oxytocin and Pituitary-Neoplasms

Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies, which are related to the anterior and/or posterior gland and can have an onset in childhood or adulthood. The most common aetiology is a sellar or suprasellar lesion, often an adenoma, which causes hypopituitarism due to tumour mass effects, or the effects of surgery and/or radiation therapy. However, other clinical conditions, such as traumatic brain injury, and autoimmune and inflammatory diseases, can result in hypopituitarism, and there are also genetic causes of hypopituitarism. Furthermore, the use of immune checkpoint inhibitors to treat cancer is increasing the risk of hypopituitarism, with a pattern of hormone defects that is different from the classic patterns and depends on mechanisms that are specific for each drug. Moreover, autoantibody production against the pituitary and hypothalamus has been demonstrated in studies investigating the development or worsening of some cases of hypopituitarism. Finally, evidence suggests that posterior pituitary damage can affect oxytocin secretion. The aim of this Review is to summarize current knowledge on non-classic and emerging causes of hypopituitarism, so as to help clinicians improve early identification, avoid life-threatening events and improve the clinical care and quality of life of patients at risk of hypopituitarism.

Topics: Adenoma; Adrenocorticotropic Hormone; Autoimmune Hypophysitis; Brain Injuries, Traumatic; Dwarfism, Pituitary; Empty Sella Syndrome; Endocrine System Diseases; Genetic Diseases, Inborn; Humans; Hypoglycemia; Hypogonadism; Hypophysitis; Hypopituitarism; Hypothyroidism; Immune Checkpoint Inhibitors; Oxytocin; Pituitary Apoplexy; Pituitary Neoplasms; Subarachnoid Hemorrhage

Oxytocin is a neuropeptide known to affect social behaviour and cognition. Craniopharyngioma patients are considered to have an oxytocin-release-deficit caused by a rare tumour affecting the pituitary and/or the hypothalamus relevant for oxytocin production and release. To assess social behaviour and socio-cognitive abilities in this patient group, we tested 13 patients and 23 healthy controls on self-report questionnaires and an eye-tracking paradigm including fast facial emotion recognition. Additionally, saliva oxytocin levels acquired before and after a physical stress induction were available from a previous study, representing the reactivity of the oxytocin system. The data revealed three major results. First, patients with an oxytocin-release-deficit scored higher on self-reported autistic traits and reduced levels of hedonia for social encounters, although they showed no impairments in attributing mental states. Second, patients showed more difficulties in the fast emotion recognition task. Third, although automatic gaze behaviour during emotion recognition did not differ between groups, gaze behaviour was related to the reactivity of the oxytocin system across all participants. Taken together, these findings demonstrate the importance of investigating the reactivity of the oxytocin system and its relationship with social cognition. Our findings suggest that reduced emotional processing abilities may represent a pathological feature in a group of craniopharyngioma patients, indicating that this patient group might benefit from specific treatments within the social domain.

Topics: Adult; Craniopharyngioma; Eye Movements; Female; Humans; Male; Middle Aged; Oxytocin; Pituitary Gland; Pituitary Neoplasms; Saliva; Social Cognition; Young Adult

Patients with childhood-onset craniopharyngioma (CP) often suffer from tumour or treatment-related hypothalamic lesions (HL). These lesions may alter production of oxytocin, which plays a major role in the regulation of eating behaviour and body composition.. In CP with different degrees of HL, we investigated associations between HL, eating behaviour/eating attitudes, and oxytocin saliva concentrations (OSC).. In a cross-sectional case-control study on 34 CP and 73 healthy controls, OSC were measured before, and 60 minutes after breakfast by immunoassay. Eating behaviour, attitudes, and habits were assessed by standardized questionnaires.. CP with anterior + posterior HL presented with more adverse eating behaviours/symptoms of eating disorders than CP without HL, CP with anterior HL, and controls. Eating behaviour in CP with anterior HL was similar to controls, except for their tendency towards high dietary restraints. Decreases in postprandial compared with fasting OSC were associated with adverse eating behaviour in CP and controls and with higher BMI in CP.. CP with anterior HL and CP with anterior + posterior HL present with distinct patterns of eating behaviour. Reduced postprandial compared with fasting OSC is associated with weight problems in CP and with adverse eating behaviour and symptoms of eating disorders in both CP and controls.

