Diagnosis and Management of Central Diabetes Insipidus in Adults.

Central diabetes insipidus (CDI) is a clinical syndrome which results from loss or impaired function of vasopressinergic neurons in the hypothalamus/posterior pituitary, resulting in impaired synthesis and/or secretion of arginine vasopressin (AVP). AVP deficiency leads to the inability to concentrate urine and excessive renal water losses, resulting in a clinical syndrome of hypotonic polyuria with compensatory thirst. CDI is caused by diverse etiologies, although it typically develops due to neoplastic, traumatic, or autoimmune destruction of AVP-synthesizing/secreting neurons. This review focuses on the diagnosis and management of CDI, providing insights into the physiological disturbances underpinning the syndrome. Recent developments in diagnostic techniques, particularly the development of the copeptin assay, have improved accuracy and acceptability of the diagnostic approach to the hypotonic polyuria syndrome. We discuss the management of CDI with particular emphasis on management of fluid intake and pharmacological replacement of AVP. Specific clinical syndromes such as adipsic diabetes insipidus and diabetes insipidus in pregnancy as well as management of the perioperative patient with diabetes insipidus are also discussed.

Acquired forms of central diabetes insipidus: Mechanisms of disease.

Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by pressure or infiltration, 2) damage to the vasopressin neurons by surgery or head trauma, and 3) autoimmune destruction of the vasopressin neurons. Because the vasopressin neurons are located in the hypothalamus, lesions confined to the sella turcica generally do not cause diabetes insipidus because the posterior pituitary is simply the site of the axon terminals that secrete vasopressin into the bloodstream. In addition, the capacity of the neurohypophysis to synthesize vasopressin is greatly in excess of the body's needs, and destruction of 80-90% of the hypothalamic vasopressin neurons is required to produce diabetes insipidus. As a result, even large lesions in the sellar and suprasellar area generally are not associated with impaired water homeostasis until they are surgically resected. Regardless of the etiology of central diabetes insipidus, deficient or absent vasopressin secretion causes impaired urine concentration with resultant polyuria. In most cases, secondary polydipsia is able to maintain water homeostasis at the expense of frequent thirst and drinking. However, destruction of the osmoreceptors in the anterior hypothalamus that regulate vasopressin neuronal activity causes a loss of thirst as well as vasopressin section, leading to severe chronic dehydration and hyperosmolality. Vasopressin deficiency also leads to down-regulation of the synthesis of aquaporin-2 water channels in the kidney collecting duct principal cells, causing a secondary nephrogenic diabetes insipidus. As a result, several days of vasopressin administration are required to achieve maximal urine concentration in patients with CDI. Consequently, the presentation of patients with central diabetes insipidus can vary greatly, depending on the size and location of the lesion, the magnitude of trauma to the neurohypophysis, the degree of destruction of the vasopressin neurons, and the presence of other hormonal deficits from damage to the anterior pituitary.

Central diabetes insipidus in children: Diagnosis and management.

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of conditions (genetic, congenital, inflammatory, neoplastic, traumatic) that arise mainly from the hypothalamus. The differential diagnosis between diseases presenting with polyuria and polydipsia is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating the sellar-suprasellar region in CDI. Pituitary stalk size at presentation is variable and can change over time, depending on the underlying condition, and other brain areas or other organs - in specific diseases - may become involved during follow up. An early diagnosis and treatment are preferable in order to avoid central nervous system damage and the risk of dissemination of germ cell tumor, or progression of Langerhans Cell Histiocytosis, and in order to start treatment of additional pituitary defects without further delay. This review focuses on current diagnostic work-up and on the role of neuroimaging in the differential diagnosis of CDI in children and adolescents. It provides an update on the best approach for diagnosis - including novel biochemical markers such as copeptin - treatment and follow up of children and adolescents with CDI; it also describes the best approach to challenging situations such as post-surgical patients, adipsic patients, patients undergoing chemotherapy and/or in critical care.

