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PubMed1992

Radiation therapy of acromegaly.

Conventional megavoltage irradiation of GH-secreting tumors has predictable effects on tumor mass, GH, and pituitary function. 1. Further growth of the tumor is prevented in more than 99% of patients, with only a fraction of a percent of patients requiring subsequent surgery for tumor mass effects. 2. GH falls predictably with time. By 2 years GH falls by about 50% from the baseline level, and by 5 years by about 75% from the baseline level. The initial GH elevation and the size and erosive features of the sella turcica do not affect the percent decrease in GH from the baseline elevation. 3. With prolonged follow-up, further decrease in GH is seen at 10 and 15 years, with the fraction of surviving patients achieving GH levels less than 5 ng/mL approaching 90% after 15 years in our experience. Gender, previous surgery, and hyperprolactinemia do not seem to affect the response to treatment. Patients with initial GH greater than 100 ng/mL are significantly less likely to achieve GH values less than 5 ng/mL during long-term follow-up. 4. Hypopituitarism is a predictable outcome of treatment, is delayed, and may be more likely in patients who have had surgery prior to irradiation. There is no evidence that this complication is more common in patients with acromegaly than in patients with other pituitary adenomas receiving similar treatment. 5. Vision loss due to megavoltage irradiation--using modern techniques and limiting the total dose to 4680 rad given in 25 fractions over 35 days, with individual fractions not exceeding 180 rad--is extremely rare. The reported cases have occurred almost entirely in patients who have received larger doses or higher fractional doses. The theory that patients with acromegaly are prone to radiation-induced injury to the CNS and optic nerves and chiasm because of small vessel disease is not supported by a review of the reported cases. 6. Brain necrosis and secondary neoplasms induced by irradiation are extremely rare. 7. Although anecdotal evidence raises the question of changes in intellectual function following irradiation, this has not been studied in adults receiving pituitary irradiation.

Acromegaly↗
PubMed1992

Living with acromegaly.

Acromegaly is an unusual insidious but potentially serious chronic pituitary disorder. The delay in diagnosis results not only in unique somatic disfigurement but is also associated with significant mental and emotional dysfunction. This article reviews and describes some of these nonclassic and often overlooked features of acromegaly. Particular emphasis is placed on presenting the patients' perspectives of the condition. The author offers some suggestions on the care and counseling of the acromegalic patient.

Acromegaly↗
PubMed2004

Coexisting acromegaly and primary empty sella syndrome.

The normal functions of the pituitary gland may be suppressed when the gland is compressed onto the sella floor by arachnoid tissue extending through an impaired sella diaphragm. Interestingly, pituitary hormone hypo- and hypersecretion, including acromegaly, have been observed in patients with an 'empty sella'(1-4). This 'empty sella syndrome' has been classified into a primary form, in which no inciting factor (pituitary irradiation or surgery for a pituitary tumor) is present, and a secondary form, in which the empty sella occurs after pituitary procedures. In this report we describe a patient who presented with clinical and biochemical features of acromegaly and who had an empty sella on pituitary magnetic resonance imaging (MRI).

Acromegaly↗
PubMed2003

The use of a GH receptor antagonist in patients with acromegaly resistant to somatostatin analogs.

Pegvisomant, a GH receptor antagonist, is a new pharmaceutical approach to acromegaly. It enables IGF-I levels to return in the age- and sex-reference range in approximately 90% of patients. This new approach is particularly beneficial in those patients who do not experience control of hormone hypersecretion after surgery and/or medical treatment with somatostatin analogs. In our preliminary experience, out of 16 patients unsuccessfully operated on by transsphenoidal surgery and resistant to 40-mg octreotide-LAR or 120-mg lanreotide for at least 6 months, 13 normalized their IGF-I levels within 6 months from treatment beginning. Normalization of IGF-I levels was accompanied by a significant decrease of ring size. We did not observe any increase of tumor remnant in this short period of treatment. In two cases we observed a significant increase of liver transaminases levels. In conclusion, more than 80% of patients with acromegaly unsuccessfully treated by surgery or currently available somatostatin analogs can achieve normal IGF-I levels after short-term treatment with pegvisomant.

Acromegaly↗
PubMedDate not supplied

Somatomedin C/insulin-like growth factor I levels after treatment of acromegaly.

