A case of normotensive incidentally discovered adrenal pheochromocytoma.

Pheochromocytomas are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla. The clinical presentation includes headache, palpitation, and hypertension, but pheochromocytomas are sometimes clinically silent. The present case highlights the importance of biochemical testing for pheochromocytoma in patients with adrenal incidentaloma, even if they are completely normotensive and asymptomatic.

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.

Lung adenocarcinoma and adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by heterozygous germline mutations in the tumor suppressor gene MEN1, which encodes a nuclear protein, menin. MEN1 is characterized by the combined occurrence of tumors involving the pituitary gland, pancreatic islets, and parathyroid glands. Additionally, patients with MEN1 often exhibit adrenal tumors. Although most MEN1-associated tumors are benign, malignant lesions arising in these endocrine organs have been reported. Additionally, malignant diseases of non-endocrine organs concomitant with MEN1 have also been reported. Here, we report a rare case of a MEN1 patient who exhibited adrenocortical carcinoma (ACC) and lung adenocarcinoma (LAC). A 53-year-old Japanese woman was diagnosed with genetically proven MEN1 that initially manifested as parathyroid, pancreatic, and adrenal tumors. During the course of the disease, she developed LAC harboring the epidermal growth factor receptor gene mutations and cortisol-secreting ACC. Both tumors were surgically resected. The tumor cells were immunohistochemically negative for menin. Studies have suggested a causative link between MEN1 gene mutations and ACC, and menin expression may decrease in MEN1-related ACCs. In contrast, there are few reports suggesting a specific role of MEN1 gene mutations in LAC. Menin is often inactivated in the LACs of patients without MEN1. Thus, our patient's ACC probably occurred as part of MEN1, whereas the latter had no evident etiological association with her LAC. This case demonstrates the need for physicians to consider the potential development of malignant diseases originating from both endocrine and non-endocrine organs in MEN1 patients.

A case of central diabetes insipidus associated with cardiac dysfunction.

Central diabetes insipidus (CDI) results from a deficiency of arginine vasopressin (AVP) secretion. It is treated by replacement therapy with the synthetic AVP analogue desmopressin. To prevent heart failure in patients with CDI accompanied by cardiac dysfunction, controlling sodium and water intake is essential, using the minimum effective dose of desmopressin.

Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.

BACKGROUND: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. CASE PRESENTATION: A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years. CONCLUSIONS: Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.

Isolated Adrenocorticotropin Deficiency Concomitant with Graves' Disease: A Case Report and Literature Review.

A 73-year-old Japanese woman with untreated Graves' hyperthyroidism developed glucocorticoid-induced adrenal insufficiency (AI) after a supraphysiological dose of prednisolone therapy for bronchial asthma. Days later, she had high plasma adrenocorticotropic hormone (ACTH) levels and was expected to recover from glucocorticoid-induced AI. Her plasma ACTH levels remained high over 3 months during a physiological dose of hydrocortisone replacement. However, she suffered a further decrease in her serum cortisol level and was diagnosed with isolated adrenocorticotropin deficiency (IAD), in which bioinactive ACTH likely caused the high ACTH value. IAD should be considered as an unusual disorder associated with Graves' disease, especially in older patients.

Vildagliptin-induced acute lung injury: a case report.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. CASE PRESENTATION: A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. CONCLUSIONS: The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.

Rapid Normalization of High Glutamic Acid Decarboxylase Autoantibody Titers and Preserved Endogenous Insulin Secretion in a Patient with Diabetes Mellitus: A Case Report and Literature Review.

A 59-year-old Japanese woman developed diabetes mellitus without ketoacidosis in the presence of glutamic acid decarboxylase autoantibody (GADA) (24.7 U/mL). After the amelioration of her hyperglycemia, the patient had a relatively preserved serum C-peptide level. Her endogenous insulin secretion capacity remained almost unchanged during 5 years of insulin therapy. The patient's GADA titers normalized within 15 months. The islet-related autoantibodies, including GADA, are believed to be produced following the autoimmune destruction of pancreatic beta cells and are predictive markers of type 1 diabetes mellitus. Therefore, the transient appearance of GADA in our patient may have reflected pancreatic autoimmune processes that terminated without progression to insulin deficiency.

Fulminant Type 1 Diabetes Mellitus Associated with Coxsackie Virus Type A2 Infection: A Case Report and Literature Review.