Topics: Adolescent; Adult; Case-Control Studies; Child; Cohort Studies; Craniopharyngioma; Cross-Sectional Studies; Feeding and Eating Disorders; Feeding Behavior; Female; Humans; Hypothalamic Neoplasms; Hypothalamus; Male; Middle Aged; Oxytocin; Pituitary Neoplasms; Saliva; Surveys and Questionnaires; Time Factors; Young Adult

Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline oxytocin levels and stimulated OT-responses might have different effects on affective function, which should be considered in future substitution paradigms.

Topics: Adult; Affective Symptoms; Anxiety; Craniopharyngioma; Depression; Female; Humans; Hypopituitarism; Hypothalamus; Male; Middle Aged; Oxytocin; Pituitary Neoplasms; Prospective Studies

Hypothalamic obesity, a treatment-resistant condition common to survivors of craniopharyngioma (CP), is strongly associated with a poor quality of life in this population. Oxytocin (OT), a hypothalamic neuropeptide, has been shown to play a role in the regulation of energy balance and to have anorexigenic effects in animal studies. Naltrexone (NAL), an opiate antagonist, has been shown to deter hedonic eating and to potentiate OT's effects.. In this parent-observed study, we tested the administration of intranasal OT for 10 weeks (phase 1), followed by a combination of intranasal OT and NAL for 38 weeks (phase 2) in a 13-year-old male with confirmed hypothalamic obesity and hyperphagia post-CP resection. Treatment resulted in 1) reduction in body mass index (BMI) z score from 1.77 to 1.49 over 10 weeks during phase 1; 2) reduction in BMI z score from 1.49 to 0.82 over 38 weeks during phase 2; 3) reduced hyperphagia during phases 1 and 2; 4) continued hedonic high-carbohydrate food-seeking in the absence of hunger during phases 1 and 2; and 5) sustained weight reduction during decreased parental monitoring and free access to unlocked food in the home during the last 10 weeks of phase 2.. This successful intervention of CP-related hypothalamic obesity and hyperphagia by OT alone and in combination with NAL is promising for conducting future studies of this treatment-recalcitrant form of obesity.

Topics: Administration, Intranasal; Administration, Oral; Child; Craniopharyngioma; Humans; Hypothalamic Diseases; Male; Naltrexone; Neurosurgical Procedures; Obesity; Oxytocin; Pituitary Neoplasms; Treatment Outcome

The hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions.. In our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire.. All patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions.. Oxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.

Topics: Adult; Affect; Craniopharyngioma; Cross-Sectional Studies; Emotions; Female; Humans; Male; Oxytocin; Pilot Projects; Pituitary Neoplasms; Recognition, Psychology; Saliva; Surveys and Questionnaires; Treatment Outcome; Young Adult

Social and emotional impairment, school dysfunction, and neurobehavioral impairment are highly prevalent in survivors of childhood craniopharyngioma and negatively affect quality of life. As surgical resection of craniopharyngioma typically impairs hypothalamic/pituitary function, it has been postulated that perhaps post-operative deficiency of the hormone oxytocin may be the etiology of social/emotional impairment. Research on the benefits of oxytocin treatment as a hormone facilitating social interaction is well established. However, no research has yet been conducted on patients with known pituitary/hypothalamic dysfunction due to structural lesions or surgery. This case report investigates the effects of oxytocin therapy on a youngster with pituitary/hypothalamic dysfunction after craniopharyngioma removal. In this individual, treatment with low dose intranasal oxytocin resulted in increased desire for socialization and improvement in affection towards family. In light of these findings, the authors believe that further research into the potential benefits of intranasal oxytocin therapy for patients with panhypopituitarism is necessary to determine whether a broader population may also benefit from intranasal oxytocin therapy.

