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Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest. This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals. Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes. This review highlights that for better success, VD deficiency needs to be corrected at multiple levels: (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action. This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.
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Cisteína , Suplementos Nutricionais , Glutationa , Regulação para Cima , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/genética , Vitamina D/sangue , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Glutationa/metabolismo , Glutationa/sangue , Animais , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismoRESUMO
Significance: Excess oxidative stress and neuroinflammation are risk factors in the onset and progression of Alzheimer's disease (AD) and its association with amyloid-ß plaque accumulation. Oxidative stress impairs acetylcholine (ACH) and N-methyl-d-aspartate receptor signaling in brain areas that function in memory and learning. Glutathione (GSH) antioxidant depletion positively correlates with the cognitive decline in AD subjects. Treatments that upregulate GSH and ACH levels, which simultaneously decrease oxidative stress and inflammation, may be beneficial for AD. Recent Advances: Some clinical trials have shown a benefit of monotherapy with vitamin D (VD), whose deficiency is linked to AD or with l-cysteine (LC), a precursor of GSH biosynthesis, in reducing mild cognitive impairment. Animal studies have shown a simultaneous decrease in ACH esterase (AChE) and increase in GSH; combined supplementation with VD and LC results in a greater decrease in oxidative stress and inflammation, and increase in GSH levels compared with monotherapy with VD or LC. Therefore, cosupplementation with VD and LC has the potential of increasing GSH, downregulation of oxidative stress, and decreased inflammation and AChE levels. Future Directions: Clinical trials are needed to determine whether safe low-cost dietary supplements, using combined VD+LC, have the potential to alleviate elevated AChE, oxidative stress, and inflammation levels, thereby halting the onset of AD. Goal of Review: The goal of this review is to highlight the pathological hallmarks and current Food and Drug Administration-approved treatments for AD, and discuss the potential therapeutic effect that cosupplementation with VD+LC could manifest by increasing GSH levels in patients. Antioxid. Redox Signal. 40, 663-678.
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Doença de Alzheimer , Vitamina D , Animais , Humanos , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Cisteína , Vitaminas , Estresse Oxidativo , Glutationa/metabolismo , Suplementos Nutricionais , Inflamação/tratamento farmacológico , Acetilcolina/farmacologiaRESUMO
OBJECTIVE: In an adult endocrine clinic, the majority of patients referred for evaluation of an incidentally discovered adrenal mass are aged more than 30 years, for which many national and international societies have developed management guidelines. However, adrenal incidentalomas in children and young adults are uncommon. We report the case of an 18-year-old woman with an incidentally discovered right-sided adrenal mass. METHODS: We present the adrenal tests, computed tomography, and magnetic resonance imaging results and treatment of a young woman with an adrenal mass that proved to be a ganglioneuroma. RESULTS: A computed tomography scan showed a 2.2 × 2.6 cm right-sided adrenal mass with noncontrast Hounsfield units >10 and <50% washout. Magnetic resonance imaging was not typical of a lipid-rich adenoma. Blood and urine tests demonstrated normal secretion of cortisol, aldosterone, adrenal androgens, and catecholamines. Based on the patient's age and imaging studies, she underwent a right adrenalectomy, removing a 2.2 × 2.0 × 2.7-cm ganglioneuroma. CONCLUSION: The differential diagnosis of an adrenal mass in children and adolescents is quite different compared with adult patients. There are no standardized guidelines for the management of adrenal masses in these younger age groups, although some authors recommend removing all adrenal masses, regardless of size or imaging characteristics, in all children aged more than 3 months. This case emphasizes how the management of adrenal masses in pediatric patients and young adults differs from guidelines published by endocrine and urologic societies.
