Masatoshi Ishimori

Effects of long-term interferon-α treatment on glucose tolerance in patients with chronic hepatitis C

Abstract Background/Aims: Interferon-α has been reported to acutely induce insulin resistance and glucose intolerance. The effects of long-term treatment with interferon-α on glucose metabolism remain unclear. Methods: Thirty-two Japanese patients with chronic hepatitis C were given interferon-α (6×10 6 U/day) daily for 2 weeks and thereafter 3 times weekly up to 6 months. The patients received a 75-g oral glucose tolerance test before the treatment. Fifteen patients also had an intravenous glucose tolerance test for an assessment of insulin sensitivity with Bergmans minimal model. These tests were repeated 3 months after the treatment. Results: Insulin sensitivity was not affected by the treatment (5.7±3.8 vs 5.2±3.8 10 −4 ·min −1 ·mU −1 ·l, not significant) and a statistically significant but minimum decrease in area under the curve of plasma glucose (1012±332 vs 928±282 mmol·1 −1 ·min, pvs 294±334 mU·l −1 ·min, p Conclusion: Contrary to the known acute metabolic effects, interferon-α therapy for 3 months in patients with chronic hepatitis C did not have deleterious effects on insulin sensitivity and glucose tolerance.

Increased insulin sensitivity in patients with aldosterone producing adenoma

OBJECTIVE Primary aldosteronism is a recognized endocrine cause of glucose intolerance. A blunted insulin response to glucose in patients with primary aldosteronism is well known, but insulin sensitivity has not been thoroughly determined. We investigated insulin sensitivity and insulin secretion in patients with aldosterone producing adenoma.

Effects of troglitazone on dexamethasone-induced insulin resistance in rats

Troglitazone, a thiazolidinedione derivative, has been shown to counteract insulin resistance in obesity and non-insulin-dependent diabetes mellitus (NIDDM). To test its effects on dexamethasone-induced insulin resistance, we measured hepatic glucose production (HGP) and the insulin-stimulated glucose disposal rate (Rd) by a euglycemic-hyperinsulinemic glucose clamp technique coupled with 3-3H-glucose infusion in male Wistar rats treated with low-dose dexamethasone ([LoDex] 0.05 mg/kg/d, n = 7), high-dose dexamethasone ([HiDex] 0.1 mg/kg/d, n = 7), or dexamethasone plus troglitazone (LoDex + T, n = 8; HiDex + T, n = 6). Dexamethasone was injected subcutaneously for 4 days. Troglitazone was administered orally at 20 mg/d for 3 days before and for 4 days along with the dexamethasone treatment. The glucose clamp study was performed after an overnight fast in chronically catheterized conscious rats with a continuous insulin infusion of 57.4 pmol/kg/min. Basal HGP was comparable among the control (45.8 +/- 2.1 micromol/kg/min, n = 7), LoDex (47.9 +/- 4.7 micromol/kg/min), LoDex + T (46.0 +/- 2.6 micromol/kg/min), and HiDex + T (54.7 +/- 3.4 micromol/kg/min) groups. It increased about twofold in the HiDex group (80.1 +/- 5.2 micromol/kg/min, P < .05 v control). Under hyperinsulinemia, HGP was suppressed to a similar level in the control (11.3 +/- 8.8 micromol/kg/min), LoDex (10.2 +/- 8.4 micromol/kg/min), and LoDex + T (7.8 +/- 7.9 micromol/kg/min) groups. The suppressive effect of insulin on steady-state HGP during the clamp was impaired in HiDex (63.7 +/- 9.7 micromol/kg/min, P < .05) and HiDex + T (64.0 +/- 6.5 micromol/kg/min, P < .05). Rd decreased 27% in LoDex (81.5 +/- 5.8 micromol/kg/min, P < .05) and 36% in HiDex (71.3 +/- 9.4 micromol/kg/min, P < .05) compared with the controls (111.4 +/- 7.4 micromol/kg/min). Troglitazone prevented the decrease in Rd in LoDex + T (102.6 +/- 5.7 micromol/kg/min), but not in HiDex + T (67.0 +/- 6.4 micromol/kg/min). These results indicate that the development of peripheral insulin resistance was prevented by troglitazone in LoDex rats. Troglitazone may be a useful drug to treat steroid-induced diabetes.

