High Urine Osmolality Research Articles

A PUZZLING DIAGNOSIS: UNUSUAL LARYNGEAL CARCINOMA PRESENTING AS PARANEOPLASTIC SYNDROME

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: The Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is one of the most common causes of euvolemic hyponatremia. The most common malignancy associated with SIADH is small cell lung cancer. We present a case of a patient with SIADH secondary to well differentiated squamous cell carcinoma of the vocal cords. CASE PRESENTATION: A 62-year-old Caucasian male with a history of alcohol abuse and 80 pack-year smoking history presented with recurrent hyponatremia. He was initially admitted to the ICU for altered mental status due to hyponatremia of 111 which was thought to be a combination of beer potomania/SIADH/low solute intake. He required hypertonic saline boluses twice and a one dose of DDAVP to prevent overcorrection, along with fluid restriction with an improvement of Na to 132. (Image 1) Chest CT was obtained that did not reveal any malignancy. He was discharged with fluid restriction and follow up with his PCP. At his follow up, he was found to have again developed severe hyponatremia of 112. He was admitted again to the ICU for appropriate normalization of sodium, required isotonic saline and then fluid restriction. SIADH was confirmed by low Serum Osmolality at 245mosm/kg, high Urine osmolality of 502mosm/kg, Urine sodium of 41mEq/l,and normal serum Potassium of 4.3mEq/l along with low serum uric acid of 3.4mg/dl. Upon review of the CT chest with the radiologist he had some density on his left aryepiglottic fold. Upon closer discussion with him, he endorsed progressive hoarseness for the past year to the point of losing his voice. He also lost about 20 pounds over the last year, with a 10-pound weight loss over the past month. CT neck with IV contrast showed a 4.5cm laryngeal mass (Image 2) and direct laryngoscopy and microscopic laryngoscopy with biopsy of the tumor on the left vocal cord with multiple biopsies taken of the terminal vocal cords finally revealed squamous cell carcinoma. He is scheduled to follow up with oncology, ENT and radiation oncology after a PET scan for tumor staging to decide on further treatment with concurrent chemotherapy and radiation. DISCUSSION: There is a possible relationship between the tumor mass burden and the severity of the hyponatremia. This has been shown in another laryngeal carcinoma but was not seen with recurrence of the tumor.[1] The mechanisms leading to the associated hyponatremia could have been related to tumor ADH productions or other factors yet unknown.[2] CONCLUSIONS: SIADH is well known to occur with squamous cell lung cancer. Other types of squamous cell carcinomas are known to cause SIADH as a paraneoplastic syndrome, particularly squamous cell carcinoma of the tongue.[3] It has not been well documented to be from squamous cell carcinoma of vocal cords. Reference #1: Talmi YP, Hoffman HT, McCabe BF (1992) Syndrome of inappropriate secretion of arginine vasopressin in patients with cancer of the head and neck. Ann Otol Rhinol Laryngol 101:946-949 Reference #2: Roth Y, Lightman SL, Kronenberg J. (1994). Hyponatremia associated with laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 251: 183-185 Reference #3: Zohar Y, Talmi YP, Finkelstein Y, Nobel M, Gafter U (1991) Syndrome of inappropriate antidiuretic hormone secretion in cancer of the head and neck. Ann Otol Rhinol Laryngol 100:341-344 DISCLOSURES: No relevant relationships by Sofia Adamidi, source=Web Response no disclosure on file for Steven Lamontagne; No relevant relationships by Preeyanka Sundar, source=Web Response

Abstract P144: Integrin β1 in Tubular Epithelium Protects From Acute Injury Induced Fibrosis

