Background: Some pituitary adenomas exhibit fast growth and invade surrounding structures. To date, there is no robust marker to predict invasiveness. Aim: To evaluate Ki-67, p53 and aryl hydrocarbon receptor-interacting protein (AIP) expression and compare these between invasive and noninvasive somatotropinomas and nonfunctioning pituitary adenomas (NFPAs). Methods: Protein expression was determined by immunohistochemistry. Tumors were classified according to percentage of immunolabeled nuclei for Ki-67 and p53. AIP immunopositivity was graded according to a score encompassing pattern and intensity. Invasiveness was defined according to radiological and surgical criteria. Results: Thirty-eight sporadic somatotropinomas were studied. Median Ki-67 labeling index in invasive and noninvasive tumors was 1.6 (range 0–20.6) and 0.26 (0–2.2), respectively (p = 0.01). With a 2.3% cut-off point obtained by ROC curve analysis, invasive adenomas were distinguished with 100% specificity, 39% sensitivity, and 63% accuracy. Low AIP expression was also correlated with tumor invasiveness (p = 0.001), with sensitivity, specificity and accuracy of 78, 80, and 79%, respectively. Expression of p53 was not different among tumors. Twenty-nine NFPAs were studied, with no significant difference between Ki-67, p53 and AIP expression in invasive and noninvasive tumors. High AIP expression was more frequent in NFPAs, with Ki-67 >3% (p = 0.051), especially when only gonadotrope cell adenomas (n = 25) were considered (p = 0.012). Conclusions: These data suggest, for the first time, that AIP is a better marker of invasiveness in somatotropinomas than Ki-67 and p53. In addition, low AIP expression is observed in invasive somatotropinomas, in contrast with high AIP expression in NFPAs (mainly gonadotrope cell tumors) with high proliferative indices.

SUMMARYWe present four FIPA kindred discussing clinical and molecular data and emphasizing the differences regarding AIP status, as well as the importance of genetic screening. Family 1 consists of five patients harboring somatotropinomas with germline E24X mutation in AIP. In one of the patients, acromegaly was diagnosed through active screening, being cured by surgery. Families 2 and 3 are composed of two patients with non-functioning pituitary adenomas. Family 4 comprises patients harboring a prolactinoma and a somatotropinoma. No mutations in AIP were found in these families. No patient in Family 1 was controlled with octreotide treatment, while the acromegalic patient in Family 4 was controlled with octreotide LAR. In conclusion, FIPA is a heterogeneous condition, which may be associated with AIP mutation. Genomic and clinical screening is recommended in families with two or more members harboring pituitary adenomas, allowing early diagnosis and better outcome. Arq Bras Endocrinol Metab. 2010;54(8):698-704 SUMÁRIOApresentamos dados clínicos e moleculares de quatro famílias com adenoma hipofisário familiar isolado (FIPA) enfatizando as diferenças na presença ou não de mutação do AIP e a importância da triagem genética. A Família 1 é composta por cinco pacientes portadores de somatotropinomas com mutação germinativa E24X no AIP. Um dos pacientes foi diagnosticado por meio de rastreio ativo, com cura cirúrgica. As Famílias 2 e 3 apresentam em sua composição dois pacientes com adenomas hipofisários não funcionantes. A Família 4 compreende dois pacientes, um com prolactinoma e outro com somatotropinoma. Não foi encontrada mutação no AIP nessas famílias. Na Família 1, não houve resposta ao octreotide, enquanto o paciente acromegálico da Família 4 foi controlado com a medicação. Em conclusão, a FIPA é uma condição heterogênea que pode estar associada à mutação do AIP e o rastreio genético/clínico é recomendado nas famílias com dois ou mais membros portadores de adenoma hipofisário. Isso permite um diagnóstico precoce, com melhor prognóstico. Arq Bras Endocrinol Metab. 2010;54(8):698-704

Background: Osteoporosis is common among elderly people, and identifying those at high risk for fracture is very important. Aim: To evaluate whether the use of quantitative calcaneal ultrasound (QUS), the Sitting–rising test (SRT) and handgrip test (HT) are additional tools for tracking fragility fracture risk when compared to FRAX and NOGG. Methods: During the national campaign against osteoporosis, held in 2018 in Rio de Janeiro, participants were randomly selected to perform QUS, SRT and HT, besides categorization of the risk of major and hip fractures by FRAX and NOGG. The following adequacy values ​​were used: QUS T-score> -1.05 (adequate) or ≤ -1.05 (inadequate); Sitting – rising test (SRT) (composite score): age-reference values at quartiles 3 and 4 (adequate); quartiles 1 and 2 (inadequate); best result 3 attempts of the dominant arm handgrip test, according to age and gender: percentile ≥50 (adequate) and <50 (inadequate); FRAX tool: suggests high risk for major osteoporotic fractures if > 20% and for hip fractures when > 3%; NOGG (complement to FRAX): patient′s risk for major and for hip fractures considered as low (green zone), medium (yellow zone) or high (red zone). Qui square test was used for associations. Results: We included 162 individuals: 118 females, mean age 66.8 years and 44 males, mean age 71.8 years. High risk of hip fractures by FRAX was observed in 51% of those patients with a QUS T-score ≤-1.05 while it was observed in 28% of those with a QUS T-score> -1.05 (p=0.005). An inadequate QUS T-score was also associated with a higher risk of hip fracture by NOGG (p=0.007). An inadequate SRT and HT were not associated with a high fracture risk. Conclusions: As densitometry, a method established in clinical practice for the diagnosis of osteoporosis, has limitations in its use, other tools are necessary for tracking the risk of fragility fractures in these events. Quantitative calcaneal ultrasound was a good predictor of hip fracture risk, while SRT and HT were not capable of evaluate for fracture risk stratification in our study, reinforcing the need for QUS for screening in large populations. Having strength and functional ability did not eliminate the need for investigation.

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