Fulminant type 1 diabetes complicated by leukemoid reaction.

A 28-year-old woman with severe ketoacidosis was admitted to our hospital on day 11 after giving birth. However, her HbA(1C) level was normal (5.2%) and both GAD and anti-insulin autoantibody were negative, and the WBC count was extremely high (57,500/ml) with immature leucocytes in the peripheral blood. Her WBC count decreased along with control of ketoacidosis and reduction of the plasma glucose level, and was normalized on day 5 after admission. Bone marrow aspiration subsequently showed no malignant cells, so the final diagnosis was fulminant type 1 diabetes combined with a leukemoid reaction. This is the first report of a patient with both fulminant type 1 diabetes and a leukemoid reaction. The mechanism that triggered the leukemoid reaction could not be clarified, but severe ketoacidosis may have been involved.

Asymmetric dimethylarginine (ADMA) in the aqueous humor of diabetic patients.

Asymmetric dimethylarginine (ADMA) is an endogenous NO synthase (NOS) inhibitor whose production is enhanced by oxidative stress. Recent studies have shown that ADMA may also directly stimulate the production of reactive oxygen species (ROS) by up-regulation of the renin-angiotensin system independently of NOS inhibition. In this study, to investigate the clinical association of ADMA with diabetic retinopathy, we evaluated the levels of ADMA and NO oxides (NO2- and NO3-) in serum and aqueous humor obtained during cataract surgery from non-diabetic subjects (n = 21) and diabetic patients (n = 17). We found that the ADMA existed in aqueous humor and its level was similar to that in serum. The ADMA levels in both serum and aqueous humor were higher in diabetic patients, especially those with severe retinopathy, than in the non-diabetic group (serum ADMA: 0.67 +/- 0.26 vs. 0.53 +/- 0.08 micromol/l, p<0.05; aqueous humor ADMA: 0.55 +/- 0.20 vs. 0.32 +/- 0.16 micromol/l, p<0.05). Also, the aqueous humor level of ADMA, but not the serum level, was correlated with HbA1c on analysis of all the patients (R = 0.33, p<0.05 by simple regression analysis). However, a correlation between the ADMA levels in serum and aqueous humor was not observed in either the non-diabetic group or the diabetic group. Furthermore, serum and aqueous humor levels of NOx did not differ between the two groups, and no correlation with ADMA levels was observed in either group. These results suggest that ROS production may be enhanced in the eyes of diabetics. Since ADMA may act to potentiate ROS production independently of its inhibition of NOS, further investigation is required to clarify the possible contribution of ADMA to the development or progression of retinopathy.

Hormone profiles after intramuscular injection of testosterone enanthate in patients with hypogonadism.

To examine hormone levels after androgen replacement therapy (ART) in Japanese male patients with hypogonadism, nine Japanese male patients with hypogonadism (serum total testosterone (tT) or free testosterone (fT) levels of < or = 2.7 ng/mL or < or = 10 pg/mL, respectively; average age, 59 years) were enrolled. They were treated with 125 mg of testosterone enanthate by single intramuscular injection. Blood samples were collected on the morning of the day of treatment, pre-ART, as well as on days 1 to 7 and day 14 after administration. Serum levels of tT, fT, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were determined. On day 1 after administration, the mean serum levels of tT and fT were 7.62 ng/mL and 23.22 pg/mL, respectively. Serum levels of tT and fT on day 14 after administration were lower than their pre-ART values. One patient exhibited abnormally high serum tT and fT levels of 19.6 ng/mL and 44.4 pg/mL, respectively. Serum levels of LH and FSH began to decrease gradually on day 5 after administration. Serum levels of SHBG did not change throughout the observation period. Serum levels of E2 increased 1.7 times on day 1 after administration but returned to its pre-ART value by day 14 after administration. The dose of testosterone enanthate for male patients with hypogonadism requiring ART should be determined carefully because some patients exhibited high serum levels of androgen beyond the physiological range and gonadotropin was suppressed in all treated patients.

Successful long-term treatment with once-daily injection of low-dose octreotide in an aged patient with insulinoma.

The patient was an 83-year-old woman who was admitted to our hospital for evaluation and treatment of chronic hypoglycemia that was first identified 3 years earlier. Serum insulin and C-peptide levels were both elevated during hypoglycemia. Contrast abdominal computed tomography revealed a tumor in the body of the pancreas with blushing during the early phase, and insulinoma was diagnosed. The patient declined surgery because of advanced age, so treatment was started with octreotide, a somatostatin analogue. Hypoglycemia has been successfully controlled with low-dose, once-daily octreotide over 33 months. Few reports have described long-term octreotide administration for benign insulinoma. Moreover, this case is interesting from the perspective of hypoglycemic control using only low-dose, once-daily octreotide. Although somatostatin may induce hypoglycemia in insulinoma, treatment may be useful in patients who are not candidates for surgery, provided that careful monitoring is maintained.

Discrepancies in results of low-and high-dose dexamethasone suppression tests for diagnosing preclinical Cushing's syndrome.

According to the diagnostic criteria for adrenal preclinical Cushing's syndrome (PreCS) established by a group headed by the Ministry of Health, Labor and Welfare (MHLW), low- and high-dose dexamethasone suppression tests (DSTs) must be performed to prove autonomous cortisol secretion, i.e., > or =3 microg/dL serum cortisol following 1-mg DST administration, and > or =1 microg/dL serum cortisol following 8-mg DST administration. However, discrepancies have been documented in the results of low-and high-dose DSTs. We therefore investigated the validity of the DST for diagnosing PreCS by performing 1-mg and 8-mg DSTs in 39 patients with adrenal incidentaloma, but no characteristic Cushingoid symptoms. In about half of these patients (20/39, 51.3%), high-dose DST was positive but low-dose was negative, and one or more of the other abnormalities of hypothalamus-pituitary-adrenal axis dysfunction was seen in 75% of these patients. Furthermore, no significant difference in incidence of glucose intolerance and hypertension was noted in patients with positive high-dose DST and negative low-dose DST compared with patients with positive low- and high-dose DST. Under the current MHLW diagnostic criteria, patients with positive high-dose DST and negative low-dose DST are not diagnosed with PreCS, but some of these patients should be. Discrepancies in the results of low- and high-dose DSTs appear attributable to the current cutoff values, and further investigations are necessary to resolve these discrepancies.