Hypothalamic type of hypopituitarism and central diabetes insipidus probably linked to Rathke's cleft cyst.

A 73-year-old woman was admitted due to weight loss and generalized malaise. The basal levels of all the anterior pituitary hormones, except for prolactin, were reduced. However, they were all elevated in response to exogenous hypothalamic hormones. After starting hydrocortisone replacement, the patient had polyuria of >5,000 mL/day. T1-weighted MRI depicted a low signal of an oval mass in the sella turcica and an iso-intense signal of another mass at the pituitary stalk. These findings indicate a hypothalamic type of hypopituitarism and masked central diabetes insipidus which possibly derived from the atypical occupation of Rathke's cleft cyst at the pituitary stalk.

Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes.

There is evidence that betatrophin, a hormone derived from adipose tissue and liver, affects the proliferation of pancreatic beta cells in mice. The aim of this study was to examine circulating betatrophin concentrations in Japanese healthy controls and patients with type 1 and type 2 diabetes. A total of 76 subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were enrolled in the study. Circulating betatrophin was measured with an ELISA kit and clinical parameters related to betatrophin were analyzed statistically. Circulating betatrophin (Log transformed) was significantly increased in patients with diabetes compared with healthy subjects (healthy controls, 2.29 ± 0.51; type 1 diabetes, 2.94 ± 0.44; type 2 diabetes, 3.17 ± 0.18; p<0.001, 4.1 to 5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log triglyceride were strongly associated with Log betatrophin in all subjects (n=76) in correlation analysis. In type 1 diabetes, there was a correlation between Log betatrophin and Log CPR. These results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes. The findings of this pilot study also suggest a possibility of association between the level of betatrophin and the levels of glucose and triglycerides.

Prompt efficacy of tolvaptan in treating hyponatremia of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) closely associated with rupture of a gastric artery aneurysm.

A 78-year-old man with abdominal pain was diagnosed with a rupture of a gastric artery aneurysm. The serum Na level promptly decreased from 135 to 110 mmol/L within several days. Brain magnetic resonance angiography revealed severe vasoconstriction of the cerebral basilar artery and anterior cerebral artery. There was neither dehydration nor edema. The plasma arginine vasopressin level was 3.3 pg/mL, despite hypoosmolality. These findings indicated a diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) derived from severe vasoconstriction of the cerebral arteries. The administration of 7.5 mg of tolvaptan rapidly increased the serum Na level from 123 to 138 mmol/L within the first 24 hours, thereafter continuously maintaining a normal level. Treatment with tolvaptan corrected the patient's dilutional hyponatremia.

Combination therapy of angiotensin II receptor blocker and thiazide produces severe hyponatremia in elderly hypertensive subjects.

Thiazide diuretics are known to produce severe hyponatremia as well as hypokalemia. The present study demonstrated severe hyponatremia in three hypertensive patients who had received combination therapy consisting of an angiotensin II receptor blocker (ARB) and thiazide. The serum sodium (Na) levels in all three cases were markedly reduced to below 116 mmol/L, and the patients exhibited augmented urinary excretion of Na with a reduced circulatory blood volume. After withdrawing the ARB and thiazide treatment, the serum Na levels normalized within one to two weeks. Combination therapy with ARBs and thiazide may cause hyponatremia in elderly patients.

Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes.

BACKGROUND: Osteoprotegerin is a member of the tumor necrosis factor-related family and inhibits RANK stimulation of osteoclast formation as a soluble decoy receptor. The goal of this study was to determine the relationship of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. METHODS: The subjects were 124 patients with type 2 diabetes mellitus, including 88 males and 36 females with a mean (± SD) age of 65.6 ± 8.2 years old. Serum levels of osteoprotegerin, osteocalcin, fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D3 and adiponectin were measured by ELISA. Vascular calcification in the cervical artery was examined by ultrasound sonography. The subjects were divided into 4 quartiles depending on serum osteoprotegerin levels. RESULTS: Vascular calcification was significantly higher in the 4th quartile and significantly lower in the 1st quartile of serum osteoprotegerin levels, compared to other quartiles. There were no differences in serum osteoprotegerin and vascular calcification among patients with different stages of diabetic nephropathy, but serum FGF23 levels were elevated in those with stage 4 diabetic nephropathy. Simple regression analysis showed that serum osteoprotegerin levels had significant positive correlations with age, systolic blood pressure and serum adiponectin levels, and significant negative correlations with BMI and serum 25-hydroxyvitamin D3. CONCLUSIONS: These findings suggest that elevated serum osteoprotegerin may be involved in vascular calcification independently of progression of diabetic nephropathy in patients with type 2 diabetes.

