Carbon dioxide degassing by advective flow from Usu volcano, Japan.

Magmatic carbon dioxide (CO2) degassing has been documented before the 31 March 2000 eruption of Usu volcano, Hokkaido, Japan. Six months before the eruption, an increase in CO2 flux was detected on the summit caldera, from 120 (September 1998) to 340 metric tons per day (September 1999), followed by a sudden decrease to 39 metric tons per day in June 2000, 3 months after the eruption. The change in CO2 flux and seismic observations suggests that before the eruption, advective processes controlled gas migration toward the surface. The decrease in flux after the eruption at the summit caldera could be due to a rapid release of CO2 during the eruption from ascending dacitic dikes spreading away from the magma chamber beneath the caldera.

Relationship between triglyceride concentrations and LDL size evaluated by malondialdehyde-modified LDL.

BACKGROUND: Hypertriglyceridemia is associated with decreased HDL-cholesterol (HDL-C) and increased small dense LDL. In addition, small dense LDL is known to be susceptible to oxidation. METHODS: We measured LDL particle size, using gradient gel electrophoresis, and malondialdehyde-modified LDL (MDA-LDL), using an ELISA, and investigated the association between triglyceride (TG) concentrations, LDL size, and MDA-LDL. RESULTS: TG concentrations correlated negatively with the predominant LDL size (r = -0.650) and HDL-C concentration (r = -0.556). The relationship between TG concentration and LDL size, evaluated by measuring MDA-LDL, distinguished subgroups derived from four subfractions of TG concentrations and four distribution ranges of LDL size. These experiments indicated that there is a threshold for oxidation susceptibility at an LDL size of 25.5 nm and a TG concentration of 1500 mg/L. To investigate the relationship between LDL size, MDA-LDL concentration, and other lipids (TGs, HDL-C, apolipoprotein B, and total cholesterol), we evaluated them in control subjects and patients with diabetes mellitus or hypertriglyceridemia. When the size range for normal LDL was postulated to be 25.5 < or = phi (LDL diameter) < 26.5 nm, the MDA-LDL concentration was significantly higher in the subgroups of patients with LDL in the size range 24.5 < or = phi < 25.5 nm compared with patients with normal LDL. This result also suggests that the threshold is at a LDL size of 25.5 nm. CONCLUSION: The threshold for oxidation susceptibility coincided with the point of LDL size separation between the LDL subclass patterns A and B as an atherosclerotic risk.

Triphasic changes in thyroid function in a patient with primary hypothyroidism in the course of pregnancy and the early post-partum period.

We report a rare case of primary hypothyroidism in which thyroid function was changed from hypothyroidism to hyperthyroidism in the course of pregnancy and finally returned to hypothyroidism in the early post-partum period. She delivered an infant with neonatal Graves' thyrotoxicosis. Serum thyroid-stimulating antibodies (TSAb) and thyroid stimulating-blocking antibodies (TSBAb) coexisted in these patients. The triphasic changes in thyroid function may be explained by altered balance between TSAb and TSBAb in relation to pregnancy and delivery in the present case, although cellular immunity could be independently involved in atrophic changes in the postpartum period.

Clinical courses and thyroid conditions in three infants born to a mother with thyroid stimulating-blocking antibodies.

The clinical courses including thyroid conditions of three infants born to a mother with primary hypothyroidism due to Hashimoto's thyroiditis were studied. The mother was positive for both TSH-binding inhibitor immunoglobulins (TBII) and thyroid stimulating-blocking antibodies (TSBAb) in her serum. The first infant died because of septic shock due to fistula formation between the large intestine and the bladder. Serum thyroid hormone levels during the first pregnancy were extremely low because of incomplete replacement therapy with levothyroxine. The second infant had almost normal thyroid function, so that the replacement therapy was not necessary. The third infant had transient and overt primary hypothyroidism. The replacement therapy was carried out for six months after birth. TSBAb activities in this mother were high in the third pregnancy. In general, these activities gradually increases with the clinical course in TSBAb-positive Hashimoto's patients. From these findings, it was suspected that the thyroid conditions in the second and the third infants reflected the natural course of TSBAb activities in this mother.

Incidence of hyperprolactinemia in patients with Hashimoto's thyroiditis.

