pain in some pituitary adenomas.

Acromegaly↗
PubMed2006

Acromegaly in an orthodontic patient.

A 32-year-old white man presented for orthodontic treatment with the chief complaint of mandibular prognathism; he was later found to have acromegaly. General information about pituitary adenomas, specifically growth hormone adenomas, is given, and treatment options are discussed.

Acromegaly↗
PubMed2003

Medical treatment in acromegaly.

Acromegaly is a rare disabling disorder that results in premature death. The excess mortality and morbidity are the result of prolonged elevation of growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, and vigorous control of these improves well-being and restores life expectancy to normal. Recognition of the benefits of treatment has emphasised the need for optimal control of the GH/IGF-I axis. Transsphenoidal surgery is first-line therapy in the majority of patients; however, as most tumours are macroadenomas, cure rates are low. The role of radiotherapy is evolving and, although extremely effective at controlling tumour growth, it can take up to 15 years to control GH & IGF-I levels. In the interim, medical therapy is necessary. Dopamine agonists are inexpensive oral agents but, although most patients experience some benefit, GH and IGF-I levels are only normalised in around 35-40% of patients, and side effects are common. Somatostatin analogues are the gold standard of medical treatment. They can induce tumour shrinkage in a proportion of patients and can normalise the GH/IGF-I axis (at best) in approximately 65% of individuals; however, this leaves a significant cohort uncontrolled. The advent of the GH receptor antagonist pegvisomant provides the potential for IGF-I to be normalised in virtually every patient, but this novel form of therapy, which does not act on the pituitary, also raises many questions.

Acromegaly↗
PubMed2006

Acromegaly due to a somatroph adenoma in a dog.

A 10-year-old uncastrated male Dalmatian dog was referred for gait abnormalities consisting of chronic progressive stiffness and rigidity. Other symptoms were polyphagia associated with weight gain, polyuria and polydipsia, excessive panting, and an inspiratory stridor. The owner had noticed progressive thickening of the skin and enlargement of the tongue over the last 3 years. Physical examination revealed thickening of the skin, redundant skin folds, and enlargement of the tongue. The only remarkable abnormalities found on routine laboratory examination were mild anaemia and an increased serum fructosamine concentration. Circulating concentrations of total thyroxine, free thyroxine, and cTSH, and the results of an ACTH stimulation test were all within reference ranges. The basal serum growth hormone (GH) concentration was markedly elevated (23microg/l) and did not decrease during a glucose tolerance test or after somatostatin administration. The serum insulin-like growth factor-1 concentration was also markedly elevated (1254microg/l). Basal serum insulin concentration was high (95mU/l) and insulin concentrations increased considerably after glucose loading, consistent with insulin resistance. Abdominal ultrasonography showed no abnormalities. Survey radiographs of the vertebral column showed severe spondylosis deformans extending from the cervical to the lumbosacral spine. CT scanning of the skull showed an enlarged pituitary gland with normal enhancement pattern. On post-mortem examination, the entire vertebral column appeared as a single and inflexible structure due to the presence of multiple fused osteophytes. The pituitary gland contained an acidophilic adenoma that immunostained positively for GH (and negatively for ACTH and alpha-MSH). In conclusion, this Dalmatian dog with acromegaly and insulin resistance represents the first case of GH hypersecretion proven to be due to a somatotroph adenoma.

Acromegaly↗
PubMed2006

A prospective analysis of 151 cases of patients with acromegaly operated by one neurosurgeon: a follow-up of more than 23 years.

BACKGROUND: Transsphenoidal adenomectomy has been the accepted surgical management for treatment of growth hormone (GH)-secreting pituitary adenomas. Although the goal of treatment might be to keep the GH level in the reference range, the actual definition of success in control of acromegaly is not yet clear. METHODS: The aim of this study was to analyze prospectively the result of transsphenoidal adenoctomy performed over 23-year period by a single neurosurgeon in one center. The analysis has been performed to determine which preoperative factor could significantly influence the long term outcome. This series consisted of 151 patients. The preoperative hormonal studies documenting the high GH and/or insulin-like growth factor were available in all the cases. At least 1 laboratory report documenting the postoperative level of hormones was also available for all of them. Transsphenoidal microsurgical adenomectomy was performed in all the cases. RESULTS: There were 90 patients with pure GH-secreting adenoma (59.6%) with the highest GH level of 235 mU/L. A second group of 12 patients had normal GH level but elevated serum level of insulin-like growth factor 1 (8%). The group with mixed secretion of GH and prolactin included 49 cases (32.4%). There was no postoperative mortality. Cerebrospinal fluid leakage occurred in 12 patients. Transient diabetes insipidus was encountered in 19 cases (12.6%) and long lasting diabetes insipidus in 2 patients (1.3%). Early and minor hypopituitarism was encountered in 14 patients, whereas a persistent condition occurred mainly after irradiation in 14 other cases. Normal postoperative serum GH level could be achieved in 98 patients (94.2%) of 104 cases with full follow-up. CONCLUSION: In the developing countries, early diagnosis and proper surgical extirpation of the GH-secreting adenoma by an experienced and dedicated pituitary surgeon is mandatory to reduce the mortality and increase the chance of cure of this rather mortal endocrionopathy.

Acromegaly↗
PubMed1995

Cardiopulmonary performance during exercise in acromegaly, and the effects of acute suppression of growth hormone hypersecretion with octreotide.

We studied 10 adult patients with active acromegaly (4 men and 6 women, mean age 55 +/- 5 years and mean body mass index 27.9 +/- 1.1 kg/m2). Control values for the echocardiographic and exercise studies were obtained from 10 normal subjects matched for sex and age (5 men and 5 women, age 51.1 +/- 3.7 years and body mass index 25.3 +/- 1 kg/m2). Each patient underwent: (1) blood sampling for growth hormone (GH) assay every 3 hours; (2) a 2-dimensional, guided M-mode echocardiographic study; and (3) a cycloergometric exercise test at baseline and after treatment with a portable pump infusing octreotide, 500 micrograms/24 hours subcutaneously. All patients had left ventricular hypertrophy. Systolic function indexes did not significantly differ among normal subjects, whereas baseline Doppler studies showed abnormalities in left ventricular diastolic filling in acromegalic patients. At anaerobic threshold and at maximal exercise, acromegalic subjects sustained a significantly (p < 0.05) decreased workload (54 +/- 23 vs 94 +/- 11 and 87 +/- 37 vs 152 +/- 15 W) compared with control subjects. After octreotide, baseline heart rate (79 +/- 7 vs 87 +/- 8 beats/min, p < 0.05) and serum GH levels significantly decreased compared with levels before administration of octreotide. Systolic and diastolic functional indexes at rest significantly improved after octrotide in acromegalic patients. Both at anaerobic threshold and at maximal exercise, workload and oxygen consumption were significantly increased after octretide administration. Exercise capacity at anaerobic threshold was not significantly different in acromegalic subjects after octreotide when compared with normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