The differential sensitivity of the hypothalamic-hypophysial-ovarian axis to 5-hydroxytryptophan alters the secretion of estradiol.

Serotonin [5-hydroxytryptamine (5-HT)] modulates ovarian function. The precursor of 5-HT, 5-hydroxytryptophan (5-HTP), has been used to treat depression. However, the effects of 5-HTP on ovarian and reproductive physiology remain unknown. In this research, we analysed the impact of 5-HTP on the monoaminergic system and its interactions with the reproductive axis and ovarian estradiol secretion when administered by distinct routes. Female rats 30 days of age were injected with 5-HTP i.p. (100 mg/kg), into the ovarian bursa (1.5 µg/40 µL) or into the median raphe nucleus (20 µg/2.5 µL) and were killed 60 or 120 min after injection. As controls, we used rats of the same age injected with vehicle (0.9% NaCl). Monoamine, gonadotrophin and steroid ovarian hormone concentrations were measured. The injection of 5-HTP either i.p. or directly into the ovarian bursa increased the concentrations of 5-HT and the metabolite 5-hydroxyindole-3-acetic acid in the ovary. For both routes of administration, the serum concentration of estradiol increased. After i.p. injection of 5-HTP, the concentrations of luteinizing hormone were decreased and follicle-stimulating hormone increased after 120 min. Micro-injection of 5-HTP into the median raphe nucleus increased the concentrations of 5-HT in the anterior hypothalamus and dopamine in the medial hypothalamus after 120 min. Our results suggest that the administration of 5-HTP either i.p. or directly into the ovarian bursa enhances ovarian estradiol secretion.

Psycho-Neuroendocrinology in the Rehabilitation Field: Focus on the Complex Interplay between Stress and Pain.

Chronic stress and chronic pain share neuro-anatomical, endocrinological, and biological features. However, stress prepares the body for challenging situations or mitigates tissue damage, while pain is an unpleasant sensation due to nociceptive receptor stimulation. When pain is chronic, it might lead to an allostatic overload in the body and brain due to the chronic dysregulation of the physiological systems that are normally involved in adapting to environmental challenges. Managing stress and chronic pain (CP) in neurorehabilitation presents a significant challenge for healthcare professionals and researchers, as there is no definitive and effective solution for these issues. Patients suffering from neurological disorders often complain of CP, which significantly reduces their quality of life. The aim of this narrative review is to examine the correlation between stress and pain and their potential negative impact on the rehabilitation process. Moreover, we described the most relevant interventions used to manage stress and pain in the neurological population. In conclusion, this review sheds light on the connection between chronic stress and chronic pain and their impact on the neurorehabilitation pathway. Our results emphasize the need for tailored rehabilitation protocols to effectively manage pain, improve treatment adherence, and ensure comprehensive patient care.

Pituitary multi-hormone cells in mammals and fish: history, origin, and roles.

The vertebrate pituitary is a dynamic organ, capable of adapting its hormone secretion to different physiological demands. In this context, endocrinologists have debated for the past 40 years if endocrine cells are mono- or multi-hormonal. Since its establishment, the dominant "one cell, one hormone" model has been continuously challenged. In mammals, the use of advanced multi-staining approaches, sensitive gene expression techniques, and the analysis of tumor tissues have helped to quickly demonstrate the existence of pituitary multi-hormone cells. In fishes however, only recent advances in imaging and transcriptomics have enabled the identification of such cells. In this review, we first describe the history of the discovery of cells producing multiple hormones in mammals and fishes. We discuss the technical limitations that have led to uncertainties and debates. Then, we present the current knowledge and hypotheses regarding their origin and biological role, which provides a comprehensive review of pituitary plasticity.

Post-Traumatic Hypopituitarism: A Neglected Consequence of Traumatic Brain Injury.

Post-traumatic hypopituitarism (PTHP), described for the first time in 1918, used to be neglected and only considered a rare consequence of traumatic brain injury (TBI). The research conducted in the past 20 years, however, elucidated that it has been significantly underestimated. A PubMed search was conducted in order to find literature on the topic of PTHP. Efforts were made to identify the wide point of view on this problem, from the historical perspective to the most recent data. The pathogenesis of PTHP is heterogenous, and various hypotheses concerning the etiology of this condition have been proposed. Unrecognized and untreated PTHP has negative socioeconomic consequences and influences the quality of life. Although a few attempts to create a screening algorithm have already been performed, there is still no clear answer regarding follow-up. The prevalence of PTHP, a rare consequence of TBI, has been significantly underestimated in the past 20 years. The issue is multifaceted so in order to make reliable guidelines a collaboration of specialists from different fields is required. Due to the increasing prevalence of TBI, and because patients after initial treatment at emergency department usually remain under control of a neurologist, both neurologists and emergency medicine specialists should be aware of clinical picture and mechanisms of PTHP.

