Hypothalamic-pituitary Function Research Articles

Research Progress in the Pathogenesis of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrine disorders. Most pathophysiological changes of PCOS begin in the peripubertal phase, and these pathophysiological changes will continuously affect women's health in the later stages of their lives. The pathogenic mechanisms of PCOS remain unclear, involving key aspects such as the regulation of hypothalamic-pituitary function, ovarian cellular functions, androgen levels, and insulin resistance. Herein, we summarized the latest findings on the pathogenesis of PCOS from the perspectives of the genetic background, intrauterine development, neuroendocrine function, inflammatory factors, gut microbiome, and environmental factors. This review will help provide new ideas for a deeper understanding of the disease, as well as its clinical diagnosis and treatment.

CP-11. BODY MASS INDEX INCREASE FOLLOWING CHILDHOOD CRANIOPHARYNGIOMA SURGERY IS MOST SEVERE IN THE FIRST THREE MONTHS; TIME TO ACT!

Abstract BACKGROUND Centralization of care for childhood craniopharyngioma (cCP) in the Netherlands (June 2018), including the involvement of a multidisciplinary team, has resulted in a decreased prevalence of hypothalamic obesity. Unfortunately, in certain patients, increasing body mass index standard deviation scores (BMI SDS) are still encountered after tumor resection. The aim of this analysis is to identify timing of BMI change, incidence/prevalence and predictive factors for BMI changes enabling early preventive strategies. METHODS A retrospective cohort study was performed of all newly diagnosed cCP patients since centralization of care in the Netherlands (June 2018). Data on anthropometrics, radiology, tumor treatment (surgery, radiotherapy, interferon and tocilizumab), hypothalamic-pituitary function, medication and visual function, were collected. Uni- and multivariate analyses were done with the ‘mean’ change in BMI SDS at 3, 6 and 12 months after resection as primary endpoint. Body mass index trends were assessed as secondary outcome. RESULTS Of 34 patients, median age 8.93 (range 0.79-17.36), mean ∆BMI SDS was most pronounced at 3 months (+1.09 SDS (SD 1.17), p<0.01), followed by a further mean increase of +0.25 SDS from 3 to 6 months (SD 0.50, p=0.01). In 17 patients, BMI SDS increased with ≥1.0 SDS in the first 3 months after resection (50%). A Muller grade 2 at diagnosis was associated with ∆BMI SDS at 3 months. Children with the highest BMI at diagnosis had the highest BMI at three months, but not the highest ∆BMI SDS. CONCLUSION Changes in BMI SDS ≥1.0 are observed in half of cCP patients following surgical resection despite expert multidisciplinary care, with most pronounced BMI changes during the first 3 months. These observations are a plea for more early interventions to prevent (morbid) hypothalamic obesity.

Modulatory Effects of Ethinyl Estradiol Plus Drospirenone Contraceptive Pill on Spontaneous and GnRH-Induced LH Secretion

Background: Combined oral contraceptives (COCs) work mostly by preventing the pre-ovulatory gonadotropin surge, but the action of COCs on spontaneous episodic and GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) release has been poorly evaluated. Oral contraceptives are known to act on the spontaneous hypothalamic–pituitary functions reducing both GnRH and gonadotropin release and blocking ovulation. Aim: To evaluate spontaneous and GnRH-induced LH release during both phases of the menstrual cycle or under the use of the contraceptive pill. Methods: A group of 12 women, subdivided into two groups, volunteered for the study. Group A (n = 6, controls) received no treatments, while Group B (n = 6) received a 21 + 7 combination of ethinyl-estradiol (EE) 30 µg + drospirenone (DRSP) 3 mg. Both groups were evaluated twice: Group A during follicular and luteal phases, Group B during pill assumption and during the suspension interval, performing a pulsatility test, GnRH stimulation test, and hormonal parameters evaluation. Spontaneous and GnRH-induced secretory pulses were evaluated, as well as the instantaneous secretory rate (ISR). Results: COC treatment lowered LH and FSH (follicle stimulating hormone) levels significantly if compared to the follicular phase of spontaneous cycles. During the suspension interval, hormone levels rapidly rose and became comparable to those of the follicular phase of the control group. The LH pulse frequency under COC administration during the suspension interval was similar to that observed during the follicular phase (2.6 ± 0.3 pulses/180 min and 2.3 ± 0.2 pulses/180 min, respectively). The GnRH-induced LH peaks were greater in amplitude and duration than those observed after ISR computation in both groups. The GnRH-induced LH release during the luteal phase of the control subjects was higher than in the follicular phase (51.2 ± 12.3 mIU/mL and 14.9 ± 1.8 mIU/mL, respectively). Conversely, subjects under COC showed a GnRH-induced LH response similar during COC and during the suspension interval. Conclusions: Our data support that the EE + DRSP preparation acts on both spontaneous pulsatile release and GnRH-induced LH release during the withdrawal period of the treatment, and that after 5–7 days from the treatment suspension, steroidal secretion from the ovary is resumed, such as that of androgens. This suggests that in hyperandrogenic patients, a suspension interval as short as 4 days might be clinically better.