Hyponatremia is the valuable manifestation for initiating diagnosis of hypopituitarism in elderly.

The present study was undertaken to determine clinical features of hypopituitarism in elderly subjects. Thirty-one elderly patients with hypopituitarism were enrolled. They were 19 males and 12 females, with the ages of 70.7±5.4 years ranging from 62 to 80 years. High prevalence of hyponatremia (80.6%) and hypoglycemia (29.0%) was found, and it was totally different from that in hypopituitarism from general population. There were two groups of hyponatremia derived from their clinical courses, namely, acute deterioration of hyponatremia and chronically persistent hyponatremia. Analysis for deficient hormones clearly showed that ACTH deficiency was highly found in 30 of 31 patients. There was no difference in serum cortisol levels between the hyponatremic and normonatremic patients. Despite hypoosmolality, plasma arginine vasopressin (AVP) was apparently high in the hyponatremic patients compared with in the normonatremic ones. The present study indicates that hyponatremia is the valuable finding for initiating diagnosis of hypopituitarism, and that augmented release of AVP may be involved in developing hyponatremia in elderly patients with hypopituitarism.

Prompt increases in retinol-binding protein 4 and endothelial progenitor cells during acute exercise load in diabetic subjects.

The present study was undertaken to determine whether acute exercise load alters serum retinol-binding protein 4 (RBP4) and numbers of endothelial progenitor cells (EPC) in diabetic subjects. Sixty-two subjects with type 2 diabetes mellitus were enrolled in the present study. They were 50 males and 12 females with the ages of 65.1±8.1 (mean ± SD) years. Cardio-pulmonary exercise stress test (CPX) was carried out, and the numbers of EPC and serum RBP4 levels before and after the CPX were measured. RBP4 is a cytokine synthesized in hepatocytes, white adipose tissues and skeletal muscles, and serum RBP4 was determined by ELISA. EPC was determined as CD34(+)/133(+) cells by FACS. The subjects were subgrouped into two groups with or without nephropathy. Serum RBP4 levels promptly increased from 48.2±4.3 (mean±SEM) to 54.3±4.2 µg/mL after the CPX (mean exercise time of 8 min) in the diabetic subjects without nephropathy (p=0.0006), but did not in those with nephropathy. There was a positive correlation between changes in serum RBP4 during the exercise and estimated glomerular filtration rate (r=0.30, p=0.018). Also, an acute exercise load promptly increased the number of EPCs in the diabetic subjects with and without nephropathy. These findings suggest that a prompt increase in exercise-induced RBP4 is retarded by progression of nephropathy, and that an exercise-induced mobilization of EPCs could maintain endothelial cells in diabetic subjects.

Central diabetes insipidus and hypothalamic type of hypopituitarism associated with atypical location of Rathke's cleft cyst.

