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We analyzed the effects of 100 mg/day sitagliptin and a switch to mitiglinide calcium hydrate/voglibose compound tablets (MIT/VOG) in patients with type 2 diabetes mellitus (T2DM) treated with 50 mg/day sitagliptin. Five patients with T2DM treated with 50 mg/day sitagliptin and hemoglobin A1c (HbA1c) of ≥6.5% were switched to MIT/VOG, or the dose of sitagliptin was increased to 100 mg/day. The effects of the changes in therapy were compared in a crossover fashion by continuous glucose monitoring. The primary endpoint was mean amplitude of glycemic excursions (MAGE), and the secondary end points were 24-hour mean blood glucose level and mean blood glucose level from 0:00 a.m. to 7:00 a.m. and from 7:00 a.m. to 0:00 a.m., percentage of time with blood glucose level of ≥200 mg/dl and <70 mg/dl, maximum and minimum blood glucose levels, and increases in postprandial blood glucose levels. MAGE was significantly lower with MIT/VOG (P = 0.016), whereas mean blood glucose levels were lower between 0:00 a.m. and 7:00 a.m. with 100 mg/day sitagliptin. The percentage of time with blood glucose level ≥200 mg/dl was significantly shorter with MIT/VOG (P = 0.041). The maximum blood glucose level was significantly lower with MIT/VOG (P = 0.043), and the minimum was significantly lower with 100 mg/day sitagliptin (P = 0.043). Blood glucose levels after dinner and mean increases in postprandial blood glucose levels were significantly lower with MIT/VOG (P = 0.090 and P = 0.045 respectively). In patients with T2DM, treatment with MIT/VOG improves MAGE and postprandial hyperglycemia and 100 mg/day sitagliptin lowers early morning glucose levels. This trial was registered with the University Hospital Medical Information Network (UMIN) (No. UMIN R000008274).

A 54-year-old woman was admitted to our hospital for detailed examination of acromegaly because she noticed bilateral hand and finger swelling at the age of 43 and plantar thickening, facial changes and unclear articulation at the age of 49. She had prominent brow ridges, mandibular protrusion, and enlargement of the hands, feet, nasal wings, lips and tongue. Her growth hormone (GH) level was 39.8 ng/ml, insulin-like growth factor-1 (IGF-1) level was 717 ng/ml, GH level was not suppressed (22.9 ng/ml) during a 75-g oral glucose tolerance test (OGTT). Radiography showed cauliflower-like enlargement of the distal phalanx of the fingers, thickening/enlargement of the plantar soft tissues, and increased antero-posterior diameter of the sella turcica. Magnetic resonance imaging showed a mass (21×17 mm) growing towards the right suprasellar region and invading the cavernous sinus. She was diagnosed with acromegaly based on the characteristic physical findings, GH excess, high IGF-1, lack of GH suppression during the 75-g OGTT, and the presence of a pituitary tumor. She was started on octreotide long acting release (Oct-LAR) 20 mg/4w for tumor shrinkage. After three doses, her GH and IGF-1 levels decreased to 2.19 ng/ml (1.69 during the 75-g OGTT) and 205 ng/ml, respectively, meeting cure criteria for acromegaly. In this case, a decrease in GH and IGF-1 levels, tumor shrinkage, and resolution of cavernous sinus invasion allowed the patient to undergo surgery with curative intent (the first-line treatment for acromegaly) without postoperative complications. Thus, preoperative Oct-LAR administration has the potential to improve treatment outcomes of acromegaly.

Approximately 140 different mutations of thyroid hormone receptor β (TRβ) have been identified in resistance to thyroid hormone (RTH). We report herein a middle-aged man with a negative family history who was diagnosed with RTH based on persistent palpitations. Genetic analysis showed a TRβ mutation causing the substitution of alanine for proline 453 (P453A) in exon 10. Since treatment of RTH is different from that of Graves' disease and thyroid stimulating hormone-producing adenoma (TSHoma), a genetic analysis should be performed even in patients who have a negative family history of RTH and who are free of TSHoma when they present with persistent inappropriate secretion of thyroid stimulating hormone (SITSH).

