Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands.

CONTEXT: Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. OBJECTIVE: To develop a prediction model of therapeutic response of acromegaly to fg-SRL. METHODS: Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). RESULTS: A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P = .014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. CONCLUSION: We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

Steroidogenesis in patients with adrenal incidentalomas: Extended steroid profile measured by liquid chromatography-mass spectrometry after ACTH stimulation and dexamethasone suppression.

OBJECTIVE: Describe the secretion and profile of adrenal steroids in patients with adrenal incidentalomas compared to control subjects. DESIGN, SETTING AND PARTICIPANTS: A prospective study, 73 patients with adrenal incidentalomas, 21 bilateral and 52 unilateral and 34 matched controls in University Hospital. METHODS: Collect fasting blood sample before and 60 min after ACTH test (250 µg IV). One week later, perform overnight 1 mg dexamethasone test. The following steroids were measured by liquid chromatography-mass spectrometry (LC-MS): pregnenolone, 17-OH pregnenolone, 17-OH progesterone, 11-deoxycorticosterone, 11-deoxyortisol, 21-deoxycortisol, corticosterone, cortisol, androstenedione and aldosterone. RESULTS: Mean baseline serum cortisol was higher in incidentalomas, bilateral 361 ± 124, (range 143-665) nmol/L,(p < .0001), unilateral 268 ± 89 3.2 (range 98-507) nmol/L (p < .019) compared to controls 207 ± 100 (range 72-502) nmol/L. ACTH stimulation showed significantly higher levels in bilateral and unilateral cases compared to controls. After dexamethasone, mean serum cortisol levels suppressed in bilaterals 89 ± 69 (range 30-3) nmol/L (p < .0001), 58 ± 52 (range 16-323) nmol/L in unilateral (p < .01) compared to 26 ± 9 (range 7-46) nmol/L in controls. Mean baseline serum corticosterone was higher in bilateral 9.3 ± 4.8 (range 2.4-18.4) nmol/L (p < .005) and unilateral 7.3 ± 5.7 (range 0.1-30.3) nmol/L (p < .01) compared to controls 4.2 ± 2.4 (range 1.1-10.2) nmol/L, after ACTH stimulation significantly increased to higher levels in bilateral (p < .0002) and unilateral cases (p < .044) compared to controls. After dexamethasone, mean levels were 2.5 ± 2.6 (range 0.5-12.5) nmol/L in bilateral (p < .0006), 1.5 ± 1.6 (range 0.3-9.3) nmol/L in unilateral (p < .09) and 0.75 ± 0.46 (range 0.1-2.1) nmol/L in controls. Mean baseline serum 11-deoxycorticosterone (DOC) was higher in bilaterals 0.32 ± 0.23 (range 0.08-1.1) nmol/L (p < .03) compared to controls 0.15 ± 0.21 (range 0.08-1.1) nmol/L. ACTH stimulation increased levels to 3.27 ± 1.72 (range 0.5-7.4) nmol/L in bilateral cases compared to controls 1.369 ± 1.53 (range 0.1-7.1) nmol/L (p < .0001). Dexamethasone decreased levels to baseline (p ns). There were significant differences in serum 21-deoxycortisol (p < .0002) and serum pregnenolone (p < .004) only after ACTH stimulation. CONCLUSIONS: There is increased activity in several steroid biosynthesis pathways and higher steroid levels in bilateral compared to unilateral cases and evidence of hypercortisolism in 30% unilateral and 62% of bilateral incidentalomas.

Serum Cortisol Levels via Radioimmunoassay vs Liquid Chromatography Mass Spectrophotometry in Healthy Control Subjects and Patients With Adrenal Incidentalomas.

BACKGROUND: Adrenal incidentalomas (AIs) are present in 4% of adults. As many as 30% may secrete cortisol autonomously in the absence of specific signs of overt hypercortisolism, in a phenomenon called subclinical hypercortisolism (SH). Diagnosis of SH is established by serum cortisol resistance to dexamethasone suppression. METHODS: We compared serum cortisol concentrations, as determined by radioimmunoassay (RIA) and liquid chromatography/tandem mass spectronomy (LC/MS-MS), in 73 patients with AI group (52 with unilateral AI) and 34 control subjects in 3 scenarios: basal; after 1-mg dexamethasone suppression; and after 0.25-mg stimulation with cosyntropin, a synthetic derivative of adrenocorticotropic hormone (ACTH). To bolster evidence for the diagnosis of SH, we also measured salivary cortisol levels at 11 PM and after DST, as well as plasma ACTH and serum dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: We observed significant positive correlation (r = 0.9345, P <.001) for all 318 pairs of serum cortisol values, as measured by both methods. CONCLUSIONS: Serum cortisol concentrations in patients with AI and in control subjects were very similar, as measured by RIA and LC/MS-MS.

