Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

BACKGROUND: Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. CASE PRESENTATION: A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. CONCLUSIONS: The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.

Type 1 Diabetes Mellitus and Pernicious Anemia in an Elderly Japanese Patient: A Case Report and Literature Review.

We herein report the case of a 66-year-old Japanese man with acute-onset type 1 diabetes mellitus (T1D) accompanied by pernicious anemia. After 2 weeks of polyuria, the patient developed insulin-deficient hyperglycemia with diabetic ketoacidosis in the absence of verifiable islet-related autoantibodies and began insulin therapy in 2001. Eight years later, he developed gastric autoantibody-positive pernicious anemia and began methylcobalamin treatment. Previous studies have reported cases of slowly progressive autoimmune T1D concomitant with pernicious anemia. The present case suggests that potential associations with organ-specific autoimmune disorders should be considered during the long-term follow-up of T1D patients, even though verifiable islet-related autoantibodies are undetectable.

Usefulness of home blood pressure measurement in the morning in patients with type 2 diabetes: long-term results of a prospective longitudinal study.

Previous cross-sectional studies have demonstrated that blood pressure measurements at home (HBP) in the morning display stronger predictive power for micro- and macrovascular complications in type 1 and 2 diabetic patients than casual/clinic blood pressure (CBP) measurements. This longitudinal study investigated which of these measurements offers stronger predictive power for outcomes over 6 years. At baseline, 400 Japanese patients with type 2 diabetes were classified as hypertensive or normotensive based on HBP and CBP measurements. Mean (+/-SD) survey duration of all patients was 42.1 +/- 20.0 months (range, 3-72 months). Primary and secondary endpoints were death and new, worsened, or improved micro- and macrovascular events, respectively. Differences in outcomes for each endpoint between hypertensive and normotensive patients in each group were analyzed using survival curves from Kaplan-Meier analysis and log-rank testing. Associated risk factors related to outcomes were assessed using Cox proportional hazards modeling. On the basis of HBP, cumulative events of death and new or worsened microvascular diseases were significantly higher in hypertensive patients than in normotensive patients. On the basis of CBP, no significant differences were identified. New or worsened macrovascular events were significantly higher in hypertensive patients than in normotensive patients on the basis of both HBP and CBP. One associated risk factor was morning hypertension. A longitudinal study of type 2 diabetic patients demonstrated that elevated HBP in the morning is predictive of micro- and macrovascular complications.

Multiple brown tumors in primary hyperparathyroidism caused by an adenoma mimicking metastatic bone disease with false positive results on computed tomography and Tc-99m sestamibi imaging: MR findings.

We encountered an unusual case of hyperparathyroidism with both hemosiderin deposits on the ribs and low intensity on T2-weighted magnetic resonance imaging (MRI) caused by a parathyroid adenoma with multiple brown tumors that mimicked metastatic bone tumor due to false positive results on computed tomography (CT) and Tc-99m sestamibi (MIBI) imaging. The patient, a middle-aged woman, had very high serum levels of calcium (14.1 mg/dl), alkaline phosphatase (9,369 IU/l) and intact-PTH (12,400 pg/ml), and a large tumor (2.5 cm in diameter) in the lower portion of the left lobe of the thyroid. Plain X-ray revealed a soft tumor in the left chest wall. On CT scan, there were multiple destructive masses in the ribs, including large intramedullary masses on both 3rd ribs. On MIBI scintigraphy, there was strong late uptake in the lower portion of the left cervical region, both 3rd ribs, and the left 7th, 8th, and 10th ribs. T2-weighted image MRI scans showed that both 3rd ribs had a low intensity with hemosiderin deposits. These findings suggested that the patient had hyperparathyroidism with multiple bone metastases due to carcinoma of the parathyroid gland. However, on pathology, the resected tumor of lower portion of the left lobe of thyroid was diagnosed as a parathyroid adenoma, and the tumors of the left 3rd and 7th ribs, as well as the right 2nd rib, were shown to be brown tumors. After resection, the patient's serum levels of calcium, alkaline phosphatase, and intact-PTH normalized. At 1.5-years follow-up, CT, MIBI, and MRI scans showed no abnormal findings. It is necessary to determine whether MRI can be used to distinguish between brown tumors and metastases caused by carcinoma of the parathyroid gland.

Comparison of patient's preference, pain perception, and usability between Micro Fine Plus 31-gauge needle and Microtapered NanoPass 33-gauge needle for insulin therapy.

