Chronic Idiopathic Hyponatremia in Older People Due to Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Possibly Related to Aging

OBJECTIVE: To determine the prevalence of syndrome of inappropriate antidiuretic hormone secretion (SIADH) among older hyponatremic patients in a subacute geriatric facility, to identify patients with no apparent cause for the SIADH (idiopathic SIADH), and to determine their clinical characteristics. DESIGN: Prospective analysis of a cohort of older patients over a period of 3 months. SETTING: Two wards in a geriatric rehabilitation hospital. PARTICIPANTS: Patients aged 65 and older. MEASUREMENTS: All patients with hyponatremia (serum sodium <135 mmols/l) were clinically examined and relevant investigations were performed to determine the etiology of hyponatremia. Patients were observed for symptoms of hyponatremia. Hyponatremia was classified into possible SIADH and non-SIADH types. Patients with SIADH type hyponatremia were screened for possible causes. Past medical histories were obtained from the general practitioners. RESULTS: Of the 172 patients studied, 43 (25%) had hyponatremia. It was symptomatic in only four patients. Twenty-two (51%) had SIADH etiology. In nine (mean age 84 +/- 4), no cause for the SIADH was evident (presumed idiopathic SIADH) and in seven, hyponatremia (128-135 mmols/l) was chronic (12 to 72 months). Further reduction in serum sodium, which was symptomatic, was noted in two of these patients with the onset of pneumonia. CONCLUSION: Most older hyponatremic patients in a rehabilitation setting seem to have SIADH etiology. This study confirms the presence of a group of older individuals with chronic idiopathic hyponatremia in whom the underlying mechanism may be SIADH related to aging. Hyponatremia is modest in these patients and has little clinical significance. However, they may be at increased risk of developing symptomatic hyponatremia with intercurrent illnesses.     

Hyponatremia after transsphenoidal surgery for hypothalamo-pituitary tumors

Transient diabetes insipidus is a well-known complication after transsphenoidal surgery (TSS). On the other hand, transient hyponatremia has been reported as being a delayed complication of TSS. Transient hyponatremia has been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but the details of hyponatremia have not been clarified. In the present study, we retrospectively reviewed 110 consecutive patients (39 males and 71 females, age 9-80 years) operated on transsphenoidally for pituitary and hypothalamic tumors. We investigated the frequency, time of onset, duration of hyponatremia after TSS, and analyzed possible factors associated with it. A postoperative sodium concentration <135 mEq/l was observed in 29 (26%) patients. Five patients were excluded from this study because their hyponatremia could be due to either overdose of desmopressin or SIADH for meningitis. Therefore, we investigated 24 (22%) patients with hyponatremia in this study. The sodium levels in the patients with hyponatremia ranged from 110 to 134, with a mean of 126.2 +/- 5.3 mEq/l. Hyponatremia was observed on average on postoperative day 9.5 +/- 2.4, the serum sodium levels normalized within 3.8 +/- 1.7 days. Hyponatremia occurred in patients with non-functioning pituitary adenoma (26%, 11/42), Rathke's cleft cyst (29%, 5/17), prolactinoma (31%, 4/13) and acromegaly (15%, 4/27). 18 patients (75%, 6/24) who developed hyponatremia had macrotumor (>10 mm), and 6 patients (25%, 6/24) had microtumor. The plasma arginine vasopressin (AVP) levels in the patients with hyponatremia ranged from 0.21 to 2.1, with a mean of 0.79 +/- 0.46 pg/ml, and the levels were inversely correlated with plasma osmolality (r = -0.80, p = 0.002). The urine to plasma osmolality ratios were >1. All the patients received appropriate hormonal replacement, including hydrocortisone. These data showed that postoperative hyponatremia after TSS was not rare, and the hyponatremia was mainly associated with SIADH. As the hyponatremia could be a life-threatening complication, all patients should be screened for serum electrolytes after TSS.     

Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency

Patients with hyponatremia related to adrenocorticotropic deficiency are not easily distinguished by routine laboratory studies from patients with nonendocrine inappropriate secretion of antidiuretic hormone (SIADH). We wanted to investigate whether, in the routine biological analysis of such patients, some parameters could help to better identify this subgroup of hyponatremic patients. The biochemical profiles of 13 consecutive patients with hyponatremia related to ACTH deficiency were analyzed and compared with 30 consecutive patients with classical SIADH. Patients with adrenocorticotropic deficiency presented low uric acid and urea levels as in nonendocrine SIADH, but their total carbon dioxide was significantly lower (total CO(2), 20.5 +/- 3 vs. 25.5 +/- 2.4 mmol/liter; P < 0.001). Nine of the 13 patients presented a value lower than 22 mmol/liter, although this was not observed in the nonendocrine SIADH patients (P < 0.001). Arterial blood gas analysis was available in eight patients and showed a compensated respiratory alkalosis in most of them (pH 7.42 +/- 0.02; PCO(2), 30 +/- 5 mm Hg; HCO(3)(-), 20 +/- 2 mmol/liter; base excess, -3.4 +/- 1.8 mmol/liter). Aldosterone levels were much lower in ACTH deficiency patients during the hyponatremic state (33 +/- 40 pg/ml) when compared with the nonendocrine SIADH (120 +/- 60 pg/ml; P < 0.01). Correction of hyponatremia by cortisone therapy normalized total CO(2) and aldosterone levels. Low carbon dioxide level is a frequent observation in hyponatremia related to ACTH deficiency and could help to differentiate it from classical SIADH.     

Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion complicating stem cell transplantation

Hyponatremia is a common electrolyte disorder in hospitalized patients. Although there are a few case reports of hyponatremia following stem cell transplantation (SCT), no reports concerning the incidence are currently available. We describe the occurrence of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following SCT. In a single center analysis of 140 patients, hyponatremia and SIADH were observed in 40 and 11.4% of patients, respectively, following SCT. Risk factors for SIADH included young age, transplantation from an HLA-mismatched or unrelated donor, cord blood transplantation, and graft-versus-host disease prophylaxis with methyl prednisolone. Multivariate analysis revealed that transplantation from an HLA-mismatched donor and performance of SCT in a child below 4 years of age were risk factors for SIADH. For patients who underwent SCT from an HLA-mismatched or unrelated donor, those with SIADH showed a significantly higher overall survival rate (90.9 vs 40.2%) and event-free survival rate (77.8 vs 33.8%) compared to those without SIADH. Overall, our data show that hyponatremia and SIADH are relatively common complications following SCT, especially in children below 4 years of age and after SCT from an HLA-mismatched donor.     

Syndrome of inappropriate secretion of antidiuretic hormone and thrombocytopenia caused by cytomegalovirus infection in a young immunocompetent woman

We report the first case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with cytomegalovirus (CMV) infection. A 32-year-old woman was admitted to our hospital because of pandysautonomic signs and symptoms. Thrombocytopenia and hyponatremia were present. Serum anti-CMV IgM and IgG antibodies were positive. Despite hyponatremia, urinary osmolality exceeded plasma osmolality and plasma vasopressin levels related to plasma osmolality were high. Restriction of water intake and administration of dimethylchlorotetracycline improved hyponatremia, suggesting this patient had SIADH. In this patient, SIADH may have been caused by acute pandysautonomia that developed following CMV infection.     

Urinary retention: a cause of hyponatremia?

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in elderly hospitalized patients; however in many patients the etiology remains unclear even after routine investigations. OBJECTIVE: To report our experience of the association of hyponatremia and urinary retention in elderly hospitalized patients. PATIENTS: Six patients with hyponatremia and urinary retention who were admitted to the geriatric department in our hospital during a four-year period (2001-2004). RESULTS: The mean age of the patients was 85 years. The mean serum sodium level was 120 mEq/l, average volume of retained urine was 933 ml (range 500-1,500 ml). All patients underwent a comprehensive work-up seeking a possible cause for the hyponatremia. The diagnostic work-up was negative. In 5 of the patients the laboratory findings fulfilled the criteria for SIADH. In all patients hyponatremia resolved following urinary catheterization and fluid restriction. All patients made a complete recovery. CONCLUSIONS: Potentially, urinary retention by itself may cause hyponatremia. The possible mechanism for this is SIADH, triggered by bladder distention or pain due to bladder distention. Urinary catheterization may be the key to treatment in these cases of hyponatremia.     

Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea

Recent data have shown the role of urea in the urinary concentrating mechanism. We studied the effects of exogenous urea administration in hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In 20 patients with SIADH, we observed a positive correlation between serum sodium and blood urea levels (r = 0.65; p < 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p < 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p < 0.001). The short-term administration of low doses of urea (4 to 10 g) resulted in correcting the “salt-losing” tendency of this patient. Longer term administration of high doses of urea (30 g/day) was attempted with the same patient as well as with a healthy volunteer subject with Pitressin^®-induced SIADH. In both patients, urea treatment lowered urinary sodium excretion as long as hyponatremia was significant (< 130 meq/liter). Urea treatment also induced a persistent osmotic diuresis, allowing a normal daily intake of water despite SIADH. This was clearly shown during the long-term treatment of a third patient with SIADH who was taking 30 g urea/day during 11 weeks.It is concluded that urea is a good alternative in the treatment of patients with SIADH who present with persistent hyponatremia despite the restriction of water intake.     

Hyponatremia among institutionalized elderly: Prevalence and associated clinical factors

PurposeTo study the prevalence of hyponatremia and clinical factors that are associated with increased risk, in a population of institutionalized elderly.MethodsA retrospective record review and prospective analysis of a cohort of elderly in a long-term governmental facility in Bahrain was carried over a period of 5 months. Elderly residents 60 years and older were clinically assessed and laboratory investigations were done including: hemoglobin, fasting blood sugar, blood urea nitrogen, serum creatinine, serum albumin, total proteins, total cholesterol, triglycerides, serum uric acid, serum electrolytes, and thyroid stimulating hormone (TSH) serum level. Hyponatremia was diagnosed with serum sodium level less than 135 mmol/L. Serum osmolality, serum cortisol, and urine osmolality, and urinary electrolytes were done for hyponatremics. Hyponatremia was then classified into syndrome of inappropriate antidiuretic hormone secretion (SIADH) and non-SIADH type. Water loading test was done for SIADH cases to differentiate from reset osmostat.ResultsAmong the 69 studied residents, the prevalence of hyponatremia was 39.1% (27/69). Twenty-three out of 69 (33.3%) had at least one episode of hyponatremia during the previous 12 months. Hyponatremics had lower serum albumin and cholesterol levels, higher prevalence of diuretics usage and subclinical hypothyroidism. Eighteen out of 27 (66.7%) had SIADH type among which 33.3% (6/18) idiopathic. Water loading test revealed reset osmostat prevalence of 27.3%, and SIADH of 72.7%.ConclusionHyponatremia is common among institutionalized elderly and mostly of SIADH etiology with diuretics and malnutrition increasing the risk. Subclinical hypothyroidism can carry risk for hyponatremia.     

Endocrinopathy-induced euvolemic hyponatremia

Euvolemic hyponatremia results from either the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, or adrenal insufficiency. Furthermore, the criteria for diagnosis of SIADH entail the exclusion of hypothyroidism and hypoadrenalism. We aim to assess the yield of euvolemic hyponatremia workup focusing on underlying endocrinopathies in a real-world setting. A single-center retrospective study includes all patients diagnosed with euvolemic hyponatremia in a tertiary hospital between 1.1.2007 and 1.1.2013. Demographic, clinical, and laboratory data were collected from medical charts. Euvolemic hyponatremia was detected in 564 patients. Thyroid function was tested in 69% (391/564) and adrenal function was assessed in 29% (164/564) of cases. Endocrinopathy-induced euvolemic hyponatremia was diagnosed in nine (1.6%) patients: three patients were diagnosed with hypothyroidism-induced hyponatremia, three with adrenal insufficiency as an underlying cause, and three with central hypothyroidism and central hypoadrenalism. All nine had medical history and symptoms suggestive of endocrine deficiencies other than the hyponatremia, which resolved within 1–3 days after administration of hormone replacement therapy. Yield of performed workup for hypothyroidism and hypoadrenalism in euvolemic hyponatremia was low. However, in this real-world study, only a limited number of patients underwent a full ascertainment of hypoadrenalism and hypothyroidism, which was diagnosed only in patients with additional findings supportive of these endocrinopathies; a higher rate of undiagnosed endocrinopathies cannot be ruled out. As both hypoadrenalism and hypothyroidism are easily treatable, potentially life-threatening conditions, there are insufficient data to change current recommendation for their universal evaluation in patients with euvolemic hyponatremia.     