Empty Sella Syndrome, Case Report and Literature Review

Rarely has empty sella syndrome been documented in children, and radiographic imaging frequently identifies subarachnoid herniation through the sellar diaphragm and pituitary gland compression. In this correspondence, we report the discovery of an empty sella turcica on a brain magnetic resonance imaging (MRI) of a short 5-year-old kid. He identified hypopituitarism in form growth hormone deficiency and central adrenocortical insufficiency but normal thyroid function `during neuroendocrine examination of hypothalamic-pituitary function. Before beginning growth hormone therapy, this knowledge is essential to prevent the dangerous effects of an adrenal crisis. This matter was brought to light.

Hypothalamic–pituitary–gonadal function, pubertal development and fertility outcomes in male and female medulloblastoma survivors: a single centre experience

Hypothalamic–pituitary–gonadal function, pubertal development and fertility outcomes in male and female medulloblastoma survivors: a single centre experience

Assessing hypothalamic pituitary gonadal function in reproductive disorders.

Reproductive conditions secondary to disorders of the hypothalamic-pituitary-gonadal (HPG) axis are common and are associated with important health implications and considerable psychosocial impact. Basal and dynamic tests enable interrogation of individual components of the HPG axis, facilitating diagnosis and understanding of the pathophysiology of reproductive disorders. Onset of puberty is controlled by hypothalamic gonadotrophin-releasing hormone (GnRH) neuronal function. To date, a dynamic test of hypothalamic function is not yet available. Therefore, accurate differentiation of pubertal disorders such as constitutional delay of growth and puberty (CDGP) and congenital hypogonadotrophic hypogonadism (CHH) as causes of delayed puberty is challenging due to similar clinical presentations and hormonal profiles. Likewise, although the two commonest reproductive disorders in women, polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhoea (FHA) have disparate hypothalamic function, oligo/amenorrhoea frequently poses a diagnostic conundrum owing to the overlap in the criteria used to define both conditions. This review aims to describe pubertal and reproductive disorders secondary to pathologies affecting the HPG axis. Challenges encountered in clinical practice in differentiating pubertal and reproductive conditions are reviewed in conjunction with the utility of baseline and dynamic endocrine tests to interrogate specific components of the HPG axis. We also highlight putative hypothalamic, pituitary, and gonadal markers in development that could improve the diagnosis of patients presenting with disorders of puberty or reproduction.

Characteristics and factors influencing hypothalamic pituitary dysfunction in patients with craniopharyngioma.

