This case report details the unusual presentation and successful management of a 25-year-old male diagnosed with both hyperthyroidism and adrenal insufficiency. The patient initially presented with symptoms of fatigue, weight loss, and palpitations, with no significant past medical history. Further evaluation revealed elevated thyroid hormone levels and decreased cortisol levels, confirming the diagnosis of concurrent hyperthyroidism and adrenal insufficiency. The complexity of managing these coexisting endocrine disorders required a multidisciplinary approach. Techniques utilized included detailed hormonal assays, imaging studies, and dynamic endocrine testing. The therapeutic regimen involved the administration of antithyroid medications, beta-blockers for symptom control, and glucocorticoid replacement therapy. This report underscores the importance of considering multiple endocrine disorders in patients with nonspecific systemic symptoms and highlights the need for individualized treatment plans to address the unique challenges presented by such comorbidities.

Thyrotoxicosis, also known as hyperthyroidism, is a condition characterized by the excessive production of thyroid hormones by the thyroid gland. Besides Graves\' disease, other common causes of thyrotoxicosis include toxic multinodular goiter, toxic adenoma, and subacute thyroiditis. The treatment of thyrotoxicosis depends on the underlying cause and may include medications (e.g., antithyroid drugs, beta-blockers), radioactive iodine therapy, or surgical removal of the thyroid gland (thyroidectomy). In this report, we present two instances of thyrotoxicosis where conventional high doses of antithyroid treatment failed to control the condition effectively. This failure prompted the exploration of alternative therapeutic interventions. These cases highlight the intricacies involved in managing thyrotoxic crises that do not respond to methimazole (MMI), emphasizing the necessity for innovative approaches such as plasmapheresis and thyroidectomy. Understanding such scenarios is vital for enhancing the care provided to patients encountering resistance to standard treatments. The distinct clinical pathways and treatment strategies adopted in these cases offer valuable insights into this disease management, particularly concerning resistance to MMI.

OBJECTIVE: To assess the therapeutic outcome and factors predicting remission in hyperthyroid patients treated with low-dose I-131 (radioactive iodine) from a tertiary care hospital in South India.
METHODS: This 20-year single-institutional retrospective study was carried out on 3891 hyperthyroid adult patients. Only those patients with complete clinical records were audited. Selection criteria were based on patients with scintigraphic diagnosis of either Graves\' disease (GD), toxic multinodular goitre (TMNG) or autonomous toxic nodule (ATN) and the records of those who received low-dose I-131 therapy (LDT) between March 2000 and 2020 at Amrita Institute, Cochin were analysed. SPSS 10 software was used for statistical analysis.
RESULTS: The records of 3891 hyperthyroid predominantly female patients were analysed. 65% patients had GD, 33% had TMNG and 3% were ATN. High rates of remission as early as 12 weeks (in 61% patients) was observed with a single dose of LDT while on strict iodine-free diet for 3-4 weeks prior to LDT. Study reveals that those with lower free T4 (fT4), small goitre (thyroid volume < 25 cm3), < 15% thyroid trapping function, shorter time duration from onset of hyperthyroidism to LDT, and treatment-naïve patients were factors determining high remission rates. Mann Whitney U test and Chi-square test was used to correlate variables in the remission and relapse groups. We found a positive correlation between fT4, thyroid volume (r = 0.35, p < 0.01) and trapping function (r = 0.34, p < 0.01), which were independent of age, sex, body mass index and TSH levels in our study.
CONCLUSIONS: High therapeutic outcome was observed with a single dose of LDT while on iodine-free diet. Remission with single dose of LDT occurred in 90% patients by 5th month. Of them 56% patients were treatment naive prior to LDT. LDT is thus a safe and effective therapy in hyperthyroid patients and can be recommended as a primary modality of management.

