The tortuous diagnosis of one case of neonatal hyperthyroidism.

OBJECTIVE: To outline the clinical signs, diagnosis, and course of care for a single case of neonatal hyperthyroidism while also summarizing common diagnostic errors related to this condition. METHODS: Medical records of the neonate of hyperthyroidism were collected and analyzed in combination with literature. RESULTS: The neonate's mother had thyroid disease, but her thyrotropin receptor antibody (TRAb) levels were not monitored during pregnancy. The neonate exhibited typical symptoms of hyperthyroidism on the day of birth but was not diagnosed until 15 days later. Impaired liver (cholestasis, elevated liver enzymes) and cardiac function (pulmonary hypertension, right heart enlargement) are the main manifestations. Treatment with methimazole (1.0 mg /kg·d) and propranolol (2.0 mg /kg·d) led to recovery, and the neonate stayed in the hospital for 27 days before being discharged with medication. The diagnosis was temporary hyperthyroidism, and the medication was discontinued at 72 days of age. CONCLUSION: It is important to strengthen the management of high-risk pregnant women with thyroid disease. Monitoring TRAb levels in both mothers and neonates should be done dynamically to enable early prediction and diagnosis of neonatal hyperthyroidism. Most neonates with hyperthyroidism have a good prognosis when timely and appropriate medical treatment is provided.

The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves' Disease.

BACKGRUOUND: To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves' disease (GD) in real-world practice. METHODS: This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year). RESULTS: Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (-84.7 [TSI slope, -198.2 to 8.2] vs. -120.1 [TSI slope, -204.4 to -45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII, P=0.001). CONCLUSION: Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

A retrospective study of clinical features and prognosis of patients with Graves' disease and ophthalmopathy.

OBJECTIVE: To retrospectively investigate the clinical characteristics of patients with Graves' disease (GD) accompanied by ophthalmopathy (GO) and the prognosis of single 131I therapy. METHODS: In total, 665 patientswith Graves' disease were enrolled in this study, including 115 patients with GO and 550 patients without GO. On the one hand, the clinical characteristics of the two groups were recorded. On the other hand, the prognosis after more than 6 months of 131I therapy was divided into three groups: recovered, hypothyroidism and unhealed. RESULTS: Compared with GD-alone patients, GD patients with GO were younger, had a higher thyrotrophin receptor antibody (TRAb), heavier thyroid mass and higher dose of single 131I therapy (all P < 0.05). Furthermore, patients were younger in the clinical active score ≥3 group and had higher FT4 level in the mild GO group (all P < 0.05). Among these, age and TRAb were independent risk factors for GO in GD patients (P < 0.05). When age was <52.5 years and TRAb was >24.01 IU/L, GD patients were more likely to develop GO (P < 0.001). After at least 6 months of single 131I therapy, compared with GD-alone patients, the prognosis was poor in GD patients with GO (P < 0.05). CONCLUSION: Young GD patients with heavy thyroid mass and high TRAb are more likely to have GO. Younger GO patients are more likely to be active stage and the level of thyroid function was inversely correlated with the severity of GO. When the age and TRAb have exceeded the cutoff value, we should pay more attention to the occurrence of GO and shorten the follow-up interval appropriately. Patients with GD combined with GO have a poor prognosis.

Tocilizumab for the Management of Thyroid-Associated Orbitopathy.

PURPOSE: To describe the efficacy of tocilizumab in the treatment of a cohort of patients with active thyroid-associated orbitopathy. METHODS: Patients were identified with active thyroid-associated orbitopathy who were intolerant of or had progression of disease despite systemic corticosteroids and subsequently were treated with tocilizumab between January 2015 and December 2020. Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels were assessed prior to initiation of tocilizumab, following the first dose, and after the completion of treatment. RESULTS: Eleven patients were candidates for and underwent treatment with tocilizumab, 9 of which met criteria for analysis. Average age was 55.6 years. Average time between onset of active thyroid-associated orbitopathy and completion of tocilizumab was 6.5 months. Average number of infusions was 4.2. There was a statistically significant reduction in Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels when comparing pre-treatment values (mean Clinical Activity Score 6.78 ± 1.09, mean Thyroid-Associated Ophthalmopathy Scale score 10.2 ± 1.92, mean thyroid-stimulating immunoglobulin level 440.6 [%]) to values immediately following completion of treatment (mean Clinical Activity Score 0.44 ± 0.53, mean difference 6.3 points, p < 0.001 [95% CI, 5.5-7.2]; mean Thyroid-Associated Ophthalmopathy Scale score 1.2 ± 1.09, mean difference 9.0 points, p < 0.001 [95% CI, 7.2-10.8]; mean thyroid-stimulating immunoglobulin level 200.7 [%], mean difference 239.9 [%], p = 0.001 [95% CI, 124.3-355.4]). One patient had elevation of cholesterol following therapy induction. Patients were followed for an average of 23.6 months after treatment. No patients had recurrence of active disease after completion of tocilizumab. CONCLUSIONS: This study supports the use of tocilizumab as a therapy for the inflammatory phase of thyroid-associated orbitopathy.