A 65-year-old Japanese man presented to our hospital in June 2013 with a 6-day history of fever and fatigue, a 24-h history of thirst, and polyuria. His temperature was 37.8°C and he was alert. However, laboratory tests revealed severe hyperglycemia, undetectable C-peptide levels, and diabetic ketoacidosis. Serum antibody testing confirmed a Coxsackie virus A2 infection. A variety of viral infections are reported to be involved in the development of fulminant type 1 diabetes mellitus (FT1D). Our patient is the first reported case of FT1D associated with Coxsackie virus A2 infection and supports the etiological role of common viral infections in FT1D.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis Following Treatment for Cushing's Syndrome.

A 64-year-old Japanese man with mild reticular shadows in both lungs developed a lung tumor causing ectopic Cushing's syndrome. He was prescribed an adrenal inhibitor, which controlled his hypercortisolemia. However, he developed acute exacerbation of idiopathic pulmonary fibrosis (IPF) and died within weeks. Previous studies have suggested a dosage reduction of corticosteroids for IPF as a triggering event for acute exacerbation. The present case suggests that IPF coexisting with Cushing's syndrome may have been exacerbated after the correction of hypercortisolemia. Therefore, close monitoring of cortisol levels along with the clinical course of IPF is required in similar cases that require the correction of hypercortisolemia.

Type 1 diabetes mellitus and isolated adrenocorticotropin deficiency manifested by parkinsonism: a case report and literature review.

A 67-year-old woman developed isolated adrenocorticotropin deficiency (IAD), which manifested as lethargy, a 20-kg body weight loss, hypoglycemia, and parkinsonism, and began corticosteroid replacement. Her symptoms resolved rapidly, and her weight returned to normal within six months. However, she then developed slowly progressive type 1 diabetes mellitus (T1D) with co-existing Hashimoto thyroiditis, and commenced insulin therapy. To our knowledge, this is the first reported case of parkinsonism associated with IAD. In addition, because diabetes mellitus, including T1D, could be latent in patients with untreated IAD, careful assessment of glucose metabolism is needed after commencing corticosteroid replacement until weight regain is achieved.

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.

Fulminant type 1 diabetes mellitus and fulminant viral myocarditis. A case report and literature review.

A 35-year-old Japanese woman was admitted with coma following flu-like symptoms. She was diagnosed with diabetic ketoacidosis and fulminant type 1 diabetes (FT1D) and received intravenous infusion of insulin and saline. The next day, the ketoacidosis disappeared, and she recovered consciousness. However, extensive ST-segment elevations in the electrocardiogram appeared with a positive troponin test, and the patient developed pulmonary edema on day 3. An echocardiogram showed globally reduced wall motion of the left ventricle and mild pericardial effusion. Despite medical therapy with intravenous furosemide, carperitide, and catecholamines, her cardiac function deteriorated rapidly, with the left ventricular ejection fraction decreasing to 26% within 7 hours, and progressed to cardiogenic shock that afternoon. The patient received mechanical circulatory support for 4 days with intra-aortic balloon pumping and percutaneous cardiopulmonary support, and recovered fully from circulatory failure. A paired serum antibody test showed a significantly elevated titer against parainfluenza-3 virus, indicating a diagnosis of fulminant viral myocarditis. She was discharged on multiple daily insulin injection therapy, and her subsequent clinical course has been uneventful. In summary, we present a case of concurrent FT1D and fulminant viral myocarditis. Parainfluenza-3 viral infection was confirmed serologically and was considered to be a cause of both the FT1D and fulminant myocarditis.

Usefulness of morning home blood pressure measurements in patients with type 2 diabetes mellitus: results of a 10-year, prospective, longitudinal study.

Previous cross-sectional studies and 6-year longitudinal study have demonstrated that home blood pressure (HBP) measurements upon awakening have a stronger predictive power for death, micro- and macrovascular complications than clinic blood pressure (CBP) measurements in patients with type 2 diabetes (T2DM). This study investigated which of these measurements offers stronger predictive power for outcomes over 10 years. At baseline, 400 Japanese patients with T2DM were classified as having hypertension (HT) or normotension (NT) based on HBP and CBP. The mean survey duration was 95 months. Primary and secondary end-points were death and new or worsened micro- and macrovascular complications, respectively. Differences in outcomes for each end-point between HT and NT patients were analyzed using Kaplan-Meier survival curves and log-rank testing. Associated risk factors were assessed using Cox proportional hazards analysis. Based on HBP, death and micro- and macrovascular complications were significantly higher in patients with HT than with NT at baseline and end-point. Based on CBP, there were no significant differences in incidence of death, micro- or macrovascular complications between patients with HT and NT at baseline and end-point, although a significant difference in incidence of death was observed between the HT and NT groups at end-point. However, the significance was significantly lower in CBP than in HBP. One risk factor associated with micro- and macrovascular complications in patients with HBP was therapy for HT. This 10-year longitudinal study of patients with T2DM demonstrated that elevated HBP upon awakening is predictive of death, and micro- and macrovascular complications.

