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.

Unexpectedly high mutation rate of cyp11b1 compared to cyp21a2 in randomly-selected turkish women: a large screening study.

PURPOSE: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from enzyme deficiencies associated with steroidogenesis. The clinical presentation of non-classic CAH (NCAH) in females is often indistinguishable from other hyperandrogenic disorders like polycystic ovary syndrome (PCOS). The data on the prevalence of NCAH in unselected women in the literature is scanty. The research aimed to evaluate the prevalence of NCAH, carrier frequencies, and the correlation between clinical symptoms and genotype in Turkish women. METHODS: The study group comprised two hundred and seventy randomly-selected unrelated asymptomatic women of reproductive age (18-45). Subjects were recruited from female blood donors. All volunteers underwent clinical examination and hormone measurements. The protein-encoding exons and exon-intron boundaries of the CYP21A2, CYP11B1, HSD3ß2 and CYP21A2 promoter were sequenced by direct DNA sequencing. RESULTS: After genotyping, seven (2.2%) individuals were diagnosed with NCAH. The heterozygous carrier frequencies of CYP21A2, CYP21A2 promoter, CYP11B1, and HSD3ß2 genes with 34, 34, 41, and 1 pathologic mutation were determined at 12.6%, 12.6%, 15.2%, and 0.37% of volunteers, respectively. Gene-conversion (GC) frequencies between CYP21A2/CYP21A1P and CYP11B1/CYP11B2 were determined as 10.4% and 14.8%, respectively. CONCLUSION: Despite GC-derived higher mutation frequency determined in the CYP11B1 gene, the reason for the low frequency of NCAH due to 11OHD compared to 21OHD might be that gene-conversion arises with active CYP11B2 rather than an inactive pseudogene. HSD3ß1 exhibits high homology with HSD3ß2 located on the same chromosome; remarkably, it demonstrates low heterozygosity and no GC, most probably the outcome of a tissue-specific expression pattern.

Ovarian functions and polycystic ovary syndrome in adult women with type 1 diabetes mellitus in a Turkish population.

PURPOSE: The effect of gonadotropin-releasing hormone agonist (GnRHa) stimulation has not been studied in adult women with type 1 diabetes mellitus (DM). We investigated the baseline and stimulated hormone levels after GnRHa and the frequency and relationship between polycystic ovary syndrome (PCOS) and type 1 DM in adult women with type 1 DM. METHODS: We included 55 adult women (age, 17-35 years) with type 1 DM and 15 healthy women (age, 20-29 years). Hormones including total testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS), follicle-stimulating hormone (FSH), luteinising hormone (LH), estradiol, prolactin, and thyroid-stimulating hormone were measured in the early follicular phase of the menstrual cycle. All participants underwent GnRHa stimulation test, and FSH, LH, estradiol and 17-OHP response levels were measured every 6 h for 24 h. PCOS was diagnosed according to ESHRE/ASRM (Rotterdam) criteria. RESULTS: Between patients with type 1 DM and healthy controls, no significant differences were noted in mean age and body mass index (BMI) as well as baseline and stimulated hormone levels after buserelin stimulation, except for baseline serum 17-OHP levels, which was higher in patients with type 1 DM. Polycystic ovary morphology (PCOM) was detected in 14 (25%) patients, clinical hyperandrogenism in 16 (29%), hyperandrogenemia in 25 (45%), anovulatory cycle in 72%, and PCOS in 20 (36%). CONCLUSION: All parameters representing androgen excess disorders, except 17-OHP level, of both groups were similar, and frequencies of PCOS and anovulatory cycle in adult women with type 1 DM were 36% and 72%, respectively.

Molecular skin changes in Cushing syndrome and the effects of treatment.