Topics: Child; Craniopharyngioma; Female; Humans; Interpersonal Relations; Oxytocin; Parents; Pituitary Neoplasms; Postoperative Period; Prognosis; Quality of Life; Social Behavior; Survivors

Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

Topics: Adolescent; Adult; Child; Circadian Rhythm; Craniopharyngioma; Female; Humans; Male; Meals; Middle Aged; Oxytocin; Pituitary Neoplasms; Saliva; Sex Factors; Survivors; Young Adult

Prolactin (PRL) has been reported to promote antidiuresis and increase intestinal water-electrolyte absorption, whereas osmolar changes have been shown to influence PRL secretion. However, the mechanisms of action of PRL on the salt-water balance remain unclarified. The present clinical study targeted the effects of hyperprolactinaemia on the secretion of arginine-8-vasopressin (AVP), oxytocin (OXT) and cortisol. Plasma AVP and OXT were measured by radioimmunoassay, and cortisol by fluorimetry. In healthy women (21-39 y, n=6), an oral water load (OWL, 20 ml/bw) significantly suppressed the plasma levels of AVP, OXT and cortisol, and the PRL level too tended to decrease. In hyperprolactinaemic females (22-41 y, n=6, three with pituitary adenomas), water retention was registered following an OWL, together with paradoxical AVP and OXT level increases, whereas the cortisol response remained normal, and the PRL level did not change at all. Histamine (0.5 mg sc) stimulated the release of AVP, OXT and cortisol in the control and hyperprolactinaemic groups alike. These data suggest that alterations in AVP and OXT hypersecretion may contribute to the water retention in hyperprolactinaemia.

Topics: Administration, Oral; Adult; Arginine Vasopressin; Blood Pressure; Female; Histamine; Humans; Hydrocortisone; Hyperprolactinemia; Oxytocin; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Pituitary Neoplasms; Prolactin; Prolactinoma; Sodium; Time Factors; Water; Water-Electrolyte Balance

Familial hypothalamic diabetes insipidus is an autosomal dominant disorder characterized by deficient vasopressin synthesis. Different point mutations in the vasopressin-neurophysin (VP-NP) precursor gene have been found in affected families. In a Dutch kindred, a single G to T transversion in the NP-encoding exon B of one allele converts the highly conserved glycine 17 to a valine residue. In order to examine whether this point mutation affects the processing and transport of the VP-NP precursor, the normal (HV2) and mutant (MT6) vasopressin cDNAs were stably expressed in the mouse pituitary cell line AtT20. The normal precursor was correctly glycosylated and processed, and NP was detected in the culture medium. Secretion of NP was stimulated by 8-bromo-cAMP, indicating that the normal precursor was targeted to the regulated secretory pathway. In contrast, the mutant precursor was synthesized, but processing and secretion were dramatically reduced. The mutant precursor was core-glycosylated but remained endoglycosidase H-sensitive, suggesting that the protein did not reach the trans-Golgi network. These results were supported by immunocytochemical studies. In HV2 cells, NP derived from the precursor was concentrated in the tips of the cell processes where secretory granules accumulate. In MT6 cells, NP staining was restricted to the endoplasmic reticulum (ER) as determined by colocalization with an ER-resident protein, BiP. These results suggest that the mutation within the conserved part of NP alters the conformation of the precursor and thus triggers its retention in the ER.

Topics: Amino Acid Sequence; Animals; Arginine Vasopressin; Cell Line; Conserved Sequence; Cyclic GMP; Diabetes Insipidus; Fluorescent Antibody Technique; Glycine; Glycosylation; Humans; Mice; Netherlands; Neurophysins; Oxytocin; Pituitary Gland; Pituitary Neoplasms; Point Mutation; Protein Precursors; Recombinant Proteins; Transfection; Valine; Vasopressins

Spontaneous pituitary adenomas are common in certain strains of the laboratory rat. Investigations of Wistar rats of two years chronic toxicity studies revealed pituitary tumors in 50% of the females and 26% of the males. The morphology of the spontaneous changes in the pituitary gland was investigated with immunohistochemical and histological methods. The peroxidase-antiperoxidase (PAP) technique was used to localize different hormones (LH, ACTH) in cells of the pars intermedia and pars distalis as well as neurophysin, oxytocin and vasopressin the terminals of the classic neurosecretory system of the pars nervosa. The results show that most of the neoplasms were endocrinologically inactive chromophobe adenomas of the pars distalis.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; Female; Immunoenzyme Techniques; Luteinizing Hormone; Male; Neurophysins; Oxytocin; Pituitary Gland; Pituitary Neoplasms; Rats; Rats, Inbred Strains; Vasopressins

