Dynamic changes of central thyroid functions in the management of Cushing's syndrome.

OBJECTIVE: The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. MATERIALS AND METHODS: We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. RESULTS: The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. CONCLUSION: Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome

ABSTRACT Objective The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. Materials and methods We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. Results The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Conclusion Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

Management and follow-up results of an incidental thyroid carcinoma in a young woman with ovarian teratoma.

Thyroid cancer in ovarian teratoma is reported to be rare and experiences are limited. A 26-year-old woman had undergone bilateral cystectomy and omentectomy for bilateral cystic adnexial masses. Pathological examination showed 1.5 cm follicular variant papillary thyroid carcinoma on the basis of unilateral mature cystic teratoma. Increased CA-125 and CA19-9 levels decreased to normal reference ranges after surgery, but postoperative magnetic resonance imaging indicated multiple abdominal cystic loci. After total thyroidectomy, high dose I-131 was administered to ablate thyroid tissue. Thereafter, levothyroxine was started to achieve subclinical hyperthyroidism. No iodine uptake was detected in post-therapeutic whole body scan (WBS) other than thyroid bed. This finding supported that tumor did not show dissemination to abdomen. No uptake on the first-year evaluation with low-dose I-131 WBS suggested the complete ablation of the thyroid gland. It is recommended that thyroid carcinoma arising from ectopic thyroid tissue in a teratoma should be managed as thyroid carcinoma in thyroid. However, direct dissemination to contiguous regions in abdomen and hematogenous dissemination to distant organs should be in mind. Radical surgery including total abdominal hysterectomy, bilateral salphingo-oopherectomy, pelvic and paraaortic lymph node excision and thyroidectomy is recommended. Fertility preserving surgery may be the surgical procedure as in the present case.

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

INTRODUCTION: During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain <300 mg/dl. In women with genetic forms of hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. MATERIALS AND METHODS: We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. RESULT AND CONCLUSION: When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

Tissue and plasma thioredoxin reductase expressions in patients with glioblastoma multiforme.

BACKGROUND AND STUDY AIMS: Thioredoxin reductase (TrxR) is a redox protein that is considered to play a role in tumor progression. The purpose of this study was to assess the expression of TrxR in blood and tumor samples of glioblastoma multiforme (GBM) patients. PATIENTS: TrxR levels were evaluated in blood and GBM tissues extracted from 27 patients, in normal brain tissues of 12 autopsy cases, and in blood samples of 12 healthy subjects. The results were compared between tumor and control groups. RESULTS: The mean level of TrxR in GBM tissues (74.5 ± 14.9 U/g wet tissue) was remarkably higher than in normal brain tissues (14.8 ± 3.4 U/g wet tissue). The mean TrxR levels in blood were significantly higher in GBM patients (296.3 ± 43.6 U/mL) than in the controls (203.0 ± 11.3 U/mL). CONCLUSIONS: These findings suggest that high levels of TrxR may be related to progression of GBM.

Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults.

There is concern about an emerging diabetes epidemic in Turkey. We aimed to determine the prevalence of diagnosed and undiagnosed diabetes, prediabetes and their 12-year trends and to identify risk factors for diabetes in the adult Turkish population. A cross-sectional, population-based survey, 'TURDEP-II' included 26,499 randomly sampled adults aged ≥ 20 years (response rate: 87 %). Fasting glucose and biochemical parameters were measured in all; then a OGTT was performed to identify diabetes and prediabetes in eligible participants. The prevalence of diabetes was 16.5 % (new 7.5 %), translating to 6.5 million adults with diabetes in Turkey. It was higher in women than men (p = 0.008). The age-standardized prevalence to the TURDEP-I population (performed in 1997-98) was 13.7 % (if same diagnostic definition was applied diabetes prevalence is calculated 11.4 %). The prevalence of isolated-IFG and impaired glucose tolerance (IGT), and combined prediabetes was 14.7, 7.9, and 8.2 %, respectively; and that of obesity 36 % and hypertension 31.4 %. Compared to TURDEP-I; the rate of increase for diabetes: 90 %, IGT: 106 %, obesity: 40 % and central obesity: 35 %, but hypertension decreased by 11 % during the last 12 years. In women age, waist, body mass index (BMI), hypertension, low education, and living environment; in men age, BMI, and hypertension were independently associated with an increased prevalence of diabetes. In women current smoking, and in men being single were associated with a reduced risk. These results from one of the largest nationally representative surveys carried out so far show that diabetes has rapidly become a major public health challenge in Turkey. The figures are alarming and underscore the urgent need for national programs to prevent diabetes, to manage the illness and thus prevent complications.