Pituitary gland volumes in children with normal endocrine function.

BACKGROUND: Magnetic resonance imaging (MRI) is often the first modality of choice in the detection of pituitary pathologies due to its excellent contrast resolution and high spatial resolution. However, evaluating the size of the pituitary gland is somewhat difficult since the gland morphology varies widely among individuals. OBJECTIVE: The aim of this study was to provide normal reference values for pituitary volumes in the pediatric population using three-dimensional (3-D) MRI data. We also aimed to compare the volumetric data measured through 3-D images with the mathematical volumes obtained by the ellipsoid formula from 2-D images, considering the demographic subgroups of age and sex. MATERIALS AND METHODS: This study was performed retrospectively using PACS-archived brain MRIs obtained in the Pediatric Radiology Unit. Eight hundred children under the age of 18 who underwent brain MRI between January 2014 and May 2018 for headaches, seizures or trauma and who had no brain anomaly or endocrine pathology were recruited. Pituitary volumes were separately calculated from those brain MRIs by means of ellipsoid formula and volumetry. The mean, standard deviation, maximum and minimum and median values were achieved for each 1-year age group in both sexes. Normal reference ranges containing 5th -10th -25th -50th -75th -90th -95th percentiles of volumetric pituitary values were tabulated. RESULTS: Pituitary gland volumes in both sexes were found to increase gradually with age. The average 3-D volume values were greater in girls than boys except for the age groups 1-2 years and 8-9 years. Pituitary volumes showed a growth spurt during early puberty, which was more prominent in girls. Moreover, a strong positive correlation was noted between the 2-D calculated and 3-D measured volumes in both sexes. CONCLUSION: Normative data obtained through this study can be used for clinical diagnostic purposes as well as a reference for future research. The 2-D calculated volumes be used where it is not possible to obtain 3-D volumetric values.

Treatment outcome of metastasis to the pituitary gland: a case series of 21 patients with pathological diagnosis.

OBJECTIVE: The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis). METHODS: The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected. RESULTS: The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months). CONCLUSIONS: Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.

Sonography of the pituitary gland in pet rats.

Pituitary gland (PG) tumors are common in rats over the age of 2. CT and MRI can be difficult to apply in this species, whereas ultrasound is more feasible and useful. To our knowledge, there are no studies on PG ultrasound in rats. The aim of this prospective, analytical study was to evaluate the reliability of ultrasound in identifying PG, to define the ultrasound dimension of the gland in a group of rats with no evidence of pituitary diseases, and to examine its correlations with age, sex, and weight. After localizing the PG with an MRI study on one rat, the gland was identified in 21 rats by ultrasound by two sonographers using a ventral neck approach and a transversal scan with a linear probe. The gland appears as a hypoechoic oval structure with a thin hyperechoic margin. The rats (15 male and 6 female) ranged from 4 to 18 months in age (median 6 months) and from 270 to 640 g in weight (median 370 g). The median pituitary width was 3.96 mm (interquartile range 25-75%: 6-4.5 mm), and the median height was 1.48 mm (interquartile range 25-75%: 1.3-1.67 mm). There was no statistically significant correlation between PG size and rat weight, gender, or age. We believe that these ultrasound measurements could be useful for the diagnosis of pituitary disease, irrespective of whether neurological symptoms are present. We report a clinical case of a rat with a pituitary mass detected by ultrasound and CT.

Nobiletin protects against diabetes-induced testicular injury via hypophysis-gonadal axis upregulation and amelioration of oxidative stress.

