Hyponatremia due to preserved non-osmotic arginine vasopressin secretion in adipsic diabetes insipidus: a case report with review of literature.

Adipsic diabetes insipidus (ADI) is characterized by central diabetes insipidus and an impaired thirst response to hyperosmolality, leading to hypernatremia. Hyponatremia observed in patients with ADI has been considered a complication of desmopressin therapy. Herein, we present a case of impaired thirst sensation and arginine vasopressin (AVP) secretion without desmopressin therapy, in which hyponatremia developed due to preserved non-osmotic AVP secretion. A 53-year-old woman with hypopituitarism, receiving hydrocortisone and levothyroxine, experienced hyponatremia three times over 5 months without desmopressin treatment. The first hyponatremic episode (120 mEq/L) was complicated by a urinary tract infection with a plasma AVP level of 33.8 pg/mL. Subsequent hyponatremia episodes occurred after administration of antipsychotic (124 mEq/L) and spontaneously (125 mEq/L) with unsuppressed plasma AVP levels (1.3 and 1.8 pg/mL, respectively). Hypertonic saline infusion did not affect AVP or copeptin levels. Regulating water intake using a sliding scale based on body weight prevented the recurrence of hyponatremia without the use of desmopressin. Except during infection, plasma AVP levels (1.3 ± 0.4 pg/mL) were not significantly correlated with serum sodium levels (rs = -0.04, p = 0.85). In conclusion, we present a unique case of impaired thirst sensation and AVP secretion in which hyponatremia developed without desmopressin therapy. Preserved non-osmotic AVP secretion, possibly stimulated by glucocorticoid deficiency, may contribute to the development of hyponatremia in patients with ADI.

Carney Complex Complicated with Primary Pigmented Nodular Adrenocortical Disease without Cushing's Syndrome Recurrence for Five Years after Unilateral Adrenalectomy.

We herein report a case of Carney complex (CNC) complicated with primary pigmented nodular adrenocortical disease (PPNAD) after unilateral adrenalectomy. A 44-year-old woman was admitted to our hospital for PPNAD surgery. She had previously undergone surgery for cardiac myxoma and had a PRKAR1A mutation with no family history of CNC. She had Cushing's signs, but her metabolic abnormalities were mild. Adrenal insufficiency due to poor medication adherence was a concern, so she underwent unilateral adrenalectomy. Cushing's signs improved postoperatively and without recurrence for five years. Treatment plans for PPNAD should be determined based on the patient's condition, medication adherence, and wishes.

Determinants and impact of physical impairment in patient-reported outcomes among older patients with type 2 diabetes mellitus in Japan.

OBJECTIVE: To investigate the predictive factors associated with physical impairment among older patients with type 2 diabetes mellitus (T2DM) in Japan and to examine the potential impact of physical impairment on patient-reported health outcomes in this population. METHODS: A cross-sectional analysis was conducted using patient-reported data from the 2012-2014 Japan National Health and Wellness Survey. Physical impairment was measured using the Physical Component Summary (PCS) score of the Short-Form 36-Item Health Survey (SF-36) three-component model (using Japanese norms). Older T2DM patients (≥65 years old; n = 1511) were dichotomized into physically impaired (PCS ≤ 25th percentile; n = 378) and non-physically impaired (PCS > 25th percentile; n = 1133). Work productivity (absenteeism, presenteeism and overall work impairment), activity impairment and healthcare resource utilization were compared between these groups. RESULTS: Age, female sex, low and high body mass index (BMI), diabetes-related complications, cardiovascular events, unawareness of having hypoglycemic events in the past 3 months, and lack of regular exercise were significant factors associated with physical impairment in multivariable analysis. The physically impaired group reported significantly more regular outpatient visits (13.48 vs. 10.16, respectively, p < .001), 1% or greater absenteeism (16.7% vs. 4.1%, p = .005), greater presenteeism (27.8% vs. 12.2%, p = .001), overall work impairment (30.0% vs. 13.0%, p = .001) and overall activity impairment (39.5% vs. 17.2%, p < .001) than the non-physically-impaired group after adjusting for covariates. CONCLUSIONS: This study identified age, BMI, diabetes-related comorbidities, history of cardiovascular events and lack of exercise as key predictors associated with physical impairment in older patients with T2DM in Japan, which predicted low work productivity as well as activity impairment. This study provides support that physical impairment in patients with T2DM may lead to low work productivity and activity impairment.Supplemental data for this article is available online at https://doi.org/10.1080/03007995.2020.1846170.

