ACTA ENDOCRINOLOGICA (BUC)

Background/Aims. Growth hormone deficiency (GHD) in children and adolescents is managed with growth hormone (GH) therapy and aims to achieve optimal height development. However, treatment adherence can be poor, reducing the likelihood of a successful outcome. Adherence varies between geographic regions. This observational study assessed satisfaction and adherence to NutropinAq (somatropin, recombinant human GH) treatment in Romanian children with GHD. Methods. Patients ≥3 years of age with GHD for which GH replacement therapy with NutropinAq had been initiated were recruited from 13 centres in Romania (protocol number: A-38-58035-016). The primary variable was patient/caregiver-reported treatment adherence (assessed at 3, 6 and 12 months on a 5-item Likert scale), secondary variables included treatment satisfaction assessed by the treating physician and patient/caregiver on a 5-point scale. Results. Most patients did not miss any treatment injections in any 3-month period between assessments (≥79.8% of patients were 100% compliant). The incidence of missed injections was higher among patients <7 years of age than older children, but no differences between genders was observed. At study end, 94.3% of patients/caregivers and 94.3% of physicians reported complete satisfaction with treatment. Conclusions. Overall treatment adherence to NutropinAq was high in the Romanian GHD paediatric population, and a high level of treatment satisfaction was reported by patients/caregivers. This suggests reliable treatment outcomes can be anticipated in this population.

Context. Understanding factors delaying recovery in thyrotoxicosis patients is crucial for optimizing treatment plan. Objective. This study aimed to identify predictive factors for the delayed thyroid function recovery in thyrotoxicosis patients. Design. The study is a retrospective review of medical records of adult thyrotoxicosis patients diagnosed at Kaohsiung Veterans General Hospital, Taiwan, from January 2014 to December 2021. The duration of follow-up for the main outcome was at least 18 months. Subjects and Methods. Patients newly diagnosed with thyrotoxicosis who were age > 18 years old, had a TSH level <0.1 μIU/mL, received CBZ or PTU treatment, and demonstrated a subsequent TSH increase to above 0.4 μIU/ mL, were included. Results. The study included 443 patients. The average time to achieve normalized TSH levels was 6.9 months. Key factors associated with delayed TSH normalization included higher body mass index (BMI) [odds ratio (OR) = 1.06, confidence interval (CI): 1.01–1.12], elevated serum free T4 levels (OR = 1.97; CI, 1.44–2.69), and treatment with propylthiouracil (OR = 2.66; CI, 1.33–5.32). In contrast, factors such as sex, age, season of diagnosis, and comorbidities did not significantly impact the rate of TSH normalization. Conclusion. The study highlights the importance of considering individual patient characteristics, such as BMI and initial free T4 levels, in thyrotoxicosis management. The findings suggest a potential preference for carbimazole over PTU in achieving faster TSH normalization. This research contributes to the understanding of thyrotoxicosis recovery and supports the need for personalized treatment approaches in clinical practice.

Context. Thyrotropin-receptor antibodies (TRAb) are biomarkers of Graves’ disease (GD) and Graves’ orbitopathy (GO). Elevated immunoglobulin E (IgE) and antinuclear antibodies (ANA) were also found in GD patients. Objective. We aimed to assess TRAb, IgE and ANA in GD and GO patients and to evaluate the relationship between the immunological markers and smoking. Design. This was a comparative cross-sectional study carried out in a single tertiary care center from June 2018 to January 2020. Subjects and Methods. A total of 103 GD patients (mean age 51.2, 84 females) were divided into three subgroups: moderate-to-severe GO (n=36), mild GO (n=32) and “only GD” subgroup (n=35). Forty healthy controls (HC) (mean age 51.2, 36 females) were also included. TRAb were measured by a thyrotropin-binding inhibitory immunoglobulin (TBII) assay in GD patients; IgE and ANA - by an enzyme-linked immunosorbent assay in all subjects. Results. GD patients had higher IgE-positivity rate (p=0.04) and similar ANA-positivity compared to HC. Moderate-to-severe GO subgroup had the highest TBII (p<0.01), the lowest TBII-negativity rate (p<0.01) and the highest ANA-positivity rate (p=0.03) and was the only subgroup whose IgE-positivity rate was significantly higher than HC (25% vs. 7.5%). Mild GO and “only GD” patients had comparable TBII, TBII-negativity rate, IgE and ANA. Both GO subgroups had significantly higher smoking rate than “only GD” patients. Smoking was positively associated with IgE positivity (φ=0.22, p=0.03), and negatively with TBII negativity rate (φ=-0.24, p=0.02). Conclusions. GD patients exhibit different immunological patterns depending on the presence and severity of GO. Smoking might be just one of the factors responsible for the clinical and immunological variety of GD. Further studies are needed.

