Cutaneous findings in patients with acromegaly and its relationship with concomitant endocrinopathies.

OBJECTIVES: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies. DESIGN, PATIENTS, AND MEASUREMENTS: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated. RESULTS: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035). CONCLUSIONS: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier.

Diagnosis of hypoprolactinemia.

Prolactin is a polypeptide hormone composed of 199 amino acids, synthesized by lactotroph cells. Its primary effects are on the mammary gland and gonadal axes, but it also influences different organs and systems, particularly metabolic functions. Current literature has mainly focused on the diagnosis, monitoring, and treatment of hyperprolactinemia. Due to the lack of a well-established effective treatment for hypoprolactinemia, it is not clinically emphasized. Therefore, data on its diagnosis is limited. Hypoprolactinemia has been associated with metabolic dysfunctions such as type 2 diabetes mellitus, fatty liver, dyslipidemia, fertility problems, sexual dysfunction, and increased cardiovascular disease. While often seen as a part of combined hormone deficiencies due to pituitary damage, isolated prolactin deficiency is rare. Hypoprolactinemia can serve as a marker for extensive pituitary gland damage and dysfunction.Low or undetectable serum prolactin levels and the absence of a sufficient prolactin peak in the thyrotropin-releasing hormone (TRH) stimulation test are considered diagnostic for hypoprolactinemia. Gender appears to influence both basal prolactin levels and TRH stimulation test responses. Basal prolactin levels of, at least, 5 ng/mL for males and 7 ng/mL for females can be used as cut-off levels for normal prolactin reserve. Minimum peak prolactin responses of 18 ng/mL for males and 41 ng/mL for females to TRH stimulation can exclude hypoprolactinemia. However, larger population studies across different age groups and sexes are needed to better define normal basal prolactin levels and prolactin responses to the TRH stimulation test.

Alterations in Serum miR-126-3p Levels over Time: A Marker of Pituitary Insufficiency following Head Trauma.

INTRODUCTION: Traumatic brain injuries (TBIs) pose a high risk of pituitary insufficiency development in patients. We have previously reported alterations in miR-126-3p levels in sera from patients with TBI-induced pituitary deficiency. METHODS: To investigate why TBI-induced pituitary deficiency develops only in some patients and to reveal the relationship between miR-126-3p with hormone axes, we used mice that were epigenetically modified with miR-126-3p at the embryonic stage. These modified mice were subjected to mild TBI (mTBI) according to the Marmarou's weight-drop model at 2 months of age. The levels of miR-126-3p were assessed at 1 and 30 days in serum after mTBI. Changes in miR-126-3p levels after mTBI of wild-type and miR-126-3p* modified mouse lines validated our human results. Additionally, hypothalamus, pituitary, and adrenal tissues were analyzed for transcripts and associated serum hormone levels. RESULTS: We report that miR-126-3p directly affects hypothalamus-pituitary-adrenal (HPA) axis upregulation and ACTH secretion in the acute phase after mTBI. We also demonstrated that miR-126-3p suppresses Gnrh transcripts in the hypothalamus and pituitary, but this is not reflected in serum FSH/LH levels. The increase in ACTH levels in the acute phase may indicate that upregulation of miR-126-3p at the embryonic stage has a protective effect on the HPA axis after TBI. Notably, the most prominent transcriptional response is found in the adrenals, highlighting their role in the pathophysiology of TBI. CONCLUSION: Our study revealed the role of miR-126-3p in TBI and pituitary deficiency developing after TBI, and the obtained data will significantly contribute to elucidating the mechanism of pituitary deficiency development after TBI and development of new diagnostic and treatment strategies.

The diagnosis and prevalence of hypoprolactinemia in patients with panhypopituitarism and the effects on depression and sexual functions.