OBJECTIVE: We investigated newly diagnosed patients with endogenous CS for molecular changes in skin by biopsy before and a year after treatment of CS. PATIENTS AND METHODS: 26 Patients with CS and 23 healthy controls were included. All the patients were evaluated before and a year after treatment. Skin biopsies were obtained from abdominal region before and a year after treatment in patients with CS and once from healthy volunteers. Total RNA was isolated from the skin biopsy samples and the real-time PCR system was used to determine the expression levels of 23 genes in the skin biopsy. RESULTS: Skin expression levels of HAS 1, 2 and 3 mRNAs were lower and COL1A2, COL2A1, COL3A1 mRNAs were higher in patients with CS than in normal controls. MMP-9, TIMP-1 and elastin mRNA expression levels were similar in two groups. Skin IL-1ß mRNA expression level was significantly higher in patients with CS. None of these parameters changed significantly 12 months after treatment. Patients with CS showed higher skin GH and HSD11B1 mRNA expressions and lower GHR and IGF-1R mRNA expression compared to control. Expression levels of IGF-1, GR and HSD11B2 mRNA were similar in two groups. None of these parameters changed significantly 12 months after treatment. CONCLUSION: CS is associated with increased expression levels of skin COL1A2, COL2A1, COL3A1 mRNAs (which are correlated with increased expression level of skin GH mRNA). Decreased skin HAS may cause decreased synthesis of HA that contributes to thinning of skin in CS. Increased local inflammatory cytokine and HSD11B1 mRNAs may be related to the acne formation in CS. Treatment of CS was not able to reverse these changes and ongoing changes were detected after treatment.

The role of androgen receptor CAG repeat polymorphism in androgen excess disorder and idiopathic hirsutism.

PURPOSE: The study aimed to investigate whether repeat number in the androgen receptor (AR) gene has any contribution to phenotypes of the disease of androgen excess (polycystic ovary syndrome (PCOS), idiopathic hyperandrogenemia (IHA) and idiopathic hirsutism (IH) in a cohort of Turkish women. METHODS: Three hundred and fifty-four voluntary premenopausal women (172 healthy controls and 182 patients with androgen excess disorders and idiopathic hirsutism) 18-45 years of age seen at an outpatient endocrine clinic at Erciyes University Hospital between January 2013 and December 2014 were included. All volunteers have undergone physical examination and biochemical evaluation. The polymorphic (CAG)n repeat of the human AR was determined by fragment analyses. RESULTS: Detailed clinical analyses of the patients ended up with 137 PCOS, 24 IHA, and 21 IH. Pairwise comparisons revealed the CAG repeat number differences between the PCOS and controls (p = 0.005) and IH and controls (p = 0.020). Women with CAG repeat length ≤ 17 had a significantly increased twofold risk for PCOS than those women with > 17 CAG repeats OR: 2.0 (95% CI 1.2-3.3, p = 0.005). Women with CAG repeat length ≤ 17 had a significantly increased threefold risk for IH than those women with > 17 CAG repeats OR: 2.9 (95% CI 1.2-7.3, p = 0.020). When correlation analysis was performed, a weak negative correlation was detected between the short allele and FGS score (r = - 0.131, p = 0.013) and a positive relationship between total testosterone and longer allele in the IHA group (r = 0.425, p = 0.039). Median repeat length of the shorter allele between oligomenorrhea and woman with normal menstrual cycle was found to be statistically significant (p = 0.017). CONCLUSION: This study indicated that the risk of PCOS and IH is associated with the inheritance of ARs with shorter CAG repeats.

Comprehensive genotyping of Turkish women with hirsutism.

