Hyponatremia: a case report of SIAD

Hyponatremia, defined as serum sodium concentration <136 mEq/l, represents one of the most frequently encountered electrolyte disorder in clinical practice. Among hospitalised patients up to 15-30% present mild hyponatremia (130-135 mEq/l), whereas moderate to severe forms are seen in up to 7% of inpatients. Hyponatremia is associated with significant morbidity and mortality especially in patients with underlying diseases. According to volume status hyponatremia can be classified as hypovolemic, hypervolemic or euvolemic. An accurate diagnostic algorithm has to be performed in order to optimize the therapeutic approach. Acute and severe forms are accompanied by neurological symptoms due to cerebral edema and can cause death if not appropriately treated. Moreover, even a too rapid correction can be associated with serious complications, such as the osmotic demyelination syndrome. Hypovolemic forms have to be treated with isotonic saline infusion, whereas eu-hypervolemic forms require hypertonic saline when symptomatic, and fluid restriction or vaptans when asymptomatic. Here, we report the case of a 79-year-old woman with hyponatremia admitted to the Emergency Department of XXX

Gestione della terapia adiuvante con mitotane nei pazienti affetti da carcinoma corticosurrenalico

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Problemi interpretativi del dosaggio delle metanefrine

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DIAGNOSIS of ENDOCRINE DISEASE: SDHx mutations: Beyond pheochromocytomas and paragangliomas

Mutations in one of the five genes encoding the succinate dehydrogenase (SDHx) or mitochondrial complex II cause the corresponding family syndromes characterized by the occurrence of pheochromocytomas (PHEO) and paragangliomas (PGL). Recently, other solid growths, such as gastrointestinal stromal tumors (GISTs), renal cell carcinomas (RCCs) and pituitary adenomas (PAs) have been associated with these syndromes. In the absence of prospective studies assessing their frequency, at present, their occurrence seems too infrequent to suggest systematic screening for SDHx mutation carriers. However, SDHB immunohistochemistry (IHC) on tumor tissues or SDHx genetic testing on blood or tumor samples should be performed in patients affected by GISTs, RCCs or PAs with clinicopathologic phenotypes suggesting an etiologic role of SDHx genes.</jats:p

Parathyroid Carcinoma in the Setting of Tertiary Hyperparathyroidism: Case Report and Review of the Literature

Introduction. Parathyroid carcinoma is one of the rarest cancers in normal population, and it is extremely uncommon in the setting of tertiary hyperparathyroidism. Indeed, only 24 cases have been reported in the literature. Presentation of the Case. We report the case of parathyroid carcinoma in a 51-year-old man, with a history of end-stage renal disease due to a horseshoe kidney treated with haemodialysis since 2013. He came to our attention due to an increase in calcium and parathyroid hormone serum levels. Neck ultrasound (US) showed a solid hypodense mass, probably the right inferior parathyroid gland, with an estimated size of 25 × 15 × 13 mm; the 99mTc-sestamibi SPECT/CT scan revealed a large radiotracer activity area in the right cervical region, compatible with a hyperfunctioning right inferior parathyroid gland. So, a tertiary hyperparathyroidism diagnosis was made. In April 2018, resection of three parathyroid glands was performed. Histopathological examination demonstrated the right inferior parathyroid gland specimen to be a parathyroid carcinoma, due to the presence of multiple, full-thickness, capsular infiltration foci, and a venous vascular invasion focus. Discussion. Diagnosis of parathyroid carcinoma in tertiary hyperparathyroidism is remarkably complex because of the lack of clinical diagnostic criteria and, in many cases, is made postoperatively at histopathological examination. Conclusion. To date, radical surgery represents the mainstay of treatment, with a five- and ten-year survival rates overall acceptable