PURPOSE: We aimed to investigate the prevalence and the diagnostic criteria of hypoprolactinemia in patients with panhypopituitarism and the effects of hypoprolactinemia on depression and sexual functions. MATERIALS AND METHODS: Forty-eight patients with panhypopituitarism and 20 healthy volunteers were included. Basal hormone levels were measured and a TRH stimulation test was performed. For the evaluation of sexual functions, questionnaries of Female Sexual Functional Index (FSFI) for females and International Erectile Functional Index for males were performed to the subjects. Depressive symptoms were evaluated by Beck Depression Envontory score (BDI-II). RESULTS: The peak PRL response to TRH stimulation test at 5th percentile in the control group was 18.6 ng/ml in males and 41.6 ng/ml in females and accepted as the cut-offs for sufficient response of PRL. Prolactin was insufficient in 42(87.5%) patients. A basal PRL level of ≤ 5.7 ng/ml in males and 7.11 ng/ml in females was 100% specific in predicting an inadequate response to TRH stimulation test with 80% and 70% sensitivity respectively. A basal PRL level of ≥ 8.5 ng/dl in males was 100% specific and 76% sensitive, and in females a level of ≥ 15.2 ng/dl was 96% specific and 66% sensitive in predicting an adequate response to TRH. PRL deficient patients with panhypopituitarism had higher depression scores compared to the controls, lower sexual function scores in males. CONCLUSION: PRL deficiency is prevalent among individuals with panhypopituitarism, with the potential to result in elevated depression scores in both sexes and impaired sexual functions in males. A basal PRL level seems to be sufficient for the diagnosis of hypoprolactinemia in routine clinical practice.

The comprehensive evaluation of oral and fecal microbiota in patients with acromegaly.

PURPOSE: The alteration of the microbiota in the mouth and gut could potentially play a role in the pathogenesis of various diseases, and conversely, these diseases may have an influence on the composition of the gut microbiota. Acromegaly disease can potentially affect physiological processes in the mouth and gut. The present study was designed to investigate the relationship between acromegaly and the oral and gut microbiota, as data on this topic are scarce. METHODS: This was a multicenter, cross-sectional study. Our study included individuals diagnosed with acromegaly (who were treated and followed up, and also as an another group of patients with newly diagnosed acromegaly) and healthy participants. All three groups were assessed and compared based on age, sex, serum IGF-1, body mass index BMI as well as their stool and oral microbiota We collected demographic information from the patients, collected fecal and oral samples, performed DNA isolation followed by 16 S rRNA sequencing, and then performed bioinformatic analysis. We also analyzed the oral and fecal samples with respect to medical and surgical treatment and disease control status, specific treatments received for acromegaly, presence of comorbidities, hypopituitarism status, presence of intestinal polyps. RESULTS: One hundred and three patients with acromegaly, 15 newly diagnosed patients with acromegaly without comorbidities and 34 healthy controls were included in the study. The Firmicutes/Bacteroidetes ratio was significantly lower in patients with acromegaly who received treatment (medical and/or surgical) than in healthy controls. In addition, a significant difference was found in the fecal and oral microbiota of patients with acromegaly with disease control compared to healthy controls. Furthermore, a significant difference was found in the fecal and oral microbiota of patients with acromegaly without disease control. Nevertheless, it was not possible to establish a clear relationship between disease control status, the presence of intestinal polyps, the presence of type 2 diabetes and the composition of the oral and gut microbiota in acromegalic patients who had received different forms of treatment. CONCLUSION: Patients with acromegaly show distinct gut microbiota profiles, and it is evident that factors beyond the GH/IGF-1 axis play a role in shaping the gut microbiota of individuals with acromegaly.

Hypoprolactinemia. Does it matter? Redefining the hypopituitarism and return from a mumpsimus : "Absence of proof is not the proof of absence".

Prolactin (PRL) is secreted by the lactotroph cells in the anterior pituitary gland which is under inhibitory control of dopamine. The mature human PRL has more than 300 physiological actions including lactation, reproduction, homeostasis, neuroprotection, behavior, water and electrolyte balance, immunoregulation and embryonic and fetal development. PRL is involved in the growth and development of mammary gland, preparation of the breast for lactation in the postpartum period, synthesis of milk, and maintenance of milk secretion. Abnormalities in the synthesis and secretion of PRL may result in hyperprolactinemia or hypoprolactinemia. Although hyperprolactinemia has been extensively investigated in the literature, because of the subtle or unclearly defined symptoms, hypoprolactinemia is a less-known and neglected disorder. Failure of lactation is a well-known clinical manifestation of hypoprolactinemia. Recent studies reveal that hypoprolactinemia may have some effects beyond lactation such as increased risk for metabolic abnormalities including insulin resistance, abnormal lipid profile, obesity and sexual dysfunction. Very low level of PRL is suggested to be avoided in patients receiving dopamin agonist treatment to prevent unwanted effects of hypoprolactinemia. Another important point is that hypoprolactinemia is not included in the classification of hypopituitarism. Anterior pituitary failure is traditionally classified as isolated, partial and complete (panhypopituitarism) hypopituitarism regardless of prolactin level. Therefore, there are two kinds of panhypopituitarism: panhypopituitarism with normal or high PRL level and panhypopituitarism with low PRL level. In this review, we present two personal cases, discuss the diagnosis of hypoprolactinemia, hypoprolactinemia associated clinical picture and suggest to redefine the classification of hypopituitarism.

