Cardiovascular evaluation and endothelial dysfunction in Cushing syndrome following remission: a prospective study.

PURPOSE: Cushing syndrome (CS) is a well-known risk factor for cardiovascular morbidities. We aimed to evaluate endothelial and cardiovascular functions, endothelial mediators and pro-inflammatory cytokines in patients with CS before and after remission. METHODS: Adult patients with newly diagnosed endogenous CS were included. Metabolic [body mass index (BMI), glucose, and lipid values] and cardiovascular evaluation studies [24-h ambulatory blood pressure monitoring, carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and echocardiography] were performed, and endothelial mediators [asymmetric dimethyl arginine (ADMA) and endothelin-1 (ET-1)] and pro-inflammatory cytokines [interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α)] were measured. Control group was matched in terms of age, gender, and BMIs. RESULTS: Twenty-five patients, mean age 40.60 ± 14.04 years, completed the study. Compared to controls (n = 20) mean arterial pressure (MAP) and CIMT were higher (p < 0.005 and p = 0.012, respectively), and FMD (p < 0.001) and mitral E/A ratio (p = 0.007) lower in the patients during active disease. Baseline serum ADMA, ET-1, and IL-1ß were similar between the groups, while TNF-α was lower in the patients (p = 0.030). All patients were in complete remission 1 year following surgery. BMI, LDL cholesterol, serum total cholesterol, fasting plasma glucose, MAPs, and CIMT significantly decreased (p < 0.005), while there was no improvement in FMD (p = 0.11) following remission. There was no significant change in ADMA, IL-1ß, and TNF-α levels, but ET-1 increased (p = 0.011). CONCLUSIONS: Remission in CS improves some cardiovascular parameters. ADMA and ET-1 are not reliable markers for endothelial dysfunction in CS. Metabolic improvements may not directly reflect on serum concentrations of TNF-α and IL-1ß following remission of CS.

A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders.

CONTEXT: Diagnosis of secondary adrenal insufficiency and GH deficiency requires evaluation by dynamic stimulation tests in most cases. Although insulin tolerance test (ITT) is accepted as the gold-standard test for the evaluation of both hypothalamo-pituitary-adrenal (HPA) and (GH)-IGF-1 axes, the test is cumbersome. In clinical practice, low-dose adrenocorticotrophic hormone (ACTH) stimulation test is a sensitive, safe and easily applicable alternative to ITT. Although it takes more time, glucagon stimulation test (GST) is also a good alternative to ITT and can evaluate both axes. OBJECTIVE: The primary aim of this study was to compare the ITT, low-dose ACTH and GSTs in the evaluation of HPA and GH-IGF-1 axes in patients with pituitary disorders and to evaluate the repeatability of all three tests. DESIGN: ITT, low-dose ACTH and GSTs were performed in all 129 patients, and the tests were repeated in 66 of these patients. SETTING: Erciyes University Medical School, Department of Endocrinology. PATIENTS OR OTHER PARTICIPANTS: One hundred and twenty-nine adult patients (76 women, 53 men) with pituitary disorder were included in the study. MAIN OUTCOME MEASURE(S): The cortisol and GH responses of patients to dynamic tests. RESULTS: Peak cortisol levels obtained during ITT were significantly lower than the values obtained during both low-dose ACTH and GSTs. Peak cortisol levels obtained during the GST were lower than those found during the low dose ACTH stimulation test. Peak GH responses were found to be higher in GST than in ITT. All three tests had good reproducibility. CONCLUSIONS: Any of 3 tests can be used in the evaluation of the HPA axis and either GST or the ITT can be used in the evaluation of the GH-IGF-1 axis but cut-off levels for the insufficiency of HPA or GH-IGF-1 axis should be individualized for each test.

