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1.
J Endocr Soc ; 6(1): bvab174, 2022 Jan 01.
Article de Anglais | MEDLINE | ID: mdl-34909517

RÉSUMÉ

PURPOSE: Excessive aldosterone secretion causes a high risk of cardio-cerebrovascular events. Mineralocorticoid receptor antagonist (MRA) is 1 of the treatment strategies for primary aldosteronism (PA). However, current MRA treatment is insufficient because MRA-treated patients with suppressed plasma renin activity (PRA) < 1 ng/mL/h still had a higher risk of cardiovascular disease than those with unsuppressed PRA. This is a prospective interventional study to determine the effects of an increase in MRA dosage on blood pressure (BP) control and urinary albumin excretion (UAE) in MRA-treated PA patients. METHODS: Thirty-four PA patients were recruited, and 24 patients (6 male, 18 female) completed this study. Serum potassium concentration was assessed every two months to adjust the dosage of MRA safely for 6 months. The primary outcomes were the changes in BP and UAE between baseline and 6 months. RESULTS: Systolic BP (SBP) and log10UAE decreased significantly as the daily dose of MRA increased. Diastolic BP (DBP) tended to decrease. We divided the PA patients into two groups (baseline PRA < 1 ng/mL/h and baseline PRA ≥ 1 ng/mL/h) according to PRA. In the group with baseline PRA < 1 ng/mL/h but not that with baseline PRA ≥ 1 ng/mL/h, SBP, DBP and log10UAE after 6 months were significantly lower than those at baseline. CONCLUSIONS: The increase in MRA dosage improved BP and UAE in PA patients with suppressed PRA.

2.
J Clin Endocrinol Metab ; 105(7)2020 07 01.
Article de Anglais | MEDLINE | ID: mdl-32275055

RÉSUMÉ

CONTEXT: The prevalence of diabetes mellitus (DM) in patients with primary aldosteronism (PA) is higher than in those with essential hypertension and the general population. Although DM is a common major risk factor for cardio-cerebrovascular (CCV) diseases and renal complications, details of its effects in PA have not been demonstrated. OBJECTIVE: The aim of this study was to determine the effects of coexistent DM on the risk of CCV events and progression of renal complications in PA patients. DESIGN: A multi-institutional, cross-sectional study was conducted. PATIENTS AND METHODS: PA patients experienced between January 2006 and October 2016 and with available data of CCV events and DM were enrolled from the Japan PA registry of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Diseases Study (n = 2524). CCV events and renal complications were compared between a DM group and a non-DM group by logistic and liner-regression analysis. RESULTS: DM significantly increased the odds ratio (OR) of CCV events (OR 1.59, 95% CI: 1.05-2.41) and that of proteinuria (OR 2.25, 95% CI: 1.59-3.16). DM correlated significantly with declines in estimated glomerular filtration rate (ß = .05, P = .02). CONCLUSIONS: This the first report to demonstrate the presence of DM as an independent risk factor for CCV events and renal complications, even in PA patients. Management of DM should be considered in addition to the specific treatment of PA.


Sujet(s)
Angiopathies intracrâniennes/étiologie , Diabète de type 2/complications , Hyperaldostéronisme/complications , Maladies du rein/étiologie , Angiopathies intracrâniennes/épidémiologie , Études transversales , Évolution de la maladie , Femelle , Humains , Incidence , Maladies du rein/épidémiologie , Mâle , Adulte d'âge moyen , Enregistrements , Études rétrospectives , Facteurs de risque
3.
Intern Med ; 58(23): 3433-3439, 2019 Dec 01.
Article de Anglais | MEDLINE | ID: mdl-31391398

RÉSUMÉ

We herein report a 28-year-old woman with type 1 diabetes with an asymptomatic pontine lesion and diabetic amyotrophy. She had suffered from diabetes from 10 years old. Treatment in a hospital reduced the hemoglobin A1c level from 14.2% to 7.2% for approximately 2 months. She suffered from acute-onset pain and weakness of the lower limb muscles without central nervous system manifestations. Magnetic resonance imaging showed high-intensity lesions at the brainstem and lower limb muscles on T2-weighted images. These findings and symptoms gradually resolved. Rapid treatment of poor glycemic control might increase the risk of asymptomatic pontine lesions and diabetic amyotrophy.