Metformin as a new anti-cancer drug in adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare heterogeneous malignancy with poor prognosis. Since radical surgery is the only available treatment, more specific and effective drugs are urgently required. The anti-diabetic drug metformin has been associated with a decreased cancer prevalence and mortality in several solid tumors, prompting its possible use for ACC treatment. This paper evaluates the in vitro and in vivo anti-cancer effects of metformin using the ACC cell model H295R. Metformin treatment significantly reduces cell viability and proliferation in a dose- and time-dependent manner and associates with a significant inhibition of ERK1/2 and mTOR phosphorylation/activation, as well as with stimulation of AMPK activity. Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector. Metformin interferes with the proliferative autocrine loop of IGF2/IGF-1R, which supports adrenal cancer growth. Finally, in the ACC xenograft mouse model, obtained by subcutaneous injection of H295R cells, metformin intraperitoneal administration inhibits tumor growth, confirmed by the significant reduction of Ki67%. Our data suggest that metformin inhibits H295R cell growth both in vitro and in vivo. Further preclinical studies are necessary to validate the potential anti-cancer effect of metformin in patients affected by ACC

Sunitinib in the therapy of malignant paragangliomas: report on the efficacy in a SDHB mutation carrier and review of the literature

SUMMARY Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors

2D-DIGE proteomic analysis identifies new potential therapeutic targets for adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare aggressive tumor with poor prognosis when metastatic at diagnosis. The tumor biology is still mostly unclear, justifying the limited specificity and efficacy of the anti-cancer drugs currently available. This study reports the first proteomic analysis of ACC by using two-dimensional-differential-in-gel-electrophoresis (2D-DIGE) to evaluate a differential protein expression profile between adrenocortical carcinoma and normal adrenal. Mass spectrometry, associated with 2D-DIGE analysis of carcinomas and normal adrenals, identified 22 proteins in 27 differentially expressed 2D spots, mostly overexpressed in ACC. Gene ontology analysis revealed that most of the proteins concurs towards a metabolic shift, called the Warburg effect, in adrenocortical cancer. The differential expression was validated by Western blot for Aldehyde-dehydrogenase-6-A1,Transferrin, Fascin-1,Lamin A/C,Adenylate-cyclase-associated-protein-1 and Ferredoxin-reductase. Moreover, immunohistochemistry performed on paraffin-embedded ACC and normal adrenal specimens confirmed marked positive staining for all 6 proteins diffusely expressed by neoplastic cells, compared with normal adrenal cortex. In conclusion, our preliminary findings reveal a different proteomic profile in adrenocortical carcinoma compared with normal adrenal cortex characterized by overexpression of mainly metabolic enzymes, thus suggesting the Warburg effect also occurs in ACC. These proteins may represent promising novel ACC biomarkers and potential therapeutic targets if validated in larger cohorts of patients

Diffuse C-Cells Hyperplasia Is the Source of False Positive Calcitonin Measurement in FNA Washout Fluids of Thyroid Nodules: A Rational Clinical Approach to Avoiding Unnecessary Surgery

Purpose: The FNA-CT is useful for the diagnosis of MTC. The aim of this study was to evaluate the performance of FNA-CT in TNs coexisting with CCH. Methods: This study retrospectively reviewed the records of 11 patients with TNs submitted to thyroidectomy on the basis of elevated basal and/or stimulated serum CT values, which at histology were not confirmed to be MTC. The results obtained in this group were compared with those of a previously reported group of histologically proven MTC patients submitted to an identical presurgical evaluation. All patients, negative for known mutations in the RET proto-oncogene, were preoperatively submitted to neck ultrasound, FNA-cytology, and FNA-CT. Results: Approximately 6 of 11 patients showed increased (&gt;36 ng/mL, as established in previous studies not involving patients with CCH) FNA-CT. All these patients showed diffuse CCH at histology in the thyroid lobe submitted to FNA; 5 of them were benign at histology, while only one was malignant (papillary thyroid carcinoma, PTC). The remaining 5 of 11 patients had low FNA-CT (&lt;36 ng/mL), and all of them showed only focal CCH in the lobe submitted to FNA; three of them were malignant (2 PTC, 1 follicular carcinoma), while two were benign. Conclusions: Employing the currently proposed cut-off values, false-positive FNA-CT results may be observed in benign/malignant TNs with coexisting diffuse CCH. FNA-CT must therefore be cautiously used in the diagnostic approach for patients with TNs and a slightly increased basal or stimulated serum CT concentration in order to avoid unnecessary surgery