Serum calcium (Ca) level is maintained within a narrow range mainly by actions of parathyroid hormone (PTH) and 1,25-dihydroxyvitmain D [1,25(OH)₂D]. While it is not rare to encounter hypocalcemia in clinical practice, there is currently no practical guideline for the differential diagnosis of hypocalcemia. We therefore propose flowcharts for the differential diagnosis of hypocalcemia and hypoparathyroidism, especially PTH-deficient hypoparathyroidism in which many genetic or other causes have been identified recently. Hypocalcemia can be divided into two categories, hypocalcemia with low serum phosphate level, and one with normal to elevated serum phosphate level. Deficient actions of 1,25(OH)₂D, loss of Ca into urine, and deposition of Ca in bone or soft tissues are main causes of hypocalcemia with low to low normal serum phosphate level. Hypocalcemia with high normal to high serum phosphate level includes chronic renal failure and hypoparathyroidism. Hypoparathyroidism is subdivided into PTH-deficient hypoparathyroidism and pseudohypoparathyroidism. Recent investigations identified several causes of PTH-deficient hypoparathyroidism, including genetic abnormalities and parathyroid autoantibodies, which should be differentiated from idiopathic hypoparathyroidism. Physical and laboratory findings, the time of the onset of diseases and accompanying illness can be clues for identifying causes of PTH-deficient hypoparathyroidism.

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The human endometrium undergoes cyclical changes including proliferation, differentiation, tissue breakdown, and shedding (menstruation) throughout a woman's reproductive life. The postovulatory rise in ovarian progesterone induces profound remodeling and differentiation of the estradiol-primed endometrium. This change, termed decidualization, is crucial for embryo implantation and maintenance of the pregnancy. To date, activation and crosstalk of cAMP- and progesterone-mediated signaling pathways have emerged as key cellular events to drive integrated changes at both the transcriptome and the proteome levels. This results in the induction and maintenance of the decidual phenotype and function. Our recent series of studies highlights the critical role of SRC kinase activation (v-src sarcoma viral oncogene homolog) and STAT5 (signal transducer and activator of transcription 5) phosphorylation in decidualization. After separation of the functional layer of the differentiated endometrium that follows progesterone withdrawal, i.e., menstruation, the basal layer of the endometrium, under the influence of estradiol, regrows and initiates a unique form of angiogenesis and regenerates a new functional layer. The molecular and cellular mechanisms for this process remain elusive, mainly because of difficulties in reproducing menstrual tissue breakdown, shedding, and subsequent tissue regeneration in vitro. We have recently developed a "humanized" mouse model in which a functional human endometrium is reconstituted. It may be used as an in vivo experimental tool for the study of endometrial angiogenesis and regeneration. This model may also be used to identify and test new therapeutic strategies for endometriosis, endometrial cancer, implantation failure, and infertility related to endometrial dysfunction.

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The adipocytokine retinol binding protein-4 (RBP4) has recently been shown to link obesity and insulin resistance, although their relationship remains controversial in human studies. The influence of weight reduction with changes of fat distribution on serum RBP4 concentration in nondiabetics is also unknown. We assessed the effect of weight reduction (especially abdominal visceral fat loss) on serum RBP4 levels after a structuralized weight-reduction program. We conducted a prospective intervention study consisting of a 16-week weight reduction program, including lifestyle modification and adjuvant appetite suppressants. A total of 52 nondiabetic subjects aged 37.4 ± 11 years with a body mass index of 27.4 ± 4 kg/m ² were included. Serum RBP4 concentrations with other metabolic parameters and abdominal adipose tissue areas as determined by computed tomography scan were measured both before and 16 weeks after the weight reduction program. Subjects had a 10.9% loss of body weight accompanied by a 25.5% decrease in serum RBP4 levels, with improved insulin sensitivity after the program. The changes in RBP4 levels were significantly correlated with the amounts of abdominal visceral fat loss (r = 0.38, p<0.01) but were not associated with the amount of total body fat loss or abdominal subcutaneous fat loss. Weight reduction, especially the loss of abdominal visceral fat, lowers serum RBP4 concentrations in nondiabetic subjects. The relationship between individual changes in RBP4 and abdominal visceral fat indicated that RBP4 may be involved in the beneficial effect of visceral fat reduction on the improvement of insulin resistance and metabolic syndrome.

