OBJECTIVE: Hyperthyroidism guidelines have not been updated over the past five years, despite numerous data on the subject, and recent studies providing a wide variation in treatment success rates. We aim to compare the effectiveness and safety of treatment modalities in patients with Graves\' disease or toxic nodular disease.
METHODS: Single center retrospective cohort study of Graves\' disease and toxic nodular disease patients treated between 1983 and 2023.
RESULTS: A total of 411 patients were treated for hyperthyroidism, 245 due to Graves\' disease and 166 due to or toxic nodular disease, followed for a median of 7 years. In Graves\' disease, 90.2% were treated with antithyroid drugs over 250 cycles, achieving 41.7% cumulative remission. Half of all relapses (50.9%) occurred in the first year, 76.3% in the first three years, and 98.3% within nine years. Treatment periods of 12-24 months showed higher remission and lower relapse rates than longer periods. I-131 was used in 103 cycles with 82.5% remission and 7.1% relapse. A total of 29 thyroidectomies resulted in 100% remission, with no relapse. In toxic nodular disease, surgery was the most frequently used treatment (54.5%), followed by I-131 (37.1%).
CONCLUSIONS: Our findings support antithyroid drugs as the preferential first-line treatment for Graves\' disease, allowing for euthyroidism with minimal adverse effects. Given the propensity for relapse, we suggest a rigorous monitoring, particularly within the first three years. In toxic nodular disease, surgery should be the preferred option, with I-131 being reserved for single adenomas and small goiters.

Due to the high mortality rate of TS, effective guidance for its diagnosis and treatment is essential. The diagnostic criteria introduced by the JTA in 2012, along with the Burch-Wartofsky Point Scale, constitute valuable tools for the diagnosis of TS. In 2016, Guidelines on the management of TS were produced by the JTA and the JES. Recently, a prospective multicenter register-based study compared the prognosis and outcome of 110 new-onset TS patients with the results of previous comparable studies and evaluated the efficacy of the Guidelines. The study revealed higher APACHE II scores and significant correlations between lower BMI, post-resuscitation shock, and fever with outcomes and, overall, improved TS prognosis. Most patients in the study received methimazole and potassium iodide, the timely administration of which was linked to lower fatality rates. Adherence to treatment guidelines correlates with lower mortality rates, emphasizing the importance of experienced multidisciplinary teams in ICU settings and the necessity for periodic review of the guidelines to enhance therapeutic approaches and reduce mortality.

A case of a 43-year-old male with a history of Graves\' disease treated with propylthiouracil was investigated for vasculitis and lymphoproliferative disease. However, his clinical picture was complicated by recurrent episodes of neurological symptoms resembling stroke syndrome, which widened the breadth of the diagnostic workup. Extensive investigations, including imaging and biopsies, excluded other possibilities. The patient was treated as probable cerebral vasculitis after identifying new narrowing in the left middle cerebral artery and was treated with pulsed intravenous methylprednisolone, followed by high-dose oral prednisolone and cyclophosphamide. Repeated brain imaging showed further narrowing of the large vessels, which reaffirmed the likelihood of vasculitis necessitating continuation of induction therapy with further maintenance treatment, which led to stabilization of neurological burden and symptom recovery. This case elucidates complexities in reaching the diagnosis of drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which can present heterogeneously and mimic other clinical entities such as stroke.

OBJECTIVE: Graves\' disease (GD) is an auto-immune cause of hyperthyroidism. First-line treatment often consists of a 12-18 month course of antithyroid drugs (ATD). After discontinuation of ATD, GD relapses in approximately 50% of patients. The \'Graves recurrent event after therapy+ \' (GREAT+) score may predict individual relapse chances after ATD discontinuation more accurately based on clinical and laboratory parameters at diagnosis. We investigated the need for the GREAT+ score through an online questionnaire among GD patients and physicians treating GD.
METHODS: An anonymous online questionnaire was distributed to patients and physicians between June 2022 and August 2023.
RESULTS: The questionnaire was completed by 532 patients and 44 physicians. Results showed that 94% of patients were interested in knowing their GREAT+ score at the start of treatment. 55% would consider definite treatment (radioiodine/thyroidectomy) as first-line treatment in case of a high relapse chance. 98% of the physicians indicated the GREAT + score would support patient counseling. 84% may change their advice for first-line treatment if a patient has a high relapse chance based on the score.
CONCLUSIONS: Patients and physicians considered the GREAT+ score as a valuable addition to the current available information which could change treatment decisions. Therefore, external validation of the GREAT+ score is justified to implement this score in clinical practice.

