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Diabetes insipidus as a presenting symptom of acute myelogenous leukemia.

This report describes a case of diabetes insipidus associated with acute myelogenous leukemia. An 11-year-old boy presented with fatigue, polydipsia and polyuria. His evaluation revealed a diagnosis of acute myelogenous leukemia FAB-M2, and a water deprivation test confirmed the diagnosis of central diabetes insipidus. His brain magnetic resonance imaging (MRI) showed a thickened, enhancing pituitary stalk with absence of the normal hyperintense signal in the posterior pituitary. He was treated with systemic chemotherapy, intensive intrathecal therapy, and 1,000 cGy to the pituitary. The patient achieved a remission but continued to need desmopressin therapy to control his diabetes insipidus. Diabetes insipidus is a rare complication of acute myelogenous leukemia that can be caused by leukemic infiltration of the pituitary. The diabetes insipidus is irreversible despite intensive systemic and central nervous system chemotherapy and radiation.

Child↗

Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel.

Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na(+) concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na(+) transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and alpha-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of gamma-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na(+) transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.

Animals↗

Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement.

PURPOSE: Nocturia is a common condition often attributed in aging men to benign prostatic enlargement. Older adults are prone to nocturnal sleep disturbance, of which disturbed circadian rhythm may be a component since it improves with nighttime administration of melatonin. This study was designed to investigate melatonin as a potential treatment for nocturia associated with bladder outflow obstruction in older men. MATERIALS AND METHODS: A total of 20 men with urodynamically confirmed bladder outflow obstruction and nocturia were entered into a randomized, double blind, placebo controlled crossover study assessing the effect of 2 mg controlled release melatonin at night on nocturia. Symptoms were assessed at baseline and after each 4-week treatment period using a frequency volume chart, the International Prostate Symptom Score and symptom problem index. Maximum urinary flow rate and post-void residual urine volume were also assessed. RESULTS: Baseline frequency of nocturia was 3.1 episodes per night. There were 7 men (35%) with detrusor overactivity and 10 (50%) had nocturnal polyuria. Melatonin and placebo caused a decrease in nocturia of 0.32 and 0.05 episodes per night (p = 0.07) and a decrease in the nocturia bother score of 0.51 and 0.05, respectively (p = 0.008). Nocturia responder rates (a reduction from baseline of at least -0.5 episodes per night) differed between the active medication and placebo groups (p = 0.04). Daytime urinary frequency, International Prostate Symptom Score, relative nocturnal urine volume, maximum urinary flow rate and post-void residual were unaffected by melatonin treatment. CONCLUSIONS: Melatonin treatment is associated with a significant nocturia response rate, improvement in nocturia related bother and a good adverse effect profile. However, it is uncertain whether the observed changes in this study are clinically significant.

Aged↗

Monosymptomatic nocturnal enuresis is associated with abnormal nocturnal bladder emptying.

PURPOSE: We investigate the nature of enuresis episodes in monosymptomatic nocturnal enuresis using a fluid provocation model. MATERIALS AND METHODS: The study included 18 children 7 to 13 years old with monosymptomatic nocturnal enuresis. Based on basal home recordings patients were subgrouped into those with a normal nocturnal urine output and those with nocturnal polyuria (mean nocturnal urine production on wet nights exceeding 130% of functional bladder capacity, normal functional bladder capacity for age provided). Children were admitted to the hospital for 4 consecutive nights. After an adaptation night all children received orally 25 ml/kg water, 30 minutes before bedtime on the remaining 3 nights. A cordless alarm device enabled registration of enuretic episodes from another room and diapers allowed the measurement of enuresis volumes. Post-void residual volumes were measured by ultrasound. Pelvic floor electromyography was continuously recorded throughout the night, and its association to bladder emptying was investigated. RESULTS: A total of 95 enuresis and 14 nocturia episodes were recorded. Significantly more enuresis episodes were registered on nights with oral fluid load, whereas no increase in number of nocturia episodes was seen. Of the enuresis episodes 46 were associated with incomplete bladder emptying (post-void residual volume greater than 10% of total bladder volume at time of enuresis). No difference between patient groups regarding post-void residual volume was seen. Abnormal bursts of electromyography activity were associated with incomplete micturitions. CONCLUSIONS: Enuresis nocturna episodes in polyuric and nonpolyuric patients are frequently incomplete micturitions. The present findings question the definition of nocturnal enuresis episode as normal complete voiding.

Adolescent↗

Long-term efficacy and predictive factors of full spectrum therapy for nocturnal enuresis.