Acute kidney injury (AKI) results in the sudden loss of renal function primarily due to renal tubular injury. Repeated injury or maladaptive recovery lead to chronic kidney diseases. All forms of chronic kidney disease are characterized by excessive extracellular matrix (ECM) accumulation. The proximal tubule cells that are injured but not detached from the basement membrane are critical for the restoration of renal functions after the injury incidence. Renal tubular epithelial cell adhesion, migration, and proliferation are required for the kidney to recover from sub-lethal injury. These processes require the ability of cells to interact with the ECM. Integrin, which exists as a complex of α and β subunits, are the principal receptors for ECM proteins. Integrin β1 is the major integrin subunit present in kidney and critically regulates renal epithelial cell functions. We investigated the importance of Integrin β1 in kidney proximal tubule epithelial cells. Integrin β1 was deleted from these cells using the γ-gt cre. These KO mice had no morphological abnormalities but have a higher urine osmolality (2369±881 mΩ) compared to WT (2098±945 mΩ). By using a nephrotoxic injury model, we investigated the role of integrin β1 in AKI. Samples were collected on 3, 5, 7 and 14 days after injury to assess the nature of injury and recovery. Integrin β1 KO mice were more susceptible to injury as evident by protein casts and tubule dilation of tubules. The blood urea nitrogen (BUN) from the plasma showed increased BUN level in KO animals compared to WT controls (26.78±8.23 and 34.05±7.11). After the injury the level was increased to 52.26±18.37 in WT and 60.34±11.58 KO suggesting both were injured to a similar extent. After 14 days the WT recovered better than KO animals (BUN 37.33±10.12 and 48.73±15.92). After 14 KO mice had more collagen deposition compared to WT animals. This data suggests the importance of integrin β1 in the tubular epithelium in promoting the recovery from injury and preventing its progression to chronic kidney disease.

Recent developments in the management of acute and chronic hyponatremia.

The aim of the study is to review recent studies on the management of acute and chronic hyponatremia. In acute symptomatic hyponatremia, bolus infusion of hypertonic saline improves hyponatremia and neurological status more quickly than continuous infusion. In chronic hyponatremia, newly identified predictors of nonresponse to fluid restriction include a high urine osmolality (>500 mOsm/kg) and high urine sodium (>133 mmol/l). Vasopressin-receptor antagonists effectively raise the serum sodium concentration in patients with euvolemic or hypervolemic hyponatremia but have a risk of overcorrection, even at low doses. Several observational studies now support the use of urea for a more gradual correction of hyponatremia without a risk of overcorrection. Recently identified risk factors for overcorrection include lower serum sodium at presentation, polydipsia, hypovolemia, and early urine output during treatment. Specific treatments with potential efficacy are the use of intravenous albumin for hyponatremia because of liver cirrhosis, and fludrocortisone for hyponatremia in tuberculous meningitis. The recent data will help to further optimize and personalize the management of patients with acute and chronic hyponatremia. However, most data are still observational and retrospective. Therefore, the field is in need of prospective studies comparing interventions for chronic hyponatremia and focusing on patient-relevant outcomes.

誤嚥性肺炎後に生じた鉱質コルチコイド反応性低ナトリウム血症の1例(Mineralocorticoid–responsive hyponatremia of the elderly secondary to aspiration pneumonia: a case report)

要旨 67歳の男性。路上で倒れているところを発見され救急要請された。救急隊接触時はJCS I–3R，頚動脈触知可，脈拍 45/分，冷感が強く体温測定不可能であった。当院搬送時はGCS E4V2M5，血圧 69/45mmHg，脈拍53/分，膀胱温は27.1℃，血清Naは109mEq/Lであった。偶発性低体温症，低Na血症による意識障害で救命救急センターに入院となった。補正による血清Naの改善に伴い意識レベルも徐々に改善を認めた。しかし誤嚥性肺炎を合併したため人工呼吸管理が必要であった。人工呼吸管理中より再度低Na血症が進行した。経口，経静脈的にNaの補正を行ったが改善せず，第22病日には121mEq/Lまで低下した。低浸透圧血症，高浸透圧尿症，ADH高値，エコーにて体液過剰が否定的であることから鉱質コルチコイド反応性低Na血症と診断した。輸液負荷，塩分補充に対する反応に乏しかったことから鉱質コルチコイドの補充を追加した。ADHを経時的に測定し正常化したのを確認後に鉱質コルチコイドを漸減し，第78病日に中止した。その後は血清Na値の低下を来すことなく，リハビリ目的に転院した。高齢者はストレスに対する予備力が低下しているため電解質異常を合併しやすい。高齢者の低Na血症の診断において治療が異なるためSIADHとの鑑別が重要である。また血清Na正常化後も鉱質コルチコイドの長期投与が必要である。

Urinary extracellular vesicular release of aquaporins in patients with renal transplantation

