Mediators of energy homeostasis in hyperthyroidism

ABSTRACT Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) ( P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL ( P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL ( P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

Mediators of energy homeostasis in hyperthyroidism.

Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) (P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL (P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL (P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

Effect of Correction of Hyperthyroidism with Anti-thyroid Drugs on the Glycated Hemoglobin in Non-diabetic Patients with Primary Hyperthyroidism.

BACKGROUND: Glycated hemoglobin (HbA1c) levels are dependent not only on the average blood glucose levels over the preceding 2 - 3 months but also on the turnover of erythrocytes. Hyperthyroidism is known to be associated with an increase in erythrocyte turnover that may falsely lower the HbA1c in relation to the level of glycemia. OBJECTIVES: To assess the impact of medical correction of hyperthyroidism on HbA1c, independent of changes in the fasting plasma glucose and 2-hour post-oral glucose tolerance test plasma glucose. METHODS: Adult patients with overt hyperthyroidism (n = 36) were tested for their hemoglobin, reticulocyte percentage, HbA1c and fasting and post-oral glucose tolerance test (OGTT) 2-hour plasma glucose, both at baseline and following at least three months of near normalization of serum thyroxin on Carbimazole treatment. RESULTS: Correction of hyperthyroidism in 36 patients was associated with an increase in the hemoglobin (P = 0.004) and a rise in HbA1c (P = 0.025), even though no significant change was observed in both the fasting (P = 0.28) and post OGTT two-hour plasma glucose (P = 0.54). Also, the proportion of patients with HbA1c ≥ 5.7% rose from 3/36 to 10/36; P = 0.016, while the proportion of patients with either abnormal fasting or abnormal post OGTT 2-hour plasma glucose or both did not show any significant change (P = 0.5). The sensitivity of HbA1c to diagnose prediabetes increased from 20% to 50% post- treatment. CONCLUSIONS: Glycated hemoglobin is falsely low in relation to glycemia in patients with untreated hyperthyroidism.

Secondary amyloidosis associated with heroin use and recurrent infections - A case report.

A 49-year-old lady with history of polysubstance use disorder, recurrent cutaneous abscesses, spinal diskitis and septic thrombophlebitis presented to the emergency room with complaints of intermittent fevers, worsening right hip pain and bilateral lower extremity edema. A month before the presentation, she had left another hospital against medical advice after being diagnosed with Methicillin-resistant Staphylococcus aureus bacteremia and right hip septic arthritis. Post discharge, she was off antibiotics, but continued heroin and methamphetamine use. On admission, she had right hip chronic osteomyelitis and was also in acute renal failure with evidence of nephrotic range proteinuria. Her renal biopsy subsequently revealed acute tubular necrosis and secondary (AA) amyloidosis with the classic apple green birefringence and positive immunohistochemical stain for serum amyloid A protein. Secondary amyloidosis, where there is deposition of fibrils composed of fragments of the acute phase reactant - serum amyloid A protein, often complicates chronic diseases with ongoing or recurring inflammation like spondyloarthropathies, inflammatory bowel disease and heredofamilial periodic fever syndromes. Epidemiological studies now indicate that chronic inflammation as noted in illicit drug users, especially heroin users is on the rise as the etiology for AA amyloidosis in some parts of the developed world. The most common organ system involved in AA amyloidosis is the kidney. Given the opioid epidemic, clinicians are more likely to encounter similar cases of secondary amyloidosis.

A study to assess expression of human papillomavirus types 16 and 18 in oral squamous cell carcinoma using polymerase chain reaction.

OBJECTIVE: The diverse subset of oral squamous cell carcinoma (OSCC) with different clinical appearance and outcome, independent of traditional risk factors has led to increasing attention in human papillomavirus (HPV) infection. MATERIALS AND METHODS: The investigation followed a case-control design. Information pertaining to the subjects was retrieved from hospital records. Twenty cases of OSCC and twenty age-matched controls were analyzed to ascertain the prevalence of HPV types 16 and 18. DNA was extracted from the blocks of formalin-fixed paraffin embedded tissues, and HPV-DNA was amplified using HPV type-specific primers by polymerase chain reaction (PCR) method. Data analysis was carried out using Chi-square test. RESULTS: HPV-DNA was detected in 55% of cases (11/20; HPV 16 = 6, HPV 18 = 3 and HPV 16 and 18 = 2) and 30% of controls (6/20; HPV 16 = 3, HPV 18 = 1 and HPV 16 and 18 = 2) indicating higher percentage of HPV presence among OSCC cases. No significant association was found between the presence of HPV and gender, age, site and grade of differentiation of OSCC. CONCLUSION: Although the presence of HPV was higher in cases compared to controls, none of these differences were statistically significant. HPV 16 and 18 are commonly found in normal oral mucosa mandating the need for distinguishing clinical, subclinical and latent HPV infections.