Conservative treatment for leg oedema and the effect on nocturnal polyuria in patients with spinal cord injury.

OBJECTIVES: To evaluate the possible influence of non-pharmacological interventions, such as compressive bandages and intermittent pneumatic compression (IPC), on leg oedema and nocturnal polyuria (NP), and the possible interrelation between both pathologies in patients with spinal cord injury (SCI), as patients with SCI often have leg oedema and during the night the oedema decreases as a result of natural drainage mechanisms that can cause NP. PATIENTS AND METHODS: Patients with SCI who followed their first rehabilitation after their SCI with bilateral leg oedema and/or with as much or a larger urine volume at night as during the day. The patients were all wheelchair users and followed the rehabilitation programme daily for 3 weeks. In all, 24 patients, aged between 21 and 63 years, were selected for participation in the 3-week rehabilitation programme. During the first week, baseline data were collected. During the second week, IPC was executed from the moment the patient went to lie down. During the third week, the patients wore multilayer compressive bandages. Leg circumference was measured in the morning before sitting up and at the moment they went to lie down in bed. During each study week, a daily frequency-volume chart (24 h) was completed. RESULTS: The leg volume of both legs was significantly different between the morning and evening (right leg F = 103.90, P < 0.001; left leg F = 100.77, P < 0.001) and between the three treatments (right F = 9.70, P < 0.001; left F = 9.66, P < 0.001). There was a significant difference between the compressive bandages and the baseline period (right and left leg, both P < 0.001) and between the compressive bandages and IPC (right leg P = 0.009 and left leg P = 0.015). There was no significant difference between IPC and the baseline. When no treatment or IPC was used, urine production was significantly higher during the bed-rest period. The urine production was significantly lower comparing the use of compressive bandages to baseline and IPC, during bed rest (P = 0.009) and during sleep (P < 0.001). There was a significant decrease in absolute voided volume at night with the compressive bandages as treatment (P < 0.001). There was a significant positive association between the leg volume change during the day and the urine-production ratio, 100 mL increase in leg volume was associated with 8% increase in the log-transformed urine-production ratio. CONCLUSION: There are alternative treatment options for patients with SCI who have oedema or NP. Oedema formation and urine production appear to be related to each other. Therefore, the use of compressive bandages was shown to be a valuable treatment option to improve both leg oedema and NP.

Enfoque práctico para el diagnóstico y tratamiento de los estados poliúricos en pacientes con injuria cerebral aguda / Diagnosis and therapy of polyuric states in patients with acute cerebral injury

In patients with acute cerebral injury, polyuric states can potentially trigger, maintain and aggravate the primary neurological damage, due to hypovolemia, arterial hypotension and alterations of osmolarity. The true incidence of the condition in this population is unknown. A widely validated definition of polyuric state is lacking and its etiology is multifactorial. There are two principal classes of polyuria: a) aqueous polyuria with diabetes insipidus as the main cause; and b) osmotic polyuria in which sodium, glucose or ureaplay the main role. Polyuric states are in close association with disorders of water and sodium metabolism and with alterations in acid-base balance. A detailed analysis of the history, clinical picture and simple laboratory determinations in blood and urine, are required for an adequate assessment of these polyuric states. The problem must be faced with pathophysiological reasoning and a systematic and sequential approach, because each disorder needs a specific therapy.

Polyuria associated with high-dose methotrexate in two patients with acute lymphoblastic leukaemia.

Although methotrexate has an established safety profile in clinical practice, severe morbidity can still occur on rare occasions. We report two patients with leukemia treated with high dose methotrexate. Both patients developed profound polyuria that required aggressive fluid resuscitations during the treatments. Renal toxicity is a known complication of methotrexate, but polyuria associated with its use has not been reported before. Polyuria started shortly after the initiation of the medicine in both patients. The polyuria resolved as the drug level in blood became undetectable. The episodes of polyuria were transient and recurred every time when the patients received methotrexate. The clinical pictures were not compatible with classical drug induced nephrogenic diabetes insipidus. It is possible that the drug interferes with adenosine metabolism, which in turn alters the tubular ability of solute and fluid reabsorption.