BackgroundDiuresis has been observed within a week following renal transplantation, suggesting that the procedure causes acute disturbance of renal water homeostasis. Aquaporin (AQP) 1 and AQP2, important proteins for renal water reabsorption, have been identified in urinary extracellular vesicles (uEV-AQP1 and -AQP2), and experimental studies have shown that the presence of uEV-AQP1 and -AQP2 may be an indicator of their levels of expression in the kidney. However, the release patterns of uEV-AQP1 and -AQP2 during the acute phase following renal transplantation are largely unknown.MethodsIn this study, we examined the release of uEV-AQP1 and -AQP2 in recipients until 6 days (day 6) after renal transplantation. At Miyazaki prefectural Miyazaki Hospital, Japan, uEVs were obtained from 7 recipients, all of whom had received renal allografts from living donors. uEVs were isolated by differential centrifugation.ResultsImmunoblotting analysis showed that the release of uEV-AQP2 was significantly decreased on day 1 in comparison with a control sample (from 3 healthy volunteers), accompanied by high urine output and low urine osmolality. Thereafter, the level increased gradually to the control level by day 6. The release pattern of uEV-AQP1 was similar to that of uEV-AQP2, but the levels did not reach statistical significance in comparison with the control level at any of the time points examined. Evaluation of the relationship between urinary osmolality and uEV-AQPs revealed a significant correlation for uEV-AQP2, but not for uEV-AQP1.ConclusionThese results indicate that acute diuresis after renal transplantation might be due to a decrease in the renal expression of AQP2, whose level can be estimated from the amount released in uEVs.

SUN-436 Severe Hyponatremia as the Presenting Feature of Partially Empty Sella

Introduction: We report a case of severe acute on chronic hyponatremia meeting the laboratory diagnostic criteria of SIADH. Subsequent evaluation showed secondary adrenal insufficiency due to partially empty sella. Hyponatremia completely resolved following hydrocortisone treatment. Clinical Case: A 76-year-old man with history of hypothyroidism and SIADH was admitted with weakness, fatigue, and leg cramps for the past 3 months. He was staying in a cabin with a broken air conditioner during the summer when his symptoms started. Physical exam revealed mild dry mucus membranes, normal skin turgor, capillary refill less than 2 sec., bradycardia, and no skin hyperpigmentation. He was found to have acute-on-chronic hyponatremia with a serum sodium of 115 mEq/L (baseline 124 mEq/L-130 mEq/L), which worsened with initial volume resuscitation. Lasix and salt tablets were not effective treatment. Other labs showed a low serum osmolality (241 mOsm/kg), high urine osmolality (598 mOsm/kg), high urine sodium (121 mmol/L), low serum uric acid (2.7 mg/dL, n 3.3-8.5 mg/dL), normal TSH, and a low normal AM cortisol (5.7 ug/dL, n 4.0-17.0 ug/dL). A subsequent cosyntropin stimulation test confirmed adrenal insufficiency with a 60 min cortisol of 10.3 ug/dL. ACTH was inappropriately normal (23 pg/mL, n 7-69 pg/mL) indicating a central etiology. In addition, he had a mildly elevated prolactin (23 ng/mL, n 4-15 ng/mL), inappropriately normal TSH (2.83 uIU/mL, n 0.30-4.50 uIU/mL), low normal total T4 (5 ug/dL, n 4.9-11.7 ug/dL), and a mildly low total T3 (52.3 ng/dL, n 58.0-159.0 ng/dL) suggesting a possible secondary hypothyroidism. A pituitary MRI revealed partially empty sella without evidence of pituitary adenoma. The patient was started on stress-dose hydrocortisone with subsequent increased urine output (4 L within 8 h of initial treatment) and increased serum sodium as well. To prevent rapid sodium correction, one dose of desmopressin was given with a low rate hypertonic saline to equilibrate the desmopressin effect. Hydrocortisone was tapered to maintenance dose, and the fluid restriction was discontinued to prevent dehydration. His home Levothyroxine dose was increased, and he was discharged with a serum sodium of 133 mEq/L. As an outpatient, his sodium has normalized with continued treatment. Discussion: Secondary adrenal insufficiency is characterized by euvolemic hyponatremia with biochemical features of SIADH without hyperkalemia. ADH increases due to the lack of cortisol negative feedback loop and the reduction in systemic blood pressure and cardiac output from cortisol deficiency. Hyponatremia corrects rapidly with steroid treatment, which turns off ADH and causes free water excretion. Desmopressin and hypertonic saline can be effectively used to prevent or stop rapid sodium correction. An interesting feature about this case is that partially empty sella is the cause for hypopituitarism.