Prevalence and clinical demographics of cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage

Hyponatremia is a frequent complication following subarachnoid hemorrhage (SAH), and is commonly attributed either to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSW). The object of this study is to elucidate the clinical demographics and sequelae of hyponatremia due to CSW in subjects with aneurysmal SAH. Retrospective chart review of patients >18 years with aneurysmal SAH admitted between January 2004 and July 2007 was performed. Subjects with moderate to severe hyponatremia (serum sodium <130 mmol l⁻¹) were divided into groups consistent with CSW and SIADH based on urine output, fluid balance, natriuresis, and response to saline infusion. Clinical demographics were compared. Of 316 subjects identified, hyponatremia (serum sodium <135 mmol l⁻¹) was detected in 187 (59.2%) subjects and moderate to severe hyponatremia in 48 (15.2%). Of the latter group, 35.4% were categorized with SIADH and 22.9% with CSW. Compared to eunatremic subjects, hyponatremia was associated with significantly longer hospital stay (15.7 ± 1.9 vs. 9.6 ± 1.1 days, p < 0.001). Subjects with CSW had similar mortality and duration of hospital stay vs. those with SIADH. Though less common than SIADH, CSW was detected in approximately 23% of patients with history of aneurysmal SAH and was not clearly associated with enhanced morbidity and mortality compared to subjects with SIADH. Further studies regarding the pathogenesis and management, along with the medical consequences, of CSW are important.     

Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder

Hyponatremia occurs in about 30% of hospitalized patients and syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. SIADH should be differentiated from other causes of hyponatremia like diuretic therapy, hypothyroidism and hypocortisolism. Where possible, all attempts should be made to identify and rectify the cause of SIADH. The main problem in SIADH is fluid excess, and hyponatremia is dilutional in nature. Fluid restriction is the main stay in the treatment of SIADH; however, cerebral salt wasting should be excluded in the clinical setting of brain surgeries, subarachnoid hemorrhage, etc. Fluid restriction in cerebral salt wasting can be hazardous. Sodium correction in chronic hyponatremia (onset >48 hours) should be done slowly to avoid deleterious effects in brain.     

Close association of urinary excretion of aquaporin-2 with appropriate and inappropriate arginine vasopressin-dependent antidiuresis in hyponatremia in elderly subjects

The present study was undertaken to determine whether urinary excretion of aquaporin-2 (AQP-2) participates in the involvement of arginine vasopressin (AVP) in hyponatremia less than 130 mmol/L in 33 elderly subjects (> or =65 yr old) during the last 5-yr period. Subjects were separated into euvolemic hyponatremia groups: 13 with hypopituitarism, 8 with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), 8 with mineralocorticoid-responsive hyponatremia of the elderly, and 4 with miscellaneous diseases. Approximately 40% of those with hyponatremia was derived from hypopituitarism, but severe hyponatremia was found in the patients with SIADH and mineralocorticoid-responsive hyponatremia of the elderly. Plasma AVP levels remained relatively high despite hypoosmolality and were tightly linked with exaggerated urinary excretion of AQP-2 and antidiuresis in the 3 groups of patients, except for one miscellaneous one. An acute water load test verified the impairment in water excretion, because the percent excretion of the water load was less than 42% and the minimal urinary osmolality was not sufficiently diluted. Also, plasma AVP and urinary excretion of AQP-2 were not reduced after the water load. The inappropriate secretion of AVP was evident in the patients with SIADH and hypopituitarism, and hydrocortisone replacement normalized urinary excretion of AQP-2 and renal water excretion in those with hypopituitarism. In contrast, the appropriate antidiuresis seemed to compensate loss of body fluid in the patients with mineralocorticoid-responsive hyponatremia of the elderly, who lost circulatory blood volume by 7.3% (mean). Fludrocortisone acetate increased renal sodium handling and body fluid, resulting in the reduction in AVP release and urinary excretion of AQP-2 in mineralocorticoid-responsive hyponatremia of the elderly. These findings indicate that urinary excretion of AQP-2 may be a more sensitive measure of AVP effect on renal collecting duct cells than are plasma AVP levels, and that increased urinary excretion of AQP-2 shows exaggerated AVP-induced antidiuresis in hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive hyponatremia of the elderly has to be carefully differentiated from SIADH in elderly subjects.     

