Background. Neuroendocrine tumors (NETs) are characterized by having behavior and prognosis that depend upon tumor histology, primary site, staging, and proliferative index. The symptoms associated with carcinoid syndrome and vasoactive intestinal peptide tumors are treated with octreotide acetate. The PROMID trial assesses the effect of octreotide LAR on the tumor growth in patients with well-differentiated metastatic midgut NETs. The CLARINET trial evaluates the effects of lanreotide in patients with nonfunctional, well-, or moderately differentiated metastatic enteropancreatic NETs. Everolimus has been approved for the treatment of advanced pancreatic NETs (pNETs) based on positive PFS effects, obtained in the treated group. Sunitinib is approved for the treatment of patients with progressive gastrointestinal stromal tumor or intolerance to imatinib, because a randomized study demonstrated that it improves PFS and overall survival in patients with advanced well-differentiated pNETs. In a phase II trial, pasireotide shows efficacy and tolerability in the treatment of patients with advanced NETs, whose symptoms of carcinoid syndrome were resistant to octreotide LAR. An open-label, phase II trial assesses the clinical activity of long-acting repeatable pasireotide in treatment-naive patients with metastatic grade 1 or 2 NETs. Even if the growth of the neoplasm was significantly inhibited, it is still unclear whether its antiproliferative action is greater than that of octreotide and lanreotide. Because new therapeutic options are needed to counter the natural behavior of neuroendocrine tumors, it would also be useful to have a biochemical marker that can be addressed better in the management of these patients. Chromogranin A is currently the most useful biomarker to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy.

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Purpose “Non thyroidal illness syndrome” (NTIS) or “euthyroid sick syndrome” (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T 3 (fT3), sometimes followed by reduction of serum T 4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. Methods We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. Results Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. Conclusions COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

To investigate the association between sex hormones and the severity of coronavirus disease 2019 . Furthermore, associations between sex hormones and systemic inflammation markers, viral shedding and length of hospital stay were studied. Design and methods: This case-control study included a total of 48 male patients with COVID-19 admitted to an Italian reference hospital. The 24 cases were patients with PaO 2 /FiO 2 <250 mmHg and who needed ventilatory support during hospitalization (severe COVID-19). The 24 controls were selected in a 1:1 ratio, matched by age, from patients who maintained PaO 2 /FiO 2 >300 mmHg at all times and who may have required low-flow oxygen supplementation during hospitalization (mild COVID-19). For each group, sex hormones were evaluated on hospital admission. Results: Patients with severe COVID-19 (cases) had a significantly lower testosterone level compared with patients with mild COVID-19 (controls). Median total testosterone (TT) was 1.4 ng/mL in cases and 3.5 ng/ mL in controls (P = 0.005); median bioavailable testosterone (BioT) was 0.49 and 1.21 in cases and controls, respectively (P = 0.008); and median calculated free testosterone (cFT) was 0.029 ng/mL and 0.058 ng/mL in cases and controls, respectively (P = 0.015). Low TT, low cFT and low BioT were correlated with hyperinflammatory syndrome (P = 0.018, P = 0.048 and P = 0.020, respectively) and associated with longer length of hospital stay (P = 0.052, P = 0.041 and P = 0.023, respectively). No association was found between sex hormone level and duration of viral shedding, or between sex hormone level and mortality rate.Conclusions: A low level of testosterone was found to be a marker of clinical severity of COVID-19.

