A Case of Lymphocytic Infundibulo-neurohypophysitis Exhibiting Spontaneous Regression.

Lymphocytic infundibulo-neurohypophysitis (LINH) is a rare autoimmune inflammatory process that selectively affects the neurohypophysis and the pituitary stalk, typically presenting with central diabetes insipidus (CDI). LINH is considered underdiagnosed because the definitive diagnosis requires invasive pituitary surgery with a high risk of complications. We present a case of CDI resulting from LINH, which was treated with conservative management, eschewing both glucocorticoid treatment and pituitary surgery. At presentation, the hormonal assessment indicated the presence of CDI without anterior pituitary dysfunction. Magnetic resonance imaging revealed stalk thickening without a posterior pituitary bright spot, and anti-rabphilin-3A antibodies were positive in serum. Collectively, we made a diagnosis of LINH. Considering that the patient did not exhibit any symptoms of mass effect, we chose conservative treatment with desmopressin acetate. One year later, the stalk thickening regressed spontaneously without surgical or glucocorticoid treatment, although the posterior pituitary bright spot remained absent, and CDI did not improve. The inflammatory process of LINH is mostly self-limited and recovers spontaneously, whereas life-long desmopressin treatment may be required because of pituitary stalk fibrosis and atrophy. Our case highlights the importance of noninvasive diagnosis and careful follow-up in preventing unnecessary interventions for patients with LINH.

Ovarian Hyperstimulation Syndrome Caused by Functional Gonadotroph Pituitary Adenoma.

Functional gonadotroph adenomas (FGAs) are rare, manifesting symptoms like menstrual irregularities or ovarian hyperstimulation syndrome (OHSS). We present a case of OHSS caused by an FGA during the follow-up of a pituitary tumor initially considered nonfunctioning. The patient presented with lower abdominal pain, abdominal swelling, and dyspnea. Magnetic resonance imaging (MRI) revealed 15 cm enlarged ovarian cysts and pleural effusion. Laboratory examination showed an elevated serum estradiol (E2) level (5741.4 pmol/L [1564.0 pg/mL]), suppressed luteinizing hormone, and nonsuppressed follicular-stimulating hormone (FSH). However, no pituitary hormone disorders were observed when a 19 mm pituitary tumor was discovered 11 months prior. Given the absence of human chorionic gonadotropin (hCG) administration, OHSS due to the FGA was suspected. Cabergoline, known for alleviating the severity of OHSS, was administered, but the ovarian cysts continued to enlarge. Subsequently, endoscopic transsphenoidal surgery was performed, and immunohistochemical analysis confirmed the diagnosis of the FSH-producing adenoma. Follow-up MRI scans showed reduced ovarian cysts and successful pituitary tumor resection with a reduced E2 level. This case highlights the importance of considering FGAs when encountering OHSS without hCG administration or following up on pituitary tumors in premenopausal female patients to take appropriate measures for accurate diagnosis and management.

Exploratory study on glycemic control improvement for patients with diabetes mellitus by appropriate re-education on insulin self-injection technique during COVID-19 pandemic.

AIMS: To conduct a study on glycemic control improvement by appropriate re-education on the self-injection technique (SIT) in patients with diabetes mellitus undergoing insulin therapy. METHODS: Patients who received appropriate SIT and were treated with insulin for more than a year were re-educated. For the observation period of six months, the subjects' SIT was checked, and hemoglobin A1c (HbA1c) levels were measured at each visit. HbA1c levels, insulin doses, and behavioral changes in SIT were investigated at baseline and at the end of the observation period. RESULTS: In the per-protocol set population, the HbA1c level decreased by 0.2 % (2.0 mmol/mol) on average, showing a significant difference (p = 0.009). No significant difference was observed in the proportion of subjects with decreased HbA1c levels, changes in total daily insulin doses, or blood glucose levels. Four of the six SIT items covered by re-education were improved. CONCLUSIONS: Providing re-education on insulin SIT was considered effective in reducing HbA1c levels and improving adherence to proper SIT.