Preconception evaluation of couples wishing to conceive is an important step toward a healthy pregnancy and it is especially important in people with a chronic condition or at genetic risk. The most common endocrine disorders in women at reproductive age are those involving the thyroid gland and it is well recognized that hyperthyroidism (HT), over-function of the thyroid gland, is associated with risks of maternal, fetal, and neonatal complications. The aim of this paper is to review the latest evidence regarding the components of preconception counseling in women with HT that contemplate a pregnancy. We also want to raise awareness among healthcare professionals about the importance of periconceptional counseling in improving pregnancy outcomes and avoid maternal and fetal complications related to thyroid dysfunction. In women with Graves\' disease seeking pregnancy, it is essential to discuss all the treatment options along with the associated risks and benefits. Extensive prospective studies are still needed to understand the implications of current recommended strategies for the management of HT in preconception and during pregnancy.

BACKGROUND: Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database.
METHODS: We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV.
RESULTS: Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake.
CONCLUSIONS: This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

UNASSIGNED: Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver transplantation requirement and mortality.
UNASSIGNED: The primary objective of the systematic review was to assess the clinical characteristics and outcomes of patients with drug induced liver injury (DILI) due to ATDs.
UNASSIGNED: We conducted a systematic review of PUBMED, SCOPUS, and EMBASE on characteristics and outcomes of adults (>18 years) with DILI due to ATDs. We defined DILI as bilirubin ≥2.5 mg/dL or international normalized ratio >1.5 with any rise in alanine aminotransferase (ALT), aminotransferase (AST), or alkaline phosphatase (ALP), or an elevation of ALT or AST >5 times or ALP >2 times the upper limit of normal without jaundice/coagulopathy.
UNASSIGNED: The review included 100 articles describing 271 patients; 148 (70.8%) were female (N = 209). Mean age was 42.9 ± 17.2 years. Graves\' disease was the most common indication for ATDs. Carbimazole/methimazole (CBM/MMI) was the most common offending agent (55.7%). DILI pattern was hepatocellular in 41.8%, cholestatic in 41.3%, and mixed in 16.9%. Outcomes included death in 11.8%, liver transplantation in 6.4%, partial improvement in 2.2%, and complete resolution in 79.6% with a median time (IQR) to resolution of 45 (20-90) days. Patients in the propylthiouracil (PTU) group had higher initial bilirubin, initial AST, initial ALT, peak ALT, peak AST, severe and fatal DILI, liver transplantation, and mortality than CBM/MMI. Rechallenge of antithyroid medication was infrequently reported (n = 16) but was successful in 75%.
UNASSIGNED: DILI due to ATDs can present with different patterns and should prompt immediate drug discontinuation. Referral to a hepatologist should be considered if severe as transplantation is sometimes required. PTU-induced DILI may have worse outcomes than CBM/MMI.

