pituitrin and Autoimmune-Diseases

Diabetes insipidus is a heterogeneous condition characterised by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. The clinical and laboratory diagnosis is confirmed by standard tests, but recent advances in molecular biology and imaging techniques have shed new light on the pathophysiology of this disease. In many patients, central diabetes insipidus is caused by a germinoma or craniopharyngioma; Langerhans' cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma from surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Tumour-associated central diabetes insipidus is uncommon in children younger than 5 years old. Biopsy of enlarged pituitary stalk should be reserved for patients with hypothalamic-pituitary mass and progressive thickening of the pituitary stalk since spontaneous recovery may occur. Molecular biology in selected patients may identify those with apparently idiopathic diabetes insipidus carrying the vasopressin-neurophysin II gene mutation.

Topics: Autoimmune Diseases; Brain Neoplasms; Child; Diabetes Insipidus, Neurogenic; Germinoma; Humans; Neurophysins; Vasopressins

Rodent animal models of inflammatory and autoimmune disease have been important tools in the study of the interaction between neuroendocrine physiology and the immune responses. The rat has been particularly useful in part because, in contrast to other species, most rat models of autoimmune/inflammatory disease are induced rather than spontaneous. This allows for systematic and controlled manipulations of the neuroendocrine system in relation to exposure to the antigen or proinflammatory trigger. The most frequently used immune challenges include lipopolysaccharide-induced septic shock, carrageenan-induced local inflammation and adjuvant or bacterial cell wall-induced arthritis. By analyzing the responses to these challenges in different strains of rats and mice it has been possible to define the relationships between the neuroendocrine and immune systems and to identify some mechanisms through which these connections confer susceptibility and resistance to autoimmune and inflammatory diseases. The present review will discuss data obtained from rodent physiology, indicating that an important component in the susceptibility or resistance to development of these diseases is due to dysfunctional regulation of the immune response by the neuroendocrine hypothalamic-pituitary-adrenal axis. In particular, the importance of neurons of the paraventricular hypothalamic nucleus in determining susceptibility or resistance to autoimmune and inflammatory disease will be discussed.

Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Disease Susceptibility; Environment; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Hypothalamo-Hypophyseal System; Immunity, Innate; Inflammation; Mice; Mice, Knockout; Neurosecretory Systems; Neurotransmitter Agents; Pituitary-Adrenal System; Rats; Rats, Inbred Strains; Vasopressins

Topics: Autoantibodies; Autoimmune Diseases; Child; Diabetes Insipidus; Fetus; Humans; Hypothalamus; Vasopressins

Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

Topics: Arthritis, Reactive; Autoantibodies; Autoimmune Diseases; Diabetes Insipidus, Neurogenic; Female; Humans; Middle Aged; Neurophysins; Protein Precursors; Ureaplasma Infections; Ureaplasma urealyticum; Vasopressins

A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and still showed impaired water diuresis during glucocorticoid replacement therapy is reported. A 45-year-old woman was initially admitted for nausea, vomiting, and general malaise. Her serum sodium and plasma osmolality, ACTH and cortisol values were low, but her urine osmolality was high. Other pituitary hormone levels, thyroid hormone levels, and a computed tomogram of the pituitary gland were normal. The patient was treated with hydrocortisone and followed in the outpatient clinic; however, she was lost to follow up 18 months after admission. Three years later she presented with hypoglycemia and hyponatremia. Her serum or plasma ACTH, FT3, FT4, cortisol levels were low and her serum TSH level was high. Pituitary stimulation tests revealed a blunted response of ACTH to CRH and an exaggerated response of TSH to TRH. Plasma ADH was inappropriately high, and a water-loading test revealed impaired water diuresis and poor suppression of ADH. Although ADH was suppressed, impaired water diuresis was observed in the water loading test after hydrocortisone supplementation. Thyroxine supplementation completely normalized the water diuresis. Her outpatient clinic medical records revealed a gradual increase in TSH levels during follow up, indicating that she had developed hypothyroidism during glucocorticoid replacement therapy. The hyponatremia on the first admission was due to glucocorticoid deficiency, whereas the hyponatremia on the second admission was due to combined deficiencies of glucocorticoid and thyroid hormones.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Autoimmune Diseases; Blood; Diuresis; Female; Hormone Replacement Therapy; Humans; Hydrocortisone; Hyponatremia; Hypothyroidism; Middle Aged; Osmolar Concentration; Thyrotropin; Thyroxine; Triiodothyronine; Urine; Vasopressins

