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Immune checkpoint inhibitor drugs can trigger autoimmune endocrine reactions as a known side effect. Several cases of immunotherapy-induced autoimmune endocrinopathies have been described, but multiple sequential endocrine toxicities are a rare occurrence. A 39-year-old patient with metastatic melanoma started adjuvant therapy with pembrolizumab. One month later he presented with asymptomatic thyrotoxicosis and, within several weeks, overt hypothyroidism, for which he started levothyroxine therapy. Subsequently the patient developed central adrenal insufficiency due to probable hypophysitis, and steroid replacement therapy was started. Pembrolizumab therapy was then discontinued. After a few months, a full recovery of pituitary function was observed, but primary adrenal insufficiency occurred, requiring additional fludrocortisone therapy. The described clinical case is a very uncommon case of triple endocrinological toxicity from immunotherapy. The clinical and biochemical manifestations of immunotherapy-induced endocrinopathies can be variable and atypical; therefore, it is necessary to pay special attention to any clue of hormonal dysfunction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Type 2 diabetes mellitus (T2DM) is a disease characterized by a prolonged hyperglycemic condition caused by insulin resistance mechanisms in muscle and liver, reduced insulin production by pancreatic β cells, and a chronic inflammatory state with increased levels of the pro-inflammatory marker semaphorin 3E. Phytochemicals present in several foods have been used to complement oral hypoglycemic drugs for the management of T2DM. Notably, dipeptidyl peptidase IV (DPPIV) inhibitors have demonstrated efficacy in the treatment of T2DM. Our study aimed to investigate, in in vitro models of insulin resistance, the ability of the flavanones naringenin and hesperetin, used alone and in combination with the anti-inflammatory natural molecules curcumin, polydatin, and quercetin, to counteract the insulin resistance and pro-inflammatory molecular mechanisms that are involved in T2DM development. Our results show for the first time that the combination of naringenin, hesperetin, curcumin, polydatin, and quercetin (that mirror the nutraceutical formulation GliceFen ® , Mivell, Italy) synergistically decreases expression levels of the pro-inflammatory gene SEMA3E in insulin-resistant HepG2 cells and synergistically decreases DPPIV activity in insulin-resistant Hep3B cells, indicating that the combination of these five phytochemicals is able to inhibit pro-inflammatory and insulin resistance molecular mechanisms and could represent an effective innovative complementary approach to T2DM pharmacological treatment.

Objective: Dysnatremia is common in hospitalized patients, often worsening the prognosis in pneumopathies and critical illnesses. Information on coronavirus disease-19 (COVID-19)-related hyponatremia is partially conflicting, whereas data on hypernatremia in this context are scarce. We assessed, in a cohort of COVID-19 inpatients: the prevalence of sodium alterations at admission and throughout their hospitalization; their association with inflammation/organ damage indexes; their short-term prognostic impact., Study Design and Methods: 117 patients (81 males, 64 ± 13 years) hospitalized for COVID-19 between 1 March and 30 April 2020 were retrospectively followed-up for their first 21 days of stay by collecting all serum sodium measurements, basal CRP and serum lactate levels, maximum IL-6 and information on care setting, required ventilation, length of hospitalization, in-hospital death., Results: At admission, 26.5% patients had hyponatremia, and 6.8% had hypernatremia. During their hospitalization, 13.7% patients experienced both disorders ('mixed dysnatremia'). Lower sodium levels at admission were correlated with higher C reactive protein (CRP) (P = 0.039) and serum lactate levels (P = 0.019), but not interleukin-6 (IL-6). Hypernatremia and a wider sodium variability were associated with maximum required ventilation, need for ICU assistance and duration of the hospitalization. Mean estimated time to Intensive Care Unit (ICU) admission was 20 days shorter in patients exposed to sodium alterations at any time of their hospital course (log-rank test P = 0.032)., Conclusions: Sodium alterations frequently affect hospitalized COVID-19 patients. Hyponatremia could indicate pulmonary involvement, whereas hypernatremia is associated to prolonged hospitalization and the need for intensive care/mechanical ventilation, particularly when resulting from prior hyponatremia. Optimizing in-hospital sodium balance is crucial to improve patients' prognosis.

Magnetite-based magnetic nanoparticles have been successfully coupled to an organic system constituted of a fluorescent molecule, a tripeptide specifier and a spacer. The system is able to selectively release the fluorescent molecule upon targeted enzymatic hydrolysis promoted by a lysine/arginine specific protease.