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Thyroid hormone has many effects on the heart and cardiovascular system. Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. However, the relationship between thyroid hormone excess and the cardiac complications of angina pectoris and myocardial infarction remains largely speculative. Moreover, few studies have been reported on the effect of thyroid hormone levels within normal range on coronary artery disease (CAD). Therefore we examined the association of thyroid function with coronary artery diseases in euthyroid angina patients. Total 192 subjects (mean age; 60.8 yrs) were enrolled in which coronary angiograms were performed due to chest pain. We measured free thyroxine (FT₄), thyroid stimulating hormone (TSH), serum lipid levels and high-sensitivity C-reactive protein (hsCRP) levels and analyzed their association with the presence of CAD. Serum FT₄ levels were higher in patients with CAD compared with the patients without CAD (1.31 ± 0.30 vs 1.20 ± 0.23, p = 0.006), and high FT₄ level was associated with the presence of multi-vessel disease. Multivariate analysis showed that age (odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01-1.07, p = 0.007), hypertension (OR 2.04; 95% CI 1.06-3.90, p = 0.036) and FT₄ (OR 4.23; 95% CI 1.12-15.99, p = 0.033), were the determinants for CAD. The relative risk (RR) for CAD in highest tertile of FT₄ showed increased risk compared with the lowest tertile (RR 1.98; 95% CI 0.98-3.99, p<0.001). Our study showed that FT₄ levels were associated with the presence and the severity of CAD. Also, this study suggests that elevated serum FT₄ levels even within normal range could be a risk factor for CAD. Further studies will be necessary to confirm the relationship of thyroid function and CAD.

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The present study was designed to determine the effects of leptin on lipid metabolism and gene expression during differentiation and maturation of the 3T3-L1 murine preadipocyte. The preadipocytes were induced to differentiate in a growth medium containing 10% calf serum and a hormonal cocktail for 2 days. The cells were next allowed to maturate for 14 days in the growth medium supplemented with 10 μg/ml insulin or 500 ng/ml insulin-like growth factor (IGF)-I in the absence or presence of supplemented leptin. Leptin, at a dose of 5 to 500 ng/ml, had no effect on proliferation of undifferentiated 3T3-L1 cells. However, leptin suppressed the insulin- or IGF-I-stimulated lipid accumulation and enhanced the release of glycerol, a measure of lipolysis, in a dose-dependent manner during and after the maturation of the cell. Moreover, leptin at a dose of 50 ng/ml inhibited IGF-I gene expression during the entire differentiation and maturation and also peroxisome proliferator activated receptor (PPAR)-γ expression during late maturation as monitored by semi-quantitative reverse transcription-polymerase chain reaction. However, leptin exerted no effect on the expression of transforming growth factor-β, CCAT/enhancer binding protein-α and PPAR-δ. Taken together, results suggest the anti-lipogenic and lipolytic effects of leptin in differentiating and mature adipocytes may have been partly mediated by suppressing the expression of PPAR-γ and IGF-I genes.