BACKGROUND: How smoothly insulin is injected is one of the major concerns when patients commence insulin injection therapy. Improving its usability may be important in initiation therapy and adherence, resulting in clinical benefits to the patient. METHODS: In a single-center, open-label and randomized two-period crossover trial, the effect of the tapered needle of NanoPass (33 gauge, 5 mm) on usability in comparison with the standard needle of Micro Fine Plus (31 gauge, 5 mm) was examined using a questionnaire. Patients with insulin-dependent diabetes (n = 40, self-injecting insulin four times daily for more than 3 months) were randomized to use NanoPass or Micro Fine Plus needles for 1 week and then use the alternative for 1 week. Patients completed the questionnaire before and after each test week. Each evaluation was scored from -100 (worst) to +100 (best) by a visual analogue scale. A higher score indicated a more favorable outcome compared with the other needle. RESULTS: The NanoPass needle was significantly less painful to insert and caused less bruising than the Micro Fine Plus needle. However, there was no significant difference in the overall patient satisfaction score between the two needles. Meanwhile, the NanoPass needle, which had less resistance in insertion with a new lubricant coating method, had a significantly superior (P < 0.001) overall patient's satisfaction score, including less frightening use, less bleeding, and less dribbling of injected insulin in comparison with the former evaluation. CONCLUSIONS: For overall patient satisfaction in using an insulin needle, developing a thinner needle and improving other factors, such as lubricity coating the needle, are important.

Effect of the 2004 Mid-Niigata Prefecture earthquake on home blood pressure measurement in the morning in type 2 diabetic patients.

A major earthquake struck the Niigata Prefecture, Japan, on October 23, 2004. This study investigated the effect of the earthquake on morning home blood pressure (MHBP) measurements, as well as clinic blood pressure (CBP) and associated complications, in 222 type 2 diabetic patients who measured MHBP and CBP before the earthquake. Physical and laboratory examinations were assessed at every three months. Each patient completed a questionnaire on MHBP measurement, Japanese intensity grade (JIS), patient's lifestyle and psychological impact using posttraumatic stress disorder (PTSD) symptom score. Median JIS showed all patients lived in areas affected by strong aftershocks. Most patients stayed in their own houses, while one-third of patients sought refuge in other houses. No new clinical manifestations of disease were noted. Median PTSD score was low. Patients in public refuge houses had daytime blood pressure, but MHBP was not measured. In the first month, the number of patients who continued MHBP measurements decreased to 27% of pre-shock level. Many patients were unable to measure MHBP for several reasons, including losing MHBP equipment, having equipment destroyed, or suffering from anxiety due to the extensive devastation. Mean systolic MHBP and median urinary albumin excretion rate (UAER) increased significantly within three months and returned to pre-earthquake level at six months. On multiple regression analysis, increased systolic and diastolic MHBPs were significantly associated with UAER elevation. In type 2 diabetic patients following an earthquake, it is important to develop a device of MHBP measurement for maintaining control of MHBP to prevent vascular complications.

A case of preclinical Cushing's syndrome associated with diurnal rhythms of ACTH and cortisol in blood: correlation with histological findings.

We describe a case of adrenocortical adenoma with preclinical Cushing's syndrome demonstrating diurnal rhythms of ACTH and cortisol in blood. A 50-year-old man was admitted to the hospital for the evaluation of incidental right adrenal mass with hyperglycemia and hypertension. On admission, there were no signs of clinical manifestation of hypercortisolism. The basal levels of cortisol (9.3 microg/dl) and ACTH (9.4 pg/ml) at 0800 h were not elevated and these diurnal rhythms were maintained. One or 8 mg of dexamethasone given orally overnight suppressed the plasma ACTH but not serum cortisol. Ultrasonogram, CT and scintiscan of (131)I adosterol all demonstrated an enlarged adrenal mass in the right adrenal gland. The right adrenal gland was subsequently resected by laparoscopic surgery. Histopathological findings of resected adrenal tumor were consistent with adrenocortical adenoma. Adjacent non-neoplastic adrenal tissue demonstrated adrenocortical atrophy but DHEA-sulfotransferase immunoreactivity in the zona reticularis was detected.

Effect of the 2004 mid niigata prefecture earthquake on patients with endocrine disorders.