The causes of hyperprolactinemia, the correlation between serum levels of PRL and thyroid function and magnetic resonance imaging (MRI) of the pituitary were studied in patients with chronic thyroiditis. Seventy-four female patients and 15 normal control women participated in this clinical survey. Fourteen of 74 patients with various thyroid conditions had increased serum PRL. The incidence of hyperprolactinemia in the overt primary hypothyroid group was 42.4% and was significantly higher than in any other group with normal serum thyroxine. There was a close association between the increment in serum PRL and of free triiodothyronine above the basal level after TRH administration. There were 14 patients with hyperprolactinemia in three of which serum PRL was over 60 micrograms/L. PRL producing tumor, severe primary hypothyroidism and liver cirrhosis were detected in these three patients, respectively. These results indicate that the pathogenesis of increased serum PRL was not uniform in patients with Hashimoto's thyroiditis, although there was a correlation between hyperprolactinemia and impaired thyroid function. It is proposed, therefore, to measure and follow serum levels of PRL and MRI of the pituitary in patients with chronic thyroiditis, especially with impaired thyroid function.

Correlation of plasma free thyroxine levels with insulin sensitivity and metabolic clearance rate of insulin in patients with hyperthyroid Graves' disease.

Insulin sensitivity, metabolic clearance rate of insulin (MCR-I) and basal posthepatic insulin delivery rate (BIDR) were investigated by means of euglycemic clamp technique in 8 normal subjects and 8 patients with hyperthyroid Graves' disease. The mean (+/- SD) steady-state glucose infusion rate (SSGIR) was lower in hyperthyroid Graves' patients than in normal subjects (228.9 +/- 57.0 vs. 290.9 +/- 49.4 mg/m2/min, p < 0.05). Both MCR-I and BIDR were higher in hyperthyroid Graves' patients than in normal subjects (1162.9 +/- 517.1 vs. 463.5 +/- 103.9 ml/m2/min, p < 0.005; 17.7 +/- 12.6 vs. 3.6 +/- 0.9 mU/m2/min, p < 0.01, respectively). Plasma free T4 levels showed a close correlation with MCR-I (r = 0.77, p < 0.05) and BIDR (r = 0.81, p < 0.05), respectively, in Graves' patients. These findings indicate that hyperthyroidism is characterized by not only a decrease in insulin sensitivity, but also an increase in basal insulin secretion and the metabolic clearance rate of insulin, which are correlated with plasma free T4 levels.

[Unconsciousness due to hyponatremia in a patient with short stature with panhypopituitarism].

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.

Isolated adrenocorticotrophin deficiency associated with anti-pituitary antibodies, pituitary cyst, sphenoidal cyst and pineal tumor.

This paper reports a rare case of isolated ACTH deficiency associated with anti-pituitary antibodies, pituitary cyst, sphenoidal cyst and pineal tumor. A 68-year-old man consulted our clinic for general fatigue. Laboratory data showed low plasma adrenocorticotrophin (ACTH) and cortisol levels with blunted responses to insulin-induced hypoglycemia and corticotrophin releasing factor (CRF). Urinary 17-OHCS was low but responded to ACTH-Z administration. No other pituitary functions were impaired. Antibodies to the cytoplasm of rat pituitary and the surface of GH3 cells were detected in the serum. The magnetic resonance imaging (MRI) showed a high signal intensity mass in the anterior pituitary and in the sphenoidal sinus in both T1 and T2 weighted images as well as a low signal intensity mass in a T1 weighted image of the pineal region. Transsphenoidal surgery was performed to resect the mass in the sphenoid sinus and in the pituitary. Pathological studies showed a benign cyst in the sphenoid sinus, and fibrous degeneration and decreased basophils in the pituitary. No infiltrative mononuclear cells were detected in the pituitary. Immunohistochemical studies revealed a decrease in the number of ACTH-producing cells in the pituitary. The patient was well maintained by glucocorticoid replacement without any growth of a possibly benign pineal tumor.

[Effect of arotinolol on insulin secretion and insulin clearance rate in patients with Graves' disease].