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Introduction: Reduced circulating levels of 25(OH)VD are associated with an increased incidence of chronic lung diseases. Alpha-1-antitrypsin (AAT) is needed to maintain healthy lung function.Objective: This study examined the hypothesis that circulating levels of AAT are lower in adult type 2 diabetic patients and that a positive association exists between circulating AAT levels and 25(OH)VD levels in these patients.Methods: Fasting blood was obtained after written informed consent from type 2 diabetic patients (n = 80) and normal siblings or volunteers (n = 22) attending clinics at LSUHSC according to the protocol approved by the Institutional Review Board for Human studies. Plasma AAT and 25(OH)VD levels were determined using ELISA kits. HbA1c levels and chemistry profiles were analyzed at the clinical laboratory of LSUHSC hospital.Results: ATT and 25(OH)VD levels were significantly lower in type 2 diabetic patients compared with those of age-matched healthy controls. There was a significant positive correlation between 25(OH)VD and ATT deficiency. AAT levels showed significant positive correlation with HDL cholesterol levels in type 2 diabetic patients. There was no correlation between AAT levels and those of HbA1c or with the duration of diabetes of T2D patients.Conclusions: These results suggest that 25(OH)VD deficiency may predispose type 2 diabetic patients to AAT deficiency. Whether reduced levels of circulating AAT indeed contribute to the increased risk for lung dysfunction in subjects with type 2 diabetes needs further investigation.
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Diabetes Mellitus Tipo 2 , Deficiência de Vitamina D , Vitamina D/sangue , alfa 1-Antitripsina/sangue , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Jejum , Humanos , VitaminasRESUMO
Primary hyperparathyroidism is not commonly diagnosed during pregnancy. For pregnant women with mild, asymptomatic disease, surgery can be avoided unless the degree of hypercalcemia becomes more severe or they develop complications. However, there are no evidence-based guidelines to assist clinicians regarding the management of primary hyperparathyroidism during pregnancy. When surgery is deemed necessary during pregnancy, the second trimester is generally considered to be the optimal time. We report the case of a 31-year-old female G1P0 who presented at 6 weeks gestation with symptoms of nausea, vomiting, polyuria, and corrected calcium of 14.8 mg/dL. Due to the extreme degree of hypercalcemia and refractory to medical treatment, it was decided that surgery could not be delayed until the second trimester. At 7w3d gestational age the patient had resection of a 37 gram, 5 × 4 × 3 cm right inferior parathyroid adenoma.
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OBJECTIVES: Transient hyperthyroidism has been documented following surgical manipulation or direct trauma to the normal thyroid gland. This has best been studied in patients following parathyroidectomy and also reported following trauma to the neck, strangulation, and vigorous palpation of the thyroid gland. It has not previously been reported following a thyroid ultrasound. METHODS: We report the case of a 58-year-old euthyroid woman with a large nontoxic multinodular goiter who developed transient hyperthyroidism following an ultrasound of the thyroid gland. She was not treated with anti-thyroid medications. RESULTS: Two weeks later, her free T3 and free T4 were normal, and 11 weeks after the ultrasound, all thyroid tests, including her TSH, were within the reference range. CONCLUSIONS: We believe this is the first report of a euthyroid individual who developed hyperthyroidism caused by thyroid ultrasonography. We hypothesize that pressure from the ultrasound probe during the examination compressed her large nodules, releasing stored hormone.
