Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia compared to healthy controls.

OBJECTIVE: Distinguishing arginine vasopressin deficiency (AVP-D; central diabetes insipidus) from primary polydipsia (PP), commonly referred to as psychogenic polydipsia, is challenging. Psychopathologic findings, commonly used for PP diagnosis in clinical practice, are rarely evaluated in AVP-D patients, and no comparative data between the two conditions currently exist. DESIGN: Data from two studies involving 82 participants [39 AVP-D, 28 PP, and 15 healthy controls (HC)]. METHODS: Psychological evaluations were conducted using standardized questionnaires measuring anxiety [State-Trait Anxiety Inventory (STAI)], alexithymia [Toronto Alexithymia Scale (TAS-20)], depressive symptoms (Beck's Depression Inventory-II (BDI-II), and overall mental health [Short Form-36 Health Survey (SF-36)]. Higher STAI, TAS-20, and BDI-II scores suggest elevated anxiety, alexithymia, and depression, while higher SF-36 scores signify better overall mental health. RESULTS: Compared to HC, patients with AVP-D and PP showed higher levels of anxiety (HC 28 points [24-31] vs AVP-D 36 points [31-45]; vs PP 38 points [33-46], P < .01), alexithymia (HC 30 points [29-37] vs AVP-D 43 points [35-54]; vs PP 46 points [37-55], P < .01), and depression (HC 1 point [0-2] vs AVP-D 7 points [4-14]; vs PP 7 points [3-13], P < .01). Levels of anxiety, alexithymia, and depression showed no difference between both patient groups (P = .58, P = .90, P = .50, respectively). Compared to HC, patients with AVP-D and PP reported similarly reduced self-reported overall mental health scores (HC 84 [68-88] vs AVP-D 60 [52-80], P = .05; vs PP 60 [47-74], P < .01). CONCLUSION: This study reveals heightened anxiety, alexithymia, depression, and diminished overall mental health in patients with AVP-D and PP. The results emphasize the need for careful interpretation of psychopathological characteristics to differentiate between AVP-D and PP.

ADHD symptoms in a young patient with central diabetes insipidus.

Diabetes insipidus is known to be associated with neurodevelopmental disorders. In this case report, we present a child suffering from a central diabetes insipidus (DI) and an attention-deficit/hyperactivity disorder (ADHD). The DI was due to a mutation on the vasopressin gene, impairing its secretion. We discuss the effects of this impairment on the central nervous system and how it might be linked to ADHD symptoms.

Hypopituitarism is associated with lower oxytocin concentrations and reduced empathic ability.

PURPOSE: Central diabetes insipidus is characterised by arginine vasopressin deficiency. Oxytocin is structurally related to vasopressin and is synthesised in the same hypothalamic nuclei, thus we hypothesised that patients with acquired central diabetes insipidus and anterior hypopituitarism would display an oxytocin deficiency. Moreover, psychological research has demonstrated that oxytocin influences social and emotional behaviours, particularly empathic behaviour. We therefore further hypothesised that central diabetes insipidus patients would perform worse on empathy-related tasks, compared to age-matched and gender-matched clinical control (clinical control-isolated anterior hypopituitarism) and healthy control groups. METHOD: Fifty-six participants (age 46.54 ± 16.30 yrs; central diabetes insipidus: n = 20, 8 males; clinical control: n = 15, 6 males; healthy control: n = 20, 7 males) provided two saliva samples which were analysed for oxytocin and completed two empathy tasks. RESULTS: Hypopituitary patients (both central diabetes insipidus and clinical control groups) had significantly lower oxytocin concentrations compared to healthy control participants. Hypopituitary patients also performed significantly worse on both the reading the mind in the eyes task and the facial expression recognition task compared to healthy control participants. Regression analyses further revealed that central diabetes insipidus patients' oxytocin concentrations significantly predicted their performance on easy items of the reading the mind in the eyes task. CONCLUSIONS: Hypopituitarism may therefore be associated with reduced oxytocin concentrations and impaired empathic ability. While further studies are needed to replicate these findings, our data suggest that oxytocin replacement may offer a therapeutic approach to improve psychological well-being in patients with hypopituitarism.

Quality of life in the patients with central diabetes insipidus assessed by Nagasaki Diabetes Insipidus Questionnaire.

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.

Radiological remission and recovery of thirst appreciation after infliximab therapy in adipsic diabetes insipidus secondary to neurosarcoidosis.