Successful desensitization to imiglucerase of an adult patient diagnosed with type I Gaucher disease.

Gaucher disease is the most common lysosomal storage disorder, and enzyme replacement therapy, such as administration of imiglucerase, is the standard therapy. Anaphylaxis to imiglucerase is rarely reported. Here, we report a 26-year-old female who was diagnosed with type 1 Gaucher disease and referred to our Allergy Outpatient Clinic because of an anaphylactic reaction due to imiglucerase enzyme therapy. A desensitization protocol was administered with two different dilutions with an increasing rate of administration delivered in 10 consecutive steps by intravenous infusion in an intensive care setting. No reactions occurred during the procedure, and the total final dose of 2,000 U was successfully administered. To our knowledge, this is the first adult case with successful desensitization to imiglucerase. Desensitization protocols to drugs in chronic disease patients for whom no alternative therapies are available can be lifesaving.

Transcranial superior orbitotomy for the treatment of intraorbital intraconal tumors: surgical technique and long-term results in single institute.

In this article, the authors are presenting their experience and the results with the surgical treatment of intraorbital intraconal tumors based on a review of 33 constitutive cases. Our data were evaluated in comparison to other major series, and possible factors that might influence surgical outcome and survival are discussed. Thirty-three patients diagnosed with intraorbital intraconal tumors between 1998 and 2009 were treated by transcranial approach. Of these patients, there were 14 males (42.4 %) and 19 females (57.8 %). The age ranged between 2 and 70 years (mean = 36 ± 16.6 years). The follow-up period ranged between 2 and 13 years (mean = 7.3 ± 3.2 years). The most common presenting symptoms were exophthalmus and decreased visual acuity, which was seen in 21 (63.6 %) and 19 patients (57.6 %), respectively. Total resection was achieved in 23 patients (69.7 %) while subtotal resection was done in ten patients (30.3 %). Cavernoma and optic nerve sheath meningioma were the most common histologic variants, which were found in 11 (33.3 %) and 10 (30.3 %) patients, respectively. In the long-term follow-up, 54.5 % of the patients showed total ophthalmologic improvement, 9.1 % showed partial improvement, 21.2 % demonstrated unchanged ophthalmologic status, and 15.2 % showed worse ophthalmologic outcome. Transcranial approach for the treatment of intraorbital intraconal tumors is an effective approach for the management of these pathologies. The effectiveness is clearly demonstrated by the clinical results and outcomes of these patients' groups.

Combined craniofacial resection of anterior skull base tumors: long-term results and experience of single institution.

In this article, the authors are presenting their experience and the results with combined craniofacial resection of anterior skull base tumors based on a review of 27 constitutive cases. Our data are evaluated in comparison to other major centers in other parts of the world, and possible factors that might influence surgical outcome and survival are discussed. Twenty-seven patients diagnosed with anterior skull base tumors between 1999 and 2009 were treated by combined craniofacial resection. Of these patients, there were 19 males (70, 3%) and eight females (29, 7%). The age ranged between 11 and 75 years (mean = 45.9 ± 17.6 years). The follow-up period ranged between 14 and 123 months (avarage = 74 months). The most common presenting symptoms were nasal obstruction and vision disturbance (11 patients for each -40.7%). Total resection was achieved in 24 patients (89%), while subtotal resection was done in three patients (11%). The most common complication was CSF fistule with rhinorrhea, which occurred in five patients (18.5%). Eight patients had recurrences at the time of this long-term follow-up. There were two mortalities in the early postoperative period and seven deaths in the long-term follow-up (overall mortality, 33.3%). The overall 5-year overall survival for all patients in our series was 70.4%. The 5-year overall survival was 62% for patients with malignant tumors and 100% for patients with benign tumors. Combined craniofacial resection of tumors of the anterior skull base is an effective approach for the management of these pathologies. The effectiveness is clearly demonstrated by the clinical results and outcomes of these patients' groups. The favorable prognosis is enhanced by significantly by total resection with negative tumor margins.

