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BACKGROUND: The prognostic significance of molecular staging using thyroglobulin (Tg)-based RT-PCR analysis in the peripheral blood of patients with differentiated thyroid cancer (DTC) was investigated. Herein, the specificity of molecular staging in DTC patients after thyroidectomy and 131I ablation therapy was analysed, using different specific cDNA primers in qualitative nested and classical RT-PCR protocols. PATIENTS AND METHODS: Ninty-five patients receiving TSH suppressive therapy were included, of whom 51 were disease-free and 44 presented residual/recurrent or metastatic disease as evidenced by biochemical and/or 131I whole-body scan. RESULTS: Our analysis detected RT-PCR products suggestive of the presence of Tg mRNA in all the blood samples tested, including healthy controls. A splice variant (350 bp) of Tg transcript (missing exon 3) was detected by nested RT-PCR in 34% of blood samples, however, without correlation to disease status. CONCLUSION: Qualitative Tg-based molecular staging in the peripheral blood of patients with DTC shows poor specificity in assessing DTC disease status.

The identification of a primary endobronchial non-Hodgkin lymphoma (NHL) is rare. We hereby present the case of a primary solitary endobronchial NHL lesion in an 80-year-old patient with prostate cancer who did not present any systemic involvement at the time of diagnosis.

Journal URL: http://www.sciencedirect.com/science/journal/00275107

Background: The aim of this study was to examine whether the presence of microalbuminuria (20-200 mu g/min) can predict in-hospital morbidity and mortality in non-diabetic patients with acute myocardial infarction. Methods: Two hundred twenty-three (172 men and 51 women) non-diabetic patients with acute myocardial infarction were studied prospectively. The main outcome measures of the study were based on a comparison of in-hospital mortality and major non-fatal in-hospital events (pulmonary edema, post-infarction angina, infarct extension, mechanical complications, conduction disturbances and ventricular arrhythmias) between microalbuminuric and normoalburninuric patients. Results: A significant proportion of patients (33.6%) had microalbuminuria. Seventy-six patients (34%) developed an in-hospital event (fatal or non-fatal). Six patients (2.7%) with acute myocardial infarction died in the hospital. Patients with microalbuminuria had a higher mortality rate in comparison with normoalbuminuric patients (6.6% vs. 0.68%, p=0.01). For non-fatal events, the incidence of pulmonary edema and ventricular arrhythmias was significantly higher in patients with microalbuminuria (14.6% vs. 3.4%, p < 0.001 and 12% vs. 3.4%, p=0.01, respectively). The combined end-point of the total number of fatal and non-fatal events was significantly higher in patients with microalbuminuria (57.3% vs. 22.3%,p < 0.001). In multiple logistic regression analysis, microalbuminuria (p

Background: Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited. Methods: To investigate this, a meal was given to 11 hypothyroid (HO; aged 45 ± 3 yr) and 10 euthyroid subjects (EU; aged 42 ± 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V) glucose(BF), lipoprotein lipase as (A-V)Triglycerides(BF), and lipolysis as [(V-A)glycerol(BF)]-lipoprotein lipase. Results: The HO group had higher glucose and insulin levels than the EU group (P < 0.05). In HO vs. EU after meal ingestion (area under curve 0-360 min): 1) BF (1290 ± 79 vs. 1579 ± 106 ml per 100 ml tissue in forearm and 706 ± 105 vs. 1340 ± 144 ml per 100 ml tissue in adipose tissue) and glucose uptake (464 ± 74 vs. 850 ± 155 μmol per 100 ml tissue in forearm and 208 ± 42 vs. 406 ± 47 μmol per 100 ml tissue in adipose tissue) were decreased (P < 0.05), but fractional glucose uptake was similar (28 ± 6 vs. 33 ± 6% per minute in forearm and 17 ± 4 vs. 14 ± 3% per minute in adipose tissue); 2) suppression of lipolysis by insulin was similar; and 3) plasma triglycerides were elevated (489 ± 91 vs. 264 ± 36 nmol/liter·min, P < 0.05), whereas adipose tissue lipoprotein lipase (42 ± 11 vs. 80 ± 21 μmol per 100 ml tissue) and triglyceride clearance (45 ± 10 vs. 109 ± 21 ml per 100 ml tissue) were decreased in HO (P < 0.05). Conclusions: In hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue. Copyright © 2006 by The Endocrine Society.

