Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

Sixteen years post radiotherapy of nasopharyngeal carcinoma elicited multi-dysfunction along PTX and chronic kidney disease with microcytic anemia.

BACKGROUND: The hypothalamic-pituitary (h-p) unit is a particularly radiosensitive region in the central nervous system. As a consequence, radiation-induced irreversible, progressively chronic onset hypopituitarism (RIH) commonly develops after radiation treatments and can result in variably impaired pituitary function, which is frequently associated with increased morbidity and mortality. CASE PRESENTATION: A 38-year-old male subject, previously having received radiotherapy for treatment of nasopharygeal carcinoma (NPCA) 16 years ago, appeared at OPD complaining about his failure in penile erection, loss of pubic hair, atrophy of external genitalia: testicles reduced to 2×1.5 cm; penile size shrunk to only 4 cm long. Characteristically, he showed extremely lowered human growth hormone, (HGH, 0.115 ng/mL), testosterone (<0.1 ng/mL), total thyroxine (tT4: 4.740 g/mL), free T4 (fT4, 0.410 ng/mL), cortisol (2.34 g/dL); lowered LH (1.37 mIU/mL) and estradiol (22 pg/mL); highly elevated TSH (7.12 IU/mL). As contrast, he had low end normal ACTH, FSH, total T3, free T3, and estriol; high end normal prolactin (11.71 ng/mL), distinctly implicating hypopituitarism-induced hypothyroidism and hypogonadism. serologically, he showed severely lowered Hb (10.6 g/dL), HCT (32.7%), MCV (77.6 fL), MCH (25.3 pg), MCHC (32.6 g/dL), and platelet count (139×103/L) with extraordinarily elevated RDW (18.2%), together with severely lowered ferritin (23.6 ng/mL) and serum iron levels; highly elevated total iron binding capacity (TIBC, 509 g/dL) and transferrin (363.4 mg/dL), suggesting microcytic anemia. Severely reduced estimated glomerular filtration rate (e-GFR) (89 mL/mim/1.73 m2) pointed to CKD2. Hypocortisolemia with hyponatremia indicated secondary adrenal insufficiency. Replacement therapy using androgen, cortisol, and Ringer's solution has shown beneficial in improving life quality. CONCLUSIONS: To our believe, we are the first group who report such complicate PTX dysfunction with adrenal cortisol insufficiency concomitantly occurring in a single patient.

Efectos del traumatismo craneoencefálico sobre la función hipofisaria / Impact of head trauma on pituitary function

En la última década ha habido una auténtica eclosión de trabajos que relacionan el traumatismo craneoencefálico (TCE) con hipopituitarismo. Esta condición puede afectar el proceso de rehabilitación por lo que se requiere identificar a estos pacientes, pero hasta ahora, la metodología utilizada ha sido muy diversa y los resultados muy dispares. Es probable que la indidencia del hipopituitarismo haya sido sobrevalorada. Esta revisión se centra en el impacto del TCE sobre la función hipofisaria, el método diagnóstico, factores de riesgo y opciones de tratamiento (AU)

There have been in the past decade a growing number of studies relating head trauma to hypopituitarism. This condition may affect the rehabilitation process, and identification of such patients is therefore required. However, the widely different methods used so far for this purpose have provided inconsistent results. The incidence rate of hypopituitarism has probably been overestimated. This review focuses on the impact of head trauma on pituitary function, the diagnostic method, risk factors, and treatment options(AU)

Stiletto stabbing: penetrating injury to the hypothalamus with hyperacute diabetes insipidus.

Diabetes insipidus (DI) is a well documented complication observed after traumatic head injuries. We report a case of hyperacute onset DI in a 19-year-old male who sustained a hypothalamic-pituitary injury when he was stabbed in the head with a 30-cm long thin-bladed knife. At CT, our patient showed significant hemorrhagic contusions of the lower hypothalamus. He developed polydipsia, polyuria, and mild hypernatremia in the Emergency Department. Diagnostic digital subtraction angiography showed a hypervascular congestive pituitary gland with prominent draining veins. On the third day his hypernatremia became severe (183mEq/L). He was managed with parenteral fluids and a regimen of intranasal DDAVP (1-desamino 8-d-arginine vasopressin), leading to improved plasmatic sodium levels, urine output, and urinary specific gravity. In patients presenting with hyperacute posttraumatic DI, emergency room physicians and neurosurgeons should rule out direct injury to the hypothalamus and/or the posterior lobe of the pituitary, and initiate early pharmacological treatment.