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Bócio/diagnóstico , Hipertireoidismo/etiologia , Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/efeitos adversos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Primary hypothyroidism can cause both hyperprolactinemia and pituitary hyperplasia. The degree of hyperprolactinemia is generally modest, and rarely do prolactin concentrations exceed 100 ng/mL (4.34 nmol/L). This combination of hyperprolactinemia and pituitary gland enlargement might raise suspicion for a prolactinoma or a nonfunctioning adenoma limiting the ability of hypothalamic dopamine to inhibit prolactin production, the so-called "stalk effect." CASE DESCRIPTION: We describe a 30-year-old female with headaches, galactorrhea, and hyperprolactinemia with a presumptive diagnosis of a prolactinoma. She had hypothyroidism after treatment of Graves disease at age 17 years but was noncompliant with levothyroxine replacement. Thyroid-stimulating hormone (TSH) was 263 mIU/L, FT4 was 3.01 pmol/L, and prolactin was 323 ng/mL (14.06 nmol/L). Magnetic resonance imaging (MRI) demonstrated increased volume of the pituitary gland with homogeneous enhancement with gadolinium. Levothyroxine treatment for 2 weeks decreased her TSH to130 mIU/L, but her total prolactin remained elevated at 386 ng/mL (16.78 nmol/L). Further testing identified that 76% of the total prolactin was macroprolactin. CONCLUSIONS: Primary hypothyroidism can cause hyperprolactinemia, and prolonged disease may lead to pituitary hyperplasia. However, a marked elevation of prolactin should raise suspicion to investigate additional etiologies for hyperprolactinemia. Our case exemplifies a dual etiology for hyperprolactinemia and pituitary hyperplasia caused by both hypothyroidism and macroprolactin. This knowledge is invaluable for clinicians to avoid unnecessary management with dopamine agonists and/or surgery. This patient's prolactin was 323 ng/mL (14.06 nmol/L). Before our case, the highest prolactin in a hypothyroid patient reported in the literature was 253 ng/mL (11.0 nmol/L).
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Hiperprolactinemia/etiologia , Hipotireoidismo/metabolismo , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Hiperprolactinemia/diagnóstico por imagem , Hipotireoidismo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hipófise/diagnóstico por imagemRESUMO
AIMS: Vitamin D (VD) deficiency has become a worldwide epidemic, particularly affecting African Americans (AA). VD deficiency has been implicated in the excessive rate of complications associated with diabetes in AA. Blood levels of VD binding protein (VDBP) and glutathione (GSH) are lower in AA compared with those in Caucasians. This study tested the hypothesis that lower GSH levels are linked to VDBP and VD deficiency in AA-type 2 diabetic (AA-T2D) patients. Blood was analyzed from T2D and nondiabetic subjects (N). Experiments examining GSH deficiency and l-cysteine (LC) supplementation were performed using THP-1 monocytes. RESULTS: Plasma levels of LC, GSH, VDBP, and VD were significantly lower in AA-T2D compared with age-matched AA-N or Caucasian-T2D. Lower levels of LC and GSH showed a significant positive correlation with lower VDBP and VD levels in AA-T2D. GSH deficiency investigated using an antisense approach depleted VDBP/vitamin D receptor (VDR); LC supplementation caused significant upregulation of GSH and of VDBP/VDR, while supplementation with VD+LC caused a significantly greater GSH and VDBP/VDR upregulation compared with that of VD alone in monocytes. INNOVATION AND CONCLUSION: The reported observations suggest that VD deficiency may be linked to GSH and LC status and lead to a novel hypothesis that supplementation with LC in combination with VD will be effective in increasing VD levels and reducing health disparities in AA.