[Clinical manifestations of urinary disorders and their treatment in ageing men]. / Manifestations cliniques des troubles urinaires chez l'homme vieillissant et leur traitement.

PROBLEMS OF THE PROSTATE: Benign hypertrophy of the prostate (BHP), when it occurs, is manifested by an obstruction or irritation related to overactivity of the bladder. The obstructive syndrome is defined by urodynamic tests. Urge incontinence and study of the pressure-flow ratio are the tests of choice. The functional handicap and impact on quality of life are assessed using the International Prostatism Symptoms Score (I-PSS). Efficient and fairly well tolerated medical treatment has reduced the indications for surgery. It relies on alpha-blockers, 5a-reductase inhibitors and phytotherapy. When indicated, the surgical treatment of choice is endoscopic resection of the prostate. Among the non-prostatic micturition disorders, urge micturition with, in extreme cases, incontinence are due to detrusor instability. This is of multifactor origin; enhanced by the local irritation or environmental factors, it usually occurs within a context of acute or chronic pathologies. Treatment is recommended with anticholinergic agents. New molecules have recently been launched, better tolerated than oxybutinine. Electrostimulation can be a good alternative in mentally normal patients. Micturition due to excess urine may be due to overactivity of the bladder, the major risk of which is acute urine retention. It can also be observed during neurological affections such as Parkinson's disease or during administration of certain drugs. Nocturnal polyuria is a frequent problem. However, simple hygiene and dietary measures and the control of certain concomitant diseases can usually relieve the symptoms. Medical treatment relies on desmopressine.

Modified techniques of S3 foramen localization and lead implantation in S3 neuromodulation.

INTRODUCTION: We describe a reproducible and less invasive surgical approach to sacral neuromodulation (InterStim Therapy) in the treatment of voiding dysfunction. Twenty patients underwent modified lead implantation (mean operative time 45 minutes) without any difficulties or complications, with a mean follow-up of 8 months (range 1 to 14).Technical Considerations. The highlights of these modifications include (a) fluoroscopy to localize the S3 foramen; (b) paramedian incision; (c) use of a cutoff S3 finder needle and a 14-gauge Angiocath to direct permanent lead into the S3 foramen without dissection; (d) use of lateral fluoroscopy to determine the depth of the Angiocath insertion; and (e) anchoring the lead to the lumbodorsal fascia (superficial to the sacral periosteum) using a moveable lead anchor system. These modifications simplify and minimize the invasiveness of this therapy without compromising the efficacy. CONCLUSIONS: Because of the simplicity of these modifications, we are currently using an implanted lead, rather than the temporary percutaneous lead, to assess patients' clinical response before implanting a pulse generator.

[Massive natriuresis and polyuria after triple craniocervical subarachnoid hemorrhage: cerebral salt wasting syndrome?]. / Massive Natriurese und Polyurie nach dreimaliger kraniozervikaler Subarachnoidalblutung: Cerebral-Salt-Wasting-Syndrome?

A thirty-year-old male patient suffered subarachnoidal haemorrhage from an angioma positioned in the cranio-cervical transition. After rebleeding twice the patient developed a hydrocephalus internus malresorptivus and excessive natriuresis and polyuria, accompanied by depressed renin activity and extremely low aldosterone plasma levels. Neither fluid restriction and sodium substitution, nor administration of hydro-chlorothiazide/indomethacin affected natriuresis and polyuria. It was only after treatment with fludrocortisone-acetate/hydrocortisone that hyponatraemia and polyuria were resolved. At the same time a ventriculo-peritoneal shunt was applied. Differential diagnosis excluded the syndromes of inadequate antidiuretic hormone secretion, renal and cerebral diabetes insipidus, osmotic receptor hypofunction, chronic renal dysfunction and tubular necrosis. Natriuresis and polyuria developed under dexamethasone therapy. Since patient history, physical examination and laboratory criteria could not explain the electrolyte and fluid imbalance, this might be attributed to the hydrocephalus. Similar disturbances have been reported from other patients with intracranial disorders. Mechanical pressure exercised on the hypothalamus might cause the disturbance of fluid and sodium balance. Assuming a cerebral salt wasting syndrome, a putative natriuretic factor coming from the brain or an imbalance in the cerebral renin-angiotensin-system, as described in rats and dogs, must be discussed.

