ACTA ENDOCRINOLOGICA (BUC)

At least one fifth of pituitary adenomas exhibit plurihormonality when using immunohistochemistry for anterior pituitary hormones. However, the correlation with clinical features is weak, without an agreement upon pathological predictors of tumor behavior. The aim was to determine the immunoreactivity for anterior pituitary hormones and alpha subunit in 276 consecutive pituitary adenomas patients, aged 22-79 years (44.3 ? 8), 154 F/ 122 M: 83 acromegalics (ACM), 173 nonfunctioning adenomas (NFA) and 20 prolactinomas (PRM) submitted to surgery via transfrontal (81) or transsphenoidal (195) along 10 years (1995-2005). In addition, clinical data, hormonal secretion and tumour size were evaluated before pituitary surgery. Local ethical committee approved the study design. The immunoreactivity performed by the avidin-biotin-complex method was evaluated for beta FSH, LH, TSH, alpha subunit, PRL and GH, using a semiquantitative scale of stained cells: strong (>20%), positive (10-20%), weak (5-10%) and negative (<5%). CT or MRI tumor size (less than 1 cm, 1-2 cm, 2-4 cm and over 4 cm on maximal diameter) were considered together with the Hardy neuroradiological stage. The results showed that 16/83 ACM, 53/173 NFA and 4/20 PRM exhibited immunoreactivity for beta FSH and LH. TSH immunoreactivity was positive in 13/83 ACM, 11/173 NFA and 1/20 PRM. Tumor size in gonadotrophin - positive group (> 10% of stained cells) was between 1-2 cm in 6 ACM, 21 NFA and 2 PRM, while positive bigger tumors (2-4 cm) were in 7 ACM, 24 NFA and 2 PRM. Giant, over 4 cm tumors were positive in 3 ACM, 8 NFA and no PRM. A similar trend of the tumor size distribution was observed in the monohormonal or null cell adenomas. In conclusion, tumor size and gonadotrophin plurihormonality are independent factors in the management of pituitary adenomas.

In this study we aimed to evaluate and quantify optic nerve damage caused by long standing compressive pituitary macroadenomas with conventional (ophthalmoscopy) and modern techniques such as fundus camera, confocal scanning laser tomography for quantitative measurements of the thickness of retinal layers as well as visual evoked potentials (VEP) for electrophysiological quantification. Seven patients with large, long standing pituitary macroadenomas were submitted to ophthalmologic evaluation, including a visual field (VF), visual acuity (VA) and eye fundus (F). Heidelberg retinal tomography (HRT) was used for retinal thickness and evaluation of nerve fibers loss, and VEP were measured by pattern reversal and flash stimulus. In addition, all patients underwent tumor imaging (MRI/CT) and specific endocrine evaluation. All cases presented with macroadenomas with suprasellar extension and residual or progressive optic chiasma syndrome; all but one (prolactinoma) were nonfunctioning adenomas, after radical treatment (surgery ? radiotherapy). Adrenal and thyroid substitutive treatment was instituted in all cases due to associated pituitary failure. Evaluation of VF showed 9 eyes with temporal hemianopia, 2 with nasal islands of vision and 1 with nasal hemianopia in a homonymous hemianopia case; another case presented for left 3rd nerve palsy due to a cavernous sinus syndrome, therefore the visual field was not measurable in 2 eyes. Visual acuity was very low (counting fingers) in 4 eyes, while in the rest the VA was between 0.5-0.9. The fundus revealed total atrophy in 2 eyes, band atrophy in 4, temporal pallor in 5 and global pallor in 1. Cup/disk ratio in the case with 3rd nerve palsy was 0.5 (RE) and 0.3 (LE). HRT II stereometric analysis of the optic nerve head showed abnormal values, documenting retinal nerve fiber layer (RNFL) loss that correlated with fundus appearance and visual field defects. Mean RNFL thickness had abnormal values in 8 eyes (from 0.074 to 0.173 &#956;m), correlated with RNFL cross sectional area in 7 eyes (from 0.362 to 0.846 &#956;m2) and 1 eye with low limit values (1000 &#956;m2). In agreement with these data, VEP&#8211;P100 presented increased latency over 120 ms in 8 eyes, borderline (100-120 ms) in 5 and 97.5 ms in only 1 eye. In conclusion, HRT can document the papilla and nerve fiber layer more objective, permitting quantification of the disc&#8217;s alterations due to compressive pituitary macroadenomas. HRT is useful in quantifying RNFL loss in other conditions than glaucoma, when other optic disc imaging tools are not available.