Craniopharyngioma is a benign tumor originating from the sellar region. Damages in this area caused by the tumor itself, surgery, or radiotherapy may result in severe hypothalamic-pituitary dysfunction (HPD) and eventually lead to a significant impairment in the long-term quality of life of patients. This study aimed to investigate the characteristics of HPD in patients with adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) and to identify the factors affecting HPD after surgery. In this single-center retrospective study, a total of 742 patients with craniopharyngioma were included. The neuroendocrine function of these patients before and after surgery was investigated. The differences in hypothalamic-pituitary function between the ACP and PCP groups were compared. The factors influencing the aggravation of HPD after surgery were identified. The median follow-up after surgery was 15 months. Before surgery, the proportion of patients with diabetes insipidus (DI) and hyperprolactinemia in the PCP group was significantly higher than that in the ACP group (P<0.01), and the proportion of patients with adrenocortical hypofunction in the PCP group was significantly lower than that in the ACP group (P=0.03). Most cases of ACP originated in the sellar region, while most cases of PCP originated in the suprasellar region (P<0.01). More patients experienced adenohypophyseal hypofunction, DI, and hypothalamic obesity at postoperative follow-up than at onset in both the ACP and PCP groups (both P<0.01), with a higher increase observed in the ACP group (P<0.01). Older age at CP onset, tumor recurrence or progression, and ACP type were risk factors for postoperative aggravation of HPD in CP patients. Surgical treatment significantly aggravated HPD in both the ACP and PCP groups, but the specific characteristics and risk factors leading to aggravation were different between the two groups.

Subacute high-refined carbohydrate diet leads to abnormal reproductive control of the hypothalamic-pituitary axis in female rats

We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHβ+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHβ+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.

IFN-γ differential expression in the hypothalamus-pituitary-ovary axis of thyroidectomized rats

IFN-γ is critical for both thyroid and ovarian function, while thyroxine, secreted from the thyroid gland, regulates the ovarian function via the hypothalamus-pituitary -ovary axis. However, the effect of thyroxine on INF-γ involved in the regulation of hypothalamic pituitary ovarian axis ovarian function is hitherto unknown. Therefore, we set up three groups including a sham-operated group, an experimental thyroidectomized group, and an experimental thyroidectomized group treated with T4 to reveal the IFN-γ expression levels in the in the hypothalamus, pituitary gland, and ovary by immunohistochemical staining, RT-PCR, and Western blotting. IFN-γ-like immunoreactive-positive substances were visualized in the hypothalamus, pituitary gland, and ovary, which were located mainly in the cytoplasm of the hypothalamic neurons anterior pituitary cells, luteal cells, and theca cells in the ovary of hypothyroidism rats, respectively. RT-PCR and Western blotting showed that the rats in the experimental thyroidectomized group treated with T4 had significantly elevated expression of IFN-γ at both the mRNA and protein levels. Thyroxine affects the expression of IFN-γ in the thalamus-pituitary-ovarian axis, which may influence the secretion of IFN-γ to regulate ovarian function during hypothyroidism. This work highlights the potential effect of thyroxine on the involvement of INF-γ in the modulation of the ovarian function in the hypothalamic-pituitary-ovarian axis.

Endocrine Disorders in Children with Brain Tumors: At Diagnosis, after Surgery, Radiotherapy and Chemotherapy.

Brain tumors are the second most frequent type of all pediatric malignancies. Depending on their localization, patients with brain tumors may present neurological or ophthalmological symptoms, but also weight anomalies and endocrine disorders ranging from growth hormone deficiency, anomalies of puberty, diabetes insipidus to panhypopituitarism. Immediately at diagnosis, all patients with brain tumors require a complete assessment of the hypothalamic-pituitary function in order to address eventual endocrine disorders. Moreover, children and adolescents undergoing brain surgery must receive peri- and postoperative hydrocortisone stress therapy. Post-operative disorders of water homeostasis are frequent, ranging from transient diabetes insipidus, as well as syndrome of inappropriate antidiuretic hormone secretion to persistent diabetes insipidus. Late endocrine disorders may result from surgery near or within the hypothalamic-pituitary region. Pituitary deficits are frequent after radiotherapy, especially growth hormone deficiency. Thyroid nodules or secondary thyroid cancers may arise years after radiotherapy. Gonadal dysfunction is frequent after chemotherapy especially with alkylating agents. Early detection and treatment of specific endocrine disorders at diagnosis, perioperatively, and during long-term follow-up result in improved general and metabolic health and quality of life.

Functional hypothalamic amenorrhea: Impact on bone and neuropsychiatric outcomes.

