ACTA ENDOCRINOLOGICA (BUC)

Introduction: Prolactinomas may grow during pregnancy. Dopamine agonists (DA) prevent tumor growth, but usually suppress prolactin (PRL) both in mother and fetus. Possible long-term consequences on fetal development remain unknown.\r\nAim: to assess whether DA treatment throughout pregnancy in a dosage able to maintain physiological gestational serum levels of prolactin (PRL) still prevents prolactinoma growth.\r\nPatients and methods: We evaluated 68 pregnancies in 49 women with prolactinoma (PRM) and 46 pregnancies in healthy women as controls. Thirty-three pregnancies were recorded in 27 women treated throughout pregnancy with bromocriptine (BRC) (n = 25) or cabergoline (CAB) (n = 2) divided in 2 groups: group A (22 pregnancies in 18 patients) had suppressed serum PRL (below the 5th percentile of the control group Z during the last trimester); group B (11 pregnancies in 10 patients) had physiological serum PRL levels. Other 26 pregnancies in 21 patients were incompletely evaluated and included only in the pregnancy outcome and cure rate analysis. Treated patients were compared with the control group Y 8 women with PRM who discontinued DA after pregnancy induction (9 pregnancies) and a control group Z of 46 healthy pregnant women, randomly selected from two departments of Obstetrics. Patients with multiple pregnancies were recorded in each corresponding study group.\r\nResults: In the control group Y, tumor size showed an increase in 2 (intrasellar macroPRM) out of 8 cases (25%). DA treatment throughout gestation in 27 women with PRM prevented the growth in all cases and induced a shrinkage of more than 30% of tumor mass in 8/14 macroPRM (57.1%), i.e., in 4/7 (57.1%) of macroPRM with physiological serum PRL levels during pregnancy, and in 5/8 (62.5%) of macroPRM with suppressed PRL levels (p = NS) (1 patient had pregnancies in both groups). Low dose DA (BRC 2.5 ? 5 mg/day or CAB 0.5 mg/week) maintains physiological PRL levels in 6/12 (50%) macroPRM, but suppressed PRL in 80% of microPRM. Cure was recorded in 6/49 (12.2%) of patients. Two patients with PRM-induced neuroophthalmic syndrome were successfully treated with DA throughout 1 and respectively 3 pregnancies.\r\nConclusions: Some women with prolactinomas showed a tumour size increase if they were not treated with dopamine agonists throughout pregnancy. Maintaining physiological serum PRL levels during pregnancy (frequently with low doses of DA) prevented tumor growth, avoiding a PRL suppression that may have subtle influence on long-term foetal development.

The subCarpathian areas of Arges county are now characterized by a moderate endemia of iodine deficiency disorders (IDD) due to salt iodization. However, we found some cases of endemic cretinism (EC), that is the major expression of anomalies in the physical and intellectual development caused by a severe iodine deficiency. There are presented 5 patients, 4 men and 1 woman, with neurological endemic cretinism (NEC) (n=2) and mixed forms of the disease (n=3), coming from 2 old endemic areas (medium urinary iodine excretion in the studied patients 20.8 g/day), diagnosed and treated in outpatients clinics or in hospitals. Four patients are members of the same family. The age of the patients is between 36 and 84 years old, the average age being 69. The intellectual capacity was assessed by using the Wechsler and Raven tests, the average intelligence quotient (IQ) value was of 20.8 points ? 1.47. The thyroid volumes (TV) were estimated by palpatory method and by ultrasonography and were between 8.7-200 ml. TSH values in studied patients ranged between 3.8-26 IU/ml and free T4 ranged between 0.272-1.22 ng/dl. Aggregation of more cases of endemic cretinism in the same family suggests the occurrence of some genetic factors. In conclusion, the old age (over 70 years old) of 4 cretins shows they are remnants of the old IDD endemia. However, there is also an isolated case of middle age (36 years old) suggesting an inadequate iodine intake, despite a law regarding salt iodization which has been operating since 1962. More attention to the universal salt iodization and to consumption of iodized salt in the rural areas is necessary.

