Accurate classification of postsurgical remission, and early recognition of recurrence are crucial to timely treat and prevent excess mortality in Cushing’s Disease, yet the criteria used to define ...remission are variable and there is no consensus to define recurrence. Remission is defined as postsurgical hypocortisolemia, but delayed remission may occur. Recurrence is the return of clinical manifestations with biochemical evidence of hypercortisolism. The proper combination of tests and their timing are controversial.
Reliable predicting tools may lead to earlier diagnosis upon recurrence. Many factors have been studied independently for prediction with variable performance. Novel artificial intelligence approaches seek to integrate these variables into risk calculators and machine-learning algorithms with an acceptable short-term predictive performance but lack longer-term accuracy. Prospective studies using these approaches are needed.
This review summarizes the evidence behind the definitions of remission and recurrence and provide an overview of the available tools to predict and/or diagnose them.
ObjectiveFibroblast growth factor 21 (FGF21) levels have been linked with beneficial effects on glucose and lipid metabolism in animals. It is elevated in humans with the metabolic syndrome. This ...study investigates independent factors associated with serum FGF21 levels.DesignCross-sectional study done in healthy blue-collar workers.MethodsA medical history was taken, and FGF21 (measured using an ELISA commercial kit), glucose, uric acid, plasma lipids, total/high-molecular weight (HMW) adiponectin, and retinal-binding protein 4 (RBP4) were measured in 210 individuals with (n=81) and without (n=129) metabolic syndrome.ResultsThe median of serum FGF21 levels were higher in subjects with metabolic syndrome (339.5 vs 276.4 ng/l, P=0.01). Serum FGF21 levels correlated positively with body mass index (BMI; r=0.23, P=0.001) and age (r=0.17, P=0.01). After adjusting for age and BMI, a significant positive correlation persisted for fasting glucose, uric acid, and physical activity in both males (r=0.21, r=0.11, and r=0.19, all P<0.05) and females (r=0.20, r=0.19, and r=0.14, all P<0.05). In addition, FGF21 also correlates negatively with RBP4 (r=−0.27, P=0.02), total (r=−0.26, P=0.03), and HMW adiponectin (r=−0.30, P=0.01) in women. A multiple linear regression model analysis identified that BMI (standardized β (SB)=0.247; P=0.008), glucose (SB=0.226; P=0.003), uric acid (SB=0.191; P=0.04), and physical activity (SB=0.223; P=0.004) are independent factors influencing serum FGF21 levels (F=10.05, r2=0.19, P<0.001). In addition, fasting hyperglycemia ≥100 mg/dl, excess body weight with BMI ≥25 kg/m2, and uric acid ≥5.5 mg/dl predicted higher serum FGF21 levels.ConclusionSerum FGF21 levels are influenced by BMI, fasting glycemia, uric acid, and physical activity.
Ectopic ACTH-secretion causing Cushing's syndrome is unusual and its diagnosis is frequently challenging. The presence of high-molecular-weight precursors throughout pro-opiomelanocortin (POMC) ...translation by these tumors is often not reported. We present the case of a 49-year-old woman with a 3-month history of proximal muscular weakness, skin pigmentation, and weight loss. Upon initial evaluation, she had a full moon face, hirsutism, and a buffalo hump. Laboratory workup showed hyperglycemia, hypokalemia and metabolic alkalosis. ACTH, plasma cortisol, and urinary free cortisol levels were quite elevated. Serum cortisol levels were not suppressed on dexamethasone suppression testing. An octreo-SPECT scan showed enhanced nucleotide uptake in the liver and pancreas. Transendoscopic ultrasound-guided biopsy confirmed the diagnosis of a pancreatic ACTH-secreting neuroendocrine tumor (NET). Surgical excision of both pancreatic and liver lesions was carried out. Western blot analysis of the tumor and metastases revealed the presence of a high-molecular-weight precursor possibly POMC (at 30 kDa) but not ACTH (normally 4.5 kDa). ACTH-precursor secretion is more frequent in ectopic ACTH-secreting tumors compared with other causes of Cushing's syndrome. Hence, the measurement of such ACTH precursors warrants further evaluation, especially in the context of ACTH-dependent hypercortisolism.
