A case of pheochromocytoma associated with liver abscess and intestinal pseudo-obstruction.

Pheochromocytomas can present with various symptoms. Nonspecific manifestations of pheochromocytoma include intestinal pseudo-obstruction and weight loss. Here, we present a case of pheochromocytoma in which prolonged intestinal pseudo-obstruction due to excess catecholamines was one of the factors leading to the development of a liver abscess. An 18-year-old male patient with a history of status epilepticus and severe intellectual disability was transferred to our hospital for a thorough examination of fever and constipation that had lasted for 2 months. When admitted to our hospital, he had fever, and his body mass index was 9.5 kg/m2. Upon comprehensive examination of the patient's fever, the blood culture was found positive for Bacteroides. Computed tomography showed findings of intestinal pseudo-obstruction and a low density region in the liver that indicated a liver abscess. Imaging studies also revealed a right adrenal mass and endocrinological test showed elevated plasma norepinephrine and urine normetanephrine levels. In addition, the right adrenal mass showed uptake on 123I-metaiodobenzylguanidine scintigraphy. These findings led to a definite diagnosis of pheochromocytoma. The patient was eventually diagnosed with a pheochromocytoma coexisting with a liver abscess. After treating the liver abscess with antibiotics and ultrasound-guided drainage, an adrenalectomy was performed. The pathological findings were consistent with pheochromocytoma. Postoperatively, the catecholamine excess normalized and intestinal pseudo-obstruction and weight loss improved. We suspected that prolonged intestinal pseudo-obstruction resulted in bacterial translocation and development of a liver abscess. To the best of our knowledge, this is the first report of a pheochromocytoma associated with a liver abscess. Moreover, the clinical presentation of this patient was unusual for pheochromocytoma, as the patient did not have typical symptoms such as hypertension or tachycardia, but rather presented with constipation, intestinal pseudo-obstruction, and weight loss. This case provides valuable insight regarding the impact of catecholamine excess on the intestinal tract and body weight.

HLA analysis of immune checkpoint inhibitor-induced and idiopathic isolated ACTH deficiency.

PURPOSE: Isolated adrenocorticotropic hormone deficiency is a rare disease; however, since immune check point inhibitors (ICIs) have become widely used, many more cases have been reported. In this study, we compared the human leukocyte antigen (HLA) signatures between ICI-induced isolated adrenocorticotropic hormone deficiency (IAD) and idiopathic IAD (IIAD). DESIGN AND METHODS: Clinical features and HLA frequencies were compared among 13 patients with ICI-induced IAD, 8 patients with IIAD, and healthy controls. HLA frequencies of healthy controls were adopted from a HLA database of Japanese population. RESULTS: Age and body mass index were higher, while the rate of weight loss was lower, in patients with ICI-induced IAD than in those with IIAD. No HLA alleles had a significantly higher frequency in patients with ICI-induced IAD than in healthy controls, whereas the frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02, and DQB1*03:03 were significantly higher in patients with IIAD than in healthy controls. CONCLUSIONS: ICI-induced IAD and IIAD were different in terms of HLA frequencies. There were no specific HLAs related to ICI-induced IAD, whereas several HLAs in strong linkage disequilibrium were associated with IIAD. This might suggest that the two diseases have different pathological mechanisms. HLAs unique to IIAD may be helpful in predicting its pathophysiology.

Proportion of serum thyroid hormone concentrations within the reference ranges in athyreotic patients on levothyroxine monotherapy: a retrospective study.