INTRODUCTION: Hirsutism is a medical sign rather than a disease affects 5-8% of women of reproductive age. Hirsutism is associated with hyperandrogenemia in most patients excluding those with idiopathic hirsutism (IH). The most common cause of hirsutism is polycystic ovary syndrome (PCOS) followed by IH and idiopathic hyperandrogenemia (IHA); however, the clinical presentation of non-classical congenital adrenal hyperplasia (NCAH) in females is often indistinguishable from other hyperandrogenic disorders with common clinical signs such as hirsutism. OBJECTIVE: The primary aim of the study is to examine the physical properties of the three genes and to make a detailed comparison of the mutations with the clinical data to contribute the etiology of hirsutism. SUBJECTS AND METHODS: 122 women admitted to the Endocrinology Clinic at Erciyes University Hospital with hirsutism were enrolled in the study between 2013-2014. All the participants were clinically evaluated. Protein-encoding exons, exon-intron boundaries of CYP21A2 (including proximal promoter), CYP11B1 and HSD3B2 genes were analyzed via state-of-the-art genetic studies. RESULTS: DNA sequencing analyses revealed two homozygous and three compound heterozygous 21-hydroxylase deficient (21OHD) NCAH patients. Additionally, three novel CYP21A2 mutations (A89V, M187I and G491S) and two novel CYP11B1 mutations (V188I and G87A) were determined. The frequencies of heterozygous mutations in CYP21A2 (including promoter), CYP11B1 and HSD3B2 genes were determined as 26.5% (15% coding region, 11.5% promoter), 11.5% and 0%, respectively. CONCLUSION: 21OHD-NCAH prevalence was determined to be ~4%. Unexpectedly, high heterozygous mutation rates were observed in CYP11B1 gene and CYP21A2 promoter region. CYP11B1 and HSD3B2 deficiencies were not prevalent in Turkish women with hirsutism despite the existence of higher heterozygous mutation rate in CYP11B1.

How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey.

OBJECTIVE: Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. METHODS: The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. RESULTS: One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. CONCLUSION: Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.

Thyroid Hormone Withdrawal Further Exacerbates Oxidative Stress in Patients with Thyroid Carcinoma.

PURPOSE: Hypothyroidism has profound effects on multiple organs and systems including cellular oxidative damage. Thus, we aimed to investigate the effects of acute hypothyroidism on oxidative stress in patients with differentiated thyroid carcinoma (DTC). PATIENTS: 33 patients with DTC were involved in the study. 23 healthy subjects matched for age and body mass index (BMI) served as control group. Fasting blood sample was obtained for the determination of blood chemistry, lipids, myeloperoxidase (MPO) activity, total lipid hydroperoxide (LHP), pyrrolized protein, protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP) and thiol levels before and after thyroid hormone withdrawal (THW) in patients with DTC. RESULTS: MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels were significantly higher, but thiol levels were significantly lower in patients with DTC while on L-thyroxine treatment than those of healthy subjects. At acute hypothyroid status after THW, MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels further increased, thiol levels further decreased in patients with DTC as compared to healthy subjects and to their on L-thyroxine treatment period. CONCLUSIONS: This study showed an increased oxidative stress in patients with DTC which is further exacerbated with acute hypothyroidism upon THW. This situation may have treatment implications such as antioxidant therapy, at least during THW.

Prevalence of AIP mutations in a series of Turkish acromegalic patients: are synonymous AIP mutations relevant?

CONTEXT: In sporadic acromegaly, overall AIP(mut) prevalence is reported as 3, 4.1 and 16 % in studies carried out across Europe. However, it is not known whether the prevalence shows any changes across different ethnicities. The aim of the study was to identify prevalence of AIP(mut) in a series of Turkish acromegalic patients. PATIENTS AND METHODS: Direct sequencing of AIP gene was performed in 92 sporadic acromegalic patients. RESULTS: One patient was found to have a new mutation in exon 6: g67.258,286 (G/A) heterozygote; (GGC/GAC; gly/asp). Apart from this new mutation, previously defined synonymous mutations in AIP gene were detected in seven patients (Exon 4; rs2276020; (GAC/GAT; asp/asp) and six patients were found to have five different intronic mutations in AIP gene which were not previously defined. The patient with pathogenic AIP(mut) presented at a young age and had an aggressive and treatment resistant tumour. The prevalence of AIP(mut) in Turkish patients was found to be 1 % in sporadic acromegaly in the present study. In addition, one synonymous mutation which was previously defined and six new intronic mutations have been described in Turkish acromegalic patients. All acromegalic patients with synonymous AIP(mut) presented with macroadenoma and majority of them had invasive tumour. CONCLUSION: The prevalence of AIP(mut) in Turkish patients was found to be 1 % in sporadic acromegaly in the present study. This ratio increases when younger age groups are taken into account 6 % among patients <30 years of age at the time of diagnosis of acromegaly. The clinical features of acromegaly, such as having large and invasive tumours, may be affected by the presence of synonymous AIP(mut).