Background. Patients that recovered from COVID-19 may remain with symptoms which can persist for an uncertain period of time. Aim. The purpose of this study was to investigate the reasons why patients who passed the acute phase of COVID-19 presented themselves to the Emergency Department. Patients and Methods. We selected 87 patients admitted to the Emergency Department of the Bucharest University Emergency Hospital between 01.01.2021- 31.05.2021. Patients had pulmonary fibrosis (11.49%), pleural effusion (16.09%) or a history of hypertension (73.56%), type 2 diabetes (42.53%), stroke (24.14%), malignant diseases (10.34%). Results. Association between neutrophil levels and acute stroke and between fibrinogen levels and alveolar condensation were identified. The percentage of deaths was significantly higher in the subgroup of subjects that had maxim 11 days of hospitalization (p=0.004); we observed a trend of association between the age of more than 51 years old and admission in the Emergency Unit at less than a month after the SARS Cov2 infection, the positive result at the RT-PCR test or a lung damage of over 30% (p<0.05). Conclusion. A significant percentage of patients that were admitted to the Emergency Unit post COVID-19 had chronic pathologies and their characteristics were associated with neutrophilia, high fibrinogen levels or length of hospitalization.

Background and aim. Antithyroid drugs are first treatment for Graves hyperthyroidism worldwide. Although remission can be achieved in approximately 40-50% of patients in 12-18 months with antithyroid drugs, this period can be extended up to 24 months. We aimed to evaluate the effect of individual clinical/biochemical variables and GREAT score in predicting response to antithyroid drug in Graves disease. Material and methods. This is a retrospective single-center study including 99 patients with the first episode of Graves disease treated for at least 18 months. The patients were classified into two groups as those who responded to antithyroid medication at 18-24 months (group 1) and those who did not respond at 24 months and continued with low-dose antithyroid medication (group 2). Results. Medical treatment response was obtained in 38 (38.3%) of the patients at 18 months, and in 19 (19.1%) patients at 24 months. Long-term medical treatment (>24 months) was given to the remaining 43 patients due to the lack of response to medical treatment. Thyroid volume and free T4 levels were higher in those followed up with longterm antithyroid drugs, and orbitopathy was more common in this group. Median anti TPO value was significantly higher in group 1 when compared to group 2 (593 U/l and 191.6 U/l respectively). More patients were classified as GREAT class 3 in group 2 when compared to group 1 (46.5% and 12,5% respectively). We analyzed the Thyroperoxidase Antibody(anti TPO) titers, which we divided into three levels, according to groups 1 and 2. Post-hoc Chi-Square analysis revealed that falling into the highest anti TPO category was significantly associated with response to medical therapy in 24 months (p <0.05). Conclusion. According to our study, GREAT score and anti TPO Ab titers at presentation may help predict response to ATD in Graves disease

Context. It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. Objective. To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. Design and Methods. Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. Results. Nine out of 21 patients were diagnosed as having Cushing’s disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. Conclusion. The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

We present the case of severe hypocalcaemia in a 5 weeks old baby, secondary to pre and postnatal vitamin D deficiency. The symptomatic hypocalcaemia led to several life threatening episodes of seizures. Following initial calcium gluconate infusion, multiple phospho-calcic deposits in the soft tissue and cerebral tissue were observed. A multifactorial etiology of calcinosis cutis was suggested by the association between infusion of high and repeated doses of calcium gluconate in a severely hypocalcaemic baby, with a low 25- hydroxyvitamin D3 level, associated to a renal and bone relative resistance to the high level of PTH. The aim of this report is to raise pediatric health care professionals awareness on the relatively rare entity known as calcinosis cutis.