Plant sterol hyperabsorption caused by uncontrolled diabetes in a patient with a heterozygous ABCG5 variant.

Plant sterol intake is widely recommended for patients with cardiovascular risk factors based on the inhibitory effect on intestinal cholesterol absorption. Although plant sterols, once absorbed, can promote atherosclerosis, their intake is believed to be safe because of poor absorption, except in rare hyperabsorbers with homozygous ABCG5/8 mutations. We report a case of new-onset type 1 diabetes accompanied by hypercholesterolemia. At the initial presentation with diabetic ketoacidosis, the patient showed marked hypercholesterolemia. Whole-exome sequencing revealed a heterozygous pathogenic variant in ABCG5 (p.R419H). The initial serum plant sterol levels were markedly high (sitosterol 32.5 µg/mL, campesterol 66.0 µg/mL), close to the range observed in patients with homozygous ABCG5/8 mutations, which were largely reduced by insulin treatment without ezetimibe. The addition of ezetimibe normalized plant sterol levels. These findings provide the first evidence that uncontrolled diabetes plays a causal role in the pathogenesis of phytosterolemia.

Exploring a Suitable Marker of Glycemic Response to Dulaglutide in Patients with Type 2 Diabetes: A Retrospective Study.

INTRODUCTION: Previous studies suggested that ß-cell function markers such as fasting and postprandial serum C-peptide and C-peptide increment (FCPR, PCPR, and ΔCPR, respectively) may be useful in estimating glycemic response to glucagon-like peptide-1 receptor agonists. However, it remains elusive whether baseline glycemic control confounds these markers. Here we aimed to identify the least confounded ß-cell function markers and investigate whether these markers could predict glycemic response to dulaglutide. METHODS: We evaluated FCPR, PCPR, and ΔCPR levels in patients with type 2 diabetes who initiated dulaglutide treatment after a standardized meal tolerance test (MTT). We first investigated the confounding effects of baseline HbA1c on ß-cell function markers using Pearson's correlation test. Then, we evaluated the association between each ß-cell function marker and glycemic response (HbA1c change 0-6 months) to dulaglutide using generalized linear model and logistic regression analysis with adjustment for baseline HbA1c. RESULTS: In 141 patients, baseline HbA1c was significantly inversely correlated with PCPR and ΔCPR (P < 0.01 for both) but not with FCPR (r = 0.02; P = 0.853), suggesting that FCPR was the marker least confounded by baseline glycemic control. Of all patients, 59 continued dulaglutide for at least 6 months without initiating any additional glucose-lowering medications. Mean ± SE HbA1c change 0-6 months was - 1.16 ± 0.17% (P < 0.001 vs. baseline). The ß-cell function markers were significantly associated with HbA1c change 0-6 months in the generalized linear model. FCPR was also a significant predictor for achieving a reduction in HbA1c of at least 1% (P = 0.044) with an area under the receiver operating characteristic curve of 0.83 (sensitivity = 0.81 and specificity = 0.79). CONCLUSION: Fasting and meal-induced C-peptide levels are associated with glycemic response to dulaglutide, among which FCPR is least confounded by baseline glycemic control, suggesting its utility as a marker for glycemic response to dulaglutide.

First Japanese Family With PDX1-MODY (MODY4): A Novel PDX1 Frameshift Mutation, Clinical Characteristics, and Implications.

