Examining the Prevalence of Left Atrial Appendage Thrombus in a Cohort of Acute Stroke Patients with an Extended Computed Tomography Angiographic Protocol.

INTRODUCTION: Current guidelines recommend transthoracic echocardiography (TTE) for routine screening of cardiac emboli; however, the visualization of the left atrial appendage (LAA) where the thrombi are commonly found is poor. Transesophageal echocardiography (TEE) would provide better detectability of LAA thrombus, but it is a time-consuming and semi-invasive method. Extending non-gated carotid computed tomography angiography (CTA) examination to the LAA could reliably detect thrombi and could also aid treatment and secondary prevention of stroke. METHODS: We extended the CTA scan range of acute stroke patients 4 cm below the carina to include the left atrium and appendage. During the review, we evaluated LAA thrombi based on contrast relations. We then used gradient boosting to identify the most important predictors of LAA thrombi from a variety of different clinical parameters. RESULTS: We examined 240 acute stroke patients' extended CTA scans. We detected LAA thrombi in eleven cases (4.58%), eight of them had atrial fibrillation. 23.75% of all patients (57 cases) had recently discovered or previously known atrial fibrillation. Windsack morphology was the most commonly associated morphology with filling defects on CTA. According to the gradient-boosting analysis, LAA morphology showed the most predictive value for thrombi. CONCLUSION: Our extended CTA scans reliably detected LAA thrombi even in cases where TTE did not and showed that 2 patients' LAA thrombus would have been untreated based on electrocardiogram monitoring and TTE. We also showed that the benefits of CTA outweigh the disadvantages arising from the slight amount of excess radiation.

[Plasmapheresis in the treatment of hypertriglyceridemia]. / Hypertriglyceridaemia kezelése plazmaferézissel.

The authors present the case of a 38-year-old woman with severe hypertriglyceridemia-induced acute recurrent pancreatitis (triglyceride 16 761 mg/dl, 189.4 mmol/l). According to the knowledge of the authors, such a high triglyceride has not been previously reported in Hungarian and international scientific literature. The patient received conventional treatment (fluid replacement, analgesic, antibiotics, discontinuation of oral intake) and plasmapheresis too. After two sessions of plasmapheresis with one month interval the clinical and laboratory parameters greatly improved. Severe hypertriglyceridemia (triglyceride level more than 1000 mg/dl, ≈11.3 mmol/l) is an independent risk factor for acute pancreatitis. Plasmapheresis seems to be safe and effective to rapidly decrease triglyceride levels and to remove the causative agent for pancreatitis in a patient with severe hypertriglyceridemia.

ACTH-secreting Crooke cell carcinoma of the pituitary.

PURPOSE: While pituitary adenomas are common, pituitary carcinomas are rare. It is unclear whether pituitary carcinomas arise de novo or evolve from adenomas. METHODS: We studied the clinical characteristics and tissue samples from eight pituitary surgeries and the autopsy from a patient with pituitary carcinoma. A 16-year-old female patient was diagnosed with an aggressive Crooke cell macroadenoma. Following transsphenoidal surgery, clinical signs of Cushing disease quickly reappeared. During the 14-year course of the illness, eight pituitary surgeries, three courses of extracranial irradiation and two (90) Yttrium-DOTATOC treatments were undertaken. A bilateral adrenalectomy was performed. The patient died of metastatic disease and uncontrolled hypercortisolism due to an adrenal remnant. A systematic morphologic study (histologic staining, electron microscopy) of all available surgical and autopsy specimens was undertaken. RESULTS: Brisk mitotic activity, high Ki-67 and p53 immunolabelling were present in the pituitary samples from the onset. High proportion of tumour cells showed irregular nuclei and large nucleoli, and gradual increase in MGMT staining was observed. The tumour remained of Crooke cell type throughout the course. Autopsy disclosed a postirradiation sarcoma in the pituitary area. CONCLUSIONS: The question whether pituitary carcinomas arise de novo or transform from an adenoma cannot be answered at present with certainty.

Evaluation of transorbital sonography measures of optic nerve diameter in the context of global and regional brain volume in multiple sclerosis.