Functional hypothalamic amenorrhea is a state of reversible hypogonadism common in adolescents and young women that can be triggered by energy deficit or emotional stress or a combination of these factors. Energy deficit may be a consequence of (i) reduced caloric intake, as seen in patients with eating disorders, such as anorexia nervosa, or (ii) excessive exercise, when caloric intake is insufficient to meet the needs of energy expenditure. In these conditions of energy deficit, suppression of the hypothalamic secretion of gonadotrophin-releasing hormone (with resulting hypoestrogenism) as well as other changes in hypothalamic-pituitary function may occur as an adaptive response to limited energy availability. Many of these adaptive changes, however, are deleterious to reproductive, skeletal, and neuropsychiatric health. Particularly, normoestrogenemia is critical for normal bone accrual during adolescence, and hypoestrogenemia during this time may lead to deficits in peak bone mass acquisition with longstanding effects on skeletal health. The adolescent years are also a time of neurological changes that impact cognitive function, and anxiety and depression present more frequently during this time. Normal estrogen status is essential for optimal cognitive function (particularly verbal memory and executive function) and may impact emotion and mood. Early recognition of women at high risk of developing hypothalamic amenorrhea and its timely management with a multidisciplinary team are crucial to prevent the severe and long-term effects of this condition.

Integrity of hypothalamic-pituitary-testicular axis in exceptional longevity.

Hypothalamic integrity increasingly is being recognized as a marker of healthy longevity in rodent models. Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic–pituitary‐testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90–106 years. We found that 94% of men exhibited preserved hypothalamic–pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging‐related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic–pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.

P-654 Arsenic Exposure During Puberty Significantly Affected Sex Maturation and Reproductive System Development of Female SD Rats

Abstract Study question Can sex maturation and reproductive hormones affected by Arsenic exposure during puberty in female rats. Summary answer Pubertal AS exposure at environmental-relevant levels significantly enhanced sexual precocity but reduced reproductive functions and capacity by adult. What is known already Arsenic (AS) is widely distributed in the earth’s surface and its toxic effects have been known for a long time. About 130 million people, mainly in the developing countries, are overly exposed to the chemical of AS through the drinking water. AS contaminations in drinking water (10 - 50 ug/L) were associated with human reproductive defects, such as spontaneous abortion, stillbirth, lower birth weight, and smaller birth size. As exposures in adult rats were have been related to inhibition of steroidogenic enzymes and decreased estradiol levels. Study design, size, duration Forty female rats of 21 days of age were exposed to AS at different doses (0, 0.02, 0.2, or 2 mg/L, n = 10/group) through drinking water for about 44 days until the rats reached adulthood. In a second experiment, 24 rats were exposed to AS with a similar protocol and doses, in order to examine the effects of AS on the pregnancy and reproductive capacity. Participants/materials, setting, methods Sex maturation day and estrus cycles were recorded. When rats reached adult, serum pituitary and ovarian sex hormones were assayed. Ovarian steroidogenic pathway and its regulatory signaling molecules were analyzed by qPCR and/or Western blots. The parameters compared include Mating Index, Days with Copulatory Vaginal Sperm Plug, Pregnancy Rate, Fertility Index, Weight of Pups, Litter Size and Ratio of Male/Female Pups. Main results and the role of chance AS exposure significantly reduced the weights of both ovary and uterus without affecting the overall body weight. AS promoted sexual precocity, disturbed estrus cycles, significantly reduced the numbers of primordial follicles while increased atretic follicles. AS also reduced serum levels of estradiol, progesterone and testosterone but increased the LH and FSH levels in dose-dependent manners. In addition, AS selectively down-regulated steroidogenic-related proteins FSHR, STAR, CYP17A1, HSD3B1 and CYP19A1 and signaling molecules PKA-ERK/JNK-cJUN, without affecting AKT and CREB. As about reproductive capacity, AS significantly reduced pup weights, litter size and the number of male pups. Limitations, reasons for caution Future works are need to examined how AS may affect the hypothalamic-pituitary functions during the prepubertal period. Further studies are required to address how AS may affect the environment of female reproductive tract and the egg qualities. Wider implications of the findings AS exposure at environmental-relevant level during puberty significantly affected female reproductive system development. Since the concentrations tested overlaps the environmental levels recorded, the results may have important public health significance. Trial registration number NA

Syndrome of inappropriate secretion of antidiuretic hormone as an initial sign of primary central nervous system lymphomas in the hypothalamus.

