Adrenal Insufficiency and Thyrotoxicosis Following Combined Immune Checkpoint Inhibitor Use: A Case Report and Literature Review.

Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the timing at which each event occurs most frequently after drug administration varies, and cases where multiple events occur simultaneously are rare. We encountered a patient who concurrently suffered from thyrotoxicosis and adrenal insufficiency. An 80-year-old woman with a history of type 2 diabetes mellitus (DM) was diagnosed with stage IVA squamous cell carcinoma of the lungs. Treatment with a combination of nivolumab and ipilimumab was initiated. Although she tested positive for thyroglobulin antibody and transient subclinical hyperthyroidism was observed after two courses, treatment with ICIs was continued. Four months later, treatment was discontinued due to drug-induced lung disease. One month after the last administration, the patient became unconscious and was admitted to another hospital, diagnosed with diabetic ketoacidosis, urinary tract infection, and sepsis. After acute-phase treatment, she was transferred to our hospital due to persistent fever and tachycardia. Thyrotoxicosis and adrenal insufficiency were observed, with high levels of free thyroxine, low thyroid-stimulating hormone (TSH), and cortisol levels. Treatment with extracellular fluids, potassium iodide, beta-blockers, and hydrocortisone was initiated, and the patient's condition improved. No other pituitary hormone deficiencies were observed. She was diagnosed with painless thyroiditis and secondary adrenal insufficiency based on the positive thyroglobulin antibody, negative TSH receptor antibody, decreased Doppler flow in thyroid ultrasonography, low adrenocorticotrophic hormone (ACTH), and low response of ACTH and cortisol to corticotropin-releasing hormone loading test. MRI revealed no abnormalities. We report a case of thyrotoxicosis and secondary adrenal insufficiency five months after the first administration of nivolumab and ipilimumab. Careful follow-up and early detection of endocrine disorders are critical in patients treated with a combination of ICIs.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report.

BACKGROUND: Although vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported. CASE PRESENTATION: An 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 µg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 µIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient's disease course was stable with continued thyroid and adrenal corticosteroid supplementation. CONCLUSIONS: Herein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

Serum Growth Differentiation Factor 15 Levels Predict the Incidence of Frailty among Patients with Cardiometabolic Diseases.

INTRODUCTION: Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty. METHODS: A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38-39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference. RESULTS: During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3-12.0) and 2.7 (95% CI: 1.1-6.9), respectively. CONCLUSION: High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition.

Categorization using the Dementia Assessment Sheet for Community-Based Integrated Care System 8-items (DASC-8) based on cognitive function and activities of daily living predicts frailty, disability and mortality in older adults.

AIM: This longitudinal study aimed to determine whether categorization by the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) is associated with risk of frailty onset, disability, and mortality. METHODS: We analyzed longitudinal data from outpatients aged 65 years and older evaluated for the DASC-8 at the Frailty Clinic. The outcomes during the 3-year follow-up period were (Study A) frailty onset (Kihon Checklist ≥8) and (Study B) disability (new certification of nursing care needs) or mortality. Multivariate Cox regression analyses were performed to examine independent associations between the DASC-8 category and outcomes, and hazard ratios and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, and the presence or absence of diabetes, hypertension, and dyslipidemia. RESULTS: (Study A) Out of the 216 patients without frailty in Categories I or II at baseline, 40 (20.4%) and 11 (55.0%) developed frailty, respectively. The adjusted hazard ratio was 3.62 (95% CI: 1.69-7.76, P < 0.001). (Study B) Out of the 350 patients who did not require long-term care at baseline, disability or death occurred for 20 (7.3%) in Category I, 14 (23.0%) in Category II, and 9 (56.3%) in Category III. The adjusted hazard ratios were 2.40 (Category I vs. II; 95% CI: 1.13-5.11, P = 0.023) and 5.43 (Category I vs. III; 95% CI: 2.23-13.3, P < 0.001). CONCLUSION: Categorization according to DASC-8 is associated with the risk of frailty, disability, and mortality in older patients. Geriatr Gerontol Int 2024; 24: 150-155.

