Efficacy of zoledronic acid treatment in Paget disease of bone.

UNLABELLED: Clinical trials have shown that zoledronic acid was more effective than other bisphosphonates in the treatment of Paget disease. We retrospectively reviewed remission and relapse statuses of 12 patients with Paget disease. Remission was achieved in all patients after treatment. We recommend zoledronic acid in the first-line treatment of Paget disease. INTRODUCTION: Paget disease is a disease of bone of unknown etiology with increased bone turnover that results in defective bone microarchitecture and bone deformity. Bisphosphonates are used in symptomatic Paget disease of bone. Clinical trials have shown that zoledronic acid was more effective than other bisphosphonates in the treatment of Paget disease. METHODS: In this study, we retrospectively reviewed the remission and relapse statuses of 12 patients with Paget disease of bone who were seen as outpatients between October 2011 and October 2013.We evaluated alkaline phosphates, osteocalcin, and deoxypyridinoline levels measured before and at 6th, 12th, and 18th months of treatment. RESULTS: Pretreatment and posttreatment values for alkaline phosphates, deoxypyridinoline, and osteocalcin were as follows: 473 ± 256 U/L, 14.99 ± 7.63 mmol/L, 21.09 ± 3.18 ng/ml, and 82 ± 13 U/L, 5.14 ± 1.11 mmol/L, and 8.57 ± 4.31 ng/ml. Remission was achieved in all patients after treatment. The levels indicated that remission continued at 12th and 18th months of treatment. There was statistically significant difference between pretreatment and posttreatment values. No statistically significant difference between the levels measured at 6th, 12th, and 18th months of treatment was detected. CONCLUSION: We recommend zoledronic acid in the first-line treatment of Paget disease of bone in achieving and maintaining remission.

Pituitary apoplexy in an adrenocorticotropin-producing pituitary macroadenoma.

Adrenocorticotropin (ACTH) producing macroadenomas and pituitary apoplexy are unusual in Cushing' s disease. A 20-year-old man who had been diagnosed Cushing' s disease 2 months ago, presented with sudden headache, nausea, and vomiting. His serum cortisol level was 0.4 µg/dl and ACTH level was 23.9 pg/ml. Magnetic resonance imaging of the pituitary gland disclosed a hemorrhage in the pituitary macroadenoma (22×19 mm). He was treated with IV methylprednisolone immediately and then the symptoms were relieved within the first day of the treatment. The hemorrhagic lesion was resected by transsphenoidal surgery successfully. Impaired secretion of pituitary hormones may be seen after the pituitary apoplexy. We communicate a case with pituitary apoplexy of an ACTH secreting pituitary macroadenoma, causing acute glucocorticoid insufficiency.

Plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in diabetic foot ulcers.

Plasma TAFI may participate in arterial thrombosis in cardiovascular diseases (CVD) and may be involved in the mechanism of vascular endothelial damage in diabetic patients. The aim of this study was to investigate the association of plasma TAFI antigen level in the development of diabetic foot ulcer in Type 2 diabetes. The TAFI antigen levels were determined in 50 patients with diabetic foot ulcers and 34 patients without diabetic foot ulcers and 25 healthy individuals. We measured TAFIa/ai antigen in plasma samples with a commercially available ELISA Kit. Diabetic foot ulcer group and diabetic group were similar in terms of mean age and sex distribution. Diabetes duration, retinopathy, neuropathy, macrovascular disease and infection were related to diabetic foot ulcers. HbA1c, HDL-cholesterol and Folic Acid levels were decreased in the diabetic foot ulcer group. TAFI levels were 99.44 ± 55.94% in control group, 135.21 ± 61.05% in diabetic foot ulcer group, 136.75 ± 59.38% in diabetic group and was statistically different (P < 0.05). But no difference was seen in TAFI levels between the diabetic foot ulcer group and diabetic group (P > 0.05). No significant difference in plasma TAFI levels were seen between diabetic foot ulcer stages. TAFI antigen levels are increased in Type 2 diabetic patients, but are not related to diabetic foot ulcer development.

Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy.

Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy (DN). The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene polymorphism in the healthy and patients with and without DN. The MCP-1 genotypes were determined in 43 patients with nephropathy and 43 without nephropathy and a control group of 105 healthy individuals. The genotype MCP-1 (-2518G/A) distribution did differ between the control group and the type 2 diabetic patients (P = 0.004). The frequency of the polymorphic G allele was also no similar for the group with type 2 diabetes as for the control group with 20.9 and 32.4%, respectively (P = 0.012). The AA genotype and A allele at MCP-1 -2518 was an independent risk factor for the progression of type 2 diabetes. In conclusion, MCP-1 AA genotype and A allele may play a specific role(s) in determining diabetic susceptibility, but do not seem to be important in the clinical manifestations of DN.

The importance of anti-insulin antibody in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion or multiple daily insulin injections therapy.

To investigate the influence of two insulin administration modalities, continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) therapy with insulin analogues, on the development of insulin antibodies (IAs) in patients with type 1 diabetes mellitus and to assess the impact of IAs on glucose control and hypoglycaemia. 96 patients with type 1 diabetes mellitus treated with CSII (n = 48) or MDI (n = 48) were included in the study. Age, duration of diabetes, A1c, preprandial and postprandial blood glucose and hypoglycaemic events were compared between IA positive and negative patients. IA levels were higher in the CSII group (% 24.6 ± 14.2) than the MDI group (% 13.2 ± 9.9). Duration of diabetes and age were not associated with IA positiveness. While A1c, preprandial blood glucose and the frequency of hypoglycaemic events were similar in two groups, postprandial blood glucose was lower in IA positive group (P = 0.03). Patients with type 1 diabetes mellitus treated with CSII with insulin analogues had higher IA levels when compared to MDI therapy. However, the development of IAs did not impair the glycaemic control.

Human multidrug resistance-1 gene expression levels in graves-basedow disease.

OBJECT: Multidrug resistance 1 gene is responsible for the resistance of a large variety of drugs in human cells. We tried to evaluate this in the present study in thyroid stimulant hormone receptor antibody positive subjects. METHOD: In study enrolled 23 female and 10 male subjects. Hyperthyroid subjects were treated with PTU and remission was assured between 6-12 months. Blood samples were collected before the start of this treatment. Permission for this study was taken from the patients and the local ethical committee. RESULTS: Serum F-T3, F-T4 levels in Graves subjects were markedly high, whereas TSH levels were markedly low than normal range. We also found that with increased age of the Graves' subjects, MDR-1 gene expression decreased. There was also a direct correlation between blood MDR-1 gene expression and TSH-R Ab levels in patients with Graves's disease. We observed that the duration of being euthyroid was lengthened with the elevation of MDR-1 gene expression. There was a direct correlation between blood MDR-1 gene expression levels and ultrasonografic size of thyroid gland. CONCLUSION: As a result, raised blood MDR-1 gene expression levels in patients with Graves-Basedow disease may be associated with the activity of the disease and the resistance to its treatment. The more blood MDR-1 expression increases the more the duration of being euthyroid increases.

Evaluation of beta cell dysfunction by mixed meal tolerance test and oral L-arginine in patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND AND AIMS: Defective insulin secretion is required for the development of frank diabetes mellitus. We evaluated the secretory response of pancreatic beta cells after the ingestion of mixed meal plus oral L-arginine in newly diagnosed type 2 diabetic patients. MATERIALS AND METHODS: Twenty-four newly diagnosed type 2 diabetic patients were enrolled in this study. All patients were ingested a mixed meal of 553 kcal. Serum insulin levels were measured at time 0 just before the mixed meal and at 1, 2, 3, 4 and 5 h after the ingestion of the mixed meal. Twenty-four hours later, all patients ingested mixed meal followed by oral 8 g L-Arginine, and insulin levels were again measured at 0, 1, 2, 3, 4 and 5 h after the ingestion of the meal. RESULTS: Insulin levels reached to peak values at the 2 (nd) hour, and decreased to baseline levels at the 5 (th) hour measurements both after the ingestion of mixed meal only and after the ingestion of mixed meal plus oral L-Arginine. First and 2 (nd) hour insulin levels were significantly higher after the ingestion of mixed meal plus oral L-Arginine. CONCLUSION: In this study we used for the first time the combination of oral L-arginine with mixed meal test to evaluate the beta cell dysfunction in type 2 diabetic patients. Increments regarding serum insulin levels after the ingestion of mixed meal plus oral L-Arginine suggest that oral L-Arginine could be benefical for the evaluation of beta cell function and secretory defects.