PURPOSE: We determine the effect and predictive factors of relapse 1 year after combination therapy of an enuresis alarm, bladder training, motivational therapy and retention control training for nocturnal enuresis. MATERIALS AND METHODS: In 68 of 77 children the relapse rate 1 year after full spectrum therapy for nocturnal enuresis was investigated. Gender, age, sleep arousal, family history, monosymptomatic, bladder capacity, overactive bladder, nighttime polyuria, duration of treatment, over learning and psychosocial factors were investigated. RESULTS: The relapse rate during the whole year was 50%, with 33.8% of subjects being dry and 16.2% sometimes wet. The relapse rate after 1 year was 16%. Nine patients could not be reached and, thus, were considered dropouts. Only overactive bladder and psychosocial problems were significantly related to relapse. CONCLUSIONS: The relapse rate during the year was high while the relapse rate after 1 year was low. Psychosocial problems and overactive bladder were the only 2 predictive factors for relapse.

Adolescent↗

Behavioral and medical treatment of chronic polydipsia in a patient with schizophrenia and diabetes insipidus.

OBJECTIVE: This case report describes a novel outpatient behavioral treatment intervention for chronic polydipsia. The program was used in an effort to reduce excessive fluid intake in a woman with chronic paranoid-type schizophrenia who also had a diagnosis of diabetes insipidus. METHODS: The 12-session individual behavioral intervention incorporated self-monitoring, stimulus control, coping skills training, and reinforcement components. RESULTS: The patient engaged fully in the treatment program, and she successfully restricted her fluid intake. Her diabetes insipidus could therefore be treated with desmopressin, a medication that requires fluid restriction, and she experienced a concomitant reduction in polyuria and urinary incontinence. CONCLUSIONS: The outpatient behavioral intervention demonstrated promising outcomes in a chronically mentally ill patient whose polydipsia had underlying psychogenic and physiological components. This case highlights the efficacy of combining behavioral and medical interventions.

Ambulatory Care↗

Isolated vertical diplopia as the initial manifestation of presumed pretectal and anterior hypothalamic germinomas.

A 21-year-old man with a 5-month history of diplopia caused by isolated vertical ocular misalignment had normal laboratory studies, including brain magnetic resonance imaging (MRI). Eight months after the onset of diplopia, he reported dry mouth, polydipsia, polyuria, and absent sweating. Examination now disclosed light-near dissociation of the pupillary responses, convergence-retraction nystagmus, and upgaze palsy. MRI revealed enhancing suprasellar and pretectal masses presumed to be germinomas. Two years after brain irradiation and systemic chemotherapy, no lesions are apparent on MRI and hypothalamic dysfunction has partially resolved. In a young patient with isolated vertical diplopia and normal brain imaging, one should consider an early pretectal syndrome and inquire after manifestations of hypothalamic dysfunction.

Adult↗

Laboratory support for rural health care.

Lack of technical facilities to support diagnostic and curative medicine discourages physicians from providing rural health care. In developing countries, therefore, the first decision on most health problems is often made by auxiliaries. Such staff, in conducting basic community medicine, collect specimens for appropriate investigations. Simple tests performed by the auxiliaries themselves can assist in routine surveillance, in establishing priorities of medical care and in systematizing referrals to health centres. The simplest screening tests--of weight, temperature and haemoglobin--are the most useful. Serial weighing in childhood can monitor malnutrition, acute or chronic infections and infestations; in young adults, it can point to ill-health requiring further investigation. The finding of fever and examination of a blood film may reveal acute bacterial infection, malnutrition, malaria, hookworm, bilharzia and sickling, and thus be followed up by a thin blood film, or tests for sickle-cell and stool hookworm ova, pus cells or amoeba. The repertoire of simple laboratory investigations is largely completed by examination of sputum for acid-fast bacilli, or diplococci; by urine microscopy, with haematuria; and tests for protein or sugar, in cases of oedema or polyuria. A limited range of more elaborate tests may be available in the laboratories of district or regional hospitals. Human and technological factors which bear on the modus operandi of rural laboratories are identified and discussed.

Clinical Laboratory Techniques↗

Diurnal variations in serum lithium and renal lithium clearance in rats given lithium as a single small dose or as multiple high doses.

Clearance determinations were carried out in three groups of rats: A high lithium group given food to which 70 mmol/kg of lithium were added for 4-6 weeks leading to a mean serum lithium concentration of 0.85 mmol/l, a low lithium group given food to which 15 mmol/kg of lithium were added for two days before the clearance period leading to a mean serum lithium concentration of 0.22 mmol/l, and a group given the same food without lithium. The sodium and potassium contents of the food were kept high in order to avoid lithium-induced development of negative sodium balance and excessive polyuria. The rats were housed in four rooms with 6-hour displaced 24-hour light-dark cycles. The results showed that high doses of lithium led to a significant increase of the lithium clearance and the urine flow. Small amounts of lithium influenced neither the clearance values nor the urine flow. All renal variables were increased by about 50-100% during the dark period. The serum lithium concentration was least influenced by the diurnal rhythm. It is concluded that serum lithium concentrations measured at any time of the day are fairly representative of the 24 hours. A lithium clearance measured during daytime is valid for this period only. Long-term lithium treatment leads to an increase of the renal lithium clearance but does not diminish the normal diurnal rhythm of the kidney function.