The cross-sectional area of erector spinae muscle and the liver-to-spleen ratio are associated with frailty in older patients with diabetes: a cross-sectional study.

BACKGROUND: Older patients with diabetes mellitus are more susceptible to frailty. Although some imaging markers of appendicular skeletal muscle mass obtained using dual-energy X-ray absorptiometry or computed tomography (CT) imaging can reflect frailty status, the association between imaging indices obtained by abdominal CT scans and frailty in older inpatients has not been reported. METHODS: A total of 151 older inpatients with diabetes mellitus (median age, 79 years; men, 42%) who underwent abdominal CT scans close to the admission date were studied to examine the associations between abdominal CT indices and frailty. Two frailty definitions were used: the modified Cardiovascular Health Study (mCHS) criteria and Kihon Checklist (KCL) criteria. Using the imaging analysis software SYNAPSE VINCENT®, we compared the cross-sectional areas (CSA) of four truncal muscles (erector spinae, iliopsoas, rectus abdominis, and abdominal oblique muscles) and the liver-to-spleen ratio (L/S), the ratio of the CT values of the liver and spleen between frail and non-frail patients. The muscle areas that showed the strongest associations with frailty were also investigated in relation to grip strength and walking speed. Finally, multivariate binominal logistic regression analyses were performed to assess the independent associations of CSA of muscle and L/S with the prevalence of frailty. RESULTS: The prevalence of frailty defined by the mCHS and KCL criteria was 55% and 52%, respectively. The CSA of the erector spinae muscle was most significantly associated with frailty, and was significantly smaller in both sexes of mCHS-defined frail patients and in men with KCL-defined frailty. The CSA of erector spinae muscle was also positively correlated with grip strength and walking speed. In contrast, the L/S was higher in men with KCL-defined frailty. Multivariate logistic regression analyses revealed that the CSA of the erector spinae muscle was independently associated with mCHS-defined frailty in women, and the L/S was associated with KCL-defined frailty in men. CONCLUSIONS: The CSA of erector spinae muscle and low liver fat content could be indices of frailty in older patients with diabetes.

Impact of a history of cardiovascular disease and physical activity habits on the incidence of functional disability.

We examined the impact of a history of coronary artery disease (CAD) or cerebrovascular disease (CVD) and physical activity habits on functional disability among community-dwelling Japanese adults. This population-based retrospective cohort study included 10,661 people aged 39-98 years in Japan (5054, men). Median follow-up was 3.7 years. During the study period, 209 functional disabilities occurred in the overall study population. In multivariable analysis, a history of CVD (hazard ratio [HR] 1.57 [95% CI: 1.00-2.45]) and no physical activity habit (HR 1.74 [1.27-2.39]) presented increased risks for functional disability. HRs for functional disability among patients with a CVD history with and without a physical activity habit were 1.68 (0.75-3.74) and 2.65 (1.49-4.71), respectively, compared with individuals without a history of CVD with a physical activity habit. Similar results were observed for CAD. We found no significant difference in the incidence of functional disability between the group with a history of CAD or CVD and physical activity habits and the group with no history of CAD or CVD and without physical activity habits. Physical activity habits had a favorable influence on avoiding functional disability regardless of a history of CAD or CVD. Future prospective studies are needed to clarify these associations.

Association between white matter alterations on diffusion tensor imaging and incidence of frailty in older adults with cardiometabolic diseases.

Diffusion tensor imaging (DTI) can be used for the early detection of abnormal changes in the integrity of cerebral white matter tracts, and we have previously reported that these changes are associated with indices of early atherosclerotic lesions. Although these changes have been demonstrated to be associated with the incidence of frailty in older adults, no studies have investigated this relationship in patients at high risk for vascular disease. In this longitudinal study, we followed outpatients with cardiometabolic diseases for a maximum of 6 years (median, 3 years) and evaluated the association of baseline DTI data of seven white matter tracts with the incidence of frailty. The modified version of the Cardiovascular Health Study criteria and the Kihon Checklist were used as indices of frailty; fractional anisotropy (FA) and mean diffusivity (MD) were used as indices of white matter changes. Patients who developed frailty based on both indices had low FA and high MD in many of the tracts tested, with the most significant difference found in the MD of the anterior thalamic radiation (ATR). Cox proportional hazard model analysis revealed a significantly high risk of frailty defined by both indices in the groups with high MD values in the left ATR. Similar results were found in patients with diabetes mellitus but not in those without diabetes mellitus. Therefore, abnormalities in the integrity of the left ATR could be associated with the progression of frailty in older adults with cardiometabolic disease, particularly those with diabetes mellitus.