Objetivo: Describir el caso de un paciente masculino de 19 años que presenta bradicardia e hipotensión después de una picadura de abeja haciendo una revisión de la literatura y fisiopatología de los ...cambios cardiovasculares y electrocardiográficos después de una picadura de abeja. Métodos: Se inspeccionó y aseguró la vía aérea del paciente. Un rastreo de ECG realizado al ingreso reveló ritmo idioventricular a una ritmo de 41 latidos por minuto. Se administró oxígeno, se estableció un acceso IV y se colocaron los cables del marcapasos transcutáneo en el tórax del paciente, luego se indujo el manejo de las guías publicadas. Resultados: El electrocardiograma mostró un ritmo idioventricular a una frecuencia de 41 latidos por minuto que se resolvió a un ritmo sinusal normal después del tratamiento. Conclusiones: Se debe realizar una evaluación cardiovascular completa y rápida en todos los pacientes que se presentan al departamento de emergencias después de una picadura de abeja, y se deben seguir las pautas publicadas sobre el manejo de la bradicardia y la anafilaxia para lograr resultados exitosos.
Type 2 diabetes mellitus has become one of the most important public health concerns worldwide. Due to its high prevalence and morbidity, there is an avid necessity to find new therapies that slow ...the progression and promote the regression of the disease. Imatinib mesylate is a tyrosine kinase inhibitor that binds to the Abelson tyrosine kinase and related proteins. It enhances β-cell survival in response to toxins and pro-inflammatory cytokine. The aim of this study is to evaluate the effect of imatinib on fasting plasma glucose in subjects with normal fasting glucose, subjects with impaired fasting glucose and in subjects with type 2 diabetes mellitus.
We identified 284 subjects diagnosed with chronic myeloid leukemia or gastrointestinal stromal tumors from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran database. 106/284 subjects were treated with imatinib. We compared the effect of imatinib on fasting plasma glucose after 1 and 6 months of treatment. We used ANOVA test of repeated samples to determine statistical significance in fasting plasma glucose before imatinib treatment and the follow-up. Statistical analysis was performed with Statistical Package for the Social Sciences v22.
We included a total of 106 subjects: 76 with fasting plasma glucose concentrations < 100 mg/dL (normal FG), 19 subjects with fasting plasma glucose concentrations ≥100 mg/dL (impaired fasting glucose), and 11 subjects with ≥126 mg/dL (type 2 diabetes mellitus). We found a significant increase in fasting plasma glucose concentration in the normal fasting glucose group (p = 0.048), and a significant decrease in fasting plasma glucose concentration in the type 2 diabetes mellitus group (p = 0.042). In the impaired fasting glucose group, we also found a tendency towards a decrease in fasting plasma glucose (p = 0.076). We identified 11 subjects with type 2 diabetes mellitus, of whom, 7 (64%) had a reduction in their fasting plasma glucose concentrations after 6 months. A significant glycosylated hemoglobin reduction (p = 0.04) was observed.
Subjects with chronic myeloid leukemia or gastrointestinal stromal tumor with type 2 diabetes mellitus had a significant reduction in fasting plasma glucose and glycosylated hemoglobin at 1 and 6 months while using imatinib.