Effects of troglitazone on hepatic and peripheral insulin resistance induced by growth hormone excess in rats

It is well known that short-term growth hormone (GH) administration in humans and animals induces insulin resistance and glucose intolerance. The purpose of the present study was to clarify whether troglitazone, a new insulin-sensitizing drug of the thiazolidinedione class, counteracts the insulin antagonistic effects of recombinant human (rh) GH on glucose metabolism in rats. Male Wistar rats weighing 184 to 226 g were treated either with rhGH (n = 8) or rhGH plus troglitazone (n = 8). rhGH (20 IU/kg body weight/d) was given by subcutaneous injection twice daily for 2 days. Troglitazone was given at 100 mg/kg/d orally for 5 days before and 2 days during rhGH. Saline was injected to the control rats (n = 7). Euglycemic clamp studies with an insulin infusion rate of 8 mU/kg/min were performed in these rats after an overnight fast. Hepatic glucose output (HGO), glucose infusion rate (GIR), and glucose disappearance rate (GDR) were measured. Fasting levels of plasma glucose (6.6 +/- 0.1, 6.1 +/- 0.3, 6.5 +/- 0.2 mmol/L), insulin (187.5 +/- 24.1, 206.4 +/- 24.1, 182.3 +/- 31.0 pmol/L), and serum free fatty acid (FFA) (1.58 +/- 0.18, 1.43 +/- 0.16, 1.61 +/- 0.25 mEq/L) were comparable among rats treated with rhGH, rhGH plus troglitazone, and controls, respectively. Basal HGO was also comparable among the three treatment groups. HGO was suppressed significantly during the hyperinsulinemic glucose clamp in control rats, but not in rhGH rats. When troglitazone was coadministered with rhGH, suppressibility of HGO during the glucose clamp was comparable to that of controls. GIR (13.5 +/- 4.5 v 24.1 +/- 4.1 mg/kg/min) and GDR (18.1 +/- 5.8 v 30.3 +/- 5.2 mg/kg/min) were decreased by rhGH treatment compared with control values. They returned to normal levels in rats treated with both rhGH and troglitazone (GIR, 22.4 +/- 5.9; GDR, 24.7 +/- 7.1). From these results, it is evident that rhGH treatment impaired insulins ability to suppress HGO and stimulate peripheral glucose utilization. Troglitazone could block the insulin antagonistic effects of GH on hepatic glucose output and peripheral glucose utilization.

Paraneoplastic Neurologie Syndrome and Autoimmune Addison Disease in a Patient with Thymoma

A 48-year-old man with autoimmune Addison disease developed the following paraneoplastic neurologic syndromes (PNNS): limbic encephalitis, opsoclonus/myoclonus, and sensorimotor and autonomic neuropathies. An anterior mediastinal mass detected on a chest computed tomographic scan was found on resection to be a noninvasive lymphocytic thymoma. The PNNS went into remission 1 year after the thymectomy. This is the first case of thymoma associated with autoimmune Addison disease and PNNS to be described in the literature.

Association of Papillary Thyroid Carcinoma with Primary Aldosteronism

Objective The association of primary aldosteronism (PA) with thyroid disease has already been suggested. The aim of this study was to examine the presence of PA in patients with papillary thyroid carcinoma (PC) and to characterize such PC patients with PA. Methods We examined the presence of PA in 81 consecutive patients with PC, whose random sitting blood pressure (BP) was ≥140/90 mmHg in the office (n= 68), who had an incidental adrenal tumor or adrenal enlargement (n=9), or who showed hypokalemia (n=4). Thirty-one of these 81 patients had been treated with anti-hypertensive drugs. The plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were first measured before operation in 16 patients and after operation in 65 patients. PA was diagnosed according to the guidelines of the Japan Endocrine Society. Results Forty patients with PC with a random PAC/PRA ratio of over 200 were subjected to a further study (12 of these patients had been treated with anti-hypertensive drugs). Ultimately, 15 patients with PC were diagnosed with PA. Adrenal venous sampling was done in 9 out of 15 patients with PC associated with PA. No patients were diagnosed as having unilateral lesions. Among the 15 patients, white-coat hypertension was observed in 5 patients, and normotension was observed in 1 patient. Conclusion These findings suggest that the prevalence of PA may be high among patients with PC. An active examination is needed to detect PA, as its signs and symptoms may be mild in patients with PC associated with hypertension.

Dual ectopic thyroid associated with thyroid hemiagenesis

Summary We report a case of a 15-year-old girl with a midline neck mass that was first noted 2 or 3 years previously. She had been treated with levothyroxine (L-T4) for congenital hypothyroidism until 11 years of age. Ultrasonography revealed an atrophic right thyroid (1.0 × 1.6 × 2.6 cm in size) and a mass (2.3 × 1.0 × 3.5 cm in size) in the upper part of the neck. No left lobe of the thyroid was detected. On further evaluation, Tc-99m pertechnetate thyroid scintigraphy and CT showed ectopic thyroid tissue in the lingual region and infrahyoid region. Thus, she was diagnosed as having dual ectopic thyroid and thyroid hemiagenesis. The atrophic right thyroid was thought be non-functional. Treatment with L-T4 was started to reduce the size of the dual ectopic thyroid tissue. This may be the first reported case of dual ectopic thyroid associated with hemiagenesis detected only by ultrasonography. Learning points: Ultrasonography can confirm the presence or absence of orthotopic thyroid tissue in patients with ectopic thyroid. The cause of congenital hypothyroidism should be examined. Clinical manifestation of ectopic thyroid may appear when the treatment with L-T4 is discontinued. Annual follow-up is needed in all children when their thyroid hormone replacement is stopped.