A Consensus on Criteria for Cure of Acromegaly

Harvard University, Cambridge, Massachusetts, United States
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 07/2010; 95(7):3141-8. DOI: 10.1210/jc.2009-2670
Source: PubMed

ABSTRACT The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000.
Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. EVIDENCE/CONSENSUS PROCESS: Relevant assays, biochemical measures, clinical outcomes, and definition of disease control were discussed, based on the available published evidence, and the strength of consensus statements was rated.
Criteria to define active acromegaly and disease control were agreed, and several significant changes were made to the 2000 guidelines. Appropriate methods of measuring and achieving disease control were summarized.

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    • "After surgery, a random GH level < 1 ␮g/l and an IGF-1 level within our age-and sex-adjusted normal range were documented in 7 cases. Oral glucose tolerance testing to check whether GH was suppressible to a nadir of level < 1 ␮g/l was not routinely performed, unfortunately, so that the number (percentage) of patients achieving values defining biochemical remission as proposed by Giustina [5] cannot be given; 1 case (case 1) required further stereotactic radiotherapy. We did not observe any mortality or serious morbidity associated with surgery in these cases. "
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    ABSTRACT: Objective: To describe an association of growth hormone (GH) secreting pituitary microadenomas and empty sella (ES), which has been described in case reports - the underlying mechanisms are unclear. Methods: We retrospectively analyzed patients operated for GH-producing pituitary adenomas between February 2004 and February 2009. Magnetic resonance imaging (MRI), computed tomography (CT) imaging, and pituitary function testing were performed. All cases underwent transsphenoidal surgery (TSS). Mean follow up was 38 months (range 12-80 months). Results: Out of 152 patients with acromegaly due to GH-producing pituitary adenomas (female:male = 73:79; age range 17-63 years), 69 patients had microadenomas (45.4%; 38 females, 31 males). We found 14 cases (14169, 20.3%), all microadenomas, with presurgical evidence of ES 10 females (71%) and 4 males (29%) (female:male = 2.5:1). When compared with 103 patients with GH-negative microadenomas treated in the same time period (ES in 4 of 103; 3.9%), ES was highly significantly associated with GH production by the microadenoma (p = 0.001). In acromegalics with empty sella, no cases of ectopic adenoma were found. Postoperatively, GM and IGF-1 levels fell in all patients, and 7 cases had random GM and IGF-1 levels consistent with cure. Conclusion: The combination of GH-producing microadenomas and empty, enlarged sella is not rare. In this setting, preoperative CT scans are very useful and the transsphenoidal approach is efficient and safe. The mechanism underlying the association of GH-producing microadenomas and empty sella remains unclear and requires further studies.
    Clinical Neurology and Neurosurgery 08/2014; 126C:18-23. DOI:10.1016/j.clineuro.2014.08.012 · 1.25 Impact Factor
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    • "Ideally, IGF-1 should normalise and glucosesuppressed GH should be low after surgery for acromegaly. Most often, 1 ng/ml has been used as a cut-off value (Giustina et al., 2010). However, this ideal scenario is often not clinical reality, with 9–39% of patients showing abnormal GH suppression during oGTT despite a normal IGF-1 level and 24–62% of patients showing elevated IGF-1 levels despite adequate GH suppression (Freda, 2009). "
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    ABSTRACT: BACKGROUND: Acromegaly is an illness usually defined by excessively high growth hormone (GH) and insulin like growth factor 1 (IGF-1) levels, the latter mainly reflecting GH action on the liver. IGF-1, also known as somatomedin C, mediates several actions of GH. The diagnosis and management of acromegaly is relatively straight forward, but long-term follow-up of patients can be difficult, as elevated IGF-1 levels can occur in the presence of apparently normalised GH levels and late recurrence of acromegaly may arise despite previous suppression on oral glucose tolerance testing. Data suggest this applies especially to patients in whom the GH receptor lacks exon 3. In such patients, GH may not always be a useful marker of disease, and traditional GH cut-offs may be misleading. Recent data suggest that soluble Klotho (sKlotho), besides and in addition to IGF-1, may help monitor the activity of GH-producing adenomas (presumably reflecting GH action on the kidneys) and may be a useful supplementary tool. METHODS: GHR genotyping was performed in 112 patients with acromegaly. IGF-1 and sKlotho levels were measured in the sera of patients before and after transsphenoidal surgery, with emphasis on patients judged inconclusively cured by surgery or with small residual tumour masses shortly after surgery. Patients were assessed for recurrence of acromegaly with GH levels (random or nadir during an oGTT). RESULTS: Of the 48 patients who underwent surgery between 2000 and 2009 and who had well-documented longer term follow-up at our institution, 29 had no biochemical evidence of residual disease activity after transsphenoidal surgery (marked reduction in IGF-1 and sKlotho levels, GH suppressible to <1 ng/ml) and were classified as in remission. 2 of these patients developed recurrent symptoms of acromegaly during follow-up with increasing levels of IGF-1 and sKlotho, and both patients were carriers of the d3-GHR genotype. CONCLUSIONS: Acromegalic patients with the d3-GHR polymorphism might be - for a given low postsurgical GH level - at higher risk for recurrence and may require a lower GH nadir during oGTT to be classified as in remission. Soluble Klotho could be useful in the follow-up of acromegalic patients. The question arises whether sKlotho not only reflects the activity of GH-secreting pituitary adenomas but whether Klotho (ectodomain clipping?) could also mediate selected actions of GH.
    General and Comparative Endocrinology 05/2013; 188. DOI:10.1016/j.ygcen.2013.04.024 · 2.67 Impact Factor
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    ABSTRACT: A particularly challenging case of concurrent acromegaly and follicular thyroid carcinoma in a patient of the Clinic of Endocrinology, UJCM in Krakow is discussed. A 59-year-old male with post total thyroidectomy performed in 2005 and histopathologically confirmed metastases of the follicular thyroid carcinoma to the lungs was admitted to the Clinic in April 2006 for complementary ¹³¹I treatment. Acromegaly was treated in 1996 by trans-sphenoidal surgery. In December 2005 a relapse of pituitary adenoma was shown by MRI, which correlated with increased levels of hGH and IGF-1. Biochemical control of acromegaly was achieved with Sandostatin LAR. Pre-therapeutic whole-body scintigraphy (WBS) revealed numerous conjoined hot spots of ¹³¹I accumulation in both lungs and in thyroid remnants. In May and November 2006 the patient received ¹³¹I treatment. Post-therapeutic WBS in November 2006 revealed complete ablation of the thyroid remnants. Laboratory tests confirmed lowering of thyroglobulin concentration. In the years 2007, 2008, and 2009 the patient was qualified for therapy with ¹³¹I aided by rhTSH, achieving further reduction of Tg levels. Post-therapeutic WBS performed in 2009 revealed weak bilateral tracer uptake in the lung parenchyma. In 2010, chest CT revealed fibrosis in left lung segments, no infiltrative changes, and no lymph node enlargement. Patient follow-up continues at our Department. Disseminated thyroid cancer in a patient with pituitary insufficiency may be successfully treated by rhTSH-supported ¹³¹I treatment.
    Endokrynologia Polska 61(5):497-501. · 1.21 Impact Factor
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