Background. The pro-thrombotic potential of the anabolic androgenic steroids (AAS), worldwide misused substances, has increasingly become a subject of current interest. Conversely, taurine, a sulfur-amino acid ubiquitous in human body, in addition to other beneficial effects, is thought to have an inhibitory effect on platelet aggregation. Purpose. To assess platelet aggregation both taurine and high doses of AAS were simultaneously chronically administered in rats. Methods. The experiment was conducted on 40 male Wistar rats, divided into 4 equal groups: control (C) – no treatment; AAS (A) – treated with 10 mg/kg/week of nandrolone decanoate (DECA); taurine (T) – daily treated with oral supplementation of 2% taurine in drinking water; androgen and taurine group (AT) – concomitant administration of DECA and taurine. After 12 weeks of treatment, blood samples were collected and platelet aggregation induced by ADP was performed using the turbidimetric method. Results. The platelet aggregation magnitude was significantly higher (p<0.001) in group A (62.1±6.10%) than in group C (47.8±5.39%), while in group T (40.3±6.49%) it was significantly lower (p=0.04). Moreover, the platelet aggregation response was significantly lower in group AT (54.5±6.38%) than in group A (p=0.04), without a significant difference between group AT and group C (p=0.08). Conclusion. Our findings provide additional evidence regarding harmful potential of high doses of DECA, chronically administered. The increased platelet aggregation induced by AAS may be decreased by diet supplementation with taurine.

INTRODUCTION: The aim of our study was to evaluate the cure rate of macroprolactinomas treated for a long term (> 4 years) or a short term (<4 years) with dopamine agonists (DA) alone or combined with radiotherapy (RT). Sometimes pituitary\r\nsurgery was performed.\r\nMATERIAL AND METHODS: We performed a retrospective study in 111 patients with macroprolactinomas, hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005. There were two groups, according to the length of DA therapy: group\r\nA =41 patients, treated more than 4 years and group B =70 patients, treated less than 4 years. Overall, 25 patients underwent additional radiotherapy, 13 in group A and 12 in group B. 28 patients were submitted to pituitary surgery, 9 in group A and 19 in group B.\r\nRESULTS: The cure rate (i.e. normalization of prolactin=PRL level and absence or minimal residual tumor mass, stable minimum 2 years after DA withdrawal) was 5/41 (12.1%) in group A and none in group B. 48 out of 111 patients achieved significant improvement (serum prolactin level less than 20 ng/ml and tumor shrinkage more than 50%) during DA therapy, but not after DA withdrawal: 17/41patients (41.5%) in group A and in 31/70 patients (44.3%) in group B, p=NS. Radiotherapy produced an additional improvement: in serum PRL levels only in group A, in 4/13 patients- 2/8 patients responsive to DA therapy and 2/5 patients resistant to DA therapy. In group B, the 3 patients resistant to DA submitted to radiotherapy were evaluated before the interval necessary for maximal effect of radiotherapy, but in 4/9 patients responsive to DA, we noticed further reduction in tumor volume, 2/4 progressing from mild to significant tumor shrinkage and ? progressing from no shrinkage to mild shrinkage. After radiotherapy, the medium prolactin level was 5.1 ng/ml in 10 patients from both groups on low bromocriptine (BRC) dose (7.5 mg/day), significantly less than in patients without radiotherapy, i.e. than in 19 patients from group A (serum PRL 49.5 ng/ml, p=0.02) and in 29 patients from group B (serum PRL 30.3 ng/ml, p=0.01). So, the daily BRC dose could safely decrease from 30 mg/day to 7.5 mg/day in those patients previously submitted to radiotherapy. Among 23 patients resistant to initial DA treatment, only 8 patients were submitted to radiotherapy, 2 became responsive to DA thereafter and 2 others obtained a significant decrease of prolactin levels.\r\nCONCLUSIONS: The overall cure rate is quite low in prolactinomas and it was noticed only after long-term treatment with dopamine agonists; it was improved up to 12.1% by the additional high voltage radiotherapy, useful even in DA resistant cases. The addition of radiotherapy is indicated for the cure of most prolactinomas.