A major earthquake (Richter scale magnitude 6.8) struck the Chuetsu district of Niigata Prefecture, Japan, a rural area with mountain villages, on October 23, 2004. Strong aftershocks (Grade 5-6 on the Japanese intensity scale, JIS) continued for 2 months. We analyzed the earthquake's impact on 229 patients with various endocrine disorders [6 central diabetes insipidus (CDI), 16 adrenal insufficiency (AI) including 5 panhypopituitarism, 10 ACTH isolated deficiency and 1 Addison's disease, 145 Graves' disease and 62 Hashimoto's disease]. The status of patients with CDI or AI was not adversely affected by the earthquake. Twenty-eight (19%) patients with Graves' disease developed more severe hyperthyroidism; the incidence of developing more severe hyperthyroidism increased with greater degrees of hyperthyroidism. Three (5%) patients with Hashimoto's disease developed increased TSH concentrations. Most patients stayed in their own houses following the first shock. The median PTSD total score for all patients was low. However, the PTSD total score in patients with CDI or Hashimoto's disease was significantly higher than in other patients, while the subscore of mental status in patients with AI was significantly much lower than in other patients. In patients with Hashimoto's disease, patients whose hypothyroidism worsened had higher total and environmental effects score than patients whose hypothyroidism remained stable. Comparing patients whose hyperthyroidism became more severe to those in whom it remained stable, as well as on multiple logistic regression analysis, serum TRAb was found to be a risk factor for developing more severe hyperthyroidism. In conclusion, our findings indicate that Graves' disease patients need to maintain their euthyroid state with a low serum TRAb titer to prevent the development of further thyroid dysfunction after an earthquake, and that all patients should continue to take their medication, since it is likely that their lives will be interrupted by environmental effects owing to earthquake-shock, especially patients with CDI or Hashimoto's disease. Due to the risk of medical facility closure during a disaster, all patients should always have a note or copy of their medical records, including medical history and medications used, to avoid relying on patients remembering their drug names and doses. Furthermore, appropriate information should be provided by all means possible, including the mass media, to affected individuals, particularly those with AI, to decrease the occurrence of adverse consequences.

Effect of the 2004 Mid Niigata Prefecture earthquake on glycemic control in type 1 diabetic patients.

At 5:56 p.m. on October 23, 2004, a major earthquake of magnitude 6.8 on the Richter scale struck the Chuetsu district of Niigata Prefecture, Japan, a rural area with mountain villages. Strong aftershocks of grade 5-6 on the Japanese Intensity Scale continued for 2 months. We investigated changes in the HbA1c levels of 65 type 1 diabetic patients with insulin therapy before and throughout the 12 months of aftershocks that followed the earthquake. All patients received insulin therapy via pens with replaceable cartridges or continuous subcutaneous insulin infusion (CSII). Most patients needed four daily insulin injections with rapid- and long-acting insulins. Nineteen percent of patients had the CSII therapy using rapid-acting insulin. The mean HbA1c level in all patients increased significantly (P<0.01) from 6.7+/-0.9% to 7.0+/-1.0% in the third month, peaked at the fifth month, and decreased at 12 months. Sixty percent of the patients stayed in their own houses after the initial shock, while 40% of patients moved into other houses. Seventeen percent of the patients had severely destroyed houses. The median PTSD score was low in all patients. Within 1 month after the earthquake, the pens with replaceable cartridges were discontinued and disposable pens with prefilled insulin cartridges were used. The incidence of nephropathy increased by 7% by the third month and returned to the pre-earthquake level by the sixth month. Over the 12-month observation period, no other micro- or macro-vascular diseases were newly diagnosed. One patient had transient severe acute hyperglycemia and one needed hemodialysis. However, none of the patients had ketoacidosis, and no other clinical manifestations of disease were noted. In conclusion, it is essential that neighboring organizations respond quickly with sufficient medical support for diabetic patients with insulin therapy following an earthquake. In particular, treatment with rapid- and long-acting insulin injections via disposable pens with prefilled insulin cartridges or CSII therapy is useful during a disaster. To take the medical support, patients should always have a note or copy of their medical records, including medical history and medications used.

A quality-of-life assessment of intensive insulin therapy using insulin lispro switched from short-acting insulin and measured by an ITR-QOL questionnaire: a prospective comparison of multiple daily insulin injections and continuous subcutaneous insulin infusion.

We examined quality-of-life (QOL) of patients with a prospective comparison of multiple daily insulin injections therapy (16 patients in MDI group) and continuous subcutaneous insulin infusion therapy (12 patients in CSII group) using insulin lispro (LP), which was switched from short-acting insulin on the basis of a questionnaire about insulin-therapy-related QOL measure (ITR-QOL). The overall score of ITR-QOL before using LP in the CSII group was significantly higher (P<0.02) than the MDI group. In four subscales of ITR-QOL, the scores of social and daily activities and of therapy-related feelings in the CSII group were significantly higher (P<0.02) than those in the MDI group, respectively, while there was no significant difference in the score of physical function between the two groups. Three months after using LP, the score of daily activities in the MDI group was significantly higher (P<0.02) than that before using LP, while there were no significant differences in other scores of the two groups. There were no significant differences in HbA1c between two groups before and after using LP. The frequency of hypoglycemic events in the MDI group before using LP was higher than that in the CSII group and decreased after using LP. These results show that QOL of patients treated by CSII is superior to that treated by MDI and demonstrate that insulin lispro has a more beneficial effect on daily activities in patients treated by MDI than short-acting insulin.