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Background. Usually, silver stain is needed to differentiate between normal or hyperplastic hypophysis and pituitary adenomas. Many papers reported the lack of reticular fibers network as mandatory for pituitary adenoma diagnosis. \r\nAim. Differences between the architecture of reticular fibers in normal pituitary and pituitary adenomas \r\nMethods. Gordon- Sweet silver staining of pituitary specimens, prelevated during pituitary surgery performed in 138 patients with the endocrine and imagistic diagnosis of pituitary macro-adenomas. \r\nResults.Pituitary specimens of pituitary adenomas was confirmed in 133 cases; 3 specimens were with normal pituitary tissue, 1 with pituitary hyperplasia, 1 with pituitary apoplexy.Twelve of 133 pituitary adenomas specimens were associated also with normal pituitary tissue.There was a loss of acinar network of reticular fibres in 115 cases, but the present study describes the persistence of reticular fibers networks in 18 (13,53%) of 133 pituitary adenomas. We identified five distribution patterns of remanent reticular fibers network in pituitary adenomas using silver staining. \r\nIn conclusion, persistence of reticular fibers in a small number of pituitary adenomas could be a possible pitfall in the discrimination between the normal hypophysis and pituitary adenoma.

Gangliocytomas are extremely rare tumors, accounting for 0.1-0.5% of all brain tumors. We present a 25 years old woman with several characteristics of restrictive anorexia nervosa in association with a gangliocytoma of pineal region. The patient has been diagnosed with hydrocephalus shortly after birth. A ventriculoperitoneal shunt was initially inserted. At the age of 19 she underwent 2 consecutive occipital craniotomies for a well-defined large mass in the pineal region. Histopathological examination of this tumor revealed a gangliocytoma. Our patient began to reduce her food intake due to the concept that ”the tumor must not be fed”. After an almost 30 kg weight loss over 5 years, the patient weighs 39 kg at 165 cm height (BMI 14.3 kg/sqm), associated with a 1 year history of secondary amenorrhea and a tumor remnant of 4 cm. The weight loss, amenorrhea and some other psychosocial traits are common for anorexia nervosa. We discuss the difficulty of the differential diagnosis between anorexia nervosa and a hypothalamic eating disorder induced by the pineal gangliocytoma.

Background. Advances in imaging techniques have led to increasing discovery of\r\nadrenal and pituitary &#8220;incidentalomas&#8221;, tumors with normal endocrine function and no\r\ncompression mass effects. We evaluated the age at diagnosis (AD) in patients with benign\r\nnon-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors,\r\nin a series of patients from a national center of endocrinology. Methods. From 2,123\r\nconsecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009,\r\n2,069 patients were analysed. The study groups included: group A - 137 patients with\r\nadrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI).\r\nControl groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or\r\nbenign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary\r\nsecreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was\r\ndone by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or\r\npneumoencephalography before 1981. Results. Mean age AD is more advanced in patients\r\nwith AI (53 ? 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ? 13.1 years, range\r\n10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors,\r\nbut similar in patients with adrenal malignancy. There is an age-related increase in the\r\nproportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among\r\npatients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal\r\ntumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have\r\nNFA. AD in NFA (49.3 ? 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01).\r\nAD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0\r\n? 2.8 yr) and only in 0.7% of PI, p<0.01 (follow-up 3.1 ? 2.5 yr).\r\nConclusions. Adrenal non-functioning benign tumors show a clear association with ageing,\r\nin contrast with pituitary incidentalomas. It seems unlikely that most pituitary incidentalomas in\r\nyoung patients become large NFA, whose development seems to be also age-related. It is tempting\r\nto suggest that pituitary tumorigenesis starts earlier than adrenal tumorigenesis.

