CENTRAL DIABETES INSIPIDUS INDUCED BY TUBERCULOSIS IN A RHEUMATOID ARTHRITIS PATIENT

Tuberculosis, a polymorphic disease, is a diagnostic challenge, particularly when arises concomitantly to an autoimmune disease such as rheumatoid arthritis (RA). Herein, the authors describe a 33-year-old woman with nodular RA who was being treated with methotrexate, sulfasalazine and corticosteroids and presented with subcutaneous nodules simultaneously with aseptic meningitis. Mycobacterium tuberculosis was identified in cultures from a biopsy of an axillary nodule. The patient also developed polyuria and polydipsia with normal glycemia; antidiuretic hormone (ADH) treatment before and after a 3% saline infusion test was performed and diabetes insipidus was diagnosed. An encephalic MRI showed sellar and suprasellar masses, suggesting central diabetes insipidus (CDI). The patient received standard tuberculosis (TB) treatment for 6 months and also DDAVP (desmopressin acetate) during this period. Control of CDI was observed. A pre-surgical magnetic resonance imaging (MRI) showed no pituitary mass. It is known that intrasellar tuberculoma occurs in only 1% of TB patients. TB should be considered in the differential diagnosis of CDI, especially in immunosupressed patients and in countries where this infection is a serious public health problem.

Acquired central diabetes insipidus in children: A 12 year Brisbane experience

Objective: To study the clinical, endocrine and radiological features and progress of children presenting with acquired diabetes insipidus (CDI). Methodology: Chart review of children presenting because of CDI to Brisbane paediatric endocrine clinics between 1987 and 1999. Results: Thirty-nine children (female/male ratio 21/18) aged 0.1-15.4 years (mean age 6.7 years) were identified. Aetiologies were head trauma or familial in eight cases (20.5%) each, central nervous system (CNS) tumours in five cases (12.8%), CNS malformations in four cases (10.2%), histiocytosis in three cases (7%) and hypoxia and infection in two cases (5.1%) each. Seven cases (17.9%) remain undiagnosed. Of the 32 (82%) cases with isolated anti-diuretic hormone deficiency at presentation, 24 cases (61.5%) experienced no further endocrine deficit. Additional endocrine deficits occurred mainly in the tumour or undiagnosed groups. On follow-up brain magnetic resonance imaging (MRI) scans in the seven undiagnosed cases, six patients bad mild or no change and one patient had marked improvement of MRI findings. These changes occurred 10-48 months (mean 18 months) after presentation. Conclusions: Children without an aetiological diagnosis for the uncommon condition of acquired CDI require careful follow-up. More intensive investigation at presentation (e.g. estimation of cerebrospinal fluid human chorionic gonadotrophin) promises to lessen the number of such cases. Pituitary stalk biopsies should be reserved for those patients with progressive MRI changes. If these changes do not occur early, our experience suggests that follow-up MRI scans may need to be performed only yearly.

Acute Sheehan's Syndrome Presenting as Central Diabetes Insipidus

Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome.

L'infundibulite, une cause rare (?) de diabète insipide central [Infundibulitis, an unusual case of central diabetes insipidus].

We report the case of a 53 year old patient who was admitted with polyuria, polydipsia associated with fatigue, depression and sexual dysfunction. Central diabetes insipidus with hypogonadotrophic hypogonadism was diagnosed by a water restriction test and different static and dynamic hormonal dosages. Nodular thickening of the pituitary stalk was noted on the MRI and the biopsy permitted a histological diagnosis of infundibulitis.

Trauma-induced central diabetes insipidus in a cat

A 1-year-old neutered male domestic shorthair cat presented with a 4-week history of polydipsia that began immediately after an 8 metre fall, Trauma-induced central diabetes insipidus was suspected on the basis of the identification of hyposthenuria, normal haematology and serum biochemistry profile and unremarkable abdominal ultrasound examination. Failure to concentrate urine with water deprivation followed by production of hypersthenuric urine with administration of the synthetic antidiuretic hormone, Deamino-8-D-arginine vasopressin (DDAVP), confirmed the diagnosis of central diabetes insipidus. Treatment via conjunctival administration of DDAVP failed to attenuate the polydipsia, however, resolution of polydipsia was achieved with subcutaneous administration of DDAVP and the cat remains eudipsic with twice daily subcutaneous DDAVP administration 17 months after diagnosis.