Paroxetine-induced hyponatremia in an elderly man due to the syndrome of inappropriate secretion of antidiuretic hormone

We report an 82-year old man prescribed paroxetine who had hyponatremia and in whom the syndrome of inappropriate secretion of antidiuretic hormone was diagnosed. He had taken sulpiride for depressed mental status. However, he showed parkinsonism, which was an adverse effect from the treatment of sulpiride. Therefore sulpiride was changed to selective serotonin reuptake inhibitor, paroxetine 10mg daily. His depressed mental status deteriorated after paroxetine treatment started. His depression had not lessened after 12 days, and the dosage was increased to 20mg daily. On the 15th day after starting paroxetine, routine laboratory tests showed that his serum sodium level was 126 mEq/l. We recognized that his confusion and loss of appetite were symptoms of hyponatremia, rather than of worsening depression. Laboratory data revealed hyponatremia, low serum osmolarity (242 mOsm/kg) with a relatively high level of serum antidiuretic hormone, and concentrated urine (439 mOsm/kg). We diagnosed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), associated with paroxetine. The dosage of paroxetine was reduced gradually and the serum sodium level returned to normal on day 2 after medication ceased completely. Paroxetine produces fewer adverse effects than other types of antidepressants. However, its use can be associated with inappropriate secretion of antidiuretic hormone in the body and may lead to SIADH, which is characterized by hyponatremia, a potentially fatal condition that is typically asymptomatic until it becomes severe. SIADH is more likely in some populations, including the elderly. Serum sodium levels should be monitored closely, especially in elderly patients.     

Recurrent hyponatremia after traumatic brain injury

Dysregulation of the neuroendocrine system is a frequent complication after traumatic brain injury (TBI). Symptoms of these hormonal abnormalities might be subtle and thus easily ignored. Hyponatremia usually indicates underlying disorders that disrupt fluid homeostasis. In most patients with TBI, hyponatremia is a feature of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion due to pituitary dysfunction after head injury. Usually TBI-associated hyponatremia is transient and reversible. We report the case of a 48-year-old man with TBI-associated hyponatremia with delayed recovery and recurrent hyponatremia precipitated by subsequent surgery. In this report, we emphasize the importance of identifying patients with slow recovery of the injured brain, which could complicate with SIADH and acute hyponatremia. Differentiating TBI-associated SIADH from other important causes of hyponatremia such as cerebral salt wasting, and hypocortisonism are also reviewed. Prevention of its recurrence by avoiding further risk is mandatory in managing patients with TBI.     

Hyponatremia in patients treated with lorcainide, a new antiarrhythmic drug

The effects of lorcainide, a new antiarrhythmic drug, on serum electrolytes and osmolality are described in a series of 33 patients with organic heart disease and complex ventricular arrhythmias treated with lorcainide. In eight patients, a mean decrease in serum Na+ of 8.25 +/- 3.2 mEq/L was observed after a single 200 mg intravenous dose of lorcainide. Sixteen of 33 patients developed significant hyponatremia and hypoosmolality during oral treatment with lorcainide. In all except two patients, serum Na+ returned to normal values within 3 to 12 months of continued lorcainide therapy. Low serum Na+ and hypoosmolality in the absence of volume depletion, clinically manifest edema, and unaltered renal, adrenal, cardiac, or thyroid function suggest that this antiarrhythmic drug produced the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH appeared to be transient and asymptomatic in our patients. One patient developed severe hyponatremia with serum Na+ of 108 mEq/L when hydrochlorothiazide was given to control hypertension. It is concluded that SIADH is an important side effect of lorcainide therapy. We recommend that serum Na+ be carefully monitored in patients started on lorcainide therapy, and extreme caution should be exercised in prescribing diuretics to patients with persistent hyponatremia.     

Severe hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone developed as initial manifestation of human herpesvirus‐6–associated acute limbic encephalitis after unrelated bone marrow transplantation

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo‐SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus‐6–associated post‐transplantation acute limbic encephalitis (HHV‐6 PALE) after allo‐SCT. A 45‐year‐old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus‐mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV‐6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV‐6 PALE, and close monitoring of serum sodium levels in high‐risk patients for HHV‐6 PALE is necessary for immediate diagnosis and treatment initiation.     