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This retrospective study was aimed 1) to compare the difference of the findings between adrenal CT scan and adrenal venous sampling (AVS) in 35 cases with definite primary aldosteronism (PA) for assessment of the diagnostic efficacy of PA subgroup (unilateral and bilateral adrenal hypersecretion: UAH and BAH), and 2) to determine the clinical and biochemical parameters as potential predictors for PA subgroup. There were significant discordant results based on AVS and CT scan in subgrouping PA; 9 of 17 BAH patients (53%) had unilateral lesion on CT scan, while 4 of 18 UAH patients (22%) had no apparent or bilateral lesions on CT scan. Among three diagnostic criteria, absolute values of plasma aldosterone concentration (PAC) in both adrenal veins, lateralized and contralateral ratios of aldosterone/cortisol after ACTH stimulation during AVS to determine the laterality, none of them showed 100% diagnostic accuracy if applied alone. Among several clinical and biochemical parameters, hypokalemia (<3.4 mEq/l), younger age (<52 y) and poor response of PAC (<1.45) after furosemide-upright posture, proved to be significant predictors for UAH, with higher specificities (100%, 88%, 94%, respectively). Therefore, despite AVS as a gold standard method to determine the laterality of aldosterone hypersecretion in PA, our study shows that no single criterion could provide definite diagnostic value for its laterality by AVS. It is also suggested that most PA patients, if not all, with a distinct unilateral adrenal lesion on CT accompanied by hypokalemia, younger age and poor aldosterone response to renin stimulation, could undergo adrenalectomy without prior AVS.

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Although the responsible gene has not yet been identified, patients with differentiated thyroid carcinoma, including papillary and follicular carcinomas, demonstrating a family history have been reported and patients having one or more family members with differentiated carcinoma among their first-degree relatives are designated as having familial nonmedullary thyroid carcinoma (FNMTC). In this study, we investigated the biological characteristics, including prognosis, of familial follicular carcinoma. Three hundred and nineteen patients who underwent initial surgery for follicular thyroid carcinoma between 1987 and 2004 who were enrolled in this study. Of these 319 patients, 6 patients (1.9%) in 6 families were classified as having familial follicular carcinoma based on the criteria described above. The incidence of aggressive characteristics such as male gender, age 45 years or older, poor differentiation, widely invasive carcinoma, tumor larger than 4 cm and distant metastasis at diagnosis did not differ between familial and sporadic follicular carcinomas. One patient with familial follicular carcinoma underwent re-operation because of newly detected papillary carcinoma in the remnant thyroid 160 months after the initial surgery, but none of the 6 patients with familial carcinoma showed recurrence or died of follicular carcinoma. We can therefore conclude that FMNTC of the follicular type is very rare and there is no evidence that familial follicular carcinoma is more aggressive or has a worse prognosis than sporadic follicular carcinoma. The therapeutic strategy for follicular carcinoma might depend on conventional prognostic factors such as poor differentiation and distant metastasis at diagnosis, but not on whether the carcinoma is familial or sporadic.

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Flow-mediated vasodilatation (FMD) is a vascular functional test to detect endothelial dysfunction at the early stage of cardiovascular diseases. Patients with active acromegaly have higher morbidity and mortality due to cardiovascular events. To determine whether active acromegaly is associated with endothelial dysfunction, we studied 17 patients with active acromegaly for measurements of FMD, carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV), and other biochemical parameters before and 3 months after transsphenoidal surgery (TSS). Baseline %FMD in patients with active acromegaly was significantly lower than that in age- and sex-matched control subjects. After TSS, the mean %FMD in acromegaly significantly increased from 5.3% to 7.4%; 12 patients had increased %FMD (responders), whereas 5 patients had decreased or unchanged %FMD (non-responders). However, neither carotid IMT nor baPWV changed after TSS. Serum levels of GH, insulin-like growth factor (IGF)-1, total cholesterol, low-density lipoprotein cholesterol (LDL-C), hemoglobin HA_1C, fasting plasma glucose and insulin levels, and homeostasis model assessment (HOMA)-R significantly decreased, whereas high-density lipoprotein cholesterol significantly increased. Responders had significantly lower baseline %FMD than did non-responders and both insulin levels and HOMA-R significantly decreased in responders, but not in non-responders after TSS. Simple regression analysis revealed that the change of %FMD showed a significant negative correlation with that of LDL-C, but not of IGF-1 or GH, in responders. In conclusion, it is suggested that endothelial dysfunction associated with active acromegaly improves soon after TSS, which is related to LDL-C and/or insulin resistance, but not to excess GH and/or IGF-1 itself.

