The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly

Marinis, Laura De; Bianchi, Antonio; Mazziotti, Gherardo; Mettimano, Marco; Milardi, Domenico; Fusco, Alessandra; Cimino, Vincenzo; Maira, Giulio; Pontecorvi, Alfredo; Giustina, Andrea

doi:10.1007/s11102-007-0062-6

Cited by 49 publications

(35 citation statements)

References 53 publications

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“…Although it is unlikely that a patient with biochemical control may show increase in tumor size during SSA treatment, it has been reported that tumor shrinkage may occur also in patients with ''biochemical'' resistance to lanreotide treated with a maximal dose of the drug [11][12][13], such as already reported in patients with prolactinomas treated with dopamine agonists [44]. Such a dissociation may be explained by a dose dependent effect of SSA on the tumor consistent with the hypothesis of a direct SSA effect, as previously suggested for other target organs such as the heart and bone [45][46][47]. Moreover, different mechanisms regulate the antimitotic and antisecretory actions of SSA [48,49].…”

Section: Discussionsupporting

confidence: 79%

Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review

Mazziotti,

Giustina

2009

Pituitary

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Long-acting somatostatin analogs (SSA) are widely used for the treatment of acromegaly achieving biochemical control of the disease in 50-75% of the patients. One of the goals of the treatment of acromegaly is the control of tumor growth, especially in patients in whom SSAs are used as first-line therapy. Over the recent years, there has been growing evidence that SSAs are able to induce tumor shrinkage in patients with acromegaly. However, most of the data are from patients under treatment with octreotide, either subcutaneously or intramuscularly with long-acting formulation, whereas the data on lanreotide SR or Autogel are very few. Indeed, octreotide and lanreotide, i.e. the two commercially available SSAs, show slight differences in pharmacokinetics and patterns of receptor affinities with potentially different therapeutic effects. We aimed to perform a systematic review of literature data concerning the shrinkage effects of long-acting lanreotide in patients with acromegaly. The analysis was focused on the following issues: differences in shrinkage effects between primary and secondary medical treatment, predictive value of baseline tumor volume and correlation between biochemical control and shrinkage effects. The peer-reviewed medical literature was searched to identify clinical trials studying the effects of lanreotide SR or Autogel on adenoma size in acromegaly. To be included in this analysis, studies had one of the following designs: randomized controlled trial; prospective, nonrandomized trial; retrospective study. Twenty-two studies were found to be eligible for the final analysis, in which tumor size was measured as an end-point for lanreotide treatment. Overall a total of 32.8% of patients experienced a variable degree (from 10 to 77%) of tumor shrinkage during lanreotide SR or Autogel treatment. The analysis showed that tumor shrinkage was more frequent in naïve patients as compared with those previously treated by radiotherapy, surgery or drugs other than lanreotide. The data on the correlation between tumor shrinkage and baseline tumor size were discordant, but when baseline tumor size was specified, more than 80% of patients undergoing shrinkage under lanreotide Autogel had macroadenomas. Finally, with lanreotide Autogel there was no evident correlation between biochemical response and tumor shrinkage. Our systematic review of the literature shows that lanreotide particularly when used as first-line therapy is able to quite frequently induce tumor shrinkage in patients with acromegaly. This finding suggests that this drug may have a role in the primary treatment of acromegaly.

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Section: Discussionsupporting

confidence: 79%

Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review

Mazziotti,

Giustina

2009

Pituitary

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“…In general, the mortality rate of patients with DM or impaired glucose tolerance is significantly higher than in individuals with normal glucose tolerance [22] and its improvement or normalization in our patients may have contributed to their prolonged survival. Although our study did not evaluate its effect on cardiomegaly, in acromegalics, surgery has been reported to improve ventricular hypertrophy and cardiovascular functions [23,24]. According to Minniti et al 9 of their 11 surgically cured elderly acromegalics with left ventricular enlargement manifested postoperative normalization of the cardiac mass [4].…”

Section: Discussionmentioning

confidence: 77%

Treatment of Elderly Acromegalics

et al. 2008

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Abstract. We assessed the incidence of elderly patients in Japanese acromegalics and the characteristics of their clinical presentation. We also evaluated the safety and efficacy of transsphenoidal surgery (TSS) in this patient group. During the 28-year period from 1980 to 2007 we treated 290 patients with acromegaly at our hospitals. Of these, 9 (3.1%) were elderly, i.e. 70 years old or older. They comprised 0.7% of acromegalics treated during the first-and 4.5% of patients with acromegaly treated during the 2nd 14-year period. Before treatment, all manifested abnormal glucose tolerance; 6 had diabetes mellitus (DM), 6 presented with hypertension, and 2 had cardiovascular disease, malignant neoplasms, or hyperlipidemia. Of the 7 elderly acromegalics who underwent TSS none manifested surgical morbidity or new pituitary hormone deficiencies. Postoperatively, the nadir growth hormone (GH) level at the oral glucose tolerance test (OGTT) was under 1.0 ng/mL in 5 patients, insulin-like growth factor (IGF-1) levels normalized in 4. Glucose tolerance improved in all operated patients. Only 1 of 6 patients with preoperatively diagnosed DM continued to manifest DM post-treatment, anti-hypertensive drugs could be tapered in 3 of patients with preoperative hypertension. In conclusion, we found that there was a high incidence of abnormal glucose tolerance and hypertension in elderly acromegalics, that surgical treatment was effective and safe in this population, and that it was useful for the control of co-morbidities.

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“…In this regard, however, it has been recently reported that treatment with somatostatin analogues, associated with neurosurgery, leads to additional improvement of cardiac parameters, when compared with neurosurgery alone (33). Therefore, it cannot be ruled out that the same positive effect of medical therapy could be observed also on SAS parameters if the sample size of medically treated patients, either in active or in inactive phase, was larger.…”

Section: Discussionmentioning

confidence: 98%

Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease

Davì

Carbonare

Giustina

et al. 2008

European Journal of Endocrinology

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129

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Background: Whether sleep apnoea syndrome (SAS) subsides after biochemical and clinical remission of acromegaly is controversial. Objective: To assess the presence of SAS in a cohort of acromegalic patients, which included a subgroup with active disease and a subgroup in remission, and to evaluate clinical and biochemical independent predictors of SAS. Design: Cross-sectional and longitudinal study. Setting: Italian university department of internal medicine. Patients: About 36 acromegalic patients: 18 active and 18 controlled. Measurements: Polysomnography was performed in all patients and repeated in six with active acromegaly and SAS after achieving disease control. Echocardiographic parameters were also measured. Results: The prevalence of SAS was 47% in the overall acromegalic population: 56% in the active group and 39% in the controlled one. In a multivariate analysis IGF1, male gender, age, body mass index, and disease duration were associated with SAS. Impaired glucose tolerance or diabetes was more prevalent in patients with SAS, particularly in the severe cases. Among the six patients of the longitudinal study, five showed improvement of SAS, but none recovered. No correlation was found between echocardiographic parameters and severity of SAS. Conclusion: SAS can persist after recovery of acromegaly in several patients. Given the negative prognostic significance of this respiratory disorder, polysomnography should be included as routine procedure in the work-up of the acromegaly, even if in remission, being mandatory in those patients considered at high risk (elderly males, overweight, diabetic). Appropriate intensive treatment should be implemented to minimize the clinical impact of SAS in acromegaly.

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The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly

Cited by 49 publications

References 53 publications

Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review

Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review

Treatment of Elderly Acromegalics

Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease

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