SUN-435 SIADH Precipitated by Pneumonia in a Background of Hypothyroidism and SSRI Use

Introduction: Hyponatremia is serum sodium levels below 135 meq/L. SIADH is a disorder of impaired water excretion caused by the inability to suppress the secretion of ADH leading to hyponatremia. Important causes of hyponatremia are heart failure, cirrhosis, diuretic induced, hypothyroids, cortisol deficiency and SIADH. Causes of SIADH are CNS disorders, malignancies, surgery, pulmonary disease (particularly pneumonia), hormone deficiency (both hypopituitarism, hypothyroidsm), HIV, drugs- esp. SSRIs. Clinical Case: 74 y/o F with past medical history of Diabetes, HTN, hypothyroidism, depression and chronic compensated hyponatremia under carvedilol, losartan, levothyroxine, citalopram, presented to ER with SOB with wheezing. Patient was admitted for pneumonia and treated with azithromycin and ceftriaxone. In Day 2, he developed intractable nausea and vomiting despite zofran and phenargan. IV NS was started. Patient developed hyponatremia, Na of 126 mEq/L, serum osmolality 240, Urine osm 457 mOsm/, TSH was 41 mIU/L. Levothyroxine was increased to 175 mcg. Fluid & Citalopram was stopped. Na was closely monitored. Over the next few days, patient and Na levels slowly improved with fluid restriction and Na tablets. Conclusion: Not all hyponatremia is SIADH while SIADH is a cause of hyponatremia. The diagnosis is often confusing. SIADH should be suspected in any patient with serum Na <135 mmol/L, serum osmolality <280 mOsm, and a inappropriate and relatively high urine osmolality (compared to serum osmolality). SIADH is more common in patients above age 65 years. Finding out the cause and fluid restriction is the mainstay of treatment in SIADH. Exception to this is brain surgeries & Sub Arachnoid Hemorrhage where there may be ongoing cerebral salt wasting and, fluid restriction can be deleterious as it can cause cerebral vasospasm. However for most cases of non-SIADH hyponatremia, Sodium chloride, (oral tablet or isotonic saline) is the therapy. Other ways to treat hyponatremia would be treating the underlying cause, restricting water intake or vasopressin receptor antagonist. For severe case (with seizure and severe neurological abnormalities) of any hyponatremia, intravenous hypertonic saline is the choice.

Ad libitum water consumption prevents exercise-associated hyponatremia and protects against dehydration in soldiers performing a 40-km route-march

BackgroundIt remains unclear if ad libitum water drinking, as a hydration strategy, prevents exercise-associated hyponatremia (EAH) during prolonged exercise. The aim of this study was to determine the incidence of EAH within the broader context of fluid regulation among soldiers performing a 40-km route-march ingesting water ad libitum.MethodsTwenty-eight healthy male soldiers participated in this observational trial. Pre- and post-exercise body mass, blood and urine samples were collected. Blood samples were assessed for serum sodium ([Na+]), glucose, creatinine, urea nitrogen (BUN), plasma osmolality, creatine kinase (CK), and plasma arginine vasopressin (AVP) concentrations. Plasma volume (PV) was calculated using hematocrit and hemoglobin. Urine samples were analyzed for osmolality and [Na+]. Water intake was assessed by weighing bottles before, during and after the march. The mean relative humidity was 55.7% (21.9–94.3%) and the mean dry bulb temperature was 27.1 °C (19.5 °C - 37.0 °C) during the exercise.ResultsTwenty-five soldiers (72 ± 10 kg) (Mean ± SD) completed the march in 09:11 ± 00:43 (hr:min). Participants consumed 736 ± 259 ml/h of water and lost 2.8 ± 0.9 kg (4.0% ± 1.4%, P < 0.05) of body mass. Significant (pre-march vs. post-march; P < 0.05) decreases in serum [Na+] (141 mmol/L vs. 136 mmol/L), plasma osmolality (303 mOsmol/kg H2O vs. 298 mOsmol/kg H2O), and serum creatinine (111 μmol/L vs. 101 μmol/L) and urine [Na+] (168 mmol/L vs. 142 mmol/L), as well as significant increases in plasma AVP (2 pg/ml vs. 11 pg/ml), plasma CK (1423 U/L vs. 3894 U/L) and urine osmolality (1035 mOsmol/kg H2O vs. 1097 mOsmol/kg H2O) were found. The soldier (72 kg) with the lowest post-exercise sodium level completed the march in 08:38. He drank 800 ml/h, lost 2% body mass, and demonstrated (pre-post) increases in plasma osmolality (294–314 mOsmol/kg H2O), BUN (20–30 mg/dl), AVP (2–16 pg/ml) and PV (41%). His urine osmolality decreased from 1114 mOsmol/kg H2O to 1110 mOsmol/kg H2O. No participants finished the route-march with a serum [Na+] indicating hypernatremia (range, 134–143 mmol/L).ConclusionsAd libitum drinking resulted in 4% body mass loss with a 2 mmol/L serum [Na+] reduction in conjunction with high urine osmolality (> 1000 mOsmol/kg H2O) and plasma AVP. No single hydration strategy likely prevents EAH, but hypernatremia (cellular dehydration) was not seen despite > 2% body mass losses and high urine osmolality.