Transorbital sonography (TOS) could be a swift and convenient method to detect the atrophy of the optic nerve, possibly providing a marker that might reflect other quantitative structural markers of multiple sclerosis (MS). Here we evaluate the utility of TOS as a complementary tool for assessing optic nerve atrophy, and investigate how TOS-derived measures correspond to volumetric brain markers in MS. We recruited 25 healthy controls (HC) and 45 patients with relapsing-remitting MS and performed B-mode ultrasonographic examination of the optic nerve. Patients additionally underwent MRI scans to obtain T1-weighted, FLAIR and STIR images. Optic nerve diameters (OND) were compared between HC, MS patients with and without history of optic neuritis (non-ON) using a mixed-effects ANOVA model. The relationship between within-subject-average OND and global and regional brain volumetric measures was investigated using FSL SIENAX, voxel-based morphometry and FSL FIRST. OND was significantly different between HC-MS (HC = 3.2 ± 0.4 mm, MS = 3 ± 0.4 mm; p < 0.019) and we found significant correlation between average OND and normalised whole brain (ß = 0.42, p < 0.005), grey matter (ß = 0.33, p < 0.035), white matter (ß = 0.38, p < 0.012) and ventricular cerebrospinal fluid volume (ß = - 0.36, p < 0.021) in the MS group. History of ON had no impact on the association between OND and volumetric data. In conclusion, OND is a promising surrogate marker in MS, that can be simply and reliably measured using TOS, and its derived measures correspond to brain volumetric measures. It should be further explored in larger and longitudinal studies.

[Clinical evaluation of the renin-aldosterone system: comparison of two methods in different clinical conditions]. / A renin-aldoszteron rendszer vizsgálata két módszerrel különbözo klinikai állapotokban.

INTRODUCTION: Measurement of plasma aldosterone/renin ratio is the key step in the diagnosis of primary aldosteronism. AIM: The aim of the authors was to analyze and compare the diagnostic utility of plasma aldosterone/renin activity and plasma aldosterone/renin concentration ratios. METHODS: Plasma aldosterone and plasma renin activity were determined by radioimmunoassays and plasma renin concentration was measured by immunoradiometric assay in 134 subjects (80 women and 54 men, aged 46±15.5 years) including 49 healthy blood donors (control group), 59 patients with hypertension (25 treated and 34 untreated) and 26 patients with incidentally discovered adrenal adenomas. RESULTS: There was a weak correlation (r = 0.59) between plasma renin activity and plasma renin concentration in the lower range (plasma renin activity, 0.63±0.41 ng/ml/h; plasma renin concentration, 8.1±4.9 ng/l). Considering the cut-off value of plasma aldosterone/renin ratios determined in controls (plasma aldosterone/renin activity ratio, 30 ng/dl/ng/ml/h; plasma aldosterone/renin concentration ratio, 3.0 ng/dl/ng/l), high proportion of falsely positive results were found among patients on beta-receptor blocker therapy (plasma aldosterone/renin activity ratio, 22.2%; plasma aldosterone/renin concentration ratio, 44.4%) CONCLUSION: The widely used plasma aldosterone/renin activity ratio can only be replaced with plasma aldosterone/renin concentration ratio with precaution on different clinical conditions.

[Evaluation of the accuracy of inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome]. / Sinus petrosus inferior katéterezés értékelése az adrenokortikotrop hormon dependens Cushing-szindróma elkülöníto diagnosztikájában.

The differentiation of adrenocorticotropic hormone producing pituitary adenoma (Cushing's disease) from the ectopic ACTH syndrome is always a complex and difficult task, and in rare cases it is not possible to differentiate between the two disorders, even with the use of dynamic endocrine tests and the most advanced imaging techniques. Inferior petrosal sinus sampling (IPSS) with subsequent ACTH measurements became the gold-standard method of the differential diagnostic process. 34 patients with ACTH dependent Cushing's syndrome in whom the source of ACTH secretion couldn't be identified unambiguously with imaging techniques and/or dynamic endocrine tests underwent altogether 41 IPSS between 1999 and 2005. The sensitivity of the method was calculated on the basis of 31 samplings of 25 patients who had definite endocrinological diagnosis confirmed by the recovery from Cushing's syndrome after surgical intervention and/or by histological examinations (22 patients with ACTH-producing pituitary adenoma and 3 patients with ectopic ACTH syndrome). As a result of IPSS, pituitary-dependent Cushing's disease was diagnosed with a baseline central to peripheral ACTH ratio of >2.0 or with a ratio of >3.0 after corticotropin releasing hormone (CRH) administration. IPSS correctly identified ACTH-producing pituitary adenoma in 20 of 28 sampling procedures, with a sensitivity of 71.4%. Three patients had true negative and 8 had false negative results. There was no false positive result. Four of the 8 patients with false negative first sampling had a repeat sampling procedure leading to true positive result in each patient. In patients with Cushing's disease having true positive interventions, the basal and 5 minutes post-CRH ACTH concentrations were diagnostic in 14 and 19 cases, respectively. The sensitivity of IPSS within this series, reported for the first time from Hungary, was lower than it was found in much larger series published in international literature. In addition to technical difficulties, the lower sensitivity can be accounted also for the highly selected nature of the patient group.