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Cisteína/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteína de Ligação a Vitamina D/sangue , Vitamina D/uso terapêutico , Adulto , Negro ou Afro-Americano , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Glutationa/deficiência , Humanos , Pessoa de Meia-Idade , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
CONTEXT: Hypercalcemia associated with lymphomas can be secondary to increased calcitriol [1,25(OH)2 vitamin D3], PTHrP, or osteolytic metastases. OBJECTIVE: A case of calcitriol-mediated hypercalcemia secondary to non-Hodgkin lymphoma in a patient with postsurgical hypoparathyroidism is presented. DESIGN AND SETTING: Single patient managed at a tertiary health care facility in the United States. PATIENT: A 55-year-old white woman had a total thyroidectomy and radioiodine ablation for a 3.5-cm follicular carcinoma. Surgery was complicated by permanent hypoparathyroidism treated with calcium, calcitriol, and cholecalciferol. For over 16 years she had no evidence of either residual thyroid tissue in the neck or metastasis. Her corrected serum calcium levels were appropriately maintained in the low-normal range. During a routine clinic visit, she had mild hypercalcemia; calcium and cholecalciferol were reduced by 50%, while calcitriol was continued. Two weeks later, she presented with nausea, abdominal pain, and multiple rapidly enlarging cervical and axillary lymph nodes with elevated calcium and calcitriol. A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan and lymph node biopsy were diagnostic for non-Hodgkin lymphoma. INTERVENTION: Calcium and calcitriol were stopped; hypercalcemia was corrected with iv fluids. Chemotherapy resulted in an excellent response within 7 weeks; calcitriol normalized, and the patient developed recurrent hypocalcemia. Positron emission tomography/computed tomography scans at 7 weeks and 3 months after treatment documented near-complete resolution of the lesions. Outcome and Result: Sixteen months after the treatment of lymphoma, the patient remains free of disease and is on calcium, calcitriol, and cholecalciferol. CONCLUSION: Clinicians should have a high index of suspicion for malignancy when patients presents with rapid and high elevations of serum calcium.
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Cálcio/sangue , Hipercalcemia/etiologia , Hipocalcemia/etiologia , Hipoparatireoidismo/etiologia , Linfoma não Hodgkin/diagnóstico , Tireoidectomia/efeitos adversos , Adenocarcinoma Folicular/cirurgia , Calcitriol/sangue , Calcitriol/uso terapêutico , Cálcio/uso terapêutico , Colecalciferol/sangue , Colecalciferol/uso terapêutico , Feminino , Humanos , Hipercalcemia/sangue , Hipocalcemia/sangue , Hipocalcemia/tratamento farmacológico , Hipoparatireoidismo/sangue , Hipoparatireoidismo/tratamento farmacológico , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/complicações , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
Hypercalcemia may be seen in a variety of clinical settings and often requires intensive management when serum calcium levels are dramatically elevated. All of the many etiologies of mild hypercalcemia can lead to severe hypercalcemia. Knowledge of the physiologic mechanisms involved in maintaining normocalcemia and basic pathophysiology is essential for making a timely diagnosis and hence prompt institution of etiology-specific therapy. The development of new medications and critical reviews of traditional therapies have changed the treatment paradigm for severe hypercalcemia, calling for a more limited role for aggressive isotonic fluid administration and furosemide and an expanded role for calcitonin and the bisphosphonates. Experimental therapies such as denosumab show promise.
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Cálcio/metabolismo , Hipercalcemia , Hiperparatireoidismo Primário , Unidades de Terapia Intensiva , Cálcio/sangue , Diagnóstico Diferencial , Hidratação , Homeostase , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hipercalcemia/metabolismo , Hipercalcemia/fisiopatologia , Hipercalcemia/terapia , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/terapia , Hormônio Paratireóideo/metabolismoRESUMO
Pituitary adenomas are the most common tumors of the sellar region, but the occurrence of spherical amyloid deposits in a pituitary adenoma is rare. We describe the clinical features, radiologic characteristics, and pathologic findings of 45-year-old man who presented with galactorrhea, hypogonadism, and hyperprolactinemia who had a pituitary adenoma with extensive spherical amyloid deposits. Approximately 30 cases have been reported, almost exclusively in patients with prolactinomas. Treatment with dopaminergic agonists will result in the expected reduction in prolactin levels; however, in most cases, macroadenomas with spherical amyloid deposits fail to decrease in size. The source of the amyloid deposits in prolactinomas is not clearly defined but may be due to abnormal processing of prolactin or its prohormone. These adenomas with spherical amyloid have a characteristic appearance on magnetic resonance imaging with low or heterogeneous intensity on T1 and low intensity on T2-weighted images. Following infusion of gadolinium, there is enhancement of the periphery but not most of the tumor mass. These magnetic resonance imaging characteristics are different than those of typical pituitary adenomas. These differences should alert clinicians to the possibility of extensive spherical amyloid deposits in a prolactin-secreting pituitary adenoma, which may have important clinical implications. In this report, we correlate the radiologic finds with the pathology and compared them with other sellar and parasellar lesions.
