oxytocin and Inappropriate-ADH-Syndrome

This is a clinical case presentation of a full term newborn infant who suffered severe hyponatremia and early seizures, associated with maternal fluid overload with electrolyte free solutions and high doses of oxytocin for labor augmentation. Although this condition has been recognized since the 1960's with isolated reports, this particular case has features that needs further investigation, not only for the unsually severe hyponatremia, but most importantly we think, for the prominent signs of fluid retention, the infant had, that suggest excessive antidiuretic activity probably due to oxytocin. These findings are consistent with syndrome of inappropriate secretion of antidiuretic hormone. Although until now there is no proof that oxytocin by itself produces this syndrome. We think the association is possible in certain clinical circumstances, such as those found in this case. We also, briefly discussed the pathophysiology of perinatal hyponatremia, the neonatal treatment of this condition and the current guidelines for the women in labor. Hyponatremia should not be considered a benign condition, since in the neonate, it may affect brain function.

Topics: Cesarean Section; Epilepsy, Generalized; Female; Fluid Therapy; Humans; Hyponatremia; Inappropriate ADH Syndrome; Infant, Newborn; Labor, Induced; Maternal-Fetal Exchange; Oliguria; Oxytocics; Oxytocin; Pregnancy; Thymol; Water Intoxication; Young Adult

Topics: Abortion, Threatened; Biological Assay; Biomarkers; Depression, Postpartum; Diagnostic Techniques, Endocrine; Female; Humans; Hydatidiform Mole; Inappropriate ADH Syndrome; Labor, Obstetric; Oxytocin; Pregnancy; Radioimmunoassay; Specimen Handling; Uterine Neoplasms

Topics: Biomarkers, Tumor; Carcinoma, Small Cell; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Neoplasms; Neurophysins; Oxytocin; RNA, Messenger; Vasopressins

A great deal of information has been accumulated on the synthesis and release of AVP, oxytocin, and their associated neurophysins under normal circumstances. In 1957, Schwartz and Bartter first described SIAD in patients with lung cancer and postulated that the clinical findings were the results of excessive vasopressin secretion. Tumors have been known since 1964 to produce vasopressin, and small cell (oat cell) carcinoma of the lung is by far the most frequent malignant cause of SIAD. The biosynthetic pathway for the synthesis of AVP and its associated neurophysin (and to a lesser extent, oxytocin and its neurophysin) is well described and is similar if not identical to the synthesis of these peptides in the hypothalamus. However, there is little reliable information on the control of peptide synthesis and release by these tumors. The clinical picture of SIAD is well described and occurs in 20% to 40% of patients with SCCL, although up to 88% of patients with extensive SCCL have elevated circulating levels of one or more neurohypophyseal peptides. This information has led to considerable interest in the use of these peptides as tumor markers for the diagnosis, evaluation, and assessment of therapy in these patients. With the recognition of the high incidence of secretion of neurohypophyseal peptides by SCCL, studies have been initiated to determine the value of radioactive vasopressin neurophysin antibodies in localizing tumors that synthesize these peptides. The studies provide potentially useful information in diagnosing and following patients with SCCL and also offer some promise that radiolabeled antineurophysins could eventually be used to treat these patients.

Topics: Biomarkers, Tumor; Fluid Therapy; Hormones, Ectopic; Humans; Hypothalamic Hormones; Hypothalamus; Inappropriate ADH Syndrome; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Sodium; Vasopressins

This chapter has reviewed briefly the neuroanatomy relevant to the synthesis and release of AVP and OXT. Osmoregulation and baroregulation of AVP secretion has been discussed in detail, emphasizing the importance of osmotic control under normal physiological conditions. The remainder of the text has covered the two major pathophysiological disturbances of AVP secretion. In considering diabetes insipidus a pragmatic approach has been taken in the differentiation of the causes of polyuria and its treatment. A similar approach has been applied to the syndrome of inappropriate antidiuresis. Brief mention was made of the function of OXT.

Topics: Adult; Animals; Arginine Vasopressin; Blood Pressure; Brain; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Kidney; Oxytocin; Pituitary Diseases; Pituitary Gland, Posterior; Pressoreceptors; Sodium; Water-Electrolyte Balance

Arginine vasotocin, arginine vasopressin, and oxytocin play a critical role in the stimulation of labor and delivery and in salt and water homeostasis in the newborn infant. The authors present information on their chemistry, secretion, and metabolism, and discuss the clinical effects upon target organs of their presence or absence.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Female; Fetus; Humans; Inappropriate ADH Syndrome; Infant, Newborn; Infant, Newborn, Diseases; Oxytocin; Pituitary Gland; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Pregnancy; Vasopressins; Vasotocin

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.

Topics: Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Neurophysins; Osmolar Concentration; Oxytocin; Vasopressins

Oxytocin (OXT) secretion has been shown to be abnormally elevated in patients who develop syndrome of inappropriate secretion of antidiuretic hormone (SIADH)-related hyponatremia after transsphenoidal pituitary surgery (TPS). While OXT was previously reported to increase natriuresis in the kidney, a potential role for this hormone in postoperative sodium balance and dysnatremias has not been studied. The objective of this study was to analyze the correlation between patients' urinary output of OXT and natremia and natriuresis after TPS.. The authors measured and correlated the urinary output of OXT with natriuresis and natremia in 20 consecutive patients who underwent TPS.. The ratio of urinary secretion of OXT between days 1 and 4 showed a strong, significant correlation with patient natriuresis at day 7 after pituitary surgery. Concomitantly, patient natremia showed a moderate, inverted correlation with OXT secretion in the urine.. Together, these results show for the first time that urinary OXT secretion correlates with patient natriuresis and natremia after pituitary surgery. This observation suggests a notable role for this hormone in sodium balance.