Novel mutant vasopressin-neurophysin II gene associated with familial neurohypophyseal diabetes insipidus.

We describe a novel missense mutant of arginine vasopressin (AVP)-dependent neurohypophyseal diabetes insipidus in an autosomal dominant family. A 54-year-old woman was admitted to our hospital because of thyroidectomy for thyroid cancer. After thyroidectomy she was found to have hypernatremia and polyuria and polydipsia both of which had been present from childhood. She had no obstructive hydronephrosis. Her father, father's younger sister and her third son also had polyuria and polydipsia. Basal plasma AVP concentration at normal plasma osmolality was normal but did not respond to increased plasma osmolality despite hyperosmolality during infusion of hypertonic saline infusion, indicating that plasma AVP secretion was impaired. Sodium concentration in urine and urine osmolality were low and increased after nasal administration of DDAVP. There was a diminished but bright signal of pituitary posterior gland on magnetic resonance T1 weighted image. Molecular genetic analysis demonstrated that the patient and her son had a single heterozygous missense mutation (G-->A) at nucleotide 1829 in 1 AVP allele, yielding an abnormal AVP precursor with lacking Glu-47 in its neurophysin II moiety. The abnormal AVP precursor may be related to the impaired AVP secretion.

A case of a novel mutant vasopressin receptor-dependent nephrogenic diabetes insipidus with bilateral non-obstructive hydronephrosis in a middle aged man: differentiation from aquaporin-dependent nephrogenic diabetes insipidus by response of factor VII and von Willebrand factor to 1-diamino-8-arginine vasopressin administration.

We describe a case of a novel mutant vasopressin 2 receptor (V2R)-dependent nephrogenic diabetes insipidus (NDI) with bilateral non-obstructive hydronephrosis in a middle aged man. This could be distinguished from aquaporin 2 (AQP2)-dependent NDI by the response of factor VIII and von Willebrand factor (vWF) to 1-deamino-8-D-arginine vasopressin (DDAVP) administration. A 47-year-old man was admitted to hospital because of polyuria, which had been present from infancy and was suspected of causing non-obstructive hydronephrosis. His mother's father, the older brother of his mother and his second daughter also all had polyuria. Sodium concentration, osmolality and vasopressin in blood were high, while sodium concentration and osmolality in urine were low. There were no changes in urine osmolality, factor VIII and vWF in response to DDAVP infusion. Neither was heart rate, diastolic blood pressure nor facial flushing affected. These findings suggested this case was V2R-dependent NDI rather than AQP2-dependent NDI. Molecular genetic analysis demonstrated that the patient had a V2R missense mutation involving a substitution of cysteine for arginine at position 104 (R104C) located in the first extracellular loop of the V2R. It was also found that the patient's mother and his second daughter were heterozygous for this R104C mutation.

Usefulness of home blood pressure measurement in the morning in type 2 diabetic patients.

OBJECTIVE: Recently, repeated home blood pressure (HBP) measurements in the morning for a long period have been shown to have a stronger predictive power for mortality in patients with hypertension than occasional casual/clinic blood pressure (CBP) measurements. We studied whether HBP in the morning in type 2 diabetic patients is useful for prediction of diabetic complications. RESEARCH DESIGN AND METHODS: The occurrence of diabetic complications (nephropathy, retinopathy, coronary heart disease [CHD], and cerebrovascular disease [CVD]) were examined in relation to morning HBP as well as to CBP in 170 type 2 diabetic patients treated with antidiabetic and antihypertensive drugs. Blood pressure was measured at the clinic during the day and at home after awakening in the morning. Clinic hypertension (CH) and morning hypertension (MH) were defined as systolic blood pressure (SBP) > or =130 mmHg and/or diastolic blood pressure (DBP) > or =85 mmHg. The relation of CH and MH to the prevalence of these events was examined. RESULTS: There were no significant differences in the prevalence of nephropathy, retinopathy, CHD, and CVD between the two groups with (n = 131) and without CH (n = 39), whereas the prevalences of these events in the patients with MH (n = 97) were significantly higher (P < 0.05) than in those without MH (n = 73). The prevalence of nephropathy was highly associated with systolic MH. CONCLUSIONS: Elevations of HBP in the morning in diabetic patients are strongly related to microvascular and macrovascular complications, especially nephropathy. It is concluded that the control of MH may prevent vascular complications in type 2 diabetic patients.