Inappropriate secretion of antidiuretic hormone treated with frusemide.

Seven out of nine patients with chronic inappropriate secretion of antidiuretic hormone were successfully treated with 40 mg frusemide daily. One patient needed 80 mg, and the remaining patient achieved only a small increase in diuresis after 40 mg frusemide; this was probably related to his low creatinine clearance. In order to maintain a salt intake high enough to compensate for the loss of urine electrolytes 3 to 6 g sodium chloride was added as tablets to the sodium-free diet in six patients. Hypokalaemia occurred in five patients but was easily corrected with either supplements of potassium chloride or a potassium-sparing diuretic. These findings add further weight to evidence that Frusemide is a good alternative for the treatment of patients with inappropriate secretion of antidiuretic hormone who cannot tolerate water restriction.     

Severe Hyponatre mia Due to Rosiglita zone Use in an Elderly Woman With Diabetes Mellitus: A Rare Cause of Syndrome of Inappropriate Antidiuretic Hormone Secretion

ObjectiveTo describe the first case of syndrome of inappropriate antidiuretic hormone secretion with lifethreatening hyponatremia due to rosiglitazone therapy.MethodsWe describe the clinical, laboratory, and imaging findings of the study patient.ResultsAn 89-year-old woman with a 5-year history of type 2 diabetes mellitus was admitted to the emergency department because of unconsciousness. She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L). She had normal renal, cardiac, and adrenal function, and she did not have edema or volume depletion. The cause of hyponatremia was syndrome of inappropriate antidiuretic hormone secretion. We did not find any cause for her condition other than rosiglitazone, an antihyperglycemic drug that is increasingly being used in patients with type 2 diabetes mellitus. According to her medical history, rosiglitazone was prescribed 1 month previously after withdrawal of gliclazide. We stopped the rosiglitazone and administered hypertonic saline infusion to treat the hyponatremia. Saline infusion was stopped and blood sodium levels were stabilized in the normal range after 2 days. The patient’s plasma sodium concentration has remained in the reference range at follow-up visits.ConclusionsThis is the first reported case of syndrome of inappropriate antidiuretic hormone secretion as an adverse effect of rosiglitazone, and this drug should possibly be considered for addition to the list of drugs that cause this condition. (Endocr Pract. 2008;14:1017-1019)     

Effect of two-week infusion of deamino D-arginine vasopressin in rats

Our purpose was to investigate a method of prolonged desmopressin (DDAVP) infusion in a free roaming rat to better understand the SIADH (syndrome of inappropriate antidiuretic hormone secretion) syndrome in man. DDAVP was infused for 2 weeks from implanted self-powered osmotic minipumps. At the end of that time, plasma DDAVP and urine osmolality were both significantly elevated in experimental as compared with control animals. However, hyponatremia and hypoosmolality, which are characteristic in the SIADH, did not develop. Our observations suggest that inappropriate high antidiuretic hormone levels do not necessarily lead to the SIADH either by urine sodium loss or by water retention if animals decrease water intake.     

Clinical Analysis of Brain Trauma-Associated SIADH

The objective of this study was to analyze the clinical features of brain trauma associated syndrome of inappropriate antidiuretic hormone secretion. A retrospective analysis was performed for the electrolytes and osmolality of blood and urine samples of brain injury patients, which have been collected in our department since last 20 years. Four cases of brain injury patients met the criteria of SIADH, and three of them were cured but one patient died. In conclusion, the pathogenesis and treatment of SIADH associated with brain injury are different from hyponatremia. Early diagnosis and treatment can reduce the morbidity and mortality of patients with traumatic brain injury.     

Hyponatremia in the postoperative craniofacial pediatric patient population: a connection to cerebral salt wasting syndrome and management of the disorder.

