A case of subacute thyroiditis after influenza vaccination.

Summary: A 40-year-old Japanese woman presented to the outpatient clinic with fever and palpitations 2 days after receiving the influenza vaccine (Influenza HA Vaccine 'KMB'®) following the second dose of coronavirus disease 2019 (COVID-19) vaccine (COVID-19 vaccine Moderna intramuscular injection®). At the first visit, the patient presented with a swollen thyroid gland with mild tenderness, and she was diagnosed with subacute thyroiditis (SAT) based on the presence of thyrotoxicosis (free T3: 5.42 pg/mL; free T4: 2.34 ng/dL; and thyroid-stimulating hormone (TSH): <0.01 µIU/mL), a high C-reactive protein level (5.77 mg/dL), a negative TSH receptor antibody, and characteristic ultrasound findings. The patient's human leukocyte antigen types were A2, A11, B35, B51, DR4, and DR1403. Prednisolone (15 mg/day) was given as an initial dose, after which the fever subsided, and the dose was tapered and discontinued after 6 weeks. The patient was thought to have developed SAT due to influenza vaccination. SAT after influenza vaccination may be overlooked. For patients with SAT, it is necessary to obtain information regarding their vaccination history. Learning points: After influenza vaccination, subacute thyroiditis (SAT) may develop. If persistent fever, anterior neck pain, swelling, tenderness of the thyroid gland, and symptoms of thyrotoxicosis are observed immediately after vaccination for several viruses, including influenza, an examination to rule out the onset of SAT is recommended. Human leukocyte antigen type A2 (HLA-A2) and HLA-B35 may be linked to the development of SAT following influenza vaccination. The two doses of the coronavirus disease 2019 (COVID-19) vaccine given before the influenza vaccine may affect the onset of SAT.

Prolonged postoperative hypoaldosteronism related to hyperkalemia in patients with aldosterone-producing adenoma.

Hyperkalemia is developed in a part of patients with aldosterone-producing adenoma (APA) after adrenalectomy, suspected to be due to the insufficiency of aldosterone secretion. The purpose of this study is to determine the frequency and characteristics of prolonged postoperative hypoaldosteronism (PPHA) using chemiluminescent enzyme immunoassay (CLEIA). We studied 58 patients with APA with long time after adrenalectomy and whose PAC was measured using a CLEIA kit. The PAC value measured using CLEIA was significantly lower than that of using RIA between two consecutive visits before and after the shift of measuring method of PAC (median [interquantile range], 123.0 [99.8-164.0] vs. 39.5 [15.8-64.2] pg/mL, p < 0.01). PAC was below the minimum limit of quantification (4.0 pg/mL) of the CLEIA kit at least once in nine patients (15.5%) who had PPHA. The PPHA group were older (mean ± standard deviation, 61.3 ± 8.5 vs. 50.5 ± 10.1 years, p < 0.01) and had lower eGFR (60.3 ± 14.0 vs. 82.3 ± 22.8 mL/min/1.73 m2, p < 0.01) than the non-PPHA group. The frequency of postoperative hyperkalemia (maximum serum potassium >5.5 mEq/L) was higher in the PPHA group than in the non-PPHA group (55.6% vs. 8.2%, p < 0.01). In conclusion, a few patients with APA long time after adrenalectomy had unmeasurable PAC using CLEIA. PPHA is likely to develop in patients with APA after adrenalectomy who are older and have impaired renal function. Additionally, PPHA is related to the occurrence of postoperative hyperkalemia.

Subacute thyroiditis associated with thyrotoxic periodic paralysis after COVID-19 vaccination: a case report.