Introduction. This study evaluates the clinical efficacy of androgen replacement therapy with the new long-acting intramuscular (i.m.) testosterone undecanoate (T.U.) in comparison to oral T.U. in adult men with hypogonadotropic hypogonadism.\r\nPatients and methods. In 41 patients with central hypogonadism (30 with pituitary tumors or craniopharyngiomas, 11 with non-tumor hypogonadism), aged 20-62 years, we evaluated, before and after androgen replacement therapy, morning serum total testosterone\r\n(T), hemoglobin, hematocrit, cholesterol, triglycerides (measured with commercial kits in venous blood sampled at 8.00-9.30 a.m) and the sexual dysfunction (SD) by questions on libido, frequency and quality of erections.\r\nResults. In group A, including 28 patients treated with oral T.U. median dose 120 mg/day (range 80-160) in 3 divided doses, for 4-60 (median 14) months, T rose from 0.37 ? 0.40 ng/mL (mean ? standard deviation) to 1.43 ? 1.36 ng/mL (p<0.01), reaching normal levels only in 4 patients (14%). In group B, including 20 patients treated with 1000 mg i.m. T.U. at 12 weeks intervals, for 1-12 (median 6) months, T rose from 0.88 ? 0.83 ng/mL to 5.88 ? 3.50 ng/ml (p<0.01). T was low in 1 patient (5%) and above normal in 6 patients (30%). A subgroup (C) of 7 patients was switched from oral to i.m.T.U. T was higher after i.m. than after oral T.U in group B vs. A and within subgroup C (p < 0.01). SD improved in 7/16 patients (43.7 %) on oral T.U. and in 11/12 patients (91.6%) on i.m. T.U (p < 0.05). Hematocrit increased significantly from baseline in both groups, while serum cholesterol and triglycerides did not change significantly on either T.U. treatment.\r\nConclusions. Clinical efficacy, judged by normal morning T and sexual dysfunction improvement, was reached in over 90% of patients with central hypogonadism after i.m.T.U. and in less than half after oral T.U.

Background. Alcohol ingestion can induce either a hypoglycemia or a hyperglycemia,\r\nin patients with acute and chronic ethanol poisoning, unknown with diabetes mellitus.\r\nAim. The aim of this study was to evaluate whether 5 hours prolonged oral glucose\r\ntolerance test (5h-OGTT) is useful in evaluating the abnormalities of glucose metabolism in\r\nacute and chronic ethanol poisoning, in comparison with standard methods (fasting blood\r\nglucose - FBG, and/or 2h-OGTT).\r\nMethods. 497 consecutive patients were enrolled in a 34 months cross sectional study.\r\nIn all cases, glucose tolerance was assessed by a 75-g oral glucose tolerance, OGTT 2 hours,\r\nprolonged to 5 hours. The relationship between clinical and biochemical variables of ethanol\r\npoisoning (liver status, lipid profile, metabolic syndrome) and glucose tolerance was\r\ninvestigated. Risk factors for hypoglycemia in ethanol poisoning were identified.\r\nResults. 349 subjects presented acute ethanol poisoning, and 148 subjects had chronic\r\nethanol poisoning. 254 patients (51.10%) had documented alcoholic liver disease (ALD -\r\nclinical, biochemical and imagistic criteria). Glucose metabolism abnormalities were\r\nrecorded in 143 subjects with chronic ethanol poisoning and ALD (96.63%), and in 207\r\ncases with acute alcohol poisoning (59.31%). 371 patients (74.65%) showed normal FBG,\r\ndiabetes mellitus (DM) was diagnosed in 54 subjects (10.86%), impaired glucose tolerance\r\n(IGT) in 43 subjects (8.65%), delayed hypoglycemia in 172 subjects (34.60%) and normal\r\nglucose tolerance (NGT) in 147 subjects (29.57%) using OGTT and ADA diagnosis criteria.\r\nHypoglycemia was recorded in more than two thirds of acutely poisoned patients, when alcohol\r\nlevel was 0.5-1.5 g/L. Impaired glucose tolerance (IGT) were recorded in half of patients with\r\nblood ethanol levels > 2.5 g/L.\r\nConclusions. OGTT 2 hours and OGTT 5 hours revealed the same number of patients\r\nwith diabetes mellitus. Frequent co morbidities in patients with ethanol poisoning influence\r\nthe prolonged OGTT and revealed .especially delayed hypoglycemia, and IGT, as an indicator\r\nof alcoholic liver disease (ALD).