An in-house method was used, including dissociation of Somatomedin C/insulin-like Growth Factor I (Sm-C/IGF-I) binding proteins with acid and extraction of Sm-C/IGF-I by C-2 cartridge before radioimmunoassay, to measure plasma Sm-C/IGF-I levels in three groups of patients--total of 19--with acromegaly who underwent transsphenoidal removal of pituitary tumors. In group A (n = 7), the Sm-C/IGF-I levels did not decrease to normal on postoperative day 1 even though the growth hormone concentration had decreased to normal. In group B (n = 4), the Sm-C/IGF-I level decreased to normal in three of the four patients on postoperative day 4, but it remained elevated in one. At two months postoperatively, all four patients had normal values. Group C patients (n = 8) had had an operation two to 23 years previously, and all remained in remission with normal Sm-C/IGF-I levels. Our findings indicate that the Sm-C/IGF-I assay is useful for monitoring acromegaly after transsphenoidal removal of pituitary tumors, but it should be ordered at least four days postoperatively.

Acromegaly↗
PubMed2005

Pegvisomant: new preparation. A last resort in acromegaly.

(1) The first-line treatment for acromegaly is transsphenoidal surgery. As an adjunct to surgery, and for patients with inoperable tumours, the first-line drug therapy is a somatostatin analogue (octreotide or lanreotide). (2) Pegvisomant, a growth hormone (GH) receptor antagonist, is licensed for patients who have a poor response to surgery and/or radiation therapy and in whom somatostatin analogue therapy has failed. (3) There are no published comparative trials evaluating pegvisomant as alternative for patients who have already tried a somatostatin analogue. Most of the evaluation data comes from a single randomised, placebo-controlled trial in 112 patients treated for three months. It showed that pegvisomant, at a dose of 10 mg to 20 mg/day subcutaneously, normalised the level of insulin-like growth factor type 1 (IGF-1) and improved some symptoms. However, the patients were very heterogeneous, and no information was provided on the efficacy of previous treatments. This trial does not provide enough evidence to support the approved indication. (4) Pegvisomant lowers the IGF-1 level but also increases the GH level. An increase in the size of the pituitary adenoma, due to the resulting hyperfunctioning, was observed in four of the 160 patients treated in clinical trials. (5) Evaluation data on pegvisomant does not resolve the question of possible hepatic toxicity. (6) In practice, pegvisomant therapy is justified for patients with serious complications of acromegaly and who have no other treatment options. But the patients concerned, who are few in number, must be closely monitored and included in an appropriate register.

Acromegaly↗
PubMed2005

Diagnostic and therapeutic consensus on acromegaly.

In February 1999 and May 2000, two workshops were held in Cortina, Italy and Montecarlo, respectively, to develop a consensus defining the diagnosis and treatment of acromegaly. The workshops were sponsored by the Italian Society of Endocrinology, the Pituitary Society and European Neuroendocrine Association. Partecipants from all over the world included endocrinologists, neurosurgeons and radiotherapists skilled in the management of acromegaly. This review paper summarizes the main points of the two consensus statements published following these two workshops.

Acromegaly↗
PubMed2005

New roles and challenges in neurosurgery of acromegaly.

Acromegaly is a disease that shortens life expectancy (1-3) and causes severe systemic problems during life (4). It can arise and be recognized quickly if the onset is rapid, as in gigantism. Unfortunately there is usually a delay in diagnosis, on average 9 yr (4). The longer the delay the more likely patients are to develop partially or completely irreversible systemic problems, such as sleep apnea (5) and arthritis. Although some of the signs and co-morbidities of acromegaly are permanent, there is good evidence that cure of the disease reverses early mortality (3, 6, 7). It has been estimated that life expectancy is shortened by about 10 yr overall, and longer when diabetes or heart disease are already present at the time of diagnosis.

Acromegaly↗
PubMed2005

Short term use of octreotide in acromegaly.

A 44-year gentleman with acromegaly underwent transphenoidal excision of pituitary macroadenoma followed by radiotherapy. Since he had poor glycemic control necessitating multiple insulin doses, he was started on subcutaneous octreotide. With this, his blood sugars came under control rapidly and insulin could be withdrawn fully. This case report highlights the use of octreotide in a specific clinical situation in acromegaly to improve the quality of life.

Acromegaly↗
PubMed2005

Diagnosis and treatment of acromegaly and its complications: consensus guidelines.

In February 1999, May 2000 and April 2002, three workshops were held in Cortina, Montecarlo and Versailles, respectively, to develop a consensus defining the diagnosis and treatment of acromegaly and its complications. The workshops were sponsored by the Pituitary Society and European Neuroendocrine Association. Invited international participants included endocrinologists, neurosurgeons and radiotherapists skilled in the management of acromegaly. This review paper summarizes the main points of the three consensus statements published following these three workshops.

Acromegaly↗
PubMed2005

New perspectives in the medical treatment of acromegaly.

