Amit Tirosh

The effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipids, and inflammation in type 2 diabetes mellitus patients.

AIMnThis study evaluated the effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipid profile, oxidative stress, and high-sensitivity C-reactive protein (hsCRP) in type 2 diabetes mellitus patients.nnnSUBJECTS AND METHODSnForty diabetes patients, inadequately controlled on metformin, were randomly assigned to either sitagliptin (100u2009mg/day) or glibenclamide (5u2009mg/day) for 3 months. Following a 1-month washout period, a crossover switch from glibenclamide to sitagliptin and vice versa was performed for an additional 3 months. Arterial stiffness, 24-h ambulatory blood pressure monitoring, lipids, hsCRP, glycated hemoglobin, fasting glucose, STAT-8-isoprostane (a measure of oxidative stress), body mass index (BMI), and waist circumference were measured at baseline and at 3 months with each of the study drugs.nnnRESULTSnThirty-four patients completed the study. Glibenclamide had a better glucose-lowering effect than sitagliptin, but this was associated with more hypoglycemic events. BMI increased following glibenclamide treatment, whereas sitagliptin proved weight-neutral. Mean BMI gain was +0.5±1.0u2009kg/m(2) for glibenclamide versus -0.01±0.9u2009kg/m(2) for sitagliptin (P<0.001). Triglyceride levels significantly dropped following sitagliptin, although they remained unaltered after glibenclamide treatment. Mean triglyceride decrease was -18.4±45u2009mg/mL after sitagliptin but -0.2±57u2009mg/dL following glibenclamide treatment (P=0.018). There was no change in low-density lipoprotein, high-density lipoprotein, arterial stiffness, blood pressure monitoring, hsCRP, or STAT-8-isoprostane with each of the study drugs.nnnCONCLUSIONSnSitagliptin, but not glibenclamide, demonstrated a significant beneficial effect on BMI and triglyceride levels. However, arterial stiffness, blood pressure, oxidative stress, and inflammatory status were not significantly affected by adding sitagliptin or glibenclamide to metformin-treated type 2 diabetes patients.

Carbapenems Versus Piperacillin-Tazobactam for Bloodstream Infections of Nonurinary Source Caused by Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae.

A recent, frequently quoted study has suggested that for bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) Escherichia coli, treatment with β-lactam/β-lactamase inhibitors (BLBLIs) might be equivalent to treatment with carbapenems. However, the majority of BSIs originate from the urinary tract. A multicenter, multinational efficacy analysis was conducted from 2010 to 2012 to compare outcomes of patients with non-urinary ESBL BSIs who received a carbapenem (69 patients) vs those treated with piperacillin-tazobactam (10 patients). In multivariate analysis, therapy with piperacillin-tazobactam was associated with increased 90-day mortality (adjusted odds ratio, 7.9, P=.03). For ESBL BSIs of a non-urinary origin, carbapenems should be considered a superior treatment to BLBLIs.

Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas

ObjectivesProlactin (PRL)-secreting macroadenomas usually measure between 10 and 40xa0mm. Giant (adenoma size ≥40xa0mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter ≥60xa0mm) are rare, and their management outcomes have not been well characterized.MethodsWe have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size ≥60xa0mm; PRLxa0>xa01000xa0ng/ml) and summarized their characteristics and response to treatment.ResultsMean age was 36.3xa0±xa013.5xa0years (range 12–59xa0years). Mean adenoma size was 71.8xa0±xa010.2xa0mm (60–92xa0mm). Complaints at presentation included headaches in 11 patients, visual deterioration in 9, sexual dysfunction in 9 males, and behavioral changes in two. Fourteen (78xa0%) had visual field defects. Mean PRL at presentation was 28,465xa0ng/ml (range 1300–270,000). All patients were treated with cabergoline (3.9xa0±xa02.0xa0mg/week), except for one who received bromocriptine. Treatment achieved PRL normalization in 11/18 patients within a median interval of 20xa0months. Visual improvement occurred in 12/14 patients with pre-treatment visual abnormalities. Nine patients underwent surgery (transsphenoidal, 7; transcranial, 2). None of the seven patients with elevated PRL before surgery achieved remission post-operatively. After a follow-up of 7.8xa0±xa05.1xa0years, 15/18 patients had significant adenoma shrinkage. Eleven patients are normoprolactinemic, 3 are partially controlled (PRLxa0<xa03xa0×xa0ULN), and 4 remain with significantly elevated PRL. Most patients reported disappearance or improvement of their complaints.ConclusionsThese enormous PRL-adenomas are invasive but respond fairly well to medical treatment. Long-term therapy with high dose cabergoline together with a pituitary surgery in some patients was the key for their successful management, achieving biochemical and clinical remission in most patients.