[A geriatric case of hyperosmolar hyperglycemic state with osmotic demyelination syndrome that manifested with dysphagia].

The patient was an 84-year-old man who had been on insulin therapy for type 2 diabetes mellitus for 55 years. He had undergone bile duct stenting to avoid obstruction due to adenocarcinoma of the bile duct. The patient had suffered from fever and anorexia for two weeks, and had subsequently stopped insulin therapy. Since he showed signs of impaired consciousness, he was taken to the emergency room, and was diagnosed with a hyperosmotic hyperglycemic state (HHS) based on the following laboratory findings: blood glucose, 632 mg/dL; plasma osmolality, 391 mOsm/kg·H2O; and serum Na, 163 mEq/L, with urine ketone bodies±and sepsis (Klebsiella pneumoniae). He was therefore admitted to the hospital. His blood glucose and serum Na levels slowly improved following the administration of fluids, insulin, and antibiotics. The patient's consciousness disturbance also improved. However, on the third day after admission, dysphagia was newly observed when the patient resumed eating, and swallowing endoscopy revealed a delayed gag reflex and pharyngeal retention of saliva. Cranial magnetic resonance imaging showed a high-intensity area in the central pontine, which was considered to be caused by osmotic demyelination syndrome (ODS). The patient's oral intake ability recovered with swallowing rehabilitation. ODS is a rare complication of HHS. We report a case of HHS with ODS, in which the patient's chief complaint was dysphagia, which should be distinguished from other diseases.

Dynapenic abdominal obesity is associated with mild cognitive impairment in patients with cardiometabolic disease: a cross-sectional study.

BACKGROUND: Dementia is an important health issue for older people and requires early intervention in the mild cognitive impairment (MCI) stage to manage risk factors. Both dynapenia (DP) and abdominal obesity (AO) are associated with inflammation and oxidative stress, which may be involved in the pathogenesis of cognitive impairment. Therefore, in this cross-sectional study, we aimed to evaluate the association between MCI and dynapenic abdominal obesity (DAO), a combination of DP and AO. METHODS: A total of 417 older outpatients with cardiometabolic diseases without severe cognitive impairment were studied to compare cognitive function in four groups: control, DP, AO, and DAO groups. DAO was defined as the combination of DP (handgrip strength of < 28 kg and < 18 kg in men and women, respectively) and AO (waist circumference of ≥ 85 cm and ≥ 90 cm in men and women, respectively). MCI was defined as a score of ≤ 25 in the Japanese version of the Montreal Cognitive Assessment. Multiple regression analyses were performed to examine if MCI was independently associated with DAO, low handgrip strength, or high waist circumference. RESULTS: The DAO group obtained the lowest cognitive test scores and had the highest prevalence of MCI. Furthermore, after adjusting for covariates, the logistic regression analysis showed that patients in the DAO group were at an increased risk of MCI (odds ratio [OR] = 3.98, 95% confidence interval [CI]: 1.15-13.77). Further logistic regression analyses revealed that both low handgrip strength (OR = 2.19, 95% CI: 1.11-4.29) and high waist circumference (OR = 2.03, 95% CI: 1.03-3.99) were associated with MCI. CONCLUSIONS: DAO, which can be easily diagnosed by a combination of handgrip strength and waist circumference, was associated with MCI in patents with cardiometabolic metabolic disease. This study suggests that screening for MCI in DAO patients could be important for early intervention of dementia prevention.

Subclinical Atherosclerosis, Vascular Risk Factors, and White Matter Alterations in Diffusion Tensor Imaging Findings of Older Adults With Cardiometabolic Diseases.

