Platelet-activating factor contracts guinea pig esophageal muscularis mucosae by stimulating extracellular Ca2+ influx through diltiazem-insensitive Ca2+ channels.

Platelet-activating factor (PAF) is expected to increase esophageal motility. However, to the best of our knowledge, this has not been examined. Thus, we investigated the contractile effects of PAF on guinea pig (GP) esophageal muscularis mucosae (EMM) and the extracellular Ca2+ influx pathways responsible. PAF (10-9-10-6 M) contracted EMM in a concentration-dependent manner. PAF (10-6 M)-induced contractions were almost completely suppressed by apafant (a PAF receptor antagonist, 3 × 10-5 M). In EMM strips, PAF receptor and PAF-synthesizing/degrading enzyme mRNAs were detected. PAF (10-6 M)-induced contractions were abolished by extracellular Ca2+ removal but were not affected by diltiazem [a voltage-dependent Ca2+ channel (VDCC) inhibitor, 10-5 M]. PAF (10-6 M)-induced contractions in the presence of diltiazem were significantly suppressed by LOE-908 [a receptor-operated Ca2+ channel (ROCC) inhibitor, 3 × 10-5 M], SKF-96365 [an ROCC and store-operated Ca2+ channel (SOCC) inhibitor, 3 × 10-5 M], and LOE-908 plus SKF-96365. Among the tested ROCC/SOCC-related mRNAs, Trpc3, Trpc6, and Trpv4/Orai1, Orai3, and Stim2 were abundantly expressed in EMM strips. These results indicate that PAF potently induces GP EMM contractions that are dependent on extracellular Ca2+ influx through ROCCs/SOCCs, and VDCCs are unlikely to be involved.

The prevalence of polycystic thyroid disease in hypothyroid patients with negative thyroid autoantibodies.

BACKGROUND: We previously reported that multiple thyroid cysts may be a cause of hypothyroidism in patients with a relatively high iodine intake and we termed it polycystic thyroid disease (PCTD). The aim of this study was to investigate the prevalence of PCTD in patients who visited our thyroid center. We hypothesized that patients with PCTD are not rare in a region with a high iodine intake. METHODS: We retrospectively studied the cause of hypothyroidism based on medical histories and ultrasonography in new patients to our hospital from April 2008 to March 2009 whose serum tests for antithyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) were negative. Serum thyroid hormones, thyrotropin (TSH), TgAb, and TPOAb were measured in 8243 patients. Patients with four or more thyroid cysts, negative tests for TgAb and TPOAb, no evidence for thyroid diseases other than their thyroid cysts, and no exposure to thyroid-perturbing influences were defined as having PCTD. RESULTS: Three hundred seven patients had overt hypothyroidism (TSH level above 10.0 µU/mL and free thyroxine level below 0.7 ng/dL), of whom 71 patients were both TgAb and TPOAb negative. There were 546 patients with subclinical hypothyroidism (TSH level above 5.0 µU/mL and normal free thyroxine), of whom 193 patients were both TgAb and TPOAb negative. There were 24 patients with overt hypothyroidism and PCTD, accounting for 7.8% (24/307) of all causes of overt hypothyroidism. There were 42 patients with subclinical hypothyroidism and PCTD, accounting for 7.7% (42/543) of all causes of subclinical hypothyroidism. PCTD was more common among elderly people than young people. CONCLUSIONS: PCTD appears to be a minor but not negligible cause of hypothyroidism, at least in iodine-rich regions. PCTD with hypothyroidism may have been misdiagnosed as thyroid antibody-negative Hashimoto's thyroiditis in many reports.

Misdiagnosis of two cases of primary aldosteronism owing to failure of computed tomography to detect adrenal microadenoma.

Recent studies have suggested that primary aldosteronism (PA) is a common form of hypertension. However, some cases of PA are overlooked because microadenoma is difficult to detect by imaging. The author report 2 cases in which aldosterone-producing microadenoma was diagnosed by selective adrenal venous sampling (AVS) and furosemide plus upright test. These adenomas were resected by laparoscopic adrenalectomy. Both cases presented with hypertension and hypokalemia. Experimental data, including those obtained from furosemide plus upright test, suggested PA. In both cases, computed tomography imaging revealed a normal adrenal gland without any tumor. However, selective AVS indicated unilateral hypersecretion of aldosterone. Laparoscopic adrenalectomy was performed, and clinical symptoms of the patients improved. The histopathologic findings revealed aldosterone-producing microadenomas with diameters of 6 and 3 mm, respectively, in cases 1 and 2. In conclusion, AVS should be performed to confirm the diagnosis of PA when computed tomography imaging does not provide definite results.