Hypopituitarism patterns and prevalence among men with macroprolactinomas

AbstractPurposenMen with prolactin-secreting tumors usually harbor macroadenomas. The degree of pituitary dysfunction may vary among different adenoma size subgroups, as is recovery after treatment. Our study purpose was to characterize hypopituitarism and recovery after treatment in men with macroprolactinomas.MethodsA retrospective study, including a consecutive group of 81 men with pituitary macroadenomas (≥10xa0mm) and hyperprolactinemia (>7×ULN). Patients were divided into three categories according to adenoma size at presentation: 10–19xa0mm (group A), 20–39xa0mm (group B), and ≥40xa0mm (group C). We compared total testosterone, gonadotropins, cortisol, thyroid hormones and hemoglobin levels at presentation and after treatment.ResultsEighty-one patients were included; 24, 31 and 26 patients in groups A, B and C, respectively. Pretreatment hypogonadism prevalence was 75.0, 93.5 and 90.9xa0% (pxa0=xa00.046; A vs B and C), central hypocortisolism − 0, 6.9 and 33.3xa0% (pxa0=xa00.005), and central hypothyroidism − 6.7, 17.9 and 26.1xa0% (NS) in groups A, B and C, respectively. Only 26.7xa0% of all patients presented with hypocortisolism and/or hypothyroidism (42.9xa0% in group C). Anemia (Hbxa0<xa013.5 gxa0%) was detected in 31.3, 57.1 and 80.0xa0% in groups A, B and C, respectively (pxa0=xa00.04). Larger adenoma diameter correlated strongly with lower FT4 levels following treatment (rxa0=xa0−0.42, pxa0=xa00.043).ConclusionsMacroprolactinomas in men caused partial hypopituitarism, affecting testosterone in all adenoma size groups and cortisol more in patients with larger adenomas. However, most of the men did not have pituitary hormones affected, beside testosterone. Most patients recovered central hypocortisolism but not hypothyroidism following treatment.

Complications of acromegaly: thyroid and colon

IntroductionIn acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon.Materials and MethodsWe will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly.ResultsThis review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly.ConclusionThyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

Papillary Thyroid Cancer: Factors Involved in Restaging N1 Disease After Total Thyroidectomy and Radioactive Iodine Treatment

CONTEXTnThe presence of cervical lymph node metastases is a strong predictor of persistent disease in papillary thyroid cancer (PTC).nnnOBJECTIVEnThe objective of the study was to investigate factors associated with improved outcome in patients with PTC and lymph node metastases.nnnDESIGNnRetrospective Cohort Setting: The study was conducted at a tertiary university-affiliated medical center.nnnPATIENTSnPATIENTS treated for PTC and N1 disease since 1995 participated in the study. Partial thyroidectomy, distant metastases, and poor differentiation were the exclusion criteria.nnnINTERVENTIONSnThe intervention was a data search of the Thyroid Registry.nnnMAIN OUTCOME MEASURESnSignificant association of clinical and disease-related factors with persistent disease was measured.nnnRESULTSnOf 800 patients treated for PTC during the study period, 182 (69% female; mean age at diagnosis 46.5 ± 15 y) had N1 disease (47% N1a, 53% N1b). Most (93.4%) had a classical/follicular variant; 65% had T1-2 disease; and 42.6% had extrathyroid extension. All patients were treated with total thyroidectomy and radioactive iodine (mean first dose 147 ± 26 mCi). Lateral neck dissection was performed in 53% patients. Mean follow-up was 9.2 ± 4.5 years. On regression analysis, factors significantly and independently associated with persistent disease at 1 year (94 of 182, 52%; 40% of N1a group, 59% of N1b group) were primary tumor size, focality, and extrathyroid extension and at the last follow-up (62 of 182, 34%; 27% of N1a group, 33% of N1b group), primary tumor size, 1-year stimulated thyroglobulin level, and cumulative I(131) dose. Stimulated thyroglobin less than 2.1 ng/mL at 1 year predicts the absence of disease at the last follow-up with an 86% negative predictive value.nnnCONCLUSIONnPATIENTS with PTC and N1 disease treated with total thyroidectomy and radioactive iodine have a significant risk of persistent disease at early and late follow-up. The extension of the primary tumor at diagnosis appears to be the only significant predictor of persistency in these patients.

IgG4-related thyroiditis: a case report and review of literature

Summary A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patients complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimotos thyroiditis. Learning points IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them. IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimotos thyroiditis. Patients with suspected IgG4-thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible.