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.

Evaluation of long-term pituitary functions in patients with severe ventricular arrhythmia: a pilot study.

INTRODUCTION: Traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), stroke and cerebrovascular disease (CVD) are identified as risk factors for hypopituitarism. Pituitary dysfunction after TBI, SAH, and CVD may present in the acute phase or later in the course of the event. Chronic hypopituitarism, particularly growth hormone (GH) deficiency is related to the increased cardiovascular morbidity and mortality. In patients with serious ventricular arrhythmias, who need cardiopulmonary resuscitation, brain tissue is exposed to short-term severe ischemia and hypoxia. However, there are no data in the literature regarding pituitary dysfunction after ventricular arrhythmias. PATIENTS AND METHODS: Forty-four patients with ventricular arrhythmias [ventricular tachycardia (VT), ventricular fibrillation (VF)] (mean age, 55.6 ± 1.8 years; 37 men, 7 women) were included in the study. The patients were evaluated after mean period of 21.2 ± 0.8 months from VT-VF. Basal hormone levels, including serum free triiodothyronine (fT3), free thyroxine (fT4), TSH, ACTH, prolactin, FSH, LH, total testosterone, estradiol, IGF-1, and cortisol levels were measured in all patients. To assess (GH)-insulin like growth factor-1 (IGF-1) axis, glucagon stimulation test was performed and 1 µg ACTH stimulation test was used for assessing hypothalamic-pituitary-adrenal (HPA) axis. RESULTS: The frequencies of GH, gonadotropin and TSH deficiency were 27.2, 9.0, 2.2%, respectively. Mean IGF-1 levels were lower in GH deficiency group, but it was not statistically significant. CONCLUSION: The present preliminary study showed that ventricular arrhythmias may result in hypopituitarism, particularly in growth hormone deficiency. Unrecognized hypopituitarism may be responsible for some of the cardiovascular problems at least in some patients.

Unusual effects of GH deficiency in adults: a review about the effects of GH on skin, sleep, and coagulation.

Based on the literature data in the last two decades, growth hormone deficiency (GHD) in adults has been accepted as a clinical entity. Due to the presence of GH and IGF-I receptors throughout the body, the physiological effects of the GH-IGF-I axis are still under investigation. The effects of GH on skin, sleep, and coagulation parameters in adults have only been investigated in detail only in the recent years. In this review, our aim was to summarize the literature regarding the effects of GHD and GH replacement treatment on the skin, sleep, and coagulation parameters in adults.

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.

Routine screening for Cushing's syndrome is not required in patients presenting with hirsutism.

CONTEXT: Prevalence of Cushing's syndrome (CS) in patients presenting with hirsutism is not well known. OBJECTIVE: Screening of CS in patients with hirsutism. SETTING: Referral hospital. PATIENTS AND OTHER PARTICIPANTS: This study was carried out on 105 patients who were admitted to the Endocrinology Department with the complaint of hirsutism. INTERVENTION: All the patients were evaluated with low-dose dexamethasone suppression test (LDDST) for CS. MAIN OUTCOME MEASURE: Response to LDDST in patients presenting with hirsutism. RESULTS: All the patients had suppressed cortisol levels following low-dose dexamethasone administration excluding CS. The etiology of hirsutism was polycystic ovary syndrome in 79%, idiopathic hirsutism in 13%, idiopathic hyperandrogenemia in 6%, and nonclassical congenital hyperplasia in 2% of the patients. CONCLUSION: Routine screening for CS in patients with a referral diagnosis of hirsutism is not required. For the time being, diagnostic tests for CS in hirsute patients should be limited to patients who have accompanying clinical stigmata of hypercortisolism.

Posterior pituitary functions are not altered after growth hormone replacement therapy in hypopituitarism due to Sheehan's syndrome.

