It is known that glycation among various proteins is increased in diabetic patients compared with non-diabetic subjects. Currently, among these glycated proteins, glycated hemoglobin (HbA_1C) is used as the gold standard index of glycemic control in clinical practice for diabetes treatment. However, HbA_1C does not accurately reflect the actual status of glycemic control in some conditions where plasma glucose changes during short term, and in patients who have diseases such as anemia and variant hemoglobin. In comparison, another index of glycemic control, glycated albumin (GA), more accurately reflects changes in plasma glucose during short term and also postprandial plasma glucose. Although GA is not influenced by disorders of hemoglobin metabolism, it is affected by disorders of albumin metabolism. This review summarizes diseases and pathological conditions where GA measurement is useful. These include the status of glycemic control changes during short term, diseases which cause postprandial hyperglycemia, iron deficiency anemia, pregnancy, chronic liver disease (liver cirrhosis), chronic renal failure (diabetic nephropathy), and variant hemoglobin.

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Anaplastic thyroid carcinoma (ATC) is a very aggressive disease showing a high mortality. However, long-term survival is expected when patients do not show distant metastasis at diagnosis and undergo locally curative surgery. In this study, we investigated the optimal surgical procedure for locally curative surgery for ATC in a series of 34 patients. Twenty patients underwent total thyroidectomy but there were no detectable skip lesions of ATC in the contralateral lobe on pathological examination. Cause-specific survival (CSS) of Stage IVA or IVB patients who underwent limited thyroidectomy did not differ from that of those who underwent total thyroidectomy. Clinical node metastasis on ultrasonography was not detected in 15 patients but 11 of these patients underwent lymph node dissection. Three of these were node-positive on pathological examination but only one showed metastatic node of ATC that was involved in the primary lesion. Of 19 patients having clinical node metastasis, 10 were ATC node positive on pathological examination. Taken together, for locally curative surgery in ATC patients, 1) total thyroidectomy may not be mandatory unless patients have clinical lesions in the contralateral lobe; 2) prophylactic modified radical neck dissection may not be mandatory for patients who do not demonstrate clinical signs of lymph node metastasis; and 3) extensive and careful therapeutic node dissection may be required for patients demonstrating clinical signs of node metastasis.

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Growth without growth hormone (GH) has occasionally been described in patients who have had tumors removed in the hypothalamic-pituitary area. Most of these patients have metabolic abnormalities such as obesity, dyslipidemia and fatty liver. This report describes the metabolic beneficial effects of GH replacement in pediatric patients with growth without GH. Two children in whom the growth without GH phenomenon occurred after therapy for brain tumors participated in this study. Case 1 is a 15-yr-old Japanese girl, diagnosed as having Langerhans cell histiocytosis with multiple intracranial lesions at the age of two. She showed a slight body fat increase, dyslipidemia and fatty liver. Case 2 is a 10-yr-old Indonesian boy, diagnosed with craniopharyingioma at the age of three. He was obese and had low bone mineral density (BMD). In both cases, GH replacement therapy was started at 0.042 mg/kg/week for 12 months. Body composition, BMD, and visceral abdominal area were measured every 3 months. Serum fasting blood glucose, insulin, ALT, lipid profile, leptin, and adiponectin levels were also measured every 3 months. Case 1 showed improvement of transaminase (ALT from 64 to 16 IU/L) and triglyceride (from 239 to 129 mg/dL) over 12 months, but did not show a decrease in visceral fat area or of body fat percentage. Case 2 showed a decrease in body fat percentage and visceral fat area, accompanied by elevated serum adiponectin and decreased leptin levels. In conclusion, twelve months GH replacement therapy improves metabolic abnormalities in pediatric patients with growth without GH.

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Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA_1c) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA_1c, fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We observed a faster, and better decrease of body weight, HbA_1c, FPG, PPG, LDL-C, HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat. We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded.