Clinical challenge: An orbital Hickam's dictum.

A 53-year-old man with hyperthyroidism presented with asymmetric proptosis and diplopia. Thyroid-stimulating immunoglobulin was elevated, suggesting active thyroid eye disease. Imaging of the orbits revealed enlargement of the extraocular muscles, including irregular enlargement of the left lateral rectus muscle. Biopsy of the lateral rectus muscle demonstrated infiltration of the muscle with Bcl-2 positive B lymphocytes consistent with chronic lymphocytic leukemia (CLL). Evaluation for systemic lymphoproliferative disease was negative. The patient was treated with orbital radiotherapy at specific dosages for both TED and CLL. He responded well to therapy with a reduction in proptosis and diplopia and no evidence of recurrent CLL.

Graves' disease after interleukin-2 therapy in a patient with human immunodeficiency virus infection.

Interleukin-2 (IL-2) is a cytokine that regulates the proliferation and differentiation of lymphocytes, and is currently used clinically in the treatment of assorted malignancies. Additionally, IL-2 is being actively investigated in clinical trials for treatment of human immunodeficiency virus (HIV) infection. Patients treated with IL-2 are susceptible to autoimmune thyroid disease (AITD), presenting as thyroiditis, which leads to either thyrotoxicosis or hypothyroidism, if not correctly and promptly identified and treated. IL-2-induced hypothyroidism can also sometimes follow a thyrotoxic phase. However, the development of Graves' disease (GD) in this clinical setting has not been reported to date. Here, we report the case of a 39-year-old HIV-infected man in whom GD developed after IL-2 therapy. We correlated the immunologic parameters pertinent to the patient's HIV infection status with clinical, hormonal, and serologic evidence of GD during its emergence. This revealed an association between peripheral blood cell numbers of specific lymphocyte subpopulations (CD4(+), CD3(+)CD25(+), and naïve T-cells) and serum levels of markers for AITD (free thyroxine [T(4)] and thyroid-stimulating immunoglobulin). Interestingly, no association was found between natural killer (NK) cell numbers and AITD markers. The immunopathogenesis of GD in this patient may be similar to that hypothesized for the GD that occurs in immune-reconstituted patients after combination antiretroviral therapy. From a practical standpoint, we propose that patients who have received or are receiving treatment with IL-2 who show signs of hyperthyroidism need to be carefully evaluated for GD.

Comparison between mycophenolate mofetil- and azathioprine-based immunosuppressions in clinical lung transplantation.

BACKGROUND: The aim of the study was to assess the impact of mycophenolate mofetil (MMF) on the early phase after lung transplantation. PATIENTS AND METHODS: Thirty-eight consecutive patients between November 1994 and January 1997 were treated with cyclosporine, prednisolone, antithymocyte globuline induction therapy, and either MMF (n = 21) or azathioprine (Aza) (n = 17). Four patients from the MMF group and 2 patients from the Aza group were intubated and in the ICU prior to transplantation. Demographic data and primary diagnosis were comparable. MMF was administered at a dosage of 2 gm/day whereas Aza was initiated at 2 mg/kg/day and adapted by leukocyte count. Three-month survival and incidence of rejections and infections were compared. RESULTS: Six-month survival in the MMF group was 76% compared to 65% in the Aza group (n.s.). The mean number of acute rejection episodes in the MMF and Aza group were 0.29+/-0.10 and 1.53+/-0.29 (p<0.01) respectively. Transbronchial biopsy (TBB) results > or =grade 2 ISHLT were seen in 10% of MMF and in 43% of Aza-treated patients; completely free from rejection were 17 MMF and 3 Aza patients. The mean number of infections per patient in the MMF and Aza group were 1.57+/-0.29 and 2.29+/-0.40 respectively, bacterial (1.10 vs. 1.71), viral (0.35 vs. 0.33), and fungal (0.14 vs. 0.24) infections were the same in both groups. CONCLUSIONS: These data result suggest that mycophenolate mofetil therapy is more effective in preventing rejection episodes in patients early after lung transplantation than therapy with azathioprine. We therefore conclude that MMF is a safe and effective drug to optimize immunosuppressive therapy in the early phase after lung transplantation.