Glucose-induced insulin secretion, 24-h urinary C-peptide (CPR) and euglycemic clamp were examined in five patients with hyperthyroid Graves' disease before and 2 weeks after treatment with arotinolol (20 mg/day, p.o.). Plasma glucose and insulin responses to oral administration of 75 g glucose were not changed by arotinolol treatment. 24-h urinary CPR and basal posthepatic insulin delivery rate (BPIDR) as an indicator of insulin secretion were significantly suppressed by arotinolol. Glucose infusion rate (GIR) as an indicator of insulin sensitivity and glucose clearance rate (GCR) were not influenced by arotinolol therapy. Insulin clearance rate (ICR) was significantly suppressed by arotinolol. These findings suggest that arotinolol inhibits insulin secretion by decreasing ICR but does not attenuate insulin release induced by glucose in hyperthyroid patients, and that insulin sensitivity and GCR are not affected by arotinolol.

[A case of Cushing's disease associated with a non-functioning adrenal tumor].

A 52-year-old woman was admitted to our hospital for further examination of central obesity, hypertension and hirsutism suggesting Cushing's syndrome. Hirsutism had been remarkable for two years, and muscle weakness of the lower extremities gradually developed during the past year. CT scan revealed a tumor in the left adrenal gland which was 1 cm in diameter, round, well-circumscribed, homogeneous and not enhanced. Endocrine data disclosed increased urinary 17-OHCS (11.5-16.4 mg/day) and elevated plasma ACTH (125 pg/ml) and cortisol (19 micrograms/dl) with a lack of diurnal rhythm. Administration of the single-dose dexamethasone (1mg) did not suppress plasma cortisol. However, consecutive administration of either 2mg or 8mg of dexamethasone for 2 days suppressed both plasma cortisol and urinary 17-OHCS. Administration of metyrapone raised both urinary 17-OHCS and plasma ACTH levels. Rapid ACTH test resulted in a hyperresponse of plasma cortisol. CRF injection raised plasma ACTH and cortisol. Bilateral adrenal glands were well demonstrated by 19-iodocholesterol (I-131) scintigraphy during the administration of dexamethasone. MRI with Gd-contrast revealed a microadenoma in the sella turcica. With the diagnosis of Cushing's disease, the microadenoma was removed by the transsphenoidal approach and adrenal function was normalized. However, the left adrenal tumor remained on CT scan but was not demonstrated by scintigraphy. These findings indicate that this is a very rare case of Cushing's disease which was associated with an unilateral non-functioning adrenal tumor.

[Effect of subcutaneous administration of interleukin-1 beta on blood platelet count and serum GM-CSF in patients with myelodysplastic syndrome and aplastic anemia].

Subcutaneous administration of recombinant human Interleukin-1 beta (IL-1 beta) in a dose of 1-3 x 10(4) U/day for 14 to 72 days resulted in an increase in circulating granulocytes and bone marrow monocytes in all the 4 patients examined. Circulating platelet count was also increased in two of four patients with myelodysplastic syndrome (MDS) and aplastic anemia (AA). Bone marrow examination revealed an increase in megakaryocyte count in these patients, whereas the percentage of blast was not changed. An increase in blood platelet count was accompanied by an increase in serum GM-CSF in a patient with AA, whereas serum IL-6 level was not changed throughout the treatment with IL-1 beta. These findings suggest that IL-1 beta may be useful for the treatment of a proportion of patients with MDS and AA who are associated with thrombocytopenia.

[Clinical use of serum erythropoietin determination by the recombigen EPO RIA kit].

Serum erythropoietin (EPO) levels were determined by the recombigen EPO RIA kit (DPC) in normal subjects and patients with renal dysfunction, diabetes mellitus, hypothyroidism and a variety of hematological disorders. Mean (+/- SD) serum EPO levels were 18.6 +/- 5.6 mU/ml in 180 normal subjects and no sex difference was obtained. Serum EPO levels in older subjects were slightly greater than those in younger subjects. There was a negative correlation between serum EPO levels and Ht values in anemic patients with normal renal function, whereas serum EPO levels were within the normal range in anemic patients with renal disorders, suggesting that serum EPO levels were relatively low in patients with chronic renal failure. Serum EPO levels were rather increased in patients with diabetes mellitus and hypothyroidism. High serum EPO levels were obtained in patients with a variety of hematological disorders such as acute leukemia, multiple myeloma, myelodysplasia syndrome, aplastic anemia and pure red cell aplasia. In a patient with pure red cell aplasia treated with glucocorticoids, serum EPO levels were lowered before anemia was recovered and reticulocytes were increased. These findings indicate that measurement of serum EPO levels are useful for not only differential diagnosis of anemia but also clinical evaluation of the treatment.