Hypothalamic-pituitary axis deficiency following traumatic brain injury in a dog.

OBJECTIVE: To describe endocrine dysfunction associated with traumatic brain injury in a dog. SUMMARY: A 12-week-old dog presented with traumatic brain injury and did not respond to traditional supportive care. Continued hypothermia, electrolyte derangements, hypotension, and hyposthenuria prompted screening for and detection of several hypothalamic-pituitary disorders including: hypoadrenocorticism, central diabetes insipidus, hypothyroidism, and growth hormone deficiency. Electrolyte abnormalities, urine osmolarity, and blood pressure improved with treatment for the associated disorders. NEW OR UNIQUE INFORMATION PROVIDED: This is the first report of generalized hypothalamic-pituitary dysfunction or panhypopituitarism following traumatic brain injury in a dog.

Valoración del eje hipotálamo-hipofisario en la fase precoz del traumatismo craneoencefálico grave / Assessment of hypothalamo-pituitary axis in early phase of severe cranioencephalic brain injury

Objetivo. Analizar las características de la función hipofisaria en la fase inicial de pacientes críticos con traumatismo craneoencefálico grave (TCEG). Diseño. Estudio observacional, prospectivo. La función hipofisaria se evaluó siempre el tercer día tras el TCEG. Ámbito. Unidad de cuidados intensivos (UCI) neurotraumatológica de un hospital universitario. Pacientes. Se incluyó a 136 pacientes con TCEG (intervalo, 16-65 años), durante un período de 2 años y 9 meses y estancia en UCI mayor de 48 h. Intervención. Ninguna. Medidas y datos recopilados. Se recogieron durante las primeras 72 h tras el traumatismo: variables demográficas, severidad de la lesión, parámetros de neuromonitorización, lesiones cerebrales secundarias, uso de fármacos vasoactivos y el tipo de traumatismo craneoencefálico (TCE) acorde a los hallazgos encontrados en la tomografía computarizada (TC). La evaluación de la función hipofisaria se determinó por medición de hormonas hipofisarias y las de los órganos diana, con la excepción de la función somatotropa, que se evaluó midiendo las concentraciones séri- cas basales de insulin-like growth factor-1 (IGF-1). Resultados. Se observó disfunción hipofisaria en 101 (74,2%) pacientes; 79 (58%) pacientes tenían afectado solamente un eje hipofisario, la afectación de ejes es la siguiente: gonadotropo, el 63,7% (87 pacientes); tirotropo, el 8,8% (12 pacientes), y corticotropo, el 0,7% (1 paciente). Se observaron concentraciones plasmáticas bajas de IGF-1 acorde a la edad en 90 (66,7%) pacientes, aunque sólo 26 de ellos mostraron un valor menor de 90 ng/ml. Conclusiones. Nuestros datos muestran que la disfunción hipofisaria ocurre precozmente y con gran frecuencia tras un TCEG, aunque el significado real de estos hallazgos están aún por determinar