Hyponatremia after cranial vault remodeling has been noted in a pediatric patient population. If left untreated, the patients may develop a clinical hypoosmotic condition that can lead to cerebral edema, increased intracranial pressure, and eventually, to central nervous system and circulatory compromise. The hyponatremia has traditionally been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH); however, in our patients the treatment has been resuscitation with normal saline as opposed to fluid restriction (the accepted treatment of SIADH), thus placing the diagnosis of SIADH in question. Patients who developed hyponatremia after intracranial injury or surgery were, until recently, grouped together as having SIADH. However, there are diagnosis and treatment differences between SIADH and another distinct but poorly understood disorder that is designated cerebral salt wasting syndrome (CSW). CSW is associated with increased urine output and increased urine sodium concentration and volume contraction, and it is frequently seen after a central nervous system trauma. We therefore developed a prospective study to evaluate the cause of the sodium imbalance.Ten consecutive pediatric patients who underwent intracranial surgery for various craniosynostotic disorders were postoperatively monitored in the pediatric intensive care unit for hemodynamic, respiratory, and fluid management. The first four patients were evaluated for electrolyte changes and overall fluid balance to determine the consistency with which these changes occurred. The remaining six patients had daily (including preoperative) measurement of serum electrolytes, urine electrolytes, urine osmolarity, serum antidiuretic hormone (ADH), aldosterone, and atrial natriuretic hormone (ANH). All patients received normal saline intravenous replacement fluid in the postoperative period.All of the patients developed a transient hyponatremia postoperatively, despite normal saline resuscitation. Serum sodium levels as low as 128 to 133 mEq per liter (normal, 137 to 145 mEq per liter) were documented in the patients. All patients had increased urine outputs through the fourth postoperative day (>1 cc/kg/h). The six patients who were measured had an increased ANH level, with a peak value as high as 277 pg/ml (normal, 25 to 77 pg/ml). ADH levels were low or normal in all but one patient, who had a marked increase in ADH and ANH. Aldosterone levels were variable. On the basis of these results, all but one patient showed evidence of CSW characterized by increased urine output, normal or increased urine sodium, low serum sodium, and increased ANH levels. The other patient had similar clinical findings consistent with CSW but also had an increase in ADH, thus giving a mixed laboratory picture of SIADH and CSW.The association of CSW to cranial vault remodeling has previously been ignored. This study should prompt reevaluation of the broad grouping of SIADH as the cause of all hyponatremic episodes in our postoperative patient population. An etiologic role has been given to ANH and to other, as yet undiscovered, central nervous system natriuretic factors. All of the patients studied required normal saline resuscitation, a treatment approach that is contrary to the usual management of SIADH. These findings should dictate a change in the postoperative care for these patients. After cranial vault remodeling, patients should prophylactically receive normal saline, rather than a more hypotonic solution, to avoid sodium balance problems.     

The syndrome of inappropriate antidiuretic hormone secretion

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the commonest form of normovolaemic or dilutional hyponatraemia. The diagnosis of SIADH should be considered if the five cardinal criteria are fulfilled (hypotonic hyponatraemia, natriuresis, urine osmolality in excess of plasma osmolality, absence of oedema and volume depletion, normal renal and adrenal function). The clinical features are principally neuro-muscular and gastro-intestinal, the severity of which is related to both the absolute serum sodium concentration and its rate of fall, particularly if greater than 0.5 mmol/1/h. The dilutional hyponatraemia of SIADH develops due to persistent detectable or elevated plasma arginine vasopressin (AVP) concentrations in the presence of continued fluid intake. Osmoregulated inhibition of thirst failures to curb fluid intake. The major groups of causes of SIADH are: (i) neoplasia, (ii) neurological diseases, (iii) lung diseases and (iv) a wide variety of drugs. Inappropriate infusion of hypotonic fluids in the post-operative state remains a common cause. Four categories of osmoregulated AVP secretion have been described: (i) erratic AVP release, (ii) reset osmostat, (iii) persistent AVP release at low plasma osmolality and (iv) normal osmoregulated AVP secretion. For symptomatic patients with chronic SIADH, the mainstay of therapy remains fluid restriction. New antagonists to the antidiuretic action of AVP offer a new therapeutic approach.     

Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Coproporphyria: Case Report and Review of Literature

ObjectiveTo remind physicians to consider the hepatic porphyrias in the differential diagnosis of the syndrome of inappropriate antidiuretic hormone secretion.MethodsWe present a case report of a patient seen in the hospital for severe hyponatremia, who was discovered to have the syndrome of inappropriate antidiuretic hormone secretion attributable to coproporphyria. Results of laboratory tests of the patient and her family are presented.ResultsA 54-year-old woman was seen in the hospital because of severe hyponatremia accompanied by generalized seizures. Her serum sodium concentration was 112 mEq/L, with concomitant serum and urine osmolalities of 235 and 639 mOsm/kg, respectively. Renal, thyroid, and adrenal functions were normal. Brain, chest, abdominal, and pelvic imaging studies were negative for occult malignant disease. Urinary excretions of porphobilinogen and aminolevulinic acid were substantially elevated. Results of follow-up urine, plasma, and fecal porphyrin studies were consistent with coproporphyria. Results of porphyrin metabolic studies of the patient’s family showed normal findings in her parents and a minimally increased fecal coproporphyrin concentration and urinary uroporphyrin excretion in her sister.ConclusionAn endocrinology consultation is often requested for patients with hyponatremia. It is important to consider the acute hepatic porphyrias in the differential diagnosis, even though these are rare disorders and the family history may not always be helpful because of the high frequency of asymptomatic carriers. (Endocr Pract. 2007;13:164-168)     