Pembrolizumab-induced fulminant type 1 diabetes with C-peptide persistence at first referral.

SUMMARY: A 72-year-old man with no history of diabetes was referred to our department due to hyperglycemia during pembrolizumab treatment for non-small-cell lung carcinoma. His blood glucose level was 209 mg/dL, but he was not in a state of ketosis or ketoacidosis. Serum C-peptide levels persisted at first, but gradually decreased, and 18 days later, he was admitted to our hospital with diabetic ketoacidosis (DKA). The patient was diagnosed with fulminant type 1 diabetes (FT1D) induced by pembrolizumab. According to the literature, the insulin secretion capacity of a patient with type 1 diabetes (T1D) induced by anti-programmed cell death-1 (anti-PD-1) antibody is depleted in approximately 2 to 3 weeks, which is longer than that of typical FT1D. Patients with hyperglycemia and C-peptide persistence should be considered for hospitalization or frequent outpatient visits with insulin treatment because these could indicate the onset of life-threatening FT1D induced by anti-PD-1 antibodies. Based on the clinical course of this patient and the literature, we suggest monitoring anti-PD-1 antibody-related T1D. LEARNING POINTS: Immune checkpoint inhibitors, such as anti-PD-1 antibodies, are increasingly used as anticancer drugs. Anti-PD-1 antibodies can cause immune-related adverse events, including T1D. FT1D, a novel subtype of T1D, is characterized by the abrupt onset of hyperglycemia with ketoacidosis, a relatively low glycated hemoglobin level and depletion of C-peptide level at onset. In patients being treated with anti-PD-1 antibody, hyperglycemia with C-peptide level persistence should be monitored through regular blood tests. Because of C-peptide persistence and mild hyperglycemia, it is possible to miss a diagnosis of life-threatening FT1D induced by anti-PD-1 antibody. In particular, in patients who have no history of diabetes, hyperglycemia without DKA is likely to be the very beginning of anti-PD-1 antibody-induced T1D. Therefore, such patients must be considered for either hospitalization or frequent outpatient visits with insulin injections and self-monitoring of blood glucose.

Hungry bone syndrome after thyroidectomy for thyroid storm.

A 39-year-old man was admitted to our hospital with the diagnosis of thyroid storm due to Graves' disease. Near-total thyroidectomy was performed after 1 month's pharmacological treatment, and he presented with tetany next morning. Serum corrected calcium value was 5.7 mg/dL. Procollagen type 1 N-terminal propeptide increased considerably, while tartrate-resistant acid phosphatase 5b decreased. These changes indicated that bone formation exceeded bone resorption in reverse after thyroidectomy. Calcium gluconate was administered intravenously for 14 days, before the patient was discharged. Oral administration of calcium and active forms of vitamin D was continued for 4 months. Rapid skeletal uptake of calcium from blood caused severe and persistent hypocalcaemia, which is called hungry bone syndrome. When patients with Graves' disease have severe thyrotoxicosis, high serum alkaline phosphatase levels and low bone mineral densities, they are at high risk for hungry bone syndrome after thyroidectomy, and should be educated for the symptoms of hypocalcaemia.

Tuberculous Addison's disease with increased hydrocortisone requirements due to administration of rifampicin.