Three years prospective investigation of pituitary functions following subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) is known to be related to pituitary dysfuntion in retrospective and short-term prospective studies. We aimed to investigate pituitary functions in patients with SAH in longer follow-up periods to demonstrate if pituitary hormone deficiencies recover, persist or new hormone deficiencies occur. Twenty patients with SAH, who were followed up for 3 years, were included in the present study. Patients were evaluated with basal hormone levels and glucagon stimulation test (GST).Serum basal cortisol and adrenocorticotropic hormone (ACTH) levels were found to be significantly elevated at 3rd year of SAH compared to 1st year. Other basal hormone levels at 3rd year did not show a significant change from the levels found at 1st year. One of the patients had ACTH deficiency at 1st year of SAH and recovered at 3rd year. Growth hormone (GH) deficiency, according to GST,was diagnosed in 4 patients. One patient with GH deficiency at first year was still deficient, 3 of them recovered and 3 patients were found to have new-onset GH deficiency 3 years after SAH. SAH is associated with anterior pituitary dysfunction and GH is the most frequently found deficient hormone in the patients. Although one year after SAH seems to be an appropriate time for the evaluation of pituitary functions, further follow-up may be required at least in some cases due to recovered and new-onset hormone deficiencies at 3rd year of SAH.

Comparison of primary octreotide-lar and surgical treatment in newly diagnosed patients with acromegaly.

OBJECTIVE: The primary aim of the study was to compare the efficacy of Oct-LAR and surgery in terms of controlling IGF-1 and GH levels and tumour volumes. The second aim was to compare two primary treatment modalities in terms of side effects such as pituitary insufficiency, cholelithiasis, metabolic parameters and the effect on quality of life (QoL). DESIGN: The study was a randomized, prospective study. PATIENTS: The 22 patients were consecutively randomized to Oct-LAR and surgical treatment groups. RESULTS: Baseline serum IGF-1 level, tumour volume and GH levels were comparable in the Oct-LAR and surgery groups. No significant differences were detected between the Oct-LAR and the surgery groups in terms of IGF-1 and GH levels at the 3rd and 6th months, but at 12th month, preglucose GH was found to be lower in the surgical treatment group. IGF-1 control and complete biochemical response rates were found to be 27% and 64%, in the Oct-LAR and surgical treatment groups, respectively. The mean percentage of tumour volume reduction was found to be 26%, 30% and 31% in the Oct-LAR group vs 64%, 74% and 79% in the surgery group at the 3rd, 6th and 12th months, respectively. CONCLUSION: Primary surgical treatment seems to be slightly more effective than Oct-LAR in terms of biochemical response and IGF-1 control, besides tumour volume reduction, in patients with acromegaly with noninvasive tumours. Oct-LAR is associated with more side effects such as cholelithiasis and glucose metabolism disorders and is more expensive.

Can basal cortisol measurement be an alternative to the insulin tolerance test in the assessment of the hypothalamic-pituitary-adrenal axis before and after pituitary surgery?

BACKGROUND: The aims of this study were to evaluate the validity of preoperative basal serum cortisol levels measured in predicting preoperative adrenal insufficiency and also the validity of basal serum cortisol levels and early postoperative insulin tolerance test (ITT) in predicting postoperative adrenal insufficiency. METHODS: The study was prospectively designed and included 64 patients who underwent pituitary surgery for conditions other than Cushing's disease. An ITT was performed preoperatively, on the 6th postoperative day and at the 1st postoperative month. Basal serum cortisol levels were measured on the 2nd, 3rd, 4th, 5th, and 6th postoperative days. RESULTS: Patients with a preoperative basal cortisol level of <165 nmol/l (6 microg/dl) showed insufficient cortisol response and those with levels higher than 500 nmol/l (18 microg/dl) had sufficient cortisol response to the preoperative ITT. The positive predictive value of the ITT performed on the 6th postoperative day was 69.7%, and the negative predictive value in predicting adrenal insufficiency at the 1st postoperative month was 58%. Patients were considered to have an insufficient cortisol response to ITT at the 1st postoperative month if their basal cortisol levels were <193 nmol/l (7 microg/dl) or 220 nmol/l (8 microg/dl) or 193 nmol/l (7 microg/dl) or 165 nmol/l (6 microg/dl) or 83 nmol/l (3 microg/dl) on the 2nd-6th postoperative days respectively. CONCLUSION: Serum basal cortisol levels may be used as the first-line test in the assessment of the hypothalamic-pituitary-adrenal axis both preoperatively and postoperatively. Dynamic testing should be limited to the patients with indeterminate basal cortisol levels.