The relation of adiponectin and tumor necrosis factor alpha levels between endothelial nitric oxide synthase, angiotensin-converting enzyme, transforming growth factor beta, and tumor necrosis factor alpha gene polymorphism in adrenal incidentalomas.

OBJECTIVE: The aim of our study was to demonstrate demographic characteristics, presence of inflammatory markers, distribution of angiotensin-converting enzyme (ACE), tumor necrosis factor (TNF), endothelial nitric oxide synthase (eNOS) genotypes and relations among these parameters in these patients and control subjects. RESEARCH DESIGN AND METHODS: Study samples were collected from 50 patients with adrenal mass and 30 control groups. The eNOS, ACE, TNF-alpha, transforming growth factor (TGF)-beta genes polymorphisms, TNF-alpha, adiponectin levels were analysed in 50 unrelated Turkish patients with a diagnosis of adrenal incidentaloma (AI). RESULTS: There was statistically significant difference between TNF-alpha levels of patient and controls (p=0.048). We have not detected the connection between TGF-beta, TNF-alpha, ACE, eNOS gene polymorphism with serum TNF-alpha and adiponectin levels. In this study, we demonstrated that there were significant differences for ACE genotypes in the patients when compared to the controls (p<0.05). The percentages of the ID, DD, II genotypes for ACE gene polymorphism in the patients group were 30.0, 13.0, 7.0%, respectively. CONCLUSIONS: According to different cases of eNOS, TGF-beta, ACE, and TNF-alpha gene genotypes; no statistical significant difference was found between basal cortisol, ACTH, DHEAS, metanephrine, renin, aldosterone, normetanephrine, 17-hydroxyprogesterone, 1 mg low-dose dexamethasone suppression test-cortisol response and AI size. In this study, I/D genotype was determined to be statistically higher in ACE gene in patients with AI (p=0.014).

The (-174) G/C polymorphism in the interleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish patients.

INTRODUCTION: Interleukins and cytokines play an important role in the pathogenesis of many cancers.We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in patients with papillary thyroid carcinoma (PTC) and control subjects. MATERIAL AND METHODS: In this study, 42 patients with PTC and 340 healthy controls were included. Peripheral blood samples were taken from control group and patients, and blood samples were preserved at -80 C in tubes containing Na-EDTA. RESULTS: We also found a statistically significant difference between patients with PTC and the control group with respect to IL-6 genotype (p<0.05). IL-6 gene polymorphism in patients with PTC patients did not reveal statistically significant difference between the 2 groups (size of tumor >1 cm and <1 cm), multicentricity, RET-PTC types and capsule invasion (p>0.05).We also did not find a statistically significant difference between patients with PTC and the control group with respect to IL-6-gene allele frequency (p>0.05). DISCUSSION: Our data suggest that the IL-6 G-174 C polymorphism could play a role in thyroid cancer risk, but there is no effective role as a prognostic factor.

Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population.

OBJECTIVE: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. RESULTS: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). CONCLUSIONS: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.

Association of the angiotensinogen M235T and angiotensin-converting enzyme insertion/deletion gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy.

OBJECTIVE: Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T(m)) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. RESULTS: The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively (P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively (P=.758). CONCLUSIONS: There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.

The prevalence of RET/PTC mutations in papillary thyroid cancers in Turkish population and its relation between tumor histopathology and prognostic factors.

