Familial dysalbuminemic hyperthyroxinemia combined with Graves' disease: a rare case report.

BACKGROUND: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disease characterised by an abnormally increased affinity of albumin for serum thyroxine. Assay interference and differential diagnosis remain challenging for FDH. The condition is more complicated when FDH is combined with primary thyroid diseases. Co-occurrence of FDH and Graves' disease is rare. CASE PRESENTATION: We report the case of a 28-year-old woman with complex FDH and coexisting Graves' disease. Initially, the existence of FDH was not recognised. Graves' disease was relieved after treatment with antithyroid drugs and two administrations of radioactive iodine therapy. She subsequently developed primary hypothyroidism and was prescribed levothyroxine replacement. However, thyroid function failed to normalise despite frequent levothyroxine dose adjustments. Ultimately, syndromes involving the inappropriate secretion of thyroid-stimulating hormone (IST) were considered, and FDH was successfully differentiated from other causes of IST. CONCLUSIONS: A greater focus on FDH when investigating the causes of IST is critical to correctly evaluate thyroid function status and avoid inappropriate treatment, especially in complicated cases with concurrent FDH and primary thyroid diseases.

Characteristics and response cutoff of octreotide suppression test in thyrotrophin (TSH)-secreting pituitary adenomas.

CONTEXT: Somatostatin analogs are recommended for preoperative therapy in thyrotrophin secreting pituitary adenomas (TSHomas). Octreotide suppression test (OST) was designed to differentiate TSHomas with resistance to thyroid hormones, while its ability to test the sensitivity of SSA has not been fully studied. OBJECTIVE: To test the sensitivity of SSA in TSHomas with OST. PATIENTS: We collected 48 pathologically confirmed TSHoma patients with complete 72 h' data of OST into analysis. INTERVENTION: Octreotide suppression test. MAIN OUTCOME: Sensitivity timepoint and cutoff of OST. RESULTS: During the entire OST, the TSH descended maximally 89.07% (73.85%, 96.77%), while the FT3 and FT4 declined slowly [43.40% (37.80%, 54.44%) and 26.59% (19.01%, 33.13%), respectively]. The 24th hour was the timepoint wherein the stability occurs for TSH, and the 48th hour for FT3 and FT4 during OST. In the patients who received both short- and long-acting somatostatin analogs (SSA), the 24-h timepoint was the most predictive timepoint for the percentage of TSH decline (Spearman's rank correlation analysis, r = .571, p < .001), while the 72-h timepoint was optimal for predicting the magnitude of TSH decline (Spearman's rank correlation analysis, r = .438, p = .005). In the 24th timepoint, a positive correlation was also observed between TSH suppression rate and the percentage decrease and absolute value decrease of FT3 and FT4. Furthermore, in patients treated with long-acting SSA, the 72-h timepoint was optimal for predicting both the percentage (Spearman's rank correlation analysis, r = .587, p = .01) and magnitude (Spearman's rank correlation analysis, r = .474, p = .047) of TSH decline. The 24th hour was the optimal timepoint with 44.54% (50% of median value of TSH in 72-hOST) decrease of TSH being the observing cutoff. The adverse effect of OST was predominantly occurred in the gastrointestinal system and no severe event occurred during OST. Paradoxical response could occur in OST and it did not influence the effect of SSA as long as sensitivity was confirmed. A high level of hormonal control was achieved in the SSA-sensitive patients. CONCLUSION: OST can be used as an efficient tool to guide the adequate use of SSA.

Thyroid dysfunction after immune checkpoint inhibitor treatment in a single-center Chinese cohort: a retrospective study.

BACKGROUND: Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanisms remain unclear. PURPOSE: To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. METHODS: We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. RESULTS: The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient thyrotoxicosis), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to first clinical presentation was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.67; P < 0.001), previous thyroid disease (OR 4.30, 95% CI 1.54-11.99; P = 0.005), and a higher baseline thyroid-stimulating hormone level (OR 2.76, 95% CI 1.80-4.23; P < 0.001). Thyrotoxicosis was only associated with the baseline thyroid-stimulating hormone (TSH) level (OR 0.59, 95% CI 0.37-0.94; P = 0.025). Thyroid dysfunction after initiation of ICI therapy was associated with better progression-free survival (hazard ratio [HR] 0.61, 95% CI 0.44-0.86; P = 0.005) and overall survival (hazard ratio 0.67, 95% CI 0.45-0.99; P = 0.046). Anti-thyroglobulin antibody positivity increased the risk of thyroid irAEs. CONCLUSIONS: The occurrence of thyroid irAEs with diverse phenotypes is common. Distinct clinical and biochemical characteristics suggest heterogeneity among different subgroups of thyroid dysfunction, which requires further research to explore the under mechanism.