Sujet(s)
Encéphalopathies/étiologie , Diabète de type 1/diétothérapie , Neuropathies diabétiques/diétothérapie , Pont , Adulte , Glycémie/métabolisme , Diabète de type 1/complications , Diabète de type 1/traitement médicamenteux , Neuropathies diabétiques/complications , Neuropathies diabétiques/traitement médicamenteux , Femelle , Hémoglobine glyquée/métabolisme , Humains , Hypoglycémiants/usage thérapeutique , Insuline/usage thérapeutique , Plexus lombosacral , Imagerie par résonance magnétique , Faiblesse musculaire/étiologie , Douleur/complications , Douleur/diétothérapie , Douleur/traitement médicamenteux , Neuropathies périphériques/complications , Neuropathies périphériques/diétothérapie , Neuropathies périphériques/traitement médicamenteux , Résultat thérapeutique
4.
J Clin Endocrinol Metab ; 104(12): 5814-5822, 2019 12 01.
Article de Anglais | MEDLINE | ID: mdl-31290981

RÉSUMÉ

CONTEXT: Low serum adiponectin and high-density lipoprotein-cholesterol (HDL-C) levels are risk factors for cardiovascular disease. Patients with primary adrenal insufficiency are at higher risk of cardiovascular complications compared with healthy subjects. However, there is no information on the relationship between adiponectin and glucocorticoid replacement therapy in patients with secondary adrenal insufficiency (SAI). OBJECTIVE: To determine the effects of intrinsic adrenal function and glucocorticoid replacement therapy on serum adiponectin levels and lipid profile in patients with SAI. DESIGN: Part 1: a cross-sectional study. Part 2: a randomized, double-blind, crossover study. SETTING: Osaka University Hospital, Osaka, Japan. PATIENTS: Part 1: 58 patients diagnosed with nonfunctioning pituitary adenoma who underwent insulin tolerance test (ITT) for assessment of adrenal function. Part 2: 12 SAI patients randomly received hydrocortisone replacement therapy at a dose of 10, 20, or 30 mg/d for 4 weeks per term for three terms. OUTCOME MEASUREMENTS: Part 1: we analyzed the relationship between serum cortisol levels during ITT and serum adiponectin levels and the lipid profile. Part 2: serum adiponectin levels and lipid profile were measured every 4 weeks. RESULTS: Serum levels of adiponectin and HDL-C correlated significantly with peak cortisol levels after ITT. Serum adiponectin and HDL-C levels were significantly lower in patients with SAI than non-SAI. Serum levels of adiponectin and HDL-C increased in a hydrocortisone dose-dependent manner. CONCLUSIONS: Glucocorticoid replacement therapy increased serum levels of adiponectin, an adipose-derived anti-atherogenic factor, and HDL-C in patients with SAI.


Sujet(s)
Adiponectine/sang , Insuffisance surrénale/sang , Cholestérol HDL/sang , Glucocorticoïdes/effets indésirables , Hormonothérapie substitutive/effets indésirables , Insuffisance surrénale/traitement médicamenteux , Insuffisance surrénale/étiologie , Adulte , Études croisées , Études transversales , Relation dose-effet des médicaments , Méthode en double aveugle , Femelle , Humains , Hydrocortisone/sang , Mâle , Adulte d'âge moyen
5.
Hypertens Res ; 42(8): 1186-1191, 2019 08.
Article de Anglais | MEDLINE | ID: mdl-30850754

RÉSUMÉ

Primary aldosteronism (PA) is a major cause of secondary hypertension and presents a higher risk for cardio-cerebrovascular (CCV) events compared with essential hypertension. To diagnose PA after a positive screening test, at least one of three available confirmatory tests [the saline infusion test (SIT), the captopril challenge test (CCT) or the furosemide upright test (FUT)] should be performed. The aim of our study was to investigate the relationship between the number of positive confirmatory tests using SIT and CCT and the clinical presentation and prevalence of CCV events in 398 PA patients. The number of PA patients doubled when PA diagnosis was defined by positive results on either the SIT or CCT confirmatory tests (single positive) compared to positive results on both the SIT and CCT confirmatory tests (double positive). We also found a more typical clinical presentation of PA, such as the use of more antihypertensive drugs to control blood pressure and a higher incidence of hypokalemia, in PA patients with double positive confirmatory tests than in those with a single positive confirmatory test. The incidence of CCV events in PA patients with double positive confirmatory tests was significantly higher than that in those with a single positive confirmatory test. Our results demonstrated that the number of PA patients was doubled by the use of PA diagnostic criteria using a single positive confirmatory test compared to the use of double positive confirmatory tests. PA patients with double positive confirmatory tests were associated with a more typical clinical presentation and a higher incidence of CCV events than those with a single positive confirmatory test.


