Prednisolone Dosing Regimen for Treatment of Subacute Thyroiditis.

The rate of recurrence of subacute thyroiditis (SAT) during prednisolone (PSL) therapy is approximately 10 to 20%. However, there is little or no information on the time period to relapse following administration of a tapered dose of PSL and the factors associated with such relapse. The aim of this study was to determine the correlation between SAT recurrence and PSL tapering regimen used in the treatment of SAT. This study was a medical record-based retrospective study and involved 26 patients (3 men, 23 women) who received PSL therapy for SAT. The primary endpoint was the association between recurrence and number of days required to taper daily PSL dose to 5 mg. The secondary endpoint was the relationship between recurrence and several variables including age, clinical score, free thyroxine, inflammatory reaction, thyroglobulin, total treatment time, total dose of PSL and presence or absence of creeping thyroiditis. The SAT recurrence rate was 15.3%. There was no significant difference in the initial PSL dose between the non-recurrence and recurrence groups (27.5 mg vs 24.5 mg, P = 0.302). However, for the primary endpoint, significant differences were found between the two groups in time required for tapering PSL to 5 mg/day (non-recurrence: 44.3 ± 15.3 days, recurrence: 19.0 ± 11.9 days, P = 0.012). None of the clinical variables evaluated correlated significantly with SAT relapse. In conclusion, to prevent recurrence of SAT, consideration should be given to the period required for PSL tapering to 5 mg/day.

Secondary adrenocortical insufficiency complicated by marked hypercalcemia and eosinophilia: a case report.

A 56 year old female was admitted to a local hospital after developing symptoms, including generalized fatigue, nausea and vomiting, from trauma. She was relocated to our hospital because she developed other symptoms, including disturbance of consciousness from hypercalcemia and a rash over her entire body. Her clinical symptoms (disturbance of consciousness, loss of appetite, nausea, vomiting, decrease in blood pressure, fever) and examination findings (low blood cortisol levels (1.2 µg/dl ), hypercalcemia (11.0 mg/dl ), peripheral blood eosinophilia (1,600 /µl )) lead to a diagnosis of adrenal insufficiency. In addition, a skin biopsy indicated eosinophilic infiltration, although her condition improved in the end with an oral dose of 30 mg/day of prednisolone. Hypercalcemia and peripheral blood eosinophilia are commonly known examination findings for adrenocortical insufficiency, but it is rare for either of these to be present as clinical symptoms.

Induction of thyroid remission using rituximab in a patient with type 3 autoimmune polyglandular syndrome including Graves' disease and type 1 diabetes mellitus: a case report.

Rituximab (RTX) is a monoclonal antibody that targets the B-cell-specific CD20 antigen. Recent reports indicate that RTX is effective against type 1 diabetes mellitus (T1DM) and hematologic as well as autoimmune diseases. Other studies have indicated that RTX therapy leads to the remission of recurrent or active Graves' disease (GD). However, the efficacy of RTX in Japanese patients with autoimmune polyglandular syndrome (APS) has not been reported to date. Herein, we report the case of a patient with GD and T1DM with sustained endogenous insulin secretion capacity. To protect pancreatic ß cells, we administered RTX at a dose of 500 mg (approximately 300 mg/m2) on 2 occasions 1 week apart. After treatment, no adverse effects were observed, and thyroid stimulating hormone receptor antibody (TRAb) was no longer detectable 4 months after RTX administration. In addition, the reduction in TRAb level improved thyroid function. Notably, the treatment induced remission over a period of 1 year after the diagnosis of GD.

Type 2 diabetes mellitus complicated by hypertension in Japanese patients: switching treatment from high-dose angiotensin II receptor blockers to losartan plus hydrochlorothiazide.

OBJECTIVE: The aim of the present study was to assess changes in blood pressure and metabolism after switching treatment from maximum-dose angiotensin II receptor blocker (ARB) therapy to a mixture of conventional-dose ARBs and low-dose diuretics. METHODS: This study was conducted among 43 Japanese patients with type 2 diabetes complicated with hypertension in whom continuous treatment with high doses of ARBs did not reduce their blood pressure to the target level (a systolic blood pressure of 130 mmHg or lower and a diastolic blood pressure of 80 mmHg or lower). The antihypertensive and metabolic effects of switching from high-dose ARBs to a combination of losartan (50 mg/day) plus hydrochlorothiazide (12.5 mg/day) were examined. The primary endpoint was a decrease in blood pressure at 24 weeks. RESULTS: The combination treatment significantly decreased both systolic (baseline: 147±11; 24 weeks: 133±13 mmHg) and diastolic (baseline: 79±8; 24 weeks: 72±10 mmHg) blood pressure. This treatment was also associated with a significant increase in the HbA1c level (baseline: 7.0±0.8%; 24 weeks: 7.2±0.9%) and a significant decrease in the urinary albumin-creatinine ratio (baseline: 280±590; 24 weeks: 110±253 mg/g creatinine). However, the combination treatment had no effect on lipid metabolism or the serum uric acid or potassium levels. CONCLUSION: In patients with diabetes, sodium reabsorption in the renal tubules is enhanced, which leads to the development of salt-sensitive hypertension. Therefore, the concurrent use of a diuretic that promotes sodium excretion can increase the antihypertensive effects of other drugs. This study demonstrated that switching from high-dose ARB treatment to losartan/hydrochlorothiazide combination therapy results in significant control of blood pressure.