BACKGROUND: Testicular injury is one of the most serious problems associated with diabetes mellitus. The present study aimed to compare the effects of two different doses of nobiletin and analyze its mechanisms of action against diabetes-induced testicular impairment in rats. METHODS AND RESULTS: Streptozotocin injection was used to induce diabetes. Diabetic rats received nobiletin orally at 10 or 25 mg/kg daily for 30 days. Diabetic rats displayed significant elevations in glucose, glycosylated hemoglobin (HbA1c), Homeostatic Model of Insulin Resistance (HOMA-IR), and pro-inflammatory cytokines, while the serum levels of insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly reduced. Histological changes to positivity for caspase-3 and decreased androgen receptors (AR) immunoexpression were observed in diabetic rats. Both doses of nobiletin improved hyperglycemia, reduced pro-inflammatory cytokines, and augmented insulin, testosterone, LH, and FSH levels. LH and FSH receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) were markedly downregulated in terms of both gene and protein expression in testicular tissues of the diabetic group, effects that were markedly ameliorated with both doses of nobiletin. In addition, both doses significantly reduced lipid peroxidation and caspase-3 immunoexpression and improved the activity of the antioxidant enzymes and AR in testicular tissues of the diabetic group. CONCLUSION: Both nobiletin doses showed protective effects against diabetes-induced testicular injury by reducing oxidative stress, hyperglycemia, inflammation, and caspase-3 and upregulating the hypophysis-gonadal axis and AR. The high dose of nobiletin was more effective than the lower one.

Cottonoids (neurosurgical patties, neurosurgical pads, or micropatties) as effective instruments for safe and successful endoscopic transsphenoidal adenomectomy.

BACKGROUND: Neurosurgical cottonoids (also known as neurosurgical patties, pads, or micropatties) have been commonly used in microsurgical procedures to protect the surface of the brain, nerves, and vasculature and to aspirate blood, flushing solution, and cerebrospinal fluid. This article describes the unique applications of cottonoids in endoscopic transsphenoidal adenomectomy (eTSA). METHODS: Several sizes of cottonoids have been used in eTSA to enhance safe surgical procedures and clear the operative field. The roles of cottonoids in eTSA are divided into three types: to serve as view-ensuring devices, to protect tissue, and to function as instruments or assist with the use of other instruments. RESULTS: Appropriate cottonoid use provides a well-visualized operative field, allows easy identification of bleeding areas, enables effective adenoma detachment from the cleavage layer (tumour-hypophysis interface), and permits sensitive procedures to be performed around critical structures. CONCLUSIONS: To achieve safe and successful neurovascular-hypophysis-protective eTSA, cottonoids play an effective role in every type of eTSA procedure, in various applications, performed under higher-resolution endoscopic vision.

Detection of a pituitary macroadenoma with transcranial ultrasonography: Principles and potential clinical applications.

Transcranial color-coded duplex sonography (TCCS) allows to study intracranial vessels through the intact skull, but the visualization of normal and pathologic brain structures in adults is often suboptimal due to inadequate acoustic window. The full potential of TCCS for clinical practice remains unfulfilled. Here, we describe the ability of TCCS to detect a non-functioning pituitary macroadenoma in a 58-year-old man affected by headache. The macroadenoma was visualized as a roundish, well-defined mass, mildly hyperechogenic compared to the hypoechogenic mesencephalic brainstem but mainly hypoechogenic compared to the surrounding intracranial structures. Intracranial vessels represented useful landmarks. Using tissue harmonic imaging mode, the borders of the macroadenoma were visualized more clearly. Macroadenoma characteristics were confirmed by magnetic resonance imaging. Neurosonologists should be aware of the possibility to incidentally find, during routinary TCCS, pituitary macroadenomas or other brain tumors (as incidentalomas), worthy to be recognized and referred for further investigations.

Pituitary metastases from neuroendocrine neoplasms: case report and narrative review.

PURPOSE: Pituitary metastases (PM) are uncommon findings and are mainly derived from breast and lung cancers. No extensive review of PM from neuroendocrine neoplasms (NENs) is on record. Here we describe a clinical case of PM from pancreatic NEN and review the clinical features of PM from NENs reported in the literature. METHODS: A case of PM from a pancreatic NEN followed at our institution is described. We also reviewed the 43 cases of PM from NENs reported in the literature. RESULTS: A 59-year old female patient, previously submitted to duodeno-cephalo-pancreasectomy for a well-differentiated pancreatic NEN, with known hepatic metastases, underwent a 68 Ga-DOTATOC PET/CT that revealed an uptake in the pituitary gland. A subsequent MRI displayed a pituitary lesion, with suprasellar extension. After a hormonal and genetic diagnostic workup that excluded the diagnosis of MEN 1, the worsening of headache and visual impairment and the growth of the lesion lead to its surgical removal. A pituitary localization of the pancreatic NEN was identified. Regarding the published cases of PM from NENs, the most common tumour type was small cell lung cancer (SCLC), accounting for nearly half of the cases, followed by bronchial and pancreatic well differentiated NENs. The most frequent symptom was a variable degree of visual impairment, while headache was reported in half of the cases. Partial or total anterior hypopituitarism was present in approximately three quarters of the cases, while diabetes insipidus was less common. The most frequent treatment for PM was surgical resection, followed by radiotherapy and chemotherapy. The clinical outcome was in line with previous reports of PM from solid tumours, with a median survival of 14 months. Surgery of PM was associated with prolonged survival. CONCLUSIONS: PM from NENs have clinical features similar to metastases derived from other solid tumours, albeit the involvement of the anterior pituitary seems more frequent; a thorough pituitary hormonal evaluation is mandatory, after focused radiological studies, particularly if a surgical approach is considered. The optimal management of PM remains disputed and seems mainly driven by the aggressiveness of the primary tumour and the presence of symptoms. In well-differentiated NENs, particularly in the case of symptomatic PM, surgical removal may be a reasonable approach.