Sujet(s)
Angiopathies intracrâniennes/étiologie , Hyperaldostéronisme/complications , Sujet âgé , Angiopathies intracrâniennes/épidémiologie , Études transversales , Femelle , Humains , Hyperaldostéronisme/diagnostic , Incidence , Japon/épidémiologie , Mâle , Adulte d'âge moyen
6.
Endocrinology ; 160(3): 504-521, 2019 03 01.
Article de Anglais | MEDLINE | ID: mdl-30649271

RÉSUMÉ

In Cushing syndrome, excessive glucocorticoids lead to metabolic disturbances, such as insulin resistance, adipocyte hypertrophy, and liver steatosis. In vitro experiments have highlighted the importance of adipocyte glucocorticoid receptor (GR), but its metabolic roles in vivo have not been fully elucidated in Cushing syndrome. In this study, using clinical samples from patients with Cushing syndrome and adipocyte-specific GR knockout (AGRKO) mice, we investigated the roles of adipocyte GR and its clinical relevance in Cushing syndrome. Under chronic treatment with corticosterone, AGRKO mice underwent healthy adipose expansion with diminished ectopic lipid deposition and improved insulin sensitivity. These changes were associated with Atgl-mediated lipolysis through a novel intronic glucocorticoid-responsive element. Additionally, integrated analysis with RNA sequencing of AGRKO mice and clinical samples revealed that healthy adipose expansion was associated with dysregulation of tissue remodeling, preadipocyte proliferation, and expression of the circadian gene. Thus, our study revealed the roles of adipocyte GR on healthy adipose expansion and its multiple mechanisms in Cushing syndrome.


Sujet(s)
Adipocytes/métabolisme , Tissu adipeux/physiologie , Syndrome de Cushing/métabolisme , Récepteurs aux glucocorticoïdes/métabolisme , Adulte , Animaux , Études cas-témoins , Syndrome de Cushing/complications , Modèles animaux de maladie humaine , Stéatose hépatique/étiologie , Femelle , Humains , Insulinorésistance , Triacylglycerol lipase/génétique , Triacylglycerol lipase/métabolisme , Lipolyse , Mâle , Souris de lignée C57BL , Souris knockout , Adulte d'âge moyen , Récepteurs aux glucocorticoïdes/génétique
7.
J Clin Endocrinol Metab ; 104(5): 1637-1644, 2019 05 01.
Article de Anglais | MEDLINE | ID: mdl-30476255

RÉSUMÉ

CONTEXT: A paradoxical GH response to oral glucose (OG) is often found in acromegaly. However, the clinical characteristics of patients with acromegaly and a paradoxical GH response to OG (OG responders) remain unclear. OBJECTIVE: The aim of the present study was to define the clinical characteristics of OG responders with acromegaly. DESIGN: Retrospective study. SETTING: Hospitalized care at Osaka University Hospital. PATIENTS AND METHODS: Of 63 patients with acromegaly admitted to our hospital from January 2006 to January 2017, 19 were classified as OG responders and 44 as nonresponders. The clinical characteristics of these groups were compared. RESULTS: Before surgery, OG responders had substantially greater IGF-1 SD scores than nonresponders (P < 0.05), although no difference was found in basal GH levels between the two groups (P = 0.46). Regarding glucose metabolism, 120-minute plasma glucose and immunoreactive insulin after OG administration and hemoglobin A1c were significantly greater in OG responders than in nonresponders (P < 0.01, P < 0.05, P < 0.05, respectively). GH levels during octreotide or bromocriptine testing were decreased more significantly in OG responders than in nonresponders (P < 0.05, P < 0.05, respectively). The proportion of pituitary tumors with hypointensity on T2-weighted MRI was significantly greater in OG responders than in nonresponders (P < 0.05). The difference in IGF-1 and parameters of glucose metabolism described disappeared between the two groups after surgery. CONCLUSIONS: The paradoxical GH response reflected the clinical characteristics, especially IGF-I level, glucose metabolism, and drug efficacy in acromegaly. A paradoxical GH response, in addition to the nadir GH levels, to OG load is potentially useful for evaluation of the clinical characteristics of acromegaly.