White matter abnormalities may reflect cerebral microvessel disease. Diffusion tensor imaging (DTI) can help detect early changes in white matter integrity in each tract. However, studies investigating the relationship between subclinical atherosclerosis markers and white matter alterations in DTI findings are limited. This study aimed to examine associations between cardiovascular risk factors and indices of subclinical atherosclerosis-ankle brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and carotid artery intima-media thickness (IMT)-and altered white matter integrity in older patients. A total of 224 patients (aged ≥65 years) with cardiometabolic disease who underwent magnetic resonance imaging (MRI) and either plethysmography or cervical ultrasound at the start of the 3-year observational study period were included in this study. We measured fractional anisotropy (FA) and mean diffusivity (MD), which are indices of white matter integrity in seven white matter tracts. In a univariate analysis, lower ABI and higher baPWV values were associated with FA or MD abnormalities in several tracts, whereas IMT was scarcely associated with such change. In addition, high blood pressure and glycoalbumin/glycohemoglobin ratio (GA/HbA1c) and low body mass index (BMI) and triglyceride (TG) levels were associated with FA or MD abnormalities. In a multivariate analysis adjusted for age, sex, BMI, diastolic blood pressure, TG, and GA/HbA1c, the associations between ABI and FA or MD remained in all of either side of the following tracts: anterior thalamic radiation, forceps minor, inferior frontooccipital fasciculus (p < 0.001 for all) and superior longitudinal fasciculus (SLF; p < 0.05), whereas most of those between baPWV and FA or MD disappeared except for SLF (p < 0.05). These results indicate that low ABI could be an indicator of white matter abnormalities.

[A case of hyperammonemia caused by urinary tract infection due to urease-producing bacteria in dementia with Lewy bodies].

An 87-year-old woman diagnosed with dementia with Lewy bodies (DLB) 2 years earlier was referred to our institution because of difficulty walking. She was diagnosed with urinary tract infection and admitted to our hospital. During hospitalisation, she became delirious, which prompted the administration of haloperidol. Afterwards, an altered level of consciousness was noted, measuring 300 on the Japan coma scale. A blood test revealed hyperammonaemia without liver damage. Urine culture detected the presence of Corynebacterium urealyticum. Therefore, we diagnosed this case as one of hyperammonaemia due to urinary tract infection caused by urease-producing bacteria. Soon after the insertion of a urethral catheter, the ammonia level decreased, and the consciousness level improved. In this case, the patient took medication to preserve her bladder function, which is frequently associated with DLB. We suspected that the drug caused urinary retention, resulting in hyperammonaemia. Hyperammonaemia due to these bacteria should be considered in DLB patients with an impaired consciousness, especially in those using regulators of the urinary bladder function.

Sodium Intake and Incidence of Diabetes Complications in Elderly Patients with Type 2 Diabetes-Analysis of Data from the Japanese Elderly Diabetes Intervention Study (J-EDIT).

This study investigates the associations between sodium intake and diabetes complications in a nationwide cohort of elderly Japanese patients with type 2 diabetes aged 65-85. Data from 912 individuals regarding their dietary intake at baseline is analyzed and assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes are times to diabetic retinopathy, overt nephropathy, cardiovascular disease (CVD), and all-cause mortality during six years. We find that mean sodium intake in quartiles ranges from 2.5 g to 5.9 g/day. After adjustment for confounders, no significant associations are observed between sodium intake quartiles and incidence of diabetes complications and mortality, except for a significant trend for an increased risk of diabetic retinopathy (p = 0.039). Among patients whose vegetable intake was less than the average of 268.7 g, hazard ratios (HRs) for diabetic retinopathy in patients in the second, third, and fourth quartiles of sodium intake compared with the first quartile were 0.87 (95% CI, 0.31-2.41), 2.61 (1.00-6.83), and 3.70 (1.37-10.02), respectively. Findings indicate that high sodium intake under conditions of low vegetable intake is associated with an elevated incidence of diabetic retinopathy in elderly patients with type 2 diabetes.

Associations between sarcopenia and white matter alterations in older adults with diabetes mellitus: A diffusion tensor imaging study.

