Riedel's thyroiditis: report of 7 patients and review of literature.

Riedel's thyroiditis is a rare inflammatory-sclerosing thyroid disease, and its aetiology remains unknown. After a surgical biopsy to establish the diagnosis, the treatment of Riedel's thyroiditis is still challenging in most patients. The aim of this article is to report seven patients with Riedel's thyroiditis seen in a department of Endocrinology and Metabolic diseases over a period of 24 years, and based on the patient's data and the review of the literature to discuss the indications of surgery, glucocorticoids, tamoxifen and immunosuppressive drugs in the personalized treatment of patients with Riedel's thyroiditis.

Concurrent pretibial myxedema and thyroid eye disease following mRNA COVID-19 vaccine in a patient with history of Graves' disease.

A 70-year-old female had a history of thyroid surgery for benign nodules and Graves' disease. Following mRNA COVID-19 vaccination, she presented Graves' orbitopathy and pretibial myxedema. Symptoms of thyroid eye disease and thyroid dermopathy improved after 500-mg methylprednisolone infusions.

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study.

BACKGROUND: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence. METHODS: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete. FINDINGS: Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment. FUNDING: AIFA, ENSAT Cancer Health F2-2010-259735 programme, Deutsche Forschungsgemeinschaft, Cancer Research UK, and the French Ministry of Health.

Central Hypothyroidism is Frequent During Mitotane Therapy in Adrenocortical Cancer Patients: Prevalence and Timeline.

CONTEXT: Central hypothyroidism was described previously in mitotane-treated patients but data on its prevalence and time of occurrence are limited. OBJECTIVE: To better characterize thyroid hormone insufficiency in patients exposed to mitotane. METHODS: We reviewed medical records of patients from 2 academic centers in Montreal (Canada) and Toulouse (France) with exposure to mitotane therapy for adrenocortical cancer between 1995 and 2020. We analyzed the thyroid function parameters during and after treatment. RESULTS: In our cohort of 83 patients, 17 were excluded because of preexisting primary hypothyroidism or drug-induced hypothyroidism. During follow-up, 3/66 patients maintained a normal thyroid function and 63/66 developed central hypothyroidism. Among those 63 patients, 56 presented with an inappropriately normal or low TSH and 7 with a mildly elevated TSH. The onset of hypothyroidism was: <3 months in 33.3%, 3 to 6 months in 19.1%, 6 to 9 months in 14.3%, and 9 to 12 months in 9.5%. At least 14.3% of cases occurred after 12 months of exposure, and 6 patients had an undetermined time of occurrence. Over time, 27 patients stopped mitotane and partial (42.3%) or complete (23.1%) recovery from hypothyroidism was observed, mainly in the first 2 years after mitotane discontinuation. CONCLUSION: Mitotane therapy is frequently associated with new onset of central hypothyroidism with a prevalence of 95.5%. Most cases occurred in the first year of treatment. Partial or full recovery of thyroid function occurs in 65.4% of cases. This study supports the importance of systematic monitoring of TSH and free T4 levels during and following discontinuation of mitotane therapy.

The Use of Levothyroxine Absorption Tests in Clinical Practice.

Although levothyroxine (LT4) is a widely prescribed drug, more than 30% of LT4-treated patients fail to achieve the recommended serum level of thyrotropin with a body weight-based dose of LT4. An LT4 absorption test (LT4AT) is part of the workup for confirming normal LT4 absorption or diagnosing malabsorption. We searched PubMed with the terms levothyrox*, L-T4, LT4, TT4, FT4, FT3, TT3, test, loading, uptake, absorp*, "absorb*, bioavailab*, bioequiv* malabsorb*, and pseudomalabsorb*. A total of 43 full-text publications were analyzed. The published procedures for LT4AT differ markedly in the test dose, formulation, test duration, frequency of blood collection, analyte (total thyroxine [TT4] or free thyroxine [FT4]), metric (absolute or relative peak or increment, or area under the curve) and the threshold for normal absorption. In a standardized LT4AT for routine use, the physician could advise the patient to not consume food, beverages, or medications the morning of the test; administer 1000 µg of LT4 in the patient's usual formulation as the test dose; ensure that the patient is supervised throughout the LT4AT; perform a 4-hour test, with hourly blood samples; assay FT4; and consider that normal LT4 absorption corresponds to an FT4 increment of more than 0.40 ng/dL (5.14 pmol/L) or a TT4 increment of more than 6 µg/dL (77.23 nmol/L) for a test dose of at least 300 µg, or a percentage TT4 absorption of more than 60%. If the test indicates abnormal LT4 absorption, the physician can increase the LT4 dose, change the formulation or administration route, and/or refer the patient to a gastroenterologist.

Is systematic Gadolinium injection relevant during MRI follow-up for non-functioning pituitary macroadenomas?