Lateral sublabial endoscopic approach to foramen ovale: a novel endoscopic technique to access infratemporal fossa.

OBJECTIVE: Our aim was to define a novel endoscopic approach to selectively access the foramen ovale through the lateral sublabial route. METHODS: Lateral sublabial endoscopic approach to the foramen ovale was studied in 3 fresh cadavers. A 2.5-cm sublabial submucosal incision gained access to the foramen ovale through the corridor under the zygomatic process of maxilla and lateral to the pterygoid plate. To display the anatomic principles of the lateral sublabial endoscopic approach, the surgical anatomy of the endoscopic corridor and the neurovascular structures around the foramen ovale were studied and documented. RESULTS: Lateral sublabial endoscopic approach provided access to the foramen ovale and related neurovascular structures at the posterolateral part of the sphenoid bone without any bone resection. The branches of the pterygoid segment of the maxillary artery superficial to the lower and upper heads of the pterygoid muscles were exposed initially through the endoscopic corridor under the zygoma and lateral to the pterygoid plate. The buccal nerve, passing in between the 2 heads of the lateral pterygoid muscle and the lingual and inferior alveolar branches of the V3 segment of the trigeminal nerve, emerging from under the cover of the lower head of the lateral pterygoid muscle were exposed deep to the branches of the maxillary artery. Following the inferior alveolar nerve backward proximally under the lower head of the pterygoid muscle exposes the foramen ovale. CONCLUSIONS: Lateral sublabial endoscopic approach, a minimally invasive route to the foramen ovale, requires no bone removal and provides adequate exposure to a hard-to-reach area in the infratemporal fossa. With the advantage of visualizing the distal segment of the maxillary artery and the segments of the mandibular nerve, early in the procedure, the approach can provide a controlled endoscopic manipulation for accessing this region.

Expressions of some vital molecules: glioblastoma multiforme versus normal tissues.

OBJECTIVE: The aim of this study was to assess plasma and/or tissue levels of adhesion and apoptotic molecules, cytokines, nitric oxide metabolites, levels of lipid peroxidation, myeloperoxidase and superoxide dismutase in patients with glioblastoma multiforme and controls. METHODS: All the molecules were evaluated in 25 tumors and 30 controls: 15 were normal healthy subjects for plasma and 15 were normal brain tissues that were collected during autopsy. Commercially available kits for measurements were used. RESULTS: Superoxide dismutase was significantly lower in tumors, while all other molecules were significantly elevated compared to the controls (p=0.0001). Superoxide dismutase negatively correlated with plasma interleukin-1beta (p=0.04) and plasma Fas (p=0.016). Plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 correlated positively with plasma 3-nitrotyrosine (p=0.019) and nitrite/nitrate (p=0.019), respectively. Furthermore, plasma interleukin-1beta also positively correlated with plasma nitrite/nitrate (p=0.003). DISCUSSION: These results suggest that there is a complex relationship between pro- and anti-apoptotic molecules in glioblastoma multiforme pathogenesis. Thus, targeting multiple pathways with advanced chemotherapeutic agents or radiotheraupetic regimens following total resections might be helpful in patients with glioblastoma multiforme since preventing a single pathway does not seem to be reasonable.

Reconstruction of growing skull fracture with in situ galeal graft duraplasty and porous polyethylene sheet.

