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BackgroundGraves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease.MethodsIn this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models.FindingsWe extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05–1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29–0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96–2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08–2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality.InterpretationRegardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone.FundingNational Institute for Social Care and Health Research, Wales.

The antithyroid drugs, Carbimazole, Methimazole, and Propylthiouracil remain the mainstay of Graves' disease management in pregnancy. A series of Clinical Practice Guidelines aimed at optimising fetal and maternal outcomes in women with Graves' disease have been published in recent years. Areas covered: This review examines existing guideline recommendations on antithyroid drug management of Graves' disease in pregnancy. Expert commentary: Recent guidelines have been shaped by expanding knowledge of the adverse effect profiles of antithyroid drugs on the developing fetus. A core management strategy is to limit fetal exposure to excess thyroid hormones and to curtail adverse drug effects through effective preconception and peri-conception management. Propylthiouracil is the recommended treatment in the first trimester of pregnancy but there is uncertainty regarding antithyroid drug choices in women who continue to require treatment in later pregnancy. Further studies are needed to fully evaluate the risks of congenital anomalies following intrauterine thionamide exposure.

Introduction: Pyrexia of unknown origin (PUO) is often a diagnostic challenge. Common causes currently reported include non-infectious inflammatory disorders (NIID) (30.6%), infections (23.1%), malignancy (10.7%) and miscellaneous (12.4%). However, 23.1% remain undiagnosed despite extensive investigations. Fever is a component of subacute thyroiditis (SAT) in 28-83% of subjects reported in the literature. But its presentation as a PUO is reported only in a handful of subjects. Case Presentation: A 71-year-old Asian male presented with evening fevers of 2-3 weeks duration. He had no accompanying sweats, cough, breathlessness, or weight loss. He had a past history of TB, polio, hydatid cyst and hypertension for which he was on treatment. He was a teetotaler. Several family members living in his native land had active TB and he visited them often. Clinical examination at initial presentation was unremarkable. He interrupted investigations to go back to Asia, and became unwell for over 6 weeks with evening fevers and sweating, a weight loss of over 7 kg, and a poor appetite. At this point he had no neck pain, palpitations or bowel abnormalities. Clinical examination continued to be normal upon his return to the UK and in the Endocrine Clinic. Investigations: Investigations were done to exclude (a) infections - There was no growth of pathogenic organisms in repeated blood, urine and sputum cultures. Screening tests for TB, hepatitis, and glandular fever were negative. Blood screens for malarial parasites, amoebic and Brucella serology, and stools examination and culture were also negative. Echocardiography was normal. (b) Malignancy - Urine Bence Jones proteins and serum protein electrophoresis were normal. Bone marrow examination was suggestive of Leishmaniasis but a PCR test excluded this diagnosis. Humoral markers of malignancy were negative. CT scans of the thorax, abdomen and pelvis were normal and did not show any evidence of visceral abnormalities (c) NIID - CRP 120, ESR 130, with blood tests consistent with iron deficiency. Autoimmune screening for dsDNA, ANA, ANCA were negative. Upon return to the UK a PET/CT scan showed the diffuse tracer uptake in both thyroid lobes and changes consistent with a large left lobe. Free thryroxine was 28pmol/l (reference range 9-19.1), and TSH was undetectable (

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy.

Glioblastoma multiforme (GBM) is the deadliest form of heterogeneous brain cancer. It affects an enormous number of patients every year and the survival is approximately 8 to 15 months. GBM has driven by complex signaling pathways and considered as a most challenging to treat. Standard treatment of GBM includes surgery, radiation therapy, chemotherapy and also the combined treatment. This review article described inter and intra- tumor heterogeneity of GMB. In addition, recent chemotherapeutic agents, with their mechanism of action have been defined. FDA-approved drugs also been focused over here and most importantly highlighting some natural and synthetic and novel anti- glioma agents, that are the main focus of researchers nowadays.

Maternal hypothyroidism may adversely affect pregnancy outcomes. International practice guidelines recommend that women with hypothyroidism should attain a preconception and early gestation serum thyroid-stimulating hormone (TSH) level of2.5 mU/L. Our objective was to ascertain what proportion of women realize this target in practice and whether a TSH level above this threshold has adverse fetal and maternal consequences.This was an observational study of women with hypothyroidism referred to an endocrine antenatal clinic between 2008 and 2010 (n = 78; mean age, 30.4 years; range, 19 to 43 years). Thyroid profiles (free thyroxine [FT4] and TSH) before conception and through pregnancy were documented. Obstetrics outcomes were examined, including low birth weight, preterm births, preeclampsia, caesarean sections, and admissions to special care neonatal units.Thyroid testing was undertaken in 80% of subjects before conception, and in 64, 94, and 96% of subjects in the first, second, and third trimesters of pregnancy, respectively. TSH2.5 mU/L was seen in 49% of women before conception and in 68% of women in the first trimester. Six women were overtly hypothyroid before conception, attaining normal thyroid function at gestational ages ranging from 12 to 36 weeks. Neither the preconception nor the first postconception TSH level (2.5 mU/L or ≤2.5 mU/L) was associated with gestational age at delivery, birth weight, or rates of caesarean section or preeclampsia.The majority of women with hypothyroidism do not achieve the recommended preconception and early gestation TSH targets. Preconception and early gestation TSH2.5 mU/L was not associated with adverse fetal and maternal outcomes. Studies in larger cohorts will be required to confirm these findings, however.

