ACTA ENDOCRINOLOGICA (BUC)

A 52-year old women was diagnosed with acromegaly 5 years ago, and transseptal transsphenoidal pituitary microsurgery has been performed. Later the patient did not come to controls and the complaints prior to operation growth of the hands and feet, headache, sweating and resistant hypertension have continued. She was referred to our clinic with the same complaints. Physical examination showed typical acromegalic features without typical Cushingoid features. Magnetic resonance imaging of the brain revealed the presence of a pituitary macroadenoma. Basal plasma levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were high. GH suppression was not observed in 75 gr oral glucose suppression test. Due to refractory hypertension and central obesity hypothalamo-pituitaryadrenal (HPA) axis was evaluated. HPA showed a lack of circadian rhythm of adrenocorticotropic hormone (ACTH) and cortisol, non-suppressibility to 1 mg overnight and classical 2 day low-dose dexamethasone, but suppressibility to high-dose (8 mg) dexamethasone. The tumour resected by transsphenodial surgery was histopathologically consistent with the diagnosis of adenoma. Immunostaining showed GH and ACTH producing cells. After surgery plasma GH and IGF-1 levels decreased to normal along with normalization of HPA axis. Hypertension disappeared without medical treatment after removal of the pituitary tumour. This is a very rare case of GH-producing pituitary adenoma causing typical acromegaly with concomitant production of ACTH causing subclinical Cushing’s disease.

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient’s health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

We studied the incidence, risk factors, presentation, treatment and prognosis of calcific uremic arteriolopathy (CUA) in 140 of our hemodialysis patients. Methods. Patients with CUA in the past 3 years have been compared to controls in a cross-sectional survey of 140 hemodialysis patients. Results. Prevalence of CUA was 6/140 (4.28%); common presentation was ulcerated acral necrosis. Age, sex ratio, BMI, prevalence of diabetes were similar in case (n=6) and control (n=134) patients. CUA patients had higher serum calcium (9.58?1.25 mg/dL vs. 8.50?1.03 mg/dL, p=0.01), calcium-phosphate product (71.06?19.67 mg2/dL2 vs. 58.73?17.20 mg2/dL2, p=0.01) and parathormone levels (1854?1407 pg/mL vs. 654?776 pg/mL, p=0.0002). Differences in ingestion of calcium, active vitamin D and non-calcium containing phosphate binders in the year prior to the assessment were not significant. CUA patients had higher CRP values in the 6 preceding months than non CUA patients (6.61?9.68 mg/dL vs. 1.97?4.20 mg/dL, p=0.01); logistic regression disclosed CRP as the only predictive factor for CUA (p=0.03). 4 (66%) of the CUA patients died due to sepsis, as compared to 3(2.23%) of the control group (p=0.001). 2 of 3 parathyroidectomised patients survived. In conclusion, this is, to our knowledge, the first series of CUA reported from Eastern Europe. In our center acral, ulcerated forms of CUA in patients with severe hyperparathyroidism are predominant.

Context. COVID-19 is more than a respiratory infection, with deep implications regarding multiple systems and organs. Thyroid damage is frequent in COVID-19 and may overlap previous HCV or HCC associated diseases. Objective. The objective of this study is to determine the effects of COVID-19 in patients with HCV associated HCC and thyroid comorbidities. Design. We performed a retrospective study of the thyroid function tests and autoantibodies in patients with HCV-associated HCC prior and during COVID-19. Subjects and Methods. We included 52 consecutive patients with HCV-associated HCC and documented thyroid disease, diagnosed with COVID -19 between April and October 2020. Serum values of thyroidstimulating hormone, free T3, free T4, anti-thyroglobulin antibodies and anti-thyroid peroxydase antibodies were determined and compared to baseline levels. Results. At baseline, 44 patients had positive antithyroid antibodies, 6 had hypothyroidism in substitution and 2 had hyperthyroidism under treatment. During COVID-19 we found an increase in serum values of antithyroid antibodies, and decreased levels of TSH, freeT3 and freeT4 levels. Specific therapies were discontinued in one patient with hyperthyroidism and 3 patients with hypothyroidism. Conclusion. There is a significant impact of COVID-19 on the thyroid homeostasis; a long-term prognostic value for patients with HCC infected with COVID-19 required further extensive research.

