ACTA ENDOCRINOLOGICA (BUC)

Context. Bone mineral density (BMD) loss and progressive bone loss have been detected in patients with untreated\r\nhyperprolactinemia. It is unclear in patients with mild hyperprolactinemia.\r\nObjective. The aim of the study was to evaluate bone metabolism through bone mineral density by using dual energy X-ray absorptiometry (DXA) and bone turnover markers in premenopausal women with prolactinoma.\r\nDesign, Subjects and Methods. Twenty five patients newly diagnosed with prolactinoma and treated surgically and/or\r\nmedically, but whose prolactin levels were above the normal limits (PRL > 25 μg/L) and 25 healthy controls were included in the study, which was conducted at the Cerrahpasa Medical School, Division of Endocrinology and Metabolism outpatient\r\nclinic. Bone mineral density was measured using the DXA method. Bone turn-over markers such as alkaline phosphatase\r\n(ALP), osteocalcin, Type I collagen Ntelopeptide (NTX) and Type I collagen CTelopeptide (CTX) levels were determined.\r\nResults. The only significant difference in bone density (p=0.02) was in L4 lumbar vertebrae. There were no significant differences between the patient\r\nand the control groups in ALP, osteocalcin, NTX, and CTX levels.\r\nConclusion. There were no significant differences between the patient and the control groups in bone mineral\r\ndensity and bone turnover markers, except in the L4 lumbar vertebrae.

An 18 years old, tall man presented for circumoral numbness, paresthesias, and hypocalcaemia, without carpopedal spasm or seizures. Previous medical history revealed bilateral cataract and osseous cysts on limbs at the age of 12. Hypocalcaemia resistant to calcium treatment and mild increased TSH levels were present. At diagnosis, we noticed a normal phenotype with tall stature, moderate hypocalcaemia (5.8 mg/dL), hyperphosphatemia (5.08 mg/dL) and significantly higher than normal intact parathormone (PTH) levels (518 pg/mL), in the presence of normal serum levels of 25-hydroxy vitamin D (53.56 ng/mL). The mother and the family members have been found in good health. All these data strongly suggested sporadic pseudohypoparathyroidism type Ib (PHP-Ib), but with some features of PHP - type Ia, like the osseous cysts. We were not able to perform molecular genetic tests. The nearly complete recovery of clinical and biochemical signs (normalization of PTH, calcaemia, phosphatemia, and a normal DXA osteodensitometry) after 2 years of chronic treatment with activated 1,25- dihydroxycholecalciferol (2.00-0.75 μg/day) indirectly, but strongly confirmed the diagnosis of pseudohypoparathyroidism. The patient may have resistance to TSH evidenced by high TSH\r\n(range 4.8-7.5 mIU/L), with normal thyroid hormone levels, absence of goiter and normal TPO antibodies. The TRH test (400 μg i.v.) showed a response of TSH, and also of serum thyroxine and triiodothyronine in a range that did not clarify the diagnosis. This association of the resistance to TSH with type Ib PHP was relatively recently reported by two groups (17,20) and before them it was reported only in PHP-Ia. Our patient also showed mild thrombocytopenia, with normal bleeding time, indicating also a possible Gsα deficiency in platelets. In conclusion, our patient with sporadic pseudohypoparathyroidism without clinical phenotype of Albright hereditary osteodystrophy is highly suggestive for the type Ib PHP. A possible resistance to TSH and thrombocytopenia associated are features related to the genetic mechanisms found also in type Ia PHP. It is tempting to suggest that this case is one of the new variants of pseudohypoparathyroidism-Ib, recently reported.