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Objective: This study was designed in order to investigate the short term effects of atorvastatin on endothelial function and oxidized LDL (oxLDL) levels and to evaluate the association of endothelial dysfunction to oxLDL levels and inflammatory markers in type 2 diabetic patients. Material and Methods: Thirty type 2 diabetic and 11 healthy subjects with LDL levels between 100-160 mg/dl. without a history of cardiovascular event were included in the study. Both groups were matched with respect to age, gender, body mass indices and lipid levels. Flow- mediated dilatation (endothelium dependent, FMD) and nitroglycerine-induced dilatation (endothelium independent, NID) were measured in the brachial artery using high-resolution ultrasound in all participants and carotid artery intima media thickness (IMT) were also evaluated. OxLDL levels, lipid parameters, blood glucose, C-peptide, HbA1c and inflammatory markers including C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR) were studied. Type 2 diabetic patients received 10 mg. Atorvastatin for 6 weeks and FMD and NID were reevaluated and oxLDL levels and inflammatory markers remeasured. Results: Basal FMD, NID, IMT and oxLDL levels besides inflammatory markers were not significantly different between patients and controls. No correlation was found between inflammatory markers and FMD and NID. Only IMT correlated with fibrinogen levels obtained before treatment. In non-diabetics, IMT also correlated with oxLDL levels (p: 0.013). FMD and NID significantly improved after atorvastatin therapy ((7.62 ± 7.6 vs. 12.65 ± 7.8, p<0.001 and 18.22 ± 9.57 vs. 21.43 ± 9.6, p: 0.007, respectively). Atorvastatin significantly reduced oxLDL levels (57.85 ± 10.33 vs. 44.36 ± 6.34, p<0.001). Conclusion: Atorvastatin improves endothelial functions and reduces oxLDL levels in type 2 diabetics with average lipid levels in the short term and may have beneficial effects in the prevention of early atherosclerotic changes.

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Intracerebroventricular (icv) administration of glucagon-like peptide-1 (GLP-1) inhibits food intake and induces c-fos expression in the hypothalamus. However, the effects of GLP-1 on hypothalamic neuronal activity or neuropeptide mRNA expression are unknown. In this study, we examined the effects of GLP-1 on fasting-induced changes in the expression of hypothalamic orexigenic and anorexigenic neuropeptide. Food intake was significantly inhibited after icv injection of GLP-1 in 48 h fasted rats. Hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AgRP) mRNAs were significantly increased by fasting, whereas icv GLP-1 treatment significantly attenuated these fasting-induced increases. Both proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA levels were decreased by fasting, while GLP-1 treatment attenuated fasting-induced decreases in POMC and CART expression. We also determined the mRNA levels of AMP-activated kinase (AMPK) and found that fasting resulted in a significant stimulation of hypothalamic AMPKα2 mRNA. Fasting-induced increase in AMPKα2 mRNA was almost completely prevented by GLP-1 treatment. Analysis of phosphorylated AMPKα and acetyl CoA carboxylase showed similar results. Taken together, our observation suggests that the decreased food intake by GLP-1 is caused by preventing the fasting-induced increase in hypothalamic NPY and AgRP and the fasting-induced decrease in hypothalamic POMC and CART. Our results also suggest that the food intake lowering effect of GLP-1 is caused by reversing the fasting-induced increase in hypothalamic AMPK activity. Therefore we conclude that the anorectic effect of GLP-1 seems to be mediated by, at least in part, by the hypothalamus.