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Familial hypocalciuric hypercalcemia (FHH) is a benign disorder with heterozygous inactivating mutations in the calcium-sensing receptor (CASR) gene. The present study describes the identification and functional analysis of a novel CASR gene mutation leading to FHH. The proband is a 33-yr-old woman (Ca 11.0 mg/dL, intact-PTH 68 pg/mL, FECa 0.17 %). Leukocyte DNA was isolated in four family members and a novel heterozygous mutation (D190G, GAT>GGT) in exon 4 of CASR gene was identified by direct sequence analysis. The mutant CASR expression vector was constructed by mutagenesis procedure and its response to Ca²⁺ was characterized by transient transfection into human embryonic kidney (HEK) 293 cells and treatment with increasing extracellular Ca²⁺ concentrations. HEK cells didn't activate intracellular signaling (MAPK activation) in response to increases of extracellular Ca²⁺ concentrations when the mutant receptor was expressed normally at the cell surface. The novel heterozygous mutation (D190G) identified in the present study showed that the reduction of activity of CASR to extracellular Ca²⁺ caused FHH in patients and our study demonstrated the importance of Asp-190 participated in response to Ca²⁺ in CASR.

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Elevated levels of circulating adiponectin (ADPN), an anti- inflammatory and anti-oxidative peptide, are associated with unfavorable cardiovascular outcomes in patients with cardiovascular diseases. The aim of this study was to investigate whether plasma ADPN levels could help predict major adverse cardiovascular events (MACE) in patients with documented coronary artery disease (CAD). We prospectively enrolled 193 CAD patients, who underwent percutaneous coronary intervention (PCI), and/or stenting and coronary artery bypass graft (CABG) surgery. ELISA was used to measure plasma ADPN concentrations. MACE—myocardial infarction, PCI, CABG, stroke, carotid revascularization, and death—was evaluated during a follow-up period of median 15.3 months (range 5-21 months). Cox regression analysis revealed that diabetes status, waist circumference, and plasma ADPN levels were significantly associated with MACE occurrence. On stratification according to diabetes status, plasma ADPN levels helped predict MACE only in patients with type 2 diabetes mellitus (T2DM). Kaplan-Meier analysis revealed higher MACE rates in diabetic patients with high-plasma ADPN levels than in those with low-plasma ADPN levels. High ADPN plasma concentrations can independently be associated with MACE in CAD with T2DM but not in those without diabetes. This indicates that plasma ADPN may have potential roles in high risk T2DM patients with ischemic heart disease.

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The levothyroxine suppressive efficacy in benign thyroid nodules treatment is well described in uninodular non-toxic goiter, whereas only few controlled trials enrolled patients with multinodular disease. The aim of the present study is to evaluate the short term effects of levothyroxine treatment in never treated, pre-menopausal women affected by thyroid multinodular disease. Seventy-one pre-menopausal women with thyroid multinodular disease, still presenting normal TSH levels, from Latina area were randomly assigned to a levothyroxine treated or control group. Biochemical and ultrasonography evaluations of thyroid were monitored at the enrolment and after 6, 12 and 24 months of treatment. In the levothyroxine treated group, after 1 year of treatment, thyroid and dominant nodule volume and number of nodules >0.5 mL significantly decreased from a median of 12.0 to 9.8 mL (p <0.001), from 1.0 to 0.5 mL (p <0.001) and from 0.5 to 0, respectively. Conversely, in the control group significant augmented values of these parameters were observed (p =0.007, p <0.001 and p <0.001, respectively). Furthermore, these observations were also confirmed by results obtained after a 24 months follow-up period. Our data support previous observations on the clinical usefulness of L-T₄ treatment in preventing thyroid and nodule volume and nodule numbers growth. These findings confirm the tendency of benign nodular disease toward progression and the efficacy of TSH suppression in preventing its evolution by means of removing the major growth factor for thyroid nodules still responsive to physiological stimuli.

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Excess secretion of various adipocyte-derived molecules has been linked with insulin resistance, obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease. Retinol-binding protein 4 (RBP4), one of the new adipocytokine, is recently reported to provide a link between insulin resistance and features of metabolic factors. Hypertension is one of the most influential risk factors among cardiovascular disease. We examined the relationship between systolic blood pressure (BP) levels and metabolic factors including homeostasis model assessment of insulin resistance (HOMA-R), high sensitivity c-reactive protein (hs-CRP), adiponectin, and RBP4. The subjects were 153 men aged 59±14 years and 224 women aged 57±14 years who had undergone medical check-ups in rural communities in 2007. Systolic BP was positively correlated with HOMA-R, hs-CRP and RBP4 but not with adiponectin in women. There was a positive significant relationship between serum RBP4 levels and blood pressure in women, but such a relationship was not found in men. Serum RBP4 levels were not correlated with HOMA-R in either men or women. Serum RBP4 levels negatively were correlated with estimated glomerular filtration rate (eGFR) in women but not in men. Multiple regression analysis revealed that serum RBP4 levels significantly were related to systolic BP independently of age, sex, body mass index (BMI), total cholesterol levels and eGFR. Our study showed that increased levels of RBP4 as well as HOMA-R and hs-CRP in women were significantly associated with increased levels of systolic BP.