Neonatal metabolic screening has proven to be an important tool for the early detection of innate metabolic errors. Despite the fact that simple and effective methods of testing for metabolic diseases have been identified since the middle of the twentieth century, no consensus has been reached so far on the content of neonatal metabolic screening panels. There are large differences between countries in the number of metabolic diseases identified through national metabolic screening programs, ranging from zero to several tens, the most common testing being for phenylketonuria and congenital hypothyroidism (including in Romania). Given the fact that rare but treatable diseases have been identified in recent decades, reducing the financial burden on the health system, it would be useful to include them in the national neonatal metabolic screening program.

Context. Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. Objective. To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. Design. This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital “Pius Brinzeu” Timisoara. Subjects and Methods. We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. Results. The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). Conclusions. Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

Objective. After total thyroidectomy, radioiodine (131I) treatment is a usual treatment in patients with differentiated thyroid cancer (DTC). Since most of ingested 131I is excreted by the kidneys, one of the procedures for enhancement of 131I excretion from the body is the use of diuretics. The aim of study was to investigate the effect of hydrochlorothiazide (HCTZ) administration on the excretion of 131I in the urine in patients with DTC treated with 131I. Design. Study included 90 patients with DTC, normal renal function and low 131I uptake in the thyroid gland region. Patients were divided into two groups: the group taking HCTZ and the control group. All patients underwent whole-body measurements of the radioactivity of 131I in the urine and in blood samples. Results. Blood radioactivity was significantly higher in the HCTZ group as compared to the control group (16380.89 vs. 11731.61cpm/mL/GBq; P=0.007). The residual radioactivity in the body and the exposed dose were higher in patients taking HCTZ (71.61 vs. 60.70MBq/ GBq and 7.05% vs. 6.14%) but this difference was not significant. During the first 36h from 131I administration the patients taking HCTZ excreted a higher percentage of the 131I than the controls (65.45±12.12% vs. 62.21±11.25%, P=0.032). During the second part of the hospitalization (36- 72h) the urinary excretion as reversed, so after 72h patients taking HCT excreted less 131I than controls, however, this difference was not significant (P=0.084; 76.54±10.16% vs. 83.81±13.46%). Conclusions. HCTZ given as additional treatment decreases urinary excretion of 131I as and should not be administered in patients under 131I treatment for DTC.

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Context. Hyperparathyroidism-jaw tumour (HPTJT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. Objective. To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. Subjects and Methods. Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. Results. Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. Conclusions. We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

Background. People chew betel nut (Areca catechu) for physical work and stress reduction, but it contains arecoline, which has both therapeutic value and untoward effects on endocrine and gonadal functions. Objective. Aim of the present study is to investigate its role on adrenal with its target in metabolic stress in mice. Materials and methods. Mice were deprived of water / food, each for 5 days / treated with arecoline (10 mg / kg body wt daily for 5 days) / arecoline after water or food deprivation, for 5 days each. Results. Water or food-deprivation caused adrenocortical hyperactivity, evident from abundance of enlarged mitochondria and smooth endoplasmic reticulum (SER) with elevation of corticosterone level (C: 68.31 ± 2.30, WD: 159.31 ± 4.10 / FD: 194.12 ± 3.40 μg/ mL). Arecoline treatment alone or in water deprivation (C: 68.31 ± 2.30, AR: 144.50 ± 4.33, AR+WD: 194.42 ± 3.35 μg/ mL) / food deprivation (AR + FD: 180.89 ± 4.51 μg/ mL) stress also stimulated adrenocortical activity as recorded in metabolic stress. In contrast, adrenomedullary activity was not altered following water/ food deprivation. Arecoline treatment alone or in metabolic stress suppressed adrenomedullary activity by showing depletion of chromaffin granules (E/NE?), epinephrine (E) and norepinephrine (NE) concentrations. Both the stress decreased blood glucose and liver glycogen levels. Arecoline treatment decreased blood glucose level, with a rise in liver glycogen level, but elevated blood glucose level in water deprivation unlike in starvation. Conclusion. Arecoline alone or in metabolic stress involves adrenal and probably other endocrine glands (pancreas, posterior pituitary and rennin-angiotensin system) to maintain homeostasis in metabolic stress in mice.