Protein interference in thyroid assays: an in vitro study with in vivo consequences.

BACKGROUND: Pathological concentration of plasma proteins may cause problems in immunoanalytics. The low triiodotyronine (T3) and thyroxine (T4) levels, frequently found in seriously ill patients, may be ascribed either to laboratory artifact due to the lower thyroid hormone binding capacity or to a compensatory response of the organism to the disease. METHODS: The authors performed an in vitro experiment, in which sera of seriously ill patients with either low immunoglobulin G (IgG), and/or low albumin levels were investigated for free thyroid hormones (fT3, fT4) following stepwise adjustment of the serum IgG and/or albumin. All two hormones were measured with two different automated immunoassays: the microparticle enzyme immunoassay (MEIA) with two steps (AxSym, Abbott, USA) and the electrochemiluminescence immunoassay (ECLIA). RESULTS: The bias of fT3 and fT4 exhibited positive correlations with serum IgG and albumin. The bias of fT3 was more pronounced than that of fT4 following the addition of albumin (40-150% and 10-40%, respectively) as well as following the addition of IgG (8-30% and 0-8%, respectively). The MEIA method was more sensitively affected in case of fT4, whereas the bias of fT3 was more influenced in the ECLIA assay. In MEIA assay, the influence of albumin on the bias of fT3 and fT4 was stronger if serum IgG levels were low. CONCLUSION: The results confirm that pathological thyroid findings in seriously ill patients may largely be ascribed to some laboratory artifacts.

Epidemiology of thyroid microcarcinoma found in autopsy series conducted in areas of different iodine intake.

The prevalence of thyroid microcarcinomas found at autopsies is 100-1000 times higher than in clinical cancer. The epidemiological and histological characteristics of thyroid microcarcinomas in consecutive series of autopsies performed in two areas of different iodine intake were investigated. Iodine deficient (ID) area: n = 222 (M = 109, F = 113), median age: 74-76 years, median iodine excretion (MIE) of nursing home residents from this area: 70 microg/g creatinine. Iodine sufficient (IS) area: n = 221 (M = 132, F = 89), median age: 68 years, MIE: 500 microg/g creatinine. When compared to the IS area, the results obtained in the ID area showed a higher thyroid weight (mean 27.75 g +/- 18.43 g vs. 16.5 g +/- 9.6 g, p < 0.0001) and a larger number of goitrous glands (50/222 vs. 5/221, p < 0.0001). Altogether 21 microcarcinomas were found (4.74%) with no iodine intake- or gender-related difference: ID n = 11 (4.95%), M/F = 8/3; IS n = 10 (4.52%), M/F = 6/4. Microcarcinomas seemed to be more prevalent in the 40-59-year age group. All microcarcinomas were of the papillary type. In conclusion, compared to clinical cancer, thyroid microcarcinomas are characterized by a two-scale higher prevalence, are not related to iodine intake, gender or nodularity, are most exclusively of the papillary type.

Percutaneous Ethanol Sclerotherapy of Symptomatic Nodules Is Effective and Safe in Pregnant Women: A Study of 13 Patients with an Average Follow-Up of 6.8 Years.

Background. Because of the increased risk of surgery, thyroid nodules causing compression signs and/or hyperthyroidism are concerning during pregnancy. Patients and Methods. Six patients with nontoxic cystic, four with nontoxic solid, and three with overt hyperthyroidism caused by toxic nodules were treated with percutaneous ethanol injection therapy (PEI). An average of 0.68 mL ethanol per 1 mL nodule volume was administered. Mean number of PEI treatments for patients was 2.9. Success was defined as the shrinkage of the nodule by more than 50% of the pretreatment volume (V0) and the normalization of TSH and FT4 levels. The average V0 was 15.3 mL. Short-term success was measured prior to labor, whereas long-term success was determined during the final follow-up (an average of 6.8 years). Results. The pressure symptoms decreased in all but one patient after PEI and did not worsen until delivery. The PEI was successful in 11 (85%) and 7 (54%) patients at short-term and long-term follow-up, respectively. Three patients underwent repeat PEI which was successful in 2 patients. Conclusions. PEI is a safe tool and seems to have good short-term results in treating selected symptomatic pregnant patients. Long-term success may require repeat PEI.