Hypothalamic-Pituitary Axis Function and Adrenal Insufficiency in COVID-19 Patients.

The outbreak of COVID-19 has affected more than half a billion people worldwide and caused more than 6 million deaths since 2019. The responsible virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the lungs, but it has multisystemic effects. It is well known that dysfunction of multiple endocrine organs may occur during or after COVID-19. Impairment of the hypothalamic-pituitary-adrenal (HPA) axis is of utmost importance as it may lead to death if went undiagnosed. SARS-CoV-2 may cause both primary and secondary adrenal insufficiencies (AIs). The clinical manifestations of AI are generally non-specific and might be attributed to the complications caused by the infection itself. The underlying pathogenetic mechanisms were explained by the immunogenic, vascular effects of the infection or the direct effects of the virus. The diagnosis of AI in critically ill patients with COVID-19 is not straightforward. There is lack of consensus on the cut-off values of basal serum cortisol levels and stimulation tests during the disease. Here we review the literature with a special regard on the evaluation of the HPA axis in patients with COVID-19. We conclude that the possibility of AI should always be kept in mind when dealing with patients with COVID-19, and repeated basal cortisol measurements and the ACTH stimulation test results could guide the clinician during the diagnostic process.

The Characterization of Sex Differences in Hypoglycemia-Induced Activation of HPA Axis on the Transcriptomic Level.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis using an insulin tolerance test (ITT) is a medical diagnostic procedure that is frequently used in humans to assess the HPA and growth-hormone (GH) axes. Whether sex differences exist in the response to ITT stress is unknown. Thus, investigations into the analysis of transcripts during activation of the HPA axis in response to hypoglycemia have revealed the underlying influences of sex in signaling pathways that stimulate the HPA axis. We assessed four time points of ITT application in Balb/c mice. After insulin injection, expression levels of 192 microRNAs and 41 mRNAs associated with the HPA, GH and hypothalamic-pituitary-gonadal (HPG) axes were determined by real-time RT-PCR in the hypothalamus, pituitary and adrenal tissues, as well as blood samples (Raw data accession: https://drive.google.com/drive/folders/10qI00NAtjxOepcNKxSJnQbJeBFa6zgHK?usp=sharing ). Although the ITT is commonly used as a gold standard for evaluating the HPA axis, we found completely different responses between males and females with respect to activation of the HPA axis. While activation of several transcripts in the hypothalamus and pituitary was observed after performing the ITT in males within 10 min, females responded via the pituitary and adrenal immediately and durably over 40 min. Additionally, we found that microRNA alterations precede mRNA responses in the HPA axis. Furthermore, robust changes in the levels of several transcripts including Avpr1b and Avpr2 observed at all time points strongly suggest that transcriptional control of these genes occurs mostly via differential signaling in pituitary and blood between males and females. Male and female HPA axis responses to ITT involve a number of sophisticated regulatory signaling pathways of miRNAs and mRNAs. Our results highlight the first robust markers in several layers of HPA, HPG and GH axis involved in ITT/hypoglycemia stress-induced dynamics.

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Acromegaly is associated with a distinct oral and gut microbiota.