CONTEXT: The PDX1 gene encodes pancreatic and duodenal homeobox, a critical transcription factor for pancreatic ß-cell differentiation and maintenance of mature ß-cells. Heterozygous loss-of-function mutations cause PDX1-MODY (MODY4). CASE DESCRIPTION: Our patient is an 18-year-old lean man who developed diabetes at 16 years of age. Given his early-onset age and leanness, we performed genetic testing. Targeted next-generation sequencing and subsequent Sanger sequencing detected a novel heterozygous frameshift mutation (NM_00209.4:c.218delT. NP_000200.1: p.Leu73Profs*50) in the PDX1 transactivation domain that resulted in loss-of-function and was validated by an in vitro functional study. The proband and his 56-year-old father, who had the same mutation, both showed markedly reduced insulin and gastric inhibitory polypeptide (GIP) secretion compared with the dizygotic twin sister, who was negative for the mutation and had normal glucose tolerance. The proband responded well to sitagliptin, suggesting its utility as a treatment option. Notably, the proband and his father showed intriguing phenotypic differences: the proband had been lean for his entire life but developed early-onset diabetes requiring an antihyperglycemic agent. In contrast, his father was overweight, developed diabetes much later in life, and did not require medication, suggesting the oligogenic nature of PDX1-MODY. A review of all reported cases of PDX1-MODY also showed heterogeneous phenotypes regarding onset age, obesity, and treatment, even in the presence of the same mutation. CONCLUSIONS: We identified the first Japanese family with PDX1-MODY. The similarities and differences found among the cases highlight the wide phenotypic spectrum of PDX1-MODY.

Sporadic Pseudohypoparathyroidism Type 1B in Monozygotic Twins: Insights Into the Pathogenesis of Methylation Defects.

CONTEXT: Sporadic pseudohypoparathyroidism type 1B (sporPHP1B) is an imprinting disease without a defined genetic cause, characterized by broad methylation changes in differentially methylated regions (DMRs) of the GNAS gene. OBJECTIVE: This work aims to provide insights into the causative event leading to the GNAS methylation defects through comprehensive molecular genetic analyses of a pair of female monozygotic twins concordant for sporPHP1B who were conceived naturally, that is, without assisted reproductive techniques. METHODS: Using the leukocyte genome of the twins and family members, we performed targeted bisulfite sequencing, methylation-sensitive restriction enzyme (MSRE)-quantitative polymerase chain reaction (qPCR), whole-genome sequencing (WGS), high-density single-nucleotide polymorphism (SNP) array, and Sanger sequencing. RESULTS: Methylation analyses by targeted bisulfite sequencing and MSRE-qPCR revealed almost complete losses of methylation at the GNAS AS, XL, and A/B DMRs and a gain of methylation at the NESP55 DMR in the twins, but not in other family members. Except for the GNAS locus, we did not find apparent methylation defects at other imprinted genome loci of the twins. WGS, SNP array, and Sanger sequencing did not detect the previously described genetic defects associated with familial PHP1B. Sanger sequencing also ruled out any novel genetic alterations in the entire NESP55/AS region. However, the analysis of 28 consecutive SNPs could not exclude the possibility of paternal heterodisomy in a span of 22 kb comprising exon NESP55 and AS exon 5. CONCLUSION: Our comprehensive analysis of a pair of monozygotic twins with sporPHP1B ruled out all previously described genetic causes. Twin concordance indicates that the causative event was an imprinting error earlier than the timing of monozygotic twinning.

Alu-Mediated MEN1 Gene Deletion and Loss of Heterozygosity in a Patient with Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by mutations of the tumor suppressor gene MEN1. Most of the germline MEN1 gene mutations have been small mutations, and the whole gene deletion is rarely observed. In the present study, we revealed Alu retrotransposon-mediated de novo germline deletion of the whole MEN1 gene and somatic copy-neutral loss of heterozygosity (LOH) in a patient with MEN1. The patient is a 39-year-old woman who was referred to our department for the management of prolactinoma. She was also diagnosed with primary hyperparathyroidism and suspected of MEN1. Although nucleotide sequencing did not detect any MEN1 gene mutations, multiplex ligation-dependent probe amplification (MLPA) revealed a large germline deletion of the MEN1 gene. Subsequent quantitative polymerase chain reaction (qPCR)-based copy number mapping showed a monoallelic loss of approximately 18.5-kilobase region containing the whole MEN1 gene. Intriguingly, the 2 breakpoints were flanked by Alu repetitive elements, suggesting the contribution of Alu/Alu-mediated rearrangements (AAMR) to the whole MEN1 gene deletion. Furthermore, copy number mapping using MLPA and qPCR in combination with single nucleotide polymorphism analysis revealed copy-neutral LOH as a somatic event for parathyroid tumorigenesis. In conclusion, copy number mapping revealed a novel combination of Alu/Alu-mediated de novo germline deletion of the MEN1 gene and somatic copy-neutral LOH as a cytogenetic basis for the MEN1 pathogenesis. Moreover, subsequent in silico analysis highlighted the possible predisposition of the MEN1 gene to Alu retrotransposon-mediated genomic deletion.