Thyroid cancers represent about 1% of all human cancers. Differentiate thyroid carcinomas (DTCs), papillary and follicular cancers, are the most frequent forms, instead Anaplastic Thyroid Carcinoma (ATC) is estimated to comprise 1-2% of thyroid malignancies and it accounts for 14-39% of thyroid cancer deaths. The annual incidence of ATC is about one to two cases/million, with the overall incidence being higher in Europe (and area of endemic goiter) than in USA. ATC has a more complex genotype than DTCs, with chromosomal aberrations present in 85-100% of cases. A small number of gene mutations have been identified, and there appears to be a progression in mutations acquired during dedifferentiation. The mean survival time is around 6 months from diagnosis an outcome that is frequently not altered by treatment. ATC presents with a rapidly growing fixed and hard neck mass, often metastatic local lymph nodes appreciable on examination and/or vocal paralysis. Symptoms may reflect rapid growth of tumor with local invasion and/or compression. The majority of patients with ATC die from aggressive local regional disease, primarily from upper airway respiratory failure. For this reason, aggressive local therapy is indicated in all patients who can tolerate it. Although rarely possible, complete surgical resection gives the best chance of long-term control and improved survival. Therapy options include surgery, external beam radiation therapy, tracheostomy, chemotherapy, and investigational clinical trials. Multimodal or combination therapy should be useful. In fact, surgical debulking of local tumor, combined with external beam radiation therapy and chemotherapy as neoadjuvant (before surgery) or adjuvant (after surgery) therapy, may prevent death from local airway obstruction and as best may slight prolong survival. Investigational clinical trials in phase I or in phase II are actually in running and they include anti-angiogenetic drugs, multi-kinase inhibitor drugs.

A 44-year-old man with total thyroidectomy for papillary thyroid carcinoma (PTC) performed at the age of 38 years was referred for mediastinal metastases demonstrated on chest radiograph and high serum thyroglobulin (Tg 328 ng/ml). Computed tomography revealed mediastinal lymph node enlargement with left bronchial compression and reduction of bronchial diameter, as well as two metastases in the left lung. Bronchoscopic biopsy findings showed a poorly-differentiated PTC, while a whole body scan after 131-Iodine therapy demonstrated uptake in the right subclavicular region. External beam radiotherapy and chemotherapy yielded no benefit; the neoplasm was aggressive, diffuse and experienced fast growth, leading to the formation of metastases also at unusual sites, such as the skin and thigh muscle. The patient died from a brain metastasis. We report a rare case of PTC metastasis with a poorly-differentiated component in a young patient. Rapid and diffuse metastases also to unusual sites led to death eight years after the initial diagnosis and treatment.

Background: Lithium may exert an antisuicidal effect in bipolar disorder patients, but this hypothesis requires further testing by direct comparison of patients with and without lithium treatment., Method: Risk of life-threatening suicidal acts over time and associated factors were analyzed in 310 patients with DSM-IV bipolar I (N = 186) or II (N = 124) disorder evaluated for a mean of 8.3 years before, and prospectively during, a mean of 6.4 years of lithium maintenance in a mood disorder clinic; 185 were also followed for a mean of 3.7 years after clinically discontinuing lithium., Results: In 5233 patient-years of observation, 58 patients made 90 suicide attempts (8 were fatal). Survival analyses with Weibull modeling with adjustments for covariates indicated a highly significant 6.4-fold adjusted hazard ratio during versus before and 7.5-fold ratio after versus during lithium maintenance. Suicidal acts were more common early in the course of illness before lithium and were associated with prior suicide attempts, greater proportion of time depressed, and younger age. After the discontinuation of lithium, suicidal acts were more frequent in the first year than at later times or before start of lithium treatment. Fatalities were 9 times more frequent after versus during treatment., Conclusion: Lithium maintenance was associated with marked reduction of life-threatening suicidal acts, the number of which sharply increased after discontinuing lithium. Suicidal behavior was strongly associated with prior suicide attempts, more time depressed, and younger age or recent onset. Greater attention to suicidal risk in patients with bipolar depression and assessment of all proposed mood-stabilizing agents for antisuicidal effects are strongly encouraged.

Lithium augmentation during long-term treatment with antidepressants has long been considered an effective therapeutic strategy in the treatment of depressive syndromes. This paper deals with an 'opposite' strategy, i.e. the use of serotonin reuptake inhibitors (SRIs) during maintenance lithium treatment in bipolar disorder (BP) patients who may present a breakthrough depressive syndrome. The study involved 26 patients on maintenance lithium treatment for a mean of 38 months (mean serum lithium level=0.57 mEq/l). Mean fluoxetine dose was 29.3 mg/day for a mean period of 7.36 weeks. Median HDRS scores before and after fluoxetine augmentation were 14 and 6, respectively. The results provide evidence for the efficacy of fluoxetine augmentation in the treatment of breakthrough depressions occurring in bipolar disorder patients during maintenance lithium treatment. The neuropharmacological explanation of the augmentation is not yet well understood, but it is conceivable that the improvement of the depressive symptoms may be related to the increase in serotonergic function provided by combination of the two treatments.