Agranulocytosis is a rare but life-threatening complication of methimazole and propylthiouracil, antithyroid drugs (ATDs) prescribed for the treatment of hyperthyroidism. We report the case of a 41-year-old female who presented to our institution with complaints of fevers, chills, sore throat, myalgias, and generalized weakness one month after treatment initiation with methimazole. A complete blood count at admission revealed agranulocytosis with an absolute neutrophil count of 0/μl. After discontinuation of the medication, she was treated with granulocyte-colony stimulating factor and intravenous broad-spectrum antibiotics, which improved her condition on day seven of hospitalization. Although agranulocytosis is a rare complication of antithyroid drugs, providers must maintain a high index of clinical suspicion as prompt diagnosis and treatment are essential. After the diagnosis is confirmed with an absolute neutrophil count <500/μl, management involves discontinuation of the offending agent and initiation of intravenous broad-spectrum antibiotics. Granulocyte-colony stimulating factor, commonly employed in addition to antibiotics, is a controversial treatment option and more research demonstrating its efficacy is necessitated. Preventing mortality associated with antithyroid drug-induced agranulocytosis is achieved through patient education at the time of ATD initiation.

BACKGROUND: Free T4 (FT4) determination is one of the most commonly performed biochemical tests in endocrinology. Treatment of thyroid dysfunctions is adjusted based on the severity of symptoms and biochemical test results. For Graves\' hyperthyroidism, clinical guidelines recommend using FT4 as a (rough) guide to dose antithyroid drugs, together with other clinical information. It is well known that different platforms and methods give different FT4 results; however, large non-linear method differences at high FT4 concentrations are less well recognized. Current clinical guidelines do not make it clear that method differences in the hyperthyroid range can affect recommendations.
METHODS: Serum samples from patients with very low (biochemically hypothyroid) to very high (hyperthyroid) concentrations of FT4 and/or free T3 (FT3) were analyzed using Abbott Alinity and compared to concentrations measured using Roche Cobas, Siemens ADVIA Centaur (FT4 only) and an in-house equilibrium dialysis liquid chromatography tandem mass spectrometry (LC-MS/MS) method.
RESULTS: Alinity measured markedly lower FT4 and FT3 concentrations compared to the other methods, particularly at high FT4 concentrations. Regression analysis indicated that Alinity FT4 had a non-linear (curved) relationship to FT4 measured by the other methods. The method differences affected guideline-recommended treatments for hyperthyroidism.
CONCLUSIONS: Measured free thyroid hormone concentrations are highly method-dependent, especially at high FT4 concentrations. Clinicians treating hyperthyroid patients should be aware that patients appear much less hyperthyroid from FT4-measurements performed using Alinity compared to Cobas or Centaur. Guideline-recommended antithyroid drug dosages based on FT4 (including multiples of the upper reference range) have to be adjusted to the FT4 method used. FT4 results from different methods should be clearly distinguished (e.g. separate lines) in medical records.

UNASSIGNED: Agranulocytosis is a rare but fatal side effect of antithyroid drugs (ATDs) with incidence reported at 0.1%-1%. Agranulocytosis is defined as a granulocyte count <500 cells/μL following the use of ATDs and is an absolute contraindication to the use of these drugs; in this case, radioactive iodine (RAI) or surgery are therapeutic options.
UNASSIGNED: A 28-year-old female patient was on follow-up at our clinic after she presented with anterior neck swelling of 4 years. The patient was started on propylthiouracil (PTU) and propranolol based on clinical symptoms of hyperthyroidism and low thyroid stimulating hormone (TSH) levels. After taking the ATDs for 7 months, she came to the clinic for her regular follow-up. At this point, she was declared euthyroid and booked for surgery. Investigations were sent and the complete blood count (CBC) result showed leucopenia with agranulocytosis, even though she was completely asymptomatic. The offending ATD was immediately discontinued. The patient was kept inpatient for monitoring, and lugol\'s iodine and propranolol were initiated. Eight days after discontinuing the ATD, the CBC profile was determined once again, showing normalized total leukocyte, as well as, absolute neutrophil count. Eventually, the multinodular goiter (MNG) was managed with subtotal thyroidectomy.
UNASSIGNED: Despite the fact that agranulocytosis is an extremely rare side effect of ATDs, most often PTU; it is a potentially fatal complication when it occurs. Patient education at the time of prescription should not be overlooked, and systematic programs should be put in place. The baseline granulocyte count should be determined and monitored on a regular basis.