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.

Association between physical performance during sit-to-stand motion and frailty in older adults with cardiometabolic diseases: a cross-sectional, longitudinal study.

BACKGROUND: Although physical performance tests of the lower extremities are used to assess sarcopenia and frailty, little is known about the mechanisms by which the parameters of ground reaction force (GRF) measured during sit-to-stand motion affect the frailty status in older adults. We aimed to examine the association between GRF parameters during sit-to-stand motion and the incidence of frailty in older adults. METHODS: This longitudinal study evaluated 319 outpatients aged ≥ 65 years with cardiometabolic diseases. The GRF parameters were measured using a motor function analyzer, in which the power, speed, and balance scores were calculated. Frailty was diagnosed using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). The independent associations between scores and frailty indices were assessed using multivariate binomial logistic regression analyses. Cox regression analysis was used to examine whether power and speed scores were associated with the incidence of frailty after adjusting for covariates. RESULTS: Logistic regression analyses adjusted for covariates showed that the power and speed scores were associated with frailty according to the mCHS criteria (power: OR = 0.37, 95% CI = 0.22-0.63; speed: OR = 0.64, 95% CI = 0.52-0.79) and KCL criteria (power: OR = 0.40, 95% CI = 0.26-0.62; speed: OR = 0.81, 95% CI = 0.69-0.96) at baseline. Receiver operating characteristic analyses revealed that the area under the curve values of power and speed scores for discriminating mCHS-defined frailty were 0.72 and 0.73. The Cox regression analysis showed that the speed score predicted the incidence of mCHS-defined (HR = 0.45, 95% CI = 0.22-0.92, P = 0.029) and KCL-defined (HR = 0.77, 95% CI = 0.60-0.99, P = 0.039) frailty, whereas the power score was associated with the incidence of KCL-defined frailty (HR = 0.72, 95% CI = 0.55-0.95, P = 0.02) after adjusting for covariates. CONCLUSIONS: The speed and power scores measured during sit-to-stand motion are predictive of frailty in older adults with cardiometabolic disease. Therefore, the GRF parameters measured during sit-to-stand motion could be an important indicator of frailty. Further studies are necessary to examine whether the GRF parameters can be improved by exercise or whether the changes in these parameters are associated with the improvement of frailty status.

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.

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.

[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.

Vitamin B6 intake and incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: analysis of data from the Japan Diabetes Complications Study (JDCS).

PURPOSE: Although vitamin B6 has been suspected to prevent the progression of diabetic retinopathy, evidence of this in patients with type 2 diabetes based on longitudinal studies is sparse. This study investigated the relationship between vitamin B6 intake and the incidence of diabetic retinopathy in Japanese patients with type 2 diabetes. METHODS: The study was part of an examination of a nationwide cohort of patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 48 mmol/mol. After excluding nonresponders to a dietary survey using the Food Frequency Questionnaire based on food groups, 978 patients were analyzed. Primary outcome was the 8-year risk of a diabetic retinopathy event, and Cox regression analyses estimated hazard ratios (HRs) for retinopathy according to vitamin B6 intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. RESULTS: Mean vitamin B6 intake in quartiles ranged from 1.1 to 1.6 mg/day, and half of the participants had vitamin B6 intake below the recommended daily dietary allowance according to dietary reference intakes in Japanese adults (men 1.4 mg/day; women 1.2 mg/day). After adjusting for confounders, HRs for diabetic retinopathy in the 2nd, 3rd, and 4th quartile groups of vitamin B6 intake compared with the 1st quartile group were 1.17 (95% confidence interval 0.81-1.69, p = 0.403), 0.88 (0.58-1.34, p = 0.550), and 0.50 (0.30-0.85, p = 0.010), respectively. CONCLUSIONS: Findings suggested that high vitamin B6 intake was associated with a lower incidence of diabetic retinopathy in Japanese with type 2 diabetes.

Meat intake and incidence of cardiovascular disease in Japanese patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS).

PURPOSE: Excessive meat intake has been researched as a major cause of cardiovascular disease (CVD) among healthy adults, but data on this topic in Asian patients with diabetes are sparse. The quantity and variety of available meats vary widely between Asian and Western countries. As part of a nationwide cohort study we investigated the relationship between meat intake and incidence of CVD in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 6.5%. METHODS: Analyzed were 1353 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of a CVD event, including coronary heart disease (CHD) and stroke. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. RESULTS: Mean meat intake in quartiles ranged from 9.9 to 97.7 g/day. After adjusting for confounders, HRs of CHD in the 2nd, 3rd, and 4th quartiles for meat intake compared with the 1st quartile were 2.84 (95% confidence interval 1.29-6.24, p = 0.01), 3.02 (1.36-6.70, p < 0.01), and 2.99 (1.35-6.65, p = 0.01), respectively. In two groups according to meat intake, patients consuming ≥ 20 g/day of meat had a 2.94-fold higher risk of CHD than those consuming < 20 g/day (p < 0.01). There was no significant association of stroke with meat intake. CONCLUSIONS: An elevated incidence of CHD in Japanese patients with type 2 diabetes was associated with high meat intake.

[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.

Risk factors for sodium valproate-induced renal tubular dysfunction.

OBJECTIVE: To explore the risk factors for the development of sodium valproate (VPA)-induced renal tubular dysfunction for early diagnosis and treatment. STUDY DESIGN: The subjects were selected from patients who were diagnosed with epilepsy and administered VPA. Blood and spot urine samples were collected and measured the concentration of VPA, the level of serum phosphorus, serum uric acid, serum free carnitine, serum cystatin-c, and urine ß2-microglobulin (BMG). Patients with urine BMG/creatinine levels above 219.2 were treated as renal proximal tubular dysfunction (RTD), with all others treated as non-RTD. RESULTS: Eighty-seven patients, 4-48 years, 53 men and 34 women, were studied. RTD group is 17 patients and non-RTD group is 70 patients. Univariate analyses revealed that the RTD patients were more likely to be bedridden, receiving enteral tube feeding, taking more anticonvulsants, and demonstrating significantly lower serum levels of free carnitine, uric acid, and phosphorus. Among them, bedridden, free serum carnitine, and phosphorus levels were associated with the development of RTD by multivariate analysis. CONCLUSIONS: Bedridden patients receiving VPA are susceptible to hypocarnitinemia, which can cause RTD and may lead to FS. Therefore, urinary BMG should be measured regularly in all patients receiving VPA to assess renal tubular function. An additional measurement of serum free carnitine level should be considered in patients who developed RTD. Supplementation of carnitine for those patients to prevent such complication deserves for further study.