BACKGROUND: In patients receiving thyroid-stimulating hormone (TSH) suppressive therapy with levothyroxine (LT4) after total thyroidectomy for thyroid cancer, thyroid function tests should be performed to adjust the LT4 dose. Specifically, serum TSH concentrations are commonly measured because TSH suppression is necessary according to thyroid cancer risk. The aim of the present study was to elucidate whether free thyroxine (FT4) or free triiodothyronine (FT3) indicates better for adjusting the dose in athyreotic patients on LT4 monotherapy after total thyroidectomy. METHODS: We retrospectively studied the compatibility of free thyroid hormone (FT4 and FT3) concentrations with reference ranges in athyreotic patients on LT4 monotherapy after total thyroidectomy. RESULTS: We identified 2210 consecutive patients from their medical records. Of these patients, 250 had both FT4 and FT3 concentrations in addition to TSH. Two hundred seven had serum TSH concentrations below the reference range (0.5-5.0 µIU/mL), while 43 had them within the reference range. In the 207 patients with TSH concentrations below the reference range, 61 patients (29.5%) had FT4 concentrations within the reference range (0.9-1.7 ng/dL) and 146 patients (70.5%) had FT4 concentrations above the reference range. In contrast, 10 patients (4.8%) had FT3 concentrations below the reference range (2.3-4.0 pg/mL) and 8 (3.9%) had FT3 concentrations above the reference range; 189 patients (91.3%) had concentrations within the reference range. Of the 43 patients with TSH concentrations within the reference range, 25 (58.1%) had FT4 concentrations within the reference range and 18 (41.9%) had FT4 concentrations above the reference range. While, 11 patients (25.6%) had FT3 concentrations below the reference range and one (2.3%) had FT3 concentrations above the reference range; hence, 31 patients (72.1%) had FT3 concentrations within the reference range. CONCLUSION: This study showed that measuring FT3 concentrations rather than FT4 concentrations as the subsequent parameter of thyroid function might be more useful for disease management in terms of the proportion of serum thyroid hormone concentrations within the reference ranges. Furthermore, FT3 measurement could be useful in providing more detailed treatments, including avoiding more aggressive TSH suppressive therapy and identifying the presence of low T3 syndrome in the background.

The magnitude of increased Levothyroxine dose during pregnancy in patients on thyroid-stimulating hormone (TSH) suppression treatment after total thyroidectomy for papillary carcinoma.

The dose of L-T4 replacement for hypothyroidism often needs to be increased after pregnancy. In our institution, patients are instructed to double the dose 2 days a week after pregnancy. However, there is scarce evidence supporting the need for a dose increase after pregnancy in patients with preconception thyroid-stimulating hormone (TSH) suppression (TSH <0.3 µIU/mL). This study aimed to determine the need for a dose increase in L-T4 among women with a TSH-suppressive dose of L-T4 before pregnancy. In this retrospective observational study, between January 2008 and December 2018, we analyzed 166 pregnancies in 134 patients on TSH suppression treatment after total thyroidectomy for papillary carcinoma. Thyroid function tests were performed before and in the first trimester of pregnancy. The dose was adjusted and maintained during the first trimester of pregnancy in 76 pregnancies (group A) and 90 pregnancies (group B), respectively. The median serum TSH level was significantly lower in group A than that in group B (0.014 µIU/mL (IQR, 0.005-0.071) vs. 0.155 µIU/mL (IQR, 0.021-0.657), p < 0.001). TSH suppression could not be maintained after pregnancy in 15.8% and 38.9% of the pregnancies in groups A and B, respectively. Increasing the post-pregnancy dose by an average of 27.4% resulted in maintenance of TSH suppression after pregnancy in 84.2% of pregnancies. In conclusion, this study suggests that increasing the L-T4 dose after pregnancy may be appropriate in postoperative thyroid cancer patients whose serum TSH levels should be suppressed.

Autoimmune thyroid disease and thyroid function test fluctuations in patients with resistance to thyroid hormone.

