ACTA ENDOCRINOLOGICA (BUC)

The pathogenesis of type 1 diabetes became a history longer and longer. There are 40 years since the immunogenetic theory of type 1 diabetes has been launched. Near this anniversary a challenge of this theory was recently published. We give here our interpretation of primary cause of type 1 diabetes which must be connected with the pathogenesis of other phenotypes of diabetes which has a main similar mechanism: the β-cell dysfunction.

Introduction. Biotin treatment causes false-low or false-high results in some immunoassays methods. This phenomenon is called as biotin interference. In the present article, a seven-month-old male, with renal failure and laboratory hyperthyroidism due to biotin interference is presented. Case report. High free T4 (fT4), free T3 (fT3), antithyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-TG) and low thyroid stimulating hormone (TSH) levels were detected in a seven-month-old male patient who has metabolic acidosis, renal failure, and suspected of metabolic disease. Anti-thyroid drug therapy was started. However, when he was re-evaluated due to the absence of euthyroidism with anti-thyroid therapy (methimazole 0.8 mg/ kg /day), it was found that the patient had been given 20 mg/ day biotin for acidosis for two months. Biotin interference was considered in hormone measurement. Thyroid function tests were found to be normal 12 days after discontinuation of biotin therapy. Conclusion. Immunoassay measurements which use biotin should be done 2-7days after the last dose of biotin in patients under biotin treatment, but this time may need be much longer in renal failure patients. During this period or if the biotin therapy cannot be stopped, alternative methods should be preferred for analysis.

Context. In addition to traditional risk factors for cardiovascular diseases, there are new risk factors with potentially relevant prognostic, such as vitamin D deficiency. Objective. The study aims to analyze the relationship between vitamin D deficiency and the occurrence of cardiovascular disease, in patients who already have at least one cardiovascular risk factor. Design. It is a prospective, observational study. Follow- up time was 24 months. Subjects and methods. A total of 77 patients were included in the study, aged over 18 years, who had at least one cardiovascular risk factor. Their vitamin D levels were measured and they were monitored for a period of 2 years, in order to see which one developed cardiovascular diseases. Results. Of the 77 patients, 56 (72.7%) had serum deficient levels of vitamin D and the mean serum level was 16 ng/mL (± 8.6 ng/mL). Statistically significant differences were observed only in the case of dyslipidemia (p=0.0334). The evolution to cardiovascular disease occurred in 39 of the cases (50.6%). The only independent risk factors for progression to cardiovascular disease demonstrated in this study were serum vitamin D (OR = 0.9024, 95% CI: 0.83- 0.97 and age (OR = 1.1313, 95% CI: 1.05-1.21). Conclusion. The results shows that patients with cardiovascular risk factors and advanced age are at a higher risk of developing cardiovascular disease, if they also have vitamin D deficiency.

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Background. Myocardial involvement is frequent in patients with systemic lupus erythematosus (SLE), and its early detection assures the prognosis improvement. Objective. To assess the NT-proBNP levels and its correlation with systolic longitudinal performance, during exercise testing in a SLE population Subjects and Methods. The study included 30 SLE patients (80 % females), with a mean age of 44.8 ± 9.91 years. All subjects were submitted to an echo Doppler examination, including the determination of the global longitudinal strain (GLS). Also, they performed a cardiopulmonary exercise testing (CPE) on cycloergometer, assessing the peak oxygen uptake. Venous blood samples were taken and NT-proBNP levels were determined before exercise, at peak effort and two hours after exercise. Results. The left ventricular ejection fraction was normal but GLS was low in SLE patients ( -16.96 ± 3.12%, vs. -19.5 ± 3.05% normal range) and much lower in those with diastolic dysfunction (-14.5 ± 2.3% vs. - 19.2± 1.85%, p=0.0014). During CPE, the patients performed a mean 71.96% ± 13.9% of predicted VO2 max. The mean values of NT-proBNP were: 186.84 ± 186.8 pg/mL at rest, 221.68 ± 245.76 pg/mL at peak effort and 412.48 ± 400.28 pg/mL post effort. No correlation was registered between GLS and peak VO2. We found a negative correlation between GLS ant NT-proBNP at peak effort (r = -0.508) and post exercise (r=-0.623). Conclusion. The exercise NT-proBNP levels can be used together with GLS for an early detection of systolic dysfunction in SLE patients.

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.

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.

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.