controversial. Aim. This study retrospectively reviews the tumor evolution in patients with NFA macroadenomas treated with surgery and conventional RT, as compared to surgery alone. Methods. Of 107 unselected patients with operated NFA (aged 19 - 77 years), evaluated between 1977 - 2008, 71 patients were follow-up without RT (group A), while 36 patients were submitted to RT (group B). Patients submitted to radiosurgery were not included. Both groups underwent serial imaging studies with computed tomography or magnetic resonance. Tumor evolution was conventionally defined as a change of minimum 25% of diameter. Results. The surgical approach was transfrontal in 47% of patients, transsphenoidal in 43% or both in 10% of patients, similar in both study groups. In group B, 30 patients underwent highvoltage RT (mean total dose 50.5 Gy) and 6 patients low-voltage RT (mean emission dose 16,775 R). Mean follow-up after surgery in group A was 3.4 years (range 6 months - 10 years) and after RT in group B it was 6.8 years (range 2 &#8211; 24 years), p < 0.001. In group A, 16 out of 71 patients had no visible tumor remnants. In this subgroup, 2 patients (12.5%) showed tumor recurrence. Fifty-five out of 71 patients had residual tumors, 21 with extrasellar extension after surgery. In this subgroup, 21 patients (38%) showed tumor re-growth and 7 (13%) showed tumor decrease. In group B (n=36) all patients had tumor remnants after surgery with extrasellar extension in 30 patients. After RT, tumor re-growth occurred in 5 out of 36 patients (14%) as compared to subgroup A with residual tumors (p< 0.05) and tumor decrease in 14 out of 34 (41%), as compared to the same subgroup A (p < 0.01). The 5 year-tumor re-growth free survival rate of 88% in irradiated patients was significantly better than in non-irradiated patients with residual tumors (31%, log-rank test, p < 0.01, Kaplan-Meier analysis), but similar to that in patients without remnants (87.5%). Age, sex, tumor parasellar extension and size of residual tumor were not predictors of recurrency. Conclusion. Postoperative radiotherapy provides a significant improvement of local control in patients with residual NFA compared to surgery alone. It is necessary a long term follow-up due to recurrency noticed up to 8 years postsurgery. In patients without tumor remnants, a wait-and-see policy is indicated after surgery.

Objective. This study assesses, in patients from counties with iodine deficiency (ID) and without ID, the concentrations of thyroid hormones in newborns (cord blood) and mothers at delivery, maternal and fetal thyroid volumes (less than 24 hours before delivery) and maternal urinary iodine at delivery. Another aim of this paper is to identify the interrelations between maternal and neonatal thyroid functions in the premature and full term delivery.\r\nMethods. In this study there were 83 mothers without thyroid pathology (goitre included) aged 26.51 ? 4.88 years, range 16-38 years) and their 83 newborns immediately after delivery. Four groups were identified: group A - 13 mothers from iodine sufficient area (IS) who delivered prematurely, group B - 13 mothers from iodine deficient area (ID), who delivered prematurely, group C - 38 mothers from IS area who delivered at term and group D - 19 mothers from ID area who delivered at term. The serum concentrations of TSH, total (T)T4, free (F)T4, TT3 and FT3 were evaluated by a microparticle enzyme immunoassay (MEIA). The thyroid volumes in mothers and their fetuses were measured by ultrasonography with a high resolution equipment (Accuvix XQ).\r\nResults. The values of TSH in newborns (cord blood serum), expressed as mean ? standard deviation (SD), were significantly higher in groups from ID areas (B+D) vs. groups from IS areas (A+C) (p<0.03). TSH levels were higher in group D vs. group C (6.62 ? 4.53 mU/L vs. 5.46 ? 2.83 mU/L [p<0.03]). The values of TT4 in newborns were significantly lower in group B vs group D (8.09 ? 1.68 ?g/dl vs. 9.45 ? 2.23 ?g/dl [p<0.05]), in premature group (A+B) vs term group (C+D) [p<0.007] and in groups from ID areas (B+D) vs. IS groups (A+C) vs [p<0.01]. Thyroid volumes (TV) in fetuses from IS areas (A+C) were lower than in ID areas (B+D) (p<0.002), but TV was similar in fetuses born at term or prematurely. Serum TSH levels in newborns (71.73 ? 26.54 ?g/l) were negatively correlated with maternal urinary iodine (r = -0.827, p<0.0001). Serum TSH in newborn was not correlated with maternal TSH in any group (A-D). The TV in fetuses (1.25 ? 0.1 ml) were highly correlated with TSH in newborns (r = 0.83, p<0.001), negatively correlated with maternal urinary iodine (r = -0.81, p<0.001) and correlated with maternal TV (17.12 ? 1.82 ml) (r = 0.44, p<0.02).\r\nConclusions. The status of the thyroid hormones and thyroid volumes in the newborn was dependent on the severity of iodine deficiency and in a less proportion on prematurity. The fetus is more sensitive to iodine deficiency than the mother.