Hyponatremia with Rhabdomyolysis - Unusual Presentation of Pituitary Apoplexy

Hyponatremia is increasingly being identified among hospitalized patients. It significantly alters outcome either by itself or by inappropriate correction. We report a 29-year-old man, who presented to the out-patient services with headache of 1 week and projectile vomiting of 2 days. He also had cramps in calf since a day. Had no fever and had received intramuscular injection for calf pain. Clinical examination including fundoscopy were normal except for irritability and calf tenderness. Blood chemistry and haematology were normal, except for hyponatremia (110 m Eq/L) and elevated CPK (creatine phosphokinase). SIADH was considered as he was euvolemic with low serum osmolality and high urine osmolality. Further evaluation showed hypoadrenalism and hypothyroidism suggestive of hypopituitarism. Subsequent MRI of sella revealed a 1 cm3 cystic mass with features of haemorrhage. Pituitary apoplexy with hypopituitarism was definitive, considering the acute presentation. Supplementation of steroids and thyroxine along with sodium correction improved him symptomatically. Trans-sphenoidal resection of the sellar cystic lesion was performed. Often a good clinical history, assessment and judicious investigations can identify the cause for hyponatremia. Rhabdomyolysis is known to occur in severe hyponatremia and adrenal insufficiency as with the present case. In literature, there are reports of pituitary apoplexy presenting with rhabdomyolysis and hyponatremia. Pituitary apoplexy is a medical emergency which requires early identification, hormonal supplementation and supportive care for better outcome.&#x0D; J MEDICINE JUL 2019; 20 (1) : 49-51

Turning complexity into clarity: polyuria and hypernatremia

Turning complexity into clarity: polyuria and hypernatremia

Different diuretic properties between tolvaptan and furosemide in congestive heart failure patients with diuretic resistance and renal impairment: a subanalysis of the K-STAR.

We attempted to identify the difference in diuretic properties between tolvaptan (TLV) and furosemide (FUR) in congestive heart failure (CHF) patients with loop diuretic resistance and renal impairment. We investigated 81 CHF patients with loop diuretic treatment and renal impairment included in t he Kanagawa Aquaresis Investigators Trial of Tolvaptan on Heart Failure Patients with Renal Impairment (K-STAR). Predictive baseline factors and their changes during treatment periods were analyzed for correlation with percentage change in urine volume (%ΔUV) after additive introduction of TLV or increasing doses of FUR. Higher urine osmolality at baseline (β = 0.355; p = 0.033) in the TLV group and a lower ratio of blood urea nitrogen to serum creatinine (BUN/Cr, β = - 0.405; p = 0.020) in the FUR group were predictive of higher %ΔUV. Higher Δfree-water clearance (β = 0.667; p < 0.0001) in the TLV group, and higher %ΔBUN/Cr (β = 0.344; p = 0.030), higher %Δurine sodium concentration (β = 0.337; p = 0.037), and lower %Δstroke volume (β = - 0.390; p = 0.017) in the FUR group were correlated with %ΔUV. In conclusion, baseline urine osmolality and change in free-water clearance with additive introduction of TLV and a changing ratio of BUN/Cr with increasing doses of FUR were identified as key clinical parameters related to diuretic response.Trial registration UMIN000009201.

Schwartz-Bartter Syndrome: A Subtle Complication of Small Cell Lung Carcinoma

Paraneoplastic syndromes are defined as a conglomerate of clinical disorders that are caused by neoplastic diseases, specifically lung cancer. The clinical symptomatology of paraneoplastic syndromes usually precedes the diagnosis of the associated neoplasm, however, according to our current literature; the extent of the symptoms is not associated with the size of the tumor. Syndrome of inappropriate anti-diuretic hormone release (SIADH), also known as Schwartz-Bartter syndrome, is commonly caused by small cell lung carcinoma (SCLC) and is characterized by euvolemic hypoosmolar hyponatremia, which will lead to a low serum osmolality as well as a significantly high urine osmolality in the absence of other medical conditions such as adrenal insufficiency, heart failure, cirrhosis, and diuretic syndrome among others. The clinical presentation related to SIADH varies based upon the severity of the hyponatremia as well as the acuteness of the decrease in serum sodium levels. Symptoms due to SIADH include anorexia, nausea, vomiting, and in more severe cases, cerebral edema due to rapid of onset hyponatremia thus causing confusion, restlessness, coma, seizures, and respiratory arrest.

