Objective: We have previously observed thyroid dysfunction, i.e. atypical thyroiditis (painless thyrotoxicosis associated to non-thyroidal illness syndrome), in patients with severe-acute-respiratory-syndrome-coronavirus-2 disease (Covid-19). This study aimed to analyse the evolution of thyroid dysfunction over time. Methods: 183 consecutive patients hospitalised for severe Covid-19 without known thyroid history were studied at hospital admission (baseline). Survivors were offered 12-month longitudinal follow-up including assessment of thyroid function, autoantibodies and ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive of thyroiditis (focal-hypoechogenicity) also underwent thyroid 99mTc or 123I uptake scan. Results: At baseline, after excluding from TSH analysis 63 out of 183 (34%) Covid-19 patients commenced on steroids before hospitalisation, 12 (10%) showed atypical thyroiditis. Follow-up of 75 patients showed normalisation of thyroid function and inflammatory markers, and no increased prevalence of detectable thyroid autoantibodies. Baseline US (available in 65 patients) showed focal-hypoechogenicity in 28% patients, of whom 82% had reduced thyroid 99mTc/123I uptake. The presence of focal-hypoechogenicity was associated with baseline low TSH (p=0.034), high FT4 (p=0.018) and high IL-6 (p=0.016). Focal-hypoechogenicity persisted after 6 and 12 months in 87% and 50% patients, respectively, but reduced in size. After 9 months thyroid 99mTc/123I uptake partially recovered from baseline (+28%), but was still reduced in 67% patients. Conclusions: Severe Covid-19 induces mild transient thyroid dysfunction correlating with disease severity. Focal-hypoechogenicity, associated with baseline high FT4, IL-6 and low TSH, does not seem to be related to thyroid autoimmunity and may persist after one year although decreasing in size. Long-term consequences seem unlikely.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) represents an uncommon cause of endogenous hypercortisolism. Since the first description in 2003 in a French cohort, many papers have been published describing families as well as isolated individuals affected with this condition, who were found to harbor a genetic variants in the armadillo-repeat containing 5 (ARMC5) gene, a tumor-suppressor gene with a still unknown role in the disease pathogenesis. Studies in rat models suggested a possible link between ARMC5 damaging variants and the impairment of the cell-mediated immune response, leading to a higher susceptibility to bacterial and viral infections. To our knowledge, we describe the first case of a patient affected by PBMAH with hypogammaglobulinemia and monthly relapsing human herpes simplex viral infections. After the detection of subclinical Cushing’s syndrome, a unilateral laparoscopic adrenalectomy was performed. Subsequent genetic analysis of ARMC5 performed on genomic DNA extracted both from the adrenal tissue and lymphocytes revealed a novel somatic frameshift variant in exon 1 (c.231_265del:p.A77Afs*13) and a novel germline variant in exon 6 (c.2436del: p. C813Vfs*104). After adrenalectomy, we observed a significant improvement of clinical features concerning both hypercortisolism and relapsing viral infections, thus suggesting a possible adjuvant role of hypercortisolism on a genetic-based derangement of the immune system.

M e d i c a 261 ni 5'UTR (n=71) e NS5b (n=30) ; BioEdit 7.0.0 e ClustalW sono stati utilizzati per l'allineamento delle sequenze dei campioni con quelle di riferimento. Risultati. 5'UTR-Seq ha consentito di tipizzare il 66% (46/70) dei campioni LiPA-positivi. Dal confronto 5'UTR-Seq versus LiPA, 40 campioni su 46 (87%) sono risultati concordanti per genotipo e 32 su 40 (80%) concordanti per sottotipo. Dei 12 campioni 5'UTR-Seq-negativi, 8 sono stati tipizzati mediante NS5b-Seq. Tutti i genotipi individuati con NS5b-Seq sono risultati concordanti con quelli ottenuti con LiPA. Il sequenziamento delle regioni 5'UTR e NS5b ha consentito l'attribuzione di un unico sottotipo nei casi in cui LiPA non consentiva la determinazione del sottotipo, come per i genotipi 1,2 e 4. L'utilizzo combinato del sequenziamento di 5'UTR e NS5b ha permesso di tipizzare l'81% dei campioni LiPA-positivi. Conclusioni. Questo studio evidenzia la necessità di utilizzare il sequenziamento diretto di almeno due regioni genomiche con differente livello di variabilità genetica per la tipizzazione del virus a scopo epidemiologico e clinico.