Kursad Unluhizarci

Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity?

OBJECTIVE Traumatic brain injury (TBI) is a devastating public health problem that may result in hypopituitarism. However, the mechanisms responsible for hypothalamic-pituitary dysfunction due to TBI are still unclear. Although the antibodies against neurons have been demonstrated in injured animal studies, investigations regarding the occurrence of antipituitary antibodies (APAs) in patients with TBI are lacking in the literature. In order to investigate whether autoimmune mechanisms could play a role in the pituitary dysfunction after TBI, we have planned this study aimed at investigating the presence of APA at the third year of TBI and association between the TBI-induced hypopituitarism and APA. PATIENTS AND DESIGN Twenty-nine (25 males and 4 females; age 36.5+/-2.3 years) patients who had completed a 3-year follow-up after TBI were included in the present study. APA and pituitary function were evaluated in all the patients 3 years after TBI; moreover, APAs were tested also in sera of 60 age-/sex-matched normal controls. The APAs were investigated by an indirect immunofluorescence method. Results APAs were detected in 13 out of the 29 TBI patients (44.8%), but in none of the normal controls. Pituitary dysfunction development ratio was significantly higher in APA-positive patients (46.2%) when compared with APA-negative ones (12.5%; P=0.04). There was a significant association between APA positivity and hypopituitarism due to TBI (odds ratio: 2.25, 95% confidence intervals 1.1-4.6). Moreover, there was a significant positive correlation (r=0.74, P=0.004) between APA titer ratio and peak GH response to GHRH+GH related peptide (GHRP)-6 test, suggesting that high APA titers were associated with low GH response to GHRH+GHRP-6 test. CONCLUSIONS This study shows for the first time the presence of the APA in TBI patients 3 years after head trauma. Moreover, present investigation indicates preliminary evidence that APA may be associated with the development of TBI-induced pituitary dysfunction, thus suggesting that autoimmunity may contribute in the development of TBI-induced hypopituitarism. The presence of the association between APA and TBI-induced hypopituitarism may provide a new point of view in this field and promote further clinical and experimental studies.

The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a form of functional ovarian hyperandrogenism and affects approximately 5‐10% of women of reproductive age. Insulin resistance and hyperinsulinaemia appear to be almost universal feature of the polycystic ovary syndrome. Abnormal regulation of cytochrome P450c17α causes the exaggerated secretion of ovarian androgens in PCOS. The aim of the present study was to determine whether reduction of insulin levels by metformin would attenuate FSH, LH, 17‐Hydroxyprogesterone (17‐OHP) and androstenedione hyperresponsiveness to buserelin testing in PCOS women.

Three years prospective investigation of anterior pituitary function after traumatic brain injury: a pilot study

Objective   It has been recently demonstrated that traumatic brain injury (TBI)‐mediated hypopituitarism could be more frequent than previously known. However, most of the previous data were obtained from retrospective studies, and the natural history of the hypopituitarism due to TBI is still unclear. So far no study has been reported in which the pituitary function of the same patients has been investigated more than 1 year after TBI. Therefore, we report the results of 3 years prospective follow‐up of anterior pituitary function in patients with mild, moderate and severe TBI.

Kickboxing sport as a new cause of traumatic brain injury‐mediated hypopituitarism

Objective  Traumatic brain injury, which is a frequent and a worldwide important public health problem, may result in pituitary dysfunction. Concussion, a common type of lesion after traumatic brain injury, is an injury associated with sports including boxing and kickboxing. Kickboxing is one of the most popular martial arts and approximately 1‐million people around the world participate in kickboxing sport. Head is the most common site of injury in amateur and professional kickboxers. Pituitary consequences of chronic repetitive head trauma in kickboxing have not been investigated until now. Therefore, the present study was designed to investigate the pituitary function in both retired and active amateur kickboxers.

Pregnancy and pituitary disorders

Major hormonal changes emerge during pregnancy. The pituitary gland is one of the most affected organs with altered anatomy and physiology. The pituitary gland is enlarged as a result of lactotroph hyperplasia. Due to physiological changes in the pituitary and target hormone levels, binding globulins, and placental hormones, hormonal evaluation becomes more complex in pregnant women. As a consequence of physiological hormonal changes, the evaluation of pituitary functions in pregnant women is quite different from that done in the prepregnant state. Pituitary adenomas may cause problems by their hormone secretion that affects the mother and the fetus besides causing an increased risk of tumor growth. Furthermore, diagnosis, course, and treatment of pituitary diseases point out differences. The changes in anatomy and physiology of the pituitary gland during pregnancy are reviewed. Pituitary disorders namely Cushings disease; acromegaly; prolactinoma; TSH-secreting, gonadotropin-producing, and clinically nonfunctioning adenomas; craniopharyngioma; and Sheehans syndrome, which is one of the most common causes of hypopituitarism, lymphocytic hypophysitis, and hypopituitarism, in relation to pregnancy are discussed. Being aware of all this information will prevent any serious problems which mother and child will be exposed to.

