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  • Author: Giselle F Taboada x
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Flávia R B van Haute, Giselle F Taboada, Lívia L Corrêa, Giovanna A B Lima, Rosita Fontes, Anna Patricia Riello, Michele Dominici and Mônica R Gadelha

Objectives

To determine the prevalence of sleep apnea (SA) and SA syndrome (SAS) in patients with acromegaly and correlate SA with clinical, laboratory, and cephalometric parameters.

Design and methods

Prospective and cross-sectional study of 24 patients with active acromegaly evaluated by clinical and laboratory (GH, IGF-I) parameters, polysomnography and magnetic resonance imaging (MRI) of the pharynx.

Results

Out of 24 patients, 21 had SA (87.5%), of which 20 (95.3%) had the predominant obstructive type. Median age of these 21 patients was 54 years (range 23–75) and median estimated disease duration was 60 months (range 24–300). The frequency in SA patients of impaired glucose tolerance, diabetes mellitus (DM), and hypertension was 19, 33.3, and 71.4% respectively. Goiter was found in 10 patients (47.6%) and obesity in 18 (90%). Median GH level was 14 μg/l (1.4–198) and median %IGF-I (percentage above the upper limit of normal range of IGF-I) was 181% (−31.6 to 571.2). The prevalence of SAS was 52.4%. Apnea–hypopnea index (AHI) correlated significantly with age, waist circumference, body mass index, and hypopharynx area. The AHI was significantly higher in patients with hypertension and DM.

Conclusions

The prevalence of SA and SAS in acromegaly was similar to the one previously described in other series. Age was a significant risk factor, and hypertension and DM were significantly associated complications of SA. Obesity was also significantly related to SA, as a risk factor, a complication or both. Overall, cephalometric parameters by MRI did not correlate with SA.

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Giselle F Taboada, Raul M Luque, Wildebranham Bastos, Renata F C Guimarães, Jorge B Marcondes, Leila M C Chimelli, Rosita Fontes, Paulo J P Mata, Paulo Niemeyer Filho, Denise P Carvalho, Rhonda D Kineman and Mônica R Gadelha

Objective: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1–5), within and between pituitary tumor types.

Design and methods: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA.

Results: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3≫SSTR1⋙SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2.

Conclusions: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.

Free access

Giselle F Taboada, Raul M Luque, Leonardo Vieira Neto, Evelyn de O Machado, Bruna C Sbaffi, Romeu C Domingues, Jorge B Marcondes, Leila M C Chimelli, Rosita Fontes, Paulo Niemeyer, Denise P de Carvalho, Rhonda D Kineman and Mônica R Gadelha

Objective

To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment.

Design and methods

Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging).

Results

SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046–5555), 2098 (194–23 954), 97 (0–460), 14 (0–29 480), and 0 (0–652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=−0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7–10) vs 0.3 (0.1–7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% – area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12).

Conclusions

Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.