A 68-year-old woman was admitted to determine the pathogenesis of weight loss and polyuria. Physical findings on admission showed BMI of 20.9, blood pressure of 147/69 mmHg, and that she had ciliac, axillar and pubic hair loss. Laboratory findings showed that plasma adrenocorticotropic hormone (ACTH) was 4.6 pg/mL with serum cortisol of 1.2 µg/dL. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were markedly reduced. Serum growth hormone (GH) and insulin growth factor (IGF)-1 were 0.054 ng/mL and 25 ng/mL, respectively. Serum prolactin was as high as 85.6 ng/mL. The levels of all the pituitary hormones were elevated in response to a mixture of exogenous corticotrophin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and growth hormone-releasing hormone (GRH). However, there was no response of ACTH and GH release to insulin-induced hypoglycemia and no response of LH and FSH release to clomiphene. Urine volume was more than 4,000 mL, with low urine osmolality of 134 mmol/kg. Plasma arginine vasopressin (AVP) was 0.8 pg/mL. There was no increase in urine osmolality and plasma AVP in response to 5% hypertonic saline load. Magnetic resonance imaging revealed Rathke's cleft cyst at the pituitary stalk level, but there was no abnormal finding in the hypothalamus. These findings indicate central diabetes insipidus and hypothalamic type of hypopituitarism, resulting from the atypical location of Rathke's cleft cyst.

Ectopic ACTH syndrome associated with large cell neuroendocrine carcinoma of the thymus.

A 38-year-old man was admitted for evaluation of Cushing's syndrome. Physical findings showed swelling of the face, and hypertension, but not Cushingoid stigmata. Laboratory data revealed serum cortisol level of 34.1 µg/dL and plasma ACTH of 140 pg/mL. Overnight administration of 1 and 8 mg dexamethasone did not suppress plasma ACTH or serum cortisol. Chest X-ray showed a mass at the upper-anterior quadrant of the mediastinum, and chest CT scan revealed a heterogenous tumor of approximately 60 mm in diameter, which infiltrated into the superior vena cava and ascending aorta, and caused superior vena cava syndrome. The tumor was resected. Histological examination indicated large cell neuroendocrine carcinoma of the thymus and positive immunoreactivity for ACTH. Ten days after the operation, the plasma ACTH decreased as low as 13.7 pg/mL. The present study indicates that large cell neuroendocrine carcinoma of the thymus can cause superior vena cava syndrome and ectopic ACTH syndrome.

Bilateral aldosteronoma associated with secondary aldosteronism in a chronic hemodialysis subject.

We demonstrated a rare case of bilateral aldosteronoma accompanied by secondary aldosteronism in a 37-year-old man with chronic renal failure on hemodialysis. He initially developed immunoglobulin A nephropathy at 11 years old, and had been treated with hemodialysis since the age of 17 years. His blood pressure was 110/68 mmHg, and no other abnormal findings were detected. Laboratory findings revealed that serum potassium was 3.9 mmol/L; plasma renin activity, 4.8 ng/ml/h and plasma aldosterone, 19,000 pg/mL. Abdominal computed tomography revealed bilateral adrenocortical tumors, measuring 34 and 40 mm in diameter in right and left tumors, respectively. (131)I-Adosterol scintigram showed bilateral accumulation. Left adrenalectomy was performed under laparoscopy. The tumor was encapsulated and well-circumscribed. The majority of the tumor was composed of a dark-brown portion admixed with sporadic foci of golden-yellow portions. Hyaline degeneration was detected in its central portion. The tumor was composed of clear cortical cells in viable portions. Tumor cells demonstrated immunoreactivity for the cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD II) and 21-hydroxylase, but not 17 alpha-hydroxylase. In the adjacent non-neoplastic adrenals, 3 beta-HSD II was markedly present in the hyperplastic glomerulosa zone. These findings suggest that the presence of secondary aldosteronism, which is closely related to the conditions of chronic renal failure on hemodialysis, eventually promoted the development of bilateral aldosteronoma from the zona glomerulosa hyperplasia.

Incomplete deficiency of hypothalamic hormones in hypothalamic hypopituitarism associated with an old traumatic brain injury.