A case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine.

We report a case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine (CBZ). CBZ, an antiepileptic drug, is known to cause hyponatremia. The mechanism is generally considered to be inappropriate secretion of antidiuretic hormone, whereas an experimental study suggests a direct effect of CBZ on the kidney by stimulating vasopressin receptor. An 18-year-old male with atypical autism and epilepsy has been treated with CBZ and clobazam since age 9 and 10years, respectively. At age 11, he was found to have asymptomatic hyponatremia. He had the habit of drinking tea approximately 3L/day. The low plasma osmolality and high urine osmolality and sodium concentration in the presence of normal thyroid and adrenal function were compatible with syndrome of inappropriate excretion of antidiuretic hormone. His plasma vasopressin level, however, was undetectable. Urine cyclic AMP level was higher than expected from urine osmolality despite the suppressed plasma arginine vasopressin. With fluid restriction, hyponatremia improved. CBZ tapering begun later in the course maintained normal serum sodium concentrations with less strict water intake. This case demonstrates the direct effect of CBZ stimulating vasopressin receptor in the kidney leading to nephrogenic syndrome of inappropriate diuresis.

Pituitary Stalk Thickening

Abstract: MRI revealed enlargement of the pituitary stalk in two patients with different clinical presentations. A 60 y/o female had autoimmune hypothyroidism associated with blunted cortisol response to ACTH, while the other, a 30 y/o female had amenorrhea and polyuria with high plasma and low urinary osmolality. Keywords: Pituitary stalk thickening; Hypothyroidism; Adrenal insufficiency; Amenorrhea; Polyuria Case Report: As a result of the advances in imaging technologies, the finding of pituitary stalk lesions presents a diagnostic challenge to clinicians and endocrinologists. They are usually discovered incidentally on magnetic resonance imaging (MRI), or during the investigation of symptoms related to hypothalamic-pituitary dysfunction such as central diabetes insipidus or hypopituitarism. The etiology of these lesions may be congenital/developmental, inflammatory, infectious or neoplastic. Due to its particular location and function, the pituitary stalk is not often biopsied and diagnosis is based generally on clinical evaluation and images Report of two cases Enlargement of the pituitary stalk was found during the endocrine evaluation of two patients with the following clinical presentations. Patient 1: A 64 year old woman was admitted to the emergency room for vomiting and high blood pressure. Otherwise normal, she had been suffering from proximal muscle weakness, fatigue, reduced appetite, cognitive impairment and pre-tibial myxedema during the last two months. The patient denied glucocorticoid intake. Mild hyponatremia (132 mEq/l) and anemia (hct: 30%) were detected. TSH was high (13.74 µU/ml) with low FT4: 0.57ng/dl. Anti-peroxidase antibodies were positive. Serum potassium was normal (4.2 mEq/l). Serum morning cortisol was less than 1.0 µg/dl and ACTH was 6.7 pg/ml and 5.0 pg/ ml in two different occasions. An ACTH stimulating test (Synacthen 250.0 µg, i.m) showed a blunted cortisol response at 30 and 60 min after stimulus, confirming adrenal insufficiency. The remaining pituitary function was normal. MRI showed a thickened pituitary stalk (Figure 1). The patient improved on hydrocortisone and LT4. Patient 2: A 30 year old woman complained of amenorrhea and polyuria (9 L/day). She had high plasma and low urinary osmolality (311 mOsm/kg and 136 mOsm/kg, respectively). Low serum estradiol and gonadotropins were found. Thyroid and adrenal functions were normal. MRI showed a thickened pituitary stalk (Figure 2). She started on desmopressin (0.1 mg/day) which reduced daily diuresis by 60% and lowered plasma osmolality (290 mOsm/day). Additionally she began on estrogen and progestin replacement. Discussion: Pituitary stalk lesions may be found by chance or during the evaluation of endocrine disorders. In a series of 152 patients, the etiologies were attributed to neoplasia in 32%, inflammatory lesions 20%, and congenital anomalies in 9% and in 39% remained unknown [2]. Primary hypophysitis is rare, between 0.2 and 6.5% among pituitary pathologies. Three histopathological types are described in this category: lymphocytic, granulomatous and xanthomatous hypophysitis [3].These conditions are usually confined to the pituitary. In secondary hypophysitis, a systemic disease is the cause of the pituitary lesion: Sarcoidosis, Wegener granulomatosis, Langerhans cell histyocitosis and IgG4 related plasmatic histiocytosis may affect the pituitary. Monoclonal antibodies against the cytotoxic T-lymphocyte antigen-4 (CTLA-4) for treating metastatic cancer, may induce hypophysitis [4,5]. In the setting of immunosuppression, fungal infection, tuberculosis and toxoplasmosis may involve the pituitary gland [4]. Interestingly, these two patients showed different clinical presentations. After excluding secondary etiologies, primary hypophysitis was suspected in both [4]. Although histological confirmation is needed, biopsy of a pituitary stalk lesion is technically demanding, and must be performed by an experienced neurosurgeon. In order to avoid invasive procedures, the approach was based on clinical, biochemical and radiological features. A close follow-up is mandatory to detect new symptoms and to determine if the lesions progress over time.

