ACTA ENDOCRINOLOGICA (BUC)

Objective. To evaluate obstetric and neonatal outcomes of patients with type 1 diabetes mellitus (T1DM) and compare multidose injection (MDI) and continuous subcutaneous insulin infusion (CSII). Study Design. Retrospective study of 53 pregnant patients with T1DM reaching at least 24th gestational week. Results. Fourteen patients (26.4%) hospitalized for insulin dose regulation. Ten patients had hypertensive diseases. Perinatal mortality occurred in 2 neonates owing to cardiac malformations. Neonatal hypoglycemia, small for gestational age, large for gestational age, and neonatal jaundice were demonstrated in 8, 4, 12 and 19 newborns, respectively. Sixteen newborns were admitted to the NICU for various reasons. Congenital malformations were detected in 7 newborns (6 cardiovascular and 1 central nervous system anomaly). Despite lack of statistical significance, total daily insulin doses were higher in the MDI group than in the CSII group with doses of 62 IU (18–166) and 51 IU (20–114), respectively (p=0.119). Gestational and perinatal outcomes also showed no statistical significance. However, all congenital abnormalities and perinatal deaths occurred in the MDI group. Conclusion. T1DM in pregnancy is a challenging problem in terms of having better obstetric and perinatal results. CSII may be used safely instead of MDI in appropriate patients.

Context. The effects of COVID-19 on the adrenocortical system and its hormones are not well known. Objectives. We studied serum cortisol, serum adrenocorticotropic hormone (ACTH), and their ratio in hospitalized non-critically ill COVID-19 patients. Design. A prospective case-control study. Methods. The study participants were divided into 2 groups. Group 1 consisted of 74 COVID-19 patients. The second group consisted of 33 healthy persons. Early admission above hormones levels was determined and compared between the study groups. Besides that, COVID-19 patients were grouped according to their Glasgow Coma Score (GCS), CURB-65 score, and intensive care unit (ICU) requirement, and further sub-analyses were performed. Results. There were no significant differences in the mean age or gender distribution in both groups. In the patients’ group, the serum ACTH concentration was lower than in the healthy group (p<0.05). On the other hand, the serum cortisol levels and cortisol/ACTH ratio of the patients’ group were significantly higher than of the healthy controls (p<0.05, all). Further analyses showed that, although serum cortisol and ACTH levels were not high, the cortisol/ACTH ratio was higher in COVID-19 patients with low GCS (<15) than patients with normal GCS (=15) (p<0.05). In COVID-19 in patients with different CURB-65 scores, the cortisol/ACTH ratio was significantly different (p<0.05), while serum cortisol and ACTH were not different in groups (p>0.05). Serum cortisol levels and cortisol/ACTH ratio were higher but ACTH level was lower in the ICU needed COVID-19 patients than in patients who do not need ICU (p<0.05). Conclusion. Our pilot study results showed that the cortisol/ACTH ratio would be more useful than serum cortisol and/or ACTH levels alone in evaluating the adrenocortical system of COVID-19 patients. Still, further detailed studies are needed to confirm these.

Context. Craniopharyngiomas (CPH) are benign tumors, rarely encountered in children, representing 5-6% of all intracranial tumors. Objective. This study aimed to analyze the surgical management and quality of life in a series of CPH pediatric cases. Design. This was a multicenter study performed over a 25-year period (1994 - 2019) in Bucharest. Subjects and Methods. 152 children (0-17 years old) were treated for CPH. Preoperative manifestations were intracranial hypertension, endocrine dysfunction, visual impairment, ataxia, intellectual performance decrease. Results. Considering all surgical approaches used, we advocate for pterional approach to best fit in CPH. We achieved gross-total removal (GTR) in 83 cases (54.4%), near-total resection (NTR) in 13 cases (9%), partial resection (PTR) in 51 cases (33.3%). 5 cases were biopsies (3.2%). Gamma Knife Surgery was performed in 10 cases (6.5%), all recurrences. At 6 months GOS revealed: Good Recovery 70 cases (46.2%), Moderate Disability 62 cases (40.7%), Severe Disability 13 (8.5%), Vegetative State 2 cases (1.3%), Deceased 5 cases (3.2%). Complications were: diabetes insipidus (89.3%); hypopituitarism (66.4%); hypothalamic damage (17.7%); visual deterioration (18.4%). Conclusions. Surgery remains the main option, but GTR complications prove the necessity for a multidisciplinary approach. Outcome predicting factors are: age, tumor size, hydrocephalus degree, hypothalamic dysfunction.