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We report herein the case of a 1-year-old boy with McCune-Albright syndrome (MAS) who presented with infantile-onset Cushing’ s syndrome caused by ACTH independent macronodular adrenal hyperplasia (AIMAH). Abdominal CT, MRI, and adrenal scintigraphy with ¹³¹I-adosterol identified bilateral adrenal involvement with the left adrenal gland being larger and functionally more active. Unilateral adrenalectomy of the left gland was performed and ameliorated many clinical symptoms, such as Cushingoid appearance and height restriction, and it also normalized many endocrinological data, such as diurnal rhythms of ACTH and cortisol, ACTH and cortisol responses to CRH, and urinary 24 hr free cortisol. Glucocorticoid was replaced for the first 1 year and 6 months after the operation. One adrenal crisis episode occurred at 3 weeks after the operation, but none have occurred since. These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing’ s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged.

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Menin is lost by the sequential inactivation of both MEN1 alleles in subsets of non-hereditary endocrine tumors as well as those associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant hereditary cancer syndrome characterized by multiple tumors including parathyroid, pituitary and enteropancreatic endocrine tumors. Loss of menin has been reported to be associated with lowered caspase 8 expression and resistance to apoptosis in murine fibroblasts and in pancreatic islet tumors arising in heterozygous MEN1 gene knockout mice, the animal model of the human MEN1 syndrome. We confirmed by menin-knockdown experiments with specific siRNA that menin is crucial for caspase 8 expression in human culture cells while overexpression of menin did not increase caspase 8 protein over basal levels. We then examined expression of menin, caspase 8 and cyclin-dependent kinase inhibitors p27^Kip1 and p15^Ink4b by Western blotting in human parathyroid tumors surgically resected from patients with MEN1 and those with non-hereditary primary hyperparathyroidism. The menin and p27^Kip1 expression levels were correlated with MEN1 mutation status that was confirmed by DNA analysis. The caspase 8 and p15^Ink4b protein levels were variable among tumors, and were not correlated with menin protein levels. These findings suggest that human endocrine tumors lacking menin may not always exhibit lowered caspase 8 expression and hence may not be resistant to apoptosis-inducing therapy.

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Double pituitary adenomas are rare occurences in autoptical, surgical and neuroradiological series and are mostly due to non-functioning pituitary adenomas, GH-secreting and prolactin-secreting adenomas. ACTH secreting tumours are more rare and, to our knowledge, two distinct ACTH-producing adenomas within the same pituitary have never been reported. We herewith describe a 56 year old woman with Cushing’ s disease due to two clearly distinct ACTHsecreting pituitary adenomas. She presented with signs and symptoms of hypercortisolism and hormonal testing was indicative for pituitary-dependent Cushing’ s syndrome. Sellar MRI visualized an asymmetric pituitary gland with suspect lesions in both the right and the left pituitary lobes. Both lesions were removed during transsphenoidal surgery and remission of hypercortisolism ensued. Pathology confirmed the existence of two distinct adenomas located in different sites in the gland. Both presented ACTH immunoreactivity but displayed distinct morphological features. Our case indicates that double ACTH-secreting pituitary adenomas may occur in patients with Cushing’ s disease. Careful radiological, surgical and pathological examination is necessary to recognize this condition and avoid surgical failure.

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Germline mutations in the MEN1 gene are well documented as the genetic cause of multiple endocrine neoplasia type 1 (MEN1). In this study, we performed genetic analysis by direct MEN1 gene mutation analysis on a Chinese MEN1 family. The two patients in this family were diagnosed as MEN1 by the typical clinical findings of parathyroidoma, insulinoma and pituitary adenoma. The coding sequences, including 9 coding exons and exon/intron boundaries of the MEN1 gene were amplified by polymerease chain reaction (PCR) and subjected to direct sequencing. Sequence analysis showed a same novel insertion mutation in exon 3 (c.433_434ins CTTC) in both patients, resulting in an open reading frames shift and produced a premature termination codon. None of the other family members had this insert mutation. In conclusion, we add a new mutation of MEN1 gene in Chinese patients with MEN1, and it would be useful for the diagnosis of the disease.

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