Screening guidelines for non-AIDS defining cancers in HIV-infected individuals.

PURPOSE OF REVIEW: The growing burden of non-AIDS defining malignancies (non-ADMs) among people living with HIV/AIDS (PLWHA) highlights the need for cancer prevention and early detection. In this article, we propose screening guidelines for non-ADMs in PLWHA. RECENT FINDINGS: A number of recent findings may help direct cancer screening guidelines in PLWHA. Screening for lung cancer with low-dose helical chest computerized tomography (LDCT) in the National Lung Screening Trial data demonstrated a decrease in lung cancer and all-cause mortality. Recent studies have demonstrated a favorable experience among PLWHA with liver transplantation. Overdiagnosis is common with breast and prostate cancer screening. Anal cancer rates were substantially higher for HIV-infected MSM, other men and women than for HIV-uninfected individuals. SUMMARY: Screening recommendations for the general population can be applied to PLWHA patients for breast, colon and prostate cancer. Screening for lung cancer with LDCT could be considered in PLWHA at risk. American Association for the Study of Liver Diseases screening recommendations with biennial ultrasonography may be applied to at-risk PLWHA for hepatocellular carcinoma. All HIV-infected adults should be offered anal cancer screening as part of clinical care at specialized centres.

Vanishing lung syndrome and HIV infection: an uncommon yet potentially fatal sequela of cigarette smoking.

Persons with HIV infection have a higher risk of infectious pulmonary complications, chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis than individuals not infected with HIV. Herein, we describe the clinical course of a patient with longstanding and well-controlled HIV infection and multiple previous pneumothoraces who presented to medical attention with insidious onset of shortness of breath and was diagnosed with vanishing lung syndrome (VLS). The VLS or giant bullous emphysema is a distinct clinical syndrome characterized by large bullae, predominantly in the upper lobes, occupying at least one third of the hemithorax and compressing surrounding normal lung parenchyma. It is a progressive disorder that typically occurs in young men, the majority of whom are smokers. As people with HIV/AIDS are now surviving well into middle age and beyond, clinicians are more likely to encounter VLS and severe obstructive lung disease, which are potentially fatal but preventable conditions.

Lung cancer in HIV Infection.

Lung cancer is the most prevalent non-AIDS-defining malignancy in the highly active antiretroviral therapy era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is two to four times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the most common histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Because pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early-stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies because this population is frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers.

9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol, from Eulophia ochreata, inhibits inflammatory signalling mediated by Toll-like receptors.

BACKGROUND AND PURPOSE: 9,10-Dihydro-2,5-dimethoxyphenanthrene-1,7-diol (RSCL-0520) is a phenanthrene isolated from Eulophia ochreata, one of the Orchidaceae family, known by local tradition to exhibit medicinal properties. However, no anti-inflammatory activity or any molecular mechanisms involved have been reported or elucidated. Here, for the first time, we evaluate the anti-inflammatory properties of RSCL-0520 on responses induced by lipopolysaccharide (LPS) and mediated via Toll-like receptors (TLRs). EXPERIMENTAL APPROACH: The in vitro anti-inflammatory activities of RSCL-0520 were investigated in LPS-stimulated monocytic cells, measuring activation of cytokine and inflammatory genes regulated by nuclear factor-kappaB (NF-kappaB). Tumour necrosis factor (TNF)-alpha levels in serum following LPS stimulation in mice and carrageenan-induced paw oedema in rats were used as in vivo models. KEY RESULTS: Pretreatment with RSCL-0520 effectively inhibited LPS-induced, TLR4-mediated, NF-kappaB-activated inflammatory genes in vitro, and reduced both LPS-induced TNF-alpha release and carrageenan-induced paw oedema in rats. Treatment with RSCL-0520 reduced LPS-stimulated mRNA expression of TNF-alpha, COX-2, intercellular adhesion molecule-1, interleukin (IL)-8 and IL-1beta, all regulated through NF-kappaB activation. RSCL-0520, however, did not interfere with any cellular processes in the absence of LPS. CONCLUSIONS AND IMPLICATIONS: RSCL-0520 blocked signals generated by TLR4 activation, as shown by down-regulation of NF-kappaB-regulated inflammatory cytokines. The inhibitory effect involved both MyD88-dependent and -independent signalling cascades. Our data elucidated the molecular mechanisms involved, and support the search for plant-derived TLR antagonists, as potential anti inflammatory agents.