Background: Although insulin resistance is well established in hyperthyroidism, information on the effects of insulin on adipose tissue (AD) is limited. Methods: To investigate this, a meal was given to 12 hyperthyroid (HR) and 10 euthyroid (EU) subjects. Blood was withdrawn for 360 min from veins draining the anterior abdominal sc AD and from the radial artery. Blood flow was measured with 133Xe. Lipoprotein lipase (LPL) was calculated as triglyceride flux across AD, and AD-lipolysis was calculated as glycerol flux minus LPL. Results: Both groups displayed comparable postprandial glucose levels, with the HR having higher insulin levels than the EU. In AD of HR vs. EU: 1) blood flow was increased [area under curve 0-360 min (milliliters per 100 milliliters of tissue); 1746 ± 208 vs. 1344 ± 102, P = 0.001], but glucose uptake was normal [area under curve 0-360 min (micromoles per 100 milliliters of tissue); 501 ± 114 vs. 368 ± 48]; 2) fasting rates of lipolysis (nanomoles per minute per 100 milliliters of tissue; 329 ± 75 vs. 89 ± 22, P = 0.02) and nonesterified fatty acid (NEFA) release (nanomoles per minute per 100 milliliters of tissue; 841 ± 146 vs. 316 ± 97, P = 0.01), and plasma NEFA levels (micromoles per liter; 623 ± 50 vs. 454 ± 57, P = 0.03) were increased, but were all rapidly suppressed to levels similar to those in EU after the increase in plasma insulin levels after the meal; and 3) LPL was not stimulated by insulin. Conclusions: In hyperthyroidism, AD lipolysis and glucose uptake are resistant to insulin. The defect in lipolysis is manifested in the fasting state, whereas postprandially this rate is rapidly suppressed to normal. This may relieve tissues from the burden of NEFAs after the meal, thus facilitating muscle glucose disposal by insulin. Copyright © 2006 by The Endocrine Society.

Introduction: Endocrine abnormalities in critically ill patients with stroke during the early recovery period have not been well characterized. Methods: To investigate this issue, 33 consecutive mechanically ventilated patients (27 men) with hemorrhagic (n = 21) or ischemic (n = 12) stroke having a mean age of 57 +/- 12 years were studied. Glasgow Coma Scale score on admission in the hospital was 8 +/- 3. The following basal hormones were measured within 72 hours postextubation: cortisol, corticotropin (ACTH), free thyroxine, tri-iodothyronine, thyroid-stimulating hormone, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, growth hormone, and insulin-like growth factor (IGF)-1. Subsequently, a low-dose (1 mu g) ACTH stimulation test was performed. Results: Twenty-six (79%) patients showed endocrine alterations. The most common change was low IGF-1 levels compatible with growth hormone deficiency (45%), followed by hypogonadism (39%), thyroid dysfunction (36%), and cortisol hyporesponsiveness (33%). Conclusion: Neuroendocrine changes occur with high frequency in critically ill patients with stroke during the early recovery period. It remains to be determined whether these changes have implications for functional and/or clinical outcome.

The effect of ramipril (an angiotensin [AT]-converting enzyme inhibitor), telmisartan (an AT-II type 1 receptor blocker), or their combination on inflammation and lipid peroxidation was assessed in 37 patients with type 2 diabetes who were free of coronary artery disease. All regimens were associated with a significant reduction of C-reactive protein and oxidized low-density lipoprotein cholesterol serum levels (p < 0.001). These results further enlighten the mechanisms underlying the cardiovascular beneficial effect of renin-AT system inhibition. (c) 2005 by Excerpta Medica Inc.

Background The aim of this study is to evaluate the significance of microalbuminuria (MA) as a 3-year prognostic index in nondiabetic patients with acute myocardial infarction (AMI). Methods One hundred seventy-five patients with AMI were followed prospectively for 3 years. The study end point was cardiac death or rehospitalization for an acute coronary event. Results Forty-two patients (24%) developed a new cardiac event during the follow-up. Microalbuminuria (P < .001), pulmonary edema during initial hospitalization (P < .001) and postinfarction angina (P = .0364), advanced age (P = .001), severe atherosclerosis (high Gensini score) (P = .036), ejection fraction

Pituitary morphology in patients with Prop1 gene mutations varies. Most patients demonstrate a normal or small pituitary gland. Occasionally, pituitary enlargement of undetermined origin has also been detected. In the present study we use long-term magnetic resonance imaging findings to characterize the morphological abnormalities of the pituitary gland in 15 patients (aged 2.5-45 yr) with combined pituitary hormone deficiency caused by Prop1 gene mutations (GA296del/GA296del in seven, GA296del/A150del in two, A150del/A150del in five, and GA296del/R73H in one patient) and attempt to uncover the origin and nature of the pituitary enlargement. Small pituitary gland was detected in seven patients (25.2 +/- 14.4 yr of age), normal pituitary size in three patients (10.2 +/- 5.8 yr of age), and pituitary enlargement in five patients (6.5 +/- 2.7 yr of age). The pituitary enlargement consisted of a nonenhancing mass lesion interposed between the normally enhancing anterior lobe and the neurohypophysis. The pituitary stalk was displaced anteriorly, whereas the neurohypophysis was orthotopic, displaying a normal signal. Spontaneous regression of the mass lesion with normalization of the pituitary stalk position was observed in three patients. Our data indicate that although a small pituitary gland is usually observed in older subjects, a significant number of young patients with Prop1 gene mutations demonstrate pituitary enlargement with subsequent regression. The distinct magnetic resonance imaging characteristics of the pituitary enlargement in our patients in conjunction with pertinent data from Prop1-deficient mice suggest that the mass causing the pituitary enlargement most likely originates from the intermediate lobe. J Clin Endocrinol Metab