abdominal cystic lesions should include investigation of cystic pheochromocytomas. To date only a few cases of purely cystic pheochromocytoma have been reported in the English literature. Aim. To present the management in four cases of silent pheochromocytomas patients who presented with pure or partially cystic abdominal lesions with benign (n:3) and malignant characteristics (nonspecific neuroendocrine tumor) (n:1) in histological evaluation. Results. Resection of the tumor is considered the primary treatment option in the management of pheochromocytoma, and preoperative preparation with alpha and beta antagonists is crucial in order to avoid precipitation of hypertensive crisis during surgical procedures. The absence of clinical symptoms and lack of typical radiological features may complicate the diagnosis of pheochromocytoma resulting with increased mortality and morbidity during surgery. Conclusion. Asymptomatic pheochromocytomas are rare and they are responsible for approximately 5% of adrenal incidentalomas. These lesions may be referred to surgery as clinically nonfunctional adrenal adenomas.

Background. The transport of gametes and embryos is facilitated by motile cilia lining the inside of the fallopian tube. Progesterone regulates ciliary beat frequency (CBF) through multiple types of progesterone receptors in the fallopian tube. Membrane progesterone receptors beta and gamma (mPRβ and mPRγ) are both expressed in the ciliated cell lining of the fallopian tubes of humans. This study aimed at exploring the mRNA expression of mPRβ and mPRγ in the fallopian tubes of women with ectopic pregnancy. Materials and Methods. In this Case control study, a quantitative reverse transcriptase polymerase chain reaction was performed to determine the mRNA expression of mPRβ and mPRγ in the fallopian tubes obtained from 12 women with ectopic pregnancies, 12 women with normal pregnancies, and 12 healthy nonpregnant women in the luteal phase of their menstrual cycle. Results. It was indicated that mPRβ and mPRγ were expressed in the fallopian tube of the three groups of participants. However, the expression of mPRβ and mPRγ mRNA in the fallopian tube of women with ectopic pregnancy was not significantly different from that of the nonpregnant and normal pregnant women. Conclusion. These results suggest that mPRs might play no role in etiology of ectopic pregnancies associated with disturbed progesterone signalling.

Context. Anti-Mullerian hormone (AMH) assay is becoming the best indicator of successful IVF treatment response to fertility drugs and could be a useful marker of embryo implantation potential. Various protocols are being used for controlled ovarian stimulation (COS), but there is an uncertainty regarding the implementation of the best protocol for endometriosis patients and also little evidence is available concerning the clinical value of AMH levels in endometriosis. Objective. This study aimed to evaluate the prognostic value of serum AMH levels for pregnancy in COS using GnRH-agonist(GnRH-a) and GnRHantagonist( GnRH-ant) protocols in endometriosis patients. Design. This is a cross-sectional study between March 2012 and November 2015. Subjects and Methods. Data were collected from 249 COS cycles of endometriosis patients, including 129 cycles with GnRH-a and 120 cycles with GnRH-ant. Patients in each group were classified into three subgroups based on their serum AMH levels. The outcomes of ICSI program were evaluated. Results. The ROC curve analysis showed that embryo and oocyte counts and AMH were equally predictive for pregnancy, as demonstrated by a similar area under the curve (AUC) of 0.69, 0.66 and 0.64, respectively. The sensitivity and specificity for prediction of positive pregnancy were 70.91% and 67.01% for embryo counts, 70.91% and 67.53% for oocyte counts at the cutoff values of 5 and 7, respectively, and 83.64% and 52.58% for AMH levels at the cutoff values of 1.3ng/mL. Conclusions. This study demonstrates that AMH as a single test has substantial accuracy in the prediction of pregnancy using the GnRH antagonist protocol for patients with endometriosis. In other words, AMH assay prior to ovarian stimulation initiation guides the clinicians to choose the antagonist stimulation protocol for the patients with two extreme AMH levels. AMH levels can be used to individualize control ovarian stimulation in endometriosis patients.