Criteria for Cure of Acromegaly: A Consensus Statement<sup>1</sup>†

Giustina, Andrea; Barkan, Ariel L.; Casanueva, Felipe F.; Cavagnini, F.; Frohman, Lawrence A.; Ho, Ken K. Y.; Veldhuis, Johannes D.; Wass, John; Werder, Klaus von; Melmed, Shlomo

doi:10.1210/jcem.85.2.6363

Cited by 178 publications

(85 citation statements)

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“…The great majority of AIP-related tumors are GH-and/or PRL-secreting adenomas, and the clinical diagnosis of acromegaly at onset is difficult. Therefore, we suggest that asymptomatic relatives testing positive for an AIP mutation should undergo annual PRL and IGF1 monitoring (29), as suggested for MEN1 carriers (30). Finally, we highlight the particular importance of AIP analyses in patients with a positive family history for acromegaly or with early onset of the tumor.…”

Section: Discussionmentioning

confidence: 88%

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

Georgitsi

Raitila

Karhu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

170

154

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Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12 AIP mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.immunohistochemistry ͉ growth hormone/prolacting-secreting adenomas ͉ acromegaly

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Section: Discussionmentioning

confidence: 88%

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

Georgitsi

Raitila

Karhu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

170

154

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“…Both baseline and follow-up GH and IGF1 samples were taken in the fasting state during routine hospital or outpatient assessment. Control of acromegaly in both centers after 1999 was defined as a basal GH level of !2.5 ng/ml and/or a GH level of !1 ng/ml during oral glucose tolerance test (OGTT) and normal age-adjusted IGF1 values (14). (When only one marker was present, remission was determined using it.)…”

Section: Subjectsmentioning

confidence: 99%

Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy)

Colao

Vandeva

Pivonello

et al. 2014

European Journal of Endocrinology

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Background: Mortality in acromegaly strictly depends on optimal control of GH and IGF1 levels. Modern medical therapy with somatostatin analogs (SSAs) and GH receptor antagonists (GHRAs) is not available in many countries due to funding restrictions. This retrospective, comparative, cohort study investigated the impact of different treatment modalities on disease control (GH and IGF1) and mortality in acromegaly patients. Methods: Two cohorts of patients with acromegaly from Bulgaria (nZ407) and Campania, Italy (nZ220), were compared, and mortality rates were evaluated during a 10-year period (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008). Results: The major difference in treatment approach between cohorts was the higher utilization of SSAs and GHRAs in Italy, leading to a decreased requirement for radiotherapy. Significantly more Italian than Bulgarian patients had achieved disease control (50.1 vs 39.1%, PZ0.005) at the last follow-up. Compared with the general population, the Bulgarian cohort had a decreased life expectancy with a standardized mortality ratio (SMR) of 2.0 (95% CI 1.54-2.47) that was restored to normal in patients with disease control -SMR 1.25 (95% CI 0.68-1.81). Irradiated patients had a higher cerebrovascular mortality -SMR 7.15 (95% CI 2.92-11.37). Internal analysis revealed an independent role of age at diagnosis and last GH value on all-cause mortality and radiotherapy on cerebrovascular mortality. Normal survival rates were observed in the Italian cohort: SMR 0.66 (95% CI 0.27-1.36). Conclusions: Suboptimal biochemical control was associated with a higher mortality in the Bulgarian cohort. Modern treatment options that induce a strict biochemical control and reduce the necessity of radiotherapy might influence the life expectancy. Other factors, possibly management of comorbidities, could contribute to survival rates.

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“…No patient received preoperative medical treatment for acromegaly. All patients underwent TSS, and biochemical cure was defined strictly, at 6 months, by glucose-suppressed plasma GH concentrations less than 1 mg/l and normal age-corrected IGF-I values, as recommended by the most recent consensus conference (31). Patients who failed to meet strict criteria for surgical cure, or who suffered from secondary cardiopathy, such as ischaemic or valvular disease or cardiac failure, were excluded from the study.…”

Section: Patientsmentioning

confidence: 99%

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

Jaffrain-Rea

Minniti

Moroni

et al. 2003

European Journal of Endocrinology

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Background: Cardiac abnormalities develop in patients with acromegaly as a consequence of effects of GH/IGF-I on the heart and related cardiovascular risk factors. Objective: To evaluate the possible contribution of postoperative variations in blood pressure (BP), glucose tolerance and insulin sensitivity to the cardiac improvement reported in patients who have been cured of acromegaly. Design: Thirty-one patients with acromegaly were studied before and 6 months after successful transsphenoidal surgery, defined by normal age-related IGF-I concentrations and glucose-suppressed GH concentrations , 1 mg/l. Methods: Cardiovascular parameters were assessed by Doppler echocardiography and 24-h ambulatory blood pressure monitoring. Insulin sensitivity indexes were calculated on the basis of fasting and post-load glycaemia and insulinaemia and referred to as HOMA ISI and OGTT ISI , respectively. Results: Successful surgery was confirmed to improve left ventricular mass index (LVMI) and diastolic filling significantly. Mean 24-h systolic BP values decreased ðP ¼ 0:009Þ and BP rhythm was restored in 12 of 15 patients with a blunted preoperative profile. Glucose tolerance normalized in patients with preoperative glucose intolerance ðn ¼ 7Þ or diabetes mellitus ðn ¼ 3Þ: HOMA ISI and OGTT ISI increased (P ¼ 0:0001 for each parameter), indicating a marked improvement in insulin sensitivity. The postoperative reduction in LVMI correlated with increased insulin sensitivity (P , 0:001 for both indexes), but not with other parameters. Improved diastolic filling correlated with the reduction in LVMI. Conclusions: Successful surgery in patients with acromegaly induces a significant improvement in haemodynamic and metabolic risk factors. This study suggests a direct link between insulin resistance and acromegalic cardiomyopathy.

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Criteria for Cure of Acromegaly: A Consensus Statement¹†

Cited by 178 publications

References 0 publications

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy)

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

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Criteria for Cure of Acromegaly: A Consensus Statement1†

Cited by 178 publications

References 0 publications

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy)

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

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Criteria for Cure of Acromegaly: A Consensus Statement¹†