Variation in the MRI appearance of the canine pituitary gland.

A recent publication described pathological findings in the pituitary gland incidentally discovered during routine necropsies of the brain of dogs and cats; however, imaging characteristics of these lesions were not reported. Aims of this retrospective, observational study were to characterize MRI variants and incidental lesions in pituitary glands of dogs with no clinical signs of pituitary disease. Cranial MRIs from dogs with no suspicion of pituitary disease, based on history and presenting clinical signs, were retrieved from a veterinary teleradiology database during the period of January 2014 to January 2016. Images were reinterpreted by two observers and pituitary lesions were described based on consensus. A total of 580 scans were evaluated and pituitary lesions were detected in 78 dogs (13.44%). Pituitary cystic lesions were the most common finding and occurred in 31 dogs (5.34%). Of these 31 dogs, the majority (74%) were of toy or brachycephalic breed. Partial or total empty sella lesions were detected in 14 dogs (2.41%), and all of these were small or toy breeds. A significantly increased incidence of the partial empty sella lesion was found in male dogs (P = .034). Pituitary lesions greater than 1 cm occurred rarely (0.69%). There was a significant association between low-field (LF) MRI strength and detection of a partial or total empty sella lesion (P = .0112), and detection of a pituitary lesion greater than 1 cm (P = .0125). A significant difference was present between the MRI field strength (FS) that identified pituitary cysts and the FS that detected an empty sella (P = .0068), with the former being a high FS and the latter a LF strength. The findings from this study indicated that up to 13% of dogs with no presenting clinical signs of pituitary disease may have MRI pituitary lesions.

Pituitary stalk interruption syndrome broadens the clinical spectrum of the TTC26 ciliopathy.

Ciliopathies are a heterogeneous group of disorders, related to abnormal ciliary function. Severe biliary ciliopathy, caused by bi-allelic mutations in TTC26, has been recently described in the context of a syndrome of polydactyly and severe neonatal cholestasis, with brain, kidney and heart involvement. Pituitary involvement has not been previously reported for patients with this condition. Pituitary stalk interruption syndrome (PSIS) is a congenital anomaly of the pituitary gland, diagnosed by characteristic MRI findings. We now describe four patients with TTC26 ciliopathy due to a homozygous c.695A>G p.Asn232Ser mutation and delineate PSIS as a novel clinical feature of this disorder, highlighting an important role of TTC26 in pituitary development.

Hypothalamic- and pituitary-derived growth and reproductive hormones and the control of energy balance in fish.

Most endocrine systems in the body are influenced by the hypothalamic-pituitary axis. Within this axis, the hypothalamus delivers precise signals to the pituitary gland, which in turn releases hormones that directly affect target tissues including the liver, thyroid gland, adrenal glands and gonads. This action modulates the release of additional hormones from the sites of action, regulating key physiological processes, including growth, metabolism, stress and reproduction. Pituitary hormones are released by five distinct hormone-producing cell types: somatotropes (which produce growth hormone), thyrotropes (thyrotropin), corticotropes (adrenocorticotropin), lactotropes (prolactin) and gonadotropes (follicle stimulating hormone and luteinizing hormone), each modulated by specific hypothalamic signals. This careful and distinct organization of the hypothalamo-pituitary axis has been classically associated with the existence of many lineal axes (e.g., the hypothalamic-pituitary-gonadal axis) in charge of the control of the different physiological processes. While this traditional concept is valid, it is becoming apparent that hormones produced by the hypothalamo-pituitary axis have diverse effects. For instance, gonadotropin-releasing hormone II has been associated with a suppressive effect on food intake in fish. Likewise, growth hormone has been shown to influence appetite, swimming activity and aggressive behavior in fish. This review will focus on the hypothalamic and pituitary hormones classically involved in regulating growth and reproduction, and will attempt to provide a general overview of the current knowledge on their actions on energy balance and appetite in fish. It will also give a brief perspective of the role of some of these peptides in integrating feeding, metabolism, growth and reproduction.

