ACTA ENDOCRINOLOGICA (BUC)

Context. Adrenocortical carcinoma (ACC) is a rare neoplasm with an aggressive course and poor prognosis. The worldwide incidence is about 0.5 to 2 cases per million population per year. Oncocytic adrenocortical carcinoma is a rare histopathological variant of ACC with only a few reported cases in the literature. Case report. We report a case of an oncocytic variant of adrenocortical carcinoma in a 21-year-old male patient who presented with a left adrenal mass. Imaging studies confirmed a large left adrenal mass with involvement of the left renal vein and inferior vena cava. Endocrine workup showed mildly elevated serum cortisol levels. Discussion. Oncocytic AAC is a rare histopathological variant of ACC, as well as a rare subgroup of oncocytic adrenal neoplasms Hormonally active or functioning adrenocortical carcinomas most commonly secrete cortisol whereas co-secretion of multiple steroid hormones is a rare phenomenon. Conclusions. Surgery remains the mainstay of treatment, but most of the patients present late with large masses and eventually become unsuitable for curative resection.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

As the medical utility of injectable therapeutic peptides is expanding, so is the challenge of developing technologies that allow the administration of such molecules via alternative routes, considering that chronic patients requiring treatment with parenteral formulations are less adherent and compliant to the therapeutic regimens. Hence, substantial efforts have been made to develop technologies that allow the oral formulation of peptides. Due to their importance in the field of pharmaceutical technology, we describe the latest advancements made in the development of oral salmon calcitonin and oral semaglutide, in co-formulation with absorption enhancers such as 8-[(5-chloro-2-hydroxybenzoyl) amino] octanoic acid (or 5-CNAC) and N-[8-(2-hydroxybenzoyl) amino] caprylate (or SNAC). Oral semaglutide is considered to be a landmark for oral peptide delivery technology, as it is one of the very few successful examples of peptides that can be administered orally. Unlike semaglutide, oral calcitonin is still not approved by the regulatory authorities because it failed to demonstrate the anticipated effects in phase III clinical trials conducted so far. However, the efforts for obtaining an oral form of calcitonin have significantly contributed to the development of technologies that facilitate the absorption of peptide-structure macromolecules.

Purpose. Assessing cardiovascular risk in patients with acromegaly using traditional cardiovascular risk factors is inadequate. Endothelial dysfunction seems to be a much better indicator for assessing cardiovascular risk in acromegaly. The study aims to compare from this point of view two groups of patients, with hypertension and with acromegaly. Methods. The first group consists of 54 patients with acromegaly and the second group of 64 hypertensive patients. Endothelial dysfunction was evaluated by the FMD method. The relationship between endothelial dysfunction, specific humoral markers of acromegaly and traditional cardiovascular risk factors was analysed in both groups. Results. Although the presence of cardiovascular risk factors was statistically significantly higher in the group of hypertensives (the most important were age, blood pressure, glycemia, hypertriglyceridemia and SCORE), the presence of endothelial dysfunction was higher in the acromegaly group (61.10% vs. 32.10%, p=0.02). The best correlation with endothelial dysfunction in acromegaly group was the level of GH (28.9±28 vs. 11.7±10.3, p=0.003). Conclusions. The presence of endothelial dysfunction in patients with acromegaly is highly dependent on the level of GH and traditional cardiovascular risk factors are less important. In these patients the cardiovascular risk should not be evaluated in the same way as in normal population.

Context. Diabetes insipidus (DI) is rare in the neonatal period but of great importance due to increased renal risk and mental retardation despite treatment. Objective. This report describes the case of a patient with congenital nephrogenic diabetes insipidus (NDI). Detection of this pathology during the neonatal period, especially in premature newborns, is difficult because of the electrolyte variations that occur as a result of the immature kidney function. Subjects and methods. The subject was a preterm infant with very low birth weight (VLBW) and persistent hypernatremic hyperosmolarity that developed polyuria and polydipsia in the first weeks of life. Results. Taking into account blood and urine laboratory tests, vasopressin levels, as well as family history, the infant was diagnosed with congenital NDI. Early treatment allowed a good development, proving that the prevention of long-term complications is possible through multidisciplinary care and frequent monitoring. The particularity of this case was the presence of persistently elevated presepsin levels. This association prompted the investigation into underlying renal hypernatremia. Conclusions. NDI is a rare condition and the onset in the neonatal period is a sign of severity and hereditary causality. Early diagnosis, symptomatic treatment and multidisciplinary monitoring may decrease the risk of longterm complications.

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 μg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient’s esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient’s parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).