The rate of recurrence of subacute thyroiditis (SAT) during prednisolone (PSL) therapy is approximately 10 to 20%. However, there is little or no information on the time period to relapse following administration of a tapered dose of PSL and the factors associated with such relapse. The aim of this study was to determine the correlation between SAT recurrence and PSL tapering regimen used in the treatment of SAT. This study was a medical record-based retrospective study and involved 26 patients (3 men, 23 women) who received PSL therapy for SAT. The primary endpoint was the association between recurrence and number of days required to taper daily PSL dose to 5 mg. The secondary endpoint was the relationship between recurrence and several variables including age, clinical score, free thyroxine, inflammatory reaction, thyroglobulin, total treatment time, total dose of PSL and presence or absence of creeping thyroiditis. The SAT recurrence rate was 15.3%. There was no significant difference in the initial PSL dose between the non-recurrence and recurrence groups (27.5 mg vs 24.5 mg, P = 0.302). However, for the primary endpoint, significant differences were found between the two groups in time required for tapering PSL to 5 mg/day (non-recurrence: 44.3 ± 15.3 days, recurrence: 19.0 ± 11.9 days, P = 0.012). None of the clinical variables evaluated correlated significantly with SAT relapse. In conclusion, to prevent recurrence of SAT, consideration should be given to the period required for PSL tapering to 5 mg/day.

A 42-year-old woman visited our hospital with palpitations, excessive sweating, and finger tremors in March 2011. She was diagnosed with Graves' disease based on the following test results: thyroid stimulating hormone < 0.01 μU/ml, free thyroxine 6.15 ng/ml, and thyrotropin receptor antibody 7.8 U/ml. Treatment with methimazole 30 mg and propranolol 30 mg was started, and her thyroid function showed improvement. However, significant manic symptoms, irritability, hallucinations, and delusions were noted, and she was hospitalized for her own protection in May 2011. Although treatment with aripiprazole 24 mg and lithium 400 mg was started, the hallucinatory and delusional symptoms persisted, necessitating adjustment of the antipsychotics. Her psychiatric symptoms showed amelioration in July 2011 after improvement in her thyroid function, and she was discharged from our hospital. After discharge, her thyroid function remained normal with methimazole 10 mg, and administration of the antipsychotics was discontinued. Affective psychotic symptoms such as altered mood and activity are frequently observed in cases with Graves' disease, but there have been few reports describing cases with full-blown psychiatric disorders manifesting with features such as hallucinations and delusions as the chief symptoms requiring hospitalized treatment, as in the present case. In symptomatic psychosis associated with Graves' disease, prolonged psychiatric symptoms might develop, and close cooperation with psychiatrists is thus important.

A 56 year old female was admitted to a local hospital after developing symptoms, including generalized fatigue, nausea and vomiting, from trauma. She was relocated to our hospital because she developed other symptoms, including disturbance of consciousness from hypercalcemia and a rash over her entire body. Her clinical symptoms (disturbance of consciousness, loss of appetite, nausea, vomiting, decrease in blood pressure, fever) and examination findings (low blood cortisol levels (1.2 μg/dl ), hypercalcemia (11.0 mg/dl ), peripheral blood eosinophilia (1,600 /μl )) lead to a diagnosis of adrenal insufficiency. In addition, a skin biopsy indicated eosinophilic infiltration, although her condition improved in the end with an oral dose of 30 mg/day of prednisolone. Hypercalcemia and peripheral blood eosinophilia are commonly known examination findings for adrenocortical insufficiency, but it is rare for either of these to be present as clinical symptoms.

We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummer's disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT4) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer's disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT4 and reduced the severity of heart failure. In this rare case of an elderly patient, Plummer's disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.

We describe a 59-year-old woman who presented with pathological osteoporosis, cerebral infarction, hypercalcemia, and markedly high parathyroid hormone levels. The diagnosis was primary hyperparathyroidism, and parathyroidectomy was performed. Histopathological examination showed parathyroid adenoma. Surgical exploration for recurrent parathyroid carcinoma was undertaken at 2 and 3 years after the initial neck resection. Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. The prognosis for parathyroid carcinoma is often difficult to predict due to recurrence.

It has become possible in Japan to use high-dose metformin for patients with type 2 diabetes. The aim of this retrospective study was to determine the effects and safety of metformin in elderly patients with type 2 diabetes. The study subjects (98 patients who were treated with metformin) were assigned into two groups: (Ⅰ) 59 patients who were younger, aged less than 65 years, and (Ⅱ) 39 patients who were elderly, aged more than 65 years. The primary endpoint was the change in glycosylated hemoglobin A1c (HbA1c) at 12 weeks. The secondary endpoints were the safety variables, including hypoglycemic events and adverse events. Although HbA1c decreased significantly in both group Ⅰ (-0.5%) and group Ⅱ (-0.9%), the difference between the two groups in the change in HbA1c was not significant. There were no incidences of hypoglycemia or adverse events in either group. Metformin improved glycemic control in the elderly patients as well as in the non-elderly patients. It is necessary to examine what dose of metformin and serum creatinin level (Cre), eGFR is appropriate for elderly patients.