OBJECTIVE: In growing skull fractures with large calvarial defects, it is difficult to use autografts for reconstruction and it requires alternative materials for cranioplasty. In this report, the authors describe their experience and introduce reconstruction of the growing skull fractures' defects with a porous polyethylene sheet (Medpor) and with a novel technique of duraplasty with in situ galeal graft, which avoid the potentially risky dissection and exposure of brain tissue. The goal of this study was to clarify effective surgical methods and to provide the rationale for these techniques. METHODS: We performed this technique on 8 patients with large calvarial defects resulting from growing skull fractures. The skin flap was retracted, leaving the galeal plane adherent to the underlying defect. After removing the bony edges and exposing the underlying retracted dural margins, duraplasty was performed by suturing the galeal tissue left in situ on the defect of the dural margins. Bone reconstruction was performed by placing porous polyethylene sheet (Medpor). CONCLUSIONS: Duraplasty with in situ galeal tissue is a simple, safe, and effective technique to reconstruct dural defects in growing skull fracture, which avoids the risky dissection of the brain tissue. Also, by using Medpor, growing skull fractures can be effectively reconstructed with good cosmetic results.

Duraplasty using autologous fascia lata reenforced by on-site pedicled muscle flap: technical note.

OBJECTIVE: Postoperative cerebrospinal fluid (CSF) leak is a common complication in the practice of neurosurgery, and various surgical techniques were described to overcome and manage this problem. Besides not applying watertight closure of the duraplasty, the inviability and the poor vascularization of the graft and/or the dura (eg, reoperations, multiple operations, or cranial radiotherapy) may lead to delayed healing of the suture site and resultant persistent CSF leaks. We present a simple technique that uses on-site muscle flap with pedicle to supply and vascularize the autologous fascia lata, preserving the viability of the graft and reenforcing its healing ability. METHODS: We applied this technique in 6 patients with postoperative CSF leaks. After harvesting a fascia lata graft with appropriate size from the patients, the graft was sutured to dural defect in watertight fashion. The suboccipital, temporal, and temporal muscles in 4 patients who had posterior fossa duraplasty, in 1 patient who had pterional craniotomy, and in 1 patient who had subtemporal craniotomy, respectively, were dissected, stretched, and sutured to the fascia graft covering the dura graft suture site and then reinforced by Tisseel fibrin glue (Baxter Healthcare Corporation, Deerfield, IL). Postoperatively, CSF lumbar drain was kept open for 72 hours with pressure wound dressing. The technical nuances are illustrated. RESULTS: Cerebrospinal fluid leaks were controlled successfully in 5 patients without recurrence. One patient with posterior fossa duraplasty had recurrence of CSF leak that required reexploration 21 days after the first surgery and a second dural repair in a site distant from the fascia lata attachment. During reexploration intraoperatively, the fascia lata graft was inspected and studied, which has shown the healing of the dura graft site and the graft neovascularization. CONCLUSIONS: Duraplasty using autologous fascia lata reenforced by on-site pedicled muscle flap is an effective technique to control CSF leak, especially when dura is poorly vascularized and less viable. The unfortunate recurrence of CSF leak and reexploration in the seventh patient helped us to observe the effectively healed dural defect with profound early postoperative vascularization of the graft, supporting our idea about the effectiveness of this technique.

Expression of hypoxia inducible factor-1alpha in tumors of patients with glioblastoma multiforme and transitional meningioma.

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the major transcriptional factor involved in the adaptive response to hypoxia. The aim of this study was to assess HIF-1alpha in 22 patients with transitional meningioma (TM) and 26 patients with glioblastoma multiforme (GBM). HIF-1alpha was assessed using a commercially available enzyme-linked immunosorbent assay-based HIF-1 transcription factor assay. Levels of HIF-1alpha in TM and GBM were measured using optical density at 450nm, and median values were found to be 0.35 for TM and 0.37 OD for GBM, respectively. There was no statistically significant difference between the two types of tumor (p=0.264). These findings indicate that HIF-1alpha is elevated in both TM and GBM, suggesting that although hypoxia is one of the most important and powerful stimuli for HIF-1alpha elevation and consequently angiogenesis, other mechanisms may play roles in HIF-1alpha stimulation in benign brain tumors such as TM.

A case report: a noninfantile desmoplastic astrocytoma.