OBJECTIVE: To compare the performance of coronal contrast-enhanced T1-weighted (ceT1-w) and T2-weighted (T2-w) sequences for diagnosing progression during the MRI follow-up of Non-Functioning Pituitary MacroAdenomas (NFPMAs). PATIENTS AND METHODS: 106 patients, who had at least two MRIs for the follow-up of NFPMA, were enrolled retrospectively. The largest adenoma diameter was measured on coronal ceT1-w sequences and separately on T2-w sequences for all follow-up MRIs. Interobserver variability was also assessed by 2 independent neuroradiologists in a sample series of 100 examinations. Progression was defined by an increase ≥ 2 mm in diameter between 2 MRIs. Progression thresholds of 3 and 4 mm were also tested. The results of ceT1-w and T2-w sequences were analysed for concordance. RESULTS: 93.1% concordance was achieved between ceT1-w and T2-w coronal sequences in 580 follow-up MRIs. In the case of progression detected on at least one sequence, 64.4% concordance was documented for a 2-mm threshold, 87.7% for 3-mm and 97.1% for 4-mm. Discordance was mainly observed on the first postoperative MRI and in case of NFPMAs with multiple recurrences. Kappa was better for diagnosing progression on T2-w than on ceT1-w sequences (0.67 vs. 0.54). It should be noted that 100% agreement was observed between the 2 sequences in the 82 follow-up MRIs of patients with complete surgical resection. CONCLUSION: 93.1% concordance was achieved for coronal ceT1-w and T2-w sequences during the MRI follow-up of NFPMAs, thus challenging systematic injection of gadolinium. If MRI without gadolinium injection is a first-line option, our results suggest that ceT1-w sequences should be reserved for the first postoperative MRI and for the follow-up of aggressive and recurrent NFPMAs.

Life expectancy and likelihood of surgery in multiple endocrine neoplasia type 1: AFCE and GTE cohort study.

BACKGROUND: The overall natural history, risk of death and surgical burden of patients with multiple endocrine neoplasia type 1 (MEN1) is not well known. METHODS: Patients with MEN1 from a nationwide cohort were included. The survival of patients with MEN1 was compared with that of the general population using simulated controls. The cumulative probabilities of MEN1-specific operations and postoperative mortality were assessed, and surgical sequences were analysed using sunburst charts and Venn diagrams. RESULTS: A total of 1386 patients with MEN1 were included. Life expectancy was significantly reduced in patients with MEN1 compared with simulated controls from the general population, with a lifetime difference of 15 years. Mutations affecting the JunD interaction domain had a significant negative impact on survival. Survival for patients with MEN1 compared with the general population improved over time. The probability of experiencing at least one specific MEN1 operation was above 95 per cent after 75 years, and most patients had surgery at least twice during their lifetime. Time to a 50 per cent risk of MEN1 surgery was 30.5 years for patients born after 1960, compared with 47.9 years for those born before 1960. Sex and mutations affecting the JunD interacting domain had no impact on time to first surgery. There was considerable heterogeneity in surgical sequences, with no specific clinical pathway. CONCLUSION: Life expectancy was significantly lower among patients with MEN1 compared with the general population, and further decreased in patients with mutations affecting the JunD interacting domain. Almost all patients underwent at least one MEN1-specific operation during their lifetime, but there was no standardized sequence of surgery.

Orbital inflammatory disease following mRNA SARS-CoV-2 vaccine.

A 65-year-old woman reported orbital symptoms two days after her first dose and presented exacerbation of signs after the second dose of BNT162b2 mRNA vaccine. The temporal relationship between the COVID-19 vaccination and orbital symptoms suggests a probable link between SARS-CoV-2 mRNA vaccine and this orbital inflammatory disease.

Autoimmune and inflammatory thyroid diseases following vaccination with SARS-CoV-2 vaccines: from etiopathogenesis to clinical management.

Since the Covid-19 pandemic emerged in 2019, several adenoviral-vectored, mRNA-based and inactivated whole-virus vaccines have been developed. A massive vaccination campaign has been undertaken around the world, and an increasing number of SARS-CoV-2 vaccine-induced thyroid diseases have been described in the literature. Subacute thyroiditis has been reported in 52 patients, mean age 45.5 ± 1.8 years, mainly in women (n = 39). Graves' disease is more frequent in women (n = 22) than in men (n = 10), mean age 46.2 ± 2.6 years, reported as new onset, recurrent or exacerbation of well-controlled hyperthyroidism. The mean time to symptoms onset is 9.0 ± 0.8 days in subacute thyroiditis, and 15.1 ± 2.6 days in Graves' patients. Rare patients (n = 6) present silent or painless autoimmune thyroiditis. Thyroid function and autoimmune tests, inflammatory markers, thyroid echography with colour flow Doppler, radio-activity uptake on thyroid scan, medical treatment and follow-up are described and compared in patients with SARS-CoV-2 vaccine-induced thyroid diseases. The underlying pathogenic mechanisms of vaccine-induced thyroid diseases, molecular mimicry (various SARS-CoV-2 proteins sharing a genetic homology with a large heptapeptide human protein) or autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are discussed in the context of predisposition or genetic susceptibility. The benefits of SARS-CoV-2 vaccination far outweigh the potential vaccine-induced adverse effects, but clinicians should be aware of possible autoimmune and inflammatory thyroid diseases, and can advise patients to seek medical assistance when experiencing anterior neck pain, fever or palpitations following SARS-CoV-2 vaccines. Further studies are warranted to investigate the etiopathogenesis and to clarify the factors which predispose patients to SARS-CoV-2 vaccine-induced thyroid diseases.