A 62 year-old man was admitted to determine the pathogenesis of his hypoglycemia. He was unconscious and his plasma glucose level was 26 mg/dL. When he was 31 years old, he had a traffic accident and was unconscious for several days. Physical findings on admittance showed that the patient's BMI was 17.8 and blood pressure, 114/70 mmHg. He was alert. He had a hypogonadal face with a lack of beard, and he had an atrophic testis with a volume of 1 to 2 ml. Laboratory findings showed that his fasting plasma glucose was 73 mg/dL; serum sodium, 133 mmol/l; potassium, 4.1 mmol/l; serum insulin, less than 1.0 muU/ml.; plasma ACTH, 45.8 pg/ml; serum cortisol, 5.2 microg/dL; and free cortisol urinary excretion, less than 4.5 microg/day; serum LH, 0.8 mIU/ml; serum testosterone, less than 0.05 ng/ml; serum TSH, 2.0 uIU/ml; free T(4), 0.7 ng/dL; free T(3), 1.5 pg/ml; and serum prolactin, 29.0 ng/ml. The levels of all the pituitary hormones were elevated in response to a mixture of exogenous corticotrophin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and growth hormone-releasing hormone (GRH). However, there was no increased secretion of adrenocorticotropic hormone (ACTH) in response to hypoglycemia (induced by the administration of insulin) and there was no increased secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in response to the administration of clomiphene. Magnetic resonance imaging revealed an atrophied pituitary gland with an empty sella, but there were no abnormal findings of the hypothalamus. Hydrocortisone replacement at a dosage of 20 mg/day increased the patient's plasma glucose from 73 to 100 mg/dL and his serum sodium from 133 to 138 mmol/l. These findings therefore indicate a partial impairment in hypothalamic hormone release, resulting from a traumatic brain injury that the patient had received 31 years ago.

An increase in serum retinol-binding protein 4 in the type 2 diabetic subjects with nephropathy.

UNLABELLED: The present study was undertaken to determine retinol-binding protein 4 (RBP4) levels in subjects with diabetic nephropathy. A total of 149 type 2 diabetic subjects and 19 control subjects were enrolled. Serum levels of RBP4 were measured by a method of ELISA. Serum RBP4 levels were significantly greater in the subjects with type 2 diabetes mellitus than the controls (70.5 +/- 35.3 vs. 40.1 +/- 13.0 microg/ml, mean +/- SD, p<0.01). Serum RBP4 levels were gradually increased according to the progression of diabetic nephropathy (p value in trend test: <0.001). Its elevation was significantly greater in the diabetic subjects with stages 1, 3B and 4 than the control subjects (Stage 1: 64.6 +/- 29.7, Stage 3B: 123.3 +/- 71.8, Stage 4: 91.4 +/- 33.8 vs. CONTROL: 40.1 +/- 13.0 microg/ml, p<0.01). Similar results were obtained in the subjects based on the amount of albuminuria (Normo-: 64.6 +/- 29.7, Micro-: 63.7 +/- 29.4, and Marcoalbuminuria: 90.3 +/- 44.6 microg/ml, p <0.001). Serum RBP4 levels had a positive correlation with serum creatinine levels(r = 0.377, p<0.001), and a negative correlation with 1/creatinine (r = -0.420, p<0.001). Also, there was a negative correlation between serum RBP4 and the estimated glomerular filtration rate(r = -0.436, p<0.001). Multiple regression analysis showed that estimated glomerular filtration rate was an independent determinant for increased serum RBP4 levels. There was no difference in serum RBP4 levels between the advanced nephropathy with and without macrovascular diseases. These results indicate an increase in serum RBP4 levels in the type 2 diabetic subjects, particularly complicated with advanced renal impairment.

Pathogenesis of chronic hypernatremia with dehydrated and non-dehydrated states in hypothalamic space-occupying lesions.