Usefulness of anti-rabphilin-3A antibodies for diagnosing central diabetes insipidus in the third trimester of pregnancy

We report a 27-year-old pregnant woman with polyuria, polydipsia and headache in the third trimester of pregnancy. Hypernatremia (153 mEq/L), high plasma osmolality (300 mOsm/kgH2O) and low urinary osmolality (92 mOsm/kgH2O) were observed at the admission to our hospital. Plasma arginine vasopressin (AVP) level was inappropriately low (2.2 pg/mL) compared to the high plasma osmolality. Plasma AVP responses to hypertonic-saline infusion were blunted, and her urine osmolality increased in response to desmopressin. The diagnosis of central diabetes insipidus was made from these results. Magnetic resonance imaging (MRI) of hypothalamic-pituitary region demonstrated a significant enlargement of the pituitary stalk, suggesting the presence of hypophysitis. In addition, serum anti-rabphilin-3A antibodies that have been recently reported as a biomarker of lymphocytic infundibulo-neurohypophysitis, were positive. Diabetes insipidus continued after delivery, suggesting that polyuria was not mainly due to excessive vasopressinase activity or reduced renal sensitivity to AVP by prostaglandin E2 that can cause temporal polyuria during pregnancy. We therefore clinically diagnosed central diabetes insipidus due to lymphocytic infundibulo-neurohypophysitis, without performing invasive transsphenoidal pituitary biopsy. This case suggested the usefulness of anti-rabphilin-3A antibodies for the etiological diagnosis of central diabetes insipidus during pregnancy.

Hyponatremia - A rare complication of Gitelman's syndrome

Gitelman's syndrome (GS) is a rare autosomal recessive disorder caused by mutations in thiazide-sensitive NaCl cotransporter. We report a 49-year-old, normotensive lady with prolonged hypokalemia since her 20s who was diagnosed with GS at our renal clinic. During follow-up, she was found to have mild, asymptomatic, euvolemic hyponatremia with low serum uric acid, inappropriately high urine osmolality and sodium consistent with syndrome of inappropriate antidiuretic hormone-like presentation. Despite life-long urinary sodium losses, hyponatremia has rarely been reported in GS to be due to the primary disease process. We present relevant clinical data and hypothesize on why this disease per se may be a risk factor for dilutional hyponatremia.

Collecting duct-specific knockout of nitric oxide synthase 3 impairs water excretion in a sex-dependent manner.

Nitric oxide (NO) inhibits collecting duct (CD) Na+ and water reabsorption. Mice with CD-specific knockout (KO) of NO synthase 1 (NOS1) have salt-sensitive hypertension. In contrast, the role of NOS3 in CD salt and water reabsorption is unknown. Mice with CD NOS3 KO were generated with loxP-flanked exons 9-12 (encodes the calmodulin binding site) of the NOS3 gene and the aquaporin-2 promoter-Cre transgene. There were no differences between control and CD NOS3 KO mice, irrespective of sex, in food intake, water intake, urine volume, urinary Na+ or K+ excretion, plasma renin concentration, blood pressure, or pulse during 7 days of normal (0.3%), high (3.17%), or low (0.03%) Na+ intake. Blood pressure was similar between genotypes during DOCA-high salt. CD NOS3 KO did not alter urine volume or urine osmolality after water deprivation. In contrast, CD NOS3 KO male, but not female, mice had lower urine volume and higher urine osmolality over the course of 7 days of water loading compared with control mice. Male, but not female, CD NOS3 KO mice had reduced urinary nitrite+nitrate excretion compared with controls after 7 days of water loading. Urine AVP and AVP-stimulated cAMP accumulation in isolated inner medullary CD were similar between genotypes. Western analysis did not reveal a significant effect of CD NOS3 KO on renal aquaporin expression. In summary, these data suggest that CD NOS3 may be involved in the diuretic response to a water load in a sex-specific manner; the mechanism of this effect remains to be determined.