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Resistance to TSH (RTSH [MIM 275200]) is a heterogeneous condition defined by variable degree of insensitivity to biologically active TSH. While this condition is classically caused by loss-of-function mutations of the TSH receptor gene (TSHR), several patients have exhibited RTSH-like phenotype in the apparent absence of TSHR mutations, and some of them have mutations of PAX8 or GNAS1. We identified a Japanese boy with congenital hypothyroidism who suffered from recurrent lower respiratory infection during infancy and choreoathetosis at a later age. At 14 years of age, he was diagnosed as having RTSH, on the basis of compensated hypothyroidism (TSH, 30.2 mU/L; FT4, 1.2 ng/dl), disproportionate increments of thyroid hormones and TSH during a TRH test (ΔFT3, 0.4 pg/ml; ΔT3, 13 ng/dl; and ΔTSH, 88.3 mU/L), and normal ultrasound thyroid image and radioactive iodine uptakes. Molecular analysis for TITF1 revealed a novel de novo heterozygous deletion/insertion mutation (c.470_479delinsGCG,) that is predicted to lose the entire homeodomain and the NK2-specific domain. We suggest that a heterozygous loss-of-function TITF1 mutation can also cause RTSH-compatible phenotype.

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Galectin-9 has been recently considered as a novel marker for the mid- and late-secretory phases of human endometrium and decidua. The aim of this study was to investigate the subcellular distribution of galectin-9 in the endometrial epithelium, especially during the frame of the implantation window. Endometrial biopsies in the proliferative, early, and mid-secretory phases from women with regular menstrual cycle were studied using several approaches, including scanning electron microscopy, immunostaining for light and transmission electron microscopies (TEM), immunoblotting, and statistical analysis of the area-related numerical densities of galectin-9-bound nanogold. Images of immunostaining for light microscopy demonstrated a strong expression of galectin-9 at the luminal and glandular endometrial epithelium in the mid-secretory phase compared to the proliferative and early secretory phases. Data of immunoblotting revealed a molecular weight of 36 kDa band with high intensity in the mid-secretory samples. Photomicrographs of immunogold staining for TEM illustrated the localization of galectin-9 in the uterodomes. Statistical and morphometric analysis showed a significantly higher area-related numerical density of galectin-9-bound nano-golds in the uterodomes compared to that of the uterodome-free areas of the luminal epithelium (p<0.001). This is the first demonstration of the molecular localization of galectin-9 in the bulbous ultrastructure of the human endometrial epithelium, called uterodomes. High expression of galectin-9 at uterodomes during the frame of implantation window suggests that galectin-9 can be considered as a marker of endometrial receptivity and should play an important role during the initial events of human embryo implantation.

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Among thyroid nodules arising from follicular cells, benign nodular goiter is thought not to metastasize to regional or distant organs. However, we encountered five cases that were pathologically diagnosed as benign nodular goiter but showed metastasis. The prevalence of benign nodular goiter showing metastasis was 0.17% (5 of 2978 patients). On pathology, there were no detectable signs of carcinoma or follicular adenoma lesions. Two patients showed lymph node metastasis that was pathologically confirmed as metastasis of nodular goiter. One was preoperatively and another was postoperatively detected by ultrasonography. These patients also showed distant metastases that could be ablated by radioiodine. One patient preoperatively showed lung metastasis and the remaining two showed lung and bone metastases and bone metastasis postoperatively. Pathological diagnosis of thyroid nodules has limitations, and cases diagnosed as benign nodular goiter should still undergo careful follow-up.