BACKGROUND: Graves\' disease is an autoimmune disorder of the thyroid gland associated with the overproduction of thyroid hormones. Excess secretion of thyroid hormones leads to cardiovascular consequences. Treatment options include antithyroid medications (ATM), radioactive iodine (RAI) ablation, and total thyroidectomy. We examined the cardiovascular outcomes following Graves\' disease management modality.
METHODS: A systematic search was performed up to September 22nd, 2021, using PubMed, EMBASE, and Web of Science databases. We conducted a network meta-analysis analyzing cardiovascular outcomes of interest, including congestive heart failure (CHF), arrhythmia, atrial fibrillation (AF), and hypertension.
RESULTS: Three studies were included in this analysis totaling 6700 patients with Graves\' disease, of which 74% were female. The mean age was 44.34 y. When compared to pretreatment, management options lowered the risk of maintaining arrhythmia 81% with surgery (relative risk [RR] = 0.19; 95% confidence interval [CI] = 0.12 to 0.31), 67% with ATM (RR = 0.33; 95% CI = 0.23 to 0.49), and 50% with RAI (RR = 0.50; 95% CI = 0.13 to 1.95). Risk of maintaining CHF was reduced 80% with surgery (RR = 0.20; 95% CI = 0.08 to 0.49), 41% with ATM (RR = 0.59; 95%CI = 0.52 to 0.67), and only 7% with RAI (RR = 0.93; 95%CI = 0.68 to 1.26). Treatment-ranking analysis found all parameters, including CHF, arrhythmia, AF, and hypertension, to be in favor of surgical treatment over medical treatment and RAI ablation.
CONCLUSIONS: This is the first network meta-analysis analyzing the cardiovascular outcomes in Graves\' disease patients by treatment option. Our study demonstrated that surgery is superior to RAI and medical treatment.

Carbimazole-induced agranulocytosis is a rare condition. A 48-year-old female patient with a history of hyperthyroidism for several years presented with generalized fatigue and chest pain associated with palpitations; the patient was stable on carbimazole therapy. She was previously on carbimazole 15 mg once daily (OD) and, three months later, was reduced to 10 mg OD as symptoms were controlled. She was taking propranolol, and it was stopped as she was not having any palpitations. This time, however, she presented mainly with palpitations at night associated with chest pain and generalized fatigue ongoing for the last one week. Her laboratory results showed agranulocytosis with reduced white cell count and neutrophil count in the absence of any evidence of infection. Her carbimazole was stopped, and the patient was referred to ear, nose, and throat surgeons for consideration of thyroidectomy. The patient underwent subtotal thyroidectomy, and her symptoms resolved following surgery.

Background Graves\' disease is the most common cause of thyrotoxicosis. It can be treated using three different modalities, which include anti-thyroid drugs (ATD), radioactive iodine (RAI), and near-total thyroidectomy. This cohort study aimed to assess the treatment modality preferred at King Abdulaziz Medical City (KAMC) and to compare the treatment options in relation to the prognosis of the disease. Methods A retrospective cohort study was conducted on a total of 100 patients with Graves\' disease who were treated and followed up in the endocrine clinics at KAMC between January 2013 and December 2018. Data on age at diagnosis, duration of illness, treatment modality, and response to treatment were extracted from paper and electronic medical files and analyzed. Results A total of 100 patients with Graves\' disease were included in this cohort study. The ratio of female:male was 2:1. The median age in years was 32 (16). They were treated with ATD (60%), RAI ablation (40%), and none were treated by surgery. The remission rate was 53.3% for patients treated with ATD and 95% for RAI ablation. Hypothyroidism occurred in 90% of the responders to RAI and in 12% that were treated with ATD. Most of the patients that relapsed underwent RAI as the second line of treatment. Their remission rate was 78.6%. Conclusion ATD was the treatment modality mostly used for Graves\' disease in our center. It resulted in a remission rate of 53%, which is higher than reported in national studies. Although the rate of remission post RAI ablation was as high as 95%, most patients developed hypothyroidism.