AIMS/INTRODUCTION: Older adults with diabetes mellitus are susceptible to sarcopenia. Diffusion tensor imaging studies have also shown that patients with diabetes have altered white matter integrity. However, the relationship between these structural changes in white matter and sarcopenia remains poorly understood. MATERIALS AND METHODS: The study included 284 older patients (aged ≥65 years) who visited the Tokyo Metropolitan Geriatric Hospital Frailty Clinic. We used diffusion tensor imaging to measure fractional anisotropy (FA) and mean diffusivity (MD) to evaluate changes in white matter integrity. We investigated the associations between sarcopenia, or its diagnostic components, and FA or MD in seven white matter tracts considered to be associated with sarcopenia according to the patients' diabetes status. RESULTS: We found significantly low FA or high MD values in the bilateral anterior thalamic radiations (ATR) and right inferior fronto-occipital fasciculus (IFOF) of patients with Asian Working Group for Sarcopenia 2019-defined sarcopenia, in all patients and those with diabetes. Using binominal regression analyses, we associated low FA values in the left ATR and right IFOF with sarcopenia in all patients and those with diabetes, after adjusting for age, gender, HbA1c, blood pressure, cognitive function, physical activity, depression, nutritional status, and inflammation. CONCLUSIONS: White matter alterations in left ATR and right IFOF are associated with the prevalence of sarcopenia in patients with diabetes. Specific changes to the left ATR and right IFOF tracts could play critical roles in the occurrence of sarcopenia in patients with diabetes.

Use of Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) for the screening of frailty and components of comprehensive geriatric assessment.

AIM: We examined whether the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) is useful for screening frailty and as a comprehensive geriatric assessment (CGA). METHODS: Outpatients (N = 431; 269 women; Mage = 78.9 ± 6.8 years) with cardiometabolic disease from a frailty clinic participated. Frailty status was assessed using modified Cardiovascular Health Study criteria, the Clinical Frailty Scale and the Kihon Checklist. Cognition, higher-level activities of daily living, sarcopenia, physical activities, depression, nutrition, medication adherence, social network and quality of life were assessed as CGA components. We examined the association of DASC-8 category with frailty or CGA components using multiple logistic regression analyses, adjusted for age and sex. RESULTS: Most participants (n = 310, 71.9%) were in Category I, 90 (20.9%) were in Category II and 31 (7.1%) were in Category III. There were no significant differences in sex, body mass index, or past medical history, except regarding age or cerebral infarction. Logistic regression analyses showed that, for all definitions of frailty, the odds ratios of frailty significantly increased as category progressed. Cognitive function, higher-level activities of daily living, handgrip strength, gait speed, physical activities, medication adherence, social network and quality of life decreased as the category increased. Although depressive tendency increased in Category II, there was no significant difference in muscle mass or prevalence of sarcopenia among the categories. Malnutrition was observed in Category III. CONCLUSIONS: DASC-8 category was associated with frailty and several CGA components in older patients with cardiometabolic disease. Geriatr Gerontol Int 2020; 20: 1157-1163.

Serum growth differentiation factor 15 level is associated with muscle strength and lower extremity function in older patients with cardiometabolic disease.

AIMS: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. METHODS: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. RESULTS: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. CONCLUSIONS: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.

Primary Aldosteronism Associated with Multiple Adrenocortical Micronodules in a Patient with Renal Cell Carcinoma.

A 47-year-old woman with a history of diabetes mellitus (DM) and obesity was admitted to our hospital for glucose control. She was detected to have hypertension (HT) and diagnosed with primary aldosteronism (PA) based on the high level of aldosterone to renin ratio and the results of the upright furosemide-loading test according to the criteria of the Japanese Society of Hypertension (JSH) guidelines. Computed tomography revealed left renal tumor and adrenocortical adenoma. She underwent left nephrectomy and adrenalectomy. The pathological findings were clear-cell renal cell carcinoma (RCC) and nonfunctional adrenocortical adenoma. Her nonneoplastic adrenal tissue histologically revealed CYP11B2-positive multiple adrenocortical micronodules (MNs) and concomitant paradoxical hyperplasia of the zona glomerulosa. Therefore, MNs were thought to be responsible for PA in this patient. After surgery, HT was improved, and the result of upright furosemide-loading test after 12 months of surgery did not fulfill the criteria of PA according to the JSH guidelines. However, the adrenocorticotrophic hormone stimulation test was positive; considering the possibility of slight aldosterone overproduction from the right adrenal gland, the administration of spironolactone was started. Herein, we report a rare case of RCC in conjunction with PA histologically associated with MNs.