[Acute myelogenous leukemia transformed from myelodysplastic syndrome with tetraploid chromosome constitution].

A 57-year-old female presented with general fatigue. She had neither lymphadenopathy nor hepatosplenomegaly. Laboratory data revealed anemia and leukopenia (1,500/microliters) with a differential count of 4.5% leukemic cells. The myelogram revealed 34.4% leukemic cells, of which diameter ranged from 20 to 28 microns. The diagnosis was acute myelogenous leukemia (FAB: M2) with myelodysplasia. Cytogenetic analysis revealed that the leukemic cells had chromosome abnormalities involving both diploidy and tetraploidy with structural rearrangement. Structural rearrangement included del(5) (q22q33), del(15) (q22q24), and t(3; 12) (q25;p13). Small dose aclacinomycin-A treatment was effective in reducing the number of leukemic cells in bone marrow, and both anemia and leukocytopenia were improved.

[A case of type 1 diabetes mellitus with hypothalamic amenorrhea: successful pregnancy following subcutaneous pulsatile administration of LHRH].

A 27-year-old woman with type 1 diabetes mellitus was admitted to the Shimane Medical University Hospital because of secondary amenorrhea. She had been treated with insulin since July, 1986. Fasting plasma glucose and HbA1c levels were controlled within normal limits. However, body weight gradually decreased and amenorrhea started in 1988. Physical examination revealed emaciation with BMI of 17.3. Basal levels of plasma T3, somatomedin C, LH, FSH and estradiol levels were low, whereas HGH levels were slightly elevated. Plasma LH markedly increased in response to LHRH administration. She was diagnosed as having weight loss-related hypothalamic amenorrhea. Induction of ovulation was not obtained with clomiphene citrate. Treatment with subcutaneous pulsatile administration of LHRH (20 micrograms every 120 min) resulted in an increase in plasma levels of LH, FSH and estradiol, which was accompanied by ovulation and corpus luteum formation. Further treatment with pulsatile LHRH administration was followed by conception. Two gestational sacs were detected by ultrasonography. One of them was absorbed at the early stage of pregnancy. She was delivered of one healthy female infant without complications. These findings suggest that it is important not only to control plasma glucose levels but to keep the appropriate weight and support the psychological aspects of the subject in the treatment of diabetes mellitus. Subcutaneous pulsatile LHRH therapy may be effective for the induction of ovulation in clomiphene-resistant hypothalamic amenorrhea; however, it will be necessary to solve the problem of dosage and the interval of LHRH administration in the future.

[Adult type of idiopathic paroxysmal cold hemoglobinuria].

A 78-year-old female suffered from idiopathic paroxysmal cold hemoglobinuria (PCH). Her symptom occurred immediately after she worked outside in the cold early morning. This case is characterized by the eldest case with non-syphilitic PCH reported in Japan and by the most advanced anemia (Hb 4.2 g/dl) possibly due to prolonged hemolysis after cold exposure. Analysis of the serum revealed positive Donath-Landsteiner antibody of IgG type, which could react to hemolysis not only below 15 degrees C but also at 15-20 degrees C in vitro.

Plasma free triiodothyronine response to thyrotropin-releasing hormone to predict the remission of Graves' disease treated with antithyroid drugs.