Multiple thyroid cysts may be a cause of hypothyroidism in patients with relatively high iodine intake.

BACKGROUND: Multiple cysts of the thyroid gland have not been recognized as one of the causes of hypothyroidism. Here we present six patients from a region with relatively high iodine intake in whom multiple cysts of the thyroid were associated with hypothyroidism or the development of hypothyroidism. SUMMARY: All patients were women and ranged in age from 49 to 71. Their thyroids were mildly enlarged, tests for thyroid autoantibodies were negative, and multiple cysts were detected in the thyroid by ultrasonography. By dietary questionnaire their iodine intake was estimated to range from 2 to 10 mg of iodine daily. Otherwise, there was no evidence for disorders or factors associated with hypothyroidism. All four patients who agreed to dietary iodine restriction became euthyroid at approximately 1 month after a low-iodine diet (less than 0.5 mg iodine per day) was started. CONCLUSIONS: Although these patients were from a region with high-iodine intake and had a relatively high intake compared with most regions of the world, this amount of iodine intake is not associated with hypothyroidism in otherwise healthy persons. Therefore, we propose that multiple thyroid cysts, which we have termed polycystic goiter, is probably a cause of hypothyroidism in patients with a relatively high iodine intake.

Suprasellar germinoma masquerading as lymphocytic hypophysitis associated with central diabetes insipidus, delayed sexual development, and subsequent hypopituitarism.

We report the case of an 18-year-old woman with suprasellar germinoma masquerading as lymphocytic hypophysitis, which was associated with central diabetes insipidus, delayed sexual development, and hypopituitarism. Magnetic resonance imaging revealed an enlarged pituitary gland, thickened pituitary stalk, and a mass lesion in the inferior hypothalamus; these findings are typical of lymphocytic hypophysitis. Despite the administration of prednisolone therapy for 3 months, an enlarged irregular cystic mass lesion developed in the pituitary stalk and inferior hypothalamus. Open cranial surgery of the posterior pituitary revealed the presence of a germinoma. Therefore, chemotherapy and stereotactic radiation therapy were administered, resulting in complete remission of the germinoma. This case illustrates that the presence of an intrasellar mass lesion in association with pituitary stalk thickening can often cause difficulties in differential diagnosis. We believe that lymphocytic hypophysitis in pubertal children may be the first sign of a host reaction to an occult germinoma.

Co-existence of glucagonoma with recurrent insulinoma in a patient with multiple endocrine neoplasia-type 1 (MEN-1).

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, the anterior pituitary, and the endocrine pancreas. Our patient was a 58-year-old man who manifested typical features of MEN-1 including primary hyperparathyroidism, lung carcinoid, and lipomas and insulinoma. He was admitted to our hospital because of recurrent hypoglycemia and a growth of pancreatic tumors. The first operation for insulinoma was performed when he was 20 years old. We found a germline mutation of the MEN1 gene (E45G, exon 2) in this patient. According to these examinations and his clinical course, the patient was diagnosed as having a recurrence of insulinoma. He subsequently underwent surgery for the pancreatic tumors. The majority of these tumor cells were immunohistochemically positive for insulin and negative for glucagon. A few nodules showed immunohistochemical staining positivity for glucagon but they were negative for insulin. Although it is uncommon for patients with MEN1 to exhibit insulinoma and glucagonoma, this case suggests the need for careful analysis of pancreatic tumors in patients with MEN1.

A case of Dunnigan-type familial partial lipodystrophy (FPLD) due to lamin A/C (LMNA) mutations complicated by end-stage renal disease.