Transient hypogonadotropic hypogonadism in an amateur kickboxer after head trauma.

Traumatic brain injury (TBI) is a frequent health problem and increased prevalence of neurendocrine dysfunction in patients with TBI has been reported. Sports injuries and particularly boxing may result in pituitary dysfunction. However, transient hypogonadotropic hypogonadism after an acute head trauma due to boxing and/or kickboxing has not been defined yet. We describe the case of a 20-yr-old male amateur kickboxer who was admitted to hospital complaining of decreased libido and impotence 2 weeks after an intensive bout. Basal hormone levels were compatible with mild hyperprolactinemia and hypogonadotpopic hypogonadism. GH axis was evaluated by GHRH+GHRP-6 test and peak GH level was within normal reference range. Three months later his complaints improved and abnormalities in basal hormone levels normalized. He was also re-evaluated 9 months after the first evaluation; basal hormone levels were within normal ranges and he had no complaints. In conclusion acute head trauma due to kickboxing may cause transient gonadotropin deficiency. Therefore, screening the pituitary functions of sportsmen dealing with combative sports is crucial.

Boxing as a sport activity associated with isolated GH deficiency.

Traumatic brain injury (TBI) has long been known as a cause of hypopituitarism, and it is characterized by a high prevalence of neuroendocrine abnormalities. Boxing, one of the most common combative sports, may also result in TBI. As far as we know, pituitary functions including GH status have not been investigated in boxers. Therefore, in this preliminary study, we have assessed the pituitary functions in boxers. Eleven actively competing or retired male boxers with a mean age of 38.0 +/- 3.6 yr and 7 age-, sex- and BMI-matched healthy non-boxing controls were included in the study. Biochemical and basal hormonal parameters including IGF-I levels were measured. To assess GH secretory status in boxers and healthy controls, GHRH (1 microg/kg)+GHRP-6 (1 microg/kg) test was performed. After GHRH+GHRP-6 test, mean peak GH level in boxers and in controls were 10.9 +/- 1.7 and 41.4 +/- 6.7 microg/l, respectively (p < 0.05). Peak GH levels in 5 (45%) boxers were found to be lower than 10 microg/l and considered as severe GH deficient. In the control group, mean IGF-1 levels (367 +/- 18.8 ng/ml) were significantly higher than that obtained in boxers (237 +/- 23.3 ng/dl) (p < 0.01). All the other pituitary hormones were normal including ADH as no signs and symptoms of diabetes insipidus. There was a significant negative correlation between peak GH levels and boxing duration, and between peak GH levels and number of bouts. In conclusion, we think that boxing is a cause of TBI, and GH deficiency is very common among boxers. Further studies including large number of boxers, both professional and amateur, are needed to clarify pituitary dysfunction in boxers.

Polymicrobial ventriculitis and evaluation of an outbreak in a surgical intensive care unit due to inadequate sterilization.

At the end of 1999, a case of polymicrobial ventriculitis in the Department of Neurosurgery followed by an outbreak of Serratia marcescens mediastinitis in the intensive care unit of cardiovascular surgery occurred. These nosocomial surgical infections were considered to be the result of contamination of surgical sites with inadequately sterilized instruments or theatre linen. An epidemiological survey was focused on the central sterilization unit of the hospital. The microbiological results of this survey proved that the cause of the outbreak was the use of inadequately decontaminated theatre linen. This study indicates that strict infection control measures including the control of sterilization procedures and a well-organized infection control team are necessary to prevent nosocomial surgical infections.

A comparison between the 1-microg adrenocorticotropin (ACTH) test, the short ACTH (250 microg) test, and the insulin tolerance test in the assessment of hypothalamo-pituitary-adrenal axis immediately after pituitary surgery.