[Clinical and experimental study on vascular reconstruction for one-kidney renovascular hypertension].

Several special problems were noted regarding the vascular reconstruction for renovascular hypertension of the patient with a solitary kidney. It is difficult to use the value of plasma renin activity for decisive diagnosis or determination of surgical indications because most of the one-kidney patients with renovascular hypertension showed a normal plasma renin activity preoperatively and it is theoretically impossible to obtain a ratio of the affected to the opposite renal vein renin level. Most patients presented moderate to severe degree of renal dysfunction so that vascular reconstruction should be the treatment of choice because the conservative therapy with anti-hypertensive drugs such as captopril may further worsen the renal function by decreasing the renal perfusion pressure. Patients showed extensive polyuria immediately after surgery which was attributed to sudden increases in glomerular filtration rate and urinary sodium excretion. There was no correlation between the preoperative serum osmolarity and the postoperative polyuria. Correlation was not obtained between the intraoperative clamping time of the renal artery and the aggravation of the previously existing renal dysfunction. A comparative pathohistological study of primarily vs secondarily nephrectomized kidneys revealed no evidence of parenchymal damage of the kidney after arterial reconstruction. Both acute and chronic animal experiments in which autologous whole blood was forcibly injected into the canine renal artery via extracorporeal shunt under the high pressure of 200 or 300 mmHg showed no light microscopic evidence of acute histological damage of the kidney. It is concluded that the intensive care with an aid of a Swan Ganz catheter during the postoperative polyuric period and the swift starting of hemodialysis when necessary can solve the postoperative problems of one-kidney renovascular hypertension although the sudden rise in renal perfusion pressure after reconstruction may cause an acute hypertensive damage in the level of electron microscopic findings.

Management of polyuria subsequent to pituitary surgery based on the diurnal pattern of urinary excretion.

Polyuria subsequent to pituitary surgery was studied in 64 cases. Most cases of postoperative polyuria were due to diabetes insipidus. These cases showed a triphasic pattern in daily urinary volume. Observation of hourly urinary volume in polyuria revealed four diurnal patterns of urinary excretion: rhythmic, continuous, transient, and unspecific. Clinical observation of diurnal patterns has an advantage, in terms of simplicity of procedure, in immediately determining the nature of the polyuria, prognosticating diabetes insipidus, and eliminating inappropriate procedures in treatment. Indomethacin suppository is considered to be a favorable agent in reducing polyuria without disturbing the diurnal pattern in diabetes insipidus.

[Hydrostatic distension of the bladder: technique and indications. 89 cases (author's transl)]. / Distension vésicale hydrostatique. Technique et indications. 89 observations.

One-hundred and five hydrostatic distensions of the bladder (HDB) were carried out in 89 patients. The technique is simple, and complications were uncommon: 3 cases of bacteraemia and 4 cases of ruptured bladder. No death was recorded. The main indication was tumour of the bladder (76 patients). Satisfactory results, with reduction or complete disappearance of the lesions, were obtained in superficial, non-infiltrating tumours, but in type B tumours invading the vesical muscle failures were almost constant. Eight patients with pronounced reduction of bladder capacity were also treated by HDB with varying results depending upon the underlying cause. Two out of 3 patients with severe frequencies and normal-size bladder were relieved by the treatment. HDB was also successfully used in 2 patients with intractable vesical haematuria.