A retrospective analysis of AIDS-associated Kaposi's sarcoma in patients with undetectable HIV viral loads and CD4 counts greater than 300 cells/mm(3).

OBJECTIVE: To compare the clinical course of patients with AIDS-related Kaposi's sarcoma (KS) with CD4 counts >300 cells/mm(3) and undetectable HIV viral loads (VLs) to patients with AIDS-KS with lesser CD4 counts and detectable HIV VLs. METHODS: We retrospectively analyzed a cohort of 91 patients with AIDS-KS in a multispeciality clinic. We used chi(2) and Student t tests to analyze intragroup differences; survival was determined by Kaplan-Meier analysis. RESULTS: Twenty (22%) of the 91 patients had newly diagnosed, persistent or progressive KS despite CD4 counts >300 cells/mm(3) and undetectable HIV VLs. Age, gender, ethnicity, mode and duration of HIV acquisition, type of antiretroviral therapy (ART), and KS therapy did not differ significantly (P < or = .005) between this group and the remaining 71 patients. Although tumor stage and response to KS therapy were similar, there was a significantly greater risk of death among the patients with CD4 counts <300 cells/mm(3) and detectable HIV VLs (P = .048). CONCLUSIONS: In the highly active antiretroviral (HAART) era, a substantial proportion of patients with KS had undetectable HIV VLs and CD4 counts greater than the level typically associated with opportunistic diseases. They required systemic therapy to control their KS but were significantly less likely to die and demonstrated a trend toward better 15-year survival than patients having KS with lesser CD4 counts and detectable HIV VLs.

Therapy-related acute myeloid leukemia following HIV-associated lymphoma.

In the highly active antiretroviral therapy era, an increasingly large number of HIV-infected patients are developing non- AIDS-defining cancers (NADCs). As patients survive longer, long-term therapy-related complications take on greater importance. Herein, we describe a patient with AIDS who presented to medical attention with pancytopenia 48 months postchemotherapy with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (R-EPOCH) for diffuse large B-cell lymphoma. Bone marrow biopsy showed a moderately hypocellular marrow; 51% of the nucleated cells were blasts with myelomonocytic differentiation. Cytogenetic studies revealed an abnormal karyotype with deletion of the long arm of chromosome 11 (11q21) and 2 additional copies of the MLL gene attached to the short arms of chromosome 10 in 80% of the metaphase cells examined. With the diagnosis of therapy-related acute myeloid leukemia (AML) secured, he began induction chemotherapy with idarubicin and cytarabine. Two weeks later, he died of fungal septicemia and multiorgan failure. Through a literature search, we were able to identify 4 additional cases of therapy-related AML in AIDS patients following chemotherapy for lymphomas. The median age of these patients at the time of AML diagnosis was 39 years (range, 33-59 years), the median time from the treatment of lymphoma to AML was 18 months (range, 11-48 months), and the median survival following induction chemotherapy was 4 weeks (range, 2-16 weeks). With many HIV-infected patients surviving alkylator and topoisomerase inhibitor-based treatment and radiation therapy for AIDS-defining cancers and NADCs, long-term follow-up for therapy-related complications assumes greater importance.

AIDS-associated plasmablastic lymphoma presenting as a poorly differentiated esophageal tumor: a diagnostic dilemma.

Plasmablastic lymphoma (PBL) is a rare form of diffuse large B-cell lymphoma characterized by weak/absent expression of conventional B-cell markers and strong expression of plasma cell markers. It is strongly associated with human immunodeficiency virus (HIV) and Epstein Barr virus infection, and shows an unusual tropism to the oral cavity. Herein we describe a patient with AIDS who presented with weight loss and dysphagia owing to a large gastroesophageal mass. His radiographic and endoscopic findings and long history of cigarette consumption suggested carcinoma. Biopsy demonstrated a poorly differentiated tumor stained negatively to routine lymphoid markers including CD20. However, gene rearrangement studies confirmed a B-cell process and a more detailed immunohistochemical analysis revealed the cells stained positively for CD138 (plasma cell antigen). These findings were diagnostic of PBL. Our report reviews the wide differential diagnosis of PBL and underscores the importance of a broad array of viral and molecular studies needed to establish this diagnosis.