The short ACTH stimulation test is an easy, reliable, and extensively used test in the assessment of the hypothalamo-pituitary-adrenal (HPA) axis. However, its use immediately after pituitary surgery is a matter of debate. The insulin tolerance test (ITT) is the gold standard in the evaluation of the HPA axis, but it is not always without side effects and may be unpleasant early after pituitary surgery. Our aim was to investigate the value of the 1-microg ACTH test in the assessment of the HPA axis early after pituitary surgery. We also aimed to determine the value of the 1-microg and 250-microg ACTH tests and the ITT in the estimation of HPA axis status after 3 months postoperatively. Nineteen patients subjected to pituitary tumor surgery were included in the study, and the ITT and the 1-microg and 250-microg ACTH tests were performed between the 4th and 11th days of surgery. The tests were repeated at the first month in 3 patients with subnormal peak cortisol responses (454, 125, and 301 nmol/L) and in 18 patients at the third month postoperatively. ACTH stimulation tests were performed by using 1 microg and 250 microg ACTH iv as a bolus injection, and blood samples were drawn at 0, 30, and 60 min for measurement of serum cortisol levels. The ITT was performed by using iv regular insulin, and serum glucose and cortisol levels were measured. The 1-microg and 250-microg ACTH stimulation tests and the ITT were performed consecutively. At least 48 h were allowed between each test. A peak serum cortisol level of 550 nmol/L or greater was considered as a normal response for both the ITT and the ACTH tests. The serum cortisol level was measured by RIA using commercial kits. Serum glucose was determined by glucose oxidase method. There were correlations between the peak cortisol response to the ITT and the 1-microg ACTH test (r = 0.39, P < 0.05) in the early postoperative period. No correlation was found between the ITT and the 250-microg ACTH test responses. In the early postoperative period, two patients showed normal cortisol responses (> or =550 nmol/L) to the 1-microg ACTH test and five patients showed normal cortisol responses to the 250-microg ACTH test among the six patients with subnormal cortisol responses to the ITT. Three patients with subnormal cortisol responses to ITT and baseline cortisol values less than 240 nmol/L showed normal HPA axis at the end of the first month. In the late postoperative period, at the third month, all the patients showed normal HPA axis. In the early postoperative period of pituitary surgery, the 1-microg ACTH test results are more concordant than the 250-microg ACTH test in comparison with the ITT. Our results also indicate that HPA axis dysfunction shown by ACTH stimulation tests and the ITT in early postoperative period may be normalized 1-3 months after surgery. For this reason, we think that dynamic tests including the ITT may not be useful early after pituitary surgery.

Pituitary apoplexy probably due to TRH and GnRH stimulation tests in a patient with acromegaly.

Pituitary apoplexy is the most serious and life-threatening complication of pituitary adenomas. Most of the cases occur spontaneously but it may occur also after a number of events such as the pituitary stimulation tests. We report a case of acromegaly due to a giant pituitary adenoma in which pituitary apoplexy developed 88 hours after TRH/GnRH stimulation test. The patient had severe headaches, nausea, vomiting, visual disturbance and mental alteration and the computed tomography (CT) scans revealed intratumoral and intraventricular bleeding. The pituitary mass was removed by transsphenoidal approach. The patient developed pneumonia and died on the 9th postoperative day. Pituitary apoplexy was confirmed at surgery and on histological examination. Immunohistochemical staining was positive for GH and PRL. This case indicates that pituitary apoplexy may develop several days after TRH/GnRH stimulation test.

Lymphocytic hypophysitis in a patient with Graves' disease.

A case of lymphocytic hypophysitis is described in a patients with Graves' disease and diabetes mellitus. The 62-year-old man was admitted to hospital with the complaints compatible with hyperthyroidism in April 1993. His medical history, physical examination, thyroid function tests, thyroid scintigraphy and thyroid ultrasonography revealed Graves' disease. The patient had also suffered from diabetes mellitus for three years. After this, the patient's progress was not monitored for two years. The patient presented himself again in September 1995 with complaints of hypothyroidism, hypogonadism and hypoadrenalism. Hormonal investigation showed panhypopituitarism. A magnetic resonance imaging of the pituitary gland disclosed an enlarged pituitary and a thickened infundibulum. The high intensity signal of the neurohypophysis was absent. Transsphenoidal hypophysectomy was performed which revealed a grey-white, relatively avascular pituitary mass. Histology showed diffuse infiltration of the anterior pituitary by numerous lymphocytes. The neurohypophysis also showed evidence of lymphocytic infiltration. On the basis of these findings we suggest that lymphocytic hypophysitis may be associated with Graves' disease.