Animals↗

Two sporadic cases of adult-onset progressive mucinous histiocytosis.

Progressive mucinous histiocytosis is a rare, benign, non-Langerhans' cell histiocytosis limited to the skin. Ten cases--all women--in four families and one sporadic case have been described in the literature. The disorder usually begins in childhood and progresses slowly. We report two sporadic cases of adult-onset progressive mucinous histiocytosis in unrelated African-American women, aged 48 and 55 years, respectively, who developed red-brown and flesh-coloured, asymptomatic papules on the face, the arms and the legs without truncal, mucosal or visceral involvement. The lesions showed no spontaneous regression. Both patients lacked associated systemic symptoms, including polyuria, polydipsia or seizures. There was no underlying hyperlipidaemia, paraproteinaemia or lymphoproliferative disease. No family history of similar lesions could be identified. Light microscopy revealed dermal proliferation of spindle-shaped histiocytes with abundant mucin deposition. Electron microscopy demonstrated a high number of myelin figures or zebra bodies in the cytoplasm of histiocytes. On immunohistochemistry, positive staining with macrophage markers--CD68, HAM56 and lysozyme--and factor XIIIa, a transglutaminase present in dermal dendrocytes, and negative staining with Langerhans' cell markers--CD1a and S100--and CD34, a marker present in dermal dendritic cells derived from uncommitted mesenchymal cells, were observed.

Diagnosis, Differential↗

Antidiuretic hormone and atrial natriuretic peptide in congestive heart failure.

Plasma concentrations of antidiuretic hormone (ADH) were measured in 8 patients with congestive heart failure (CHF) of NYHA functional class III-IV, before and during treatment with captopril, 6.25-25.0 mg t.i.d., added to their drug regimen. Before captopril treatment, plasma ADH was high, 2.5 times the upper limit of normal reference values. During treatment with captopril, plasma ADH levels were normalized, and remained so throughout the study, for at least 6 months. Plasma levels of angiotensin II were also reduced to a normal level. Reduction of plasma ADH during captopril treatment in CHF may partly depend on reduced angiotensin II formation, and may be beneficial by improving water balance. Atrial natriuretic peptide (ANP), was measured by radioimmunoassay in 17 patients with CHF. The highest levels were measured in the most severe CHF cases, and intermediate high values on NYHA functional class I-II patients. Plasma ANP concentrations in control patients (n = 18) without cardiac diseases ranged between 0 and 30 pg/ml. In two patients with paroxysmal supraventricular tachycardia, associated with transient polyuria, high plasma ANP concentrations were noticed during tachycardic episodes. Thus, ANP appears to be a circulating hormone in humans, and is released into the blood in clinical conditions associated with raised preload and atrial wall stretch.

Aged↗

The vitamin D3 metabolite-type activity of Solanum malacoxylon.

1. Administration of an aqueous extract of the dried leaves of Solanum malacoxylon (DLSM) to rats causes a rapid hyperphosphataemia and a decrease in plasma alkaline phosphatase activity; the two effects are typical of 1,25(OH)2D3, the hormonally active metabolite of vitamin D3. 2. DLSM, like both vitamin D3 and parathyroid hormone, increases plasma calcium and citrate levels in rats. The effect of DLSM in influencing plasma citrate, and the role of this important metabolite in mineral metabolism is discussed. 3. A decrease of plasma magnesium levels occurs in rats following treatment with DLSM. This decrease, which is associated with a renal loss of this cation, is remarkably similar to that produced by hypervitaminosis D3. 4. Prolonged administration of DLSM to vitamin D deficient rats causes a polyuria, hypercalciuria, hyperphosphaturia, hypermagnesuria, an increase in urinary total hydroxyproline, an increase in plasma total hexosamines, and a corresponding decrease in the bone total hexosamines. These effects, some of which can also be produced by hyperparathyroidism, or following the administration of parathyroid extract (PTE), large doses of vitamin D3, or 1,25(OH)2D3, suggest that DLSM, like the latter compounds, is capable of causing bone mineral mobilization, and the dissolution of bone organic matrix.

