Nihon Naibunpi Gakkai zasshi最新文献

To differentiate between ectopic ACTH syndrome and Cushing's disease, we examined the gene expression of CRF, POMC and glucocorticoid receptor in pituitary adenomas and in ectopic ACTH-producing tumors. CRF increased plasma ACTH levels in all patients with Cushing's disease and in some patients with ectopic ACTH syndrome whose tumors contained CRF and CRF mRNA. In CRF non-responders, no CRF was detected in tumors that contained no CRF mRNA or contained only long-size CRF mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in the patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRF increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRF mRNA, PMA-induced POMC gene expression, two ectopic ACTH syndrome subtypes (tumors containing ACTH with CRF and tumors without CRF), and Dex-induced decrease in ACTH release and POMC mRNA levels in some bronchial carcinoid.

Six cases with ACTH-independent bilateral adrenocortical macronodular hyperplasia (AIMAH) were presented, and 21 reported cases were reviewed. Bilateral adrenal glands in AIMAH were greater than those in any other subtype of nodular hyperplasia. They were greater than 72 g in combined weight and were occupied by numerous yellow nodular/subnodular lesions. Histologically, hyperplastic lesions were composed of small compact, small clear, and usual clear cells. All of these three elements contained cells positive for PCNA but were negative for HLA-DR alpha. Small compact cells often showed positive staining for vimentin. Small cells showed underdeveloped organelles with rare nuclear grooving and were poor in lipochrome. The results are consistent with the view that AIMAH is primarily a nodular hyperplasia of the upper zona fasciculata and that it is a distinct subtype of Cushing's syndrome. Image analyses may play a major role on preoperative diagnosis of AIMAH. Bilateral adrenalectomy is the treatment of choice.

The separation of Cushing's disease from non-pituitary ACTH-secreting tumors is rarely straightforward. Both a 16-year-old girl and a 56-year-old man exhibited typical clinical features of Cushing's syndrome. In both patients urinary 17OHCS was suppressed by 8mg dexamethasone and plasma cortisol and ACTH responded to intravenous administration of CRH. X-rays of the skull, a computed tomographic scan and a magnetic resonance imaging (MRI) of the sella turcica area showed no significant abnormality. An enhanced MRI of the pituitary gland in the first patient demonstrated a small low-density area which represented microadenoma. In the second patient, an enhanced MRI and inferior sinus sampling failed to demonstrate a pituitary tumor. The patient died of acute myocardial infarction, and an autopsy revealed a bronchial carcinoid in the right upper pulmonary lobe. It is necessary to differentiate an ectopic ACTH-secretion in patients with Cushing's syndrome who show typical biochemical features of Cushing's disease but fail to demonstrate the presence of a pituitary tumor by routine radiological evaluation.

We have studied eleven cases of the adrenal with primary pigmented nodular adrenocortical disease (PPNAD) by immunohistochemistry of all steroidogenic enzymes involved in cortisol biosynthesis, by in situ hybridization of P450C17 in seven cases in order to localize the sites of steroidogenesis and by chromosome suppression in situ hybridization of genomic DNA in five cases in order to determine possible genetic abnormalities of the disorder. Immunoreactivity of all the enzymes examined was intense in almost all the cells in adrenocortical nodules while internodular adrenal cortex, including the cases without cortical atrophy, was negative for the enzymes with the exception of 3 beta HSD. In situ hybridization studies of P450C17 yielded results consistent with those of immunohistochemistry. These results may be consistent with autonomous cortisol production by the nodular cells and indicate that almost all of the cells in the cortical nodules produce cortisol, which can explain the presence of hypercortisolism despite small sizes of adrenals in PPNAD. Chromosome suppression in situ hybridization analysis demonstrated possible genetic defects in chromosome 16 in this disorder.