Aplicação de um protocolo de espectroscopia por ressonância magnética das adrenais: experiência com mais de 100 casos / Application of a protocol for magnetic resonance spectroscopy of adrenal glands: an experiment with over 100 cases

Objetivo: Avaliar um protocolo de espectroscopia por ressonância magnética (ERM) do próton de hidrogênio (1H) bidimensional (2D) disponível comercialmente (Siemens Medical Systems; Erlangen, Alemanha), aplicado para nódulos adrenais e diferenciação das massas (adenomas, feocromocitomas, carcinomas e metástases). Materiais e Métodos: Um total de 118 pacientes (36 homens e 82 mulheres), apresentando-se com 138 nódulos/massas adrenais, foi avaliado prospectivamente (média de idade: 57,3 ± 13,3 anos). Uma sequência de ERM-1H-PRESS-CSI (espectroscopia por resolução de ponto-imagem por desvio químico) multivoxel foi utilizada. Análise espectroscópica foi realizada da esquerda-direita, sentido crânio-caudal, usando três sequências sagitais, além de sequências axiais e coronais T2-HASTE. Os seguintes índices foram calculados: colina (Cho)/creatina (Cr), 4,0–4,3 ppm/Cr, lipídio (Lip)/Cr, Cho/Lip e lactato (Lac)/Cr. Resultados: ERM-1H-2D foi bem sucedida em 123 (89,13%) lesões. Os valores de sensibilidade e especificidade encontrados para as proporções e pontos de corte avaliados foram: Cho/Cr ≥ 1,2, sensibilidade de 100% e especificidade de 98,2% (diferenciação de adenomas e carcinomas de feocromocitomas e metástases); 4,0–4,3 ppm/Cr ≥ 1,5, 92,3% de sensibilidade, especificidade de 96,9% (diferenciação de carcinomas e feocromocitomas de adenomas e metástases); Lac/Cr ≤ –7,449, sensibilidade de 90,9% e especificidade de 77,8% (diferenciação de feocromocitomas contra carcinomas e adenomas). Conclusão: Os dados da ERM-1H-2D foram eficazes e permitiram a diferenciação entre massas adrenais e nódulos na maioria das lesões com diâmetro > 1,0 cm. .

Objective: To evaluate a protocol for two-dimensional (2D) hydrogen proton (1H) magnetic resonance spectroscopy (MRS) (Siemens Medical Systems; Erlangen, Germany) in the detection of adrenal nodules and differentiation between benign and malignant masses (adenomas, pheochromocytomas, carcinomas and metastases). Materials and Methods: A total of 118 patients (36 men; 82 women) (mean age: 57.3 ± 13.3 years) presenting with 138 adrenal nodules/masses were prospectively assessed. A multivoxel system was utilized with a 2D point-resolved spectroscopy/chemical shift imaging sequence. The following ratios were calculated: choline (Cho)/creatine (Cr), 4.0–4.3/Cr, lipid (Lip)/Cr, Cho/Lip and lactate (Lac)/Cr. Results: 2D-1H-MRS was successful in 123 (89.13%) lesions. Sensitivity and specificity values observed for the ratios and cutoff points were the following: Cho/Cr ≥ 1.2, 100% sensitivity, 98.2% specificity (differences between adenomas/pheochromocytomas and carcinomas/ metastases); 4.0–4.3 ppm/Cr ≥ 1.5, 92.3% sensitivity, 96.9% specificity (differences between carcinomas/pheochromocytomas and adenomas/metastases); Lac/Cr ≤ –7.449, 90.9% sensitivity and 77.8% specificity (differences between pheochromocytomas and carcinomas/adenomas). Conclusion: Information provided by 2D-1H-MRS were effective and allowed for the differentiation between adrenal masses and nodules in most cases of lesions with > 1.0 cm in diameter. .

Application of a protocol for magnetic resonance spectroscopy of adrenal glands: an experiment with over 100 cases.

OBJECTIVE: To evaluate a protocol for two-dimensional (2D) hydrogen proton (1H) magnetic resonance spectroscopy (MRS) (Siemens Medical Systems; Erlangen, Germany) in the detection of adrenal nodules and differentiation between benign and malignant masses (adenomas, pheochromocytomas, carcinomas and metastases). MATERIALS AND METHODS: A total of 118 patients (36 men; 82 women) (mean age: 57.3 ± 13.3 years) presenting with 138 adrenal nodules/masses were prospectively assessed. A multivoxel system was utilized with a 2D point-resolved spectroscopy/chemical shift imaging sequence. The following ratios were calculated: choline (Cho)/creatine (Cr), 4.0-4.3/Cr, lipid (Lip)/Cr, Cho/Lip and lactate (Lac)/Cr. RESULTS: 2D-1H-MRS was successful in 123 (89.13%) lesions. Sensitivity and specificity values observed for the ratios and cutoff points were the following: Cho/Cr ≥ 1.2, 100% sensitivity, 98.2% specificity (differences between adenomas/pheochromocytomas and carcinomas/ metastases); 4.0-4.3 ppm/Cr ≥ 1.5, 92.3% sensitivity, 96.9% specificity (differences between carcinomas/pheochromocytomas and adenomas/metastases); Lac/Cr ≤ -7.449, 90.9% sensitivity and 77.8% specificity (differences between pheochromocytomas and carcinomas/adenomas). CONCLUSION: Information provided by 2D-1H-MRS were effective and allowed for the differentiation between adrenal masses and nodules in most cases of lesions with > 1.0 cm in diameter.