Combination of transsphenoidal endoscopic surgery and presurgical somatostatin analogs in thyrotropin (TSH)-secreting pituitary adenomas: Treatment outcome and long-term remission at a single pituitary center.

Background: Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) account for an extremely rare group of pituitary adenomas. Few studies examined the sensitivity and efficacy of presurgical somatostatin analogs (SSAs) and described the long-term remission under such treatment modality. The aim of the present study was to assess the efficacy of presurgical SSA treatment and long-term remission after surgery. Methods: A retrospective cohort of 65 TSHoma patients who received endoscopic transsphenoidal pituitary surgery between 2011 and 2020 in a single pituitary center in China was established. Data were analyzed for sex differences and different types of SSA and ultimately to explore the hormonal cutoff for remission prediction. Results: TSHomas had a predominant female preference in this cohort (43 women vs. 22 men). Baseline FT3 was higher in men [7.543 ± 2.407 vs. 5.58 (4.99, 6.58), p = 0.019], which was consistent with its longer diagnosis time and larger tumor volume. The median medication time for hormonal control was 2. 5 days for short-acting SSA and 4. 0 weeks for long-term SSA. Patients with long-acting SSA had a shrinking maximum tumor diameter at a median of 1.0 (-1.6, 4.925) mm. Only 10 patients (15.38%) were not in complete remission among whom 8 patients were not en-bloc resected and 2 patients had tumor recurrence after 81.6 and 10. 7 months of complete removal. Postsurgical thyroid hormones (within 1 week) of TSH <0.094 µIU/ml were identified as the cutoff for remission using the ROC curve. Conclusions: The combination of endoscopic transsphenoidal surgery and presurgical SSA TSHomas provided a higher long-term remission for TSHomas.

Analysis of thyroid involvement in children and adult Langerhans cell histiocytosis: An underestimated endocrine manifestation.

Background: Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal expansion of CD1a+/CD207+ LCH cells. The thyroid involvement in LCH has mostly been described in case reports. Methods: We retrospectively evaluated the clinical characteristics, diagnosis, and treatment of 27 children and adult patients with thyroid LCH in our center between 2010 and 2021. Results: The incidence of thyroid LCH was 14.00% (7/50) in children and 10.10% (20/198) in adults, respectively. Among patients with thyroid involvement, 81.5% presented with diabetes insipidus (DI) as the first symptom, and 51.9% complained of neck swelling or mass. Children and adults with thyroid LCH had higher frequencies of the hypothalamic-pituitary axis (HPA) (children: 100% vs. 62.8%, P=0.05; adult: 95% vs. 42.1%, P<0.001), the lung (children: 85.7% vs. 25.6%, P=0.004; adult: 70% vs. 50.6%, P=0.099), and a lower frequency of bone (children: 14.3% vs. 55.8%, P=0.049; adult: 45% vs. 73.6%, P=0.008) involvement than patients without thyroid involvement. Patients with thyroid LCH had a higher frequency of primary hypothyroidism and a lower frequency of euthyroidism than patients without it. The two major types of ultrasound imaging were diffuse (55%) and nodular type (45%). The standardized uptake value of thyroid on 18-F-fluorodeoxyglucose positron emission tomography/computed tomography was 5.3-12.8. The diagnoses were confirmed using thyroid aspiration (54.5%) or surgery (45.5%). In addition, thyroid LCH combined with papillary thyroid carcinoma was not rare (2/27). Conclusion: Thyroid involvement in LCH is not rare. Furthermore, identifying thyroid involvement can facilitate the pathological diagnosis of LCH. Therefore, the possibility of thyroid LCH should be fully investigated in patients with DI, primary hypothyroidism, abnormal thyroid ultrasound results, and multi-system disease. In addition, thyroid aspiration can confirm suspected thyroid LCH. Finally, special attention should be paid to evaluating HPA and pulmonary involvement in thyroid LCH.

Tumor-induced osteomalacia combined with acromegaly: A case report.

Both acromegaly and tumor-induced osteomalacia (TIO) are rare diseases caused by an excess hormone secreted by neuroendocrine neoplasms, which are growth hormone (GH) and fibroblast growth factor 23 (FGF23), respectively. GH elevates phosphate reabsorption via the effect of insulin-like factor 1 (IGF-1), while FGF23 inhibits phosphate reabsorption and reduces serum phosphate level markedly. A patient who developed a typical acromegaly appearance but was accompanied with height loss and hypophosphatemia for 2 years visited our hospital. Laboratory investigations showed GH and IGF-1 hypersecretion, as well as hypophosphatemia caused by renal phosphate wasting. Magnetic resonance image revealed a pituitary somatotroph adenoma. Octreoscan scintigraphy also found a causative tumor on the right foot for hypophosphatemia. Then, he underwent resection of the tumor on the right foot. His serum phosphate returned to normal immediately but elevated gradually. Then, we removed the pituitary adenoma of the patient, and the GH and phosphate levels returned to the normal range. Here, we report the first case with acromegaly combined with TIO, the changing process of his phosphate concentration suggests an interesting concurrent effect of excess GH and FGF23 in this rare condition.