A 58-year-old man was referred to our hospital for darkened skin, general fatigue and weight loss. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency. 18Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands, with 18fluorodeoxyglucose accumulation. Loop-mediated isothermal amplification assays of bronchoalveolar lavage fluid were positive for Mycobacterium tuberculosis The patient was diagnosed with tuberculous Addison's disease and treated with antituberculosis agents, including rifampicin. The patient's fatigue worsened gradually after initiation of rifampicin, and the dosage of hydrocortisone was increased. Serum cortisol level monitoring at 2 hours after administration of hydrocortisone was shown to be clinically useful for determining the optimal dose, especially with concurrent use of rifampicin.

[A Case of an Elderly Diabetic Patient Developing Wernicke Encephalopathy without Alcohol Abuse or an Unbalanced Diet].

A 70-year-old man with a 28-year history of type 2 diabetes mellitus was admitted due to persistent vomiting and neurological abnormalities in Nov 2012. He had developed gait disturbance and diplopia for six months during antiplatelet therapy, which was initiated following the diagnosis of a cerebellar infarction in June 2012. He had nystagmus, truncal ataxia and an ocular motility disorder, and the MRI study showed increased FLAIR and DWI signals in the peri-third ventricle and periaqueductal region, in addition to the cerebellar vermis. Wernicke encephalopathy was suspected according to his symptoms, and thiamine administration dramatically improved his condition. He did not have a history of alcohol abuse or poor eating habits; however, various coexisting factors, including diabetes mellitus, pyloric stenosis and the use of antiulcer drugs and insulin, were considered to be responsible for Wernicke encephalopathy. This case demonstrates the importance of distinguishing Wernicke encephalopathy from cerebrovascular disease in elderly patients.

[A case of an elderly diabetic patient with dementia effectively treated with weekly exenatide].

A 74-year-old man with diabetes mellitus since 64 years of age had been treated with glimepiride, metformin and alogliptin; however, his glycemic control remained poor, i.e., a casual blood glucose level of 318 mg/dl, HbA1c level of 10.6% and glycated albumin level of 24.9%. Although his blood glucose level improved with intensive insulin therapy, he exhibited dementia with an MMSE score of 9/30 and was unable to continue insulin injections by himself, thus rejecting his family's help. The extended-release form of the GLP-1 agonist exenatide (Bydureon(®)) was recently introduced in Japan. This new anti-diabetic agent enables the administration of once-weekly type 2 diabetes treatment that delivers a continuous dose of exenatide in a single weekly injection. We employed weekly exenatide therapy in combination with oral hypoglycemic agents in this case. The patient visited our outpatient clinic for injections every week, showing a remarkable improvement in his HbA1c level, from 10.7% to 7.1% in five months. Subcutaneous induration was the only side effect of weekly exenatide injection. Weekly exenatide therapy can be easily managed by other caregivers and is expected to be a useful treatment approach in elderly diabetic patients with dementia.

[Bone metabolism and cardiovascular function update. Effects of antiosteoporotic agents on glucose and lipid metabolism].

At present, antiosteoporotic agents that might affect glucose and/or lipid metabolism include bisphosphonates, Selective Estrogen Receptor Modulators ; SERMs and activated vitamin D. Bisphosphonates have little, if any, effect on lipid metabolism, while they are suggested to improve glucose metabolism, via osteocalcin or adiponectin. SERMs are shown to decrease serum triglycerides and LDL cholesterol levels, and increase HDL cholesterol level. To date, SERMs are not proven to reduce the risk of coronary events. From nutritional point of view, studies suggest that vitamin D may improve lipid and glucose metabolism, whereas its therapeutic effect on lifestyle related diseases is unknown.

[Acyclovir-induced neurotoxicity and acute kidney injury in an elderly diabetic patient treated with valacyclovir: report of a case].