Currently available medical treatment of acromegaly includes dopamine agonists, slow release formulation of somatostatin analogues and pegvisomant, a GH-receptor antagonist. Dopamine agonists are well tolerated, not expensive but poorly effective. Somatostatin analogues are highly effective in 60-70% of patients based on the receptor profile of individual tumors. Pegvisomant is reported to normalize IGF-I levels in nearly the totality of the patients, but is devoted of tumor shrinking effect. In a preliminary study in patients with acromegaly, a new somatostatin analogue with affinity to four of the five somatostatin receptors (SOM230) was shown to be similarly effective as octreotide in some patients and more effective than octreotide in other patients. Moreover, new molecules with selective activity on the somatostatin receptor type 2, or 5, or 1 have been reported in vitro to strongly suppress GH secretion. Other new promising alternatives are the chimeric compounds with both somatostatin receptor and dopamine receptor binding. These drugs have been also shown to possess strong GH-inhibitory activity in primary cultures from GH-secreting adenomas. These drugs are the future perspectives in the treatment of patients with GH-secreting or GH/PRL-secreting tumors.

Acromegaly↗
PubMed2006

[Acromegaly: multifaceted clinical presentation of a rare disease of the elderly. Report of two cases with long-term follow-up].

We report two cases of acromegaly in elderly patients. Both patients had markedly invasive GH-secreting macroadenomas, which caused hugely increased circulating GH levels (over 90 ng/ml). The first patient, 79 year-old, presented with goitre and severe osteoarthrosis, refused surgery and was treated with various somatostatin analogues (ultimately accompanied by cabergoline), without satisfactory control of the disease. The second patient, 67-year-old, presented with symptoms secondary to hypopituitarism, which had been previously misdiagnosed. These symptoms resolved with the appropriate substitutive therapy, which led to a significant improvement in her condition. However, two transphenoidal operations, radiotherapy and long-term somatostatin agonist therapy were required to control GH hypersecretion satisfactorily. The authors wish to underline that acromegaly is a rare but not negligible disorder in the elderly, which can affect the whole body functions and cause severe morbidities. In the two cases presented somatostatin agonists alone were not able to control the tumoral hypersecretion adequately. The prompt discovery (usually through a simple clinical evaluation) of this disease in the elderly, confirmed by hormonal and morphological evaluation, together with a multidisciplinary (medical, surgical, radiotherapeutic) approach can improve their quality of life and increase life expectancy.

Acromegaly↗
PubMed1991

Benign and malignant tumors in patients with acromegaly.

Growth hormone and its principal mediator insulinlike growth factor I are known promoters of normal growth. To determine whether excessive secretion of growth hormone is associated with an increased occurrence of benign and of malignant tumors, we studied records of 87 patients with acromegaly seen in the Lahey Clinic Medical Center (Burlington, Mass) from 1957 to 1988 and compared the rate of tumor occurrence with a control group of patients with pituitary tumors (198) and with findings from a cancer registry. Patients with acromegaly had a 2.45-fold increased rate of malignant tumors (95% confidence interval, 0.98 to 5.04) compared with findings from the tumor registry. Female patients had a higher rate than male patients. The rate of carcinoma of the thyroid was excessive and previously underscribed, but the rate of carcinoma of the colon was not increased as reported by others. Among benign lesions, goiters, predominantly nodular, were seen in 25% of patients in addition to a large number of mesenchymal lesions.

Acromegaly↗
PubMedDate not supplied

Establishment of reference values for endocrine tests--part V: acromegaly.

BACKGROUND: Plasma insulin-like growth factor 1 (IGF-1) and the response of growth hormone (GH) to oral glucose are frequently used in the evaluation of patients suspected of acromegaly. Because of the implementation of new assay methodology for GH and IGF-1, we have established the reference values for these tests, as well as for urinary GH excretion. METHODS: From the general population, 50 subjects were recruited, equally distributed according to sex and age between 20 and 70 years. Two consecutive 24-hour urine samples were collected to determine urinary GH. Plasma IGF-1 was measured as well as the GH response during an oral glucose tolerance test (OGTT) with 100 g glucose. Basal plasma IGF-1 was also measured in 250 subjects recruited likewise from the general population who had participated in previous studies on reference values. RESULTS: The following reference ranges were established: urinary GH < 5-46 microU/24 h; nadir GH after OGTT < or =1.5 mU/l for males and < or =2.0 mU/l for females. IGF-1 was divided into age groups: 20-30 years 8-61 nmol/l; 31-40 years 8-41 nmol/; 41-50 years 7-36 nmol/l; 51-60 years 5-37 nmol/l; and 61-70 years 7-27 nmol/l. CONCLUSION: We have established reference values with state-of-the-art assay methodology for the diagnostic tests frequently used in the evaluation of patients suspected of acromegaly.

Acromegaly↗
PubMedDate not supplied

[Severe cardiovascular complications due to the pituitary adenoma with acromegaly. An interdisciplinary approach to the treatment. A case report].