Incidencia de la hiponatremia y de sus causas en pacientes neurológicos

IntroductionHyponatremia is considered the most frequent electrolyte disorder found in hospitalized patients and seems to be a prognostic factor during hospitalization.MethodsA prospective observational study was carried out in consecutive neurological patients admitted to our hospital over a 3-month period. Blood and urinary ionogram and osmolality were determined at entry and 3–5 days after admission in all patients with hyponatremia.ResultsOf the 130 patients admitted, 19 (14.6%) had hyponatremia. The causes of hyponatremia were as follows: inappropriate fluid replacement in 4 patients (21%), antihypertensive drugs in 4 (21%), syndrome of inappropriate secretion of antidiuretic hormone in 4 (21%), cerebral salt wasting syndrome in 2 (10%), and edematous status caused by liver disease in one and digestive loss in one (5%) each. Mortality was one (5%) and 0 (0%) among patients with and without hyponatremia, respectively.ConclusionHyponatremia is common in hospitalized neurological patients and can be misdiagnosed as a worsening of the main illness.     

Coma Associated with Vincristine Therapy

Three cases of coma after vincristine therapy are described. One patient had hyponatraemia and other features of inappropriate secretion of antidiuretic hormone. The effects were temporary, and full recovery occurred in all three patients.     

Role of vagal neuropathy in the hyponatraemia of alcoholic cirrhosis.

The hyponatraemia common in decompensated cirrhosis arises in part from secretion of antidiuretic hormone attributed to a decrease in effective blood volume. Baroreceptors send inhibitory impulses to the midbrain and hypothalamus through the vagus and glossopharyngeal nerves. Since vagal neuropathy often occurs in chronic alcoholism, this might theoretically contribute to the inappropriate secretion of antidiuretic hormone, which might in turn induce hyponatraemia. In a prospective study including 34 patients with cirrhosis a high incidence of vagal neuropathy was found in the alcoholics (64%) and a clear cut increase in the incidence of hyponatraemia in patients with evidence of vagal damage and ascites (seven of eight patients (88%); p = 0.02). Results of a retrospective study of 64 patients with cirrhosis and ascitic decompensation showed hyponatraemia in 17 (50%) of 34 alcoholics but in only four (13%) of 30 patients with non-alcoholic disease (p = 0.006). Vagal neuropathy in alcoholic cirrhosis may contribute to the low serum sodium concentrations commonly found in these patients.     

Effect of acetylsalicylic acid on urinary excretion of prostaglandin E in stroke patients

In 12 of 76 stroke patients complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), a significant increase in urinary prostaglandin E (PGE) (p less than 0.005), and a significant positive relationship between the plasma arginine vasopressin (AVR) level and urinary PGE excretion were observed (r = 0.72, p less than 0.05). The experimental results are consistent with the view that renal PGE acts as a modulator of ADH. Nowadays acetylsalicylic acid (ASA), an inhibitor of prostaglandin biosynthesis, is widely used in ischemic stroke, it was felt necessary to study the effect of this drug on urinary PGE excretion. Therefore various daily doses of ASA were given orally for 3 days to patients with ischemic stroke. PGE values in 24-hour urine samples were measured every day for 3 days before administration of the drug and for 3 days during ASA administration. In 10 patients who took 75 mg of ASA, the decrease in urinary PGE excretion was not statistically significant. On the other hand when ASA was administered 300 mg once in 19 patients or 300 mg 4 times in 11 cases, urinary PGE excretion decreased significantly (p less than 0.05 and p less than 0.05 respectively). In another group of 8 patients who were observed before, during and after the ASA administration, a daily oral dose of 300 mg for 3 days caused a significant decrease in urinary PGE excretion during these 3 days (p less than 0.05). The urinary PGE excretion returned to the control level within 3 days after cessation of the ASA administration.     