The present study was undertaken to determine pathophysiology of body water control in hypernatremic subjects with hypothalamic space-occupying lesions. Eight subjects with hypothalamic space-occupying lesions were divided into two groups of hypernatremia in the presence or absence of body water deficit. In 5 dehydrated hypernatremic subjects whose ages ranged from 20 to 67 years, serum sodium (Na) levels were 156.4 +/- 3.1 mmol/l; plasma osmolality (Posm), 320.6 +/- 9.8 mmol/kg; and urinary osmolality (Uosm), 246.8 +/- 46.7 mmol/kg under ad libitum water drinking. In 3 non-dehydrated hypernatremic subjects whose ages ranged from 21 to 32 years, serum Na levels were 150.3 +/- 5.4 mmol/l; Posm, 300.3 +/- 11.6 mmol/kg; and Uosm, 738.7 +/- 237.1 mmol/kg. Serum Na levels had a positive correlation with hematocrit (Ht) in 2 of 5 subjects with dehydration, but it totally disappeared in the 3 subjects without dehydration. Plasma arginine vasopressin (AVP) levels were 0.7 +/- 0.1 pmol/l, and there was no response of AVP release to intravenous administration of 5% NaCl in the subjects with dehydration. Plasma AVP was 0.7 +/- 0.1 pmol/l, and there was the reduced response of AVP release to 5% NaCl in those without dehydration. In one of 3 subjects a positive correlation between Posm and plasma AVP levels was obtained. Drinking behavior was totally abolished in the subjects with dehydration, and partly reduced in those without dehydration. The present study indicates that hypothalamic space-occupying lesions causes central diabetes insipidus and hypodipsia, and that sporadic and paradoxical release of AVP, enhanced renal concentrating ability and reduced drinking behavior may possess body water minimally in the hypernatremic subjects without water deficit.

Clinical and laboratory features of hyponatremia-induced myopathy.

BACKGROUND: The present study was undertaken to determine the clinical and laboratory features of hyponatremia-induced myopathy. METHODS: We collected 14 hyponatremic subjects (six men and eight women) with serum creatine kinase (CK) levels of more than 500 IU/ml during the 5-year period between 2001 and 2005. The mean +/- SD patients' age was 66.5 +/- 16.7 years (range, 37 to 88 years). RESULTS: The causes of the hyponatremia were: syndrome of inappropriate secretion of antidiuretic hormone (SIADH; n = 4), mineralocorticoid-responsive hyponatremia of the elderly (MRHE; n = 2), hypopituitarism (n = 1), psychogenic polydipsia (n = 3), congestive heart failure (n = 3), and unknown cause (n = 1). The subjects were subgrouped into two groups: acute onset of myopathy and slowly progressive onset. The age at onset was 62.0 +/- 5.7 years (mean +/- SEM) in the subjects with acute onset, and 77.8 +/- 1.5 years in those with slowly progressive onset (P = 0.02). At the onset, there was no difference in serum Na levels between the acute onset and the slowly progressive onset groups, but there was a significant difference in maximal serum CK levels between the groups (7072 +/- 2317 vs 722 +/- 104 IU/ml; P = 0.02). Maximal serum CK levels were widely distributed among the ages in the subjects with acute onset, whereas maximal serum CK levels were mildly elevated in the elderly subjects with slowly progressive onset. The elevated serum CK levels were normalized at a maximum of 14 days after the onset in all the subjects. CONCLUSIONS: The present findings indicate that hyponatremia infrequently causes skeletal muscle disruption, and that there are two types of hyponatremia-induced myopathy, acute onset and slowly progressive onset.

New HLA DRB1 and DQB1 haplotypes in a pedigree of familial Graves' disease in Japan.

The present study demonstrated genetic analysis of human leukocyte antigen (HLA) in a familial Graves' disease linked to autoimmune mechanism. The proband was a 17 year-old female. At 15 years, Graves' disease was diagnosed with serum TSH was <0.015 IU/ml; free T(3), 13.6 pg/ml; free T(4), 4.51 ng/dl; and TSH receptor antibody (TRAb), 94.1%. She had two brothers (19 and 13 years-old), who manifested Graves' disease at 18 and 13 years, respectively. They also had elevated TRAb as high as 48.4 and 49.1%, respectively. There was a strong family history of Graves' disease in their maternal pedigree. Namely, their two aunts and a cousin had Graves' disease, and their onset ages of Graves' disease were also during their teen-age years. However, there was no patient with Graves' disease in the paternal pedigree. We checked HLA-DRB and -DQB haplotype in the members of maternal pedigree and proband's father. The members of maternal pedigree including both affected and unaffected Graves' disease had haplotypes of DRB1*150101 and DQB1*0602, except for the cousin who had DRB1*140301 and DQB1*030101. The haplotypes of DRB1*150101 and DQB1*0602 were different from susceptible HLA types in Japanese childhood onset Graves' disease. However, two cases of Graves' disease also had HLA types of DRB1*40501 and DQB1*0401, in addition to the haplotypes of DRB1*150101 and DQB1*0602. There was no other autoimmune disease including type 1 diabetes mellitus in their family. The present findings indicated that familial Graves' disease was found mainly in the maternal females and become overt during their teen-age years. They had new HLA haplotypes distinct from those susceptibly in Japanese Graves' patients. Further study will be necessary to analyze the mutant locus of DNA to elucidate pathogenesis of familial Graves' disease.