Influence of iodine intake on the diagnostic power of fine-needle aspiration cytology of the thyroid gland.

In order to determine whether the iodine intake influences the diagnostic power of ultrasound-guided fine-needle aspiration cytology (US-FNAC), patients with nontoxic nodular goiter from an area with sufficient iodine intake (IS) (n = 938, median iodine excretion [MIE] = 103 microg/L) and from an iodine-deficient (ID) area (n = 3,601, MIE = 75 microg/L) were investigated. Elevated rates of multinodularity (59.6% vs. 49.6%, p < 0.001), nonpalpable nodules (47.6% vs. 37.3%, p < 0.001) and nondiagnostic US-FNACs (8.8% vs. 5.1%, p = 0.008), and a lower malignancy rate (1.2% vs. 2.3%, p = 0.006) were found in the ID area. Follicular tumors were encountered among positive findings. Cytohistologic comparison (ID, n = 416; IS, n = 97) revealed that the sensitivity, specificity, and diagnostic accuracy of US-FNAC were similar in the two areas (95.5% vs. 92.3%, 78.3% vs. 71.1%, 82.4% vs. 80.6%, IS vs. ID area, respectively), while a lower malignancy rate and a higher ratio of benign to malignant tumors were observed in the ID than in the IS area (10.1% vs. 22.6%, p < 0.001, and 4.38 vs. 1.50, p < 0.001, respectively). This resulted in a lower positive predictive value of US-FNAC in the ID (36/106) than in the IS area (21/36, p = 0.001), because the rate of false US-FNAC was higher in benign (67/184) than in malignant tumors (4/61, p < 0.001).

Relapse of Graves' disease after successful outcome of antithyroid drug therapy: results of a prospective randomized study on the use of levothyroxine.

Antithyroid drugs are effective in restoring euthyroidism in Graves' disease, but many patients experience relapse after withdrawal. Prevention of recurrence would therefore be a desirable goal. In a prospective study, patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and randomly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment. The levothyroxine group was randomized to continue or discontinue levothyroxine after 1 year. End points included relapse of overt hyperthyroidism. Of 346 patients with Graves' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were randomly assigned to receive levothyroxine (114 patients) or no treatment (controls, 111 patients). Of those not randomized, 39 patients showed early relapse within 4 weeks, 61 endogenous TSH suppression, 7 TSH elevation, and 14 had to be excluded. Dropout rate during the study were 13.3%. Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group (20% after 1 year, 32% after 2 years) and the randomized controls (18%, 24%), whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH (33%, 49%). Levothyroxine therapy did not influence TSH-receptor antibody, nor did it reduce goiter size. The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs (posttreatment TSH). The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker.

Markov model-based estimation of individual survival probability for medullary thyroid cancer patients.

UNLABELLED: The relatively benign, but occasionally rapidly fatal clinical course of medullary thyroid cancer (MTC) has raised the need for individual survival probability estimation. A retrospective study on 91 MTC clinical case histories with a mean follow-up of 6 years indicated prevalences of local, regional and distant residual tumor on primary care completion of 23%, 54% and 54%, respectively. Local, regional and distant relapses during follow-up occurred in 8%, 23% and 26% of the patients, with a cause-specific death in 26% of the cases. Prognostic factors statistically significantly influencing the cause-specific survival were selected by uni- and multivariate analysis. A Markov method-based model was developed for the estimation of individual time-dependent local, regional and distant relapse-free and cause-specific survival probability functions, with parameters numerically determined via a maximum likelihood procedure. These parameters include relative risk factors related to prognosticators, a residual or recurrent local/regional/distant tumor, and combinations of these entities. In multivariate studies, the patient s age and gender, the genetic basis of the dis-ease, lymph node involvement, the existence of a general symptom (diarrhoea) at presentation, and the dosage of external irradiation proved to be prognosticators. The cause-specific survival function of the study population indicated mean 5, 10 and 15-year survival probabilities of 69%, 62% and 58%. CONCLUSION: Survival probabilities can be predicted for extrastudy cases provided that the same laws and principles govern the clinical course of these cases and those comprising the study. For individual survival probability estimation, a Pascal program (MEDUPRED) was written and is available on the home page of the National Institute of Oncology, Budapest (www.oncol.hu).