Hypoalbuminaemic hyponatraemia: a new syndrome?

Six patients with severe hyponatraemia had neurological features of hyponatraemia and pronounced hypoalbuminaemia. All had biochemical features typical of the syndrome of inappropriate secretion of antidiuretic hormone with low serum osmolality and an inappropriately high urinary osmolality. All were given infusions of whole plasma or albumin solution, or both, to restore their plasma albumin concentrations to normal, which led to a dramatic increase in plasma sodium concentrations and serum osmolality, with a concomitant fall in urinary osmolality in all patients. Neurological features were reversed in four patients. It is suggested that severe hypoalbuminaemia is an important cause of appreciable hyponatraemia; infusions of plasma and albumin in such patients may reverse the biochemical and clinical features and should form the basis of management.     

American Association of Clinical Endocrinologists And American College of Endocrinology Disease State Clinical Review: Postoperative Management Following Pituitary Surgery

Pituitary lesions are common in the general population. Patients can present with a wide range of signs and symptoms that can be related to tumor mass effects or pituitary hormonal alterations. Evaluation involves assessing patients for the extent of tumor burden and pituitary hyper- or hypofunction and includes clinical exams, hormonal testing, and brain imaging. Preoperative diagnosis and treatment planning generally require a multidisciplinary team approach with expertise from endocrinologists, neurosurgeons, neuro-ophthalmologists, and neuroradiologists. This review will outline considerations for the evaluation and management of patients with pituitary masses at each stage in their treatment including the pre-, peri- and postoperative phases.Abbreviations: ADH = antidiuretic hormone CSF = cerebrospinal fluid DDAVP = desmopressin DI = diabetes insipidus GH = growth hormone MRI = magnetic resonance imaging SIADH = syndrome of inappropriate ADH release TSS = transsphenoidal surgery     

Downward resetting of the osmotic threshold for thirst in patients with SIADH

The syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by euvolemic hyponatremia. Patients with SIADH continue to drink normal amounts of fluid, despite plasma osmolalities well below the physiological osmotic threshold for onset of thirst. The regulation of thirst has not been previously studied in SIADH. We studied the characteristics of osmotically stimulated thirst and arginine vasopressin (AVP) secretion in eight subjects with SIADH and eight healthy controls and the nonosmotic suppression of thirst and AVP during drinking in the same subjects. Subjects underwent a 2-h infusion of hypertonic (855 mmol/l) NaCl solution, followed by 30 min of free access to water. Thirst rose significantly in both SIADH (1.5 +/- 0.6 to 8.0 +/- 1.2 cm, P < 0.0001) and controls (1.8 +/- 0.8 to 8.4 +/- 1.5 cm, P < 0.0001), but the osmotic threshold for thirst was lower in SIADH (264 +/- 5.5 vs. 285.9 +/- 2.8 mosmol/kgH(2)O, P < 0.0001). SIADH subjects drank volumes of water similar to controls after cessation of the infusion (948.8 +/- 207.6 vs. 1,091 +/- 184 ml, P = 0.23). The act of drinking suppressed thirst in both SIADH and controls but did not suppress plasma AVP concentrations in SIADH compared with controls (P = 0.007). We conclude that there is downward resetting of the osmotic threshold for thirst in SIADH but that thirst responds to osmotic stimulation and is suppressed by drinking around the lowered set point. In addition, we demonstrated that drinking does not completely suppress plasma AVP in SIADH.     

Bilateral pneumonia and inappropriate secretion of antidiuretic hormone in a premature infant.

A 6-week-old infant born prematurely had severe hyponatremia and other features of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This disturbance was believed to be secondary to extensive bilateral pneumonia with collapse of the right upper lobe. Although this association has been recognized in adults, this is the first report of its occurrence in an infant. SIADH must be considered in the differential diagnosis of hyponatremia in association with pneumonia in an infant.     

Urinary excretion of aquaporin-2 and inappropriate secretion of vasopressin in hyponatremic patients after cerebral infarction.