Syndrome of inappropriate secretion of antidiuretic hormone associated with localized herpes zoster ophthalmicus

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with localized herpes zoster is rarely reported and may be under-appreciated. We describe two diabetic men with herpes zoster ophthalmicus (HZO) who developed hyponatremia (114 and 116 mmol/L) during acute illness. Both were euvolemic and had elevated urine osmolality (435 and 368 mmol/kg.H₂O) and sodium (Na⁺) concentration (61 and 63 mmol/L) along with normal cardiac, renal, liver, and endocrine function consistent with the diagnosis of SIADH. Thorough investigation for other causes of SIADH, including detailed physical examination, laboratory studies, and computed tomography of the brain, chest, and abdomen, were negative. Despite antiviral therapy (acyclovir) for herpes zoster, ophthalmoplegia, keratitis, and post-herpetic neuralgia (PHN) developed. Even with fluid restriction and high salt diet, SIADH lasted for 3 to 4 months and resolved concomitantly with resolution of PHN, suggesting an association between SIADH and HZO. These two cases raise the potential for herpes zoster infection, especially HZO, to involve the regulatory pathway of ADH secretion, contributing to SIADH. The presence of PHN, which reflects greater neural damage may, at least in part, explain the prolonged ADH secretion and hyponatremia.     

Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases

OBJECTIVE: Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. METHODS: In a retrospective study we screened the files of 185 patients with severe hyponatremia (<130 mmol/l) that had been seen in one endocrinological unit of a university hospital between 1981 and 2001 in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency. RESULTS: In 139 cases it was possible to clearly ascribe the patients to the pathophysiological groups of (i) primary sodium deficiency, (ii) edematous disorders, and (iii) normovolemic disorders including the "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH). Twenty-eight patients with severe "normovolemic hyponatremia" (serum sodium: 116+/-7 mmol/l, mean+/-s.d.) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function. In 25 cases of this group hypopituitarism (mostly due to empty sella, Sheehan's syndrome and pituitary tumors) had not been recognized previously, and in 12 cases recurrent hyponatremia during previous hospital admissions (up to four times) could be documented. The mean age of these patients (21 women, seven men) was 68 Years. The most frequently occurring clinical signs were missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in the men. Frequent symptoms like nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 patients with SIADH. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439 nmol/l (mean+/-s.d.: 157+/-123), while in 30 other severely hyponatremic patients it ranged from 274 to 1732 nmol/l (732+/-351 nmol/l). In most patients with hyponatremic hypopituitarism, plasma antidiuretic hormone levels were inappropriately high, probably due to a failure of endogenous cortisol to suppress the hormone in a stressful situation. All patients recovered after low-dose hydrocortisone substitution. Most patients had other pituitary hormone deficiencies and were appropriately substituted subsequently. CONCLUSIONS: Hypopituitarism including secondary adrenal insufficiency seems to be a frequently overlooked cause of severe hyponatremia. A high level of suspicion is the best way to recognize the underlying disorder. Treatment with hydrocortisone is very effective.     

Malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH

Patients with thymoma are likely to present with associated autoimmunologic disorders. The occurrence of syndrome of inappropriate antidiuretic hormone (SIADH) attributable to thymoma is extremely rare. We herein present an extremely rare case of a 59-year-old man patient who was discovered to have malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH. He was admitted for evaluation and treatment of hyponatremia (Na 125 mEq/l). SIADH was diagnosed, and thymoma was identified as its cause. The patient was also found to have both Graves' disease and myasthenia gravis. The hyponatremia was normalized with water restriction and 3% saline therapy before thymectomy. The thymic tumor was a Masaoka stage III thymoma that resulted in direct invasion to the wall of the innominate vein, but there was no finding of invasion to other mediastinal organs. Complete thymectomy with innominate vein graft was performed. Microscopic histopathology findings corresponded to those of a mixed-type thymoma and type B2. However, immunohistochemical stain for antidiuretic hormone was negative in the tumor cells. Adjuvant radiation therapy was employed postoperatively, and the patient's postoperative recovery was uneventful. He subsequently reached a euthyroid state. And the reversal to normal sodium and osmolality levels was continued after the tumor removal without any further management for hyponatremia. The observation of this interesting case and a literature review provided us with the opportunity to explore the pathogenesis and clinical aspects of thymoma-related autoimmune and/or endocrine disorders which must be suspected in patients with thymoma.