The extent and severity of coronary atherosclerosis were compared between 43 microalbuminuric and 87 normoalbuminuric nondiabetic patients with acute myocardial infarction. Patients with microalbuminuria had significantly greater scores of the severity (Gensini score) and extent (Hamsten score) of coronary artery disease (p < 0.001). (C) 2004 by Excerpta Medica, Inc.

Lymphocytic hypophysitis (LH) is an inflammatory disease of the anterior pituitary. The varying clinical presentation and the short-term outcome of LH have been extensively described in several case reports or small cohort studies. However, little is known about the long-term outcome of this disease. it is currently believed that if left untreated it may run a self-limited course followed by full resolution of the mass with or without persisting pituitary failure. We describe a 29-yr-old female who presented with secondary amenorrhea, headaches, visual defects, and a pituitary mass, which was removed by transsphenoidal surgery. Histology was consistent with the diagnosis of LH. following surgery the patient demonstrated a gradual recovery of gonadotroph function with restoration of menses and a successful pregnancy. However, 3 yr after delivery and 6 yr following her initial presentation she developed amenorrhea, headaches, and a pituitary mass. Institution of steroid therapy resulted in resolution of the pituitary mass. in summary, this case illustrates that similarly to many other disorders of autoimmune origin LH may run a fluctuating course and late recurrence is possible even after the successful removal of the inflammatory mass, thus necessitating long-term follow-up of these patients.

Objective. To investigate adrenal responses to the low-dose corticotropin (ACTH) stimulation test in acute traumatic or non-traumatic brain injury (BI) and to assess its value in predicting outcome. Design. Prospective study. Setting. Intensive care unit (ICU) in a university hospital. Patients and participants. Seventy-five patients with acute BI, with a median age of 45 years were investigated. BI was due to trauma (n=51), ischemic stroke (n=17), subarachnoid hemorrhage (n=4) or intracerebral hemorrhage (n=3). Interventions. Blood was taken on day 16 (median) after admission to the ICU to determine baseline cortisol and ACTH. Thereafter, a low-dose stimulation test (LDST) was performed: 1 mug of tetracosactrin was injected and 30 min later a second blood specimen was obtained to measure stimulated cortisol. Patients having a stimulated cortisol below 500 nmol/l were defined as non-responders to the LDST. Measurements and results. Median baseline and stimulated cortisol were 491 nmol/l and 690 nmol/l, respectively. The median increment in cortisol was 154 nmol/l (range 5-579 nmol/l). Mean ACTH was 46+/-21 pg/ml. Ten (13%) patients were non-responders to the LDST; these had a higher mortality rate compared to patients with adequate cortisol production (70 vs 32%, p=0.034). Logistic regression analysis revealed that APACHE II (p

Background and Purpose - To investigate the incidence, pattern, and magnitude of neuroendocrine changes in long-term survivors of aneurysmal subarachnoid hemorrhage (SAH). Methods - Thirty patients (16 women) with a mean age of 50±13 years underwent endocrine assessment between 12 and 24 months after aneurysmal SAH. SAH severity was graded clinically by the Hunt & Hess scale (median, II) and radiologically by the Fisher classification (median, II). Patients underwent measurement of basal hormone levels and dynamic assessment by the low-dose (1 μg) corticotropin stimulation test. Functional outcome was examined concurrently with endocrine testing by the modified Rankin Scale and the Barthel Index. Results - Of the 30 patients tested, 14 patients (47%) showed isolated or combined endocrine abnormalities. These included low insulin-like growth factor 1 levels compatible with growth hormone deficiency in 37%, hypogonadism in 13%, and cortisol hyporesponsiveness to the low-dose corticotropin stimulation test in 10%; thyroid dysfunction in the form of subclinical hypothyroidism was observed in 7% of patients. Median modified Rankin Scale and Barthel Index at the time of endocrine testing were 1 and 100, respectively. There was no correlation between the presence of endocrine dysfunction and SAH severity indices or functional outcome scores. Conclusions - Long-term survivors of aneurysmal SAH frequently exhibit endocrine changes, with growth hormone and gonadal deficiencies predominating. Thus, screening of pituitary function is recommended in patients surviving SAH. The relationship between late hormonal alterations and functional outcome in patients with SAH warrants further study.

