Asymptomatic Empty Sella Syndrome: A "New" Hypothalamic Pathology or Paraphysiological Variant.

INTRODUCTION: The term empty sella refers to a shrunken or displaced (by a subarachnoid diverticulum) pituitary gland. It can be primary (genetically determined) or secondary (due to trauma/surgery/radiation). It has been reported that 50% of patients are asymptomatic, and others experience symptoms, such as headache, hypertension, or visual field defects. Few cases have an empty sella syndrome, i.e., lacking functional pituitary hormones. Diagnosis is made through NMR or CT. If asymptomatic, this condition requires no treatment; otherwise, empty sella syndrome needs hormonal replacement therapy. We examined the case of asymptomatic empty sella syndrome. CASE REPORT: A 67-year-old female patient was admitted for dilatative cardiomyopathy. She had a past medical history of arterial hypertension and right ICA endovascular repair. Blood tests demonstrated hypothyroidism, hypoadrenalism, and GH deficiency, without any signs or symptoms. NRM confirmed an empty sella, hence replacement therapy with levothyroxine and cortisone acetate was started. During a follow-up evaluation, we discovered that this biochemical profile of the patient had been known for more than a decade and never treated. Despite being exposed to stress conditions, vascular surgery and angiography, she never developed an adrenal crisis, nor has she ever been symptomatic for severe hypothyroidism. Hormonal replacement therapy was performed. CONCLUSION: The described clinical scenario is rare, as usually, empty sella syndrome presents with signs of hormone deficiency, even if asymptomatic cases have been described. Some authors suggest considering it as a hypothalamic dysfunction requiring treatment; others identify it as a paraphysiological variant. However, more cases are needed to establish a correct therapeutic strategy for these patients.

Diabulimia and Type 1 Diabetes: An Unknown and Emerging Problem.

BACKGROUND: T1DM patients have a higher prevalence of eating disorders than the general population, and up to 30-40% of young T1DM patients suffer from an eating disorder, including diabulimia. Eating disorders worsen glycemic control and make insulin therapy management more difficult. Closed loop systems (HCLS) allow major therapeutic flexibility; however, proper carbohydrate (CHO) counting remains a fundamental feature for insulin dose adjustments. CASE REPORT: A 30-year-old female patient affected by T1DM (with a past medical history of drug abuse and depressive syndrome) presented with inadequate glycemic control and prandial boli management. She started a CHO counting course and had a HCLS positioned, with progressive amelioration of glycemic control. During follow-up evaluations, HCLS data showed a progressive reduction and abeyance of prandial boli; the patient also developped an excessive fear of weight gain. An integrated approach between diabetologist, psychiatrist and dietitian allowed a diagnosis of diabulimia, an eating disorder characterized by a progressive reduction and elimination of carbohydrate ingestion and insulin boli, with episodes of uncontrolled binging and purging. A multidisciplinary approach (fortnightly dietetic and psychiatric evaluations, use of bioimpedance, fixed CHO content diet) allowed the patient to reach a better glycometabolic control and disease consciousness. CONCLUSION: T1DM patients need to pay great attention to food quality and quantity; hence, an eating disorder diagnosis may be challenging. Additionally, there are currently no standard screening methods for this purpose. In our experience, an integrated approach is fundamental and may be a valid strategy to face this emerging problem.

Eating Disorders in the Time of the COVID-19 Pandemic: A Perspective.

BACKGROUND: Due to the COVID-19 pandemic, current epidemiological conditions may exacerbate the risk of new-onset, recurrence and relapse of eating disorders. This perspective aims to better analyse the phenomenon. RESULTS: Some data suggest that new-onset and recurrence/relapse of eating disorders are increasing due to the pandemic. Government restrictions, self-confinement, social isolation, restriction to healthcare facilities access, delayed access to diagnosis and cure, fear of contagion, distress and difficulties related to the telemedicine approach contribute to this burden. The Immune system dysfunction usually observed in undernourishment (e.g., anorexia nervosa) could delay the diagnosis of respiratory infections, including COVID-19, and predispose to possible bacterial superinfections. Conversely, patients with binge eating, obesity or metabolic syndrome are susceptible to high-grade systemic inflammation and poor prognosis once the infection has occurred. DISCUSSION: More detailed data combining research on eating disorders and COVID-19 are required despite some evidence. Many data show that telemedicine has beneficial aspects, but its impact on long-term mental health is still poorly understood. Short- and long-term consequences of COVID-19 in patients with eating disorders are unknown, but they will likely become more apparent over time. CONCLUSION: Working on emotion regulating strategies in a post-pandemic world, when people have inadequate control over the background of negative emotions, could be a future treatment strategy. Long-term studies with a larger sample size are essential to assess the long-term consequences of the blockade on patients and their healthcare providers and identify useful strategies to improve clinical management.

Nutraceuticals and Oral Supplements in Cancer Prevention: A Narrative Review.