Primary central nervous system lymphoma (PCNSL) rarely originates in the hypothalamus. Hypothalamic PCNSL can present with various symptoms specific to dysfunction of the hypothalamus, including consciousness disturbance, cognitive impairment, hypopituitarism, and diabetes insipidus (DI). However, it remains unclear whether syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can present as an initial sign of hypothalamic PCNSL. Ninety-nine patients with PCNSL were diagnosed between January 2006 and December 2020 at our institutes. The initial symptoms and signs, hypothalamic-pituitary functions, serum sodium (Na) value, Karnofsky Performance Status (KPS) score on admission, and duration from onset to diagnosis were retrospectively investigated from the medical charts. Eight and 91 patients had hypothalamic PCNSL (hypothalamic group) and PCNSL located in other regions (control group), respectively. Patients' pathological diagnoses were diffuse large B-cell lymphoma (97 patients) and intravascular lymphoma (two patients). Six patients presented with hyponatremia derived from SIADH or suspected SIADH, and one presented with DI. Statistically significant differences between the hypothalamic and control groups were detected only in the preoperative serum Na values and KPS scores. SIADH can be an initial presentation of hypothalamic PCNSL. Early detection of hypothalamic PCNSL from SIADH may lead to proper management and improved prognosis.

Adverse childhood experiences and implications of perceived stress, anxiety and cortisol among women in Pakistan: a cross-sectional study

ObjectivesAdverse childhood experiences (ACEs) are linked to poor maternal mental health. The goal of this study is to examine the associations between ACEs and multiple manifestations of stress (including perceived...

Reduced pituitary volume with relative T1 shortening correlates with behavior in Prader-Willi syndrome

• Reduced pituitary volumes are found in PWS patients. • Relative T 1 signal intensity is reduced in the pituitary gland in PWS patients. • Neuroendocrine-behavior correlates are potential intrinsic biomarkers for PWS. Prader-Willi syndrome is a complex endocrinological and developmental disorder characterized by hyperphagic, autistic, and obsessive behaviors, which have been considered to primarily originate from hypothalamus-pituitary axis system alterations in the brain. While the pituitary gland has been demonstrated to contribute to behavioral phenotypes associated with neuropeptide, e.g., arginine-vasopressin, the relevant alterations in Prader-Willi syndrome remain unknown. This study aimed to investigate developmental abnormalities in the pituitary gland structures and determine whether the structural abnormalities are associated with behavioral characteristics in Prader-Willi syndrome. In total, 21 Japanese individuals with Prader-Willi syndrome and 31 healthy controls with typical development were included. Compared with the control group, the Prader-Willi syndrome group showed reduced anterior and posterior pituitary volume ratios per total intracranial volume with relative T 1 shortening in an age-associated manner. Moreover, altered volume ratios and signal intensities were negatively correlated with hyperphagia and autistic questionnaire scores but positively correlated with obsessive scores. The findings suggest that structural and functional alterations, in part due to altered hypothalamus-pituitary function, may contribute to the behavior in Prader-Willi syndrome. The imaging-behavior correlates and in vivo neurochemical visualization of the pituitary gland might be potential intrinsic biomarkers for behavioral phenotypes in Prader-Willi syndrome and other neurodevelopmental disorders.

Long-term corticosteroid use, adrenal insufficiency and the need for steroid-sparing treatment in adult severe asthma.

Secondary adrenal insufficiency (AI) occurs as the result of any process that disrupts normal hypothalamic and/or anterior pituitary function and causes a decrease in the secretion of steroid hormones from the adrenal cortex. The most common cause of secondary AI is exogenous corticosteroid therapy administered at supraphysiologic dosages for ≥ 1 month. AI caused by oral corticosteroids (OCS) is not well‐recognized or commonly diagnosed but is often associated with reduced well‐being and can be life‐threatening in the event of an adrenal crisis. Corticosteroid use is common in respiratory diseases, and asthma is a representative condition that illustrates the potential challenges and opportunities related to corticosteroid‐sparing therapies. For individuals with severe asthma (approximately 5%–10% of all cases), reduction or elimination of maintenance OCS without loss of control can now be accomplished with biologic therapies targeting inflammatory mediators. However, the optimal strategy to ensure early identification and treatment of AI and safe OCS withdrawal in routine clinical practice remains to be defined. Many studies with biologics have involved short evaluation periods and small sample sizes; in addition, cautious approaches to OCS tapering in studies with a placebo arm, coupled with inconsistent monitoring for AI, have contributed to the lack of clarity. If the goal is to greatly reduce and, where possible, eliminate long‐term OCS use in severe asthma through the increasing adoption of biologic treatments, there is an urgent need for clinical trials that address both the speed of OCS withdrawal and how to monitor for AI.