Comparison of once-daily glargine plus sulfonylurea with twice-daily 70/30 aspart premix in insulin-naive Japanese patients with diabetes.

BACKGROUND: Type 2 diabetes patients insufficiently controlled with sulfonylurea (SU) are commonly treated by switching to twice-daily premix insulin replacing SU. The efficacy of glargine (GL) added on to SU compared with the premix therapy has not been analyzed in Japan. METHODS: The open-label two-arm study was conducted in 30 type 2 diabetes patients poorly controlled [hemoglobin A(1c) (HbA(1c)) >7.5%] with SU with or without other oral hypoglycemic agents (OHAs). The GL group injected once-daily GL in addition to the OHAs. The aspart 70/30 (70/30) group discontinued SU among the OHAs and injected twice-daily 70/30. Patients were recommended either method in a block random method, and if twice-daily 70/30 was rejected, once-daily GL was selected only at the first time. The insulin dose was titrated to achieve a target fasting plasma glucose of <120 mg/dL and/or HbA(1c) of <7%. RESULTS: Nineteen of 20 patients treated with GL and 11 of 14 patients treated with 70/30 completed the 6-month study. Mean HbA(1c) improved from 8.45% to 7.5% in the GL group and from 9.13% to 7.93% in the 70/30 group. The mean HbA(1c) decrease during 6 months was -0.95% in the GL group and -1.20% in the 70/30 group (P = 0.49). Mean insulin doses at 6 months were 12.0 units/day for the GL group and 26.7 units/day for the 70/30 group. Both therapies were well tolerated without severe hypoglycemia. CONCLUSION: Once-daily GL injection added on to OHAs was equally safe and effective compared with twice-daily injection of aspart 70/30 premix replacing SU in type 2 patients insufficiently controlled with OHAs.

Hypoadiponectinemia in patients with cerebral infarction: comparison with other atherosclerotic disorders.

The present study was undertaken to determine serum adiponectin level in patients with cerebral infarction and to further analyze any difference in serum adiponectin levels among atherosclerotic disorders. One hundred fifty-two subjects with atherosclerotic disorders were enrolled, 110 males and 42 females, with the age of 67.0 +/- 9.9 years (mean +/- SD). They were divided into 62 patients with cerebral infarction, 48 patients with ischemic heart disease, and 42 patients with arteriosclerosis obliterans. Thirty-two subjects matched by age, gender, and body mass index served as controls. Serum adiponectin levels were 7.2 +/- 0.6 microg/mL (mean +/- SE) in the patients with cerebral infarction, 7.2 +/- 0.8 microg/mL in those with ischemic heart disease, and 6.9 +/- 0.9 microg/mL in those with arteriosclerosis obliterans. They were significantly less than the level of 12.6 +/- 1.9 microg/mL in the control group (P < 0.01). However, there was no difference in serum adiponectin level among three groups of atherosclerotic disorders. In the patients with acute cerebral infarction, serum adiponectin level was temporarily reduced from 7.3 +/- 0.9 to 6.2 +/- 0.8 microg/mL 14 days after the hospitalization (P < 0.01), followed by recovery to the basal value. The present findings indicate that serum adiponectin levels are equivalently reduced in patients with atherosclerotic disorders, and that serum adiponectin is changeable under acute phase of cerebral infarction.

Possibly simultaneous primary aldosteronism and preclinical Cushing's syndrome in a patient with double adenomas of right adrenal gland.