A rare case of cortisol-responsive, dexamethasone-non-responsive cyclic Cushing's disease for whom a high daily dose of bromocriptine was effective was presented, and 58 cases of cushing's syndrome with variable hormonogenesis from the literature were reviewed with our own case (a total of 59 cases). In addition, the results of the high daily dose of bromocriptine treatment in our 7 cases of Cushing's disease were described. The presented case, a 57-year-old female, had a clinically and biochemically proven 3-8 day cycle length. With 40mg daily of bromocriptine, periodic hypercortisolemia disappeared and the patient was in remission with normal suppression of plasma cortisol by dexamethasone. Out of 59 cases of cyclic Cushing's syndrome, 39 were pituitary Cushing's disease or Cushing's syndrome with bilateral adrenal hyperplasia. 15 cases (25%) were adrenal adenoma and ectopic ACTH syndrome. In 22 out of 34 cases (62%), paradoxical response of plasma cortisol to dexamethasone was observed. Only 4 out of 16 cases (25%) on whom Hardy's operation was performed remitted completely. Our own presented case alone showed long-term remission with medical treatment. Seven Cushing's disease patients were treated with a high daily dose of bromocriptine (17.5-55mg/day). Three cases, in whom the highest dose of bromocriptine was 40, 55, and 35mg/day, showed clinical and biochemical long-term remission. In these 3 cases, an escape phenomenon was observed during the early treatment period with a decreased dose of bromocriptine. Thereafter the dose was increased, resulting in a beneficial outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

A 37-yr-old woman was admitted to our hospital for evaluation of diabetes mellitus, liver cirrhosis and primary amenorrhea. Serological and hematological examinations revealed that she suffered from hemochromatosis secondary to congenital dyserythropoietic anemia (CDA), characterized by ineffective hematopoiesis and erythropoietic dysplasia. Iron deposition was suggested by MRI on the pancreas, liver and pituitary gland. Endocrinological examinations demonstrated that she had isolated gonadotropin deficiency and ovarian failure, resulting in hypogonadotropic hypogonadism. In addition, despite normal responses of serum cortisol and plasma aldosterone to ACTH and furosemide-standing tests, respectively, serum dehydroepiandrosterone (DHEA) responded poorly to ACTH test, suggesting selective damage of zona reticularis in adrenocortical steroidogenesis in association with hemochromatosis.

Among 838 consecutive patients who underwent abdominal CT scan, adrenal incidentalloma was detected in 41 cases (4.7%). We performed high (8 mg/day) and low dose (2 mg/day) dexamethasone (DXM) suppression test and diurnal rhythm of plasma cortisol in these patients. Autonomic cortisol production was observed in one hypertensive patient in whom Cushigoid appearance was absent, suggesting pre-clinical Cushing's syndrome. We reviewed the endocrine results of the 65 reported cases of pre-clinical or non-Cushigoid Cushing's syndrome in world and Japanese literature. Urinary cortisol excretion was normal in 77%, plasma cortisol rhythm was absent in 70%, and high dose DXM failed to suppress plasma cortisol in 95% of cases. Plasma ACTH and cortisol showed subnormal to low responses to CRF administration similar to overt Cushing's syndrome. Therefore, CRF-test alone was considered insufficient to differentiate the two disorders. Hypertension and glucose intolerance were present in approximately 50% of cases in otherwise asymptomatic patients. Post-surgical steroid replacement was required in 55% of cases in Japan and in 75% of the cases world-wide. Women were affected more with pre-Cushing's syndrome than men. Peak incidence of the pre-Cushing's syndrome in women was in the forties which was older than that of overt Cushing's syndrome, suggesting that pre-Cushing's syndrome is not the predisposing condition to clinically symptomatic Cushing's syndrome. We consider that endocrine test is necessary in incidentally discovered adrenal tumors to exclude the presence of pre-clinical Cushing's syndrome.

