ACTA ENDOCRINOLOGICA (BUC)

OBJECTIVES: This study was carried out on 1290 patients, whose choroids plexus and pineal gland were examined on computed tomography. Aim: To check the correspondence between the choroid plexuses and the pineal gland calcifications along age groups and sex; and the connections between these calcifications and associated pathology.\r\nMATERIALS AND METHODS: The study group consisted of patients of both sexes, within six age intervals.\r\nRESULTS: In order to classify the calcification variants, eight types of combinations were ordered and can be seen in CT: two refer to extreme variants: totally uncalcified (type 1) and totally calcified (type 8); bilateral, symmetrical variants (types 4 and 5); the other four types include the asymmetrical calcifications (2, 3, 6 and 7). After the anthropological study the results demonstrate that there are significant differences between calcification of the choroids plexus and those of the pineal gland with the two sexes, on age groups and pathological ground. For type 1-totally uncalcified the maximum frequency is around 70% with ages under 19. For type 8 - totally calcified, bilateral, the maximum frequency is around 50% with age groups 48-59 and 60-71. For type 4 - calcification only of choroid plexus, one finds a continuous increase from about 10% at the first age group to about 25% at the last group, while for type 5- calcification only of the pineal gland the frequency is 10%−20%. We started from the hypothesis that the presence of these calcifications is physiological, and has an active adaptative metabolic part depending on many factors, among which the individual constitutional ground is also present.\r\nCONCLUSIONS: The age is not the main cause of the calcification types, but a process of adaptative-reactive variability of interface type, playing an integrating mediating part.

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 μm), correlated with RNFL cross sectional area in 7 eyes (from 0.362 to 0.846 μm2) and 1 eye with low limit values (1000 μm2). In agreement with these data, VEP–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’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.

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.

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.

Context. Graves' disease is the most prevalent cause of hyperthyroidism worldwide. Adiponectin, the most abundant adipokine, plays a significant role in a cluster of prevalent diseases connected to metabolic disorders. Objective. Although the association between adiponectin and Graves' disease has been studied, the existing data is inconsistent. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between adiponectin levels and Graves' disease. Methods. We performed a systematic electronic search on PubMed, EMBASE, Scopus and Cochrane Library using predefined keywords. We used the NHLBI quality assessment tools to assess the included studies. Results. There were 11 studies involving 781 subjects included in our qualitative synthesis, while 6 studies were included in our quantitative synthesis. We observed significantly increased adiponectin levels in Graves' disease patients compared to controls (MD 2.983 [95% CI 0.138– 5.828]) and hypothyroidism patients (MD 3.389 [95% CI 1.332–5.446]). Nevertheless, no significant MD was observed when comparing Graves' disease patients with and without Graves' ophthalmopathy (MD -27.124 [95% CI -88.893 – 34.645]). Conclusions. Adiponectin levels were significantly higher in patients with Graves' disease compared to controls and hypothyroidism patients. However, patients with and without Graves' ophthalmopathy did not present a significant mean difference in adiponectin levels.

Background: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are found in familial isolated pituitary adenoma syndrome (FIPA) families and in a small number of sporadic pituitary adenoma (PA) patients. Although the tumorigenic mechanisms of AIP mutations are unclear, truncating mutations are considered pathogenic, but missense mutations are difficult to evaluate. p.R16H (c.47G>A) is a controversial AIP variant of unknown significance. Aim: To describe a new PA case associated with AIP p.R16H. Patients and methods: One AIP p.R16H non-functioning pituitary adenoma (NFPA) case identified by mutation sequencing screening of sporadic PA patients; 108 controls were screened for p.R16H. Results: The 38 yrs. old male NFPA patient had no family history of PA and harboured a heterozygous p.R16H variant. The proband and two brothers presented severe intellectual disability. Severe visual impairment was the initial symptom and clinical, biochemical and imaging examination demonstrated a large NFPA invading the right cavernous sinus. After transsphenoidal debulking, the remaining tumor continued growth. One of proband’s sisters was negative for p.R16H. Among controls, we identified one heterozygous p.R16H carrier, presenting a thyroid follicular neoplasm. Loss of heterozygosity analysis of the pituitary and thyroid tumors was not performed. Conclusions: We report two new occurrences of AIP p.R16H, associated with a NFPA and with a thyroid tumor. The NFPA patient was young and presented an invasive macroadenoma, features typical of AIP-mutated patients. Because the association between p.R16H and PAs has not been conclusively established, further research of p.R16H is warranted, in view of its implications for AIP genetic testing.

Cervical lymph nodes could be a starting sign for a complex diagnosis work-up. Depending on co-morbidities, medical unit and physician’s previous experience, the differential diagnosis includes thyroid malignancy, lymphoma, chronic infectious disorders, etc.

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A 51 years old woman, diagnosed 23 years ago with acromegaly and non-insulin dependent diabetes mellitus, who denied radical treatment and took bromocriptine 2.5 - 7.5 mg/day sporadically and oral antidiabetic drugs, presented with chronic headaches, acromegalic features, bilateral temporal hemianopia, hypertension, hyperglycemia. Her pituitary function was normal (random serum growth hormone 2.5 - 2.8 ng/mL). The skull X-ray showed an enlarged sella turcica, with blurred multiple contour and an &#8222;egg-shell&#8221; calcification boarding the interior sellar floor. Cranial CT scan revealed a 1.7/0.7 cm intrasellar macrocalcification with a low-density core, lying on most of the sellar floor. In addition there were partial empty sella, asymmetrical optic chiasm, multiple cerebral,\r\nvascular and pineal microcalcifications, but no visible pituitary or tumor mass. Apoplexy within a previous large pituitary growth hormone-secreting tumor, followed by resorption and peripheral calcification, may have produced this rare case of pituitary stone associated with remission of acromegaly and sequelar visual field defect.

Background and aims. Differences in the composition of the species of microorganisms in the gut may predict the evolution toward obesity and diabetes mellitus. We carried out a systematic review of the studies dedicated to the role of gut microbiota in diabetes mellitus and obesity. Methods. A systematic literature search of electronic databases was performed, using the search syntax: “Gut microbiota and diabetes and obesity”; abstracts in English, with data about mechanisms of pathogenesis and treatment options by changing the gut composition were included (259 articles). Studies were excluded if they did not have an abstract, or they contained no data about the exact implication mechanism of microbiota. Results. There are differences regarding the composition of the gut microbiota in healthy people and type 2 diabetes mellitus patients; the later proved to have significantly decreased Clostridium components, and increased Lactobacillus and Bifidobacterium populations. The intestines of obese subjects are less rich in microbial genes, have a reduced amount of Bacteroidetes and an increased amount of Firmicutes. Fecal microbiota transplantation from obese subjects resulted in adoption of the donor somatotype. Early differences in gut microbiota composition (higher number of Bifidobacteria) function as diagnostic markers for the development of type 2 diabetes mellitus in high-risk patients. The gut endotoxins contribute to metabolic syndrome manifestation. Experimental studies with prebiotic showed lower levels of cytokines and antiobesity potential. Conclusion. Microbiota composition and its changes since childhood have an important role in the metabolic syndrome. Any intervention in order to prevent or treat obesity and diabetes mellitus should have as target the gut immune system.