[Novel pharmacologic therapies in acromegaly]. / Uj gyógyszeres terápiás lehetóségek az acromegalia kezelésére.

The primary aim of therapy should be to remove symptoms, reduce tumor bulk, prevent relapse, and improve long-term outcome. Surgery, radiotherapy and medical therapies are used to achieve these aims. Post-treatment mean "safe" serum growth hormone values of < 2.5 ng/ml should be the therapeutic goal. Transsphenoidal surgery remains the first line treatment for acromegaly. Patients with microadenoma can expect 85%, while those with macroadenoma 50% chance to achieve safe serum growth hormone levels. Less than 20% of acromegalics respond to treatment with bromocriptine, while quinagolide and cabergoline may show better clinical response; the success rate is higher for tumors secreting both growth hormone and prolactin. Dopamine agonists may be considered either in combination with somatostatin-analogues or as monotherapy in selected patients, and in those with co-secretion of prolactin. Octreotide (Sandostatin, Novartis) is a synthetic somatostatin-analogue, which is administered subcutaneously in doses between 100 and 250 micrograms 3 times daily. Long-acting octreotide (Sandostatin LAR, Novartis) contains octreotide incorporated into microspheres of biodegradable polymer. To effectively lower serum growth hormone levels, monthly injections of 10-30 mg of long-acting octreotide are needed, serum growth hormone falls to 2.5 ng/ml in 70% of cases, and serum insulin-like growth factor I normalizes in 67%. Slow release lanreotide (Somatuline SR, Ipsen) is an alternative depot long-acting somatostatin-analogue, which is administered in a dose of 30 mg intramuscularly every 14, 10 or 7 days. Both compounds are equally, if not more, effective than subcutaneous octreotide, and significantly improve patient compliance. Pegvisomant (Sensus Drug Development Corporation) is a genetically engineered growth hormone receptor antagonist, which inhibits growth hormone action. When given subcutaneously in a dose of 20 mg/day, serum insulin-like growth factor I levels return to normal in 90% of patients. Theoretical concerns of tumor expansion have not been a problem to date, but long term studies are needed. Primary medical--somatostatin-analogue--therapy is recommended if surgery fails, if the patient refuses or unsuited for surgery and it may be also considered in patients with macroadenoma with extra--but not suprasellar extension, since the surgical "cure" rates of these tumors are low.

[Macroprolactinemia in the differential diagnosis of hyperprolactinemia]. / A macroprolactinaemia és a hyperprolactinaemia differenciáldiagnosztikája.

INTRODUCTION: Biologically active prolactin and the inactive fraction of macroprolactin can be present in hyperprolactinaemic sera. The reaction of routinely used prolactin assays with macroprolactin is variable. AIMS: The present study was undertaken to analyse the leading clinical signs of hyperprolactinemia in macroprolactinemia and true hyperprolactinemia and to assess the prevalence of macroprolactinemia in hyperprolactinemic females. METHODS: 1571 consecutive female patients were investigated for hyperprolactinemia. Prolactin was measured before and after precipitation of macroprolactin by polyethylene glycol in 285 hyperprolactinemic (> 520 mlU/l) patients. Since not a single case of macroprolactinemia (recovery < 40%) was found in the range of 520-700 mlU/l, only in women with prolactin > 700 mlU/l (N = 254) entered the study. RESULTS: In 59 patients (23%) macroprolactinemia was found. In women, the occurrence of macroprolactinemia increased with advancing age (p < 0.05). "A priori" clinical signs indicating hyperprolactinemia occurred less frequently in patients with macroprolactinemia than in those with true hyperprolactinemia. Pituitary microadenoma was found in 9.8% of macroprolactinemia vs. 31.6% in true hyperprolactinemia (p < 0.01); galactorrhea: 4% in macroprolactinemia vs. 19% in true hyperprolactinemia, (p < 0.05); infertility: 17% in macroprolactinemia vs. 44% in true hyperprolactinemia (p < 0.05). In 8 out of 59 women with macroprolactinemia, true hyperprolactinemia appeared simultaneously (15.3%). Occurrence of polycystic ovaries syndrome was more frequent in the true hyperprolactinemia (12%) that in macroprolactinemia (4.5%). CONCLUSIONS: It has been shown that macroprolactin does not occur in mild hyperprolactinemia. In women, the occurrence of macroprolactinemia increases with age. "A priori" clinical signs indicating hyperprolactinemia and pituitary abnormality are less frequent in macroprolactinemia than in true hyperprolactinemia. The diagnosis of macroprolactinemia should be used only, when the PRL levels fall to the normal range after precipitation. To avoid diagnostic and therapeutic pitfalls the screening for macroprolactin of all patients with prolactin > 700 mlU/L is recommended.