Context. Inflammation-related markers may predict cardiovascular diseases. Objective. In this study, it was aimed to assess pentraxin-3 (PTX-3) levels and its relationship with carotid intima-media thickness (CIMT) and high-sensitive C-reactive protein (hsCRP) in patients with subclinical hypothyroidism. Design. Prospective cross-sectional study Methods. This study included 60 patients (aged 30-60 years) with subclinical hypothyroidism and 30 healthy volunteers as controls. The demographic characteristics and anthropometric measurements were performed in all patients and controls. In addition, sonographic carotid artery examination, thyroid functional tests, lipid profile, hsCRP, and PTX-3 levels of the participants were investigated. Results. The PTX-3, hsCRP levels and CIMT were higher in patients with subclinical hypothyroidism when compared to controls (p=0.008, p=0.001, p<0.001, respectively). The PTX-3 level was strongly correlated with hsCRP (r=0.865; p<0.001), but no such correlation was detected with CIMT (r=-0.255; p=0.50). In binominal logistic regression analysis, it was found that CIMT and serum uric acid levels were independent parameters associated with subclinical hypothyroidism. In ROC analysis, a cut-off value of >3.75 ng/mL for serum PTX-3 level predicted subclinical hypothyroidism with a sensitivity of 60% and specificity of 60.7% (AUC: 0.672, p=0.004). Conclusion. Showing inflammation and endothelial dysfunction, the PTX-3 may be a helpful marker in patients with subclinical hypothyroidism associated with increased risk for cardiovascular disease.

Context. Foetal asphyxia, a frequent birth complication, detrimentally impacts the immature brain, resulting in neuronal damage, uncontrolled seizure activity and long-term neurological deficits. Oxytocin, a neurohormone mediating important materno-foetal interactions and parturition, has been previously suggested to modulate the immature brain’s excitability, playing a neuroprotective role. Our aim was to investigate the effects of exogenous oxytocin administration on seizure burden and acute brain injury in a perinatal model of asphyxia in rats. Animals and methods. Asphyxia was modelled by exposing immature rats to a 90-minute episode of low oxygen (9% O2) and high CO2 (20% CO2). Control rats were kept in ambient room-air for the same time interval. In a third group of experiments, oxytocin (0.02 UI/g body weight) was nasally administered 30 minutes before the asphyxia episode. Seizure burden was assessed by the cumulative number of loss of righting reflex (LRR) over a two-hour postexposure period. Acute brain injury was assessed through hippocampal S-100 beta, a biomarker of cellular injury, 24-hours after exposure. Results. Asphyxia increased both LRR and hippocampal S-100 beta protein compared to controls, and these effects were significantly reduced by oxytocin administration. Conclusion. Oxytocin treatment decreased both seizure burden and hippocampal injury, supporting a potential neuroprotective role for oxytocin in perinatal asphyxia.