Adrenal cystic lymphangiomas are unusual entities with a very low prevalence that are typically discovered incidentally. We describe a 45-year-old male known for hypertension that was referred to our ...endocrinology department for right adrenal incidentaloma. Seven months prior referral, he presented right hypochondrium pain, vomiting and nausea and imaging studies included a computer tomography that revealed an irregular-shaped right adrenal lesion (42 × 23 mm), with scattered calcifications in the medial branch and heterogenous contrast enhancement and contrast-enhanced computer tomography showed an absolute wash-out of 28% and hyperattenuating areas (>90 HU). Physical examination was unremarkable. Hormonal studies were all within normal range. Due to the findings of imaging studies and lack of biochemical findings a presumptive diagnosis of non-producing adrenal carcinoma was made. Laparoscopic of right adrenalectomy was carried out. Macroscopic appearance of the resected right adrenal surface showed a 3.0 × 2.5 cm whitish-grayish multicystic lesion with solid areas that replaced all adrenal medulla and almost all the cortex. Microscopic examination revealed multiple cystic channels lined with endothelial cells without atypia or mitotic figures. On immunohistochemical examination, anti-calretinin, anti-D2-40 and anti-Factor VIII were all positive confirming the diagnosis of adrenal cystic lymphangioma. It is a rare pathology that should be considered as part of the differential diagnosis during the evaluation of adrenal gland masses.
The association between serum alanine aminotransferase (ALT) levels and hepatic insulin resistance (IR) has been evaluated with the hyperinsulinemic-euglycemic clamp. However, there is no information ...about the association of ALT with the Hepatic Insulin Resistance Index (HIRI). The aim of this study was to evaluate the association between serum ALT levels and HIRI in subjects with differing degrees of impaired glucose metabolism.
This cross-sectional study included subjects that had an indication for testing for type 2 diabetes mellitus (T2DM) with an oral glucose tolerance test (OGTT). Clinical and biochemical evaluations were carried out including serum ALT level quantification. HIRI was calculated for each participant. Correlation analyses and lineal regression models were used to evaluate the association between ALT levels and HIRI.
A total of 324 subjects (37.6% male) were included. The mean age was 40.4 ± 14.3 years and the mean body mass index (BMI) was 32.0 ± 7.3 kg/m2. Individuals were divided into 1 of 5 groups: without metabolic abnormalities (n = 113, 34.8%); with the metabolic syndrome (MetS, n = 179, 55.2%), impaired fasting glucose (IFG, n = 85, 26.2%); impaired glucose tolerance (IGT, n = 91, 28.0%), and T2DM (n = 23, 7.0%). The ALT (p < 0.001) and HOMA2-IR (p < 0.001) values progressively increased with HIRI quartiles, while ISI-Matsuda (p < 0.001) progressively decreased. After adjustment for sex, age, and BMI, we identified a significant correlation between HIRI and ALT in persons with the MetS (r = 0.22, p = 0.003), IFG (r = 0.33, p < 0.001), IGT (r = 0.37, p < 0.001), and T2DM (r = 0.72, p < 0.001). Lineal regression analysis adjusting for age, HDL-C, TG and waist circumference (WC) showed an independent association between ALT and HIRI in subjects with the MetS (beta = 0.07, p = 0.01), IFG (beta = 0.10, p = 0.02), IGT (beta = 0.09, p = 0.007), and T2DM (beta = 0.31, p = 0.003). This association was not identified in subjects without metabolic abnormalities.
ALT levels are independently associated with HIRI in subjects with the MetS, IFG, IGT, and T2DM. The ALT value in these subjects may be an indirect parameter to evaluate hepatic IR.