Development of a Predictive Enrichment Marker for the Oral GH Secretagogue LUM-201 in Pediatric Growth Hormone Deficiency.

ContextWe hypothesize, based on the degree of residual hypothalamic-pituitary function, that some, but not all, children with growth hormone deficiency (GHD) may have beneficial growth responses to the orally administered growth hormone (GH) secretagogue LUM-201.ObjectiveTo determine if pretreatment testing can identify predictive enrichment markers (PEM) for subjects with adequate residual function who are responsive to LUM-201.MethodsWe performed an analysis of a completed, randomized, placebo-controlled trial of LUM-201, a GH secretagogue receptor agonist, in which all randomized subjects had pretreatment testing. This international multicenter study conducted in pediatric endocrinology clinics included 68 naïve-to-treatment, prepubertal children with established diagnoses of GHD. Outcome measures included the sensitivity, specificity, and predictive accuracy of potential markers to predict 6-month growth responses to oral LUM-201 and daily rhGH.ResultsTwo PEM were identified for use in defining PEM-positive status: (1) baseline insulin-like growth factor I (IGF-I) concentration >30 ng/mL and (2) peak GH response of ≥5 ng/mL upon administration of single-dose LUM-201. PEM-positive status enriches a population for better growth responses to LUM-201. PEM-negative status enriches a population for better growth responses to rhGH.ConclusionCombined, the peak GH response to single-dose LUM-201 and the baseline IGF-I concentration are effective PEMs for 6-month growth responses to LUM-201 and rhGH in prepubertal children with GHD.

Effect of Tramadol Abuse on Male Fertility

Background: addiction is still an increasingly social and health issue worldwide, despite all attempts to overcome it. Analgesics are of the most prevalent substances that are abused. In Egypt and the Middle East, tramadol abuse is highly increasing. This can be correlated to its inexpensive cost, large availability, accessibility and illegal trafficking. Tramadol is a centrally-acting synthetic opioid analgesic that is commonly used to treat different intensities of pain varying from mild to extreme pain conditions. Prolonged administration of tramadol can result in abnormalities of the hypothalamic-pituitary function and decrease in testosterone production. Many experimental studies were done and showed that tramadol affects the level of luteinizing hormone, follicular stimulating hormone, testosterone, estradiol, and prolactin. It also affects sperm quality and motility. We aimed in this review: is to delineate these issues. Conclusion: There is a significant correlation between tramadol abuse and impaired gonadal and male sex hormone and sperm quality parameters.

Hypothalamic-Pituitary Axis Dysfunction after Whole Brain Radiotherapy - A Cohort Study.

Hypothalamic-pituitary (HT-P) dysfunction is one of the most common endocrine late effects following cranial radiotherapy. However, there are currently no specific data describing this complication in adult-onset cancer patients after whole brain radiotherapy (WBRT). The present cohort study aims to establish the prevalence of HT-P axis dysfunction in this group of patients. Twenty-six cancer patients previously treated with WBRT (median follow-up=20.5 months) received standardized endocrine check-up focusing on HT-P function. In 50% of the patients, impaired hypothalamic-pituitary function was detected during follow-up. While functional loss of a single hormonal axis was evident in 34.6% of patients, 7.7% showed an impairment of multiple endocrine axes, and one patient developed adrenocorticotropic hormone deficiency. Hypothalamic-pituitary dysfunction did not directly correlate with the applied WBRT total doses. In our cohort, hypothalamic-pituitary dysfunction appeared to be common after WBRT and was diagnosed as early as 6 months following radiation. This finding highlights the need for routine endocrine follow-up even in patients with limited life expectancy.