Context. The current therapeutical management of secondary hyperparathyroidism (S-HPTH) is difficult to obtain due to the lack of kidney donors. Surgical intervention on the pathologic parathyroid tissue has been suggested as a method to alleviate symptoms in patients with chronic kidney disease (CKD). Objective. The aim of our study was to evaluate the outcomes of parathyroid surgery in patients with S-HPTH and the advantages of intraoperative quick PTH (iqPTH) to improve surgical results. Material and methods. In a real-life study, we compared one group of S-HPTH with iqPTH performed after removing all suspected glands and before wound suture (Group 1) and one group in that iqPTH was not assessed (Group 2). When iqPTH dropped less than 50%, additional exploration followed. Results. Eight out of the 34 patients from Group 1, who underwent subtotal parathyroidectomy, showed elevated levels of serum PTH and calcium, which remained elevated during follow-up, thus, suggesting disease persistence. From the 21 patients in Group 2, none showed early postoperative disease persistence. Serum calcium, but not PTH was increased in one patient from the iqPTH group but normalized after one month. Overall, iqPTH allowed detection of a supplementary parathyroid gland in one case, thereby increasing early post-surgery remission to 100% in Group 2 compared to 76.47% in Group 1. Late postoperative remission of hyperparathyroidism with no further increase in the rate of hypoparathyroidism was obtained in Group 2. Conclusions. Assessment of intra-operative PTH levels proved to be a useful tool in augmenting the outcome of S-HPTH surgery. In patients which are eligible for renal transplantation who undergo a subtotal resection, iqPTH can enhance the post-operative quality of life by lowering disease recurrence rates until the kidney transplant procedure.

Context. Underweight, overweight and obesity are important global public health issues and risk factors for adverse perinatal outcomes. Objective. To assess the distribution of the body mass index (BMI) in the Romanian obstetric population in the first trimester of pregnancy and its correlation with pregnancy outcomes. We also report the distribution of blood pressure (BP) parameters and their correlation with BMI. Design. This retrospective study includes 9,064 women attending routine first trimester visit and ultrasound scan at 12.8(±0.6) gestational weeks. Characteristics, parity, method of conception, blood pressure (from 3,650 women), maternal weight and height, BMI and foetal ultrasound were recorded. Pregnancy outcomes were available for 1,607 deliveries. The Pearson correlation coefficient was assessed for each BMI group vs. blood pressure parameters, gestational age and birth weight. ANOVA analysis and post hoc tests were used to determine group differences. Linear regression was applied to estimate the contribution of BMI and gestational age to birth weight variance. Results. In our population, 66.37% pregnant women had a normal BMI, 19.29% were overweight, and 7.56% were obese. There was a weak-to-medium positive correlation between BMI and blood pressure parameters, for all weight categories. The correlation between maternal BMI and birth weight was positive for normal and overweight. Conclusions. Our findings highlight the need for more effective health strategies targeting reduction of weight-related problems in women of childbearing age.

Background. Primary hyperparathyroidism is the third most common endocrine disorder, diagnosed by elevated parathyroid hormone (PTH) in hypercalcaemia. Several biochemical factors have been described to suggest severity of disease and may be correlated with preoperative imaging. Methods. This was a retrospective study of patients who underwent parathyroidectomy over a 3-year period. Preoperative calcium, PTH, vitamin D levels, ALP (alkaline phosphatase), vitamin D, serum phosphate and US and SPECT-CT positivity was noted. Results. 176 patients underwent parathyroidectomy and these were divided into 4 groups based on preoperative calcium. Overall, 61% of patients showed concordance between imaging and operative findings. Severe hypercalcaemia was associated with higher PTH levels, lower vitamin D levels, an increased rate of abnormal ALP levels, lower phosphate, male gender and highest rate of imaging concordance. Imaging positivity was associated with severe hypercalcaemia and elevated PTH levels. Level of PTH >125 pmol/L and hypercalcaemia >2.8 mmol/L are the most accurate cut-off levels for scan positivity. Conclusion. Biochemical factors associated with severity of the disease are directly correlated with positivity of preoperative imaging while ALP and vitamin D did not influence the preoperative imaging positivity but are associated with disease adversity. Serum phosphate level independently predicted results of parathyroid US.