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Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Prolactinoma/diagnóstico por imagem , Feminino , Gadolínio DTPA , Galactorreia , Humanos , Hiperprolactinemia , Hipogonadismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Hipófise/patologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Placa Amiloide , Prolactina/metabolismo , Prolactinoma/metabolismo , Prolactinoma/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Pituitary carcinomas are rare and challenging clinical entities. Because of the paucity of cases, there is limited information in the literature on how best to diagnose and treat pituitary carcinomas. METHODS: We review the literature and describe a woman who presented with an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma that later evolved into a carcinoma with intracranial metastases. RESULTS: A 39-year-old woman presented at age 27 with classic findings of Cushing's syndrome and a pituitary macroadenoma. Her initial treatment was transsphenoidal surgery, during which we confirmed an ACTH-secreting pituitary neoplasm. For 5 years, she was asymptomatic before her first recurrence. During the next 6 years, she underwent four transsphenoidal surgeries and two craniotomies. After each surgery, there was some reduction in the size of the macroadenoma but the residual tumor mass would rapidly enlarge. Immunochemical staining was positive for ACTH, and a stain for Ki-67 antigen showed a high mitotic index. Eleven years after her initial presentation, magnetic resonance imaging revealed bilateral hippocampal and tempero-occipital masses. The patient's health continued to deteriorate, largely from complications of severe hypercortisolemia, and she died from sepsis. At postmortem, the hippocampus and tempero-occipital lobe masses proved to be a pituitary tumor with positive ACTH staining. CONCLUSIONS: Pituitary carcinomas are rare, may present many years after diagnosis of a primary pituitary adenoma, and should be suspected in patients with persistent or recurrent disease. Reliable histopathologic ways to distinguish between carcinoma and adenoma are difficult because the features of hypercellularity, nuclear pleomorphism, and mitotic figures are not always helpful.
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Adenoma Hipofisário Secretor de ACT/secundário , Adenoma/patologia , Neoplasias Encefálicas/secundário , Carcinoma/secundário , Neoplasias Hipofisárias/patologia , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/terapia , Adenoma/terapia , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Carcinoma/diagnóstico , Carcinoma/terapia , Feminino , Humanos , Neoplasias Hipofisárias/terapiaRESUMO
African Americans (AA) have a higher incidence of cardiovascular disease and vitamin D (VD) deficiency compared with Caucasians. Hydrogen sulfide (H(2)S) is an important signaling molecule. This study examined the hypothesis that blood levels of H(2)S are lower in AA type 2 diabetic patients (T2D). Fasting blood was obtained from T2D and healthy controls. Results showed a significant decrease in plasma levels of cyclic adenosine monophosphate (cAMP) and H(2)S in AA T2D but not in Caucasian T2D when compared with those of respective age- and race-matched healthy controls. Plasma VD levels were significantly lower in AA T2D compared with Caucasian T2D. Cell culture studies demonstrate that 1,25(OH)(2)-VD supplementation significantly increased expression of cystathionine-γ-lyase (CSE), H(2)S formation, and cAMP secretion, but decreased reactive oxygen species in high glucose-treated U937 monocytes. This suggests that VD supplementation upregulates CSE and H(2)S formation and decreases oxidative stress, and that VD deficiency may contribute to the malfunctioning of H(2)S signaling and thus a higher incidence of vascular inflammation in AA. These results lead to the hypothesis that VD supplementation can replenish blood concentrations of H(2)S and cAMP and lower oxidative stress and cardiovascular disease in AA T2D.
