ACTA ENDOCRINOLOGICA (BUC)

Objective. To assess in a bicentric study the current iodine status of schoolchildren, ten years after implementation of the universal salt iodization (USI) in Romania. Subjects and methods. 102 children from 2 towns, aged between 6 and 11 years, were included in the study group: 66 children from Sibiu, a previously endemic area for iodine deficiency disorders and 36 children from Bucharest, a previously borderline iodine intake area. Body mass index (BMI), total body surface area (BSA), median urinary iodine concentration (UIC) and prevalence of goiter were evaluated. Thyroid volume was measured by ultrasonography. The study was approved by the Local Ethics Committee. An informed consent from the parents was obtained. Results. From the 102 schoolchildren in the study group, 59 were girls and 43 were boys. Median UIC in the total number of samples was 175.2 mcg/L, reflecting a sufficient iodine intake, with statistically significant differences between the two urban regions. The median UIC was 187.35 mcg/L in the Sibiu subgroup and 160.2 mcg/L in the Bucharest subgroup (p < 0.001). The total percentage of goiter in the studied subjects was 5.88%. Percentage of goiter, determined by adjusting ultrasound thyroid volume to sex and BSA, was 1.51% in Sibiu and 13.88% in Bucharest, a statistically significant difference (p = 0.011). None of the subjects showed ultrasonographic pattern suggestive of Hashimoto thyroiditis or macronodules. There was no statistically significant difference between the percentages of overweight or obesity in the two subgroups. Conclusions. Ten years after implementation of USI in Romania, a bicentric study suggests that our country is iodine sufficient in urban areas. In order to prevent recurrence of mild iodine deficiency in schoolchildren, a persistent surveillance, use of sustainable measures and public awareness are required. Recurrence of mild iodine deficiency should be avoided, because even mild iodine deficiency impairs cognition in children.

In some humans, the big and big-big prolactin variants represent the majority of circulating prolactin, considered to be without biological activity. Aims: to establish the clinical expression of macroprolactinemia and the interference with immunodiagnostic tests\r\nin a randomized group of 84 consecutive patients with hyperprolactinemia. IRMA and electrochemiluminescence (Elecsys) were used for PRL assay; gel filtration chromatography (GFC) and protein A precipitation test were used to reveal macroprolactinemia. Results: Macroprolactinemia was found in 16 out of 84 patients (group A), 62 patients had hyperprolactinemia of other causes (group B) and 6 had normal PRL levels and normal GFC (group C). Of 16 patients with macroprolactinemia, 6 showed normal PRL with IRMA and hyperprolactinemia with Elecsys. The difference between the two methods used (&#8710; = PRL determined by Elecsys, -PRL determined by IRMA) correlated with big big PRL level determined by GFC with Elecsys in all patients. The strongest correlation was found in patients with macroprolactinemia (group A, r=0.82, p<0.01) as compared with group B, without macroprolactinemia (r=0.39, p<0.01). Menstrual disorders were expressed, but less frequent in group A versus B (3/15 vs. 28/56, p=0.04), and the appearance of galactorrhea and infertility were not statistically different. Conclusions: In these patients, macroprolactinemia had clinical expression, but weaker than in true hyperprolactinemic patients. It determines high apparent variability of serum PRL level in current commercial assays.