PURPOSE: Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels. METHODS: Oral and fecal samples were collected from patients with newly diagnosed acromegaly without comorbidities and from healthy controls. The composition of the microbiota was analyzed. The general characteristics, oral and stool samples of the patients and healthy control subjects were compared. The changes in microbiota composition in both habitats, their correlations and associations with IGF-1 were statistically observed using machine learning models. RESULTS: Fifteen patients with newly diagnosed acromegaly without comorbidities and 15 healthy controls were included in the study. There was good agreement between fecal and oral microbiota in patients with acromegaly (p = 0.03). Oral microbiota diversity was significantly increased in patients with acromegaly (p < 0.01). In the fecal microbiota, the Firmicutes/Bacteroidetes ratio was lower in patients with acromegaly than in healthy controls (p = 0.011). Application of the transfer learned model to the pattern of microbiota allowed us to identify the patients with acromegaly with perfect accuracy. CONCLUSIONS: Patients with acromegaly have their own oral and gut microbiota even if they do not have acromegaly-related complications. Moreover, the excess IGF-1 levels could be correctly predicted based on the pattern of the microbiome.

Investigation of pituitary functions after acute coronavirus disease 2019.

Although coronavirus disease 2019 (COVID-19) mainly involves the lungs, it also affects many systems. The hypothalamic/pituitary axis is vulnerable to hypoxia, hypercoagulation, endothelial dysfunction and autoimmune changes induced by COVID-19 infection. Given that there is no extensive investigation on this issue, we investigated the pituitary functions three to seven months after acute COVID-19 infection. Forty-three patients after diagnosis of COVID-19 infection and 11 healthy volunteers were included in the study. In addition to the basal pituitary hormone levels, growth hormone (GH) and hypothalamo-pituitary adrenal (HPA) axes were evaluated by glucagon stimulation test (GST) and low-dose adrenocorticotropic hormone (ACTH) stimulation test, respectively. The peak cortisol responses to low-dose ACTH test were insufficient in seven (16.2%) patients. Twenty (46.5%) and four (9.3%) patients had inadequate GH and cortisol responses to GST, respectively. Serum insulin-like growth factor-1 (IGF-1) values were also lower than age and sex-matched references in four (9.3%) patients. The peak GH responses to GST were lower in the patient group when compared to the control group. Other abnormalities were mild thyroid-stimulating hormone elevation in four (9.3%) patients, mild prolactin elevation in two (4.6%) patients and central hypogonadism in four (9.3%) patients. Mean total testosterone values were lower in male patients when compared to male controls; however, the difference was not significant. These findings suggest that COVID-19 infection may affect pituitary functions, particularly the HPA and GH axes. These insufficiencies should be kept in mind in post-COVID follow-up. Long-term data are needed to determine whether these deficiencies are permanent or not.

The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI).

Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic-pituitary-adrenal (HPA) axis either by primary injury to the hypothalamic-hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic-pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (Lc3, Bcln1, P150, Ulk, and Atg5) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI.

Investigation of the Hypothalamo-pituitary-adrenal (HPA) axis: a contemporary synthesis.

The hypothalamo-pituitary-adrenal (HPA) axis is one of the main components of the stress system. Maintenance of normal physiological events, which include stress responses to internal or external stimuli in the body, depends on appropriate HPA axis function. In the case of severe cortisol deficiency, especially when there is a triggering factor, the patient may develop a life-threatening adrenal crisis which may result in death unless early diagnosis and adequate treatment are carried out. The maintenance of normal physiology and survival depend upon a sufficient level of cortisol in the circulation. Life-long glucocorticoid replacement therapy, in most cases meeting but not exceeding the need of the patient, is essential for normal life expectancy and maintenance of the quality of life. To enable this, the initial step should be the correct diagnosis of adrenal insufficiency (AI) which requires careful evaluation of the HPA axis, a highly dynamic endocrine system. The diagnosis of AI in patients with frank manifestations is not challenging. These patients do not need dynamic tests, and basal cortisol is usually enough to give a correct diagnosis. However, most cases of secondary adrenal insufficiency (SAI) take place in a gray zone when clinical manifestations are mild. In this situation, more complicated methods that can simulate the response of the HPA axis to a major stress are required. Numerous studies in the assessment of HPA axis have been published in the world literature. In this review, the tests used in the diagnosis of secondary AI or in the investigation of suspected HPA axis insufficiency are discussed in detail, and in the light of this, various recommendations are made.

Cushing Syndrome is Associated with Increased Stage N2 Sleep and Decreased SWS Partially Reversible After Treatment.