Cerebral Salt Wasting Syndrome and Systemic Lupus Erythematosus: Case Report

Cerebral salt wasting (CSW) is a rare cause of hypoosmolar hyponatremia usually associated with acute intracranial disease characterized by extracellular volume depletion due to inappropriate sodium wasting in the urine. We report a case of a 46-year-old male with recently diagnosed systemic lupus erythematosus (SLE) initially presenting with neurological involvement and an antiphospholipid syndrome (APS) who was admitted because of chronic asymptomatic hyponatremia previously assumed as secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Initial evaluation revealed a hypoosmolar hyponatremia with high urine osmolality and elevated urinary sodium concentration. Clinically, the patient’s extracellular volume status was difficult to define accurately. After exclusion of other etiologies, a diagnosis of CSW was established and the patient started appropriate treatment with normalization of sodium levels. The challenge in diagnosing CSW relies on the differentiation from the SIADH, since it shares most of the laboratory features. The critical difference is the state of extracellular volume which can be difficult to access accurately in routine clinical practice. There is evidence that the fractional excretion of urate (FEUrate) can be of assistance. The relationship between SLE and hyponatremia is mostly limited to adverse pharmacological side effects, so to our knowledge, this is the first association between SLE with neurological involvement and CSW. J Med Cases. 2016;7(9):399-402 doi: http://dx.doi.org/10.14740/jmc2615w

Effects of maternal hydration status on the osmolality of maternal milk

It has been demonstrated that human milk osmolality (Mosm) is regulated within an established range, typically 290 to 300 mOsm/kg, and appears to be resistant to effects of maternal dehydration, as refl ected by high urinary osmolality (Uosm). To determine the degree of association between Mosm and Uosm at a common point in time, as well as the reproducibility of both measures over a one-week interval of sampling. Mosm and Uosm were measured with a Vogel Löser 450 osmometer on samples of the respective biological fluids collected concurrently in 31 lactating women, with infants aged between 30 and 340 days. In the first 15 women recruited, collections were repeated 7 days after the initial ones. The median Mosm for the 46 samples collected was 308 mOsm/kg with a range from 288 to 448 mOsm/kg. The corresponding values for Uosm were 598 mOsm/kg with a range from 93 to 1,678 mOsm/kg. The Spearman rank-order correlation coeffi cient for within-individual association of Mosm and Uosm was r = 0.214 (p = 0.153). The median Mosm for the 15 repeat-subjects was 309 mOsm/kg on both occasions, with a within-individual Spearman coeffi cient of r = 0.326 (p = 0.118). By contrast, for the Uosm, the within-subject association was much stronger, with r = 0.699 (p = 0.002). The osmometry technique proved to be a highly stable and reproducible measurement technique. Mosm and Uosm are not significantly associated at a point in time. Intra-subject Mosm varies more across time than intra-subject Uosm.

Yield of workup for patients with idiopathic presentation of the syndrome of inappropriate antidiuretic hormone secretion

PurposeTo determine the proportion of patients for whom the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the presenting symptom of an underlying disorder, to describe the yield of different diagnostic modalities for patients with SIADH and an unknown etiology, and to define patients for whom such a workup is indicated. MethodsA single center retrospective study including all patients diagnosed with SIADH without an apparent etiology in a large community hospital and tertiary center between 1.1.07 and 1.1.13. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. ResultsEleven of the 99 patients without an apparent etiology for SIADH at presentation were found to have an underlying cause on workup. Yield of performed workup was low, with a pathology demonstrated on 0%–30.8% of tests according to the different modalities used. Patients with presumed idiopathic SIADH at presentation who were later found to have a specific etiology were younger than patients with true idiopathic SIADH, had a significantly shorter duration of hyponatremia prior to SIADH diagnosis, had higher urine osmolality and a clinical presentation suggestive of an undiagnosed disorder. ConclusionsOur findings support a clinically-based approach to patients with idiopathic SIADH, rather than an extensive routine workup for all patients.