The responses of both plasma TSH and free T3 (FT3) to TRH were examined in 31 patients with Graves' disease who were euthyroid after treatment with antithyroid drugs, 6 patients with primary hypothyroidism, and 14 control subjects. TSH was measured 0, 15, 30, 60, 90, and 120 min and FT3 was measured 0, 30, 60, 90, 120, 150, and 180 min after TRH injection (500 microgram, iv). The increment in FT3 above the basal level (delta FT3) in normal controls ranged from 1.2-3.7 pmol/L, with a mean +/- SD of 2.2 +/- 0.8 pmol/L. The mean (+/- SD) delta FT3 in patients with primary hypothyroidism was 0.3 +/- 0.2 pmol/L. After the TRH test, antithyroid drugs were stopped in patients with Graves' disease. Nine of 31 Graves' patients relapsed within 6 months after the TRH test. The other 22 patients with Graves' disease were followed while in remission during the observation period of up to 48 months. The mean (+/- SD) delta FT3 were significantly lower in 9 Graves' patients who relapsed than in those who achieved remission (0.5 +/- 0.3 vs. 2.6 +/- 1.1 pmol/L; P less than 0.01). Eight of 9 Graves' patients who relapsed showed lower delta FT3 values than the lowest value (1.1 pmol/L) in 22 Graves' patients in remission. Although the mean increment of TSH above the basal level (delta TSH) was also significantly different between the Graves' patients who relapsed and those in remission (1.4 vs. 12.3 mU/L; P less than 0.01), there was considerable overlap between the 2 groups. These findings suggest that delta FT3 reflects the endocrinological recovery of the pituitary-thyroid axis and is a beneficial indicator for the termination of antithyroid drugs in Graves' disease.

[Incidence of abnormal thyroid function in patients with low titers of thyroid microsomal antibodies].

The incidence of abnormal thyroid function related to autoimmune disorders was examined in a district of Shimane Prefecture in 1988. Thyroid microsomal antibodies (MCPA) in sera were measured in a general population of 1,646, including 678 males and 968 females, aged 57.8 +/- 14.8 (mean +/- SD) yr. MCPA titer was defined as high (less than 1:128), low (1:16, 1:32, 1:64) or negative (less than 1:16) according to the highest dilution of test serum capable of agglutinating gelatin particles coated with the appropriate antigen. Test of MCPA revealed high titers in 141 subjects (group A), low in 43 subjects (group B) and negative in 1,462 (group C). Twenty-four patients with overt thyroid disorders were found in groups A and B: five with Graves' disease, two with Hashimoto's thyroiditis and 15 with goiter in group A, and two with goiter in group B. In the remaining 119 subjects in group A and 41 subjects in group B, serum free T4 (FT4) and TSH levels were measured. According to abnormalities in the levels of serum FT4 and/or TSH, their thyroid function was divided into the following 3 subgroups: 1) hyperthyroid (FT4 greater than 2.0 ng/dl, TSH less than 0.4 mu U/ml), 2) latent hypothyroid (0.8 less than FT4 less than 2.0 ng/dl, TSH greater than 5.0 mu U/ml) and 3) hypothyroid (FT4 less than 0.8 ng/dl, TSH greater than 5.0 mu U/ml). The hyperthyroid group consisted of two patients in group A and one in group B. Ten latent hypothyroid patients were found in group A and two in group B. Hypothyroidism was found in four patients in group A. The incidence of abnormal thyroid function was not different between group A (16 out of 119, 13.4%) and group B (three out of 41, 7.3%). Graves' disease and primary myxedema were found in one patient each in group B; these patients had no subjective symptoms but showed low titers of MCPA. These findings suggest that not only high titers of MCPA but also low titers of MCPA are closely related to abnormal thyroid function.

[Clinical epidemiology of autoimmune thyroid disorders--variation of natural history in patients with autoimmune thyroid disorders].

Clinical and epidemiological study for autoimmune thyroid disorders was performed in a rural community. Ninety-six of 1,686 subjects had asymptomatic autoimmune thyroiditis and were followed from 1979 to 1988. TRH loading test was carried out in 91 of 96 cases between 1983 and 1984. Each individual was classified into 4 subgroups. Five patients had normal levels of basal plasma TSH and had no increment of peak levels of plasma TSH (Grade G). Twenty-three had normal levels of both basal and peak plasma TSH (Grade I). The peak plasma TSH levels in 53 patients was high, but the basal was within the normal range (Grade II). Ten had high levels of both basal and peak plasma TSH (Grade III). One of the 5 Grade G cases developed overt Graves' disease in 1987 and another Grade III case suffered from goitrous Hashimoto's thyroiditis with primary hypothyroidism. Four of the ten Grade III cases and one Grade II case developed primary myxedema during the observation period. These results show that the natural history of asymptomatic autoimmune thyroiditis is variable and the prevention of overt autoimmune thyroid disorders is difficult.