The aim of the present study was to evaluate the sleep parameters of patients with Cushing syndrome (CS) at the time of diagnosis and 12-months after treatment. Thirty four newly diagnosed patients with endogenous CS (17 with ACTH-secreting pituitary adenoma, 17 with adrenal CS) and 23 controls with similar age were included in the study. Two polysomnography (PSG) recordings were performed; one at the time of diagnosis and the other 12 months after resolution of hypercortisolemia. Control group had only baseline PSG. Based on the PSG findings, stage N2 sleep was found to be prolonged, stage N3 and REM sleep were shortened in patients with CS. Average heart rate and mean Apnea Hypopnea Index (AHI) score were higher in patients with CS than the control subjects. Sixteen (47.1%) patients with CS and 4 (17.4%) controls had obstructive sleep apnea (OSA; AHI ≥5). There were no significant differences in sleep parameters of patients according to the etiology of CS (adrenal vs. pituitary) patients. Following 12-months of treatment, a significant decrease in stage N2 sleep and a significant increase in stage N3 sleep were detected, but there was no change in terms of AHI. In conclusion, Cushing syndrome has disturbing effects on sleep structure and these effects are at least partially reversible after treatment. However, the increased risk of OSA was not reversed a year after treatment indicating the importance of early diagnosis and treatment of CS.

Gut microbiota in patients with newly diagnosed acromegaly: a pilot cross-sectional study.

PURPOSE: Microbiota has crucial biological importance for human well-being. Bidirectional interaction exists between microbiota and the host, and there have been no studies investigating this interaction in patients with acromegaly. We aimed to analyze the composition of microbiota in patients with newly diagnosed acromegaly. METHOD: Stool samples were obtained from the patients with newly diagnosed acromegaly in the Endocrinology Clinic of Erciyes University Medical School. The composition of microbiota was analyzed, and the results were compared to healthy volunteers matched to the patients in terms of age, gender and body mass index. RESULTS: Seven patients (three male, four female) with a mean age of 48 ± 17.6 years were included in the study. The stool analysis revealed a significantly lower bacterial diversity in the patients with acromegaly. Bacteroidetes phylum was predominating in the patient group, and Firmicutes/Bacteroidetes ratio was altered significantly. Bifidobacterium, Collinsella, Bacteroides, Butyricimonas, Clostridium, Oscillospira, and Dialister were predominating in the control group. CONCLUSION: The gut microbiota is significantly altered in patients with newly diagnosed acromegaly. Further prospective studies are needed to elucidate the causative relationship between acromegaly, colorectal pathologies, and microbial alterations.

Treatment of male hypogonadism partially reverses oxidative stress in patients with hypogonadism.

There are some studies regarding the presence/absence of oxidative stress in patients with hypogonadism with limited number of parameters. We aimed to investigate the effects of male hypogonadism and its treatment on oxidative stress parameters. Thirteen male patients with hypogonadotropic hypogonadism and 20 healthy subjects were involved in the study. Patients with hypogonadism were evaluated before and after six months of therapy. Markers indicating lipid and protein oxidation, total oxidant status (TOS) and total anti-oxidant capacity (TAC) were evaluated. Control subjects had significantly higher serum testosterone levels in comparison to hypogonadal patients before the treatment period. After the treatment of hypogonadism serum testosterone levels increased significantly. Myeloperoxidase (MPO) activity, levels of advanced oxidation protein products (AOPP), total lipid hydroperoxide and protein carbonyl compounds (PCC) were similar between the control subjects and the patient group before treatment. Pyrrolized protein and TOS were significantly lower and thiol levels and TAC were significantly higher in the control subjects than in patients with hypogonadism. Treatment of hypogonadism resulted in a significant decrease in AOPP levels while a significant increase was determined in TAC. No significant change was found in MPO activity. In conclusion, patients with hypogonadism have an increased status of oxidative stress which is at least partially improved after appropriate therapy.

Increased hip circumference in individuals with metabolic syndrome affects serum nesfatin-1 levels.