OBJETIVO: Avaliar um protocolo de espectroscopia por ressonância magnética (ERM) do próton de hidrogênio (1H) bidimensional (2D) disponível comercialmente (Siemens Medical Systems; Erlangen, Alemanha), aplicado para nódulos adrenais e diferenciação das massas (adenomas, feocromocitomas, carcinomas e metástases). MATERIAIS E MÉTODOS: Um total de 118 pacientes (36 homens e 82 mulheres), apresentando-se com 138 nódulos/massas adrenais, foi avaliado prospectivamente (média de idade: 57,3 ± 13,3 anos). Uma sequência de ERM-1H-PRESS-CSI (espectroscopia por resolução de ponto-imagem por desvio químico) multivoxel foi utilizada. Análise espectroscópica foi realizada da esquerda-direita, sentido crânio-caudal, usando três sequências sagitais, além de sequências axiais e coronais T2-HASTE. Os seguintes índices foram calculados: colina (Cho)/creatina (Cr), 4,0­4,3 ppm/Cr, lipídio (Lip)/Cr, Cho/Lip e lactato (Lac)/Cr. RESULTADOS: ERM-1H-2D foi bem sucedida em 123 (89,13%) lesões. Os valores de sensibilidade e especificidade encontrados para as proporções e pontos de corte avaliados foram: Cho/Cr ≥ 1,2, sensibilidade de 100% e especificidade de 98,2% (diferenciação de adenomas e carcinomas de feocromocitomas e metástases); 4,0­4,3 ppm/Cr ≥ 1,5, 92,3% de sensibilidade, especificidade de 96,9% (diferenciação de carcinomas e feocromocitomas de adenomas e metástases); Lac/Cr ≤ ­7,449, sensibilidade de 90,9% e especificidade de 77,8% (diferenciação de feocromocitomas contra carcinomas e adenomas). CONCLUSÃO: Os dados da ERM-1H-2D foram eficazes e permitiram a diferenciação entre massas adrenais e nódulos na maioria das lesões com diâmetro > 1,0 cm.

Níveis séricos de hormônios de crescimento, fator de crescimento símile à insulina e sulfato de deidroepiandrosterona em idosos residentes na comunidade: correlaçäo com parâmetros clínicos / Serum levels of growth hormone, insulin like growth factor and dehydroepiandrosterone sulfate in elderly people living in the community: correlation with clinical parameters

O envelhecimento é acompanhado de alteraçöes orgânicas possivelmente relacionadas com o sistema endócrino. O eixo GH/IGF-1 e a produçäo de SDHEA declinam com a idade, caracterizando uma reduçäo de suas atividades, que podem resultar em efeitos deletérios sobre a composiçäo corporal, o sistema cardiovascular e a congniçäo. Avaliamos a concentraçäo sérica basal de GH, IGF-1 e SDHEA em 225idosos de uma comunidade (148 mulheres e 77 homens, 70 a 91 anos), 80 por cento deles com características de envelhecimento bem sucedido (Minimental >/= 3). Tanto o IMC como a pressäo arterial estavam significativamente mais elevados nas mulheres. Os níveis de GH também eram amiores nas mulheres (1,6 +/- 1,7 vs. 1,0 +/- 1,3 ng/ml, X +/- DP, p<0,001), estando acima da faixa de referência em 14 por cento e 19 por cento das mulheres e homens. Já os níveis de IGF-1 eram semelhantes (90 +/- 42 e 101 +/- 40ng/ml, NS), nao sendo elevados em nenhum deles e reduzidos em 35 por cento e 24 por cento, respectivamente. Os níveis de SDHEA eram maiores nos homens (86 +/- 58 e 54 +/- 36µg/dl, p<0,001), porém na faixa de referência em 92 por cento deles. Houve uma surpreendente correlaçäo positiva entre idade e GH nos homens (r= 0,38, p<0,005), mas uma correlaçäo negativa entre IGF-1 e idade nos dois grupos r= -0,24 e r= -0,32). Nas mulheres, houve também uma correlaçäo positiva entre SDHEA e IGF-1 (r= 0,27). Em conclusäo, níveis basais de GH podem estar elevados em uma parcela significativa dos idosos, sendo maiores nas mulheres, enquanto os níveis de IGF-1 encontram-se normais ou baixos nos dois grupos, sugerindo quadro de resistência hormonal. Os níveis de SDHEA encontravam-se na faixa de referência, sendo maiores nos homens, caracterizandoa perda da contribuiçäo oariana. Diferentemente do que se tem especulado, näo encontramos correlaçäo entre os níveis de SDHEA e qualquer parâmetro clínico investigado.