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AMP Cíclico/sangue , Diabetes Mellitus Tipo 2/sangue , Sulfeto de Hidrogênio/sangue , Estresse Oxidativo/fisiologia , Deficiência de Vitamina D/sangue , Adulto , Negro ou Afro-Americano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismoRESUMO
INTRODUCTION: Sleep deficits associated with sleep apnea and insomnia increase the risk of vascular inflammation and insulin resistance. This study examined the hypothesis that inflammation markers are higher in those diabetic patients who experience sleep deficits compared with those without any history of a sleep disorder. METHODS: Fasting blood was obtained after written informed consent, and sleep disorder histories were obtained from type 2 diabetic patients (n=81) attending clinics of the Louisiana State University Health Sciences Center. RESULTS: There was a significant correlation between body weight and leptin, and leptin in turn was significantly correlated with 10-kDa interferon-γ-induced protein (IP-10) levels and insulin resistance in type 2 diabetic patients. Fasting blood levels of leptin, IP-10, and insulin resistance were significantly elevated in patients with sleep deficits compared with diabetics with normal sleep patterns. There were no differences in glycosylated hemoglobin (HbA1c) or fasting glucose in patients with sleep deficits compared with those with normal sleep patterns. Sleep deficits increase circulating levels of leptin, IP-10, and insulin resistance compared to levels seen in patients with diabetes who reported no difficulty with sleep. Patients with sleep apnea had significantly lower hydrogen sulfide (H(2)S) levels compared with patients with normal sleep patterns or patients with insomnia. Low levels of circulating H(2)S could contribute to higher vascular inflammation in patients with sleep apnea. CONCLUSIONS: These results suggest that sleep apnea is associated with a decrease in circulating H(2)S and sleep disorders increase the risk of inflammation and insulin resistance, which can contribute to the increased risk of vascular disease in subjects with type 2 diabetes.
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Quimiocina CXCL10/sangue , Diabetes Mellitus Tipo 2/sangue , Sulfeto de Hidrogênio/sangue , Resistência à Insulina , Leptina/sangue , Síndromes da Apneia do Sono/sangue , Distúrbios do Início e da Manutenção do Sono/sangue , Adulto , Peso Corporal/fisiologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/metabolismo , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/metabolismoRESUMO
SCOPE: Chromium and cysteine supplementation have been shown to improve glucose metabolism in animal studies. This study examined the hypothesis that chromium dinicocysteinate (CDNC), a complex of chromium and l-cysteine, is beneficial in lowering oxidative stress, vascular inflammation, and glycemia in type 2 diabetic subjects. METHODS AND RESULTS: Type 2 diabetic subjects enrolled in this study were given placebo for 1 month for stabilization and then randomized into one of three groups: placebo (P), chromium picolinate (CP), or CDNC, after which they received daily oral supplementation for 3 months. Of the 100 patients enrolled in the study, 74 patients completed it. There were 25 patients in the P supplemented group, 25 in the CP supplemented and 24 in the CDNC supplemented group who completed the study. Blood markers of glycemia, vascular inflammation, HOMA insulin resistance, and oxidative stress were determined at randomization and after 3 months of supplementation with P, CP, or CDNC. There was a significant decrease at 3 months in insulin resistance (p = 0.02) and in the levels of protein oxidation (p = 0.02) and TNF-α (p = 0.01) in the CDNC supplemented cohort compared to baseline. However, there was no statistically significant change in these markers in the CP supplemented group compared to baseline. Insulin levels significantly decreased (p = 0.01) for subjects receiving CDNC but not CP. There was no significant impact of supplementation on HbA(1c) or glucose levels in either of the groups. CONCLUSION: CDNC supplementation lowers insulin resistance by reducing blood levels of TNF-α, insulin, and oxidative stress in type 2 diabetic subjects. Therefore, CDNC supplementation has potential as an adjunct therapy for individuals with type 2 diabetes.