Objective. To assess early pituitary function in asequential cohort of critical care patients after severetraumatic brain injury (TBI).Design. This was a prospective observationalstudy. The pituitary function was always tested onthe third day after TBI.Setting. Neurocritical intensive care unit (ICU)in a University hospital.Patients. A total of 136 adult patients with severeTBI (range, 16-65 years) enrolled over a 2year and 9 month period having a stay in the ICUtreated than 48 hours.Intervention. None.Measurements and data collected. The followingdata were recorded within the first 72 hoursafter injury: demographic variables, injury severity,neuromonitoring data, systemic secondarybrain insults, use of vasoactive drugs and type ofTBI according to the computerized tomography (CT) scan findings. Pituitary function was evaluatedby measurement of both the pituitary and targetorgan hormones, with the exception of the somatotrophicfunction, which was assessed bymeasurement of basal serum values of insulinlikegrowth factor-I (IGF-I).Results. Pituitary dysfunction was observed in101 patients (74.2%). Seventy-nine patients (58%)had impairment of only one pituitary axis, the axesbeing affected as follows: gonadotropic 63.7%(87 patients), thyrotropic 8.8% (12 patients) andcorticotropic 0.7% (1 patient). Low IGF-1 plasmaticlevels in accordance to the patient’s age wereobserved in 90 patients (66.7%). However, only 26of them had a value below 90 ng/ml.Conclusions. Our data show that pituitary dysfunctionoccurs early and with high frequency aftersevere TBI, but the real significance of thesefindings still needs to be elucidated

Does the pineal gland have a role in the psychological mechanisms involved in the progression of cancer?

Psychological factors, e.g., depression and psychological stress have been implicated in the progress of cancer. Similarly, the pineal gland and its principal secretion, melatonin, are known to influence the initiation and progress of cancer. Furthermore, changes in melatonin secretion have been linked with psychological stress and depression, and both the pineal gland and the cerebral cortex act via the limbic system in producing their effects. Both psychological stress and melatonin affect the immune system, as does the hypothalamus and the autonomic nervous system. The pineal gland has both a direct effect on cancer, and via the immune system. Psychological treatment and melatonin treatment have both been found to alleviate the course of cancer clinically. It is thus hypothesized that the pineal gland, and melatonin, are involved in the mechanism of psychological effects in the promotion of the progress of cancer.

Post-traumatic regeneration, neurogenesis and neuronal migration in the adult mammalian brain.

Unlike the peripheral nervous system (PNS), the mammalian central nervous system (CNS) clearly lacks the robust regenerative characteristics and capacity of the former. Despite this fact, two unique regions of the adult mammalian CNS possess such regenerative potential and are capable of active regeneration following injury or structural compromise. These unique areas are the olfactory system and the neurohypophyseal system of the endocrine hypothalamus. Furthermore, it has been clearly demonstrated that primordial neuroblasts regarded as stem cells emerge from the subependymal parenchyma of the walls and floor of the third cerebral ventricle, migrate to the ventricular surface and undergo compensatory synaptogenesis within one week following hypophysectomy. In situ hybridization studies have unequivocally demonstrated that the up-regulation of nitric oxide synthase (NOS) is essential for neural (axonal) regeneration and neuronal (stem cell) migration to occur. Moreover, neuronal migration is reliably inhibited following the administration of the NO antagonist, nitroarginine. The current investigation serves to confirm a remarkable degree of plasticity and regeneration in the adult mammalian neurohypophyseal system coupled with the emergence of primordial neuroblasts that undergo apparent differentiation, migration and compensatory synaptogenesis in response to the up-regulation of NO that occurs following the trauma of hypophysectomy. Evidence from the current investigation appears to confirm that specialized glia of the neurohypophyseal system, the so-called pituicyte, proliferate following hypophysectomy and may serve as a growth matrix or structural template that may target and direct regenerating Supraoptic (SON) and Paraventricular (PVN) axons toward endothelial primordia in the regenerating neural stem and lobe.

Human corticotropin-releasing hormone test in patients with hypothalamo-pituitary-adrenocortical disorders.

To assess the diagnostic usefulness of a synthetic human corticotropin-releasing hormone (CRH) formulation (Code No. MCI-028), we administered 100 micrograms of the peptide intravenously to 183 patients with hypothalamo-pituitary-adrenocortical (HPA) disorders, and obtained the following findings. Among the 183 patients, data from 125 patients were suitable for analyzing the effects of the test. In patients with Cushing's disease, high plasma adrenocorticotropic hormone (ACTH) and cortisol levels increased further in response to MCI-028, while in patients with adrenal Cushing's syndrome, low ACTH and high cortisol values remained unchanged. In patients with pituitary-type hypopituitarism or isolated ACTH deficiency, low ACTH and cortisol levels responded poorly or insignificantly to MCI-028, whereas those with hypothalamic hypopituitarism showed delayed and considerable degree of responses of plasma ACTH and little increase in plasma cortisol levels. In Addison's disease, high plasma ACTH increased further in response to MCI-028, but low cortisol levels did not change. In patients with Cushing's syndrome soon after successful surgical treatment, plasma ACTH responsiveness was low or different depending on the clinical course of the patient. Patients treated with high doses of glucocorticoids for non-endocrine diseases tended to show impaired ACTH and cortisol responsiveness to MCI-028. Side effects, including the transient flushing which was observed most frequently in this study, did not cause any clinical problems.