[Serum tumor marker levels during a 12-months growth hormone replacement therapy in patients with adult growth hormone deficiency]. / Egyéves növekedési hormon pótló kezelés hatása növekedési hormon hiányos felnóttek szérumbeli tumormarkerszintjeire.

INTRODUCTION: High growth hormone/insulin-like growth factor-1 level may have oncogenic potential in animal experiments, and in patients with acromegaly. There are also some data suggesting the development of different neoplasms in animals after growth hormone administration and in humans upon growth hormone replacement therapy. AIMS: The general opinion is however, that growth hormone replacement therapy has no oncogenic effect, but the tumor marker levels have not been studied so far. PATIENTS/METHODS: Nine patients participated in the study: 3 women, 6 men, aged between 21-52 years. 6 of them had multiple pituitary hormone deficiency and were on replacement therapy (thyroxine: 2, cortisone: 1, sexual steroids: 6 and desmopressin: 2 patients). The cause of growth hormone deficiency was the removal of pituitary tumor (6 patients) or craniopharyngioma (2 patients), and in 1 case the deficiency was idiopathic. The mean dose of growth hormone was 0.53 in female and 0.51 mg/day in male patients. Insulin-like growth factor-1, carcinoembryonal antigen, human choriogonadotropin hormone, alpha-fetoprotein, prostate specific antigen, tissue polypeptide antigen-M, ferritin, gastrointestinal carcinoma antigen, ovarian antigen, breast specific antigen, carcinoma antigen 50 were measured at baseline and after 3, 6 and 12 months of GH replacement. RESULTS: Insulin-like growth factor-1 standard deviation score increased: baseline: -4.1 +/- 0.5; 3 months: -0.3 +/- 0.3; 6 months: 0.7 +/- 0.2; 12 months: -0.2 +/- 0.6, P < 0.001 vs. baseline. The mean value of all tumor markers remained within the normal range and there was no significant increase within the normal range either. CONCLUSION: The lack of increase of tumor marker levels does not indicate possible oncogenic effect of one-year GH treatment in hypopituitary adults. The authors can not draw any far-reaching conclusions because of the low patient number and the short follow-up, but the measurement of tumor marker levels may provide useful means to follow up long-term therapy and for the early diagnosis of possible occult malignancy.

[Thyrotropin-secreting pituitary adenomas--diagnosis and treatment in five case]. / Thyreotrop hormont szekretáló hypophysis adenomák diagnosztikája és kezelése öt eset kapcsán.

The authors report five cases of thyrotropin secreting pituitary adenomas (4 males and 1 female) in whom the diagnosis was established by a combined occurrence of elevated serum free thyroid hormone levels and measurable serum thyrotropin concentration, as well as by visualisation of the pituitary adenomas using magnetic resonance imaging (pituitary microadenoma in two and macroadenoma in three cases). Other tests were less diagnostic: only two out of 4 patients proved to be non-responders during testing with thyrotropin releasing hormone, and serum alpha subunit was elevated in only 2 out of 3 cases. There was a significant decrease of serum thyrotropin concentration in all of the four patients tested by 100 micrograms octreotide (Sandostatin, Novartis). Somatostatin-analogue treatment (slow release preparation in two cases) restored euthyroidism in all three cases treated prior to surgery. In one case the hyperthyroidism persisted after surgery of the macroadenoma, but irradiation of the pituitary area and subsequent somatostatin-analogue treatment resulted finally in a complete cure (euthyroidism and no tumor remnant). In the three other operated patients surgery resulted in euthyroidism. These cases demonstrate the variety of diagnostic and therapeutical modalities in the management of thyrotropin secreting pituitary adenomas.

Serum thyroglobulin antibody levels within or near to the reference range may interfere with thyroglobulin measurement.