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Cisteína/análogos & derivados , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Insulina/sangue , Compostos Organometálicos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Adulto , Cisteína/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To review the association between congenital adrenal hyperplasia (CAH) and adrenal myelolipomas and report a case of bilateral, giant adrenal myelolipomas in a patient with untreated CAH due to 21-hydroxylase deficiency. METHODS: We describe the patient's clinical presentation, imaging findings, and laboratory test results and review the relevant English-language literature concerning patients with both CAH and myelolipomas. RESULTS: A 45-year-old man with untreated CAH due to 21-hydroxylase deficiency presented with increasing abdominal girth and abdominal pain. Computed tomography of the abdomen demonstrated very low-density adrenal masses (22 × 11 cm on the left side and 6 × 5.5-cm on the right side) consistent with adrenal myelolipomas. The left adrenal myelolipoma was resected (24.4 × 19.0 × 9.5 cm; 2557 g). The mass was composed of mature adipose tissue with areas of hematopoietic cells of myeloid, erythroid, and megakaryocytic cell lines. Islands of adrenal cortical cells were scattered between the adipose and hematopoietic tissue. Including the present case, we identified 31 patients with both CAH and myelolipomas who have been described in the English-language literature. The details of these cases were reviewed. CONCLUSIONS: Persons with CAH may be at increased risk of developing adrenal myelolipomas, particularly if their CAH is poorly controlled. How and whether chronic exposure of the adrenal glands to high corticotropin levels increases the risk of developing myelolipomas remains a matter of speculation.
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Neoplasias das Glândulas Suprarrenais/complicações , Hiperplasia Suprarrenal Congênita/complicações , Mielolipoma/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/patologia , Hiperplasia Suprarrenal Congênita/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mielolipoma/diagnóstico , Mielolipoma/patologia , Mielolipoma/cirurgiaRESUMO
Hydrogen sulfide (H(2)S) is emerging as a physiological neuromodulator as well as a smooth muscle relaxant. We submit the first evidence that blood H(2)S levels are significantly lower in fasting blood obtained from type 2 diabetes patients compared with age-matched healthy subjects, and in streptozotocin-treated diabetic rats compared with control Sprague-Dawley rats. We further observed that supplementation with H(2)S or an endogenous precursor of H(2)S (l-cysteine) in culture medium prevents IL-8 and MCP-1 secretion in high-glucose-treated human U937 monocytes. These first observations led to the hypothesis that lower blood H(2)S levels may contribute to the vascular inflammation seen in diabetes.
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Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Sulfeto de Hidrogênio/sangue , Inflamação/induzido quimicamente , Animais , Diabetes Mellitus Tipo 2/imunologia , Glucose/farmacologia , Humanos , Sulfeto de Hidrogênio/farmacologia , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Ratos , Ratos Sprague-Dawley , Estreptozocina/efeitos adversosRESUMO
Thyrotoxic periodic paralysis (TPP) is an unusual complication of hyperthyroidism that frequently presents in a dramatic fashion, necessitating treatment in an emergency department or admission to an intensive care unit. Thyrotoxic periodic paralysis is characterized by transient, recurrent episodes of flaccid muscle paralysis affecting proximal more severely than distal muscles. Thyrotoxic periodic paralysis is most commonly a complication of Graves' disease in Asian males, although in recent decades, an increasing number of patients from all racial and ethnic backgrounds have been reported. Thyrotoxic periodic paralysis has a higher predilection for men than women despite the fact that thyroid disease is more frequently diagnosed in women. The presence of both hypokalemia and elevated levels of triiodothyronine (T3) and thyroxine (T4) are important diagnostic features during the acute episode. Treatment of TPP involves 2 steps, immediate action to reverse the paralysis followed by measures to prevent future attacks by restoration of a euthyroid state. Although the mainstay of treating an acute attack of TPP is correction of hypokalemia to avoid fatal cardiac arrhythmias and reverse muscle weakness, it must be appreciated by treating physicians that patients with TPP do not have a total body deficiency of potassium. Close attention must be given to potassium replacement as overly aggressive treatment can result in hyperkalemia. Correction of hypokalemia and the underlying thyrotoxic state usually results in amelioration of the acute attack. This review summarizes the epidemiology, clinical manifestations, pathogenesis, diagnosis, and treatment of TPP.
