ACTA ENDOCRINOLOGICA (BUC)

Context. Permanent hypocalcemia is a rare but significant complication of thyroid surgery Objective. The aim of this study was to identify predictive factors of hypocalcemia and hypoparathyroidism after thyroidectomy . Design. Study included 134 total patients submitted to thyroidectomy from two endocrine units (January 2015 – August 2016). Methods. We measured total serum calcium (sCa) and intact PTH (iPTH) on postoperative day one and 1 month after surgery. Results. 118 patients were women with F/M ratio of 7.3/1 and a mean age of 51.8 years. 64 patients were included in group A (iPTH <12 pg/mL) and 70 patients in group B (iPTH >12 pg/mL). sCa and hypocalcemia symptoms were correlated with iPTH, measured 24 hours after surgery. The cut-off value was for sCa 8.05 mg/dL with a sensitivity of 85.29% and a specificity of 88.0% and for iPTH 11.2 pg/mL, with a sensitivity of 82.3% and a specificity of 71.0%. SCa (< 8.05 mg/dL) was a predictive factor with a 99 (IC95%:12.86- 761.58) and iPTH (<11.2 pg/mL) with a 10.77 higher risk (CI95%: 3.83-30.30) to be associated with symptoms. Conclusion. SCa and iPTH represent good predictive factors of early and safe hospital discharge and can predict the risk of prolonged and permanent hypoparathyroidism.

Objective. To compare results of treatment of primary hyperparathyroidism (PHPT) in two teaching hospitals (eastern and western Europe) and to establish conclusions regarding quality of surgery for PHPT in Romania. Methods. We reviewed two prospectively collected databases of patients submitted to open minimally invasive parathyroidectomy (OMIP) for symptomatic PHPT in two centers from Romania and the United Kingdom (UK). We included patients with biochemically proven PHPT and positive pre-operative localization studies. We excluded patients with negative localization studies, suspected multiglandular disease, concomitant thyroid disorders and chronic renal failure. Results. 60 patients were included, 27 in group A (Romanian cohort) and 33 in group B (UK cohort). We noted significant differences between groups in pre-operative serum calcium and phosphorus levels (p<0.5). There were no differences between groups regarding the presence of symptoms; in group A we had significantly more patients with renal calculi history (p=0.02), digestive symptoms (p=0.006) and osteitis fibrosa cystica (p=0.01). Two patients from the UK group had lithium associated hyperparathyroidism and 2 patients had genetic disease. Intraoperative parathyroid hormone measurement (ioPTH) was available only for group B and frozen sections were selectively used in both groups. Both the adenoma size and weights were significantly higher in group A. The median operative time was significantly longer in Romanian group (p=0.001); in this group we noted the single conversion to traditional cervicotomy (3.7%) from all studied patients. In group A we noted two patients (7.4%) with failed parathyroidectomy and persistent PHPT; the cure rate was 92.5% for Romanian group and 97% for the UK group. Conclusions. OMIP can be performed safe with a high cure rate in “small” volume endocrine centres with results comparable to western experienced endocrine centres. Romanian patients presented with more severe PHPT with more frequent end-organ damage, due probably to late diagnosis.

experience regarding the first 24 patients diagnosed with refractory secondary and/ or tertiary hyperparathyroidism (HPT) who underwent subtotal parathyroidectomy (sPTx) in our clinic between 2010 and 2012. Methods. Data were retrospectively retrieved from a prospectively maintained database. We included patients diagnosed with refractory secondary and/or tertiary HPT who underwent sPTx; we excluded patients who underwent total parathyroidectomy (tPTx) and patients followed-up for less than six months. Results. We analyzed 24 patients,16 women (66.7%) and 8 men (33.3%) who were evaluated in a prospective manner in a short (1-6 months)/ medium (6-18 months) term follow up. Preoperative intact parathyroid hormone level (iPTH) was characterized by a median of 2131 pg/ mL (range: 1141-10000); in the first month after surgery the median iPTH level was 28 pg/mL (range: 3-1263). We found a statistically significant difference (p<0.01: Student test) in calcium level between preoperative values and values in the first month after surgery. Postoperative serum phosphorus (nv: 2.7-4.5 mg/dL) normalized in 19 patients (79.16%) and serum alkaline phosphatase values decreased significantly in the interval 2-6 months postoperative versus preoperative levels (p-0.002). We tried to establish a correlation between preoperative alkaline phosphatase (Alk Phos) and postoperative calcium level in the first month postoperatively. The overall clinical response to sPtx was good and we did not encounter postoperative mortality in our series. Conclusion. We believe that subtotal parathyroidectomy is feasible, safe and effective for patients with refractory secondary and tertiary hyperparathyroidism.

Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

Background. Postoperative hypocalcemia after thyroid surgery has a high prevalence ( 16-55% in different series). Incidental parathyroidectomy (IP) is a less discussed complication of thyroidectomy with consequences not properly defined. The aim of our study was to find incidence, risk factors and how to prevent IP. Methods. Extensive search of English literature publications via PubMed was performed and 73 papers from 1980 to 2017 were analysed using the GRADE system/classification, quality of evidence was classified as “strong” when the result is highly unlikely to change existing recommendation and “weak” when opposite. Results. Incidence of IP is 3.7-24.9%, while prevalence of permanent hypoparathyroidism is less frequent 6-12%. Direct relation between IP and hypoparathyroidism/ hypocalcemia remains controversial. Female patients, ectopic parathyroids, small thyroids, Graves’, malignancy, redo surgeries and total thyroidectomy favour IP. Routine visualization of parathyroids, new hemostatic devices, magnifying instruments and fluorescence can prevent incidental removal of parathyroids. Incidence of IP during videoassisted or robotic thyroidectomies was similar to open procedures. High volume, experienced and younger surgeons have lower complication rates (including hypoparathyroidism). Conclusions. Incidental parathyroidectomy is more frequent than we might have expected. It should be avoided and parathyroid glands should be kept in situ. Majority of studies are retrospective (low degree of evidence according to previous mentioned GRADE classification) and further meta-analysis or randomized control studies are welcome in order to define the impact of incidental removal of parathyroids on postoperative outcome.

There is limited information on the long-term natural history of adrenal function in adrenal hemorrhage following sepsis. The 19-year history of a patient is described who suffered adrenal hemorrhage during pneumococcal sepsis. Adrenal reserve using Cosyntropin testing with the 250 mcg dose was evaluated at seven time points during this interval, and a close observation of the patient enabled clinical correlation with adrenal status. The cosyntropin testing showed a 60 minute cortisol level post-hemorrhage of: 303.4 nmol/L (11.0 mcg/dL), one month; 656.6 nmol/L (23.8 mcg/ dL), 1 year 10 months; and 714.5 nmol/L (25.9 mcg/dL), 19 years. Over the years the patient experienced hypoadrenal symptoms requiring both hydrocortisone and fludrocortisone until her adrenal function consistently demonstrated a 60 minute cortisol level of ~ 717.3 nmol/L (26 mcg/ dL). Adrenal calcifications were visualized by ultrasound imaging and ultimately resolved. In conclusion, the patient’s hypothalamic-pituitary-adrenal system appeared to have ultimately restored normal basal adrenal function 19 years after the initial hemorrhage, and the dynamic cosyntropin data indicate that normal adrenal function should not be assumed with a 60 minute cortisol level of 496.6 – 551.8 nmol/L (18 – 20 mcg/dL). Finally, mineralocorticoid as well as glucocorticoid may be important for improved mental acuity in primary hypoadrenalism.

Background. While exogenous obesity is consistently associated with early sexual maturation in girls, the reports in boys show conflicting results with some showing a positive association and others a negative or no association at all. Aim. To assess the pattern of sexual maturation in boys with exogenous obesity. Design: Mixed longitudinal study. Subjects and methods. In the present study, 102 boys between 8 yrs (+3 months) and 16 yrs (+3 months) of age with exogenous obesity who belonged to mixed socioeconomic strata were assessed at 6 monthly intervals for development of genitalia, pubic, facial and axillary hair as per the criteria laid down by Tanner 1962 in addition to their general anthropometric assessments. The data obtained was compared with previously published normative auxological and sexual maturity related data. Results. The attainment of G2 and G3 stage of genitalia development was earlier as compared with their Indian and western peers while G3 and G4 stages were found to be relatively delayed. None of the obese boys could attain G5 stage by the age of 16yrs. The appearance of facial (11.68±1.73yr), pubic (11.7±1.79yr) and axillary hair (12.41±1.69yr) occurred earlier than their Indian and western counterparts. Conclusion. The onset of sexual maturation amongst obese boys in this study as compared to their normal counterparts was earlier even though the progression of maturation was found to be relatively delayed.