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.

Association of serum thyrotropin levels with coronary artery disease documented by quantitative coronary angiography: a transversal study.

OBJECTIVE: The association between coronary artery disease (CAD) and thyroid function remains controversial. We evaluated the thyroid function and graduated well-defined CAD as confirmed by quantitative coronary angiography (CA). SUBJECTS AND METHODS: We evaluated the serum TSH, free thyroxine, free triiodothyronine and thyroid antibody levels in 300 consecutive patients (age 61.6 ± 9.9 years and 54% were male) undergoing CAD diagnosis as confirmed by CA. Plaques with ≥ 50% stenosis being indicative of obstructive CAD, and patients were divided into groups according to main epicardial coronary arteries with plaques (0, 1, 2, 3). Lipid profiles and a homeostasis model assessment (HOMA-IR) were determined. RESULTS: Serum median (25% and 75% percentile) TSH levels in patients with group 2 and 3 (2.25; 1.66-3.12 mU/L and 4.99; 4.38-23.60 mU/L, respectively) had significantly higher TSH concentrations (p < 0.0001) than the group 0 (1.82; 1.35-2.51 mU/L). Furthermore, patients of group 3 had higher TSH concentration (p < 0.0001) than those of group 1 (1.60; 0.89-2.68 mU/L). Group 3 were older (64 ± 8.5 vs. 59 ± 9.5, p = 0.001), had more patients with dyslipidemia (84% versus 58%, p < 0.001), male (54% versus 44%, p = 0.01), hypertension (100% versus 86%, p < 0.001), and smoking (61% versus 33%, p < 0.001) than group 0. Multivariate stepwise logistic analysis showed TSH, age, HbA1c, and HOMA-IR were the CAD associated variables. CONCLUSIONS: In this cohort, elevated TSH levels in the high normal range or above are associated with the presence and severity of CAD besides may represent a weak CAD risk factor.

Association of serum thyrotropin levels with coronary artery disease documented by quantitative coronary angiography: a transversal study

ABSTRACT Objective: The association between coronary artery disease (CAD) and thyroid function remains controversial. We evaluated the thyroid function and graduated well-defined CAD as confirmed by quantitative coronary angiography (CA). Subjects and methods: We evaluated the serum TSH, free thyroxine, free triiodothyronine and thyroid antibody levels in 300 consecutive patients (age 61.6 ± 9.9 years and 54% were male) undergoing CAD diagnosis as confirmed by CA. Plaques with ≥ 50% stenosis being indicative of obstructive CAD, and patients were divided into groups according to main epicardial coronary arteries with plaques (0, 1, 2, 3). Lipid profiles and a homeostasis model assessment (HOMA-IR) were determined. Results: Serum median (25% and 75% percentile) TSH levels in patients with group 2 and 3 (2.25; 1.66-3.12 mU/L and 4.99; 4.38-23.60 mU/L, respectively) had significantly higher TSH concentrations (p < 0.0001) than the group 0 (1.82; 1.35-2.51 mU/L). Furthermore, patients of group 3 had higher TSH concentration (p < 0.0001) than those of group 1 (1.60; 0.89-2.68 mU/L). Group 3 were older (64 ± 8.5 vs. 59 ± 9.5, p = 0.001), had more patients with dyslipidemia (84% versus 58%, p < 0.001), male (54% versus 44%, p = 0.01), hypertension (100% versus 86%, p < 0.001), and smoking (61% versus 33%, p < 0.001) than group 0. Multivariate stepwise logistic analysis showed TSH, age, HbA1c, and HOMA-IR were the CAD associated variables. Conclusions: In this cohort, elevated TSH levels in the high normal range or above are associated with the presence and severity of CAD besides may represent a weak CAD risk factor.

Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study

ABSTRACT Objective: Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). Subjects and methods: We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. Results: Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 μg/L), GO: 53.6 (43.5-60.0 μg/L), HT: 51.9 (44.6-58.5 μg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 μg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 μg/mL) and in HT patients: 0.35 (0.2-1.17 μg/mL) compared to C group patients: 1.00 (0.564.21 μg/mL) as well as to GD patients: 1.19 (0.62-2.5 μg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. Conclusion: A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study.

OBJECTIVE: Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). SUBJECTS AND METHODS: We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. RESULTS: Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 µg/L), GO: 53.6 (43.5-60.0 µg/L), HT: 51.9 (44.6-58.5 µg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 µg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 µg/mL) and in HT patients: 0.35 (0.2-1.17 µg/mL) compared to C group patients: 1.00 (0.564.21 µg/mL) as well as to GD patients: 1.19 (0.62-2.5 µg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. CONCLUSION: A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

An approach to the diagnosis and management of a case presenting with recurrent hypomagnesemia secondary to the chronic use of a proton pump inhibitor.