Acromegaly reduces life expectancy and leads to 3-5-fold increase in mortality. The main causes are cardiovascular, pulmonary and enhanced prevalence of deaths from malignancy. Successful therapy ought to normalize GH, IGF-I secretion, remove the adenoma mass and its local pressure effects and preserve pituitary functions intact to improve systemic morbidity and normalize mortality. The primary therapy for most patients with acromegaly is still transsphenoidal adenomectomy. The authors present a 64-year-old woman with diagnosed GH-secreting pituitary macroadenoma suffering from severe coronary heart disease and diabetes mellitus. Somatostatin analogue therapy was ineffective in our patient. She was unfit for transsphenoidal adenomectomy. The patient was qualified for coronary artery bypass grafting after cardiological investigation. We have decided to carry out the bypass grafting and transsphenoidal adenomectomy during one anaesthesia. Both surgical procedures and postoperative time were uncomplicated. Our patient feels well and she is in outpatient follow-up.

Acromegaly↗
PubMed2006

[Evaluation of the efficacy of long-acting somatostatin analog as adjunctive therapy in patients with active acromegaly].

UNLABELLED: Transsphenoidal surgery is the first-line therapy for patients with acromegaly, but can achieve biochemical control with normalization of somatomedin C in 40-80% of cases. All patients with continued growth hormone hypersecretion after neurosurgery require adjunctive therapy to prevent morbidity and premature mortality. The aim of our study was to evaluate the efficacy of long-acting somatostatin analog--octreotide LAR (OCT-LAR) as adjunctive therapy for patients with persistent disease. 14 adult subjects (age 45 +/- 15 years) were included into the study. All patients were diagnosed as having growth hormone secreting pituitary tumor and underwent transsphenoidal surgery (TSS). Radiotherapy (RT) was used as adjunctive therapy in 7 of investigated persons. In all subjects elevated level of somatomedin C was found, 9 have increased level of growth hormone (hGH) as well. After 6 months therapy with OCT-LAR we noticed drop in somatomedin C and hGH levels in all patients. Mean drop in somatomedin C level was 42.3% (p=0.001), in GH level was 52.3% (p=0.001). We found entire normalization of GH in 12 (85.7%) patients, nearly normalization of somatomedin C (level lower than 110% of normal upper limit) in 8 (57%) patients. We found no significant correlation between decrease in somatomedin C and its level prior to the treatment (p=0.8), but high positive correlation between decrease in hGh level and its initial value (R=0.75, p=0.002). Decreases in both somatomedin C (p=0.7) and hGH (p=0.6) levels were not correlated with patients' age. The therapeutic outcome defined as decrease in somatomedin C level was not significantly different between patients with or without adjunctive radiotherapy in the past (p=0.08) and between patients with intensive or weak isotope collection in the pituitary in 99mTc-octreotide scintiscan (p=0.2). CONCLUSIONS: Octreotide-LAR efficiently reduces somatomedin C and GH levels in patients with active acromegaly. Initial values of somatomedin C as well as age and isotopic imaging findings are not valuable predictor factors for therapeutic outcome.

Acromegaly↗
PubMed1991

[Gastric and duodenal polyps in acromegaly].

Relationship between acromegaly and occurrence of colonic cancer and polyps is well-known. A rare case of gastric and duodenal polyps in a patient with hypophyseal adenoma is described. After selective hypophysectomy a regression of the polyps was observed. Probable mechanisms of the development and the regression of polyposis are explained. The diagnostic value of gastroscopy in the screening for polyps in patients with acromegaly is discussed.

Acromegaly↗
PubMed1991

[Study on the activity of acromegaly: evaluation of IGF-I].

The evaluation of acromegaly only with GH levels can be difficult. We have evaluated in 32 acromegalic patients the clinical activity and baseline GH after oral glucose and THR. IGF-I was also evaluated. According GH suppression by glucose, three groups were established. A) minimum GH less than ng/ml, B) minimum GH 2-5 ng/ml and C) GH less than 2 ng/ml. IGF-1 in group A was 8.8 +/- 4.1 U/ml (mean +/- SD) and in group C IGF-I was 1.4 +/- 0.5 U/ml. Group B presented heterogeneous clinic and IGF-I levels. A 4 years clinical and hormonal follow-up could be performed in 20 patients. Those patients who were clinically inactive maintained their GH levels less than 2 ng/ml, with normal IGF-I titers throughout the follow-up period. In summary, IGF-I is very reliable in the evaluation of acromegaly activity and only requires a baseline determination being thus very useful in initial screening. It also determines with great reliability the treatment effectiveness in the evolutive study.

Acromegaly↗