OBJECTIVE: In recent years, thyroid cancer has been at the forefront of molecular pathology as a result of the consequences of the Chernobyl disaster and the recognition of the role of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs). Correlation of RET/PTC expression with clinical outcome is controversial. This study aims to identify the prevalence of RET/PTC oncogene expression in Turkey, and to investigate the correlation between RET/PTC oncogene expression and the known prognostic factors of PTC in 101 patients. METHODS: The RET rearrangements were examined by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region. Statistical evaluation was performed by using Independent samples t-test, One-sample Chi-square test and Pearson Chi-square or Fisher's Exact Test. RESULTS: RET/PTC was determined positive in 67(66.3%) of totally 101 patients (p<0.001). RET/PTC1 in 32(31.7%), RET/PTC3 in 21(20.8%), RET/PTC1+RET/PTC3 both in 10(9.9%) patients were found to be positive. There was RET/PTC2 positiveness in two patients, RET/PTC2,3 positiveness in one patient, and RET/PTC1,2,3 positiveness in one patient. No statistical difference was found between RET/PTC1 and RET/PTC3. None of genetico-clinical analyses showed any significant association between RET/PTC expression and the clinical and pathological features of the cancers. CONCLUSION: While this prevalence of the RET/PTC is less than RET/PTC frequency seen after Chernobyl in Belarus, its prevalence in our region is also high (66.3%). As a result, no significant correlation was found in between prognosis and RET/PTC frequency.

Fas/Fas ligand gene polymorphism in patients with papillary thyroid cancer in the Turkish population.

OBJECTIVE: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. CONCLUSIONS: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy.

BACKGROUND: Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C > T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy. METHODS: DNA was extracted from peripheral leukocytes of the subjects. Genotyping of the MTHFR C677T polymorphism for all individuals was performed by melting curve analysis of the generated amplicons after real-time online PCR. RESULTS: This genotype distribution did not differ between control subjects and type 2 diabetic patients in which 6.8% were TT, 43.7% were CT and 49.5% were CC (chi2 = 0.201, p > 0.05). The frequency of the mutant T allele was 23.4% in diabetic patients with nephropathy versus 33.0% in those without nephropathy. The genotype frequencies were TT, 2.1%; CT, 46.6%; CC, 55.3% in diabetic patients with nephropathy versus TT, 10.7%; CT, 44.6%; CC, 44.6% in those without nephropathy. CONCLUSIONS: The MTHFR genotype and allele frequencies were not different between diabetic patients with and without nephropathy (chi2 = 3, 386, p > 0.005; chi2 = 2.320, p > 0.005, respectively). Therefore, we conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients.

Power Doppler US patterns of vascularity and spectral Doppler US parameters in predicting malignancy in thyroid nodules.

AIM: The purpose of this study was to determine whether spectral Doppler ultrasound (US) parameters, including resistive index (RI) and maximal systolic velocity (MSV), or vascular pattern can be used to distinguish malignant from benign thyroid nodules. MATERIALS AND METHODS: We prospectively examined 169 thyroid nodules in 134 patients undergoing sonographically guided fine-needle aspiration biopsy (FNAB). Vascularity as determined by power Doppler US imaging was defined as absent, perinodular alone, or intranodular. For each nodule, the RI and MSV values were recorded as the average of the recordings obtained. Results of the FNAB and surgical pathological examination, if available, were used as a proof of final diagnosis to categorize all nodules as benign or malignant. RESULTS: Seven nodules were excluded from study because of non-diagnostic FNAB results due to hypocellular or insufficient cytological material. Of the remaining nodules, nine were malignant (all confirmed at surgery) and 153 were benign. Of the 145 nodules with intranodular vascularity, nine (6.2%) were malignant and the remaining 136 (93.8%) were benign. The malignant nodules had a mean RI of 0.60 on intranodular and 0.58 on perinodular arteries. These values were not significantly higher than those associated with benign nodules (RI=0.57 and RI=0.56, respectively). Malignant nodules had a mean MSV of 20.4cm/s on intranodular and 35.3cm/s on perinodular arteries that were also not significantly different from those associated with benign nodules (p>0.05). CONCLUSION: The results of this study indicate that Doppler US characteristics including vascular pattern, RI and MSV are not useful parameters for distinguishing malignant from benign thyroid nodules. Therefore, Doppler US characteristics including vascular pattern, RI and MSV values of thyroid nodules can not be used as a diagnostic method to determine which nodules should undergo FNAB.