Summary: We report a 26-year-old Japanese man who visited our outpatient clinic presenting fever immediately after i.m. injection of the second dose of a coronavirus disease 2019 (COVID-19) vaccine (Moderna®). At the first visit, the patient had a fever of 37.7°C and a swollen thyroid gland with mild tenderness. He was diagnosed with subacute thyroiditis (SAT) based on the presence of thyrotoxicosis (free tri-iodothyronine, 32.3 pg/mL; free thyroxine, >7.77 ng/dL; and thyroid-stimulating hormone (TSH) < 0.01 µIU/mL), high C-reactive protein level (7.40 mg/dL), negative TSH receptor antibody, and characteristic ultrasound findings. His HLA types were A*02:01/24:02, B*15:11/35:01, Cw*03:03, DRB1*09:01/12:01, DQB1*03:03, and DPB1*05: 01/41:01. He was initially administered prednisolone 15 mg/day, following which the fever subsided. After 10 days, he developed limb weakness and could not walk. The serum potassium level decreased to 1.8 mEq/L, which confirmed the diagnosis of thyrotoxic periodic paralysis (TPP). Potassium supplementation was initiated. The muscle weakness gradually decreased. Prednisolone therapy was terminated 6 weeks after the first visit. His thyroid function returned to normal 5 months after the first visit, through a hypothyroid state. To our knowledge, this is the first reported case of TPP-associated SAT following COVID-19 vaccination. Persistent fever following vaccination should be suspected of SAT. Additionally, TPP may be associated with SAT in Asian male patients. Learning points: Following coronavirus disease 2019 (COVID-19) vaccination, subacute thyroiditis may develop regardless of the vaccine type. If persistent fever, anterior neck pain, swelling and tenderness of thyroid gland, and symptoms of thyrotoxicosis are observed immediately after the COVID-19 vaccination, examination in consideration of the onset of subacute thyroiditis is recommended. HLA-B35 may be associated with the onset of subacute thyroiditis after the COVID-19 vaccination. Although rare, subacute thyroiditis can be associated with thyrotoxic periodic paralysis, especially in Asian men. Glucocorticoid therapy for subacute thyroiditis may induce thyrotoxic periodic paralysis through hypokalemia.

Prediction of unilateral hyperaldosteronism on adrenal vein sampling using captopril challenge test in patients with primary aldosteronism.

Captopril challenge test (CCT) is a simple and safe confirmatory test for primary aldosteronism (PA). We investigated the effectiveness of the indices after captopril administration for prediction of unilateral hyperaldosteronism (UHA) on adrenal vein sampling (AVS). We studied 238 patients with PA who had CCT and successful AVS between July 2007 and December 2019 in Sapporo City General Hospital. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic performance for prediction of UHA on AVS in regard to the reduction rate of plasma aldosterone concentration (PAC) after captopril administration was inferior to aldosterone to renin ratio (ARR) and PAC (area under the ROC curve 0.72 vs. 0.84, 0.72 vs. 0.89, respectively, both p < 0.01). Based on the optimal cut-off values in ARR (897 pg/mL/ng/mL/h, sensitivity 64.6%, specificity 93.0%) and PAC (203 pg/mL, sensitivity 73.9%, specificity 93.0%) after captopril administration, the patients were divided into three groups: (1) both positive, (2) one positive, and (3) both negative. The prevalence of UHA on AVS in the three groups were 90.0%, 52.9%, and 7.3%, respectively. In the first group, 31 of 32 patients with unilateral nodular lesion on CT had an ipsilateral unilateral AVS. In conclusion, the combination of post-captopril ARR and PAC is useful for prediction of laterality diagnosis on AVS. AVS is strongly recommended in patients with both positive or one positive results for the optimal cut-off values of post-captopril ARR and PAC and is weakly recommended in patients with both negative results.

The risk factors for hepatic steatosis in patients with primary aldosteronism.

Patients with primary aldosteronism (PA) are complicated by metabolic syndrome more frequently than those without PA. Hyperaldosteronism has been reported to be associated with a higher prevalence of non-alcoholic fatty liver disease (NAFLD). We aimed to clarify the risk factors for hepatic steatosis in the two subtypes of PA, comparing the status of hepatic steatosis in each of these subtypes. This was a retrospective observational study. We enrolled patients with an aldosterone producing adenoma (APA) (n = 33) or idiopathic hyperaldosteronism (IHA) (n = 56). Hepatic fat content was evaluated using the ratio of liver to spleen (L/S) X-ray attenuation on unenhanced computed tomography. L/S ratio <1.0 was utilized for assessing as hepatic steatosis. Age, sex distribution, visceral fat percentage (VF%), and visceral fat area (VFA) did not differ between patients with the two PA subtypes. The percentages of patients with L/S ratio <1.0 was not different between the two subtypes (APA: 21.2 % (7/33) vs. IHA: 19.6 % (11/56), p = 1.00). In both subtypes, the L/S ratio negatively correlated with VF% (APA: r = -0.66, p < 0.001; IHA: r = -0.66, p < 0.001) and with VFA (APA: r = -0.44, p < 0.01; IHA: r = -0.37, p < 0.01). The status of hepatic steatosis, evaluated using L/S ratio, did not differ between patients with APA or IHA. Hepatic steatosis was affected by the amount of visceral fat.

A case of Williams syndrome with suspected coexisting ectopic aldosterone-producing tumor in the liver.