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We assessed the incidence of elderly patients in Japanese acromegalics and the characteristics of their clinical presentation. We also evaluated the safety and efficacy of transsphenoidal surgery (TSS) in this patient group. During the 28-year period from 1980 to 2007 we treated 290 patients with acromegaly at our hospitals. Of these, 9 (3.1%) were elderly, i.e. 70 years old or older. They comprised 0.7% of acromegalics treated during the first- and 4.5% of patients with acromegaly treated during the 2nd 14-year period. Before treatment, all manifested abnormal glucose tolerance; 6 had diabetes mellitus (DM), 6 presented with hypertension, and 2 had cardiovascular disease, malignant neoplasms, or hyperlipidemia. Of the 7 elderly acromegalics who underwent TSS none manifested surgical morbidity or new pituitary hormone deficiencies. Postoperatively, the nadir growth hormone (GH) level at the oral glucose tolerance test (OGTT) was under 1.0 ng/mL in 5 patients, insulin-like growth factor (IGF-1) levels normalized in 4. Glucose tolerance improved in all operated patients. Only 1 of 6 patients with preoperatively diagnosed DM continued to manifest DM post-treatment, anti-hypertensive drugs could be tapered in 3 of patients with preoperative hypertension. In conclusion, we found that there was a high incidence of abnormal glucose tolerance and hypertension in elderly acromegalics, that surgical treatment was effective and safe in this population, and that it was useful for the control of co-morbidities.

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A 75-year-old man was admitted to our hospital because of unconsciousness. His plasma glucose was very low, but his serum levels of insulin and IGF-I were also low. He was found to have a giant solitary pleural tumor, which was completely resected, after which his hypoglycemia ameliorated postoperatively. Histologically, the tumor was consistent with the pathological diagnosis of a solitary fibrous tumor derived from the pleura. Immunohistochemical study revealed positive immunostaining for IGF-II in tumor cells. The presence of high molecular weight (HMW) form of IGF-II in the tumor tissue and patient's serum was confirmed by Western blot analysis. Steady-state mRNA levels of IGF-II and prohormone convertases (PC) 4, a potential protease responsible for IGF-II processing, as determined by RT-PCR were about 14-fold greater and 5-fold less in the tumor tissue than those in normal placental tissue, respectively. Therefore, it is suggested that biologically active, unprocessed HMW form of IGF-II generated from the impaired processing of IGF-II precursor by the defective PC4 expression in the tumor was responsible for the non-islet cell tumor hypoglycemia (NICTH) in the present case.

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Purpose of the study: Tight glycemic control is important for the prevention of microvascular complications in diabetic patients. We examined the reliability of using blood glucose levels measured at various time-points relative to a meal as an index of glycemic control in Japanese diabetic outpatients. Basic procedures followed: We examined the correlation between the fasting blood glucose (FBG) level; the one-hour (1-h), two-hour (2-h), and three-hour (3-h) post breakfast blood glucose (PBBG) levels, the 1 h, 2 h, and 3 h post lunch blood glucose (PLBG) levels and the hemoglobin A1c (HbA1c) levels in Japanese diabetic outpatients. A total of 11451 patient-visits to the Marunouchi Hospital between January 2002 and December 2002 were included in the study. The main findings: The blood glucose levels measured at all of the above time-points were significantly correlated with the HbA1c level. As calculated using local polynomial regression fitting, the FPG, 1-h, 2-h, and 3-h PBBG levels that corresponded to an HbA1c level of 6.5% were 132 mg/dL, 174 mg/dL, 170 mg/dL, and 143 mg/dL, respectively. The FPG and 2-h PBBG levels exhibited a good sensitivity and specificity for predicting a glycemic control corresponding to an HbA1c<5.8%, while the FPG and 3-h PBBG levels exhibited fair sensitivity and specificity for predicting glycemic control corresponding to an HbA1c<6.5%. The principal conclusions: The FBG, 2-hPBBG, and 3-hPBBG levels can be used as rough estimates of glycemic control in Japanese diabetic outpatients.