Alkaline Phosphatase↗

Vasopressin function in hypercalcaemia.

Vasopressin function and thirst were studied in fourteen hypercalcaemic patients (ten hyperparathyroid and four disseminated malignant disease). Ten patients had decreased renal concentrating ability which reversed within a few days in the majority of patients whose hypercalcaemia was corrected by parathyroidectomy. Although eight patients complained of thirst, none showed a lowered threshold of thirst appreciation during hypertonic saline infusion. Osmoregulation of vasopressin secretion was not reduced in any patient, but the hyperparathyroid group had an exaggerated vasopressin response to osmotic stimulation. We conclude that a partial, reversible nephrogenic diabetes insipidus occurs in at least 70% of hypercalcaemic patients irrespective of cause, which accounts for the polyuria induced by hypercalcaemia.

Adult↗

Phaeochromocytoma and diabetes mellitus: further evidence that alpha 2 receptors inhibit insulin release in man.

An insulin-dependent diabetic presenting with thirst, polyuria and weight loss was noted to be hypertensive and shown subsequently to have a right adrenal phaeochromocytoma. Pre-operative control of both diabetes and hypertension was achieved with propranolol and phenoxybenzamine, but not with propranolol alone. Full recovery with restoration of normal glucose tolerance and blood pressure followed successful surgery. Analysis of this patient's response to medical therapy provides further evidence that alpha 2 receptors inhibit insulin release in man. Since as many as one-third of phaeochromocytomas are not detected during life, this diagnosis should be considered as an uncommon cause of carbohydrate intolerance in patients with diabetes mellitus, especially if accompanied by continuous or paroxysmal hypertension.

Adrenal Gland Neoplasms↗

Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma.

We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin-releasing hormone (CRH) and corticotrophin (ACTH). A 49-year-old white woman presented with a 1-month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facies, lanugo-type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high-dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4-cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24-hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaeochromocytomas, transcribed a lone pituitary-sized (1200 nucleotide) pro-opiomelanocortin mRNA. This is the second reported case of a CRH-secreting phaeochromocytoma.

Adrenal Gland Neoplasms↗

Effect of cisplatin on renal haemodynamics and tubular function in the dog kidney.

Administration of cisplatin (5 mg/kg) to dogs results in polyuric renal failure due initially to a proximal tubular functional impairment. 48-72 h after the cisplatin administration the depressed renal function can be attributed to impairment of proximal as well as distal tubular reabsorptive capacities associated with increased renal vascular resistance. The polyuria seems to be due to the impaired reabsorption rate in the distal nephron segments.

Animals↗

Hyperglycaemic symptoms before diagnosis of non-insulin-dependent (type 2) diabetes mellitus in relation to 5-year outcome.

A group of newly diagnosed patients with non-insulin-dependent (type 2) diabetes mellitus (n = 133) were divided into two groups according to the symptoms of diabetes mellitus at diagnosis; a group (26 men and 17 women) with hyperglycaemic symptoms (polydipsia, polyuria, weight loss and tiredness) and a group (44 men and 46 women) without such symptoms. At the time of diagnosis, symptomatic patients tended to be leaner (P = NS), and they were more hyperglycaemic (P less than 0.001-0.06) and had lower insulin responses to an oral glucose load (P less than 0.01-0.05) than asymptomatic patients, but after 5 years no difference in these respects was found. No significant differences in the frequency of islet-cell antibodies or cardiovascular diseases were found between the two diabetic groups. At the 5-year examination, the initially symptomatic patients were receiving pharmacological treatment for hyperglycaemia more often than asymptomatic patients. No consistent differences in clinical characteristics and 5-year outcome were observed between those diabetic patients who were diagnosed on the basis of hyperglycaemic symptoms and those who were diagnosed for other reasons. In conclusion, in middle-aged patients with newly diagnosed diabetes mellitus classified as non-insulin-dependent, diabetic symptoms at diagnosis did not predict the 5-year outcome of the patients in terms of metabolic control or cardiovascular events.

Diabetes Mellitus, Type 2↗

A case of central diabetes insipidus with spontaneous remission after 8 years of the disease.

A 55-year-old male smoker developed polyuria and polydipsia in November 1983. A water deprivation study revealed a defect in the urine concentrating function, which was corrected by vasopressin. Plasma antidiuretic hormone (ADH) was not increased by smoking. His condition was well controlled by deamino-D-arginine vasopressin. However, since February 1992 he has become completely free from the need for medication to control his urine volume. Re-evaluation studies with water deprivation and smoking revealed dramatic improvements in the urine concentrating function and ADH response. A patient with idiopathic diabetes insipidus with spontaneous remission after 8 years is reported.

Diabetes Insipidus↗