The spontaneous development of autoimmune disease in MRL-lpr mice induces behavioral and endocrine changes that resemble effects of chronic stressors. To further examine the correspondence between autoimmune disease and chronic stress, we asked whether the brains of autoimmune mice show a shift in the corticotropin-releasing factor (CRF) to vasopressin (AVP) ratio. Using in situ hybridization histochemistry with 35S-labelled mouse riboprobes, the levels of mRNA transcripts encoding CRF and AVP were compared between autoimmune MRL-lpr and control MRL +/+ brains. CRF transcript levels were lower in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala in MRL-lpr mice. AVP transcript levels were higher in the paraventricular and the supraoptic nuclei in MRL-lpr mice compared to controls. CRF mRNA levels were inversely related to performance in stress-sensitive tasks and to measures of autoimmunity. As found previously for behavioral performance, immunosuppressive treatment with cyclophosphamide abolished the group difference in neuropeptide gene expression. These results indicate that an autoimmune disease process is necessary for the shift in the brain CRF:AVP ratio. Furthermore, they support the parallel between chronic stress and chronic autoimmunity/inflammation, and suggest common central mechanisms relevant to endocrine function and behavior.

Topics: Animals; Autoimmune Diseases; Behavior, Animal; Body Temperature; Brain Chemistry; Corticotropin-Releasing Hormone; DNA, Complementary; Gene Expression; In Situ Hybridization; Limbic System; Male; Mice; Mice, Inbred MRL lpr; Neuroimmunomodulation; Paraventricular Hypothalamic Nucleus; RNA, Messenger; Stress, Physiological; Supraoptic Nucleus; Swimming; Transcription, Genetic; Vasopressins

Cytoplasmic autoantibodies to vasopressin-cells (AVPcAb) have been detected not only in patients with overt central diabetes insipidus (CDI), but also in patients with endocrine autoimmune diseases without CDI. This suggests that complete CDI can be preceded by a preclinical stage. Among 878 patients with endocrine autoimmune diseases without CDI, 9 patients found to be AVPcAb positive and 139 AVPcAb-negative controls were enrolled in this open prospective study. They were evaluated for AVPcAb and posterior pituitary function at least yearly for about 4 yr (range, 37-48 months); during this span, magnetic resonance imaging (MRI) of posterior pituitary and stalk was performed only in the AVPcAb-positive patients. Five of the 9 AVPcAb-positive patients had normal posterior pituitary function at study entry. They were AVPcAb positive throughout the follow-up period. At later stages of the study, 3 of them developed partial CDI, and 1 developed complete CDI. The remaining 4 patients showed impaired response to the water deprivation test at study entry and were diagnosed as having partial CDI. Two of them agreed to receive desmopressin replacement for 1 yr. After this treatment, the patients became negative for AVPcAb and displayed normal posterior pituitary function until the end of the follow-up. Conversely, the 2 untreated patients with partial CDI remained AVPcAb positive. One of them developed overt CDI. None of the controls became AVPcAb positive or developed CDI. The normal hyperintense MRI signal of the posterior pituitary, present at study entry, persisted subsequently in all 9 AVPcAb-positive patients, including those developing overt CDI, only disappearing in the late phase of complete CDI. In asymptomatic subjects, the monitoring of AVPcAb, but not MRI, seems to be useful to predict a progression toward partial/overt CDI. Early desmopressin therapy in patients with partial CDI could interrupt or delay the autoimmune damage and the progression toward clinically overt CDI.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Pituitary Gland, Posterior; Prospective Studies; Vasopressins; Water Deprivation

Pharmacological strategies have been employed to manipulate the response to atriopeptin (AP-28; ANF 99-126) in rats. These approaches include: heparin infusion which blocks the natriuresis-diuresis produced by exogenous AP infusion or by acute volume expansion; and autoimmune rats with endogenous antibody that blocks the natriuresis-diuresis produced by administration of exogenous AP or by acute volume expansion in anesthetized rats. Administration of the pressor analog 1-deamino-arg8-vasopressin (dAVP) to rats produces an elevation in systemic and right atrial blood pressure and markedly increases atriopeptin blood levels. The dAVP also produces a delayed natriuresis-diuresis which is effectively blunted in the autoimmune or heparin treated rats. The above approaches provide tools, in the absence of a specific receptor antagonist, with which to validate the intrinsic involvement of AP in physiological, pharmacological, or pathophysiological events.