Pro-vasopressin mRNA, neurophysin and arginine vasopressin (AVP) were assayed in the mouse anterior pituitary gland, in mouse anterior pituitary cells in culture and in the AtT-20 corticotrophic tumour cell line. Northern blot analysis revealed the presence of an approximately 700 base pair pro-vasopressin mRNA in anterior pituitary and AtT-20 cells. Neurophysin, identified by immunoblots, and AVP, identified by high-performance liquid chromatography and cross-reactivity with AVP antiserum, were detected in anterior pituitary cells and AtT-20 cells. Immunocytochemical staining with anti-neurophysin showed that approximately 40-45% of the dissociated anterior pituitary cells in culture and greater than 95% of the AtT-20 cells were stained. Anterior pituitary cells in culture and AtT-20 cells had a basal level of release of AVP in the 0.01-0.1 nM range. These results indicate that anterior pituitary cells and AtT-20 cells have the ability to synthesize and process pro-vasopressin to AVP and neurophysin, endogenously.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Cell Line; Cells, Cultured; Corticotropin-Releasing Hormone; Immunoblotting; Immunohistochemistry; Male; Mice; Neurophysins; Oxytocin; Pituitary Gland, Anterior; Pituitary Neoplasms; Protein Precursors; Radioimmunoassay; RNA, Messenger; Tumor Cells, Cultured; Vasopressins

Preprovasopressin-neurophysin II (prepro-AVP-Np), the precursor of the cyclic, amidated nonapeptide, arginine vasopressin (AVP), is present in the central and peripheral nervous systems, adrenal glands, and gonads of rats. To study cell-specific processing of prepro-AVP-Np, a fusion gene consisting of the heavy metal-inducible promoter of the mouse metallothionein I gene and the rat prepro-AVP-Np gene was introduced by cellular transfection into several defined cell phenotypes: a fibroblast line (BHK), a pituitary growth hormone and prolactin-producing cell line (GH4), a pituitary cell line that produces several amidated peptides (AtT-20), and an insulin-producing pancreatic islet line (RIN- 1046-38). Clonal cell lines were isolated and prepro-AVP-Np-specific transcripts were detected by Northern blot hybridization analyses. Fibroblast BHK and pituitary GH4 cells transfected with the fusion gene synthesized a polypeptide (Mr = 18,000) characteristic of the glycosylated precursor, pro-AVP-Np; in metal -treated cells, this protein was the major secreted cysteine-labeled polypeptide. Extracts of RIN-1046-38 and AtT-20 cells transfected with the fusion gene contained predominantly processed neurophysin and amidated arginine vasopressin, whereas extracts of BHK and GH4 cells contained mainly precursors of AVP and neurophysin. These observations indicate that the pathways involving specific post-translational processing of pro-AVP-Np are more efficiently utilized in the prohormone-producing AtT-20 and RIN-1046-38 cells than in GH4 and BHK cells that do not synthesize any recognized prohormones.

Topics: Animals; Arginine Vasopressin; Cell Line; Cloning, Molecular; Genes; Genes, Synthetic; Metallothionein; Mice; Neurophysins; Oxytocin; Pituitary Neoplasms; Protein Biosynthesis; Protein Precursors; Transcription, Genetic; Vasopressins

A patient is described who developed diabetes insipidus during pregnancy. During a revised Carter test performed at 36 wk gestation using DDAVP (1-desamino-8-D-arginine-vasopressin), uterine activity was recorded with a maximum activity of 120 Montevideo Units. The induction of uterine activity by DDAVP in our patient might be related to the high endogenous oxytocin levels or to the far advanced state of amenorrhea. Post partum, the patient reported decreased vision, and the visual fields were found to be abnormal. A neurosurgical procedure followed, and the diagnosis of craniopharyngioma was made.

Topics: Adult; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Oxytocin; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Uterine Contraction

Topics: Animals; Chick Embryo; Diabetes Insipidus; Dogs; Hypothalamo-Hypophyseal System; Microscopy, Electron; Neurosecretion; Oxytocin; Pituitary Gland, Posterior; Pituitary Neoplasms; Vasopressins

Topics: Acetylcholine; Adenoma; Animals; Cortisone; Estrone; Female; Neoplasms, Experimental; Nicotine; Oxytocin; Pituitary Neoplasms; Rats; Sodium Chloride; Vasopressins; Water-Electrolyte Balance