Abstract
Background
Cyclic Cushing syndrome is a clinical challenging diagnosis due to an unpredictable duration of periodic hypercortisolemia shifting with normocortisolemia periods. Only small ...proportion of such cases are due to a corticotroph pituitary adenoma with cyclic activity. Clinical case: 27-year-old after she stopped nursing her baby, she had no resumption of menses. She then developed mild headache and weight gain of 20kg throughout 3 months. She also developed facial hair, acne, easy bruising and striae. She was evaluated by a local physician where Cushing syndrome (CS) was suspected. Local testing showed the following results: UFC: 1117 and 1572 mcg/24h (<403mcg/24h), low dose DST of 595.8 nmol/l (<50nmol/l) and ACTH 60 pg/mL (10-100pg/mL). An MRI identified a 6 mm pituitary adenoma. The patient was sent to our pituitary clinic under the diagnosis of Cushing disease (CD). Upon examination at our institution, the patient reported asthenia, mood changes, depression and hirsutism. The physical examination revealed classical signs of CS. No other comorbidities were detected. A seven-hour 7mg dex infusion testwas performed (1), with basal cortisol of 187.5 nmol/l, early suppression of 12.6 nmol/l and late suppression of 27.5 nmol/l which is negative for hypercortisolism. As the high suspicion of CS, the patient was followed monthly with UFC and serum cortisol. During this normocortisolemia period the patient lost 10kg of weight, recovered its menses and coloration changes of striae. Laboratory follow up UFC of 67, 71 mcg/24h and serum cortisol of 124, 270, 103.4, 358.6 and 413 nmol/l ACTH 20, 21, 23, 28, 25 pg/mL. After 6 months of no clinical sign of hypercortisolism the patient reached to us as she noticed her striae changed, started gaining weight, lost menses and changed headache frequency. Laboratories revealed UFC was 754.6 mcg/24h and low dose DST was 751.1 nmol/l and ACTH of 70 pg/mL. We conducted another continuous 7mg dex infusion for seven hours with basal cortisol of 669.2 nmol/l, early suppression of 90.2 nmol/l (>50% suppression) and late suppression of 691.5 nmol/l which was compatible with CD. Additional testing was performed, with a 18F-NOTA-Octreotide and a full body CT that did not reveal an ectopic ACTH producing tumor neither an adrenal mass. Patient underwent a transsphenoidal surgery and reached remission of her hypercortisolism.
Conclusion
CD may be difficult to be confirmed but also it is important to consider that some cases showed cyclic activity. As far as we could acknowledged, this is the first case showing a 6-month period of normocortisolemia in a cyclic ACTH-secreting pituitary adenoma.
Bibliography
Biemond P, de Jong FH, Lamberts SW. Continuous dexamethasone infusion for seven hours in patients with the Cushing syndrome. A superior differential diagnostic test. Ann Intern Med. 1990 May 15;112(10): 738–42.
Presentation: No date and time listed
Epidemiologic evidence suggests that tomato-based products could reduce the risk of cardiovascular diseases. One of the main cardiovascular risk factors is low levels of high-density lipoprotein ...cholesterol (HDL-C). This study aimed to prospectively evaluate the effect of tomato consumption on HDL-C levels.
We conducted a randomized, single-blinded, controlled clinical trial. We screened 432 subjects with a complete lipid profile. Those individuals with low HDL-C (men <40 mg/dL and women <50 mg/dL) but normal triglyceride levels (<150 mg/dL) were included. Selected participants completed a 2-week run-in period on an isocaloric diet and then were randomized to receive 300 g of cucumber (control group) or two uncooked Roma tomatoes a day for 4 weeks.
A total of 50 individuals (women = 41; 82%) with a mean age of 42 ± 15.5 years and a mean body mass index of 27.6 ± 5.0 kg/m(2) completed the study. A significant increase in HDL-C levels was observed in the tomato group (from 36.5 ± 7.5 mg/dL to 41.6 ± 6.9 mg/dL, P < 0.0001 versus the control group). After stratification by gender, the difference in HDL-C levels was only significant in women. The mean HDL-C increase was 5.0 ± 2.8 mg/dL (range 1-12 mg/dL). Twenty patients (40%) finished the study with levels >40 mg/dL. A linear regression model that adjusted for those parameters that impact HDL-C levels (age, gender, waist-to-hip ratio, body mass index, fasting triglyceride concentration, simple sugars, alcohol, physical activity, and omega-3 consumption) showed an independent association between tomato consumption and the increase in HDL-C (r (2) = 0.69; P < 0.0001).
Raw tomato consumption produced a favorable effect on HDL-C levels in overweight women.
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