Mensuration of the rabbit pituitary gland from computed tomography.

The aim of this retrospective reference interval observational study was to determine the mensuration of the pituitary gland (hypophysis cerebri) by analyzing CT studies in rabbits without clinical evidence of pituitary disease or central neurologic signs. Though diseases of the rabbit pituitary gland are uncommon, the pituitary gland is essential in regulation of the rabbit's endocrine system, as in other species. Currently, there are minimal published studies that detail the rabbit head anatomy on cross-sectional imaging, and even less specifically examining the pituitary gland. The pituitary gland was measured by one observer at a single time point from transverse and reconstructed sagittal CT images in a soft-tissue algorithm in 62 rabbits for a total of 66 rabbit head CT studies. The rabbits ranged from 0.84 to 14 years in age (mean ± SD: 5.46 ± 3.05 years) and 0.92 to 4.95 kg in weight (2.21 ± 0.83 kg). Linear pituitary measurements were performed using electronic calipers. The mean ± SD pituitary height was 4.22 ± 0.57 mm, width was 4.48 ± 0.71 mm, and length was 6.02 ± 0.70 mm. The pituitary gland height-to-brain area ratio was 1.10 ± 0.16 mm-1 , which is much higher than the values reported in normal dogs and cats. The age, weight, and sex of the rabbits were not found to have a significant impact on pituitary gland mensuration. These measurements could be useful as a reference range for future rabbit head CT studies and to rule out pituitary enlargement or disease when evaluating rabbit pituitary glands.

Development of neuroendocrine neurons in the mammalian hypothalamus.

The neuroendocrine system consists of a heterogeneous collection of (mostly) neuropeptidergic neurons found in four hypothalamic nuclei and sharing the ability to secrete neurohormones (all of them neuropeptides except dopamine) into the bloodstream. There are, however, abundant hypothalamic non-neuroendocrine neuropeptidergic neurons developing in parallel with the neuroendocrine system, so that both cannot be entirely disentangled. This heterogeneity results from the workings of a network of transcription factors many of which are already known. Olig2 and Fezf2 expressed in the progenitors, acting through mantle-expressed Otp and Sim1, Sim2 and Pou3f2 (Brn2), regulate production of magnocellular and anterior parvocellular neurons. Nkx2-1, Rax, Ascl1, Neurog3 and Dbx1 expressed in the progenitors, acting through mantle-expressed Isl1, Dlx1, Gsx1, Bsx, Hmx2/3, Ikzf1, Nr5a2 (LH-1) and Nr5a1 (SF-1) are responsible for tuberal parvocellular (arcuate nucleus) and other neuropeptidergic neurons. The existence of multiple progenitor domains whose progeny undergoes intricate tangential migrations as one source of complexity in the neuropeptidergic hypothalamus is the focus of much attention. How neurosecretory cells target axons to the medial eminence and posterior hypophysis is gradually becoming clear and exciting progress has been made on the mechanisms underlying neurovascular interface formation. While rat neuroanatomy and targeted mutations in mice have yielded fundamental knowledge about the neuroendocrine system in mammals, experiments on chick and zebrafish are providing key information about cellular and molecular mechanisms. Looking forward, data from every source will be necessary to unravel the ways in which the environment affects neuroendocrine development with consequences for adult health and disease.

Transcavernous sinus pituitary gland transposition: how I do it.

BACKGROUND: Pituitary transposition preserving gland function is possible when approaching superior clival region tumors. Clinical experience along with detailed anatomical knowledge makes this technique safe and effective. METHOD: We present a step by step description of our technique based on the most recent anatomical references to get a pituitary transposition through the different compartments of the cavernous sinus. By this technique, we achieve minor gland manipulation and a better surgical view of this area. We support this technique with an anatomical analysis on cadaveric specimens and clarifying dissection images. CONCLUSIONS: Transcavernous sinus pituitary gland transposition is an easily feasible technique and allows gland shifting preserving pituitary function.