Context. As we progress into the COVID-19 pandemic, it has become apparent that this infection is associated with a multitude of systemic effects, some involving the thyroid gland. The thyroid is also frequently affected in the HCV chronic infection. Objective. The objective of this study is to determine the effects of COVID-19 infection on the presence and severity of thyroid disorders associated with chronic HCV infection, at short and mid-term follow-up. Design. We prospectively evaluated patients with documented HCV- associated thyroid disease (with sustained virologic response after antiviral therapy). Subjects and Methods. The study group consisted of 42 patients with HCV- associated thyroid disease, diagnosed with COVID -19 infection between April and October 2020. We determined serum values of thyroidstimulating hormone, freeT3, free T4, anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies at one and three months after resolution of infection and compared them to the baseline characteristics of the patient. We also evaluated the changes in thyroid substitution treatments or antithyroid drugs. Results. At baseline, out of the 42 patients, 5 presented hypothyroidism under levothyroxine substitution therapy, while 2 presented hyperthyroidism under methimazole therapy; 37 patients had positive antithyroid antibodies. At one month follow-up, we note an increase in serum values of antibodies, with a decrease in TSH, freeT3 and freeT4 levels, correlated with the severity of COVID-19 infection. Two patients required discontinuation of levothyroxine. At 3 months follow-up, lower levels of antithyroid antibodies were recorded, with an increase in TSH levels. No medication doses were adjusted at this time. Conclusion. Among the systemic effects of COVID-19, the impact of thyroid dysfunction should not be underestimated, especially in the presence of pre-existing conditions, such as HCV infection.

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.

Nicolae Paulescu (1869-1930) was born in Bucharest in an aristocratic family. His education from childhood to maturity (Paris University of Medicine) was marked by illustrious professors, even pioneers of their field. After completing his medical and scientific education in Paris under his mentor, Etienne Lancereaux, considered the founder of modern physiology, he returned to Romania where he founded the first Department of Physiology at “Carol Davila” University of Medicine and Pharmacy. His scientific career is marked by the publishing of 88 original research articles in renown international medical journals of the time and two Treatise on Physiology (comprising in total 8 volumes and 5976 pages). His activity as an endocrinologist reaches the peak with the discovery of insulin with the article Recherche sur le rôle du pancréas dans l’assimilation nutritive published in the Archives Internationales de Physiologie (Liege, Belgium) on August 31st, 1921. While he was not internationally or even nationally acclaimed for the discovery of insulin, his contribution to the reformation of the national education and medical system and the recommendation of his students to pioneers of their fields of interest still have reverberations even today.

Background and Objectives. Levels of insulin-like growth factor-I are characteristically low in Laron syndrome which is a factor that has important roles on vascular health and development. Congenital insulin-like growth factor-I deficiency was reported to be associated with some vascular disorders. However, vasculitis diseases and Laron Syndrome association has not been reported in English literature up to date. Patient. We report the case of a two and a half years old Turkish girl, who was diagnosed as Laron syndrome when she was 12 months old. She presented with acute vasculitis lesions. Her physical examination and laboratory studies did not reveal a specific infectious agent or also an autoimmune disease was not detected. Her lesions disappeared during hospitalization without a complication. Conclusion. Since insulin-like growth factor-I reduces endothelial cell oxidative stress and maintains the structural integrity of vessels, some common mechanisms might be responsible for the occurrence of vasculitis in this patient with Laron syndome. The role of insulin-like growth factor-I and recombinant human insulin-like growth factor-I treatment choice in vasculitis diseases is a matter of investigation.

Aims. In August 2015, FDA published a black box declaring that DPP-4 inhibitors may cause severe joint pains. The impact on autoimmunity marker positivity of these drugs has not been comprehensively evaluated. We compared the incidence of arthritis/arthralgia in patients with T2DM who were using DPP-4 inhibitors and patients who were not using. Methods. A number of 93 DPP-4 inhibitor users and 107 non-users were included into the study. Arthritis/ arthralgia were found in 41 of 93 (44.1%) DPP-4 inhibitor users and in 19 of 107 (17.8%) non-users (p<0.05). Results. No inflammatory rheumatological condition was identified in 27 of 41 (65.9%) patients in DPP-4 inhibitor user group as well as in 13 of 19 (68.4%) patients in non-user group (p>0.05). After adjusting for gender the incidence for arthritis/arthralgia was significantly increased in the DPP-4 inhibitor user group (p value for any DPP-inhibitor <0.05). There was 3.77 times increased risk for arthritis/arthralgia in the DPP-4 inhibitor using group (p value= 0.001) and this risk increases 2.43 times for each year of DPP-4 inhibitor usage. Conclusions. Arthritis/arthralgia were more common among T2DM patients who were using DPP-4 inhibitors compared to non-users, but the seropositivity did not differ between DPP-4 inhibitor users and non-users.