BACKGROUND: Epidemiological studies have shown that food is a compelling means of maintaining a state of well-being and preventing diseases. Many malignant diseases are related to nutrition, and the nutrient-organism interaction could define the balance between health and disease. Nutrients and dietary components influence epigenetic phenomena and modify drug response so that food-organism interactions may influence individual predisposition to disease and its potential therapeutic response. AIMS: In this review, we highlighted emerging opinions and data on a large cluster of nutraceuticals, as well as functional foods and specific dietary patterns, with respect to cancer, including breast, pancreas, prostate, and colorectal. Only those nutraceuticals and nutritional supplements yielding sufficient and convincing data have been reported in this review; molecules with inconclusive clinical evidence will not be discussed. CONCLUSION: Growing and accumulating evidence is validating the use of nutraceuticals in cancer settings. However, a knowledge gap remains in terms of causal evidence for several compounds where a window for further clinical studies is left.

Vitamin D 25OH Deficiency and Mortality in Moderate to Severe COVID-19: A Multi-Center Prospective Observational Study.

Introduction: Several studies and meta-analyses suggested the role of vitamin D 25OH in preventing severe forms of coronavirus disease 2019 (COVID-19). However, the evidence on the clinical benefits of vitamin D 25OH adequacy in patients hospitalized for COVID-19 remain conflicting and speculative. We aimed to investigate the association between vitamin D 25OH serum levels and mortality in hospitalized patients with moderate to severe COVID-19. Method: This prospective observational multicentre study included 361 consecutive patients with moderate to severe COVID-19 admitted to the Italian hospitals involved in the NUTRI-COVID19 trial from March to August 2020. For each patient, serum vitamin D 25OH levels were assessed 48 h since admission and classified as deficient (<20 ng/mL) or adequate (≥20 ng/mL). We built a propensity score for low/adequate vitamin D 25OH levels to balance the clinical and demographic properties of the cohort, which resulted in 261 patients with good common support used for the survival analysis. Results: Two Hundred-seventy-seven (77%) of the 361 enrolled patients (207 [57%] males, median age 73 ± 15.6 years) had vitamin D 25OH deficiency. Fifty-two (20%) of the 261 matched patients died during the hospital stay, corresponding to a hazard ratio of 1.18 for vitamin D 25OH deficiency (95% confidence interval: 0.86-1.62; p = 0.29). Discussion: The prevalence of vitamin D 25OH deficiency was confirmed to be very high in hospitalized patients with COVID-19. The use of a propensity score demonstrate an absence of significant association between vitamin D deficiency and mortality in hospitalized patients.

Nutritional parameters associated with prognosis in non-critically ill hospitalized COVID-19 patients: The NUTRI-COVID19 study.

BACKGROUND & AIMS: To investigate the association between the parameters used in nutritional screening assessment (body mass index [BMI], unintentional weight loss [WL] and reduced food intake) and clinical outcomes in non-critically ill, hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: This was a prospective multicenter real-life study carried out during the first pandemic wave in 11 Italian Hospitals. In total, 1391 patients were included. The primary end-point was a composite of in-hospital mortality or admission to ICU, whichever came first. The key secondary end-point was in-hospital mortality. RESULTS: Multivariable models were based on 1183 patients with complete data. Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was found to have a negative prognostic impact for both the primary and secondary end-point (P < .001 for both). No association with BMI and WL was observed. Other predictors of outcomes were age and presence of multiple comorbidities. A significant interaction between obesity and multi-morbidity (≥2) was detected. Obesity was found to be a risk factor for composite end-point (HR = 1.36 [95%CI, 1.03-1.80]; P = .031) and a protective factor against in-hospital mortality (HR = 0.32 [95%CI, 0.20-0.51]; P < .001) in patients with and without multiple comorbidities, respectively. Secondary analysis (patients, N = 829), further adjusted for high C-reactive protein (>21 mg/dL) and LDH (>430 mU/mL) levels yielded consistent findings. CONCLUSIONS: Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was associated with negative clinical outcomes in non-critically ill, hospitalized COVID-19 patients. This simple and easily obtainable parameter may be useful to identify patients at highest risk of poor prognosis, who may benefit from prompt nutritional support. The presence of comorbidities could be the key factor, which may determine the protective or harmful role of a high body mass index in COVID-19.

Functional characterization of wild-type and a mutated form of SLC26A4 identified in a patient with Pendred syndrome.

BACKGROUND: Malfunction of the SLC26A4 protein leads to prelingual deafness often associated with mild thyroid dysfunction and goiter. It is assumed that SLC26A4 acts as a chloride/anion exchanger responsible for the iodide organification in the thyroid gland, and conditioning of the endolymphatic fluid in the inner ear. METHODS: Chloride uptake studies were made using HEK293-Phoenix cells expressing human wild type SLC26A4 (pendrin) and a mutant (SLC26A4(S28R)) we recently described in a patient with hypothyroidism, goiter and sensorineural hearing loss. RESULTS: Experiments are summarized showing the functional characterization of wild type SLC26A4 and a mutant (S28R), which we described recently. This mutant protein is transposed towards the cell membrane, however, its transport capability is markedly reduced if compared to wild-type SLC26A4. Furthermore, we show that the SLC26A4 induced chloride uptake in HEK293-Phoenix cells competes with iodide, and, in addition, that the chloride uptake can be blocked by NPPB and niflumic acid, whereas DIDS is ineffective. CONCLUSIONS: The functional characteristics of SLC26A4(S28R) we describe here, are consistent with the clinical phenotype observed in the patient from which the mutant was derived.