Assuntos
Paralisia , Potássio/uso terapêutico , Tireotoxicose , Antagonistas Adrenérgicos beta/uso terapêutico , Antitireóideos/uso terapêutico , Diagnóstico Diferencial , Feminino , Doença de Graves/complicações , Humanos , Hipopotassemia/complicações , Masculino , Paralisia/tratamento farmacológico , Paralisia/etiologia , Fatores Sexuais , Tireotoxicose/diagnóstico , Tireotoxicose/tratamento farmacológico , Tireotoxicose/etiologiaRESUMO
OBJECTIVE: To report the 12th case of a patient with a plasma cell granuloma of the thyroid, a rare cause of goiter and hypothyroidism. METHODS: We present a case report of a woman with a plasma cell granuloma of the thyroid. The clinical and pathologic features of the lesion are described, the differential diagnosis is discussed, and the relevant literature is reviewed. RESULTS: Plasma cell granulomas are uncommon benign lesions most typically located in the lung and only rarely identified in other organs. Only 11 cases of plasma cell granuloma of the thyroid gland have been reported previously. We describe the case of a 55-year-old woman with a long history of hypothyroidism and compressive symptoms from an enlarging neck mass. A thyroidectomy was performed. On gross examination, the thyroid had been replaced by firm, white, fibrotic tissue with a multinodular appearance. On microscopy, the infiltrate consisted predominantly of plasma cells that were polyclonal with the expression of both kappa and lambda light chains. A minor component of CD5- and CD20-positive (T and B) lymphocytes was observed. These features were important for establishing the diagnosis of a plasma cell granuloma and distinguishing the lesion from a plasmacytoma. CONCLUSION: This is the 12th reported case of plasma cell granuloma of the thyroid gland, a very rare cause of either a diffuse or a nodular goiter and hypothyroidism. The presence of a polyclonal plasma cell population with the expression of both kappa and lambda light chains helps to distinguish a plasma cell granuloma from a malignant plasmacytoma of the thyroid gland.
Assuntos
Granuloma de Células Plasmáticas/diagnóstico , Doenças da Glândula Tireoide/diagnóstico , Feminino , Granuloma de Células Plasmáticas/imunologia , Granuloma de Células Plasmáticas/cirurgia , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/imunologia , Doenças da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
BACKGROUND: The popularity of gastric bypass surgery for treatment of morbid obesity has been increasing in recent years. Osteomalacia and osteoporosis are commonly observed in patients who have had partial gastric resections for treatment of peptic ulcer disease. Recently, we encountered four patients with previous gastric bypass surgery who had metabolic bone disease similar to that reported in the older literature in patients who had partial gastrectomies. METHODS: Review of clinical data of four patients who developed osteomalacia and osteoporosis 9 to 12 years after gastric bypass surgery for morbid obesity. RESULTS: All subjects were women, 43 to 58 years old. Three had Roux-en-Y gastric bypass, and the other had a biliopancreatic diversion 9 to 12 years prior to presentation. Weight loss averaged 41.8 kg. Patients reported fatigue, myalgias, and arthralgias. They had symptoms for many months or years before the correct diagnosis was established. All were osteopenic or osteoporotic with hypocalcemia, very low or undetectable 25-hydroxyvitamin D levels, secondary hyperparathyroidism, increased 1,25-dihydroxyvitamin D levels, and increased serum alkaline phosphatase. CONCLUSIONS: Relatively little has been published in the general medical literature about this postoperative complication of bariatric surgery. Yet, nearly all patients after bariatric surgery will receive their long-term follow-up from a primary care physician. Physicians and patients need to be aware of this complication and take measures to identify and prevent it.