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Zuckerkandl's tubercle (ZT) is a well-documented anatomical structure. This study evaluated ZT anatomical characteristics in terms of the recurrent laryngeal nerve (RLN) and the superior parathyroid (SP). The study involved 325 (10 with benign tumors and 315 with malignancies) patients who underwent thyroidectomy between February and June 2007. ZTs were classified according to size: Grade 0 (unrecognizable), Grade I (≤5 mm), Grade II (6~10 mm) and Grade III (>10 mm). The incidence and size of the ZT and its positional relationship to the RLN and SP were investigated during thyroid surgery. ZTs were identified in most patients (right 89.3%, left 85.6%). The distribution of ZTs according to grade was as follows: Grade 0, right 10.7% and left 14.4%; Grade I, right 7.9% and left 11.1%; Grade II, right 43.5% and left 38.5%; and Grade III, right 37.9% and left 35.9%. The most common RLN course was in a groove between the ZT and the main body of the thyroid. The majority of SPs were cranial to the ZT which was located at the 1 or 2 o'clock position (96.1%) in the left, and at 10 or 11 o'clock (95.2%) in the right. The smaller the size of the ZT, the greater the distance between the ZT and the SP. There was a constant relationship between the ZT and RLN and SP. Therefore, an identification of ZT and an understanding of the relationship between the ZT and RLN and SP are essential for performing safe thyroid surgery.

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Objective: To establish the usefulness of specific ultrasound (US) features as indications for ultrasound-guided fine needle aspiration biopsy (FNAB) in incidentally found infracentimetric thyroid nodules. Methods: The ultrasonographic features and cytology of FNAB samples of 96 histopathologically-proven papillary microcarcinomas (less than 1 cm in long diameter) and 75 less than 1 cm sized benign nodules were analyzed and compared. The risk of malignancy indicated by each US feature was calculated by logistic regression analysis. Results: Among the US features examined, internal content, shape, margin, echogenicity, and calcifications showed statistically significant differences between benign and malignant infracentimetric nodules. Crude odds ratios (OR) and 95% confidence intervals (CI) for risk of malignancy were, for solid content, OR = 39.3 (95% CI = 3.3-4.64); for taller than wide shape, OR = 14.2 (95% CI = 1.43-14.1); for hypoechogenicity, OR = 3.57 (95% CI = 1.31-9.86); for marked hypoechogenicity, OR = 31.33 (95% CI = 6.63-14.8); and for coarse macrocalcifications, OR = 3.43 (95% CI = 1.04-11.3). Conclusions: Infracentimetric nodules that are solid, taller than wide, hypoechogenic or markedly hypoechogenic, and have coarse microcalcifications and macrocalcifications have a high risk of malignancy, indicating further assessment.

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The prevalence of isolated ACTH deficiency (IAD) in Japan remains to be determined. Both authors (T.Y. & K.K.) had unique opportunities to see all patients with maturity-onset IAD in particular areas. T.Y. regularly visited Tokunoshima Island in Kagoshima Prefecture (population of about 28,500) which has two acute-care hospitals. He has taken care of endocrine-metabolism cases in one hospital and kept in touch with an endocrine-oriented physician in another. K.K. has provided glucocorticoid supplementation for all patients with maturity-onset IAD as the patients' own physician in a hospital which provided medical care for the Chuetsu district in Niigata Prefecture with 527,407 inhabitants in 2005. Four male patients (average age at onset, 70.0 years; range, 67-75 years) were identified in Tokunoshima over the 10-year period and 20 patients (15 males and 5 females; average age at onset, 63.9 years; range, 49-77 years) were cared for in the Chuetsu district in 2005. The estimated prevalence of IAD from the numbers of IAD patients and of inhabitants in the periods cited from the national population survey was 7.3 per 100,000 (an average in 10-year period) in Tokunoshima and 3.8 per 100,000 in the Chuetsu district in 2005. Maturity-onset IAD in Japan thus is not very rare in the elderly.

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According to our research, we evaluated that for the ovulation function in polycystic ovary syndrome (PCOS) with IR, Homeostasis model assessment-insulin resistance (HOMA-IR) is a clinic , simple and practical and sensitive Index for assessing the ovualtion failure. Meanwhile, after anti-IR treatment, HOMA-IR is also a reliable and simple for accessing the recoverying ovulation function.

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