Comparison of the effects of the L-dopa and insulin tolerance tests on cortisol secretion.

PURPOSE: The aims of the present study are to evaluate the effect of L-dopa on the secretion of cortisol and adrenocorticotropic hormone (ACTH) in short children and compare the performance of this test with the insulin tolerance test (ITT) in a large number of patients. METHODS: A total of 29 short but otherwise healthy children [mean age 9.5 ± 3.1 years (range 3.7-14.9 years)] who had inadequate growth hormone (GH) responses to ITT, which was performed as the first test, were consecutively enrolled in this study. GH, cortisol, and ACTH levels were measured just before administration of L-dopa and then at 30-min intervals afterward over a total time of 120 min. Peak concentrations of cortisol and ACTH exceeding 18 µg/dL (496 mmol/L) and 46 pg/mL (10.2 pmol/L), respectively, were defined as an adequate response. RESULTS: While the L-dopa test revealed that 26 of the 29 children (89.7%) had peak serum cortisol levels of > 18 µg/dL, the ITT revealed that only 23 children (79.3%) had adequate cortisol responses. The L-dopa test revealed normal ACTH responses (> 46 pg/mL) in 24 (82.8%) patients. Peak cortisol levels were higher in children with normal ACTH responses than in those with subnormal ACTH responses (25.6 ± 6.2 vs. 19.5 ± 6.4 µg/dL, p = 0.054), but the difference observed was statistically insignificant. CONCLUSION: The results of the current study confirm that the L-dopa test is a reliable test of cortisol secretion. As such, this test may be applicable to assessments of the hypothalamic-pituitary-adrenal axis.

Hypothalamic-pituitary-ovarian axis perturbation in the basis of bisphenol A (BPA) reproductive toxicity in female zebrafish (Danio rerio).

Thousands of safety-related studies have been published on bisphenol A (BPA), an ubiquitous environmental pollutant with estrogenic activity and many other potential biological effects. In recent years, BPA exposure has been shown to cause anovulation and infertility through irreversible alteration of the hypothalamic-pituitary-gonadal axis in several organisms, including fish and mammals. Recently, the European Chemical Agency classified BPA as a "substance of very high concern" because of its endocrine-disrupting properties, which have serious effects on human health. Given the risk of exposure to BPA as a pollutant in the environment, food, and drinking water, the objective of our study was to assess the effects of this compound on the adeno-hypophysis by means of a histopathological and morphometric study of the gonadotroph cells. In addition, using quantitative real-time PCR (qRT-PCR) assays, we analyzed the changes in the expression of Cyp19b (an aromatase gene). Zebrafish were randomly distributed into five groups: a control group and 4 treated groups which were exposed to different BPA concentrations (1, 10, 100 and 1000 µg/L). The effects of the different doses on Cyp19b mRNA molecules followed a non-monotonic curve, with the 1 and 1000 µg/L doses causing dramatic decreases in the number of Cyp19b transcripts while the doses of 10 and 100 µg/L caused important increases. The consequences might be deregulation of gonadotropic hormones causing degeneration of gonadotropic cells, as observed in BPA treated animals. This is the first study in which the gonadotroph cells have been evaluated using histomorphological endpoints after BPA exposure in zebrafish.

[Pituitary spindle cell oncocytoma]. / Oncocitoma fusocelular hipofisario.

Spindle cell oncocytoma is an infrequent benign non-endocrine sellar neoplasm. Due to its similar morphology to pituitary adenomas, consideration of this differential diagnosis would conduce to a more careful surgical approach in order to avoid intraoperative bleeding and aiming to a complete resection, on which depends long-term outcomes. We present the case of a 60-year-old male who complained about visual abnormalities, with computerized visual field confirmation. On biochemistry, a panhypopituitarism was detected. The brain magnetic resonance images showed a sellar mass. A non-functioning pituitary macroadenoma was presumptively diagnosed and due to the visual impairment, surgical transesphenoidal treatment was indicated. The histological diagnosis was spindle cell oncocytoma. Five months after surgery, the control image demonstrated a lesion that was considered as remnant tumor, hence radiosurgery was performed. During the follow-up, the tumor reduced its size and four years after initial treatment, the sellar resonance imaging showed disappearance of the residual tumor. Communication of new cases of this rare entity will enlarge the existing evidence and will help to determinate the most effective treatment and prognosis.