Identifying risk factors for clinically significant diabetic macula edema in patients with type 2 diabetes mellitus.

It is known that clinic blood pressure (BP), gender, cigarette smoking, dyslipidemia, anemia and thiazolidenediones (TZD) treatment are predictors for clinically significant diabetic macula edema (CSDME). We examined a most risky factor for CSDME in Japanese patients with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) confirmed using optical coherence tomography by multiple regression analysis (MRA). As the risk factors, wakening-up BP was added to such factors. Seven diabetic Japanese patients with CSDME (group 1) and 124 subjects without CSDME (group 2) assonated with DR using optical coherence tomography were studied. The durations of T2DM in groups 1 and 2 were 15±10 years and 20±15 years, respectively. There was no statistically difference in means of gender, duration, age, body mass index (BMI), HbA1c, TC, LDL and TC/HDL, serum creatinine, urinary albumin excretion rate, and clinic BP between two groups. Morning systolic home BP (MSHBP), cigarette smoking and foveal thickness were significantly (p<0.001) higher in group 1 than group 2, whereas visual acuity was significantly (p<0.00?) lower in group 1 than in group 2. The patients in both groups had received various kinds of drugs for hyperglycemia, hypertension and others. There were no significant differences in the variables in both groups. MRA revealed that MSHBP, cigarette smoking and pioglitazone as TZD treatment were significantly positive predictors for CSDME, while BMI had a significantly negative predictor. Other variables were not significantly correlated to CSDME. The review summarizes a multiple regression analysis revealed that MSHBP makes an addition to predictive factors for CSDME among risk factors reported previously in patient with T2DM.

Potential correlation between plasma total GIP levels and body mass index in Japanese patients with types 1 or 2 diabetes mellitus.

Glucose-dependent insulinotropic polypeptide (GIP) secretion in diabetic Europeans with type 1 (T1DM) and type 2 (T2DM) following test meal (TM) has been shown to be normal. In Japanese patients with T2DM, GIP secretion was also normal. We determined whether GIP secretin is influenced by various factors. Plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR), and plasma total GIP (p-total GIP) levels were measured at 0, 30, and 60 minutes after TM (560 kcal) in patients with T1DM (n = 15, group 1) and T2DM (n = 29, group 2) treated with various medications. HbA1c was also measured. At baseline, means of age, BMI, HbA1c, PG, s-CPR, SUIT (secretory unit in transplantation) and p-total GIP were significantly lower in group 1 than in group 2. Each mean of postprandial p-total GIP levels after TM in all patients was more dramatically increased than other factors. The area under the curve (AUC) of p-total GIP levels in early-phase (0 to 30 min) was significantly positively correlated with BMI in group 2 but not in group 1, and not with other factors. These results indicate that the GIP secretion after TM in diabetic Japanese patients was dramatically increased, and the AUC of GIP secretion in early-phase was positively correlated with BMI in non-obese and obese patients with T2DM, but not with T1DM. The increase was not influenced by gender, age, glycemic control, duration of disease, micro- or macro-vascular disturbances, or oral drugs.

Decreased active GLP-1 response following large test meal in patients with type 1 diabetes using bolus insulin analogues.

Postprandial plasma immunoreactive active glucagon-like peptide-1 (p-active GLP-1) levels in type 1 diabetic patients who did not use bolus insulin responded normally following ingestion of test meal, while a small response of p-active GLP-1 levels was seen in type 2 diabetic patients. To determine whether p-active GLP-1 levels are affected by ingestion of test meal in type 1 diabetic Japanese patients who used bolus rapid-acting insulin analogues, plasma glucose (PG), serum immunoreactive insulin (s-IRI), serum immunoreactive C-peptide (s-CPR), and p-active GLP-1 levels were measured 0, 30, and 60 min after ingestion of test meal in Japanese patients without diabetic complications (n=10, group 1) and control subjects with normal glucose tolerance (n=15, group 2). HbA1c levels were also measured in these groups. The patients in group 1 were treated with multiple daily injections or CSII using injections of bolus rapid-acting insulin analogues before ingestion of test meal. There was no significant difference in mean of sex, age, or BMI between groups. Means of HbA1c, basal and postprandial PG, and postprandial s-IRI levels with integrated areas under curves (0-60 min) (AUC) in group 1 were significantly higher than those in group 2. Means of basal and postprandial s-CPR, and postprandial p-active GLP-1 levels with AUCs were significantly lower in group 1 than in group 2. These results indicated that postprandial p-active GLP-1 levels following ingestion of test meal in type 1 diabetic Japanese patients using bolus rapid-acting insulin analogues were decreased relative to those in controls.