Lack of MRI neurohypophyseal bright signal in a child with congenital nephrogenic diabetes insipidus

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disease characterized by the inability of the kidney to respond to arginine vasopressin (AVP). The absence of the neurohypophyseal 'bright signal' on T1 sequence magnetic resonance imaging (MRI) is considered as an argument in favour of the diagnosis of central diabetes insipidus (CDI). This observation is challenged as we hereby present a case of a child diagnosed with CNDI and who did not present MRI pituitary bright signal. A 6-month-old male presented with failure to thrive, polyuria and polydypsia. Family history revealed that the mother, 35 years of age, had been presenting polydypsia and polyuria, and she was investigated at the age of 6 years with no concluding diagnosis. The patient's physical exam showed a weight of 5215 g (−3 DS) and clinical signs of dehydration. The patient's plasma sodium level was 155 mmol/L, osmolality 305 mOsm/kg and urine osmolality 150 mOsm/kg. Brain MRI showed in T1 sequences the absence of the posterior pituitary bright signal suggesting the diagnosis of CDI (Figure 1). The child was treated with synthetic AVP analogue 1-desamino-8-d-arginine vasopressin (DDAVP) without improvement, which led to the consideration of CNDI. The diagnosis was confirmed by an elevated serum level of AVP of 214 pmol/L (reference value ≤4.34 pmol/L) and by genetic analysis demonstrating and T106C mutation in the V2R (X-linked CNDI). The child was treated with thiazide diuretic and increased fluids with restricted sodium intake. This resulted in catch-up growth and improved neurological development. A follow-up MRI was performed 6 months after the start of therapy with the same technique. At that time, the child's weight had improved to 9310 g (−1.5 DS) corresponding to a gain of 22 g per day, and he did not present any clinical signs of dehydration and had a normal plasma level of sodium (140 mmol/L). MRI showed that the bright signal was still absent.

Diagnosis of diabetes insipidus observed in Swiss Duroc boars

Background Diabetes insipidus (DI) is a rare disease in humans and animals, which is caused by the lack of production, malfunction or dysfunction of the distal nephron to the antidiuretic effect of the antidiuretic hormone (ADH). Diagnosis requires a thorough medical history, clinical examination and further laboratory confirmation. This case report describes the appearance of DI in five Duroc boars in Switzerland. Case presentation Two purebred intact Duroc boars at the age of 8 months and 1.5 years, respectively, with a history of polyuric and polydipsic symptoms had been referred to the Swine Clinic in Berne. Based on the case history, the results of clinical examination and the analysis of blood and urine, a tentative diagnosis of DI was concluded. Finally, the diagnosis was confirmed by findings from a modified water deprivation test, macroscopic examinations and histopathology. Following the diagnosis, three genes known to be involved in inherited DI in humans were analyzed in order to explore a possible genetic background of the affected boars. Conclusion The etiology of DI in pigs is supposed to be the same as in humans, although this disease has never been described in pigs before. Thus, although occurring only on rare occasions, DI should be considered as a differential diagnosis in pigs with polyuria and polydipsia. It seems that a modified water deprivation test may be a helpful tool for confirming a diagnosis in pigs. Since hereditary forms of DI have been described in humans, the occurrence of DI in pigs should be considered in breeding programs although we were not able to identify a disease associated mutation.

Blood pressure reduction and diabetes insipidus in transgenic rats deficient in brain angiotensinogen

Angiotensin produced systemically or locally in tissues such as the brain plays an important role in the regulation of blood pressure and in the development of hypertension. We have established transgenic rats [TGR(ASrAOGEN)] expressing an antisense RNA against angiotensinogen mRNA specifically in the brain. In these animals, the brain angiotensinogen level is reduced by more than 90% and the drinking response to intracerebroventricular renin infusions is decreased markedly compared with control rats. Blood pressure of transgenic rats is lowered by 8 mmHg (1 mmHg = 133 Pa) compared with control rats. Crossbreeding of TGR(ASrAOGEN) with a hypertensive transgenic rat strain exhibiting elevated angiotensin II levels in tissues results in a marked attenuation of the hypertensive phenotype. Moreover, TGR(ASrAOGEN) exhibit a diabetes insipidus-like syndrome producing an increased amount of urine with decreased osmolarity. The observed reduction in plasma vasopressin by 35% may mediate these phenotypes of TGR(ASrAOGEN). This new animal model presenting long-term and tissue-specific down-regulation of angiotensinogen corroborates the functional significance of local angiotensin production in the brain for the central regulation of blood pressure and for the pathogenesis of hypertension.

alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus.

Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic mice lacking αENaC specifically in the CD (knockout [KO] mice) and littermate controls to chronic lithium treatment. In contrast to control mice, KO mice did not markedly increase their water intake. Furthermore, KO mice did not demonstrate the polyuria and reduction in urine osmolality induced by lithium treatment in the control mice. Lithium treatment reduced AQP2 protein levels in the cortex/outer medulla and inner medulla (IM) of control mice but only partially reduced AQP2 levels in the IM of KO mice. Furthermore, lithium induced expression of H(+)-ATPase in the IM of control mice but not KO mice. In conclusion, the absence of functional ENaC in the CD protects mice from lithium-induced NDI. These data support the hypothesis that ENaC-mediated lithium entry into the CD principal cells contributes to the pathogenesis of lithium-induced NDI.