Migration of abdominal catheter of ventriculoperitoneal shunt into the scrotum.

Four cases of migration of the ventriculoperitoneal (V-P) shunt tip through patent processus vaginalis resulting in scrotal hydrocele are presented. These cases are considered a rare complication of V-P shunts and causal mechanisms are discussed with a review of the literature.

Postoperative mutism after the clipping of a distal anterior cerebral artery aneurysm. A case report.

A 40-year-old man with mutism developed after clipping a left distal anterior cerebral artery aneurysm is presented. The most characteristic presenting symptom was complete absence of speech with unimpaired consciousness which occurred on the fourth day after operation. The patient recovered spontaneously within three weeks. In this paper we discuss the possible pathogenesis and anatomical location of mutism related to a distal anterior cerebral aneurysm in view of the literature.

Ganglioglioma of conus medullaris: a case report.

A case of a ganglioglioma of the conus medullaris extending between T-12 and L2 segments is reported. The tumor was successfully removed by third stage operation. Ganglioglioma located in the conus medullaris is extremely rare. The best treatment of spinal cord ganglioglioma is totally tumor excision even when multiple stage operations are necessary.

Cranioplasty with bone flaps preserved under the scalp.

Cranial bone defects in 27 patients were repaired with bone flaps preserved under the scalp. Head trauma (thirteen patients), cerebrovascular disorder (five patients), postoperative brain swelling (seven patients), and cerebral infective disease (two patients) accounted for the cranial defects. The bone flaps are reimplanted after 14-98 days. The follow-up period was 6 to 26 months. We have encountered no complications related to this technique in 27 consecutive cases.

The effects of octreotide in a patient with Nelson's syndrome.

We have administered octreotide, 100 micrograms tid, to a 27-year-old man with Nelson's syndrome. After seven days of therapy, adrenocorticotropin levels fell to 54% of initial values, and some shrinkage of the tumour was observed. This study indicates that octreotide therapy may have a role in the treatment of Nelson's syndrome.

Migration of bullet in the spinal canal: a case report.

As the spinal canal expands at T10 level naturally, it has been thought that the migration of a bullet within the spinal canal above this level is prevented and the migration of a bullet may only occur between T10 and S1 level. Here, a very rare case of a bullet traversing the length of the spinal canal is reported.

Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase.

During the last three years, seven patients with severe intraventricular hemorrhage admitted to our clinic were treated with direct intraventricular infusion of urokinase. In each case, hemorrhage extended into the entire ventricular cavity and cast formation as well as an expansion of third and fourth ventricles were found. On the average, both the third and fourth ventricles became clear on the third day and the lateral ventricle on the ninth day after hemorrhage. Five of the seven patients showed good recovery or only moderate disability, and two died. Infection, convulsion, rebleeding, and peripheral or secondary hemorrhage due to the side effects of urokinase was not encountered during therapy. We conclude that this procedure can be applied effectively and safely in severe intraventricular hemorrhage.

Management of primary intracerebral hematomas.

112 cases of primary intracerebral hematomas treated surgically, 25 cases aspirated with urokinase infusion and 25 cases treated conservatively in the last five years were reviewed in detail. In the craniotomy group, 17 out of 44 survivors showed good recovery and returned to normal life, 18 of them went home needing no care, 8 went home needing partial care, and one was bedridden. The overall mortality rate in this group was 59.8%. In the urokinase group, 6 out of 21 survivors showed good recovery and returned to normal life, 11 of them went home needing no care, 3 went home needing partial care and one was bedridden. The overall mortality rate in this group was 16%. In the conservative group, 8 out of 19 survivors showed good recovery and returned to normal life, 9 of them went home needing no care, and two went home needing partial care. The overall mortality rate in this group was 24%. Although the mortality rate was lower in the urokinase group compared with the conservative group, there was no statistically significant difference between the two groups (P > 0.05). These results indicate that surgery is useless in deeply comatose patients and CT-guided aspiration with urokinase is a simple, effective, and safe method in appropriately selected patients.