SUMMARY: A 31-year-old man with Williams syndrome (WS) was referred to our hospital because of a 9-year history of hypertension, hypokalemia, and high plasma aldosterone concentration to renin activity ratio. A diagnosis of primary aldosteronism (PA) was clinically confirmed but an abdominal CT scan showed no abnormal findings in his adrenal glands. However, a 13-mm hypervascular tumor in the posterosuperior segment of the right hepatic lobe was detected. Adrenal venous sampling (AVS) subsequently revealed the presence of an extended tributary of the right adrenal vein to the liver surrounding the tumor. Segmental AVS further demonstrated a high plasma aldosterone concentration (PAC) in the right superior tributary vein draining the tumor. Laparoscopic partial hepatectomy was performed. The resected tumor histologically separated from the liver was composed of clear cells, immunohistochemically positive for aldesterone synthase (CYP11B2), and subsequently diagnosed as aldosterone-producing adrenal adenoma. After surgery, his blood pressure, serum potassium level, plasma renin activity and PAC were normalized. To the best of our knowledge, this is the first report of WS associated with PA. WS harbors a high prevalence of hypertension and therefore PA should be considered when managing the patients with WS and hypertension. In this case, the CT findings alone could not differentiate the adrenal rest tumor. Our case, therefore, highlights the usefulness of segmental AVS to distinguish adrenal tumors from hepatic adrenal rest tumors. LEARNING POINTS: Williams syndrome (WS) is a rare genetic disorder, characterized by a constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. WS is a disease with a high frequency of hypertension but the renin-aldosterone system in WS cases has not been studied at all. If a patient with WS had hypertension and severe hypokalemia, low PRA and high ARR, the coexistence of primary aldosteronism (PA) should be considered. Adrenal rest tumors are thought to arise from aberrant adrenal tissues and are a rare cause of PA. Hepatic adrenal rest tumor (HART) should be considered in the differential diagnosis when detecting a mass in the right hepatic lobe. Segmental adrenal venous sampling could contribute to distinguish adrenal tumors from HART.

Left-right differences in adrenal vein sampling for primary aldosteronism.

In adrenal venous sampling (AVS) for patients with primary aldosteronism (PA), adrenocorticotropic hormone (ACTH) stimulation generally increased the success rate. The effect of ACTH stimulation on the left-right differences of laterality diagnosis in AVS remains unclear. A total of 167 patients with PA underwent successful AVS were examined. Patients with autonomous cortisol secretion were excluded. The proportion of dominant side in AVS was compared before and after ACTH stimulation. Unilateral disease on AVS was defined as a lateralization index of more than 4, both before and after ACTH stimulation. Before ACTH stimulation, unilateral disease was more frequently observed on the right side than the left side (right 33.5% vs. left 13.8%, p < 0.01). After ACTH stimulation, unilateral disease was more frequently observed on the left side than the right side, without statistical significance (left 15.6% vs. right 10.8%, p = 0.20). Among the 56 patients who had right unilateral disease before ACTH stimulation, 17 patients (30.0%) also had right unilateral disease after ACTH stimulation. The affected side of AVS was changed from right unilateral to bilateral after ACTH stimulation in 34 (60.7%) out of 56 patients. These patients had milder PA and CT scans showed no nodular lesions on the right side. In AVS, ACTH stimulation not only decreased unilateral results but also shifted to the dominant side. Overestimation should be carefully considered when the surgical indication for the right adrenal gland was decided based on AVS results without ACTH stimulation.

Relationship Between Visceral Fat and Plasma Aldosterone Concentration in Patients With Primary Aldosteronism.

CONTEXT: The involvement of visceral fat in aldosterone secretion has not been reported in patients with primary aldosteronism (PA). Patients with PA are complicated by metabolic syndrome more frequently than those without PA. An excess of visceral fat has been hypothesized to cause an elevation of aldosterone secretion in patients with PA. OBJECTIVES: To clarify the role of visceral fat in the pathophysiology of PA, we investigated the correlation between plasma aldosterone concentration (PAC) and visceral fat parameters in patients with PA. DESIGN: This retrospective observational study comprised 131 patients diagnosed with PA between April 2007 and April 2017 at Sapporo City General Hospital. We divided participants into two PA subtypes, aldosterone-producing adenoma (APA; n = 47) and idiopathic hyperaldosteronism (IHA, n = 84), utilizing adrenal venous sampling. We analyzed the correlations of PAC with visceral fat percentage (VF%), visceral fat area (VFA), and subcutaneous fat area, by evaluating computed tomography studies in each subtype group. RESULTS: Patients with IHA showed a positive correlation of PAC with VF% (r = 0.377, P < 0.001) and VFA (r = 0.443, P < 0.001). The correlation was not evident in patients with APA. CONCLUSIONS: This study revealed a relationship between visceral adipose tissue and aldosterone production only in patients with IHA.

Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients.

BACKGROUND: Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. METHODS: Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. RESULTS: Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. CONCLUSIONS: Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients.

Delayed reduction in left ventricular function following treatment of non-Hodgkin's lymphoma with chemotherapy and rituximab, unrelated to acute infusion reaction.

We report 3 cases of reduced cardiac function with complications in non-Hodgkin's lymphoma patients who were treated with rituximab. Patients experienced reduced cardiac functions after the administration of rituximab; there was no evidence of any preceding infusion reactions. Reticulin fiber was observed diffusely in cardiac muscles. Transforming growth factor-beta levels were elevated after the administration of rituximab. We believe that continuous elevation of transforming growth factor-beta may promote the growth of reticulin fiber in cardiac muscles. Reduction in cardiac functions is a severe complication that must be considered when rituximab is administered.

Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura.

Helicobacter pylori (HP) eradication therapy is a useful treatment for idiopathic thrombocytopenic purpura (ITP). Some investigators have also reported the effects of proton pump inhibitor (PPI) monotherapy on ITP. We performed a randomized study of HP eradication therapy and PPI monotherapy on ITP. Four of nine patients achieved complete remission (CR), two of nine achieved partial remission (PR) in HP eradication therapy, three of eight achieved CR, and two of eight achieved PR in PPI monotherapy. No significant differences were observed in the CR + PR of these patients between HP eradication therapy and PPI monotherapy. As for cost comparisons, HP eradication therapy is cheaper than PPI monotherapy, but it is less effective.

Successful treatment of lymphoma with fludarabine combined with rituximab after immune thrombocytopenia induced by fludarabine.

A 47-year-old man was diagnosed with non-Hodgkin's lymphoma (NHL) follicular B-cell type (stage IVB). Although partial remission was observed after the administration of several combination chemotherapeutic agents, no more improvement was observed. After we finished the FND (fludarabine, mitoxantrone, dexamethasone) regimen, the patient's status improved. After the administration of the FND regimen, thrombocytopenia developed, and the platelet count did not recover to previous levels. After rituximab was administered for the treatment of thrombocytopenia, the platelet count recovered. Then we combined fludarabine and rituximab for the treatment of NHL. Although fludarabine was administered, the platelet count did not decrease when combined with rituximab. In the discussion, we analyze the characteristics and the treatment outcome of the thrombocytopenia induced by fludarabine reviewed in the literature.

Effectiveness of propagermanium treatment in multiple myeloma patients.

Interferon (IFN) is one of several drugs effective in treating multiple myeloma (MM), and propagermanium is an IFN inducer. We report on 10 MM patients who were treated with propagermanium at doses from 10 to 40 mg. Two patients achieved complete remission (CR), two patients achieved partial remission (PR), and the condition of four patients was stable (stable disease, SD). After discontinuation of propagermanium, the status of MM progressed in two patients who were in SD and in two patients who had achieved PR. The administration of propagermanium was restarted in one patient resulting in a decrease in her paraprotein.

Hepatitis B virus reactivation in a case of non-Hodgkin's lymphoma treated with chemotherapy and rituximab: necessity of prophylaxis for hepatitis B virus reactivation in rituximab therapy.

A patient with Non-Hodgkin's lymphoma is reported, in which reactivation of the hepatitis B virus was achieved from treatment with rituximab. The patient's HBs antigens were positive on admission, and she tested positive for HBs, HBe, and HBc antibodies, and negative for the HBe antigens. She was treated with a regimen of three courses of rituximab-containing anti-cancer drugs and one course of combined anti-cancer drugs. Throughout these chemotherapy courses, prednisolone was not given. After the fourth course of chemotherapy with the third rituximab she developed hepatic dysfunction, and the serum titers of HBs and HBc antibodies suddenly decreased. After administration of lamivudine, however, she gradually recovered from liver failure.

An orderly retreat: Dedifferentiation is a regulated process.

Differentiation is a highly regulated process whereby cells become specialized to perform specific functions and lose the ability to perform others. In contrast, the question of whether dedifferentiation is a genetically determined process, or merely an unregulated loss of the differentiated state, has not been resolved. We show here that dedifferentiation in the social amoeba Dictyostelium discoideum relies on a sequence of events that is independent of the original developmental state and involves the coordinated expression of a specific set of genes. A defect in one of these genes, the histidine kinase dhkA, alters the kinetics of dedifferentiation and uncouples the progression of dedifferentiation events. These observations establish dedifferentiation as a genetically determined process and suggest the existence of a developmental checkpoint that ensures a return path to the undifferentiated state.