The Use of Complementary and Alternative Medicine in Hospitalized Patients with Type 2 Diabetes Mellitus in Israel.

INTRODUCTIONnThe use of complementary and alternative medicine (CAM) has been on the rise in recent years in the general population, as well as among patients with chronic diseases such as diabetes mellitus. The aim of this study was to add information regarding the use of CAM in patients with type 2 diabetes mellitus (DM2) in Israel and explore possible interactions between CAM and prescription medication (PM).nnnMETHODSnThis is a cross-sectional study based on questionnaires. The study included type 2 diabetic patients who were hospitalized in an internal medicine department at Assaf Harofeh Medical Center, Zerifin, Israel, between December 2013 and December 2014. Possible interactions between CAM and PM were evaluated by a clinical pharmacist and a clinical pharmacologist.nnnRESULTSnOut of 111 diabetic patients, 23.4% used CAM. There was no significant difference between the consumers and nonconsumers in terms of age, education, income, smoking, or alcohol habits. Only 11 of the 26 CAM consumers informed their physician regarding the use. We found possible drug-herb interactions in 19 of the 26 CAM consumers. A major interaction was found between omega-3 and antiaggregants and was encountered in 7 (26.9%) of the CAM consumers. Other minor and major interactions were found with vitamin E, ginkgo-biloba, co-enzyme Q10, green tea, fenugreek seeds, pyridoxine, and dandelion.nnnCONCLUSIONSnSince CAM consumption is on the rise, it is desirable to improve our knowledge concerning their potential effects and adverse effects, especially in conjunction with PM. Given the complexity of pharmaceutics in patients with chronic diseases, among them patients with DM, the use of supplementary medicine cannot be ignored.

SHORT-TERM DECLINE IN PROLACTIN CONCENTRATIONS CAN PREDICT FUTURE PROLACTIN NORMALIZATION, TUMOR SHRINKAGE, AND TIME TO REMISSION IN MEN WITH MACROPROLACTINOMAS

OBJECTIVEnTo identify early follow-up measures that will predict the dynamics of prolactin (PRL) decrease and adenoma shrinkage in men harboring macroprolactinomas.nnnMETHODSnA single-center historical prospective study including a consecutive group of 71 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (PRL >7 times the upper limit of normal [ULN]) treated medically with cabergoline. Comparisons of PRL normalization rates were performed according to PRL levels achieved at 6 months, maximal adenoma shrinkage during follow-up, and other patient characteristics. Correlations were analyzed to identify characteristics of PRL suppression dynamics.nnnRESULTSnPRL levels after 6 months of treatment correlated positively with current PRL levels (r = 0.74; P<.001), with time to PRL normalization (r = 0.75; P<.001), and with adenoma diameter following treatment (r = 0.38; P = .01). Adenoma shrinkage depicted by first magnetic resonance imaging on treatment correlated with maximal adenoma shrinkage during follow-up (r = 0.56; P = .006). Five patients had nadir PRL levels ≥3 times the ULN (51 ng/mL) and showed slower response to cabergoline treatment, with consistently higher PRL levels compared with responding patients throughout follow-up (mean 6-month PRL levels, 519 ± 403 ng/mL versus 59 ± 118 ng/mL; P<.001).nnnCONCLUSIONnSix-month PRL level might serve as a surrogate marker for PRL normalization and adenoma shrinkage dynamics among men harboring macroprolactinomas.

Management of macroprolactinomas

Prolactin (PRL) secreting tumors are the most common functional neoplasms of the pituitary and are commonly subdivided into microprolactinomas (<10xa0mm) and macroprolactinomas (≥10xa0mm) according to their baseline diameter. Patients with prolactinoma present with symptoms evolving from hyperprolactinemia and with those caused by pressure of the expanding mass on surrounding tissues, including the optic chiasm and the cavernous sinuses. We hereby describe the possible complications of macroprolactinomas, including mass effects, hypopituitarism, CSF leak and apoplexy and discuss their relevant management.In general, all patients harboring macroprolactinomas should be treated, the objectives being to achieve normal or near normal PRL levels, to reduce or stabilize adenoma size and to recover altered pituitary axes. Medical therapy with dopamine agonists (DA) is the preferred initial treatment for the vast majority of patients harboring prolactinomas. Pituitary surgery is indicated in patients who cannot tolerate or are resistant to therapy with DAs, patients that seek fertility and harbor adenomas that impinge on the optic chiasm, psychiatric patients with contraindication to DA treatment and patients presenting with pituitary apoplexy or a cerebrospinal fluid (CSF) leak. In addition, in this review, several patient populations with unique clinical characteristics will be discussed separately namely postmenopausal women, the elderly, children and patients with pituitary carcinoma.