Clinical diagnostic performance of a fully automated TSI immunoassay vs. that of an automated anti­TSHR immunoassay for Graves' disease: a Chinese multicenter study.

BACKGROUND: Both thyroid-stimulating immunoglobulins immunoassay (TSI IA) and thyrotrophin receptor antibody immunoassay (TRAb IA) are commonly used for the diagnosis of Graves' disease (GD). The aim of the present study was to compare the clinical diagnostic performance of these two methods. METHODS: Sera were obtained from 1103 subjects presenting a variety of clinical conditions from three centers: 100 subjects with untreated GD, 200 with treated GD, 62 with autoimmune thyroid disease(AIT), 216 with other thyroid diseases (OTHER-T), 214 with non-thyroid autoimmune diseases (NTAD), 191 with other diseases (OD), and 120 healthy subjects (HS). Both TSI and TRAb IAs were performed for all 1013 serum samples. Bioassay was performed for 86 samples whose TSI results were inconsistent the TRAb assay results. RESULTS: Comparing untreated GD patients with the control groups (AIT, NTAD, OTHER-T, OD, and HS) resulted in an area under the curve (AUC) of 0.992 for the TSI IA and 0.989 for the TRAb IA with no statistically significant difference observed between these AUC values (P = 0.2733). The best TSI CDP (clinical decision point) value was 0.42 IU/L. The differences in sensitivity (100% vs. 95%, P = 0.7991) and specificity (97.1% vs. 97.6%, P = 0.9426) between the TSI and TRAb IA were not statistically significant. TSI IA had a higher agreement with the TSI bioassay than TRAb IA. CONCLUSION: The clinical diagnostic performance of the TSI IA for diagnosing Graves' disease was very similar to that of the TRAb IA. TSI IA can be used to diagnose GD in the Chinese.

Heterophilic antibody interference with TSH measurement on different immunoassay platforms.

INTRODUCTION: Interference due to the presence of heterophilic antibodies may lead to falsely low or high analyte concentrations, but falsely elevated values are more common in most immunoassay platforms. We report a case of a 53-y old female patient underwent radical thyroidectomy for thyroid papillary carcinoma and the results of TSH in the Siemens Advia Centaur XP after surgery were not suppressed, ranging from 5.73 and 6.61 µIU/ml. METHODS: The status of the thyroid was then assessed using 4 assay platforms from Siemens, Abbott, Roche and Beckman. RESULTS: The results of TSH were 5.52, 0.54, 0.12, and <0.015 µIU/ml, respectively. After the samples were pretreated with the heterophilic antibody blocker, results given by Siemens, Abbott, and Roche showed significant decreases of 0.003, 0.001, and 0.005 µIU/ml, respectively. Therefore, it was confirmed that the presence of heterophilic antibodies in the patient samples interfered with the TSH measurements in multiple assay systems. CONCLUSIONS: Clinicians must be aware of the possible assay interference, including the measurements of FT4, FT3 and TSH, results may be misleading in the presence of heterophilic antibodies, in particular when the results of thyroid function tests do not fit the patient clinical presentation.

Erratum to "Hypophyseal Involvement in Immunoglobulin G4-Related Disease: A Retrospective Study from a Single Tertiary Center".

[This corrects the article DOI: 10.1155/2018/7637435.].

Hypophyseal Involvement in Immunoglobulin G4-Related Disease: A Retrospective Study from a Single Tertiary Center.

This study aims to outline the clinical features and outcomes of IgG4-related hypophysitis (IgG4-RH) patients in a tertiary medical center. We reviewed clinical manifestations and imaging and pituitary function tests at baseline, as well as during follow-up. Ten patients were included. The mean age at diagnosis of IgG4-RH was 48.4 (16.0-64.0) years. An average of 3 (0-9) extrapituitary organs were involved. Five patients had panhypopituitarism, three had only posterior hypopituitarism, one had only anterior hypopituitarism, and one had a normal pituitary function. One patient in our study had pituitary mass biopsy, lacking IgG4-positive cells despite lymphocyte infiltration forming an inflammatory pseudotumor. Five patients with a clinical course of IgG4-RH less than nine months and a whole course of IgG4-RD less than two years were managed with glucocorticoids, while three patients with a longer history were administered glucocorticoids plus immunosuppressive agents. One patient went through surgical excision, and one patient was lost to follow-up. All patients showed a prompt response clinically, but only three patients had normalized serum IgG4 levels. Two patients who took medications for less than six months relapsed. Conclusions. IgG4-RD is a broad disease, and all physicians involved have to be aware of the possibility of pituitary dysfunction. Younger patients should be expected. The histopathological feature of pituitary gland biopsy could be atypical. For patients with a longer history, the combination of GC and immunosuppressive agents is favorable. Early and adequate courses of treatment are crucial for the management of IgG4-RH. With GC and/or immunosuppressant treatment, however, pituitary function or diabetes insipidus did not improve considerably.