[Lymphadenopathy and diabetes insipidus - association]

We report the case of a 62 year old women with chronic idiopathic myelofibrosis who developed acute lymphadenopathy. At the same time diabetes insipidus, osteolytic bone lesions and exanthema of the skin were diagnosed. Suspected Langerhans cell histiocytosis could be proven by repeated biopsies of affected organs. Therapy was started in accordance with the recommendations of the Histiocyte Society.

[Hereditary nephrogenetic diabetes insipidus--case report and discussion]

The history of a patient with hereditary nephrogenic diabetes insipidus is discussed. The pathogenesis and the therapeutic approach is revised.

Autosomal dominant neurohypophyseal diabetes insipidus in a Swiss family, caused by a novel mutation (C59Delta/A60W) in the neurophysin moiety of prepro-vasopressin-neurophysin II (AVP-NP II).

OBJECTIVE To study clinical, morphological and molecular characteristics in a Swiss family with autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). PARTICIPANTS AND METHODS A 15-month-old girl presenting with symptoms of polydipsia and polyuria was investigated by water deprivation test. Evaluation of the family revealed three further family members with symptomatic vasopressin-deficient diabetes insipidus. T1-weighted magnetic resonance images of the posterior pituitary were taken in two affected adult family members and molecular genetic analysis was performed in all affected individuals. RESULTS The water deprivation test in the 15-month-old child confirmed the diagnosis of vasopressin-deficient diabetes insipidus and the pedigree was consistent with autosomal dominant inheritance. The characteristic bright spot of the normal vasopressin-containing neurophypophysis was absent in both adults with adFNDI. Direct sequence analysis revealed a new deletion (177-179DeltaCGC) in exon 2 of the AVP-NP II gene in all affected individuals. At the amino acid level, this deletion eliminates cysteine 59 (C59Delta) and substitutes alanine 60 by tryptophan (A60W) in the AVP-NP II precursor; interestingly, the remainder of the reading frame remains unchanged. According to the three-dimensional structure of neurophysin, C59 is involved in a disulphide bond with C65. CONCLUSIONS Deletion of C59 and substitution of A60W in the AVP-NP II precursor is predicted to disrupt one of the seven disulphide bridges required for correct folding of the neurophysin moiety and thus disturb the function of neurophysin as the vasopressin transport protein. These data are in line with the clinical and morphological findings in the reported family with adFNDI.

Hyponatremia associated coma due to pituitary apoplexy in early pregnancy: a case report

Pituitary apoplexy in pregnancy is rare. Its clinical features may range from unspecific complaints to panhypopituitarism resulting even in coma and death. Therefore, alertness to signs and symptoms of acute loss of pituitary function in pregnancy is mandatory. We report a woman in her 7th week of her first gestation presenting with sudden coma due to severe hyponatremia. Secondary adrenal insufficiency could be identified as the underlying cause. Panhypopituitarism including central diabetes insipidus and spontaneous abortion developed during the follow-up. Magnetic resonance imaging showed pituitary apoplexy without a pre-existing pituitary mass. The clinical course was notable for severe complications, including neurological deficits through cerebral ischemia, but eventual recovery could be achieved. We discuss the diagnostic difficulties in the evaluation of pituitary disease in pregnancy.

Suprasellar germinomas in childhood and adolescence: diagnostic pitfalls

The clinical and neuro-endocrine data of seven young male patients with suprasellar germinomas seen between 1984 and 1992 are reported. The most common initial symptom was 'idiopathic' central diabetes insipidus (DI), which occurred in all seven patients. The time interval between the appearance of this first clinical sign and the definitive diagnosis of a suprasellar germinoma ranged from 3 to 66 months. Raised prolactin levels and growth hormone deficiency were indicators of a process located in the hypothalamic-pituitary region. An increased beta-HCG level in the serum or the CSF confirmed the diagnostic suspicion of a germinoma and was helpful as a tumor marker in follow-up. Neuro-radiologic studies (CT or MRI) were also disappointing in the early stage when patients presented only with DI. Later on, as patients developed additional symptoms or signs related to the tumor, imaging studies were positive. Given the variable rate of tumor progression, the nonspecific early signs of hypothalamic-pituitary dysfunction (DI) as well as the often negative early imaging studies, the diagnosis of suprasellar germinoma is difficult but should always be considered in the presence of so-called 'idiopathic' central DI. Repeated brain MRIs are mandatory in young patients with idiopathic DI in order not to miss an underlying suprasellar germinoma.

Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort

BACKGROUND & AIMS Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency. METHODS We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins. RESULTS We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears. CONCLUSIONS In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption.