We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.

抄録全体を表示

Medullary thyroid carcinoma (MTC) occurs sporadically or as an inherited disease, with the latter occurring in the form of multiple endocrine neoplasia (MEN) type 2A, MEN type 2B, or familial non-MEN medullary carcinoma (FMTC). MTC is inherited as an autosomal dominant trait and is associated with germline mutations of the RET proto-oncogene. Genetic testing identifies carriers of the mutant gene and enables preventive thyroidectomy. A nationwide questionnaire-based survey was conducted in 1996 and again in 2002, and we report here the results of the two surveys that characterize the clinical course of the inherited form of MTC. The data show a higher rate of inherited MTC than previously described, although MEN2A was found to be the most common inherited form of MTC, the same as in earlier studies. The most important finding was the difference in method of detection of MTC between the two surveys. Since the discovery of the genetic association with the disease, genetic testing has become the diagnostic method of choice, replacing indicators such as neck mass and elevated non-stimulated serum calcitonin level. Genetic testing enables early detection of the disease, which provides patients with the possibility of better outcome.

抄録全体を表示

Spindle cell tumors and reactive proliferations of the thyroid gland are rarely reported. In this report, we described a case of follicular adenoma with spindle cell component. The spindle cell proliferation constituted more than 90% of the 4.0 cm lesion and showed fascicular pattern with focal areas of collagenous stroma and hyalinized blood vessels. There was a transition from follicle like glandular structure to fascicular pattern. There was no mitosis and necrosis. Immunoreactivity with thyroglobulin proved that the spindle cell proliferation is of follicular origin. Also strong thyroglobulin and cytokeratin positivity of glandular areas and the gradual decrease in positivity of spindle cells showed epithelial-mesenchymal transformation/spindle cell metaplasia of the thyroid. We thought that it is important to differentiate spindle cell metaplasia in follicular lesions, especially follicular adenoma, from malignant thyroid neoplasms.

抄録全体を表示

The adrenal gland is one of the organs which tuberculosis infects. In most clinical settings bilateral adrenal tuberculosis has been clarified after adrenal insufficiency is overt. On the contrary, active adrenal tuberculosis is rarely detected during the survey of infectious disease. A 68-year-old man was admitted because of intermittent fever. The fever had continued for the last 3 months. The intermittent fever was accompanied with leukocytosis and elevation of C-reactive protein. Serum soluble interleukin-2 receptor was 1920 U/ml, and β2-microglobulin was 4.0 mg/l. Bacterial cultures of blood, sputa, urine, bone marrow and cerebrospinal fluid did not show any particular bacteria. Mycobacterium tuberculosis was negative in culture of sputa, and there was no tuberculin reaction. Plasma ACTH and serum cortisol were 18.5 pmol/l and 527.0 nmol/l, respectively. Abdominal CT scan showed right adrenal mass with a size of 28 × 20 mm, which was low density and had a well-encapsulated homogenous appearance. After the adrenalectomy, histology verified active adrenal tuberculosis. The intermittent fever disappeared, and white blood cells and C-reactive protein normalized. These findings indicate an atypical, rare case of unilateral, active adrenal tuberculosis closely linked to intermittent fever, and without any other organ involvement.

抄録全体を表示

The purpose of the study was to evaluate the plasminogen activator inhibitor-1 (PAI-1) levels and PAI-1 activity in young and lean women with PCOS and to compare with controls matched for age and weight. Thirty two women with PCOS and 25 weight and age-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for hematological and biochemical tests. Fasting insulin, glucose, lipid profile, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone, androstenedione, PAI-1 antigen; PAI-1 activity, insulin sensitivity indices (HOMA and QUICKI) were measured. PAI-1 Ag and activity were significantly higher in PCOS women than healthy control group. PAI-1 levels were directly correlated with BMI, insulin levels and insulin sensitivity indices. PAI-1 activity was also correlated with insulin levels and insulin resistance. As a conclusion PAI-1 Ag levels and activity were increased in lean PCOS women and these were directly correlated with insulin resistance. The finding may contribute to evidence of increase risk of cardiovascular disease and anovulatory infertility in PCOS women.

抄録全体を表示

Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. In the present study, we report two new patients of Allgrove syndrome with mutations in the AAAS gene. Patient 1 was a 22-year-old Japanese woman, born to consanguineous parents. She was confirmed to have adrenal insufficiency at the age of 3 years and 6 months. She developed alacrima and bilateral optic nerve atrophy at the age of 8 years. She had been noticed to have dysphagia. Based on these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis revealed a novel homozygous point mutation in exon 7 of her AAAS gene, changing codon 194 encoding Arg (CGA) to a stop codon (TGA) (R194X). Patient 2 was a 7-year-old Japanese boy, born to consanguineous parents. At the age of 1 year, he was noticed to be unable to produce tears. He was confirmed to have adrenal insufficiency, mental retardation and spastic diplegia at the age of 5 years and 4 months. He was tentatively diagnosed as having Allgrove syndrome, although he has never complained of dysphasia. Mutation analysis revealed a homozygous point mutation in exon 4 of his AAAS gene, changing codon 119 encoding Arg (CGA) to a stop codon (TGA) (R119X). Both of the R119X and R194X mutations are predicted to result in truncated and non-functioning ALADIN proteins, and thus the diagnosis of Allgrove syndrome was confirmed by the mutation analyses. These findings indicate that there exist significant clinical variability and mutational heterogeneities in Japanese patients with this syndrome.

抄録全体を表示

It has been reported that adult patients with growth hormone deficiency (GHD) have increased risk factors for cardiovascular disorders in Western countries. However, data on this issue in Japan have not been fully investigated. To clarify the situation on this issue in Japan, a nationwide questionnaire survey was conducted by Study Group of Hypothalamo-Pituitary Disease, and medical records of 863 adult patients were recruited. The incidences of complications and risk factors for cardiovascular diseases were compared between GH deficient patients (GHD, n = 494) and GH intact patients (GHI, n = 369). The incidence of myocardial infarction was higher in GHD (1.2%) than in GHI (0.8%), but not significantly. The incidences of angina pectoris and liver dysfunction were significantly higher in GHD than in GHI (2.8 vs 0.8%, p = 0.048, and 11.9 vs 5.5%, p<0.0001, respectively). The prevalences of obesity and hyperlipidemia (HL) were significantly higher in GHD (p = 0.004, p<0.001, respectively). Combinations of HL plus diabetes mellitus (DM) or hypertension (HT) were more common in GHD than in GHI (HL + DM; 7.2 vs. 2.9%, HL + HT; 10.9 vs. 2.9%). These results indicated that GH deficiency have an increased prevalence of cardiovascular risk factors in Japanese similar to Western countries, and suggested that GH supplement therapy may be needed to reduce those complications.

抄録全体を表示

Primary aldosteronism is a relatively common cause of secondary hypertension. It is often important to diagnose this disease accurately, since appropriate surgical therapy may result in cure of the disease. Assessment of the laterality of adrenal hyperfunction is possible using adrenal venous sampling of steroid hormones, but this procedure may not be feasible in patients with allergy to iodinated radiocontrast agents. In this paper, we report a patient with primary aldosteronism who was found to have bilateral adrenal tumors on CT. Because preoperative localization of the hyperfunctioning tumor was important, adrenal venous sampling and venography was performed by a highly-experienced radiologist using the MRI contrast agent gadolinium. After reviewing the data, the patient received a right adrenalectomy. This case report demonstrates that it was possible to perform adrenal venography using gadolinium in this patient, however the safety and efficacy should be re-assessed in individual cases.

抄録全体を表示

Reactive oxygen species are considered to play a role in the development of diabetes mellitus and its complications. Human MTH1 (mutT homologue 1) has 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase activity, which repairs oxidized forms of dGTP. This enzyme is known to have a thermolabile Met83 variant. We examined whether Val83Met polymorphism of human MTH1 gene is associated with type 1 diabetes mellitus. We recruited 156 type 1 diabetic patients (59 males and 97 females). The polymorphism was analyzed by restriction fragment length polymorphism analysis with Nsi I. The Met/Met genotype at codon 83 was very rare in both control and patient groups. Val/Met genotype tended to be more frequent in the whole type 1 diabetic patients than in controls. When subjects were divided into subgroups according to gender, there were no differences in the genotype and allele frequencies between patients and controls in males. On the other hand, in female type 1 diabetic patients, the Val/Met genotype was more frequent than in female controls (corrected P = 0.102). The Met allele was significantly more frequent in female type 1 diabetic patients than in female controls (corrected P = 0.022). Our results suggested that the Met allele at codon 83 of MTH1 gene might be involved in the development of type 1 diabetes mellitus in the Japanese female population.

抄録全体を表示

Osteopontin (OPN) is thought to play multiple roles in the progression of atherosclerotic plaque including diabetic vascular complications. However, it still remains unclear whether the level of OPN in vivo is indeed clinically associated with the progression of diabetic complications. This study evaluated whether the levels of OPN in plasma and urine are correlated with the progression of diabetic complications, such as retinopathy, neuropathy, and nephropathy in patients with type 2 diabetes. In 229 patients with type 2 diabetes, OPN level in plasma and urine was evaluated by both the severity of diabetic complications, such as retinopathy, neuropathy, and nephropathy, and the clinical characteristics and the substantial laboratory findings. Plasma OPN level increased significantly with aging and the progression of diabetic nephropathy, especially at the stage of renal failure (p<0.05). However, the level was not related to the progression of retinopathy or neuropathy, or to laboratory findings, such as HbA1c or serum lipids. In contrast, urinary OPN level was not associated with diabetic complications in any of the subjects. There was no correlation between the plasma and urinary values of OPN. The results established that the plasma OPN was elevated in proportion to the progression of diabetic nephropathy, indicating that the plasma concentration may be a potential diagnostic predictor of diabetic end-stage renal disease.

抄録全体を表示

Hyperhomocysteinemia is a risk factor for atherosclerotic vascular diseases. It is known that plasma homocysteine levels are higher in polycystic ovary syndrome (PCOS) patients than in healthy subjects. The aim of our study was to determine the relationship between plasma homocysteine level and insulin resistance in women with PCOS. Twenty-nine patients (age, 23.90 ± 5.86 years) and twenty-five healthy subjects (age, 25.24 ± 4.28 years) were involved in the study. Plasma levels of fasting insulin, glucose, homocysteine, FSH, and LH levels were measured. A statistically significant difference in plasma concentrations of HOMA index, homocysteine, basal insulin levels and LH/FSH ratios was observed between groups (P = 0.001, P = 0.001, P = 0.001, and P = 0.01, respectively). There was no relationship between Hcy and the other variables. In multiple logistic regression analysis, age, BMI and insulin resistance were not predictors of Hcy.

抄録全体を表示