BACKGROUND: Neurosarcoidosis is a rare and aggressive variant of systemic sarcoidosis which may result in hypothalamic-pituitary dysfunction. We report a case of hypothalamic hypopituitarism secondary to neurosarcoidosis complicated by adipsic diabetes insipidus (ADI). Initiation of anti-tumour necrosis factor-α (TNF-α) therapy resulted in both radiological disease remission and recovery of osmoregulated thirst appreciation after 3 months. CASE SUMMARY: A 22-year-old man was referred to the endocrinology service with profound weight gain, polyuria and lethargy. Biochemical testing confirmed anterior hypopituitarism while posterior pituitary failure was confirmed by hypotonic polyuria responding to desmopressin. Magnetic resonance imaging (MRI) demonstrated extensive hypothalamic infiltration; neurosarcoidosis was confirmed histologically after excisional cervical lymph node biopsy. Osmoregulated thirst appreciation was normal early in the disease course despite severe hypotonic polyuria. However, subsequent subjective loss of thirst appreciation and development of severe hypernatraemia in the setting of normal cognitive function indicated onset of ADI. MANAGEMENT: Clinical management involved daily weighing, regular plasma sodium measurement, fixed daily fluid intake and oral desmopressin. We initiated immunosuppressive therapy with pulsed intravenous anti-TNF-α therapy (infliximab) after multidisciplinary team consultation. OUTCOME: Infliximab therapy resulted in successful radiological disease remission and complete recovery of osmoregulated thirst appreciation. This was confirmed by subjective return of thirst response and maintenance of plasma sodium in the normal range in the absence of close biochemical monitoring.

Copeptin concentrations during psychological stress: the PsyCo study.

OBJECTIVE: The prognostic/diagnostic biomarker copeptin, an arginine vasopressin surrogate, reflects physical stress. Whether copeptin concentration increases upon psychological stress is unknown. We investigated psychological stress effects on copeptin secretion in healthy volunteers and patients with central diabetes insipidus (DI). DESIGN: A prospective observational study was conducted to study the relation between copeptin concentration and psychological stress. METHODS: A total of 20 healthy adults (ten female) and eight patients with central DI (four female) underwent the Trier Social Stress Test including, in order, 30-min waiting period, 10-min anticipation period, 10-min test period and 40-min recovery. Serum copeptin and cortisol concentrations and self-rated stress component feelings were determined in the pre-/post-anticipation period, post-test period and twice post-recovery. RESULTS: In healthy volunteers, the median (25th-75th percentile) copeptin concentration peaked immediately during the post-test period at 5.1 (3.2-7.0) pmol/l, vs 3.7 (2.6-5.4) pmol/l at baseline. Over the measurement course, copeptin concentration significantly elevated (coefficient; 95% CI) (0.14; 0.06-0.23, P=0.002). The important predictors of increase in copeptin concentration were feelings of tension (0.06; 0.04-0.08, P<0.001) and avoidance (0.07; 0.04-0.10; P<0.001). Copeptin and cortisol levels were associated (0.43; 0.13-0.72, P<0.005). Patients with DI had lower baseline concentrations (1.55 (1.2-3.1) pmol/l) when compared with healthy volunteers, P=0.006. Patients with DI showed no increase upon psychological stress (peak 2.15 pmol/l (1.5-2.28), P=0.79). By contrast, cortisol values were similar in patients and volunteers. CONCLUSIONS: In healthy volunteers, copeptin levels significantly increased after psychological stress testing; this response was blunted in patients with DI.

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.

Effect of the 2004 mid niigata prefecture earthquake on patients with endocrine disorders.