OBJECTIVE: Resistance to thyroid hormone beta (RTHß) is an inherited syndrome caused by mutations in the thyroid hormone receptor ß (THRB) gene. Patients with RTHß typically have elevated thyroid hormone levels with non-suppressed serum thyroid-stimulating hormone (TSH). We aimed to elucidate the clinical, laboratory, and imaging findings of RTHß patients and further to explore their association with THRB gene mutations. DESIGN AND METHODS: We retrospectively reviewed the clinical charts and compared the clinical findings of 68 RTHß patients (45 probands and 23 relatives) and 30 unaffected relatives in Kuma Hospital. RESULTS: Genetic testing revealed 35 heterozygous THRB gene mutations. Among all RTHß patients, autoimmune thyroid disease (AITD) was detected in 42.1% of men and 40.9% of women, showing that the prevalence of AITD in affected males was significantly higher than in unaffected relatives (P = 0.019). During the follow-up of 44 patients, 13 patients (29.5%; 8 (42.1%) with AITD and 5 (20%) without AITD) temporarily showed thyroid function test results inconsistent with RTHß. Two patients with the R383H mutation, which has little dominant-negative effect, temporarily showed normal thyroid hormone and TSH levels without AITD. CONCLUSIONS: The frequency of AITD in male RTHß patients was significantly higher compared to unaffected relatives. More than 20% of RTHß patients temporarily showed laboratory findings atypical of RTHß during their follow-up, and patients with AITD and specific THRB mutations were prone to display such findings. Therefore, genetic testing should be performed even for patients with fluctuations in thyroid function test results to avoid misdiagnosis and inappropriate treatment.

Risk Preferences, Rationality of Choices, and Willingness to Pay for Preventive Medicine in Patients with Graves' Thyrotoxicosis.

PURPOSE: Patients with thyrotoxicosis show neuropsychological changes, and these may damage the quality of informed consent in clinical practice. Therefore, we examined patients' real-life preferences to assess whether change in risk preferences was dependent on thyroid function state. PATIENTS AND METHODS: The participants were 86 patients who were newly diagnosed with Graves' thyrotoxicosis between 1 January and 31 December 2018 (group A), and an additional 33 euthyroid patients diagnosed before 2018 (group B). In a survey conducted via a questionnaire based on the concept of behavioral economics, we sought to determine risk preferences, rationality of choices, and other relevant factors. An identical second survey was completed 6-12 months later by 36 patients in group A after their thyroid functions had been normalized by treatment, and by 11 euthyroid patients in group B. We performed paired analysis of the first and second surveys in 32 patients of group A and single regression analysis of a total of 140 surveys obtained from 119 patients by combining the first and second surveys of groups A and B with serum level of FT3 as an independent variable. RESULTS: The paired analysis indicated that there was no significant difference in any survey item. The single regression analysis revealed that willingness-to-pay (WTP) for preventive medicine and monthly average out-of-pocket (OOP) expenditure on medical care were both significantly positively associated with serum level of FT3. Patients in the hyperthyroid state tend to have high WTP for preventive medicine, which may be accelerated by the anchoring effect of OOP expenditure. CONCLUSION: Almost all risk preferences of patients with Graves' disease are constant, rational, and reproducible in the hyperthyroid and euthyroid states. However, medical professionals should be aware that the willingness of patients with thyrotoxicosis to pay for medical costs may change after the normalization of thyroid function.

Poorly Differentiated Thyroid Carcinoma Coexisting with Graves' Disease Involving T3 Thyrotoxicosis due to Increased D1 and D2 Activities.

Background: Poorly differentiated thyroid carcinoma is rare and patients are typically euthyroid. We report a novel rare case of poorly differentiated thyroid carcinoma with triiodothyronine (T3) thyrotoxicosis. Patient's Findings: A 77-year-old man presented to Kuma Hospital due to a neck tumor. A thyroid ultrasonography revealed a 220-mL mass in the right lobe. Laboratory data showed low serum thyrotropin (TSH), low free thyroxine (fT4), and high free T3 (fT3) levels. Anti-TSH receptor antibodies and thyroid-stimulating antibodies were positive. 131I scintigraphy showed diffuse uptake only in the left thyroid lobe. The patient underwent a total thyroidectomy and histological examination identified as poorly differentiated thyroid carcinoma. He was diagnosed with poorly differentiated thyroid carcinoma coexisting with Graves' disease. The tumor showed elevated type 1 iodothyronine deiodinases (D1) and type 2 iodothyronine deiodinases (D2) activities compared with that of the left thyroid lobe. Summary and Conclusions: Increased D1 and D2 activities in poorly differentiated carcinoma resulted in T3 toxicosis with a high serum fT3/fT4 ratio.

Association between serum thyroid hormone balance and thyroid volume in patients treated with levothyroxine monotherapy for hypothyroidism.

Many previous studies including ours have reported that athyreotic patients on levothyroxine (LT4) have relatively low serum free triiodothyronine (FT3) levels, whereas patients with large goitrous diseases often have high serum FT3 levels. Here we investigated Hashimoto thyroiditis (HT) patients on LT4 to study the relationship between thyroid volume (TV) and thyroid hormone status in hypothyroid patients on LT4. We retrospectively studied 408 euthyroid HT patients treated with LT4 for hypothyroidism; divided them as per TV and compared serum levels of free thyroxine (FT4) and FT3 and the FT3/FT4 ratio in each patient group with those in euthyroid matched control group. We also evaluated the association between serum FT3 level and FT3/FT4 ratio and TV among HT patients on LT4. In patients with TV <15 mL, serum FT3 levels were significantly lower than those in controls. In patients with TV 15-80 mL, serum FT3 levels were equivalent to those in controls. In patients with TV ≥80 mL, the serum FT3 levels were significantly higher than those in controls. The serum FT3 level (r = 0.35, p < 0.01) and FT3/FT4 ratio (r = 0.42, p < 0.01) showed a positive correlation with TV. TVs in HT patients on LT4 caused differences in serum thyroid hormone balance, as increasing volume increases the serum FT3 level and FT3/FT4 ratio. Serum thyroid hormone balance in HT patients with smaller thyroids was similar to that in athyreotic patients. Mild thyrotropin suppression with LT4 is needed to achieve normal FT3 levels in such patients.

Different pathogenesis of glucose intolerance in two subtypes of primary aldosteronism: Aldosterone-producing adenoma and idiopathic hyperaldosteronism.

AIMS/INTRODUCTION: An increased risk of diabetes mellitus has been reported in primary aldosteronism, but the pathogenesis of glucose intolerance between the primary aldosteronism subtypes remains unclear. This study aimed to evaluate glucose metabolism in oral glucose tolerance test between aldosterone-producing adenoma and idiopathic hyperaldosteronism, and characterize patients with improved glucose intolerance after primary aldosteronism treatment. MATERIALS AND METHODS: Oral glucose tolerance test was carried out in 116 patients who were diagnosed with primary aldosteronism and received adrenal venous sampling for subtyping. Oral glucose tolerance test was re-evaluated after starting the treatment of primary aldosteronism for those who had glucose intolerance before the treatment. RESULTS: A total of 46.4% and 52.3% of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism, respectively, were diagnosed with impaired glucose tolerance or diabetes. The insulinogenic index was significantly lower in aldosterone-producing adenoma than in idiopathic hyperaldosteronism (P = 0.045), whereas the Matsuda insulin sensitivity index was significantly higher in aldosterone-producing adenoma than in idiopathic hyperaldosteronism (P = 0.022). After the treatment of primary aldosteronism, glucose intolerance was improved in 66.6% and 45.8% of aldosterone-producing adenoma and idiopathic hyperaldosteronism, respectively. The presence of obesity and central obesity were significantly lower in patients who improved glucose intolerance after the treatment of primary aldosteronism as compared with those not improved (P = 0.013 and P = 0.033, respectively). CONCLUSIONS: Insulin secretion impairment and insulin resistance play pathogenic roles for glucose intolerance in aldosterone-producing adenoma and idiopathic hyperaldosteronism, respectively. In addition, primary aldosteronism treatments can ameliorate glucose intolerance more effectively in patients without obesity and/or central obesity.