[Clinical characteristics of bullous pemphigoid in elderly patients with type 2 diabetes mellitus: The association with the use of dipeptidyl peptidase-4 inhibitors].

AIM: Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by the production of autoantibodies. Several recent reports have described the occurrence of BP in diabetic patients treated with dipeptidyl peptidase-4 (DPP-4) inhibitors. However, the clinical features of BP in diabetic patients, particularly in those treated with DPP-4 inhibitors, have not yet been examined. The aim of this study was to clarify clinical characteristics of BP in elderly type 2 diabetic patients. METHODS: We found cases of BP in 15 elderly type 2 diabetic patients (11 men, 4 women) and 20 non-diabetic patients (8 men, 12 women) from September, 2012 to September, 2016. These patients had all been treated with corticosteroid therapy. We investigated the participants' basic clinical characteristics and the course of BP treatment. The differences in variables between the two groups were analyzed using Wilcoxon's test and the chi-square test. RESULTS: The mean age of type 2 diabetes patients with BP was 81.1±5.5 years. The mean HbA1c was 7.3±1.6%. A total of 87% of diabetic patients had been treated with DPP-4 inhibitors for 11.7 months prior to the BP onset. The diabetic patients had a lower prevalence of neurogenerative disease, severe ADL disabilities, and dementia than the non-diabetic patients. Furthermore, the diabetic patients with BP tended to be younger and more frequently male than those without diabetes. After stopping the DPP-4 inhibitors, the skin lesions were successfully treated with systemic corticosteroid therapy, and glycemic control was achieved using intensive insulin therapy. DPP-4 inhibitors were used in all cases where the aniti-BP180NC16a antibody showed negative conversion. CONCLUSION: BP in patients with type 2 diabetes had different clinical features from that in non-diabetic patients, suggesting an association between BP and the use of DPP-4 inhibitors.

Background characteristics and clinical features of elderly patients with hyperglycemic hyperosmolar syndrome.

AIM: Few reports have described the characteristics of hyperglycemic hyperosmolar syndrome (HHS) in the elderly. We investigated the background characteristics and clinical features of 14 elderly patients with HHS. METHODS: HHS was diagnosed based on a blood glucose level of >600 mg/dL and an effective plasma osmolality [2 (Na) + glu/18] of >320 mOsm/kg. For 14 cases of HHS, we investigated the medical and social backgrounds of the patients, their clinical findings, and the outcomes. RESULTS: The mean patient age was 83 years, and the mean body mass index was 17.8 kg/m2. Half had a history of either cerebral infarction or hip fracture. The mean duration of diabetes was 14 years, but 4 diabetes cases were newly diagnosed. There was a high prevalence of acute infection (79%) in HHS patients, especially urinary tract infection and pneumonia, with a seasonal peak in winter. Patients who had been treated with steroids, tube feeding, or both numbered 1, 2, and 1, respectively. Most HHS patients had a history of dementia. More than half of such patients were living alone or only with their spouse, and their activities of daily living showed marked deterioration. The mean blood glucose level, HbA1c, effective serum osmolality, and pH were 881 mg/dL, 10.3%, 353 mOsm/kg, and 7.39, respectively. One patient died during hospitalization, and 9 were discharged to nursing homes or other hospitals. The mean length of hospitalization was 55 days. In most cases, the insulin secretion capacity was preserved, and 9 patients were treatable with oral hypoglycemic agents alone. CONCLUSIONS: Many cases of HHS in the elderly are associated with infection, a shortage of social support, cognitive impairment, or ADL decline. Although the survival rate in our series was high, the functional prognosis was impaired.