We reported a rare case of simultaneous primary aldosteronism and preclinical Cushing's syndrome due to unilateral double adrenocortical adenomas in a 57 year-old woman who had had hypertension for the last 10 years. Abdominal computed tomography showed double tumors in her right adrenal gland. Physical findings revealed simple obesity and hypertension, but no other abnormal findings were detected. Laboratory findings demonstrated that serum potassium was 3.8 mmol/l; plasma renin activity, 0.3 ng/ml/h; plasma aldosterone, 100 pg/ml, and aldosterone renin ratio (ARR), 33. Serum cortisol was 15.7 microg/dl. There was no circadian rhythm of serum cortisol, and no suppression of serum cortisol in response to exogenous dexamethasone administration. Right adrenalectomy was performed under laparoscopy. Two well-circumscribed tumors, whose sizes were 21 and 19 mm in greatest diameter, were detected. They were macroscopically composed of a golden-yellow portion admixed with a brown portion, which corresponded to clear cells and compact cells, respectively. Immunohistochemical staining for steroidogenic enzymes demonstrated the presence of all the enzymes involved in corticosteroidogenesis in these two adenomas, indicating that the two adenomas produced both cortisol and mineralocorticoid. Specifically, one adenoma mainly caused excessive production of cortisol as compared to the other one. These findings indicate that overproduction of both cortisol and mineralocorticoid was evident in the two adenomas of the right adrenal gland in immunohistochemical study for steroidogenic enzymes, whereas there was less clinical manifestation of primary aldosteronism and Cushing's syndrome in the present patient.

Alteration in risk factor accumulations of acute myocardial infarction during the last one decade: analysis of patients admitted in Coronary Care Unit.

The present study was undertaken to determine accumulation of risk factors in acute myocardial infarction during two periods of 2002 and 1990-1991. We collected 173 and 153 patients with acute myocardial infarction in 2002 and 1990-1991, respectively, and analyzed the history of multiple risk factors, including diabetes mellitus, impaired glucose tolerance, hyperlipidemia, hypertension and obesity, and laboratory findings. The numbers and their percentages of all the risk factors increased in 2002 compared with 1990-1991. According to plasma glucose level, the patients who had type 2 diabetes mellitus, and impaired fasting glucose or impaired glucose tolerance had increased markedly from 41 to 65%. Multiple accumulation of risk factors had increased during the last one decade, and only one or no risk factor per se was not the case in the patients with acute myocardial infarction. Hyperlipidemia and hypertension became fairly controlled in the patients, but not hyperglycemia in type 2 diabetes mellitus in the period of 2002. These findings may indicate that increased multiple accumulation of risk factors accelerates the occurrence of acute myocardial infarction in 2002 as compared to 1990-1991.

Elevation of serum adiponectin levels in Basedow disease.

The present study was undertaken to determine whether thyroid hormone affects serum adiponectin levels in the patients with Basedow disease. Sixty-four patients with Basedow disease were examined; 32 patients had hyperthyroid state and 32 patients had euthyroid state who had been treated with antithyroid drugs. In addition, 30 age- and sex-matched subjects served as a control. Serum adiponectin, free T4, free T3, thyroid-stimulating hormone, and thyroid-stimulating hormone receptor antibody (TRAb) were measured. Serum adiponectin levels were 12.9+/-1.6 microg/mL in the hyperthyroid state, a value significantly greater than that of 8.2 +/- 0.5 microg/mL in the euthyroid state (P<.05) and that of 8.6+/-0.7 microg/mL in the control subjects (P<.05). Serum adiponectin levels had positive correlations with either of serum free T4 (r=0.453, P<.001), free T3 (r=0.47, P< .001), or TRAb (r= 0.491, P<.001), but not with body mass index. Multiple regression analysis showed TRAb had the strongest contribution to serum adiponectin concentration in the patients with Basedow disease. The present findings indicate that hyper-adiponectinemia is closely associated with increases in serum thyroid hormone levels and TRAb in Basedow disease.