UNLABELLED: INTRODUCTION AND CASE DESCRIPTION: Desmoplastic infantile astrocytomas (DIA) are rare intracranial tumors of infancy with distinctive clinical and radiological features. Despite their radiologically aggressive appearance they tend to follow a benign course with favorable prognosis even after subtotal resections. Non-infantile cases are rarely encountered with only four cases reported before. The authors present a non-infantile DIA in a 4 years old female patient and discuss the clinical features, diagnosis, treatment of this rare entity. CONCLUSION: Although accepted as a tumor of infancy, DIA can also be encountered in older patients. Careful diagnosis and differentiation of DIA cases with other tumors, particularly malignant astrocytomas is important since the therapeutic strategies may differ.

Cerebral cavernomas and human leukocyte antigens: preliminary clinical results.

BACKGROUND: Although cavernomas are the most common brain vascular malformations, the etiology and risk factor(s) are still not entirely known. Recent publications focusing on the molecular basis suggest that genetic factors may play a role in the development of the brain vascular malformations. We aimed to show HLA typing in brain cavernoma in a group of Turkish patients. METHODS: This study compared HLA types of 30 patients who had brain cavernoma with 30 healthy controls. RESULTS: The analysis of HLA distribution in the patients, compared with healthy control data, revealed some statistically significant differences, even after the more rigid Bonferoni correction (P(c)). In the patients group, the frequency of following HLA antigens was significantly increased compared with the control group: HLA-A1 (P(c): .005), HLA-A24 (P(c): .02), HLA-A32 (P(c): .01), HLA-B51 (P(c): .00001), HLA-DR1 (P(c): .02), and HLA-DR4 (P(c): .004). CONCLUSION: These preliminary data suggest that brain cavernoma susceptibility may be associated with HLA antigens. Further studies should be designed to include a larger population of patients with brain cavernoma in order to expose whether there is association between HLA typing and occurrence of cavernoma more accurately.

Glutathione peroxidase, glutathione reductase and protein oxidation in patients with glioblastoma multiforme and transitional meningioma.

PURPOSE: The aim of this study was to assess glutathione peroxidase (GPx), glutathione reductase (GRx) and protein oxidation (POx) levels in patients with glioblastoma multiforme (GBM) and transitional meningioma (TM) and to compare with normal brain tissues. METHODS: GPx, GRx and POx levels were measured in 48 brain tumors obtained during surgery and 15 normal brain tissues that were collected during autopsy. Results were compared between two groups. RESULTS: GPx and GRx activities were significantly lower in GBM and TM when compared to controls and the difference was statistically significant (P = 0.0001). Furthermore, the decrease in enzyme activities was more evident in GBM than in TM. In contrast, POx levels were found to be higher in both GBM and TM compared to controls and showed statistically significant difference (P = 0.00001). Increase in POx levels was clearer in GBM than TM. CONCLUSIONS: GPx and GRx decreased and POx increased significantly in both GBM and TM when compared to normal brain tissues. Further, clinical studies with a larger patient population are required to show the role(s) of antioxidant enzymes in brain tumors more accurately.

Bilateral peninsula-shaped linear craniectomy for mild degrees of craniosynostosis: indication, technique and long-term results.

OBJECTIVE: The goals of surgery in craniosynostosis are to reduce increased intracranial pressure and to achieve a good aesthetic result with minimal mortality and morbidity. A new type of strip craniectomy according to these principles is presented. PATIENTS: The technique was applied to seven cases of oxycephaly and three cases of scaphocephaly under 5 years of age. None of them had major cranial base involvement, facial deformity or marked psychomotor retardation. There was no syndromic case of craniosynostosis included in this group. METHODS: A curvilinear parasagittal craniectomy was combined with coronal and lambdoid craniectomies bilaterally. These craniectomies were curved postero- and antero-inferiorly, respectively, in order to create bilateral 'peninsula-shaped' parieto-temporal bones with their neck still attached to the temporal bone. A linear craniectomy, crossing the superior sagittal sinus and combining right and left curvilinear craniectomies was added. RESULTS: The operative time varied between 45 min and 1h, without any complications. Correction of the skull shape was successful in all cases. CONCLUSION: This technique is simple and effective. But, it is only applicable to a minority of craniosynostoses. Patient selection is the key to better results.