PURPOSE: Magnesium is an important electrolyte for very many cell functions and its deficiency may lead to a wide spectrum of diseases. We report a clinical case of hypomagnesemia resulting from the chronic use of a proton pump inhibitor (PPI). PPIs are drugs widely used in medical practice, and a growing number of cases of PPIs causing hypomagnesemia have been described. Our aim was to monitor the clinical and electrolyte findings during recovery from hypomagnesemia caused by long-term PPI use. RESULTS: A 65-year old female who had been using omeprazole for 10 years, presented with arrhythmia and paresthesia of the lower and upper limbs that had been attributed to severe hypomagnesemia, hypocalcemia, and hypoparathyroidism. Her laboratory tests revealed the following results: magnesium 0.6 mg/dL (NR: 1.5 to 2.5 mg/dL), calcium 7.3 mg/dL (NR: 8.5 to 10.2 mg/dL), parathyroid hormone (PTH) 13.3 pg/mL (NR: 15 to 65 pg/mL), and low urinary calcium and magnesium excretion. Her electrocardiogram disclosed typical, prolonged QT interval, ST depression, and U waves. We discuss the differential diagnoses, pathophysiology, and reversibility of symptoms after effective treatment of the hypomagnesemia. CONCLUSION: this report emphasizes that even if long-term PPI users appear largely asymptomatic, life-threatening arrhythmias can present very suddenly. Long-term PPI users should be monitored for otherwise unexplained hypomagnesemia, hypocalcemia, functional hypoparathyroidism and associated symptoms.

Endocrine disturbances related to the use of lithium.

Despite recent advances in pharmacological treatment of psychiatric disorders, lithium salts remain frequently used, as they are effective and inexpensive alternatives, especially in the treatment of bipolar disorders. Their use is commonly associated with various endocrine disorders, mainly in thyroid and parathyroid function, and in mineral metabolism. This article aims at reviewing these potential endocrinopathies related to the use of lithium to make health care professionals aware and familiar with these possible complications when they follow up patients using this drug, and to make them able to monitor, identify and institute early and appropriate treatment.

Endocrine disturbances related to the use of lithium / Distúrbios endocrinológicos relacionados ao uso de lítio

Despite recent advances in pharmacological treatment of psychiatric disorders, lithium salts remain frequently used, as they are effective and inexpensive alternatives, especially in the treatment of bipolar disorders. Their use is commonly associated with various endocrine disorders, mainly in thyroid and parathyroid function, and in mineral metabolism. This article aims at reviewing these potential endocrinopathies related to the use of lithium to make health care professionals aware and familiar with these possible complications when they follow up patients using this drug, and to make them able to monitor, identify and institute early and appropriate treatment.

Apesar dos recentes avanços farmacológicos no tratamento dos transtornos psiquiátricos, os sais de lítio permanecem como uma alternativa eficaz e de menor custo, sendo usados com frequência principalmente no tratamento dos transtornos bipolares. O seu uso é comumente relacionado com diversas alterações endocrinológicas, principalmente nas funções tiroidiana, paratiroidiana e do metabolismo iônico. Este artigo tem por objetivo fazer uma revisão dessas potenciais endocrinopatias relacionadas ao uso do lítio, para que, no seguimento de pacientes em uso dessa medicação, os profissionais de saúde estejam atentos e familiarizados com essas possíveis complicações, conseguindo identificar e instituir tratamento precocemente.

[Management of the growth hormone (GH)-treated patients with diagnosis of GH deficiency (DGH) during transition from childhood to adulthood]. / Condução do tratamento com hormônio de crescimento (GH) nos pacientes com diagnóstico de deficiência GH (DGH) durante o período de transição da criança para o adulto.

Growth hormone (GH) has many beneficial effects in patients with childhood-onset GH deficiency (GHD) in addition to its promotion of linear growth. The discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant unfavorable changes in body composition, skeletal integrity, exercise capacity, and an adverse cardiovascular risk profile. These changes are reversed after the resumption of GH treatment. As the benefits of continuing GH therapy into adulthood has been well established, it is possible that GH replacement therapy will not be stopped once growth has been completed, but it will continue into adult life. Considering that a high proportion of patients with diagnosis of DGH in childhood are no longer GHD in adolescence, the GH status must be retested when growth is completed. Other factors such as clinical history, GH response in childhood, hipotalamic-pituitary MRI and IGF-1 concentration must be considered. Reconfirmation of GHD diagnosis through stimulation testing is usually required, unless there is a proven genetic or structural lesion persistent from childhood.