Facilitating screening of Klinefelter syndrome among patients with diabetes.

Klinefelter syndrome (KS) is frequently complicated by diabetes. However, it is severely underdiagnosed due to a lack of reliable screening methods. We diagnosed two patients with KS at the Center for Diabetes and Endocrinology, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan. By comparing the patients with 39 non-KS patients with diabetes, we propose a screening tool for KS in patients with diabetes.

"Switched" metabolic acidosis in mitochondrial diabetes mellitus.

A patient with mitochondrial diabetes mellitus developed diabetic ketoacidosis. During insulin treatment, although diabetic ketoacidosis improved, lactic acidosis unexpectedly worsened. This clinical course, named "switched metabolic acidosis," could reflect the unique pathophysiology of the mitochondrial disorder.

Glucose excursions and hypoglycemia in patients with type 2 diabetes treated with mitiglinide/voglibose versus glimepiride: A randomized cross-over trial.

BACKGROUND: Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy. METHODS: This cross-over trial included 20 patients with type 2 diabetes. After initiating vildagliptin 100 mg, patients were randomly assigned to receive mitiglinide 10 mg/voglibose 0.2 mg three times daily for 3 days followed by glimepiride 1 mg once daily for the subsequent 3 days as add-on therapy, or vice versa. Glucose excursions and hypoglycemia frequency were measured using 24-h continuous glucose monitoring. Metabolic profile changes were evaluated using a meal tolerance test. RESULTS: The mean glucose levels in the mitiglinide/voglibose and glimepiride phases were identical (8.01 vs 8.24 mmol/L, respectively). However, during the mitiglinide/voglibose phase compared with the glimepiride phase, the standard deviation of glucose (1.30 vs 2.10 mmol/L; P < 0.001), mean amplitude of glycemic excursions (3.47 vs 5.28 mmol/L; P < 0.001), M-value (24.6 vs 70.0; P < 0.001), continuous overlapping net glycemic action for a 1-h time interval (22.6 vs 31.0; P < 0.001), and area under the curve >10 mmol/L (0.18 vs 0.52 mmol/L per h; P < 0.001) were significantly lower. Hypoglycemia (glucose <3.8 mmol/L) was not observed during the mitiglinide/voglibose phase, but occurred 0.35 times/day in those taking glimepiride. Moreover, the mitiglinide/voglibose phase had higher premeal and lower post-meal glucose levels than the glimepiride phase. CONCLUSIONS: Adding mitiglinide/voglibose to vildagliptin therapy results in more efficient postprandial glucose control and less hypoglycemia than adding glimepiride.

Basal and Bolus Insulin Dose Changes after Switching Basal Insulin to Insulin Degludec in Patients with Type 1 Diabetes Mellitus: A Pilot Study.