Dunnigan-type familial partial lipodystrophy (FPLD) is a rare monogenic adipose tissue disorder in which the affected subjects have increased predisposition to insulin resistance and related metabolic complications, such as glucose intolerance, diabetes, dyslipidemia, and hepatic steatosis. Our patient was a 35-year-old female who had been receiving insulin injection therapy for diabetes mellitus and was transferred to our hospital. She was diagnosed with FPLD on the basis of the following symptoms: increase in subcutaneous fat in the face, neck, and upper trunk; loss of subcutaneous fat in the lower limbs and the gluteal region. We found a heterozygous CGG to CAG transition in codon 482 of exon 8 in the gene encoding lamin A/C (LMNA), which leads to an arginine to glutamine substitution (R482Q). At the time of admission, her serum creatinine level was 8.4 mg/dl, and her blood urea nitrogen (BUN) level was 81 mg/dl. Her serum creatinine level was elevated and hemodialysis was performed twice every week. However, she died of cerebral hemorrhage 9 months after hemodialysis. Although it is uncommon for patients with FPLD to exhibit renal dysfunction and require hemodialysis, this case suggests the need for careful analysis of renal function in a patient with FPLD.

A case of non-Hodgkin's lymphoma primary arising in both adrenal glands associated with adrenal failure.

It is known that adrenal insufficiency is one of the complications in primary adrenal lymphoma, especially those with bilateral adrenal involvement. A 73-year-old man was referred for general fatigue and high fever to the nearest hospital. The patient was transferred to our hospital for evaluation of bilateral adrenal tumors and hyponatremia. He was diagnosed as having non-Hodgkin's lymphoma (NHL) with primaries arising in both adrenal glands. Primary adrenal lymphoma (PAL) is a rare extra-nodal NHL. Although an appropriate treatment of this disease has not been established, our case has demonstrated that the combination of rituximab and THP-COP chemotherapy could be administered, and that it improved clinical manifestations. This case raises the suggestion that malignant lymphoma should be suspected in patients with bilateral adrenal tumors that present with progressive adrenal insufficiency.

Improvement in renal dysfunction and symptoms after laparoscopic adrenalectomy in a patient with pheochromocytoma complicated by renal dysfunction.

A 70-year-old patient who was undergoing treatment for diabetes mellitus and chronic hepatitis was admitted to our hospital for evaluation of a tumor in the left adrenal gland (50 x 45 mm) and renal failure. On the basis of the patient's increased serum concentrations of catecholamines and other metabolites and the results of positron emission tomography (PET), the patient was diagnosed with a pheochromocytoma; iodinated metaiodobenzylguanidine ([(131)I]MIBG) scintigraphy was insufficient to establish this diagnosis. Subsequently, he underwent surgery for tumor resection. Histological examination suggested the tumor to be a malignant pheochromocytoma. After left adrenalectomy was performed, the elevated catecholamine and metabolite concentrations and the blood pressure were restored to normal, and the patient's symptoms of severe headaches and vertigo reduced. Furthermore, his renal function improved (Cr 2.0-1.2 mg/dl). Our patient exhibited a rare condition of pheochromocytoma complicated by renal failure, which was successfully treated with laparoscopic surgery.

Isolated follicle-stimulating hormone (FSH) deficiency without mutation of the FSHbeta gene and successful treatment with human menopausal gonadotropin.

OBJECTIVE: To describe the case of isolated follicle-stimulating hormone (FSH) deficiency without mutation of the FSHbeta gene. DESIGN: Case report. SETTING: Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan. PATIENT(S): A 22-year-old man referred for infertility, azoospermia, and isolated FSH deficiency. INTERVENTION(S): The patient's FSHbeta gene was sequenced. Pituitary function at baseline and after repeated GnRH administration was evaluated. Testicular biopsy was performed. The patient was treated with human menopausal gonadotropin (hMG). MAIN OUTCOME MEASURE(S): Pathologic examination revealed hypospermatogenesis with isolated FSH deficiency without mutation of the FSHbeta gene. RESULT(S): The FSH levels remained below the normal range despite repeated GnRH stimulation. Hypospermatogenesis was confirmed by testicular biopsy. After 6 months of hMG treatment, spermatogenesis was successfully induced. CONCLUSION(S): We report the case of an infertile male with isolated FSH deficiency without any evidence of mutation in the FSHbeta gene.