Topics: Humans; Hyponatremia; Inappropriate ADH Syndrome; Natriuresis; Oxytocin; Pituitary Diseases; Sodium

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a well-known complication of transsphenoidal pituitary surgery, related to inappropriate secretion of arginine vasopressin (AVP). Its diagnosis is based on hyponatremia, with a peak of occurrence around day 7 after surgery and, to date, no early marker has been reported. In particular, copeptin levels are not predictive of hyponatremia in this case. Oxytocin (OXT) is secreted into the peripheral blood by axon terminals adjacent to those of AVP neurons in the posterior pituitary. Besides its role in childbirth and lactation, recent evidences suggested a role for OXT in sodium balance. The contribution of this hormone in the dysnatremias observed after pituitary surgery has however never been investigated.. We analyzed the urinary output of OXT in patients subjected to transsphenoidal pituitary surgery.. While OXT excretion remained stable in patients who presented a normonatremic postoperative course, patients who were later diagnosed with SIADH-related hyponatremia presented with a significantly increased urinary secretion of OXT 4 days after surgery.. Taken together, these results show for the first time that urinary OXT output remains normally stable after transsphenoidal pituitary surgery. OXT excretion however becomes abnormally high on or around 4 days after surgery in patients later developing hyponatremia, suggesting that this abnormal dynamics of OXT secretion might serve as an early marker for transsphenoidal surgery-related hyponatremia attributed to SIADH.

Topics: Arginine Vasopressin; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Oxytocin; Pituitary Diseases; Pituitary Gland, Posterior

Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was confirmed by using urinary drug screening pre- and post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/- 0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p < 0.001) and MDMA use, with the pattern of change being consistent with the induction of inappropriate vasopressin secretion (also known as SIADH) by MDMA. This report demonstrates SIADH in ecstasy-using "clubbers", which has important clinical implications.

Topics: Adolescent; Adult; Arginine Vasopressin; Arousal; Female; Homeostasis; Humans; Illicit Drugs; Inappropriate ADH Syndrome; Male; N-Methyl-3,4-methylenedioxyamphetamine; Oxytocin; Radioimmunoassay; Social Environment; Social Facilitation; Substance-Related Disorders; Water-Electrolyte Balance

A patient with a primary undifferentiated carcinoma of the nasopharynx manifested the clinical syndrome of inappropriate antidiuretic hormone secretion (SIADH). Immunohistochemical techniques demonstrated the presence of vasopressin, neurophysin, and their precursor (propressophysin) in the cancer cells. In situ hybridization additionally confirmed the expression of propressophysin messenger RNA in these cells. To the knowledge of the authors, this represents not only the first case of SIADH caused by carcinoma of the nasopharynx, but also the first report of pathologic confirmation of the syndrome with the use of both molecular and immunologic probes.

Topics: Arginine Vasopressin; Carcinoma, Squamous Cell; DNA, Neoplasm; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Nasopharyngeal Neoplasms; Neurophysins; Nucleic Acid Hybridization; Oxytocin; Protein Precursors; Vasopressins

Topics: Abortion, Threatened; Adult; Female; Humans; Hydatidiform Mole; Hypopituitarism; Inappropriate ADH Syndrome; Male; Oxytocin; Pituitary Function Tests; Pregnancy; Radioimmunoassay; Reference Values; Specimen Handling

At diagnosis, 65% of 103 patients with small cell carcinoma of the lung were found to have elevated plasma concentrations of vasopressin-associated human neurophysin (VP-HNP), oxytocin-associated human neurophysin (OT-HNP), or both, which were thought to be related to tumor secretion of these proteins. The remainder of patients were designated as nonsecretors (24%) or possible secretors (11%), depending upon plasma concentration of the neurophysins prior to therapy. There was a significantly higher percentage of secretors among patients with extensive disease (82%) than among those with limited disease (40%) (P = 0.001). However, within each stage group, there was no correlation between secretory status and response to therapy, survival, or histologic subtype. In addition, patients who initially were nonsecretors or possible secretors maintained this status throughout the course of disease remission and subsequent relapse. These findings suggest the possibility of biochemical differences between tumors which present as limited disease and those which present as extensive disease. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was infrequent in limited disease but was present in 33% of patients with extensive disease. SIADH was not seen without VP-HNP elevation; however, with extensive disease, 49% of patients with elevated VP-HNP had SIADH. In contrast, elevated plasma concentrations of the neurophysins were seen in only 19.6% of 56 patients with non-small cell carcinoma of the lung. The levels were in general lower than those in patients with small cell carcinoma and were seen at approximately equal frequencies in each major cellular subtype.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Neurophysins; Oxytocin; Prognosis; Vasopressins

Topics: Hormones, Ectopic; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Oxytocin; Pharyngeal Neoplasms; Sarcoma; Vasopressins