Sujet(s)
Acromégalie/traitement médicamenteux , Glucose/administration et posologie , Hormone de croissance humaine/métabolisme , Facteur de croissance IGF-I/métabolisme , Tumeurs de l'hypophyse/traitement médicamenteux , Acromégalie/métabolisme , Acromégalie/anatomopathologie , Adulte , Marqueurs biologiques/analyse , Bromocriptine/pharmacologie , Études cas-témoins , Femelle , Études de suivi , Agents gastro-intestinaux/pharmacologie , Glucose/métabolisme , Antihormones/pharmacologie , Humains , Mâle , Adulte d'âge moyen , Octréotide/pharmacologie , Tumeurs de l'hypophyse/métabolisme , Tumeurs de l'hypophyse/anatomopathologie , Pronostic , Études rétrospectives
8.
J Endocr Soc ; 2(8): 860-869, 2018 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-30324179

RÉSUMÉ

CONTEXT: GH-releasing peptide 2 (GHRP2) stimulates the hypothalamic-pituitary-adrenal axis (HPA) through the GH secretagogue receptor (GHSR) in the hypothalamus, in which ghrelin is a natural ligand. Therefore, the GHRP2 test (GHRP2T) could be used instead of the insulin tolerance test (ITT). OBJECTIVE: Can the GHRP2T replace the ITT for evaluation of HPA? DESIGN: The present retrospective study analyzed the clinical features and laboratory data from 254 patients admitted for evaluation of hypopituitarism who underwent both GHRP2T and ITT. We analyzed the association between the maximum cortisol level (Fmax) during both tests. Adrenocortical insufficiency was diagnosed by ITT. The suitability of GHRP2T was examined using the receiver operating characteristic curve. RESULTS: A strong correlation was found between Fmax measured using both tests (r = 0.777, P < 0.0001). However, the sensitivity (64%) and specificity (79%) showed that the GHRP2T was not suitable for clinical use. Various factors influenced the correlation, probably through their effects on ghrelin and/or GHSR, including functional adenoma (P < 0.05) and sex (P < 0.05). No substantial correlation was found between Fmax measured using both tests in patients with prolactinoma (n = 30). The exclusion of patients with functional adenoma revealed no factors that affected the association in male patients; however, age and menstruation significantly influenced it in female patients (P < 0.05). Analysis of the data from male subjects without functional adenoma (n = 104) showed high sensitivity (95%) and specificity (85%) for the GHRP2T. CONCLUSION: ITT can be substituted with GHRP2T for assessment of HPA in male patients free of functional adenoma.

9.
Endocr J ; 65(8): 841-848, 2018 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-29925743

RÉSUMÉ

Circadian variations impact thyrotropin (TSH) secretion; in Cushing's syndrome (CS) patients, the nocturnal serum TSH surge is abolished. The aim of this prospective study is to examine whether serum TSH surge may be a useful diagnostic method for CS. This prospective study recruited 136 inpatients for differential diagnosis of CS or subclinical CS (SCS), and 21 inpatients with depression at Osaka University Hospital. Serum TSH surge was assessed by the midnight-to-morning serum TSH ratio (2300-2400 h to 0800-0900 h). The diagnostic accuracy (sensitivity and specificity) between TSH ratio and ordinary screening tests [low-dose dexamethasone suppression test (LDDST), late-night serum cortisol and urine free cortisol (UFC)] were compared. Twenty-two patients were diagnosed as CS (12 overt CS and 10 SCS) and the remaining 120 patients were excluded for CS. The diagnostic accuracy of TSH ratio (cutoff value 1.0) yielded sensitivity 90.9% [95% confidence interval (CI) 70.8-98.9], specificity 95.0% (95% CI 89.4-98.1), and a high positive and low negative likelihood ratio [18.2 (95% CI 8.2-40.1) and 0.096 (95% CI 0.026-0.359), respectively]. The specificity of TSH ratio was significantly higher than LDDST and midnight serum cortisol test. The sensitivity of TSH ratio was significantly higher than UFC. TSH ratio showed more than 1.0 in all patients with depression and CYP3A4 inducer users. TSH ratio is a novel supportive diagnostic method with higher specificity than the current diagnostic methods for CS.


Sujet(s)
Syndrome de Cushing/diagnostic , Hydrocortisone/métabolisme , Thyréostimuline/sang , Adulte , Sujet âgé , Syndrome de Cushing/sang , Dexaméthasone , Femelle , Humains , Hydrocortisone/sang , Hydrocortisone/urine , Mâle , Adulte d'âge moyen , Tests fonctionnels de l'axe hypophysosurrénalien , Études prospectives , Sensibilité et spécificité
10.
Nihon Hinyokika Gakkai Zasshi ; 109(3): 164-168, 2018.
Article de Japonais | MEDLINE | ID: mdl-31327859

RÉSUMÉ

A 64-year-old man was diagnosed as having Cushing's disease due to multiple lumbar compression fracture in 2009. Although various treatments including three times transsphenoidal surgery and twice radiotherapy were performed, his serum cortisol level rose again and intractable cutaneous ulcer occurred. Just after discontinuation of medication to treat the progression due of severe hepatic dysfunction, deep vein thrombosis and pulmonary artery embolism occurred. To control the Cushing's disease, laparoscopic bilateral adrenalectomy was performed.