Morris Syndrome is a pathological condition which needs a special approach regarding both diagnosis and treatment\r\nbecause of its rarity. While the diagnosis is based on karyotype test, the treatment should follow the idea of harmless and cosmetic benefits as well as complete gonads removal. This paper is presenting the usefulness and advantages of minimally invasive surgery as a feasible treatment for such a disease. A retrospective study was performed for two patients with Morris Syndrome, admitted to\r\nthe ?CI Parhon? National Institute of Endocrinology, Bucharest, Romania, followed-up for 4 - 16 years, and operated to the Department of Surgery, Emergency\r\nHospital, Bucharest, Romania. Patients with primary amenorrhea have been clinically observed and three patients\r\nwith 46, XY karyotype have been identified as Morris Syndrome cases needing surgical removal of the intraperitoneal gonads because of the risk of malignant transformation. A minimally invasive surgical technique has\r\nbeen chosen for proper treatment: the anterior transperitoneal laparoscopic approach. The surgery was adapted to every case, in according with preoperative imagistic diagnosis of the intraperitoneal testes\r\n(localization, dimensions, adjacent organs involvement, surgical access). No postoperative complications were noticed and specimens' pathology confirmed the final\r\ndiagnosis. Cosmetic benefits were achieved for every young patient as well as rapid postoperative recovery (discharge after 48 hours). The authors concluded that Morris Syndrome patients could benefit from the laparoscopic surgery which is a feasible, safe and proper treatment for such cases.

experience regarding the first 24 patients diagnosed with refractory secondary and/ or tertiary hyperparathyroidism (HPT) who underwent subtotal parathyroidectomy (sPTx) in our clinic between 2010 and 2012. Methods. Data were retrospectively retrieved from a prospectively maintained database. We included patients diagnosed with refractory secondary and/or tertiary HPT who underwent sPTx; we excluded patients who underwent total parathyroidectomy (tPTx) and patients followed-up for less than six months. Results. We analyzed 24 patients,16 women (66.7%) and 8 men (33.3%) who were evaluated in a prospective manner in a short (1-6 months)/ medium (6-18 months) term follow up. Preoperative intact parathyroid hormone level (iPTH) was characterized by a median of 2131 pg/ mL (range: 1141-10000); in the first month after surgery the median iPTH level was 28 pg/mL (range: 3-1263). We found a statistically significant difference (p<0.01: Student test) in calcium level between preoperative values and values in the first month after surgery. Postoperative serum phosphorus (nv: 2.7-4.5 mg/dL) normalized in 19 patients (79.16%) and serum alkaline phosphatase values decreased significantly in the interval 2-6 months postoperative versus preoperative levels (p-0.002). We tried to establish a correlation between preoperative alkaline phosphatase (Alk Phos) and postoperative calcium level in the first month postoperatively. The overall clinical response to sPtx was good and we did not encounter postoperative mortality in our series. Conclusion. We believe that subtotal parathyroidectomy is feasible, safe and effective for patients with refractory secondary and tertiary hyperparathyroidism.

Context. Thyroid cancer is the most common endocrine malignancy. Within various subtypes of thyroid neoplasms, those with follicular growth pattern usually make diagnostic problems. Objectives. To examine ck19 expression as a diagnostic marker in thyroid neoplasms with follicular growth pattern. Design. In this cross sectional study, 86 patients were enrolled. Subjects and Methods. Totally 22 follicular adenoma (FA), 18 well differentiated tumors with undetermined malignant potential (WT-UMP) and 46 follicular variants of papillary thyroid carcinoma (FV-PTC) were enrolled and examined for Ck19 expression by immunohistochemistry staining. Membranous/cytoplasmic staining patterns were considered as positive. Specimens without staining were considered as 0, < 5% positively stained cells as 1+, 5%-25% as 2+, 25%-75% as 3+ and >75% as 4+. Result. CK19 was negative in most cases of FA while positive in most WDT-UMP and FV-PTCs, p<0.001. Additionally, most cases with 2+ and 3+ staining patterns were FV-PTC (75% and 81%, respectively, p<0.001) and none of FAs showed 3+ positivity (p<0.001). Additionally, most of strongly positive results in patients > 45 y/o were PTC (p<0.001). Conclusion. Ck19 is a useful marker in differentiating FA from FV-PTC. We found diffuse and strong (3+) staining pattern in FV-PTC but none of FAs were so. We concluded that diffuse and strong staining for ck19 in a thyroid lesion with follicular pattern of growth, especially in a patient older than 45 y/o should raise the possibility of malignancy.

Aim. The epidemic of metabolic syndrome increases worldwide and correlates with elevation in serum uric acid and marked increase in total fructose intake. Fructose raises uric acid and the latter inhibits nitric oxide bioavailability. We\r\nhypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome and treatment of\r\nhyperuricemia or increased nitric oxide may improve it.\r\nMethods. Two experiments were performed. Male Sprague-Dawley rats were fed a control diet or a high fructose diet to\r\ninduce metabolic syndrome. The latter received either sodium nitrate or allopurinol for 10 weeks starting with the 1st day of fructose to evaluate the preventive role of the drugs or after 4 weeks to evaluate their therapeutic role.\r\nResults. A high-fructose diet was associated with hyperuricemia, hypertension, dyslipidemia, insulin resistance, decreased tissue nitrite and increased adiposity index. Sodium nitrate or allopurinol was able to reverse these features in the preventive study better than the therapeutic study.\r\nConclusion. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid. Either sodium nitrate or allopurinol can\r\nprevent this pathological condition by different mechanisms of action.