BACKGROUND: This case-control study was conducted to investigate the relationship between serum nesfatin-1 levels and nutritional status and blood parameters in patients diagnosed with metabolic syndrome. METHODS: Thirty patients (case) diagnosed with metabolic syndrome according to National Cholesterol Education Program-Adult Treatment Panel III criteria were included. Thirty healthy subjects (control) matched with patients with metabolic syndrome in terms of age, gender and body mass index were included. Three-day food consumption records were obtained. Anthropometric indices were measured and body composition was determined by bioelectrical impedance method. Biochemical parameters and serum nesfatin-1 levels were measured after 8 hours of fasting. RESULTS: Serum nesfatin-1 levels were 0.245±0.272 ng/mL in the case group and 0.528±0.987 ng/mL in the control group (p>0.05). There was a positive significant correlation between serum nesfatin-1 levels and body weight, waist and hip circumferences in the case group (p<0.05). Each unit increase in hip circumference measurement affects the levels of nesfatin by 0.014 times. In the control group, there was a positive significant correlation between body weight and serum nesfatin-1 levels (p<0.05). A significant correlation was detected between HbA1c and serum nesfatin-1 levels in the case group (p<0.05). A significant relationship was detected between dietary fibre intake and the serum nesfatin-1 levels in the case group (p<0.05). CONCLUSIONS: Anthropometric indices and blood parameters were correlated with serum nesfatin-1 levels in patients with metabolic syndrome. More clinical trials may be performed to establish the relationship between serum nesfatin-1 levels and nutritional status.

Neuroendocrine changes after aneurysmal subarachnoid haemorrhage.

INTRODUCTION: The prevalence of pituitary dysfunction is high following aneurysmal subarachnoid hemorrhage (aSAH) and when occurs it may contribute to residual symptoms of aSAH such as decreased cognition and quality of life. Hypopituitarism following aSAH may have non-specific, subtle symptoms and potentially serious consequences if remained undiagnosed. METHODS: We reviewed the literature on epidemiology, pathophysiology, diagnostic methods and management of neuroendocrine changes after aSAH as well as on the impact of pituitary dysfunction on outcome of the patient. RESULTS: The prevalence rates of pituitary dysfunction after aSAH varies greatly across studies due to different diagnostic methods, though growth hormone deficiency is generally the most frequently reported followed by adrenocorticotropic hormone, gonadotropin and thyroid stimulating hormone deficiencies. Pituitary deficiency tends to improve over time after aSAH but new onset deficiencies in chronic phase may also occur. There are no clinical parameters to predict the presence of hypopituitarism after aSAH. Age of the patient and surgical procedures are risk factors associated with development of hypopituitarism but the effect of pituitary dysfunction on outcome of the patient is not clear. Replacement of hypocortisolemia and hypothyroidism is essential but treatment of other hormonal insufficiencies should be individualized. CONCLUSIONS: Hypopituitarism following aSAH necessitates screening despite lack of gold standard evaluation tests and cut-off values in the follow up, because missed diagnosis may lead to untoward consequences.

Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease.

BACKGROUND: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. METHODS: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1ß, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. RESULTS: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45-5.17] vs. 4.2 [3.45-8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1-27.49] vs. 24.9 [16.23-39.4] pg/mL; p = 0.004) and IL-1ß (21.33 [15.8-26.4] vs. 26.78 [18.22-35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09-1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09-9.87]; p = 0.035). CONCLUSIONS: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

IS THERE A ROLE OF ACTH IN INCREASED CHOROIDAL THICKNESS IN CUSHING SYNDROME?

PURPOSE: To evaluate choroidal thickness (CT) in patients with Cushing syndrome (CS) with enhanced depth imaging optical coherence tomography. METHODS: Twenty-eight patients with CS and 38 healthy volunteers were enrolled in this observational cross-sectional study. Patients with newly diagnosed CS who have been admitted to Erciyes University Department of Endocrinology in 3 years time interval were compared with age- and sex-matched healthy volunteers. Choroidal thickness was measured at the fovea and 2 points nasal and 2 points temporal to the fovea with 500-µm intervals each. RESULTS: Choroidal thickness measurements were higher in patients with CS than in the control group at all examination points; however, the difference was found to be significant at the center of the fovea (367.8 ± 94.4 µm vs. 329 ± 90.5 µm) and 1,000 µm temporal to the fovea. Choroidal thickness measurements were significantly higher in adrenocorticotrophic hormone (ACTH)-dependent CS group than in the control group at all measurement points (CT at fovea 388.2 ± 92.4 µm vs. 329.1 ± 90.5 µm). All CT measurements were found to be correlated with ACTH levels. CONCLUSION: Cushing syndrome is associated with increased CT. The ACTH-dependent CS may increase CT more than ACTH-independent CS. This effect may be directly related to ACTH itself or increased plasma cortisol levels or both.