High concentration of thyroglobulin antibodies (TgAb) is a major limiting factor of thyroglobulin measurements in patients with differentiated thyroid cancer. We investigated whether thyroglobulin antibody added to serum samples could interfere with the thyroglobulin assay. Thyroglobulin levels in serum samples with different concentrations of thyroglobulin were measured by electrochemiluminescence immunoassay before and after the addition of increasing concentrations of thyroglobulin antibody using the secondary calibrator solution of the thyroglobulin assay kit containing sheep thyroglobulin antibody to reach thyroglobulin antibody levels within or near to the reference range. Thyroglobulin and thyroglobulin antibody concentrations were also measured in 134 serum samples from 27 patients after thyroid ablation. There was a strong negative association (slope = -1.179) between thyroglobulin antibody and thyroglobulin concentrations in samples with added thyroglobulin antibody (beta = -0.86; P <0.001). Changes in thyroglobulin concentrations were described mathematically as loss of thyroglobulin% = -0.2408 x Ln(thyroglobulin antibody IU/ml) + 0.1944. Thyroglobulin concentrations were significantly lower than those calculated from experiments with added thyroglobulin antibody in 26/134 samples from patients after thyroid ablation. We conclude that if the same TgAb interference exists in the presence of naturally occurring human TgAb, our observation may prove to be useful during follow-up of patients with differentiated thyroid cancer. However, further studies are needed to explore the clinical relevance of thyroglobulin antibody levels within or near to the reference range in monitoring these patients.

Progestin-dependent effect of oral contraceptives on plasma aldosterone/renin ratio.

OBJECTIVES: Estrogens in oral contraceptives (OC) may influence plasma aldosterone/plasma renin activity (ALD/PRA) and plasma aldosterone/plasma renin concentration (ALD/DRC) ratios, but the effect of progestins on these ratios has not been sufficiently studied so far. DESIGN AND METHODS: PRA (RIA, DiaSorin), DRC and ALD (IRMA, RIA, Beckman Coulter) were measured, then ALD/PRA and ALD/DRC were calculated in 86 healthy normotensive women (aged 27.3 ± 7.5 years), 63 using progestin-containing OC: either gestodene (GTD, n=25), desogestrel (DSG, n=22) or drospirenone (DRSP, n=16). 23 OC-nonusers served as control. RESULTS: Data are presented as median and lower and upper quartiles. PRA, DRC and ALD levels were higher (p<0.001) in the DRSP group [3.1 (1.5 3.8)ng/mL/h, 25.2 (9.8 30.4)ng/L and 43.7 (28.0 61.6)ng/dL, respectively], than in the DSG [1.4 (1.1 2.1)ng/mL/h, 8.3 (6.8 12.3)ng/L and 11.5 (7.2 16.6)ng/dL], GTD [1.2 (0.8 2.2)ng/mL/h, 8.0 (4.8 10.5)ng/L, and 13.4 (7.7 22.1) ng/dL] and control [1.3 (0.7 1.6) ng/mL/h, 12.2 (7.5 21.7) ng/L, and 10.0 (4.4 14.7) ng/dL] groups. Cases of falsely elevated ALD/PRA and ALD/DRC ratios [7 (11%) and 12 cases (19%) respectively] were only found in OC users but not in the control group. In the DSG and GTD groups, but not in the DRSP group falsely elevated ALD/PRA occurred less frequently than falsely elevated ALD/DRC. CONCLUSIONS: In OC-users falsely elevated ALD/PRA and especially ALD/DRC are a common finding, particularly when the OC contains DSG or GTD. Therefore, for OC-users method- and progestin-type specific cut-off levels should be established.

The effect of sample storage on the reliability of thyroglobulin and thyroglobulin-antibody measurements.

OBJECTIVES: To investigate how sample-storage alters thyroglobulin (Tg) and thyroglobulin-antibody (TgAb) immunoreactivity. DESIGN AND METHODS: Tg and TgAb measurements at different storage-times and -temperatures. RESULTS: 48-h-storage at 4-10 degrees C (but not 8 h at room temperature) increased Tg and decreased TgAb immunoreactivity by maximum +23% and -16%. 4-weeks-storage at -17 to -20 degrees C decreased both Tg and TgAb by max. 21-31%. CONCLUSIONS: Storage of samples at 4-10 degrees C for >24-48 h, or at -17 to -20 degrees C for >2-3 weeks significantly alters Tg and TgAb immunoreactivity.