An 83-year-old Japanese man had a 29-year history of well-controlled diabetes mellitus. His HbA1c level was approximately 6.0%, with no microalbuminuria and a serum creatinine level seven days before admission of 0.8 mg/dl (eGFR: 69.67 ml/min/1.73 m(2)). Five days before admission, he visited an ophthalmologist with inflammation of the right palpebra and conjunctiva and began taking valacyclovir at a dose of 3,000 mg for the treatment of herpes zoster. Two days before admission, he was prescribed loxoprofen at a dose of 180 mg for a headache. One day prior to admission, he developed dysarthria, wandering and loss of appetite. He was subsequently admitted to our hospital with progressive deterioration of consciousness (Japan Coma Scale: II-20). On admission, he exhibited renal dysfunction, with a serum creatinine level of 5.11 mg/dl (eGFR: 9.16 ml/min/1.73 m(2)). Based on his diverse symptoms and current treatment with valacyclovir, the patient was diagnosed with acyclovir-induced neurotoxicity and his symptoms rapidly improved after hemodialysis. The serum acyclovir level on admission was found to be 9.25 µg/ml. Although acyclovir-induced neurotoxicity is commonly seen in elderly patients with renal dysfunction, there are also reports of this condition in patients with a normal renal function. Valacyclovir is frequently prescribed to the elderly to treat diseases such as herpes zoster. As valacyclovir induces renal dysfunction, which raises the serum acyclovir level to the toxic range, special attention must be paid when administering this drug in elderly subjects.

[A case of severe hypokalemia caused by a Chinese herbal remedy (Yokukansan) in an 81-year-old woman with dementia].

An 81-year-old woman had been visiting 2 hospitals for hypertension and dementia, prior to admission to our emergency room for nausea, hypertension, severe hypokalemia (K 1.29 mEq/l) and abnormal electrocardiography findings. She had been taking a Chinese herbal remedy (Yokukansan, 7.5 g/day) for the behavioral and psychological symptoms of dementia (BPSD) for 6 months before admission. On admission, she presented with metabolic alkalosis with hypokalemia, a high urinary excretion of potassium, low plasma rennin activity and hypoaldosteronism. We diagnosed pseudoaldosteronism caused by the Chinese herbal remedy Yokukansan (which includes licorice). Discontinuation of Yokukansan and the administration of potassium supplements normalized her serum potassium level within 2 weeks. However, we could not successfully control her BPSD by drugs such as tiapride hydrochloride or risperidone. BPSD is a serious problem in an aging society, with the ever-increasing incidence of dementia. The use of Yokukansan has recently been receiving attention as a new treatment modality for BPSD. Because this agent has relatively few adverse effects compared with typical antipsychotic agents, the use of Yokukansan is continuing to increase sharply. Pseudoaldosteronism, if caused by Yokukansan, may cause death by severe hypokalemia, but the early identification of hypokalemia is sometimes difficult because drug-induced hypokalemia is not dose-dependent. We think it is important to create awareness of the possible adverse effects of Yokukansan, such as hypertension and electrolyte abnormalities to make the most of this commonly used drug for the treatment of BPSD among dementia patients.

[Thiazide diuretics for hypertensive treatment induced severe hyponatremia with consciousness disturbance in two elderly cases].

The salt intake of the Japanese is among the highest in the world, leading to a high prevalence of salt-sensitive hypertension. To prevent this, salt restriction, suppression of the rennin-angiotensin-aldosterone system, and natriuresis are important. Therefore, the use of a combination of an angiotensin II receptor blocker and thiazide diuretics is used for antihypertensive treatment. Some randomized controlled studies suggested that thiazide diuretics are useful not only to lower blood pressure, but also to prevent cardiovascular events and improve prognosis in the elderly, who are prone to being salt-sensitive. We encountered 2 elderly patients referred to our emergency room because of severe hyponatremia and consciousness disturbance, who had been treated with thiazide diuretics for 1 and 2 months, respectively. In both, hypernatriuria despite hyponatremia, slight dehydration, and refractory antidiuretic hormone (ADH) excess were observed, but activation of the rennin-angiotensin-aldosterone system was absent. Thyroid and adrenal functions were unremarkable. Theses phenomena have much in common with the condition called mineralcorticoid-responsive hyponatremia of the elderly (MRHE). Several weeks after discontinuation of diuretics, serum sodium values returned to normal levels, but transtubular potassium concentration gradient (TTKG) values were depleted despite slight hyperkalemia, and relative ADH excess was sustained, which suggested mineralocorticoid dysfunction and distal renal tubulointerstitial injury. Distal tubulointerstitial dysfunction is one of the most important causes of MRHE. On the basis of these 2 cases, we speculated whether distal tubulointerstitial injury may accelerate hyponatremia in the elderly. We need to check not only serum potassium, but also sodium levels, especially in elderly persons with suspected tubulointerstitial injury.