Objective. This study examined the glycemic control among adult patients with type 2 diabetes mellitus (T2DM) and their ongoing antidiabetic therapy focusing on potential differences in attaintment of glycemic control associated with the use of specific antidiabetic regimens (ADR). Design. This was a cross sectional study conducted between September 2019 and March 2020 at a tertiary hospital, department of Internal Medicine. Subjects and Methods. Patients with T2DM who had a diagnosis of T2DM for at least one year and used their prescribed ADR for at least 3 months were included in the study. Glycated hemoglobin (HbA1c) was used for evaluation of glycemic control. Results. A total of 500 patients aged 59.4 (±10.2) years, with 9.9 (±6.7) years of diabetes duration (54% women, BMI: 29.6±5.1kg/m2) were analysed. The mean HbA1c was 8.3% (±1.9) and 34.2% of patients had a HbA1c level ≤7 %. 12%, 20% and 15.4% of diabetic patients were prescribed one, two or more than three antidiabetic drugs, 6.4% were on glucagon-like peptide 1 receptor agonists (GLP-1RA) only and 46% received insulin. Education level (OR=0.79; 95 % CI 0.66-0.94 p=0.009) and use of GLP-1RA (OR=0.19; 95 % CI 0.07-0.51 p=0.001) were associated with improved glycemic control while longer diabetes duration (OR=1.06; 95 % CI 1.02-1.11 p=0.004), use of basal insulin (OR=2.91; 95 % CI 1.70-6.88 p=0.010) and basal-prandial regiments (OR=2.49; CI 1.54-5.38 p=0.020) were associated with HbA1c >7%. Conclusions. Despite the introduction of novel drugs in the treatment of T2DM a majority of our patients fail to reach therapeutic goals.

Purpose. Previous studies have demonstrated the relationship between hyperthyroidism and increased risk of cardiac arrhythmias. The most common causes of hyperthyroidism are Graves’ disease (GD) and toxic nodular goiter (TNG). The aim of our study was to demonstrate if the underlying mechanism of hyperthyroidism, in other words autoimmunity, has an impact on the type of cardiac arrhythmias accompanying hyperthyroidism. Method. Twenty patients with TNG and 16 patients with GD who had overt hyperthyroidism were included in the study. Age, sex, thyroid hormone levels, thyroid autoantibody positivity, thyroid ultrasonography and scintigraphy results were recorded. 24-hour Holter ECG monitoring was performed in all patients. Results. Mean age was significantly higher in the TNG group compared to the GD group (62.9±11.5 vs. 48.9±8.6 years, p=0.001). Free T3 was significantly higher (7.87±3.90 vs. 5.21±1.53 pg/mL, p=0.033) in the GD group while free T4 and TSH levels were similar between the two groups. In 24-hour Holter ECG recordings nonsustained ventricular tachycardia (VT) rates were significantly higher in the GD group than in TNG group [18.75% (n=3/16) vs. 0% (n=0/20), respectively, (p=0.043)]. Paroxysmal atrial fibrillation (AF) rates were significantly higher in the TNG group compared to GD group [(30% (n=6/20) vs. 0% (n=0/16), respectively, (p=0.016)]. Conclusion. Although free T3 levels were lower, paroxysmal AF rates were found significantly higher in the TNG group which may be associated with significantly higher age of this group. On the other hand, higher rate of nonsustained VT in the GD group may be related to either significantly higher free T3 levels or autoimmunity.

Background. The cytotoxic T lymphocyteassociated molecules-4 (CTLA-4) is related to the relapse of Graves’ disease (GD) after anti-thyroid drugs (ATDs) withdrawal. We performed a meta-analysis to generate large-scale evidence on whether the CTLA-4 exon 1+49A/G polymorphism can predict the relapse of GD after ATDs withdrawal. Methods and Results. The PubMed, EMBASE,the Cochrane Library and reference lists of relevant studies were searched to identify eligible studies from inception to Jan, 2021. Ten eligible studies consisting of 1450 GD patients with a total of 848 relapsed patients were included in the meta-analysis. In Caucasians patients, the CTLA-4 exon 1+49A/G polymorphism significantly elevated the relapse risk of GD in additive (OR = 2.07, 95% CI: 1.18-3.62, P=0.011), dominant (OR = 2.52, 95% CI: 1.17-5.41, P=0.02), homozygote model(OR = 3.264, 95% CI: 1.25-8.52, P=0.016), except recessive (OR = 2.18, 95% CI = 0.98-4.86, P = 0.062) and heterozygote model (OR = 2.141, 95% CI = 0.958-4.786, P = 0.064). In Asian subgroup, none of these genotypes show any associations with the relapse of GD after ATDs withdrawal. Conclusion. This meta-analysis suggests that the CTLA-4 exon1 +49A/G polymorphism is associated with the relapse risk of GD after ATDs withdrawal in Caucasians, not Asians. Compared with the AA genotype, Caucasian patients with GG genotype have 3.264 times risk of relapse. A more aggressive treatment such as radioactive iodine or thyroidectomy, or longer periods treatment of ATDs should be recommended in Caucasian patients with the GG genotype.