Condução do tratamento com hormônio de crescimento (GH) nos pacientes com diagnóstico de deficiência GH (DGH) durante o período de transição da criança para o adulto: [revisão] / Management of the growth hormone (GH)-treated patients with diagnosis of GH deficiency (DGH) during transition from childhood to adulthood: [review]

Além de estimular o crescimento estatural, o hormônio de crescimento (GH) promove outros efeitos benéficos nos pacientes com deficiência de GH (DGH). A suspensão do GH em pacientes com DGH, durante o período de transição da criança para a vida adulta, induz a alterações metabólicas desfavoráveis na composição corporal, na integridade óssea, na capacidade para desempenhar atividade física, e também aumenta fatores de risco cardiovasculares. Estes parâmetros melhoram quando a reposição do GH é reiniciada em adultos com DGH. Com base nestas evidências, a reposição do GH não deveria ser suspensa quando o paciente atingisse sua altura final e, sim, mantida durante a vida adulta. Entretanto, considerando que muitos pacientes com diagnóstico de DGH, quando criança, não tem este diagnóstico confirmado no início da vida adulta, é necessário reavaliar a secreção de GH quando o paciente atingir a altura final. A história clínica do paciente, a resposta ao tratamento com GH, a ressonância magnética da região hipotalâmica-hipofisária e a concentração de IGF-1 podem ajudar nesta reavaliação. A realização de testes de estímulo para liberação do GH é necessária, a menos que o paciente apresente lesão estrutural ou genética que justifiquem a deficiência deste hormônio.

Growth hormone (GH) has many beneficial effects in patients with childhood-onset GH deficiency (GHD) in addition to its promotion of linear growth. The discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant unfavorable changes in body composition, skeletal integrity, exercise capacity, and an adverse cardiovascular risk profile. These changes are reversed after the resumption of GH treatment. As the benefits of continuing GH therapy into adulthood has been well established, it is possible that GH replacement therapy will not be stopped once growth has been completed, but it will continue into adult life. Considering that a high proportion of patients with diagnosis of DGH in childhood are no longer GHD in adolescence, the GH status must be retested when growth is completed. Other factors such as clinical history, GH response in childhood, hipotalamic-pituitary MRI and IGF-1 concentration must be considered. Reconfirmation of GHD diagnosis through stimulation testing is usually required, unless there is a proven genetic or structural lesion persistent from childhood.

Alteraçöes do sistema tiroideano induzidas pelo tratamento com hormônio do crescimento em crianças com hipopituitarismo / Replacement on thyroid sistem induced for the treatment with growth hormone in children with hypopituitarism

Os defeitos da reposiçäo do hormônio do crescimento (GH) nos níveis séricosrmônios tirpoidianos säo controversos. Para melhor estudar estes efeitos e procurar definir seus mecanismos, estudamos 20 pacientes (17M/3F, 9-18,5 anos) com diagnóstico de deficiência de GH (DGH), clinicamente em eutiroidismo e com dosagem de tiroxina livre (T4 livre) normal, no período sem reposiçäo de GH (antes de iniciar a terapêutica ou após suspensäo de 30 a 60 dias) e com reposiçäo de GH(0,5-7 anos). Em l2pacientes que näo receberam reposiçäo de tiroxina os níveis basais do hormônio tiroestimulante (TSH) estavam normais ou discretamente elevados (Grupo A) e em 8 que recebiam tiroxina (2,7 a 3,7 µg/Kg/dia) os níveis de TSH estavam suprimidos (Grupo B). As doses de reposiçäo de tiroxina foram mantidas constantes durante o estudo. Os níveis séricos de T4 Livre, triiodotironina total (T3 Total), T3 reverso (rT3) e do TSH basal e após estímulo com TRH foram determinados por imunoensaios específicos, sendo que as amostras do mesmo paciente foram dosadas sempre no mesmo ensaio. A secreçäo estimulada do TSH pelo TRH foi expressa como àra sob a curva (ASC). A anàlise estatística foi realizada pelo teste t pareado ou näo, e pelo teste de Wilcoxon dependendo da normalidade na distribuiçäo das amostras. O nível de significância adotado foi de 0.05. Os resultados säo expressos com média ñ DP