Pituitary function in subjects with mild traumatic brain injury: a review of literature and proposal of a screening strategy

Traumatic brain injury (TBI) is an important public health problem all over the world. The level of consciousness of the patients and the severity of the brain injury is commonly evaluated by the Glascow Coma Scale as mild, moderate and severe TBI. When we consider the high frequency of mild TBI (MTBI) among the all TBI patients the burden of the pituitary dysfunction problem in this group could not be ignored. However, one of the most important and still unresolved questions is which patients with MTBI should be screened for hypopituitarism? Another type of head trauma which could be considered as the subgroup of MTBI is sports related chronic repetitive head trauma. Therefore, in this review we will discuss the frequency, characteristics and current management of pituitary dysfunction in patients with MTBI including the subjects exposed to sports related chronic mild head trauma.

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 μg/kg) + GHRP-6 (1 μg/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 μg/l, respectively (p<0.05). Peak GH levels in 5 (45%) boxers were found to be lower than 10 μg/l and considered as severe GH deficient. In the control group, mean IGF-I 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.

Investigation of antihypothalamus and antipituitary antibodies in amateur boxers: is chronic repetitive head trauma-induced pituitary dysfunction associated with autoimmunity?

OBJECTIVE Current data clearly demonstrate that sports-related chronic repetitive head trauma due to boxing might result in hypopituitarism. However, the mechanism of sports-related traumatic brain injury-induced pituitary dysfunction is still unclear. In order to understand whether autoimmune mechanisms could play a role in the pituitary dysfunction due to sports-related head trauma, we investigated the presence of antipituitary antibodies (APAs) and antihypothalamus antibodies (AHAs) in amateur boxers. PATIENTS AND DESIGN Sixty-one actively competing (n=44) or retired (n=17) male boxers (mean age, 26 years; range, 17-53) who had been evaluated regarding pituitary functions previously were included in the study. In all boxers and in 60 age/sex-similar normal controls, AHAs and APAs were investigated by an indirect immunofluorescence method. RESULTS AHAs were detected in 13 of 61 boxers (21.3%), and APAs were detected in 14 of 61 boxers (22.9%), but in none of the normal controls. Pituitary dysfunction was significantly higher in AHA-positive boxers (46.2%) than in AHA-negative boxers (10.4%) (P=0.003). There was a significant association between AHA positivity and hypopituitarism due to boxing (odds ratio: 7.37, 95% confidence interval 1.8-30.8). There was no significant association between APA positivity and hypopituitarism. CONCLUSIONS This study demonstrates for the first time the presence of AHAs and APAs in boxers who were exposed to sports-related head trauma. Moreover, the present investigation provides preliminary evidence that AHAs are associated with the development of pituitary dysfunction in boxers, thus suggesting that autoimmunity may have a role in the pathogenesis.

Anti-hypothalamus and anti-pituitary antibodies may contribute to perpetuate the hypopituitarism in patients with Sheehan's syndrome.

OBJECTIVE While anti-pituitary antibodies (APAs) were detected in some patients with Sheehans syndrome (SS) suggesting an autoimmune pituitary involvement in the development of their hypopituitarism, hypothalamic cell anti-hypothalamus antibodies (AHAs) have not been investigated so far. DESIGN The aim of this study was to evaluate the presence of AHA and APA in SS patients to verify whether an autoimmune hypothalamic-pituitary process can contribute to their late hypopituitarism. METHODS Twenty women with SS with a duration of disease ranging from 3 to 40 years (median 25.5 years) were enrolled into the study. Out of 20 patients, 12 (60%) had panhypopituitarism and the others had partial hypopituitarism well corrected with appropriate replacement therapy. None of them had clinical central diabetes insipidus. AHA and APA were investigated by immunofluorescence method in all patients. In addition, a four-layer immunofluorescence method was used to verify whether AHA immunostained vasopressin-secreting cells (AVP-c) or not. RESULTS AHAs were found in 8 out of 20 (40%) and APAs in 7 out of 20 (35%) patients with titers ranging from 1:32 to 1:128 and 1:16 to 1:32 respectively; however, in none of these positive patients AHA immunostained vasopressin cells. None of controls resulted positive for both antibodies. CONCLUSIONS Patients with SS, even many years after the onset of SS, can show antibodies to pituitary and/or hypothalamic but not AVP-secreting cells. Antibodies to unknown hypothalamic cells (releasing factor-secreting cells) other than APAs suggest that an autoimmune process involving both the hypothalamus and pituitary gland may contribute to late pituitary dysfunction in SS patients.

High risk of pituitary dysfunction due to aneurysmal subarachnoid haemorrhage: a prospective investigation of anterior pituitary function in the acute phase and 12 months after the event

Objective  Recent investigations have provided evidence for a high prevalence of pituitary dysfunction in patients with subarachnoid haemorrhage (SAH). However, apart from one study, all of the previous data were obtained from retrospective studies. To our knowledge there is no previously reported study in which pituitary function was investigated in the same patients immediately after SAH and 12 months later. The aim of this study was to understand the prevalence and progression of anterior pituitary hormone deficiencies both in the acute phase of SAH and 12 months after the event.