Highly sensitive serum thyroglobulin and circulating thyroglobulin mRNA evaluations in the management of patients with differentiated thyroid cancer in apparent remission.

We studied the potential role of innovative diagnostic tools for the management of patients with differentiated thyroid cancer (DTC). Several methods for the detection of the tumor marker thyroglobulin (Tg) have been employed in 36 patients in apparent remission at the moment of the study. All patients had negative anti-Tg antibodies and were evaluated during L-T(4) suppressive therapy before and after stimulation with recombinant human TSH (rhTSH). Serum Tg was measured by means of conventional [nonhighly sensitive (nhs)] or highly sensitive (hs) immunoassays with positive cut-off values set at 1.0 and 0.18 microg/liter, respectively. The RT-PCR conditions for the qualitative determination of Tg mRNA from peripheral blood were optimized to prevent interference by illegitimate transcription. The patients have been classified on the basis of a hs-basal Tg testing by taking into account the results of their baseline samples in hs immunoassay and RT-PCR method; hs-basal Tg testing was considered positive when the marker was detectable in at least one of the two tests. The predictive value of hs-basal Tg testing was estimated on the basis of a global clinical evaluation, including serum Tg response after rhTSH stimulation and reports of contemporary (131)I scan and neck ultrasound. The clinical evaluation was considered positive when at least one of these criteria yielded positive results. Although nhs-Tg measurement was poorly predictive of the clinical status, basal hs-Tg evaluation was found to be concordant with the clinical evaluation in 71% of cases. Results of basal Tg mRNA detection did not vary after rhTSH stimulation and were concordant with the clinical evaluation in 66% of cases. Tg mRNA evaluation alone showed 10 apparently false-positive results, and serum basal hs-Tg was falsely negative in 11 additional cases, suggesting that a suitable predictability could be obtained by the association of these 2 parameters. Indeed, the combination of hs-Tg assay and mRNA detection in the hs-basal Tg testing allowed the identification of 22 patients with a positive persistent/recurrent disease or normal thyroid residue, as well as identification of all 6 patients with a negative clinical evaluation. In conclusion, the combined evaluation of circulating Tg mRNA and serum Tg by means of hs noncompetitive immunoassay (hs-basal Tg testing) can give useful information on the clinical status of patients with DTC who are apparently disease-free, even on L-T(4) TSH-suppressive therapy. Therefore, these combined evaluations retain a potential role in the clinical monitoring of DTC patients. In particular, a negative hs-basal Tg testing would indicate disease remission and the opportunity to lengthen the intervals between rhTSH stimulations and/or to shift patients to a less profound TSH suppression with L-T(4).

Differential diagnosis between Pendred and pseudo-Pendred syndromes: clinical, radiologic, and molecular studies.

The disease gene for Pendred syndrome has been recently characterized and named PDS. It codes for a transmembrane protein called pendrin, which is highly expressed at the apical surface of the thyroid cell and functions as a transporter of chloride and iodide. Pendrin is also expressed at the inner ear level, where it appears to be involved in the maintenance of the endolymph homeostasis in the membranous labyrinth, and in the kidney, where it mediates chloride-formate exchange and bicarbonate secretion. Mutations in the PDS gene and the consequent impaired function of pendrin leads to the classic phenotype of Pendred syndrome, i.e. dyshormonogenic goiter and congenital sensorineural hearing loss. In the present study, we performed a detailed clinical, radiologic, and molecular analysis of six families presenting with clinical diagnosis of Pendred syndrome. In two families a homozygous pattern for PDS mutations was found, whereas the affected members of the other four families were compound heterozygotes. One family did not harbor PDS mutations. Among the four novel mutations described, one is a transversion in exon 2 (84C>A), leading to the substitution S28R. Two other novel mutations lie in exon 4 (398T>A) and in exon 16 (1790T>C), leading to the substitutions S133T and L597S, respectively. The fourth novel mutation (1614+1G>A) is located in the first base pair of intron 14, probably affecting the splicing of the PDS gene. Clinically, all patients had goiter with positive perchlorate test, hypothyroidism, and severe or profound sensorineural hearing loss. In all the individuals harboring PDS mutations, but not in the family without PDS mutations, inner ear malformations, such as enlargement of the vestibular aqueduct and of the endolymphatic duct and sac, were documented. The pseudo-Pendred phenotype exhibited by the family without PDS mutations is likely caused by an autoimmune thyroid disease associated with a sensorineural hearing loss of different origin.