Background: Considerable uncertainty remains about the pattern of use of treatment options for Graves\' disease (GD) and their comparative effectiveness and safety. Methods: Between 2005 and 2013, we identified patients with GD who received antithyroid drugs (ATDs), radioactive iodine (RAI) or surgery, and were represented in a large administrative data set in the United States (OptumLabs® Data Warehouse). Results: We identified 4661 patients with GD: mean age 48 (SD ±14) years, white (63%), and female (80%). Patients received ATD, n = 2817 (60%), RAI, n = 1549 (33%), or surgery, n = 295 (6%). Success rates were 50% for ATD, 93% for RAI, and 99% for surgery. Median time to treatment failure was 6.8 months for ATD and 3 months for RAI and surgery. When patients were required to be on ATD for at least one year before assessing failure, the failure rate decreased to 25%. Adverse effects occurred in 12% of patients receiving ATD, 6% with RAI, and 24% with surgery. Factors associated with treatment success were age >55 years (for ATD) and female sex (for RAI). About 12% of patients receiving ATD continued this treatment for >24 months as initial therapy. When patients failed ATD therapy, the most common second-line therapy was reinitiation of ATD (65%), RAI (26%), and surgery (9%). Overall, 26% of patients remain on ATD therapy (combined first or second line). Conclusions: ATD therapy was the most common GD therapy and demonstrated the lowest efficacy and infrequent significant adverse effect profile. With one fourth of patients remaining on ATD treatment (initial or second modality treatment), it becomes imperative to determine the long-term efficacy, safety, costs, and burdens of this modality of treatment.

BACKGROUND: Idiosyncratic drug-induced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such as biotherapies outside the context of oncology. In the present paper, we report and discuss the clinical data and management of this relatively rare disorder, with a focus on biotherapies used in autoimmune and auto-inflammatory diseases.
METHODS: A review of the literature was carried out using the PubMed database of the US National Library of Medicine. We searched for articles published between January 2010 and May 2019 using the following key words or associations: \"drug-induced neutropenia\", \"drug-induced agranulocytosis\", and \"idiosyncratic agranulocytosis\". We included specific searches on several biotherapies used outside the context of oncology, including: tumor necrosis factor (TNF)-alpha inhibitors, anti-CD20 agents, anti-C52 agents, interleukin (IL) 6 inhibitors, IL 1 inhibitors, and B-cell activating factor inhibitor.
RESULTS: Idiosyncratic neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients with grade 3 or 4 neutropenia (neutrophil count (NC) ≤ 0.5 × 109/L and ≤ 0.1 × 109/L, respectively). Over the last 20 years, several drugs have been strongly associated with the occurrence of idiosyncratic neutropenia, including antithyroid drugs, ticlopidine, clozapine, sulfasalazine, antibiotics such as trimethoprim-sulfamethoxazole, and deferiprone. Transient grade 1-2 neutropenia (absolute blood NC between 1.5 and 0.5 × 109/L) related to biotherapy is relatively common with these drugs. An approximate 10% prevalence of such neutropenia has been reported with several of these biotherapies (e.g., TNF-alpha inhibitors, IL6 inhibitors, and anti-CD52 agents). Grade 3-4 neutropenia or agranulocytosis and clinical manifestations related to sepsis are less common, with only a few case reports to date for most biotherapies. Special mention should be made of late onset and potentially severe neutropenia, especially following anti-CD52 agent therapy. During drug therapy, several prognostic factors have been identified that may be helpful when identifying \'susceptible\' patients. Older age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 109/L have been identified as poor prognostic factors. Idiosyncratic neutropenia should be managed depending on clinical severity, with permanent/transient discontinuation or a lower dose of the drug, switching from one drug to another of the same or another class, broad-spectrum antibiotics in cases of sepsis, and hematopoietic growth factors (particularly G-CSF).
CONCLUSIONS: Significant progress has been made in recent years in the field of idiosyncratic drug-induced neutropenia, leading to an improvement in their prognosis (currently, mortality rate between 5 and 10%). Clinicians must continue their efforts to improve their knowledge of these adverse events with new drugs as biotherapies.