[Effect of glucose and bone metabolism in endocrinal disorder].

It is well known that endocrine disorders; glucocorticoid excess including Cushing syndrome, high dose or long term steroid therapy and hyperthyroidism, induce secondary osteoporosis. These common endocrinal disorders affect not only bone metabolism but also glucose metabolism. Glucose metabolisms also play a important role in the progression of osteoporosis. To prevent secondary osteoporosis, multifocal intervention such as correction of insulin resistance or glucose metabolism, lifestyle, and drug therapy, need to be added to current management of endocrinal system.

Pituitary abscess with panhypopituitarism showing T1 signal hyperintensity of the marginal pituitary area: a non-invasive differential diagnosis of pituitary abscess and pituitary apoplexy.

A 53-year-old man was hospitalized with general fatigue, headache, dizziness and polyuria. The laboratory findings revealed anterior hypopituitarism and central diabetes insipidus. He also showed eye movement disorder and facial sensory impairment. These symptoms were treated successfully with conservative medical treatment. Concurrently, abnormal pituitary MR imaging findings were revealed. Pituitary abscess was primarily suspected on MR imaging findings, although it was difficult to differentiate pituitary apoplexy by MR imaging findings, alone. In this report, we propose a new diagnostic approach of pituitary abscess, using a combination of CT, MR imaging and clinical manifestations, without either pituitary surgery or pituitary biopsy.

[A case of lactic acidosis caused by buformin in an oldest elderly diabetic patient].

A 93-year-old male was urgently admitted to our hospital with dyspnea and disturbance of consciousness. The patient had been visiting a general physician regularly for ten years, for treatment of type 2 diabetes. He had been treated with glibenclamide and voglibose, until voglibose was replaced with buformin 3 months before admission. During pre-admission treatment, his HbA1c was 10-12% and serum Cr level was around 2mg/dL, but insulin therapy had never been considered because of "being too old". The patient had started taking furosemide one year before admission, because of edema of the lower legs, and also spironolactone two months before admission. Anorexia had continued for one month before admission on May 29, 2003. On admission, his laboratory data were; blood glucose 87mg/dL, HbA1c 12.5%, BUN 75mg/dL, Cr 3.9mg/dL, lactate 253.1 mg/dL, and blood gas analysis; pH 6.97, anion gap 45.3mmol/L breathing room air, suggesting marked lactic acidosis with renal failure. Intensive care with bicarbonate and fluid therapy was successful, and his glycemic control improved markedly with insulin. On the other hand, his activity of daily living (ADL) severely deteriorated while in hospital Home follow-up was therefore not indicated, and he had to change a hospital for further follow-up. This case report gives rise to the question of how we should manage diabetes in the oldest elderly, including the use of insulin and biguanides. In addition, complications of biguanides in the elderly are reviewed.

[Osteoporosis as a lifestyle-related disease].

Although genetic factors determine the limits of peak bone mass, environmental factors can modify the outcome. Relation between lifestyle and osteoporosis is discussed, in terms of nutrition and habits. Significant link between calcium intake and bone mass has been reported. Although recommended daily allowance of calcium is 600 mg/day for adults, 850 mg/day or more shall be recommended later in life. Vitamin D insufficiency may lead to secondary hyperparathyroidism in the elderly, the condition that facilitates bone loss. Other nutrients that affect bone turnover include vitamin K, vitamin C, protein, potassium, salt, magnesium and phosphorus. Too much intake of caffeine or alcohol, as well as smoking is a risk factor of osteoporosis. Mechanical loading on the skeleton increases bone mass, therefore weight-bearing activity is recommended to gain or preserve bone mass.