Topics: Animals; Atrial Natriuretic Factor; Autoimmune Diseases; Blood Volume; Diuresis; Heparin; Natriuresis; Rats; Vasopressins

Topics: Antibody Specificity; Autoantibodies; Autoimmune Diseases; Diabetes Insipidus; Humans; Hypothalamus; Vasopressins

Topics: Autoimmune Diseases; Benzothiadiazines; Chlorpropamide; Clofibrate; Diabetes Insipidus; Diuretics; Drinking; Humans; Osmolar Concentration; Polyuria; Sodium Chloride Symporter Inhibitors; Vasopressins

Autoantibodies to vasopressin-secreting cells of human hypothalamus were detected by means of indirect immunofluorescence (IFL) in 13 patients with diabetes insipidus (DI). 11 of 30 patients (36 . 7%) with "idiopathic" and 2 of 32 (6 . 3%) with symptomatic DI were positive, and 139 control patients were negative. The specificity of the reaction vasopressin cells was demonstrated with a 4-layer double-fluorochrome IFL test in which the second sandwich consisted of rabbit antivasopressin or anti-oxytocin counterstained with rhodaminated anti-rabbit immunoglobulin. 5 patients had also antibodies to oxytocin-producing cells. The antibodies reacted with cytoplasmic components distinct from the hormone; they were of IgG, IgA, or IgM class or a combination of these classes, and half of them fixed complement. Maximum titres were 1:32, and the antibodies could not be absorbed out by incubation with vasopressin, oxytocin, neurophysin I, or neurophysin II. Some sera stained as yet unidentified small cells in the hypothalamus. This report suggests that autoimmunity extends to the hypothalamus. Vasopressin-cell antibodies may prove to be useful markers for the diagnosis of an autoimmune variant of diabetes insipidus.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Child; Diabetes Insipidus; Female; Fluorescent Antibody Technique; Humans; Hypothalamus; Male; Middle Aged; Organ Specificity; Paraventricular Hypothalamic Nucleus; Supraoptic Nucleus; Vasopressins

Autoantibodies against vasopressin (AVP)-producing cells of the human pituitary gland as well as conventional antibodies were determined in 67 patients with central diabetes insipidus and in 141 controls without diabetes insipidus using an immunofluorescence technique. Eleven out of 30 patients (37%) with nonfamilial idiopathic diabetes insipidus, two out of 28 patients (7%) with symptomatic diabetes insipidus and none of the control persons had AVP-cell antibodies. Antibody titres were between 1 : 2 and 1 : 32, in 8 of the 13 cases the antibodies were complement-binding. In 9 patients with idiopathic diabetes insipidus and in none of the symptomatic cases one or more autoimmune diseases were demonstrable. Demonstration of autoantibodies against AVP-cells of the pituitary in the serum of patients with so-called idiopathic diabetes insipidus indicates an autoimmune basis of the disease. This interpretation of the new antibody results is supported by a frequent association of idiopathic diabetes insipidus with recognized auto-immune diseases.

Topics: Adolescent; Adult; Aged; Autoantibodies; Autoimmune Diseases; Child; Child, Preschool; Cross Reactions; Diabetes Insipidus; Female; Fluorescent Antibody Technique; Humans; Hypothalamus; Infant; Male; Middle Aged; Oxytocin; Vasopressins

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Alkalosis; Autoimmune Diseases; Bone Diseases; Carcinoma, Bronchogenic; Cushing Syndrome; Endocrine System Diseases; Hypercalcemia; Hyperparathyroidism; Hyponatremia; Lung Neoplasms; Metabolic Diseases; Neoplasm Metastasis; Neurologic Manifestations; Neuromuscular Diseases; Skin Diseases; Skin Manifestations; Vascular Diseases; Vasopressins

Topics: Adult; Antibody Formation; Autoantibodies; Autoimmune Diseases; Brain; Complement Fixation Tests; Diabetes Insipidus; Female; Humans; Male; Prednisone; Time Factors; Vasopressins