11.
Intern Med ; 56(11): 1383-1385, 2017.
Article de Anglais | MEDLINE | ID: mdl-28566602

RÉSUMÉ

An impaired awareness of hypoglycemia is a serious problem in diabetic patients, which can lead to life-threatening severe hypoglycemia. Recurrent hypoglycemia attenuates the function of the central, mainly hypothalamic, nervous system and it causes an impaired awareness of hypoglycemia. Vitamin B12 deficiency is also associated with the dysfunction of central nervous system. We report a 72-year-old type 1 diabetic patient with vitamin B12 deficiency whose impaired awareness of hypoglycemia improved after 4 weeks of vitamin B12 administration with an increased counter-hormone secretion in response to hypoglycemia. We should recognize vitamin B12 deficiency as one of the causes of an impaired awareness of hypoglycemia in diabetic patients.


Sujet(s)
Conscience immédiate , Complications du diabète/physiopathologie , Hypoglycémie/physiopathologie , Carence en vitamine B12/traitement médicamenteux , Vitamine B12/usage thérapeutique , Sujet âgé , Complications du diabète/épidémiologie , Humains , Insuline , Mâle , Vitamine B12/administration et posologie , Carence en vitamine B12/épidémiologie
12.
Endocr J ; 64(5): 507-513, 2017 May 30.
Article de Anglais | MEDLINE | ID: mdl-28321052

RÉSUMÉ

Primary aldosteronism (PA) is caused by excess secretion of aldosterone and is an independent risk factor for cardio-cerebro-vascular (CCV) events. The goal of treatment of PA should include prevention of CCV events. A definitive diagnosis of PA is established by confirmatory tests [saline infusion test (SIT), furosemide upright test (FUT) and captopril challenge test (CCT)]. However, there is no information on whether the hormone levels measured by these confirmatory tests are associated with CCV events. The aim of this retrospective study was to elucidate the relationship between the results of the above confirmatory tests and prevalence of CCV disease in patients with PA. The study subjects were 292 PA patients who were assessed for past history of CCV events at the time of diagnosis of PA. CCV events were significantly higher in patients with positive than negative SIT (12.8% vs. 3.3%, p=0.04). There were no differences in the incidences of CCV events between patients with positive and negative CCT and FUT (CCT: 11.0% vs. 3.9%, p=0.13, FUT: 6.1% vs. 5.7%, p=0.93). Our results demonstrated a higher incidence of CCV disease in PA SIT-positive patients compared to those with negative test. SIT is a potentially useful test not only for the diagnosis of PA but also assessment of the risk of CCV events.


Sujet(s)
Maladies cardiovasculaires/épidémiologie , Angiopathies intracrâniennes/épidémiologie , Hyperaldostéronisme/complications , Hyperaldostéronisme/diagnostic , Sujet âgé , Captopril , Maladies cardiovasculaires/étiologie , Angiopathies intracrâniennes/étiologie , Tests diagnostiques courants , Femelle , Furosémide , Humains , Incidence , Mâle , Adulte d'âge moyen , Prévalence , Études rétrospectives , Appréciation des risques
13.
J Hypertens ; 35(5): 1079-1085, 2017 05.
Article de Anglais | MEDLINE | ID: mdl-28129245

RÉSUMÉ

BACKGROUND: Previous studies showed higher risk of cardiovascular and cerebrovascular (CCV) events in primary aldosteronism compared with essential hypertension, but the patients of these studies were limited to primary aldosteronism patients with high plasma aldosterone concentration (PAC). The introduction of the aldosterone-renin ratio as the screening test for primary aldosteronism led to the recognition of primary aldosteronism patients with normal PAC (nPA). However, there is no information on the risk of primary aldosteronism including nPA. METHOD: In this retrospectively and cross-sectional study, the clinical features and CCV event risk of primary aldosteronism at diagnosis including nPA were investigated and compared with essential hypertension. The study included 292 consecutive primary aldosteronism patients and 498 essential hypertension outpatients. All primary aldosteronism patients were diagnosed by autonomous aldosterone secretion using confirmatory tests, and then divided into nPA (n = 130) and primary aldosteronism patients with high PAC (hPA: n = 162) using a PAC cutoff level of less than 443 pmol/l (16 ng/dl), representing the normal upper limit of PAC. RESULTS: nPA patients were significantly older at diagnosis of primary aldosteronism and at onset of hypertension compared with hPA patients. They had milder hypokalemia and easier-to-control blood pressure. The results suggested that nPA could be considered a mild type of primary aldosteronism but not an early-stage hPA. Moreover, the risk of all CCV events in nPA was significantly lower than that in hPA (odds ratio 0.42, 95% confidence interval 0.18-0.90, P < 0.05) and not significantly higher than that in essential hypertension (odds ratio 0.95, 95% confidence interval 0.43-1.94, P = 0.899). CONCLUSION: This study suggests that aggressive diagnostic workout for nPA is less effective to prevent CCV events.


Sujet(s)
Aldostérone/sang , Maladies cardiovasculaires/épidémiologie , Hyperaldostéronisme/sang , Adulte , Sujet âgé , Pression sanguine , Études transversales , Hypertension essentielle , Femelle , Humains , Hypertension artérielle/physiopathologie , Hypokaliémie/complications , Mâle , Adulte d'âge moyen , Rénine/sang , Études rétrospectives , Facteurs de risque
15.
Endocr J ; 63(11): 1017-1023, 2016 Nov 30.
Article de Anglais | MEDLINE | ID: mdl-27498594

RÉSUMÉ

It is shown that glucocorticoids have discordant effects on plasma glucose concentration through their effects on hepatic glycogen deposition, gluconeogenesis and peripheral insulin resistance. Cushing's syndrome caused by cortisol overproduction is frequently accompanied with diabetes mellitus, but fasting plasma glucose (FPG) and post-glucose load plasma glucose levels are not examined in patients with Cushing's syndrome. The aim of this study was to investigate FPG, HbA1c and oral glucose tolerance test (OGTT) 2-h PG and their relationship in patients with Cushing's syndrome, in comparison with control subjects. Sixteen patients with Cushing's syndrome (ACTH-dependent 31%, ACTH-independent 69% and diabetes mellitus 50%) and 64 controls (32 patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI) were enrolled in this study. HbA1c and FPG in the patients with Cushing's syndrome were not different from the controls, whereas the FPG/HbA1c ratio was significantly lower in the patients with Cushing's syndrome than the controls. OGTT 2-h PG was significantly higher in the non-diabetic patients with Cushing's syndrome than the non-diabetic controls, while HbA1c was not different between both groups and FPG was significantly lower in the patients with Cushing's syndrome than the controls. HOMA-ß but not HOMA-R was significantly higher in the patients with Cushing's syndrome than the controls. In conclusion, FPG was rather lower in the patients with Cushing's syndrome than the controls. Postprandial PG or post-glucose loaded PG, but not FPG, is useful to evaluate the abnormality of glucose metabolism in patients with Cushing's syndrome.


Sujet(s)
Glycémie/métabolisme , Syndrome de Cushing/sang , Jeûne/sang , Période post-prandiale/physiologie , Adulte , Études cas-témoins , Femelle , Hyperglycémie provoquée , Humains , Insulinorésistance , Mâle , Adulte d'âge moyen
16.
Endocr J ; 63(11): 965-976, 2016 Nov 30.
Article de Anglais | MEDLINE | ID: mdl-27534814

RÉSUMÉ

Non-functioning pituitary adenoma (NFPA) is often associated with hypopituitarism. Diagnosis of hypopituitarism is important because of its poor prognosis and low quality of life. Among hypopituitarism, it is difficult to diagnose secondary adrenocortical insufficiency and GH deficiency without hormone stimulation test. Therefore, the aim of our study was to identify patients with NFPA who require more careful endocrinological examination. We examined the relationship between NFPA size and the prevalence of each hypopituitarism or the response of each anterior pituitary hormone by insulin tolerance test, LHRH test and TRH test. We studied 63 patients with NFPA admitted for evaluation of pituitary function and surgical indication. They were classified three groups by tumor diameter. The prevalence of GH deficiency, male secondary hypogonadism, secondary hypothyroidism and PRL deficiency were higher in the group of larger tumor diameter (p<0.0001, p<0.05, p<0.05 and p<0.05, respectively). However, that of secondary adrenocortical insufficiency only tended to be higher (p=0.07). In the group with small NFPA (less than 20 mm), the prevalence of secondary adrenocortical insufficiency was 38% although those of GH deficiency, male secondary hypogonadism, secondary hypothyroidism and PRL deficiency were 0%, 0% and 8% and 9%, respectively. Anterior pituitary hormone responses except TSH had significantly negative correlation with tumor diameter (ACTH: r=-0.40, GH: r=-0.57, LH: r=-0.69, FSH: r=-0.46, PRL: r=-0.36). The results suggested physicians should proactively suspect GH deficiency, male secondary hypogonadism and secondary hypothyroidism in patients with larger NFPA. On the other hand, adrenocortical function should be examined even in patients with small NFPA.