Clinical Characteristics of Wolfram Syndrome in Chinese Population and a Novel Frameshift Mutation in WFS1.

OBJECTIVE: Wolfram syndrome (WS) is a rare, degenerative, and hereditary disorder characterized by ear diabetes mellitus (DM) and optic atrophy (OA). We aim to characterize clinical features in Chinese patients who had been poorly studied until now. METHODS: We performed a retrospective review of patients with WS seen in the Peking Union Medical College Hospital from 2002 to 2017. Data including demographic data, clinical presentations, examination results, family history, and genetic analysis were described. RESULTS: Six patients with WS were identified, meeting the diagnostic criteria of the coincidence of DM and OA before 15 years old or the existence of two WFS1 mutations. All were male, with the median age of 14.5 years (range 10-19 years). Blood glucose impairment, OA, and diabetes insipidus were present in all (100%), hearing impairment in four (66.7%), urological abnormalities in four (66.7%), neurological abnormalities in one (16.7%), and endocrine disorder in one (16.7%). Rare presentation includes cataract, glaucoma, and spina bifida occulta. Diabetes was insulin-dependent and not ketosis onset, with antibody to glutamic acid decarboxylase and islet cell negative. Genetic analysis revealed mutations in WFS1 in three patients. A novel frameshift mutation (p.Asp151Glufs*93) was identified in exon 4 of WFS1. CONCLUSION: Our series of WS patients indicated that WS is a degenerative disease with a wide and variable spectrum, characterized by ear non-autoimmune DM and bilateral OA. Genetic analysis is recommended when suspected of WS.

The effects of screening and intervention of subclinical hypothyroidism on pregnancy outcomes: a prospective multicenter single-blind, randomized, controlled study of thyroid function screening test during pregnancy.

PURPOSE: To evaluate the effect of subclinical hypothyroidism (SCH) screening and intervention on pregnancy outcomes and explore the significance of thyroid function during early pregnancy. METHODS: Pregnant women were recruited from Peking Union Medical College Hospital (screening group for measuring thyroid function and thyroid antibody in early pregnancy) and Haidian Maternal & Child Health Hospital (control group whose serum was stored and measured shortly after delivery) from July 2011 to December 2012. Thyrotropin levels 2.5-10 mIU/L and free T4 levels in normal range were considered SCH. Some of the screening group were treated with levothyroxine and adjusted. The others did not take medicine but kept a regular follow-up visit to doctors after antenatal clinic. The pregnancy outcomes and complications were compared. RESULTS: 1671 women (675 in screening group and 996 in control group) were recruited. 419 (167 from screening group) women was diagnosed as SCH. In screening group, 105 SCH and 4 hypothyroid women received thyroid hormone replacement therapy. The miscarriage and fetal macrosomia risks were lower, and cesarean was higher in screening group than control. CONCLUSION: Screening and intervention of SCH can significantly reduce the incidence rate of miscarriage.

[Relationship between maternal milk and serum thyroid hormones in patients with thyroid related diseases].

OBJECTIVE: To explore the relationship between maternal milk and serum thyroid hormones in patients with thyroid-related diseases. METHODS: Serum and breast milk samples were collected from 56 breastfeeding mothers. Milk and serum free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine(T3), thyroxine (T4), and thyrotrophin (TSH) were determined, and T3/T4 was calculated. Using the serum thyroid hormones as the independent variables and milk thyroid hormones as the dependent variables, we performed linear regression analysis. RESULTS: The milk FT3, FT4, T3, T4, TSH, and T3/T4 were (2.30 ± 0.82) pg/ml ,(0.45 ± 0.26) ng/dl, (0.35 ± 0.20) ng/ml, (2.96 ± 1.55) Μg/dl, (0.12 ± 0.08) ΜU/ml, and 0.12 ± 0.04, respectively. Milk FT3 (r = 0.778, P = 0.000), T3 (r = 0.603, P = 0.000), T4 (r = 0.485, P = 0.004), and TSH (r = 0.605, P = 0.000) concentrations were positively correlated with those in serum. CONCLUSION: Thyroid hormones are present in human milk and are positively correlated with those in serum.