[Show abstract][Hide abstract] ABSTRACT: We report a 22-yr-old male patient with idiopathic hypothalamic hypogonadism who showed secondary resistance to gonadotropin (Gn) therapy over 3 yr after successful treatment with hCG combined with human menopausal Gn. The patient simultaneously developed subclinical hypothyroidism. Endocrine examination revealed low levels of testosterone (0.3 ng/ml), free T4 (0.91 ng/dl), and increased levels of TSH (31.1 microU/ml) in the serum. Serum autoantibodies to thyroid gland were all negative. Interestingly, thyroid function was improved after discontinuation of Gn therapy. In vitro assays by immunoprecipitation using 125I-hCG or 125I-TSH elucidated the presence of anti-hCG antibody in the serum 13 months after commencement of Gn therapy but anti-TSH antibody was not detected in the serum. Furthermore, the anti-hCG antibody specifically bound to hCG but not to other glycoproteins including TSH and FSH based on a competitive displacement assay. Bioassays using porcine thyroid cells revealed that the serum gamma-globulin fraction enables the suppression of cyclic AMP (cAMP) synthesis stimulated by TSH. Our findings suggest that anti-hCG and/or anti-idiotypic hCG antibodies induced by hCG therapy impaired TSH-dependent cAMP production through interfering with binding of TSH to its receptor, and this resulted in subclinical hypothyroidism in this patient.
No preview · Article · Dec 2003 · Journal of endocrinological investigation
[Show abstract][Hide abstract] ABSTRACT: To elucidate whether bradykinin is involved in the renoprotective effect produced by angiotensin II type 1 receptor antagonist (AT1A) in chronic salt-sensitive hypertension, Dahl salt-sensitive rats receiving a high-salt (8%) diet were treated either with an AT1A (candesartan, 1 mg/kg/day), a bradykinin B2 receptor antagonist (BKB2A; FR172357, 30 mg/kg/day) or a combination of AT1A and BKB2A for 7 weeks. None of the treatments changed the markedly increased systolic blood pressure induced by a high-salt diet. However, chronic treatment with AT1A significantly improved the histological hallmarks of renal damage-i.e., glomerular sclerosis and cell proliferation-despite the presence of severe hypertension. This beneficial action of AT1A was abolished by the concomitant administration of BKB2A. In agreement with these histologically based findings, increases in levels of creatinine clearance induced by AT1A were also reversed back to the basal levels when BKB2A was administered in conjunction with AT1A. Furthermore, urinary excretions of nitrate plus nitrite and prostaglandin E2 increased moderately in response to the administration of AT1A alone, but not in combination with BKB2A. Thus, the blockade of bradykinin signaling abrogates the renoprotective actions of the angiotensin II type 1 (AT1) receptor antagonism. Collectively, these data show that when AT1 action is chronically blocked, endogenous bradykinin plays a pivotal role in preventing the progression of glomerular injury in salt-sensitive hypertension.
No preview · Article · Apr 2003 · Hypertension Research
[Show abstract][Hide abstract] ABSTRACT: We report a Japanese family with glucocorticoid-remediable aldosteronism (GRA) in whom gene abnormality was identified by the long-polymerase chain reaction (PCR) method. The proband was a 21-year-old female incidentally found to have high blood pressure (173/107 mmHg). Laboratory tests showed hypokalemia (3.7 mmol/l), and high plasma aldosterone concentration (PAC, 234 pg/ml) with suppressed plasma renin activity (PRA, <0.1 ng/ml/h). The circadian rhythm pattern and the results of a rapid adrenocorticotrophic hormone (ACTH) test indicated ACTH-dependent changes in PAC. Imaging studies showed no adrenal mass on either side. A dexamethasone (Dexa) suppression test (1.0 mg/day orally for 7 days) showed a marked decrease of PAC 2 days after administration, and this decreased level was maintained throughout Dexa administration. High blood pressure and hypokalemia also improved during Dexa treatment. The proband's younger sister was 19 years old and had hypertension, PAC of 231 pg/ml, and PRA <0.1 ng/ml/h. The mother was 53 years old and had hypertension, PAC of 98.5 pg/ml, and PRA <0.1 ng/ml/h. The proband's elder sister was a 22-year-old normotensive with PAC of 110 pg/ml and PRA of 0.1 ng/ml. Long-PCR was performed for detection of the chimeric gene associated with GRA, using DNA samples from all four cases and two normal control subjects. Although the aldosterone synthase gene was expressed among all DNA samples, the chimeric gene was detected only in the proband, her younger sister and her mother. Our clinical data and genetic investigation confirmed the presence of GRA in this Japanese family.
No preview · Article · Oct 2001 · Hypertension Research
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of long-term treatment with calcium-antagonist, amlodipine, on angiotensin II receptors in the adrenal cortex of spontaneously hypertensive rats (SHR). Seven-week-old male SHR were treated with oral amlodipine (10 mg/kg/day) or vehicle (saline) for four weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were treated with the vehicle similar to control SHR. Systolic blood pressure (SBP) showed time-dependent increase in SHR but not in WKY rats, while amlodipine treatment significantly reduced the high SBP in SHR. Plasma renin activity was serially increased in SHR, which was further enhanced by amlodipine treatment. But the plasma aldosterone level which was increased in SHR was not changed by amlodipine. Competitive reverse transcriptase-polymerase chain reaction showed that the level of adrenocortical angiotensin II type 1 receptor (AT1R) mRNA progressively decreased in vehicle-treated SHR compared to WKY rats and that 4-week course of amlodipine treatment significantly increased AT1R mRNA in SHR to levels comparable to those in WKY rats. Amlodipine treatment reduced the level of adrenocortical angiotensin II type 2 receptor (AT2R) mRNA in SHR from 8 weeks of age. Thus, chronic amlodipine treatment differently modulates both adrenocortical AT1R and AT2R in SHR in a possibly direct manner.
[Show abstract][Hide abstract] ABSTRACT: A 27-year-old woman who presented with a left thyroid nodule was found to have hyperthyroidism caused by a syndrome of inappropriate secretion of TSH. The levels of free T3, free T4 and TSH were 9.50 pg/mL, 4.05 ng/dL and 2.16 microU/mL, respectively. Magnetic resonance imaging of the head revealed a pituitary macroadenoma. The TSH response to TRH stimulation was normal and responses of other anterior pituitary hormones to stimulation tests were also normally preserved. Administration of octreotide with iodine successfully reversed hyperthyroidism prior to total resection of pituitary adenoma, which was followed by hemithyroidectomy of the left thyroid five months later. Histologically, the resected pituitary adenoma was a TSH-producing adenoma (TSH-oma) and the thyroid nodule was a papillary adenocarcinoma. Serum TSH diminished to undetectable levels immediately following pituitary adenomectomy but gradually normalized over nine months. Coexistence of a TSH-oma with thyroid cancer is very rare and only two similar cases have previously been documented. This combination raises the possibility that TSH may be involved in tumorigenesis in the thyroid gland.
No preview · Article · Jan 2001 · Endocrine Journal