Daisuke Tamada

Glycated albumin is set lower in relation to plasma glucose levels in patients with Cushing's syndrome

BACKGROUND Glycated albumin (GA) is an indicator of glycemic control, which has some specific characters in comparison with HbA1c. Since glucocorticoids (GC) promote protein catabolism including serum albumin, GC excess state would influence GA levels. We therefore investigated GA levels in patients with Cushings syndrome. METHODS We studied 16 patients with Cushings syndrome (8 patients had diabetes mellitus and the remaining 8 patients were non-diabetic). Thirty-two patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI were used as controls. RESULTS In the patients with Cushings syndrome, GA was significantly correlated with HbA1c, but the regression line shifted downwards as compared with the controls. The GA/HbA1c ratio in the patients with Cushings syndrome was also significantly lower than the controls. HbA1c in the non-diabetic patients with Cushings syndrome was not different from the non-diabetic controls, whereas GA was significantly lower. In 7 patients with Cushings syndrome who performed self-monitoring of blood glucose, the measured HbA1c was matched with HbA1c estimated from mean blood glucose, whereas the measured GA was significantly lower than the estimated GA. CONCLUSIONS We clarified that GA is set lower in relation to plasma glucose levels in patients with Cushings syndrome.

Estimation of HbA1c response to sitagliptin by change in glycated albumin level for 2 weeks

Aims/Introduction:  Since glycated albumin (GA) reflects shorter‐term (about 2 weeks) control of plasma glucose levels compared with HbA1c, GA is thought to be a useful glycemic control indicator for the early period following commencement of the treatment of diabetes. In this study, we attempted to estimate HbA1c using the change in GA level before and after the first 2 weeks (ΔGA2w) of administration of sitagliptin, a dipeptidyl peptidase‐4 (DPP‐4) inhibitor.

Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism.

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.

Hyperthyroidism due to thyroid-stimulating hormone secretion after surgery for Cushing's syndrome : a novel cause of the syndrome of inappropriate secretion of thyroid-stimulating hormone

CONTEXT Hyperthyroidism with the syndrome of inappropriate secretion of TSH (SITSH) occurred by a decrease in hydrocortisone dose after surgery for Cushings syndrome. This is a novel cause of SITSH. OBJECTIVE The aim of this study was to describe and discuss 2 cases of SITSH patients that were found after surgery for Cushings syndrome. We also checked whether SITSH occurred in 7 consecutive patients with Cushings syndrome after surgery. PATIENTS AND METHODS A 45-year-old Japanese woman with ACTH-independent Cushings syndrome and a 37-year-old Japanese man with ACTH-dependent Cushings syndrome presented SITSH caused by insufficient replacement of hydrocortisone for postoperative adrenal insufficiency. When the dose of hydrocortisone was reduced to less than 20 mg/d within 18 days after surgery, SITSH occurred in both cases. We examined whether the change of the hydrocortisone dose induced the secretion of TSH. Free T₃ and TSH were normalized by the hydrocortisone dose increase of 30 mg/d, and these were elevated by the dose decrease of 10 mg/d. We also checked TSH and thyroid hormone levels of the 7 consecutive patients with Cushings syndrome after surgery. Six (66.6 %) of 9 patients showed SITSH. CONCLUSIONS This is the first report that insufficient replacement of hydrocortisone after surgery for Cushings syndrome caused SITSH. Hyperthyroidism by SITSH as well as adrenal insufficiency can contribute to withdrawal symptoms of hydrocortisone replacement. We need to consider the possibility of SITSH for the pathological evaluation of withdrawal syndrome of hydrocortisone replacement.

Clinical significance of screening for subclinical Cushing’s disease in patients with pituitary tumors

Cushings 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 Cushings 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.

Exenatide Alters Absorption of Hydrocortisone in a Diabetic Patient With Panhypopituitarism: Iatrogenic Adrenal Insufficiency

Exenatide, which is widely used for patients with type 2 diabetes, inhibits gastric emptying and small intestinal motility (1). We report a diabetic patient with panhypopituitarism who developed general fatigue and appetite loss with hypotension because of absorption delay of hydrocortisone in association with exenatide treatment. A 50-year-old diabetic woman was admitted to our hospital because of poor glycemic control in December 2011. She had been treated with hydrocortisone and L-thyroxine for hypopituitarism as a result from surgeries and radiotherapy for carniopharyngioma. She was started on treatment with 5 μg exenatide twice a day. Nine days after exenatide treatment, the dose was increased …

Postoperative changes in bone metabolism and bone mineral density in Japanese patients with acromegaly: a 3-year prospective study

Growth hormone and insulin-like growth factor-I play important roles in regulating bone metabolism and bone mineral density in adulthood. However, the effect of excess growth hormone on bone metabolism and bone mineral density is not fully understood. Here, we investigated the long-term changes in bone metabolism and bone mineral density after a rapid decline in growth hormone levels due to transsphenoidal surgery in acromegalic patients. Eighteen acromegalic patients (10 males and 8 females) who underwent transsphenoidal surgery were enrolled in this prospective study. Bone formation marker (serum bone alkaline phosphatase), bone resorption marker (urinary type I collagen cross-linked N-telopeptide), and bone mineral density were measured before surgery and at 3 months, 1 year, and 3 years after transsphenoidal surgery. While both serum bone alkaline phosphatase and urinary type I collagen cross-linked N-telopeptide levels decreased significantly after surgery, serum bone alkaline phosphatase/urinary type I collagen cross-linked N-telopeptide ratio was significantly increased at 3 months and 3 years after surgery. Bone mineral density did not change markedly after surgery. In conclusion, the rapid decline in growth hormone levels following transsphenoidal surgery had no marked effect on bone mineral density for up to 3 years, despite significant changes in levels of bone turnover makers post-surgery.

Serum albumin-adjusted glycated albumin is an adequate indicator of glycemic control in patients with Cushing's syndrome

OBJECTIVES We recently reported that glycated albumin (GA) in patients with Cushings syndrome is low. In the present study, we examined whether serum albumin (SA)-adjusted GA (SAaGA) is an adequate indicator of glycemic control in patients with Cushings syndrome. DESIGN AND METHODS We studied 26 patients with Cushings syndrome (13 patients without diabetes and 13 patients with diabetes). Twenty six non-diabetic subjects and 26 patients with type 2 diabetes mellitus matched for age, sex and BMI were used as the controls. SAaGA was calculated using the regression formula between SA and GA in non-diabetic patients with Cushings syndrome and non-diabetic subjects. RESULTS SA showed a significant correlation with GA in non-diabetic patients with Cushings syndrome and non-diabetic subjects. GA, but not SAaGA, in non-diabetic patients with Cushings syndrome was significantly lower than that in the non-diabetic controls. Furthermore, the GA/HbA1c ratio, but not the SAaGA/HbA1c ratio, in diabetic patients with Cushings syndrome was significantly lower than that in the diabetic controls. The measured GA in the patients with Cushings syndrome was significantly lower than the estimated GA, but there was no difference between SAaGA and the estimated GA. CONCLUSIONS The present findings suggest that SAaGA is an adequate indicator of the glycemic control in patients with Cushings syndrome.

Evaluation of Hypothalamic–Pituitary–Adrenal Axis by the GHRP2 Test: Comparison With the Insulin Tolerance Test

Abstract 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.

Saline Infusion Test highly associated with the incidence of cardio- and cerebrovascular events in primary aldosteronism

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.