Preprandial repaglinide decreases exogenous insulin requirements and HbA1c levels in type 2 diabetic patients taking intensive insulin treatment.

In this study, we investigated the effects of combining preprandial repaglinide to the insulin therapy for reducing the exogenous insulin requirements and serum HbA(1c) levels in type 2 diabetic patients whose blood glucose levels were previously regulated by multiple dose intensive insulin therapy. Fifty patients with type 2 diabetes who had been initially treated with oral antidiabetic agents without a satisfactory response were included in this study. After adequate glycemic control was achieved with intensive insulin therapy, the patients were divided into two subgroups. The first group continued with intensive insulin therapy. The second group received a combination of multiple insulin injections and oral repaglinide (1.5 mgr tid). The doses of insulin injections were gradually decreased accordingly in the second group. Both groups were followed-up for 3 months. Repaglinide was well tolerated and had no toxicity. A significant reduction regarding exogenous insulin requirements and serum HbA(1c) levels were demonstrated in patients taking preprandial repaglinide (p<0.01). Combining repaglinide to intensive insulin therapy could be a safe and effective alternative to intensive insulin therapy alone for the glycemic control and for reducing exogenous insulin requirements in type 2 diabetic patients.

Is the effect of fine-needle aspiration biopsy on the thyroid nodule volume important to evaluate the effectiveness of suppression therapy?

Fine-needle aspiration biopsy (FNAB) is recommended for the initial evaluation of thyroid nodule. If a benign cytology is obtained, suppression therapy with levothyroxine is the first choice in the management of nodular goiter with a follow-up of nodule size with ultrasonography, but the effects of FNAB have not been taken into consideration in this approach. We aimed at evaluating the effect of FNAB on thyroid volume and other ultrasonographic dimensions by measurement of these parameters before and immediately after the procedure, and in later periods, and to clarify the necessity of regarding the effects of FNAB on thyroid. Forty-six patients (34 females, 12 males; mean age: 36.3+/-10.7 yr) with solitary thyroid nodules were included in the study. The nodules were solid in ultrasonography, thyroid function tests were normal and results of FNAB were found as benign cytology. Thyroid hormone suppression therapy was not initiated. Ultrasonographic measurements were made before FNAB, repeated immediately after FNAB, and 1 month and 6 months later. There were no statistically significant changes in the mean thyroid nodule volume, nodule area and circumference of patients before, immediately after FNAB, 1 month and 6 months later. Size differences and individual variability at each time period were analyzed. These parameters changed by more than 10% in a great majority (69.5-78.2%) of patients, and more than 50% change was observed in 17.3-26.0% of patients. Changes in thyroid dimensions were bi-directional, both increment and decrement being noticed. It was thought that this is the reason why there was no significant change in mean nodule volume, area and circumference. Evaluating the difference in nodule volume according to ultrasonographic parameters obtained before FNAB may be misleading because of the individual change in these parameters with FNAB. It may be useful to evaluate the nodule size and volume closely after FNAB to make a true correspondence of these parameters in the long term.

Low basal androstenedione levels plus augmented 17alpha-hydroxyprogesterone and low dehydroepiandrosterone sulfate responses to adrenocorticotropic hormone stimulation in patients with adrenal incidentaloma.