BACKGROUND AND OBJECTIVES: Ultra-long-acting insulin degludec (DEG) has a longer duration of action and less daily variability relative to other basal insulin (BI), and thus may benefit patients with type 1 diabetes mellitus (T1DM). We examined the impact of switching BI to DEG on glycemic control and insulin dose in T1DM. METHODS: T1DM patients (n = 22; six male; mean age: 64.5 ± 12.6 years) receiving basal-bolus insulin therapy were included. Initially, the BI dose was replaced with DEG in a 1:1 ratio; 80-100% of the total dose was replaced with DEG for multiple basal insulin injections. DEG was titrated according to study protocol. Changes in HbA1c, daily insulin dose, glycemic self-monitored blood glucose variations, and hypoglycemia frequency were evaluated for 24 weeks. RESULTS: Once-daily DEG significantly decreased HbA1c levels when switched from once-daily BI (7.9 ± 0.8 vs. 7.5 ± 0.9%, p = 0.020) and maintained HbA1c when switched from twice-daily BI (8.5 ± 1.6 vs. 8.4 ± 1.2%, p = 0.457). The BI dose decreased by -7.8 ± 13.9% (p = 0.017) and -16.6 ± 16.9% (p = 0.050) when switched from once-daily BI and twice-daily BI, respectively. The total bolus insulin dose significantly decreased when switched from once-daily BI (21.7 ± 8.3 to 19.3 ± 8.8 U/day, p = 0.016) especially in the injection before breakfast and evening meal. Body weight and hypoglycemia frequency was not significantly different. CONCLUSION: DEG improved glycemic control when switched from once-daily BI and maintained glycemic control when switched from twice-daily BI without increasing hypoglycemia.

The Eradication of Helicobacter pylori does not Affect Glycemic Control in Japanese Subjects with Type 2 Diabetes.

Since infection with Helicobacter pylori has been suggested to play a pathogenic role in diabetes mellitus, we investigated whether eradication therapy for H. pylori might affect glycemic control in Japanese subjects with type 2 diabetes. A total of 72 subjects (55 males, 17 females; aged 63.7 years) with type 2 diabetes who received eradication therapy for H. pylori were included. The change of their blood glycosylated hemoglobin (A1C) levels 3 months before (-3 m) the H. pylori eradication, as well as 3 months (3 m) and 6 months (6 m) after were evaluated. Their A1C levels did not show any significant change after therapy {6.9 [0.1]% (-3 m) to 7.0 [0.1]% (3 m); P = 0.3, 7.0 [0.1] (6 m); P = 0.3}. Our findings suggest that the eradication therapy for H. pylori does not, at least profoundly, affect glycemic control in Japanese subjects with type 2 diabetes.

Safety, humoral and cell-mediated immune responses to herpes zoster vaccine in subjects with diabetes mellitus.

OBJECTIVE: To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. METHODS: A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. RESULTS: The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. CONCLUSION: The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus.

Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

Less variation of R-R interval of electrocardiogram in nonobese type 2 diabetes with nocturnal intermittent hypoxia.

Obesity is a major risk factor for sleep-disordered breathing (SDB). However, many Japanese subjects with diabetes are less obese despite compared with Caucasian. We evaluated the relationship between SDB and clinical characteristics other than obesity, especially in relation to cardiac autonomic neuropathy (CAN) in Japanese subjects with diabetes. The study included a total of 261 consecutive Japanese subjects with type 2 diabetes, including nonobese subjects defined as BMI <25 kg/m² for Japanese. SDB was screened by 4% oxygen desaturation index (ODI) level of 5 or more events per hour, which was measured by nocturnal pulse oximetry. CAN was examined with the variation of R-R intervals (CVRR). The SDB were found in 24.5% of total subjects and 16.3% of nonobese subjects with type 2 diabetes, respectively. The nonobese type 2 diabetes subjects with SDB had significantly lower coefficient of CVRR than those without SDB. Multiple regression analysis revealed that BMI and heart rate were significant independent factors for SDB in total subjects with type 2 diabetes, but CVRR was the only significant independent factor for SDB in nonobese subjects with type 2 diabetes. These findings suggest that the presence of SDB should be kept in mind in type 2 diabetic patients with abnormality in CVRR variation in electrocardiogram even though they are not obese.

The limited usefulness of the treadmill test or a risk-guided approach in screening for asymptomatic coronary heart disease in Japanese patients with type 2 diabetes.