Intrahypothalamically transected neurosecretory axons do not regenerate in the absence of glial cells.

Fifteen days after transection of the hypothalamo-neurohypophysial tract at the lateral retrochiasmatic hypothalamic area, neurosecretory axons had vigorously regenerated into transplants of explanted hypophysial neural lobe, to a lesser extent into sciatic nerve transplants, and least into optic nerve transplants. Regenerating axons were always closely associated with the specific glial cells of these grafts. When these glial cells were killed by cryotreatment prior to transplantation, neurosecretory axons did not regenerate into the abundant extracellular matrix of the transplants, including persisting basal lamina tubes in neural lobe and sciatic nerve grafts. The presence of viable glial cells is a prerequisite for neurosecretory axon regeneration.

Function tests on the neuroendocrine hypothalamo-pituitary system following acute midbrain syndrome, with special reference to computertomographical and magnetic resonance imaging results.

Seventeen patients underwent a neuroendocrinological function test at a mean 6.3 years following a severe craniocerebral trauma (CCT) accompanied by midbrain syndrome. An insulin hypoglycaemia test (IHT) and the combined pituitary anterior lobe test (CPALT) were applied. Whereas the IHT as maximum stimulator of the hypothalamo-pituitary system (HPS) showed an adequate reserve capacity, the CPALT yielded a partial limitation of the secretion dynamic in the somatotropic, adrenocorticotropic axis as well as a dysfunction in the FSH secretion. Neuroradiological tests could not establish substantial injury in the regio hypothalamica in any patient.

Restoration and maintenance of spermatogenesis by HCG therapy in patients with hypothalamo-hypophyseal damage.

Both gonadotropins are necessary to induce spermatogenesis in man and to recover hypophysectomized males. The patients who suffer from tumoral or traumatic hypothalamo-hypophyseal lesion use to have low endogenous gonadotropins (opposite to hypophysectomized patients), which can produce a minor involution of spermatogenesis. Three patients with postpubertal hypogonadotropic hypogonadism and oligozoospermia were studied. Two of them were operated on for chromophobous adenoma of pituitary, and the other patient had traumatic hypothalamo-hypophyseal lesion. The three patients were treated with 5000 IU HCG/week, associated with testosterone enanthate, in two cases and with bromocryptine in the remaining one. All the patients had normalized spermiogram, but when HCG was interrupted, the sperm count regressed to pretreatment levels in spite of the maintenance of treatment with testosterone or bromocryptine. Minimal amounts of FSH together the testosterone supplied by Leydig cell under the HCG stimulus, are able to recover and maintain the spermatogenesis in these patients.

Sexual precocity with hypothalamic hypopituitarism.

Two girls, one with septo-optic dysplasia and the other with posttraumatic brain damage, had the unusual combination of human growth hormone, thyrotropin, adrenocorticotrophic hormone, and vasopressin deficiencies that were associated with sexual precocity in one patient and early sexual maturation in the second patient, and of adult follicle-stimulating hormone and luteinizing hormone concentrations. At autopsy, the first patient had optic nerve aplasia, a normal pituitary gland, and some disorganization of myelinated fibers in the hypothalamus. The second patient had a normal thyrotropin and prolactin response to thyrotropin-releasing hormone, plus hyperphagia, deranged thirst mechanism, and temperature instability. These findings suggest that the lesion may be a defective hypothalamic regulation of pituitary hormone secretion. Congenital or traumatic hypothalamic-pituitary lesions may not affect all releasing factors or trophic hormones in a similar fashion.