OBJECTIVE: To investigate the androstenedione, 17a-hydroxyprogesterone (17-OHP), and dehydroepiandrosterone sulfate (DHEAS) basal levels and responses to adrenocorticotropic hormone (ACTH) in patients with adrenal incidentalomas in order to determine which enzyme defects are present. METHODS: In a study group of 23 patients (18 women and 5 men who ranged in age from 16 to 70 years) with incidentally discovered asymptomatic adrenal masses, ACTH stimulation was performed to evaluate the secretory responses of 17-OHP and DHEAS. The same test was performed in 15 age- and sex-matched control subjects. RESULTS: Of the 23 patients, 16 (70%) had a 17-OHP peak >30 nmol/L. The 17-OHP response to ACTH stimulation was significantly higher in patients with adrenal incidentalomas than in control subjects (P<0.001). Fourteen patients had basal DHEAS levels below the 3rd percentile of the control group (1.4 +/- 0.1 mmol/L). The mean stimulated DHEAS level was 1.7 +/- 0.2 mmol/L (range, 0.8 to 4.1) in patients with incidentalomas and 4.2 +/- 0.4 mmol/L (range, 1.8 to 5.6) in the control group (P<0.001). In 13 patients, stimulated DHEAS levels were low in association with high 17-OHP levels. Basal ACTH levels did not differ significantly between patients (8.14 +/- 1.2 pmol/L) and control subjects (8.73 +/- 0.7 pmol/L). Basal androstenedione levels were significantly lower in patients (1.9 +/- 0.3 nmol/L) than in control subjects (5.7 +/- 2.5 nmol/L) (P<0.001). No significant correlation was found between 17-OHP levels and tumor size. CONCLUSION: Enzyme defects may have an important role in adrenal incidentalomas. Two possible explanations for the observed abnormalities of steroid metabolism in patients with incidentalomas are that (1) the incidentalomas are true primary tumors that have aberrant steroid metabolic pathways or (2) such patients have underlying congenital adrenal hyperplasia that leads, over time, to development of pseudotumors. To assess these two possibilities, we need further studies such as genetic investigations, postoperative test results, and evidence relating the size of the adrenal mass to steroid-suppressible treatment.

Small cell neuroendocrine carcinoma of the thymus complicated by Cushing's syndrome. Report of a 58-year-old woman with a 3-year history of hypertension.

A 58-year-old woman with a history of Cushing's syndrome for three years presented with a mediastinal mass and received the diagnosis of small cell neuroendocrine carcinoma of the thymus invading the pericardium. On immunohistochemical study, the neoplastic cells reacted with antibodies against cytokeratin, epithelial membrane antigen, neuron-specific enolase, chromogranin, synaptophysin, and ACTH. Clinicopathologic findings of this rare case of ectopic adrenocorticotropic hormone (ACTH) syndrome are discussed with a literature review.

Hypothalamus-hypophysis-thyroid axis, triiodothyronine and antithyroid antibodies in patients with primary and secondary Sjögren's syndrome.

It has been well established that, anti-thyroglobulin antibodies (ATG) and anti-microsomal antibodies (AMC) may be present in various thyroid disorders and other systemic autoimmune diseases, including Sjögren's syndrome (SS). However, presence of circulating autoantibodies to thyroid hormones, i.e. both to triiodothyronine (T3) and tetraiodothyronine (T4), has not been studied extensively in SS. Autoantibodies to T3 and T4 are very important, because serum T3 and T4 levels may be detected spuriously higher or lower, due to the presence of these autoantibodies. Their presence should be suspected when measured serum thyroid hormone levels are not consistent with clinical status of the patient. SS is a slowly progressive, inflammatory autoimmune disease, affecting primarily the exocrine glands. Thyroid gland, being a target in some autoimmune diseases, is well known to be affected in SS as well. Keeping this possibility in mind, we investigated T3 autoantibody levels and thyroid gland involvement in patients with SS. Twenty-six SS patients (F/M:22/4) with a mean age of 46.6 years, were recruited in this study. Twelve of them were accepted as primary SS (pSS), while others had secondary SS (sSS) (7 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 3 with progressive systemic sclerosis (PSS) and 1 with sarcoidosis). Thyroid function tests, including T3, T4, fT3, fT4, TSH, ATG, AMC, T3 antibody measurements, thyroid scintigraphy, thyroid ultrasonography and TRH stimulation tests were performed in all patients. We compared our results with those of the twenty healthy normal controls. Serum ATG and/or AMC were detected in three patients with pSS (25%) and no patients with sSS. No significant difference could be shown in the other parameters, including T3 autoantibodies and thyroid function tests. TRH stimulation test was also normal, showing that the hypothalamus-hypophysis-thyroid axis was not affected in patients both with pSS and sSS. In conclusion, we found that T3 autoantibody levels in pSS, were not significantly higher than sSS and normal controls.