A 31 year old woman was diagnosed with multiple endocrine neoplasia (MEN) 2B at 10 years old. Dark pigmentation gradually developed on her skin and her serum adrenocorticotropic hormone (ACTH) was high, suggesting concurrent ectopic ACTH syndrome (EAS). Corticotropin-releasing hormone (CRH) loading test ruled out Cushing's disease and supported the diagnosis of EAS. Multiple low attenuation mass in the liver was observed in a computed tomography (CT) scan, and was suspected as ectopic ACTH-secreting metastatic tumor from medullary thyroid carcinoma (MTC). ACTH production by MTC is relatively rare, particularly in patients with MEN; patients with ectopic ACTH-secreting liver metastatic tumor from MTC in MEN 2B have never been reported previously.

Unlabelled: CASE 1: An 80-year-old man presented at our hospital with pain in both knees.He had received continuous intravenous administration of saccharated ferric oxide (SFO) over a period of five years following a diagnosis of iron-deficiency anemia.Blood tests revealed hypophosphatemia (1.4 mg/dl) and high circulating levels of fibroblast growth factor 23 (FGF23) at 248.8 mg/dl.These findings led to the diagnosis of FGF23-related osteomalacia due to SFO administration.Accordingly, the treatment plan was first to discontinue SFO, which led to a decrease in pain and normalization of phosphorus and FGF23 after 1 month.CASE 2: A 63-year-old woman presented at our hospital with leg pain.She had undergone total gastrectomy for gastric cancer at 36 years of age.Blood tests revealed hypocalcemia (8.3 mg/dl) and hypophosphatemia (2.2 mg/dl), and 25(OH)D at no more than 5 pg/ml.Bone X-rays showed significantly diminished bone shadowing.These findings led to a diagnosis of vitamin D-deficient osteomalacia due to impaired absorption following total gastrectomy.For therapy, she was treated with 1 μg/day oral alfacalcidol.Two months after initiating treatment, the pain improved., Conclusion: When a patient is diagnosed with unexplained pain, it is important to pay attention to the possibility of an iatrogenic etiology.

A 49-year-old man was referred to our clinic for suspected hypoglycemic symptoms of palpitation, cold sweat, faintness and sinking feeling at movement since 43 years old. The 75 g oral glucose tolerance test showed a decrease in plasma glucose to 56 mg/dl at five hours, but this was not associated with clear hypoglycemic symptoms, and normal plasma glucose level recovered naturally after the test. At 48-hour fasting test, plasma glucose dropped to under 50 mg/dl, but the patient didn't feel hypoglycemia symptom and plasma glucose recovered naturally, but the patient developed cold sweat and hyperventilation after returning to his own room after the test. At that stage, the heart rate increased to 140 beats/min of sinus tachycardia, as confirmed by Holter monitoring. Postural orthostatic tachycardia syndrome (POTS) was suspected because tachycardia occurred only in daytime after an event such as consumption of diet and urination. A head-up tilt test was ordered since sinus tachycardia developed especially on standing. The results showed an increase in heart rate without reduction in blood pressure, confirming the diagnosis of POTS. A repeat head-up tilt test under the use of a beta-blocker showed no increase in heart rate. Though it is generally difficult to distinguish POTS from other forms of tachyarrhythmia, such as inappropriate sinus tachycardia and sinus node reentry tachycardia, and from neutrally mediated reflex syncope (NMS), POTS should be differentiated from hypoglycemia since each condition should be treated differently.

Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with considerable clinical variability, and is considered to be mainly the result of a hypothalamic defect. PWS is characterized by hyperphagia, obesity, mental retardation and hypogonadism from a young age. Hyperphagia is one of the most serious problems, which is organic in origin, inducing morbid obesity and leading to respiratory failure. Most studies attempting to control obesity in children with PWS by dietary management reported limited success due to difficulty in controlling foraging and food stealing. Here we report 16- and 20-year-old female patients with PWS who showed marked weight loss and improvement of respiratory failure by behavior modification and improvement of the environment.