Glucose variability before and after treatment of a patient with Graves' disease complicated by diabetes mellitus: assessment by continuous glucose monitoring.

A 48-year-old woman was diagnosed and treated for Graves' disease (GD) in 1999 but she discontinued treatment at her own discretion. In 2011, she was admitted to a local hospital for management of thyrotoxic crisis. Treatment with propylthiouracil, iodide potassium (KI), and prednisolone (PSL) was started, which resulted in improvement of the general condition. PSL and KI were discontinued before she was transferred to our hospital. At the local hospital, fasting plasma glucose (FPG) was 212 mg/dL and hemoglobin A1c concentration was 11.2%; intensive insulin therapy had been instituted. Upon admission to our hospital, FPG level was 122 mg/dL, but insulin secretion was compromised, suggesting aggravation of thyroid function and deterioration of glycemic control. The FPG level increased to 173 mg/dL; continuous glucose monitoring (CGM) identified dawn phenomenon at approximately 0400 h. Resumption of KI resulted in improvement of FPG and disappearance of the dawn phenomenon, as assessed by CGM. These results indicate that in patients with compromised insulin secretion, hyperthyroidism can induce elevation of not only postprandial blood glucose, but also FPG level due to the dawn phenomenon and that the dawn phenomenon can be alleviated with improvement in thyroid function. To our knowledge, no studies have assessed glucose variability by CGM before and after treatment of Graves' disease. The observations made in this case shed light on the understanding of abnormal glucose metabolism associated with Graves' disease.

Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes.

BACKGROUND: Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus, but many of these patients fail to achieve the target LDL-C level. Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin. However, in patients with type 2 diabetes who are already being treated with satins, it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose. Therefore, this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins. METHODS: The subjects were type 2 diabetic patients under treatment with rosuvastatin (2.5 mg daily), who had LDL-C levels ≥80 mg/dL. They were randomly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day (combination group, n = 40) or an increase of the rosuvastatin dose to 5 mg/day (dose escalation group, n = 39). These two groups were compared at baseline and after 12 weeks of treatment. RESULTS: The percent change of LDL-C was -31% in the combination group and -12% in the dose escalation group. Both groups showed a significant decrease, but the decrease was greater in the combination group. In both groups, there was a significant decrease in the levels of small dense LDL-C, oxidized LDL and remnant-like lipoprotein cholesterol. For all of these parameters, the percent changes were greater in the combination group. Only the combination group showed a significant decrease of triglycerides. Multivariate analysis was performed to identify factors associated with reaching an LDL-C level <80 mg/dL. As a result, add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. CONCLUSIONS: Compared with increasing the dose of rosuvastatin, the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients, suggesting that this combination could suppress the progression of atherosclerosis. TRIAL REGISTRATION: UMIN000011005.

Iatrogenic osteomalacia: report of two cases.

UNLABELLED: CASE 1: An 80-year-old man presented at our hospital with pain in both knees.He had received continuous intravenous administration of saccharated ferric oxide (SFO) over a period of five years following a diagnosis of iron-deficiency anemia.Blood tests revealed hypophosphatemia (1.4 mg/dl) and high circulating levels of fibroblast growth factor 23 (FGF23) at 248.8 mg/dl.These findings led to the diagnosis of FGF23-related osteomalacia due to SFO administration.Accordingly, the treatment plan was first to discontinue SFO, which led to a decrease in pain and normalization of phosphorus and FGF23 after 1 month.CASE 2: A 63-year-old woman presented at our hospital with leg pain.She had undergone total gastrectomy for gastric cancer at 36 years of age.Blood tests revealed hypocalcemia (8.3 mg/dl) and hypophosphatemia (2.2 mg/dl), and 25(OH)D at no more than 5 pg/ml.Bone X-rays showed significantly diminished bone shadowing.These findings led to a diagnosis of vitamin D-deficient osteomalacia due to impaired absorption following total gastrectomy.For therapy, she was treated with 1 µg/day oral alfacalcidol.Two months after initiating treatment, the pain improved. CONCLUSION: When a patient is diagnosed with unexplained pain, it is important to pay attention to the possibility of an iatrogenic etiology.