Introduction: The dexamethasone suppression tests (DST) in the diagnosis of Cushing's syndrome (CS) give frequently equivocal results. Our study evaluated the precision of DST in the diagnosis of CS. Patients and methods: 223 patients (15 - 77 years, 130 F / 93 M) were studied for putative CS by morning and midnight serum cortisol, urinary free cortisol (UFC) and 17 hydroxycorticosteroids (17OHCS) levels at baseline and after DST as follows: 1 mg overnight (oDST), 0.5mg q.d., 2 days (LDDST) and 2 mg q.d. 2 days (HDDST). Since not all cases were evaluated by all tests, statistical analysis used available results. Results: 79 patients had CS (47 pituitary, 3 ectopic, 21 adrenal adenoma and 8 adrenal carcinoma), 45 had adrenal tumor without all the criteria for CS (NCT) and 99 were controls. All patients with CS had abnormal cortisol biorhythm, but also 31.8% patients with NCT and 50% evaluated controls. The best basal screening test for CS is UFC, with a cut-off value of 100 g/24 h. For DST with a serum cortisol cutoff level (CCL) of 5 ?g/dl, oDST correctly diagnosed all CS, while lowering the CCL at 1.8 ?g/dl increased the false positive rate to 6.8%. At LDDST, the serum CCL of 5 ?g/dl correctly identified all patients with CS, but was 2.5 % false positive in controls. A significant correlation of serum cortisol values after oDST or LDDST with basal 17OHCS and UFC was found (r=0.6, p<0.001), suggesting that patients with mild CS are more prone to test as false negatives. The classical criterion of 50% suppression for UFC after LDDST correctly identified 12/14 CS patients and all 8 controls. Better sensitivity (Sn) had an UFC cutoff level of 10?g/24h, p<0.001. A 50% suppression of 17OHCS identified 45/61 CS patients and excluded the disease in 30/37 patients. In HDDST, serum cortisol suppression by > 50% diagnosed Cushing's disease (CD) with 85 % Sn and 57% specificity (Sp). The best HDDST accuracy had UFC (83%), with 27% false negative results (3/11 patients) for a cut-off value of\r\n50% from baseline. 17OHCS were suppressed by 50% in 19/35 patients with CD (54%) and in 3/33 (9%) patients with other causes of CS. NCT patients had higher basal values of UFC and 17OHCS than controls (p<0.01) and up to 50% had an abnormal biorhythm, suggesting a degree of hypercortisolism, with an inadequate oDST or LDDST . Therefore, only 6/45 NCT fulfilled the criteria for subclinical CS.\r\nConclusion: The best screening test was oDST (100% Sn and Sp), followed by UFC (100% Sn and 92% Sp). LDDST with serum CCL at 5 ?g/dl had 100% Sn and 97% Sp. HDDST identified CD by UFC with 73% Sn and 92% Sp and by serum cortisol with 85% Sn and 57% Sp. For NCT, the standard tests identified SCS in 13%. However, a thorough evaluation including multiple tests should be undertaken for the positive and differential diagnosis of Cushing's syndrome.

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Introduction: The impaired transport of leptin into the brain through a decreased permeability of the blood-brain barrier (BBB) for leptin in obesity represents one of the important mechanisms involved in leptin resistance which is characteristic in human obesity. Some pituitary tumors can increase the blood-cerebrospinal fluid barrier (BCB) permeability for peptides. BCB is a part of BBB.\r\nObjectives: The aim of our study was to search if the by-pass of BCB for pituitary hormones produced by adenomas does influence the transport of leptin into the central nervous system in obese patients.\r\nMaterials and methods: We investigated 20 males with pituitary adenomas: group A (11 patients) had cerebrospinal fluid (CSF) to serum ratio more than one for prolactin (PRL) and in some patients for growth hormone (GH) and follicle stimulating hormone (FSH), suggesting an increased permeability of BCB and a control group C (9 patients), which had CSF/serum ratio less than one for GH, PRL or FSH, suggesting an intact BCB. Both A and C groups contain subgroups of patients with obesity (body mass index, BMI>30 kg/m2) and normal body weight (BMI<25 kg/m2). In these patients we measured the CSF to serum leptin ratio in order to clinically evaluate the leptin transport into the brain. Rapid fluoroimmunoassay method with europium was used. Leptin was assayed by ELISA method.\r\nResults: The patients of group A with pituitary adenomas show a higher level of pituitary peptides, PRL and in some cases GH, FSH in CSF as compared to serum (ratio CSF/serum over 1), both in obese and non-obese. By contrast, in the same patients, there is\r\na low level of CSF leptin as compared to serum leptin (ratio CSF/serum less than 1). In the subgroup of obese patients from group A we found even less ratio of CSF to serum leptin, than in non-obese. There is a well known higher leptin concentration in the plasma of obese patients with pituitary adenomas as compared to non-obese ones (26.4?3.8ng/ml vs 12.4?3.4ng/ml, p<0.05). In the control group C, both pituitary peptides (PRL, or GH, FSH) and leptin showed a ratio CSF/serum less than 1, in all patients.\r\nConclusions: These data show a decrease in hemato-encephalic barrier permeability for leptin in obese patients through a specific mechanism, not influenced by other peptides passing through injuries of BBB produced by pituitary adenomas. It is tempting to suggest that there is a specific by-pass of BCB for pituitary peptides, in some pituitary adenomas.