Sujet(s)
Adénomes/anatomopathologie , Hypopituitarisme/étiologie , Hormones antéhypophysaires/déficit , Tumeurs de l'hypophyse/anatomopathologie , Charge tumorale , Adénomes/complications , Adénomes/épidémiologie , Adénomes/métabolisme , Insuffisance surrénale/épidémiologie , Insuffisance surrénale/étiologie , Insuffisance surrénale/anatomopathologie , Sujet âgé , Femelle , Hospitalisation , Humains , Hypogonadisme/épidémiologie , Hypogonadisme/étiologie , Hypogonadisme/anatomopathologie , Hypopituitarisme/épidémiologie , Hypopituitarisme/métabolisme , Hypopituitarisme/anatomopathologie , Mâle , Adulte d'âge moyen , Hormones antéhypophysaires/métabolisme , Tumeurs de l'hypophyse/complications , Tumeurs de l'hypophyse/épidémiologie , Tumeurs de l'hypophyse/métabolisme , Prévalence
17.
Intern Med ; 55(9): 1143-7, 2016.
Article de Anglais | MEDLINE | ID: mdl-27150869

RÉSUMÉ

The 3243 A>G mutation in mitochondrial DNA is the most common cause of monogenic diabetes mellitus in Japan. A 45-year-old woman with mitochondrial diabetes and significant insulin resistance presented with hypoadiponectinemia despite a normal amount of visceral fat. Three months of treatment with pioglitazone (PIO) improved her blood glucose profile and response to the 75-g oral glucose tolerance test. These changes were accompanied by the amelioration of her insulin resistance and the impairment of early-phase insulin secretion. Her serum adiponectin levels increased to the normal range. In this case of mitochondrial diabetes, PIO was effective for glycemic control.


Sujet(s)
Diabète de type 2/traitement médicamenteux , Hypoglycémiants/usage thérapeutique , Récepteur PPAR gamma/agonistes , Thiazolidinediones/usage thérapeutique , Adiponectine/sang , Adiponectine/déficit , Glycémie/métabolisme , ADN mitochondrial/génétique , Diabète de type 2/sang , Diabète de type 2/génétique , Femelle , Hyperglycémie provoquée , Humains , Insuline/sang , Insulinorésistance/physiologie , Erreurs innées du métabolisme/traitement médicamenteux , Erreurs innées du métabolisme/étiologie , Adulte d'âge moyen , Mitochondries/effets des médicaments et des substances chimiques , Pedigree , Pioglitazone
18.
Endocr J ; 63(6): 545-54, 2016 Jun 30.
Article de Anglais | MEDLINE | ID: mdl-27025408

RÉSUMÉ

Cushing's disease (CD) and subclinical Cushing's disease (subCD) are both diseases caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. However, ACTH autonomy in subCD is weaker than in CD and there are no Cushingoid features in subCD. The differences of molecular mechanisms in ACTH autonomy between CD and subCD have not yet been reported. Therefore, we aimed to investigate the differences in molecular mechanisms of ACTH-secretion autonomy between CD and subCD. The study included 23 patients [7 CD, 6 subCD, and 10 non-functioning pituitary tumors (NFTs)] who underwent transsphenoidal surgery at the Osaka University Hospital between December 2009 and October 2013. Using quantitative real-time PCR, various ACTH-related gene expressions in tumor tissues from CD, subCD, and NFT were measured such as pro-opiomelanocortin (POMC), POMC transcription factor (Tpit, Pitx1, NeuroD1, and Nur77), POMC peptide processing enzymes (prohormone convertase: PC1/3 and PC2), and ACTH secretion-related factors (corticotropin-releasing hormone receptor 1: CRHR1 and glucocorticoid receptor α: GRα). Only Nur77 mRNA levels were significantly higher in CD than in subCD. Furthermore, we stained 6 CD and 6 subCD with anti-Nur77 antibody. All tumor samples from CD had Nur77 protein positive cells. On the other hand, Nur77 protein was expressed in only one tumor sample from subCD. This sample showed high expression of Nur77 mRNA. Nur77 is an important to regulate POMC transcription and negative-feedback by glucocorticoids. Nur77 gene expression levels might involve different autonomy of ACTH production between CD and subCD.