Objective. To assess thyroid function abnormalities in survivors of severe head trauma and to examine their relationship with indices of brain injury severity. Design. Prospective study. Setting. General intensive care unit (ICU) in a university hospital. Patients and participants. Twenty-two (21 men) head-injured patients, with a median age of 25.5 years at the time of injury, were investigated. Severity of brain trauma was assessed by Glasgow Coma Scale (GCS) score, Marshall Computerized Tomographic Classification, intracranial pressure levels and serum S-100b concentrations measured over a 6-day period. Interventions. Thyroid function testing was performed 1 year after ICU discharge and included the measurement of free thyroxine, triiodothyronine and thyrotropin. Measurements and results. On admission to the ICU, GCS ranged from 3 to 8. Peak S-100b was 1.49 mug/l (range: 0.37-5.26 mug/l). Median triiodothyronine and thyrotropin were 123 ng/dl and 1.60 muIU/ml, respectively. Free thyroxine was 1.08+/-0.22 ng/dl (range: 0.7-1.5 ng/dl). Overall, 7 of the 22 patients (32%) had thyroid dysfunction. Four patients had central hypothyroidism and three patients had subclinical hypothyroidism. Peak S-100b correlated negatively with free thyroxine (r=-0.47, p=0.02). There were no correlations between other brain injury severity indices and thyroid hormone levels. Conclusions. A significant subset of brain injury patients presents with changes in thyroid function 1 year after ICU discharge; these depend upon biochemical serum markers of head trauma severity.

Objective: To investigate hypothalamic-pituitary-adrenal axis function in patients requiring mechanical ventilation for traumatic brain injury and to assess the relation of hypothalamic-pituitary-adrenal axis abnormalities with vasopressor dependence and peripheral cytokine levels. Design: Prospective study. Setting: General intensive care unit in a university teaching hospital. Patients: Forty patients (33 men and 7 women) with moderate to severe traumatic brain injury (mean age, 37 +/- 16 yrs) were studied the day after termination of mechanical ventilation (7-60 days after trauma). Interventions: First, a morning blood sample was obtained to measure baseline cortisol, corticotropin, interleukin-6, and tumor necrosis factor alpha. Subsequently, 1 mug of synthetic corticotropin was injected intravenously, and 30 mins later, a second blood sample was drawn to determine stimulated plasma cortisol. Based on data derived from healthy volunteers, patients having stimulated cortisol levels

Objective. To investigate the incidence and type of endocrine abnormalities in critical care patients with traumatic brain injury (TBI) and to examine their relationships to possible predisposing factors. Design. Prospective study. Setting. General intensive care unit in a university hospital. Patients and participants. Thirty-four TBI patients (27 men, 7 women), having a mean age of 37+/-16 years, were studied after weaning from mechanical ventilation. Interventions. Baseline endocrine assessment was carried out by measuring cortisol, corticotropin, dehydroepiandrosterone sulfate, free thyroxine, thyrotropin (TSH), testosterone, oestradiol, follicle stimulating hormone (FSH), luteinizing hormone, prolactin, growth hormone and insulin-like growth factor I. Dynamic evaluation was performed by human corticotropin releasing hormone and growth hormone releasing hormone in all patients. Male patients underwent additional investigation with gonadotropin-releasing hormone. Severity of neurological derangement was graded according to Glasgow Coma Scale (GCS), Marshall Computerized Tomographic Classification and intracranial pressure (ICP) levels. Measurements and results. Eighteen of the 34 patients (53%) had an abnormal result in at least one hormonal axis tested, with cortisol hyporesponsiveness and gonadal dysfunction being equally common, affecting 24% of patients. Endocrine abnormalities were associated with a higher brain CT-scan classification score (p=0.02). The GCS on admission correlated positively with baseline FSH (r=0.37, p=0.03), peak FSH (r=0.41, p=0.03), testosterone (r=0.44, p=0.02) and TSH (r=0.39, p=0.03). There were no relations between ICPmax and any baseline or dynamic hormone measurements. Conclusions. Patients with TBI receiving critical care show changes in their neuroendocrine responses, which depend upon clinical and radiological measures of head injury severity. Most common abnormalities include cortisol hyporesponsiveness and hypogonadism.

OBJECTIVE Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. PATIENTS AND MEASUREMENTS Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of >70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method. RESULTS Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm(2): 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z -score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P < 0.05) and trochanter (BMD g/cm(2): 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P < 0.01). BMD measurements of the Ward’s triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm(2): 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm(2): 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward’s triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P < 0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72). CONCLUSIONS In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.