Successful treatment of osteomalacia caused by renal tubular acidosis associated with Sjögren's syndrome.

A 62-year-old woman was diagnosed with severe osteomalacia caused by renal tubular acidosis associated with Sjögren's syndrome. She was treated with sodium bicarbonate, risedronate, alfacalcidol, and prednisolone (1 mg/kg). By 24 months, renal tubular acidosis was improved and the bone density had normalized. Here we report the successful amelioration of bone lesions through a multidisciplinary approach that improved renal tubular acidosis, with a special focus on treatment of the underlying inflammatory disorder with glucocorticoids.

Inhibitory effects of metachromins L-Q and its related analogs against receptor tyrosine kinases EGFR and HER2.

Metachromins are a series of sesquiterpenoid quinones isolated from Okinawan marine sponges. Inhibitory effects of metachromins L-Q (1-6), sesquiterpenoid quinones with an amino acid residue, and their related analogs (7-18) prepared from metachromins A (19) and C (20) against receptor tyrosine kinases EGFR and HER2 were investigated. Two analogs 11 and 12 showed relatively stronger inhibitory activity against EGFR, while metachromins L-Q (1-6) and seven analogs (8, 10, 11, and 15-18) showed inhibitory activities against HER2.

[A case of postural orthostatic tachycardia syndrome (POTS) with difficulties in differentiation from hypoglycemic attack].

A 49-year-old man was referred to our clinic for suspected hypoglycemic symptoms of palpitation, cold sweat, faintness and sinking feeling at movement since 43 years old. The 75 g oral glucose tolerance test showed a decrease in plasma glucose to 56 mg/dl at five hours, but this was not associated with clear hypoglycemic symptoms, and normal plasma glucose level recovered naturally after the test. At 48-hour fasting test, plasma glucose dropped to under 50 mg/dl, but the patient didn't feel hypoglycemia symptom and plasma glucose recovered naturally, but the patient developed cold sweat and hyperventilation after returning to his own room after the test. At that stage, the heart rate increased to 140 beats/min of sinus tachycardia, as confirmed by Holter monitoring. Postural orthostatic tachycardia syndrome (POTS) was suspected because tachycardia occurred only in daytime after an event such as consumption of diet and urination. A head-up tilt test was ordered since sinus tachycardia developed especially on standing. The results showed an increase in heart rate without reduction in blood pressure, confirming the diagnosis of POTS. A repeat head-up tilt test under the use of a beta-blocker showed no increase in heart rate. Though it is generally difficult to distinguish POTS from other forms of tachyarrhythmia, such as inappropriate sinus tachycardia and sinus node reentry tachycardia, and from neutrally mediated reflex syncope (NMS), POTS should be differentiated from hypoglycemia since each condition should be treated differently.

Fibroblast growth factor 23-related osteomalacia caused by the prolonged administration of saccharated ferric oxide.

A 44-year-old woman with iron deficiency anemia was on a continuous course of intravenous saccharated ferric oxide (SFO). She came to our hospital because of right hip joint pain. She was found to have hypophosphatemia caused by impaired phosphorus resorption and her fibroblast growth factor 23 (FGF-23) levels were elevated. Therefore, she was diagnosed with FGF-23-related osteomalacia due to SFO administration. Discontinuation of the SFO treatment rapidly improved the impaired phosphorus resorption and also normalized the blood levels of phosphorus and FGF-23. During the treatment with SFO, it is important to regularly measure the blood levels of phosphorus in order to prevent the occurrence of osteomalacia.

Nakijiquinones J--R, sesquiterpenoid quinones with an amine residue from okinawan marine sponges.

Nine new sesquiterpenoid quinones, nakijiquinones J-R (1-9), have been isolated from three collections of Okinawan marine sponges of the family Spongiidae, and the structures and configurations were elucidated from the spectroscopic data and chemical correlations. Nakijiquinones J-L (1-3), M and N (4 and 5, respectively), O (6), P and Q (7 and 8, respectively), and R (9) are new sesquiterpenoid quinones possessing (S)-2-methylbutylamine, isopentylamine, isobutylamine, phenethylamine, and taurine residues, respectively, attached to each quinone ring.

Serratezomines D and E, new Lycopodium alkaloids from Lycopodium serratum var. serratum.

Two new Lycopodium alkaloids, serratezomines D (1) and E (2), were isolated from the club moss Lycopodium serratum var. serratum. Serratezomine D (1) is a new lucidine-type alkaloid, while serratezomine E (2) is a new phlegmarane-type alkaloid. The structures and relative stereochemistry of 1 and 2 were elucidated on the basis of spectroscopic data. Serratezomine D (1) exhibited an inhibitory activity against acetylcholinesterase.