Introduction. Obesity was considered to protect against osteoporosis. Recent studies indicate the opposite.\r\nThe study aimed to see if adipose tissue has a protective effect on bone mass and if adipocytokines can explain the\r\nrelationship between obesity and osteoporosis.\r\nSubjects and methods We designed a study enrolling 83\r\npostmenopausal women, aged over 60, without diagnosed or treated osteoporosis and no secondary osteoporosis. We formed 3 groups- group 1- osteoporosis and metabolic syndrome (MetSyn), group 2- osteoporosis, group 3- MetSyn.\r\nWe evaluated the hematological, biochemical profile, bone turnover markers and adipocytokines. DXA of the spine and\r\nthe hip (left) was performed on all the enrolled women. Insulin resistance was appreciated using HOMA index. Metsyn\r\nwas defined using the International Diabetes Federation?s criteria.Results were statistically analyzed using SPSS program, version 15.\r\nResults. All groups were vitamin D insufficient with lower vitamin D, osteocalcin and adiponectin levels in the\r\ngroups with MetSyn and higher leptin levels. BMI correlated positively with spine BMD, while leptin correlated positively with hip BMD, pointing out to the protective effect of obesity against osteoporosis due to leptin?s involvement.\r\nConclusion. Obesity seems to have a protective effect against osteoporosis, probably due to leptin.

Development of Covid-19 pandemic infection which started in December 2019 from Wuhan, China, impacted all medical specialities and societies. Endocrine professionals are involved in this battle, as far as many patients with endocrine co-morbidities (diabetes, metabolic syndrome, pituitary, thyroid, adrenal disorders) are most affected by the disease. Specific recommendations for the management of endocrine disorders were released by European experts. Most rely on the same principles of epidemiological safety measures, delaying non emergency admissions and transforming the routine follow-up in telemedicine clinics. Special attention is required to adrenal disorders, either central in the context of pituitary patients or primary. Corticosteroids are a mainstay of treatment in Covid-19 infection, therefore it is important to consider all aspects involved by high doses, including metabolic adverse reactions especially in diabetic patients. Other endocrine disorders, thyroid dysfunctions or nodules, parathyroid, adrenal, and pituitary diseases should follow specific recommendations for management. Surgery is postponed for non-emergency situations, restricting most planned surgeries, either thyroid, pituitary or adrenal. Laparoscopic surgery, if required in emergency, is including a supplementary risk, therefore all involved in the operating theater should wear PPE. In conclusion, a coordinated response should be organized in the multidisciplinary management of endocrine patients.

A 63-years old patient with severe thyrotoxicosis with cachexia and high frequency atrial fibrillation showed an inadequate secretion of TSH. A pituitary macroadenoma was revealed by computed tomography. Acute octreotide administration decreased serum TSH\r\nfrom 2.48 mU/mL to 0.06 mU/mL and T3 from 3.1 ng/mL to normal values (0.93 ng/mL) in 3 days; at the same time serum T4 remained unchanged (raised).The response to octreotide supported the diagnosis of TSH-secreting adenoma. T3 suppression test is no longer useful at present for diagnosis.Administration of long- acting somatostatin analogues (lanreotide) together with antithyroid drugs (ATD) was initially necessary. However, after removal of pituitary tumor the clinical symptoms (including atrial fibrillation) disappeared.ATD administration was no longer necessary, nor was octreotide or lanreotide. Immunohistochemistry certified that the pituitary tumor was a pure thyrotropinoma (without plurihormonal expression). Complete cure of severe thyrotoxicosis due to a TSH-secreting pituitary adenoma by pituitary surgery is possible. Thyroidectomy is not indicated.

Hyperosmolar hyperglycemic non-ketotic state is a life-threatening emergency manifested by a marked elevation of blood glucose, hyperosmolarity, and little or no ketosis. It most frequently develops in middle-aged or elderly patients, often in the setting of previously mild type 2 diabetes and in the presence of one of the established risk factors (e.g. infection, cerebrovascular accident, myocardial infarction). We present the case of a 48 years old woman with no past history of diabetes who developed hyperosmolar hyperglycemic nonketotic state after transsphenoidal surgery for a large macroprolactinoma. Despite having symptoms (secondary amenorrhoea and galactorrhoea) for many years the patient only had inconsistent medical follow-up and eventually she developed optic chiasm syndrome. She was referred for pituitary surgery performed by transsphenoidal route. After surgery there was marked improvement of the visual signs but few days after intervention the patient presented with polydipsia, polyuria and paresthesiae. Based on laboratory tests that showed a markedly elevated blood glucose level (1088 mg/dl), hyperosmolarity, no acidosis therefore, a diagnosis of hyperglycemic hyperosmolar state was made. With rehydration and insulinotherapy she recovered and the evolution was favourable over weeks with discontinuation of insulin administration. The patient still had high prolactin level after surgery (3060.3 ng/dl) so we also initiated dopamine agonist bromocriptine treatment. In addition to the well known effects of dopamine agonist upon prolactinoma it also has beneficial effects on glycemic control in diabetics (it reduces insulin resistance, both fasting and postprandial plasma glucose levels and HbA1c levels). We discuss the possible explanations of the syndrome and the effects of bromocriptine treatment.