We have investigated the effect of TRH on the release of GH in 20 acromegalic patients (14 females and 6 males) before and after selective removal of a pituitary tumour via transsphenoidal route. The follow-up period was 8 years. Pre-operatively the paradoxical response was present in 15 patients (75%). Mean GH values in TRH responders were significantly lower than in non-responders. According to the size and expansion diffusion of the adenoma, the patients were divided into 3 classes. The percentage of paradoxical response in patients in class III was significantly lower than in the other two classes. Postoperatively, mean GH values in pre-operative TRH responders were significantly lower than in nonresponders; among 15 responders, 13 (86%) had postoperative GH levels under 5 \g=m\g/l ;among 5 non-responders only 2 (40%) had GH values under 5 \g=m\g/l .Postoperatively 8 patients still had GH responsiveness to TRH: 6 with GH levels persistently (follow-up 8 years) under 5 \g=m\g/l and 2 with elevated GH values. The other 7 patients, who were responders pre-operatively and non-responders postoperatively, persistently exhibited low GH levels, except one subject who showed an increase in GH levels with reappearance of the paradoxical response, two years after surgery. These results suggest: 1. the paradoxical response may be expressed only when the hypothalamuspituitary interactions are intact; 2. the disappearance of the paradoxical response cannot surely suggest a remission, and 3. the presence of a pre-operative paradoxical response is a good prognostic feature.In acromegalic patients the GH secretion exhibits a pattern of response to various stimuli that differs from that in normal subjects. Such stimuli include oral glucose load (1), L-dopa and bromocriptine (2), apomorphine (3), GnRH and arginine (4), do¬ pamine and sulpiride (5). A »paradoxical« response to TRH was first de¬ scribed in 1972. Two different groups (6,7) ob¬ served an increase in GH values after iv TRH ad¬ ministration in about 50% of acromegalic patients tested. This response, absent in normal subjects (8), could therefore be of diagnostic importance. Sub¬ sequent studies demonstrated the altered response with in vitro systems (9,10), i.e. perfusion tech¬ niques of dispersed adenomatous cells, which sug¬ gested an alteration in membrane receptor in neoplastic clones of somatotropes, consisting in a dedifferentiation and appearance of specific recep¬ tors for TRH (11). Moreover, various authors have reported the disappearance of the »paradoxical« response after selective removal of the adenoma via transsphenoidal microsurgery (3,5,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). These observations allow to ascribe the paradoxical re¬ sponse to the presence of adenomatous tissue.On the other hand, a GH response to TRH has been described in pathological conditions, other than acromegaly, including renal failure (22), de¬ pression (23), anorexia nervosa (24), primary hypothyroidism (25), insulin-dependent diabetes mellitus (26), and schizophrenia (27), as...

The objective of this study was to investigate the relationship between growth hormone (GH) dynamic tests (thyrotropin- basal IGF-I plasma levels after an overnight fast. From 3 to 12 months after surgery we evaluated (1) GH plasma values after an OGTT, and (2) basal plasma IGF-I, free triiodothyronine (FT 3 ), free thyroxine (FT 4 ), thyroid-stimulating hormone (TSH), and urinary free cortisol. The same tests were performed every year for 5 years. All of the patients were classified into 4 subgroups according to the system of Hardy and Vezina. Preoperatively, "controlled" patients (n ‫؍‬ 29) had a GH paradoxical response to TRH (n ‫؍‬ 28) and an unresponsiveness to OGTT (n ‫؍‬ 29); 23 of them belonged to the I and II classes. Only 5 poorly controlled patients (n ‫؍‬ 21) showed a preoperative paradoxical response to TRH and 9 had a preoperative GH partial inhibition after OGTT; 19 of them belonged to the III and IV classes. Our data suggest that in the preoperative period in acromegalic patients the simultaneous presence of a GH paradoxical response to TRH and lack of GH inhibition after OGTT is inversely related to the tumor size and therefore more likely to be restored to normal by surgical treatment.releasing

Biallelic pathogenic variants in POC1A result in SOFT (Short‐stature, Onychodysplasia, Facial‐dysmorphism, and hypoTrichosis) and variant POC1A‐related (vPOC1A) syndromes. The latter, nowadays described in only two unrelated subjects, is associated with a restricted spectrum of variants falling in exon 10, which is naturally skipped in a specific POC1A mRNA. The synthesis of an amount of a POC1A isoform from this transcript in individuals with vPOC1A syndrome has been believed as the likely explanation for such a genotype–phenotype correlation. Here, we illustrate the clinical and molecular findings in a woman who resulted to be compound heterozygous for a recurrent frameshift variant in exon 10 and a novel variant in exon 9 of POC1A. Phenotypic characteristics of this woman included severe hyperinsulinemic dyslipidemia, acanthosis nigricans, moderate growth restriction, and dysmorphisms. These manifestations overlap the clinical features of the two previously published individuals with vPOC1A syndrome. RT‐PCR analysis on peripheral blood and subsequent sequencing of the obtained amplicons demonstrated a variety of POC1A alternative transcripts that resulted to be expressed in the proband, in the healthy mother, and in controls. We illustrate the possible consequences of the two POC1A identified variants in an attempt to explain pleiotropy in vPOC1A syndrome.

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