OBJECTIVE: We prospectively investigated the efficacy of the screening methods for asymptomatic coronary heart disease (CHD) in Japanese patients with type 2 diabetes using the treadmill tolerance test (TTT) as a first-line test or the American Diabetes Association (ADA) guidelines. METHODS: The subjects included consecutive inpatients with type 2 diabetes (n=331) assessed with both electrocardiogram (ECG) at rest and TTT. Subjects with abnormal TTT findings were evaluated using stress myocardial perfusion scintigraphy (MPS). RESULTS: A total of 60 out of 69 subjects with positive TTT findings underwent MPS, among whom a total of 22 subjects (6.6% of the total number of subjects) had positive MPS results. Among those with positive MPS results, a total of 14 subjects underwent coronary angiography, eight of whom were determined to have significant coronary artery stenosis. The prevalence rates of hypertension and micro/macroalbuminuria were significantly higher in the MPS-positive group (77.3% and 54.5%, respectively) than in the TTT-negative group (44.7% and 27.1%, respectively). Among the subjects with positive MPS results, 68.2% met the 1998 ADA criteria. CONCLUSION: Neither the TTT as a first-line test nor the ADA guidelines are sufficiently adequate screening methods to detect asymptomatic CHD in Japanese subjects with type 2 diabetes. Conducting routine screening for asymptomatic CHD in Japanese patients with type 2 diabetes may therefore not be very useful.

Relationship between telmisartan dose and glycaemic control in Japanese patients with type 2 diabetes mellitus and hypertension: a retrospective study.

BACKGROUND AND OBJECTIVES: Telmisartan has been reported to have beneficial effects on insulin resistance and lipid profiles by acting as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. In this study we investigated the relationship between telmisartan dose and glycaemic control in Japanese subjects with type 2 diabetes mellitus and hypertension. METHODS: Patients (n = 263) who were prescribed telmisartan 20, 40 or 80 mg/day at our clinic were retrospectively identified from our clinical database. Only patients without changes in their treatments for diabetes and hypertension for 6 months after starting telmisartan were included in this study. Glycosylated haemoglobin A(1c) (HbA(1c)) levels were measured at 0, 3 and 6 months after starting telmisartan. RESULTS: At 3 and 6 months after starting telmisartan, HbA(1c) levels were significantly decreased in patients treated with telmisartan 40 or 80 mg/day but not in patients treated with telmisartan 20 mg/day (mean ± standard error change at 6 months: -0.29 ± 0.10%, p < 0.001; -0.48 ± 0.15%, p < 0.001; and -0.03 ± 0.10%, p = 0.33; respectively). When patients were classified into two groups by telmisartan dose (20 vs ≥40 mg/day), there was no significant correlation between baseline HbA(1c) and change in HbA(1c) levels over time in the 20 mg/day group. However, in patients treated with ≥40 mg/day of telmisartan, baseline HbA(1c) was negatively correlated with the change in HbA(1c) at 6 months. Multiple regression analysis confirmed that baseline HbA(1c) and telmisartan dose were the predictive factors. CONCLUSION: Our results suggest that telmisartan influences glycaemic control in a dose-dependent manner; doses ≥40 mg/day may be needed to improve glycaemic control. Our data also suggest that patients with higher baseline HbA(1c) may experience greater improvements in glycaemic control with telmisartan.

Adrenal cavernous hemangioma with subclinical Cushing's syndrome: report of a case.

Cavernous hemangioma of the adrenal gland is a rare tumor, which does not usually have endocrinological function. We report to our knowledge, the third documented case of a functioning adrenal hemangioma. Interestingly, this tumor indicated glucocorticoid hypersecretion, whereas the two previous cases showed mineralocorticoid hypersecretion. The tumor was 5 cm in diameter with typical computed tomography and magnetic resonance imaging findings. Subclinical Cushing's syndrome was diagnosed preoperatively, as there was insufficient suppression of cortisol by low-dose dexamethasone, a low adrenocorticotropic hormone (ACTH) concentration, and diminished ACTH and cortisol circadian rhythms without the typical clinical manifestation and symptoms of hypercortisolism. Intraoperative hypotension occurred immediately after tumor removal and following postoperative adrenal insufficiency, which support that the tumor was hyperfunctioning. The postoperative adrenal insufficiency had recovered completely by 12 months after the operation.