A major earthquake (Richter scale magnitude 6.8) struck the Chuetsu district of Niigata Prefecture, Japan, a rural area with mountain villages, on October 23, 2004. Strong aftershocks (Grade 5-6 on the Japanese intensity scale, JIS) continued for 2 months. We analyzed the earthquake's impact on 229 patients with various endocrine disorders [6 central diabetes insipidus (CDI), 16 adrenal insufficiency (AI) including 5 panhypopituitarism, 10 ACTH isolated deficiency and 1 Addison's disease, 145 Graves' disease and 62 Hashimoto's disease]. The status of patients with CDI or AI was not adversely affected by the earthquake. Twenty-eight (19%) patients with Graves' disease developed more severe hyperthyroidism; the incidence of developing more severe hyperthyroidism increased with greater degrees of hyperthyroidism. Three (5%) patients with Hashimoto's disease developed increased TSH concentrations. Most patients stayed in their own houses following the first shock. The median PTSD total score for all patients was low. However, the PTSD total score in patients with CDI or Hashimoto's disease was significantly higher than in other patients, while the subscore of mental status in patients with AI was significantly much lower than in other patients. In patients with Hashimoto's disease, patients whose hypothyroidism worsened had higher total and environmental effects score than patients whose hypothyroidism remained stable. Comparing patients whose hyperthyroidism became more severe to those in whom it remained stable, as well as on multiple logistic regression analysis, serum TRAb was found to be a risk factor for developing more severe hyperthyroidism. In conclusion, our findings indicate that Graves' disease patients need to maintain their euthyroid state with a low serum TRAb titer to prevent the development of further thyroid dysfunction after an earthquake, and that all patients should continue to take their medication, since it is likely that their lives will be interrupted by environmental effects owing to earthquake-shock, especially patients with CDI or Hashimoto's disease. Due to the risk of medical facility closure during a disaster, all patients should always have a note or copy of their medical records, including medical history and medications used, to avoid relying on patients remembering their drug names and doses. Furthermore, appropriate information should be provided by all means possible, including the mass media, to affected individuals, particularly those with AI, to decrease the occurrence of adverse consequences.

Minor disturbances in central nervous system function in familial neurohypophysial diabetes insipidus.

Familial neurohypophysial diabetes insipidus (FNDI) is caused by a defect in vasopressin synthesis and release as a result of a heterozygous mutation in the gene for the vasopressin prohormone. The predominant characteristic of FNDI is excessive thirst and urine production. However, vasopressin not only has peripheral endocrine effects, but also regulates numerous brain functions. We investigated whether central functions are affected in FNDI, by studying neuropsychological functioning of 23 affected members (15 males, 8 females) of a large family carrying a T/G transition mutation at nucleotide 2110 (codon 116) of the vasopressin prohormone gene (Cys116Gly). The relatively large number of family members with FNDI made it possible to compare cognitive and other CNS effects in these subjects with those of family members without FNDI. Thirty-seven adult volunteers (20 males, 17 females) from the same family and 11 non-family members (2 males, 9 females) from northern part of The Netherlands were tested. The mean age of the subjects was 35+/-12 years. Of the 63 quantified neuropsychological parameters few were statistically different between the subjects with FDNI and control subjects. Memory retrieval processes and sustained attention were worse in the subjects with FDNI. Moreover, these individuals reported significantly fewer symptoms of agoraphobia and miscellaneous symptoms, and had significantly lower scores on a scale measuring anger. The performance of FNDI subjects on an auditory verbal learning test (the 15-word test learning trial) was worse, but not significantly so, than that of the subjects without FDNI. There were subjective complaints of forgetfulness and slow recalls and those were observed in daily life by non-affected family members. These moderate differences in neuropsychological performance indicate that in human FNDI parvocellular vasopressin systems that supply the brain may be less affected or give no such serious disabilities, than the magnocellular hypothalamo-neurohypophysial system that provides vasopressin for endocrine regulation of water homeostasis.

Identification of a novel mutation in the arginine vasopressin-neurophysin II gene affecting the sixth intrachain disulfide bridge of the neurophysin II moiety.

OBJECTIVE: Most mutations of the arginine vasopressin-neurophysin II (AVP-NPII) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). Such mutations are predicted to alter the three-dimensional structure of the prohormone, which accumulates in the cell body, ultimately leading to neuronal degeneration and hormonal deficit. In this study we describe the case of a 26-year-old female reporting a long-lasting history of polyuria/polydipsia. The father of the patient was affected by diabetes insipidus and was under desmopressin treatment until the time of his death. Nevertheless, the patient had never been subjected to endocrine evaluation. DESIGN AND METHODS: Clinical and genetic studies were performed. An 8-h fluid deprivation test plus desmopressin challenge and a 5% saline solution test were performed, in order to confirm the diagnosis. DNA was extracted from peripheral blood lymphocytes and subjected to direct sequencing of the entire coding region of the AVP-NPII gene. RESULTS AND CONCLUSIONS: Clinical assessment of the patient confirmed the diagnosis of neurohypophyseal diabetes insipidus. Desmopressin treatment was started, which effectively reversed the polyuria/ polydipsia syndrome. Genetic analysis revealed a novel mutation (1665T>A) in exon 2 of the AVP-NPII gene, disrupting one of the disulfide bonds present in the NPII moiety which play a fundamental role in determining the proper folding of the molecule. In summary, in the present study we have described a novel mutation of the AVP-NPII gene, which is consistent with the malfolding/toxicity hypothesis underlying the pathogenesis of adFNDI.