OBJECTIVE: The aim of the present study was to investigate the effects of growth hormone (GH) replacement on posterior pituitary functions of GH-deficient Sheehan's syndrome (SS) patients. DESIGN: Ten patients with SS and 14 healthy control women were included in this prospective study. All patients were given appropriate hormone replacement therapy other than GH, according to present hormone deficiencies. Patients were euthyroid and eucortisolemic at the time of baseline evaluation. Patients and the control group were evaluated with water-deprivation and saline-infusion tests at baseline and the tests were repeated in patients with SS after 3 months of GH replacement therapy. RESULTS: According to the water deprivation test, 3 patients had partial central DI at baseline. Urine osmolalities of the patients were slightly lower and plasma osmolalities were significantly higher than the control group at baseline, after water deprivation and following DDAVP injection and after hypertonic saline infusion. The osmotic threshold of serum for thirst perception was found to be significantly higher in SS patients than the control group, GH replacement therapy did not influence the results of water deprivation and saline infusion tests in SS patients. CONCLUSION: Patients with SS have subtle abnormalities in posterior pituitary functions and the threshold for thirst perception is increased. However GH replacement therapy does not seem to reverse or adversely affect the mildly deteriorated posterior pituitary functions of SS patients.

Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months. In addition, the occurrence of AHA and APA positivity due to acute infectious meningitis was demonstrated for the first time. Further longer-term prospective investigations need to be carried out on a larger cohort of patients to understand the role of autoimmunity in the pathogenesis of late hypopituitarism after acute infectious meningitis.

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.

VEGFR1 expression is related to lymph node metastasis and serum VEGF may be a marker of progression in the follow-up of patients with differentiated thyroid carcinoma.

OBJECTIVE: Vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1) are known to be related to thyroid tumorigenesis. The aim of the study was to examine the expressions and serum levels of VEGF, VEGFR1, IGF1, and IGF1 receptor (IGF1R) in patients with differentiated thyroid carcinoma (DTC) compared with patients with nodular goiter (NG). METHODS: We examined 39 patients with DTC who had a clinical history of at least 2 years and compared them with 25 patients who had a pathological diagnosis of NG after thyroidectomy. Serum VEGF, VEGFR1, and IGF1 levels were measured in both patient groups. The expressions of VEGF, VEGFR1, IGF1, and IGF1R were analyzed by the immunohistochemical method in the paraffin blocks of patients' thyroidectomy samples of the patients. RESULTS: The immunostainings scores for VEGF, VEGFR1, IGF1, and IGF1R were found to be higher in patients with DTC than in those with NG. Only VEGFR1 expression was related to lymph node metastasis at the time of surgery. None of the expressions were related to the long-term prognosis of the patients. Serum VEGF was found to be higher in patients with progressive DTC than in patients in clinical remission. CONCLUSION: The expressions of VEGF and VEGFR1 were shown to be correlated with the expression of IGF1 and IGF1R. VEGFR1 expression may be an important index for the presence of lymph node metastasis at the time of thyroidectomy. Increased serum levels of VEGF may reflect disease recurrence in DTC.

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.

Hypopituitarism due to sports related head trauma and the effects of growth hormone replacement in retired amateur boxers.

Traumatic brain injury (TBI) has been recently recognized as a leading cause of pituitary dysfunction. Current data clearly demonstrated that sports related head trauma due to boxing, kickboxing, and soccer might results in pituitary hormone deficiencies, isolated growth hormone (GH) deficiency in particular. In the present report physiologic dose GH replacement therapy (GHRT) was performed in two GH deficient retired amateur boxers for the first time. The boxers received recombinant GH for 6 months. After 6 months of GHRT there were substantial improvements, but not complete normalization, in the body composition parameters, lipid profiles and quality of life scores in both boxers. These preliminary results suggest that GHRT may have beneficial effects in retired boxers with severe isolated GH deficiency due to sports related head trauma. But more data with higher number of boxers and longer GHRT duration are warranted.