Aquaporin-2, a water-channel protein, is known to increase water permeability due to vasopressin binding to V2 receptors at the renal collecting duct and is excreted into the urine. It is still unclear whether a hyponatremic state is caused by vasopressin-dependent aquaporin-2 in patients clinically diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone. To determine this, we measured urinary aquaporin-2 and vasopressin by radioimmunoassay in normonatremic or hyponatremic patients after cerebral infarction and in healthy controls. In the normonatremia group, urinary aquaporin-2 and plasma AVP levels were higher than in controls. In the hyponatremia group, plasma AVP was relatively high despite low plasma osmolality in each patient. However, urinary aquaporin-2 in hyponatremia was significantly increased when compared with the other two groups. In conclusion, AQP-2 increment does not directly reflect non-osmotic AVP secretion in a hyponatremic state. This result indicates that the urinary excretion of AQP-2 is not only AVP-dependent in hyponatremic states.     

Endocrine and Metabolic Disorders in Bronchial Carcinoma

In an unselected series of 185 patients with histologically confirmed bronchial carcinoma 16 had endocrine disturbances attributable to the tumour (excluding pulmonary osteoarthropathy). Of these, 11 patients had hypercalcaemia; three inappropriate secretion of antidiuretic hormone; one Cushing''s disease; three hypertrophic osteoarthropathy; and one gynaecomastia. Cushing''s disease and inappropriate antidiuresis are specifically associated with oat-cell tumours, and hypercalcaemia occurs most frequently with squamous carcinoma. A negative correlation exists between gynaecomastia and osteoarthropathy on the one hand and oat-cell carcinoma on the other.     

Tolvaptan for the Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion: Lessons Learned In Titration of Dose

ObjectiveTo report a patient with idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH) who developed profound aquaresis with symptomatic extracellular fluid depletion after initiation of therapy with tolvaptan who was later successfully treated with smaller doses of compounded tolvaptan to prevent rapid correction of serum sodium.MethodsCase report and review of the literature.ResultsA 51-year-old woman was diagnosed with SIADH during admission for elective surgery resulting in multiple complications. The patient failed multiple therapies including fluid restriction, salt tablets, and demeclocycline. She was admitted to the hospital for initiation of tolvaptan therapy. After a 15-mg dose of tolvaptan, the patient had rapid increase in urine output and symptomatic hypotension. Sodium levels corrected rapidly overnight from 126 mEq/L to 139 mEq/L. A lower dose of tolvaptan resulted in similar symptoms and sodium correction. Due to continuing symptoms of hyponatremia including headaches, nausea, vomiting, and paresthesias after reinitiation of fluid restriction and salt tablets, tolvaptan was compounded to continue to titrate at lower doses. The patient was then admitted and tolvaptan was initiated at a dose of 1.5 mg with no significant improvement in sodium levels. Tolvaptan was titrated to 3 mg, which resulted in correction of sodium to 129 mEq/L with no associated symptoms of hypovolemia.ConclusionsTolvaptan should be initiated in an inpatient setting with close monitoring of serum sodium levels. In patients who are not able to tolerate recommended dosages, consideration should be given to using a compounded formulation to further titrate to lower doses.(Endocr Pract. 2011;17:e97-e100)     

Miliary tuberculosis presenting with hyponatremia and thrombocytopenia.

A 74-year-old woman with miliary tuberculosis had moderately severe hyponatremia due to inappropriate secretion of antidiuretic hormone (SIADH) and very severe thrombocytopenia without other hematologic abnormalities. She was treated with isoniazid, rifampin, ethambutol, prednisone, vincristine and fluid restriction and recovered completely. The SIADH may have been a response by the posterior pituitary to a decrease in intravascular volume resulting from the extensive pulmonary disease or associated hypoxia, or the tuberculous lung may have released ADH or an ADH-like substance. The thrombocytopenia may have resulted from a direct or indirect toxic effect of infection or, less likely, the tuberculosis may have activated latent idiopathic thrombocytopenic purpura.     

A decrease in plasma sodium ion during the course of an acute attack of porphyria

Sodium ion level disorders were analysed in 53 patients with porphyria during 84 acute attacks of the disease. Thirty two daily water-electrolyte balances in 6 patients treated at ICU were analysed in detail. A decrease in sodium ion levels in patients with porphyria is rather rare and most frequently transient during the acute attack of the disease. Noted disorders were not characteristic for the reported syndrome of the abnormal antidiuretic hormone release. The treatment of the acute attack of porphyria requires the achievement of the positive energy balance which leads to the normalization of sodium ion levels despite intensive hydratation of some patients.