Sujet(s)
Adénome à ACTH/génétique , Adénomes/génétique , Hormone corticotrope/métabolisme , Membre-1 du groupe A de la sous-famille-4 de récepteurs nucléaires/génétique , Hypersécrétion hypophysaire d'ACTH/génétique , Adénome à ACTH/métabolisme , Adénomes/métabolisme , Adulte , Sujet âgé , Maladies asymptomatiques , Études cas-témoins , Rétrocontrôle physiologique , Femelle , Expression des gènes , Humains , Mâle , Adulte d'âge moyen , Hypersécrétion hypophysaire d'ACTH/métabolisme , Voie de sécrétion/génétique , Jeune adulte
19.
Endocr J ; 63(1): 47-52, 2016.
Article de Anglais | MEDLINE | ID: mdl-26536898

RÉSUMÉ

Cushing's syndrome (CS) is a clinical state caused by chronic excess of glucocorticoid, and results in hypertension, impaired glucose tolerance, and dyslipidemia. Recently, a mild state of pituitary CS without typical Cushingoid appearance (subclinical Cushing's disease; SCD) has been identified. However, the true prevalence of SCD and its effect on metabolic disorders remain obscure. The aim of this prospective study was to determine the prevalence of SCD according to the guideline proposed by the working group of the Japanese Ministry of Health, Welfare and Labor, and to assess the outcome of surgery on metabolic disorders. The prevalence of SCD was investigated in 105 consecutive patients diagnosed with pituitary adenomas by MRI. ACTH-dependent hypercortisolism was diagnosed based on the results of the 0.5 mg dexamethasone suppression test (serum cortisol >3.0 µg/dL) plus one positive finding of the following two tests: midnight serum cortisol level >5.0 µg/dL or ACTH increase >50% after 1-deamino-5-D-arginine vasopressin (DDAVP) challenge. The final diagnosis of SCD was established by positive staining for ACTH in surgically-excised pituitary adenoma. Three patients (4.8%) were diagnosed with SCD among 62 patients with pituitary adenoma. Transsphenoidal adenomectomy partially resulted in improvement of blood pressure and glucose metabolism in SCD patients. Our results emphasize the importance of SCD screening in patients with pituitary tumors, especially in those patients with metabolic disorders.


Sujet(s)
Adénome à ACTH/sang , Adénomes/sang , Hormone corticotrope/sang , Dépistage de masse , Hypersécrétion hypophysaire d'ACTH/diagnostic , Hypersécrétion hypophysaire d'ACTH/épidémiologie , Adénome à ACTH/diagnostic , Adénome à ACTH/épidémiologie , Adénome à ACTH/chirurgie , Adénomes/diagnostic , Adénomes/épidémiologie , Adénomes/chirurgie , Hormone corticotrope/analyse , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Maladies asymptomatiques , Humains , Imagerie par résonance magnétique , Dépistage de masse/méthodes , Dépistage de masse/statistiques et données numériques , Adulte d'âge moyen , Hypersécrétion hypophysaire d'ACTH/étiologie , Hypersécrétion hypophysaire d'ACTH/chirurgie , Prévalence , Résultat thérapeutique , Jeune adulte
20.
Diabetol Int ; 7(1): 89-94, 2016 Mar.
Article de Anglais | MEDLINE | ID: mdl-30603248

RÉSUMÉ

To date, promising strategies for treating glucocorticoid (GC)-induced diabetes with antidiabetic drugs have not been established. We herein report the case of a woman with GC-induced diabetes in which we compared the efficacy of two kinds of orally administered antidiabetic drugs sitagliptin and metformin by continuous glucose monitoring (CGM) and meal-challenge test (MCT). As a result, CGM showed that daily fluctuation of blood glucose levels was reduced during administration of metformin but not during administration of sitagliptin. On the other hand, MCT showed that administration of metformin reduced plasma glucose levels accompanied by the decrease of plasma insulin levels and the increase of plasma glucagon levels, whereas administration of sitagliptin had little effects on these parameters. This case is the first report to compare the efficacy between sitagliptin and metformin in glucose homeostasis by CGM and MCT in a patient with GC-induced diabetes.

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