The relationship between prostaglandins (PGs) production and the mechanism of dysmenorrhea in endometriosis is poorly understood. Consequently, we investigated the role of PGs in dysmenorrhea of endometriosis. Slices of normal endometrium, normal myometrium, adenomyosis, leiomyoma, normal ovary and affected ovary were incubated. 6-keto PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha and PGE2 concentrations of the incubation medium were measured by RIA. The results are as follows; 1) PGs production in endometriosis was significantly higher than that of other tissues, especially 6-keto PGF1 alpha, which was a dominant product in adenomyosis. 2) There were significant differences in PGs production between severe dysmenorrhea and non dysmenorrhea, especially tissue of adenomyosis with severe dysmenorrhea which produces large amounts of 6-keto PGF1 alpha. 3) There seems to be interaction between normal endometrium and normal myometrium with regard to 6-keto PGF1 alpha production. We concluded that increased PGI2 in the tissue of endometriosis seems to induce hyperalgesia during menstruation.

A previously unknown HPLC peak was recently observed in urine samples from patients with Cushing's syndrome and disease. We analysed dansylated derivatives of 17keto steroid glucuronides in urine samples from patients with Cushing's syndrome, Cushing disease and from healthy subjects using high-performance liquid chromatography (HPLC) on reversed-phase Cap Cell PakC8. All urine samples from patients with Cushing's syndrome caused by adrenal adenoma and Cushing's disease showed an unknown large peak at the point between [110HE-G] and [110HA-G] peaks and at a retention time of 25.4 min. The same unknown peak was also observed in urine samples from a patient with asymptomatic cortisol-producing adrenal adenoma and two patients with ectopic ACTH-producing tumor, though the peak height was low for the former and one of the latter but high for the second of the two patients. In contrast, healthy male and female urine only showed a very small peak at the same retention time. Urine samples from a Cushing disease treated with op'DDD and Cushing's syndrome bilaterally adrenalectomized and treating with cortisol showed no such peak. The retention time of this unknown peak is clearly different from that of seven 17keto steroid standard glucuronide conjugates. The structure of this substance may be closely related to [110HE-G] or [110HA-G].

The association between hormone dynamics and bone turnover was statistically examined in 52 women with surgically induced menopause. The mean values of 19 laboratory items which included hormones as well as parameters of bone metabolism were obtained and analyzed by Spearman's rank test. Linear regression models were established. Based on Pearson's correlation matrices, the principal components were analyzed. Matrices were formed from factor loading derived from Varimax's rotation, and their statistical significance was evaluated. 1. Significant correlations were determined from both the examination of the data analyzed separately at the levels of artificial menopause (bilateral and unilateral) and oophorectomy (OVX) method (bilateral or unilateral). For the patients who had bilateral OVX, the pairs showing a positive correlation (0.01 < P, 0.05 < P) were 1-25-(OH)2D with E2 or ASD, 25-(OH)D with E2, E3, Progesterone, or ASD, CT with Progesterone, ASD, or Testosterone, S.A1-P with FSH or LH, and S.Ca with LH. The pairs showing a weaker positive correlation were PTH with E2 or E3, CT with E2, E3 with S.Acid-P or U.Ca/CRN, and S.Ca with FSH. The pairs showing a negative correlation (0.01 < P, 0.05 < P) were S.A1-P with E2 or Progesterone, and S.Ca with Testosterone. The pairs showing a weaker negative correlation were S.A1-P with ASD. For the patients who had unilateral OVX, the pairs showing a positive correlation were 1-25-(OH)2D with E2, ASD, or Testosterone, 25-(OH)D with E2, E3, Progesterone, or ASD, CT with Progesterone, ASD, or Testosterone, and PTH with ASD. The pairs showing a weaker positive correlation were PTH with E2 or E3, and CT with E2. The pairs showing a negative correlation were S.Ca with Testosterone. The pairs showing a weaker negative correlation were S.A1-P with ASD. There was a small but significant difference between the two groups. However, Estrogen and Androgen in sex steroids, and S.A1-P, S.Ca, CT, PTH, 1-25-(OH)2D, and 25-(OH)D in bone parameters, all changed early or late at different rates but participated concomitantly with the high bone turn-over induced by OVX, particularly in bilateral. 2. Significant correlations among all parameters were determined for data analyzed at the level of artificial menopause.(ABSTRACT TRUNCATED AT 400 WORDS)