According to Sir William Osler, Mouth is the mirror of the body which reflects systemic diseases. The oral mucosa may be affected by a variety of muco cutaneous diseases and oral les ions may occur first or very early in several muco - cutaneous disorders. Pemphigus is a group of potentially life threatening, chronic auto immune disorder characterized by epithelial blistering affecting muco - cutaneous surfaces. Autoantibodies in pemphigus vulgaris are directed against desmoglein in epithelial desmosomes, and the immune deposits result in intra - epithelial splitting (acantholysis). Oral lesions in the form of blisters and erosions are the first to manifest, and diagnosis is made by positive nikolsky’s sign, coupled with characterstic histopathology and immunofluorescent features. Corticosteroids form the mainline of treatment, but adjuvant and newer therapies are also been used at an increasing rates. This article deals about the etio pathoge nesis, clinical characterstics, diagnosis and treatment strategies for pemphigus vulgaris.

Summary TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease. Learning points Euthyroid Graves’ ophthalmopathy can present initially with negative thyroid-specific autoantibodies. Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal. Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.

Herpes zoster or shingles is a recurrence of varicella zoster virus that entered the cutaneous nerve endings during an earlier episode of chicken pox, travelled to the dorsal root ganglia, and remained in a latent form. Nerves most commonly involved are C3, T5, L1, L2 and first division of trigeminal nerve. The condition is characterized by occurrence of multiple, painful, unilateral vesicles and ulceration which shows a typical single dermatome involvement. The infection usually affects elderly individuals, and if present in the younger age group, a suspicion should be raised about the immune-compromised status such as HIV. Many patients report to the dental clinic with the complications of herpes zoster, with trigeminal nerve involved in about 15% cases and most commonly the ophthalmic division. Diagnosing these complications of herpes zoster could pose a challenge to an oral physician due to their varied presentation ranging from post herpetic neuralgia, external root resorption, osteonecrosis and tooth exfoliation. This paper reports a case of herpes zoster with unilateral vesicles over the left side of upper and middle 1/3rd of face along the trigeminal nerve tract, with intraoral involvement of buccal mucosa and palate on the same side.

Adrenal incidentalomas (AIs) are mostly benign and nonsecretory. Management algorithms lack sensitivity when assessing malignant potential, although functional status is easier to assess. We present a subject whose AI was a retroperitoneal leiomyosarcoma (RL).Case Presentation. A woman on warfarin with SLE and the antiphospholipid syndrome, presented with left loin pain. She was normotensive and clinically normal. Ultrasound scans demonstrated left kidney scarring, but CT scans revealed an AI. MRI scans later confirmed the AI without significant fat and no interval growth. Cortisol after 1 mg dexamethasone, urinary free cortisol and catecholamines, plasma aldosterone renin ratio, and 17-hydroxyprogesterone were within the reference range. Initially, adrenal haemorrhage was diagnosed because of warfarin therapy and the acute presentation. However, she underwent adrenalectomy because of interval growth of the AI. Histology confirmed an RL. The patient received adjuvant radiotherapy.Discussion. Our subject presented with an NSAI. However, we highlight the following: (a) the diagnosis of adrenal haemorrhage in this anticoagulated woman was revised because of interval growth; (b) the tumour, an RL, was relatively small at diagnosis; (c) this subject has survived well over 60 months despite an RL perhaps because of her acute presentation and early diagnosis of a small localised tumour.

2 Jul 2012 2.39 1.90 Calcitriol 2.25 mcg BD + Sandocal 1g (1 tab QDS)+ Weekly intravenous calcium & magnesium infusion 3 Aug 2012 1.78 2.04 Calcitriol 2.25 mcg BD + Sandocal 1g (1 tab QDS) + Teriparatide 20 mcg SC injections BD ) + Weekly intravenous calcium & magnesium infusion 4 Jan 2013 1.94 1.64 Calcitriol 2.25 mcg BD + Sandocal 1g (1 tab QDS) + Teriparatide 40mcg BD SC injections )+ Weekly intravenous calcium & magnesium infusion 5 Jun 2013 1.70 1.89 Teriparatide infusion 40 mcg / 24 hours only

Background: Magnetic resonance imaging (MRI) and ultrasonography are used widely for the diagnosis of Morton’s neuroma. The aim of this study was to assess the accuracy of these two modalities as diagnostic tools in Morton’s neuroma. Methods: Fifty feet of 47 consecutive patients (39 women and 8 men; mean age, 46 years; age range, 36–64 years) who presented between January 1, 2005, and June 30, 2008, were included in the study. Twenty-five feet were investigated with ultrasonography and 25 with MRI. Morton’s neuroma was confirmed surgically and histologically in all of the patients. A Student unpaired t test was applied. Results: Twenty-two MRIs were diagnostic (sensitivity, 88%). Three patients with negative MRI findings underwent ultrasonography and were found to have a neuroma smaller than 5 mm. Twenty-four ultrasound scans demonstrated the neuroma (sensitivity, 96%), with five neuromas being smaller than 5 mm. Conclusions: Ultrasonography has a slightly higher sensitivity in the diagnosis of Morton’s neuroma, particularly of neuromas smaller than 5 mm, and should be the preferred imaging modality in suspected cases, and MRI should be reserved for cases with equivocal diagnosis. (J Am Podiatr Med Assoc 102(3): 184–186, 2012)

Oral cavity functions as an early indicator for a variety of systemic diseases. Early and accurate diagnosis of these underlying systemic disorders entails thorough examination of the oral mucosa, gingiva, teeth, tongue and other oral tissues. Although gingival changes may be related to local factors in the oral cavity, it can also be an expression of systemic conditions such as blood dyscrasias, endocrinal imbalance, and nutritional deficiencies. Leukemia, a malignancy of white blood cells is a dreadful disease, which, if not diagnosed properly and treated early may result in significant morbidity and mortality. Oral changes may be the first and only presenting signs in leukemic patients. This paper aims to throw light on an interesting case of acute leukemia diagnosed on the basis of oral signs and emphasizes the importance of thorough oral examination to identify the threatening condition.