Aims. Earlier studies suggested that patients with nonfunctioning pituitary adenoma (NFPA) experience premature mortality, mostly from vascular diseases. The present study aims to identify risk factors associated with mortality in patients with NFPA. Methods. All consecutive patients admitted to a tertiary neuroendocrinology center for pituitary adenoma during 2001-2010 were screened. Only those with a final diagnostic of NFPA were retained. All 196 NFPA subjects (57.7% males, mean age 52.7±0.9 years) were followed-up for allcause mortality until December 31, 2011 (1298 person-years of follow-up). PAMCOMP software was used to calculate standardized mortality ratio (SMR), using the corresponding general population as reference. Cox regression analysis evaluated the independent hazards for mortality. Results. There were 26 deaths among 196 patients as compared to 20 expected. Standard Mortality Ratio (SMR) was 1.2 (95% Confidence interval (CI) 0.83-1.86). Females had a doubled mortality ratio: SMR 2.03 (95%CI 1.01-3.64), but males had a mortality ratio similar with general population: SMR 0.87 (95%CI 0.48-1.44). More patients with hypopituitarism for at least one axis deceased (22/156, 14.10%), as compared with patients without pituitary failure (1/22 patient deceased –2.07%), p=0.03. Prednison replacement for corticotrophin insufficiency (HR 1.46 (95%CI 1.12-1.90)) was correlated to mortality in females, but not in males, and mortality rose progressively with prednison dose (log rank: p=0.01). In males, last known maximal pituitary tumour diameter (HR 1.04 (95%CI 1.001-1.08) and age at baseline (HR 1.1 (95%CI 1.05-1.1) were modestly related to mortality. Conclusions. Females with nonfunctioning pituitary adenomas and hypopituitarism had a reduced life expectancy as compared with general population, possibly related to glucocorticoid substitution or a more severe pituitary insufficiency.

The 2011 American Thyroid Association (ATA) guidelines recommended that the interpretation of thyroid function in pregnancy be based on trimester specific reference ranges: TSH values should be 0.1-2.5 mIU/L (first trimester), 0.2-3.0 mIU/L (second trimester), and 0.3- 3.5 mIU/L (third trimester)(1). Recently, a study performed on a nationwide cohort of 6671 Danish healthy pregnant women and published in June 2016 in Journal of Clinical Endocrinology and Metabolism (4) showed first trimester values of TSH varied according to gestational week. Up to sixth week of pregnancy, TSH levels had nonpregnant reference ranges. During weeks 9- 12, TSH serum level were 0.4 mUI/L lower than non-pregnancy upper limits, with lower range of 0.1 mUI/l. So, the use of uniform limits of TSH normality for the entire first trimester may lead to frequent misclassification and unnecessary treatment given. Although with indolent behavior, patients with encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are often treated as classical papillary thyroid carcinoma. In a retrospective study recently published in the Journal of the American Medical Association Oncology(5), authors reevaluated 268 EFVPTC. In group 1(noninvasive EFVPT), patients observed for 10 -26 years and all were alive with no evidence of disease. Based on this low risk of adverse outcomes of patients from group 1, authors suggested a new nomenclature for this thyroid tumor: “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)”.