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)     

Hyponatremia: Mechanisms and Newer Treatments

ObjectiveTo review the neural and renal mechanisms of osmotic homeostasis, provide a rationale for the sensitivity of the central nervous system to hyponatremia, and outline modern approaches to therapy of acute and chronic hyponatremia.MethodsReview of relevant literature with focus on physiologic mechanisms.ResultsWith careful monitoring, acute hyponatremia can be managed, while minimizing risks both of continued hyponatremia and the osmotic demyelination that can occur with overly rapid correction of severe hyponatremia. Chronic hyponatremia due to disorders of volume regulation (congestive heart failure or cirrhosis) or to syndrome of inappropriate antidiuretic hormone release can be managed effectively with vasopressin V2 receptor antagonists, but there is no evidence that controlling the hyponatremia enhances survival associated with the underlying diseases.ConclusionsTherapy in the acute setting balances the risk of the osmotic disturbance with the risk of overly rapid correction. The V2 receptor antagonist tolvaptan has enhanced our ability to improve chronic hyponatremia in conditions such as congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormone hypersecretion. (Endocr Pract. 2010;16:882-887)     

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.     

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)     

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.     

Salt and water: a simple approach to hyponatremia

HYPONATREMIA IS COMMON IN BOTH INPATIENTS and outpatients. Medications are often the cause of acute or chronic hyponatremia. Measuring the serum osmolality, urine sodium concentration and urine osmolality will help differentiate among the possible causes. Hyponatremia in the physical states of extracellular fluid (ECF) volume contraction and expansion can be easy to diagnose but often proves difficult to manage. In patients with these states or with normal or near-normal ECF volume, the syndrome of inappropriate secretion of antidiuretic hormone is a diagnosis of exclusion, requiring a thorough search for all other possible causes. Hyponatremia should be corrected at a rate similar to that at which it developed. When symptoms are mild, hyponatremia should be managed conservatively, with therapy aimed at removing the offending cause. When symptoms are severe, therapy should be aimed at more aggressive correction of the serum sodium concentration, typically with intravenous therapy in the inpatient setting. CaseA 72-year-old woman presents to your office with a 2-day history of presyncope when rising from a chair. She has been taking hydrochlorothiazide, 25 mg/d, for 5 years for systolic hypertension. Over the last week she has had a bout of viral gastroenteritis with marked diarrhea. She has been trying to replace the lost fluids by drinking 2–3 L of water per day. You determine that when she rises from a seated position, her blood pressure drops 20 mm Hg; her jugular venous pressure is low. Serum levels are as follows: sodium 128 mmol/L, potassium 3.1 mmol/L, creatinine 125 mmol/L and urea nitrogen 10 mmol/L.What is your approach to this woman''s hyponatremia?Hyponatremia is common in both inpatients and outpatients. Its causes are numerous and often elusive. Having a simple approach to assessment and treatment can be helpful in most cases that present in clinical practice. This review is meant to be a simplified, clinically based overview of the diagnosis and management of hyponatremia. Pathophysiological details of common and rare causes of hyponatremia and a detailed laboratory approach to diagnosis can be found elsewhere.¹     

Urea for long-term treatment of syndrome of inappropriate secretion of antidiuretic hormone.

The efficacy of oral urea in producing a sufficiently high osmotic diuresis was tested in seven patients with the syndrome of inappropriate secretion of antidiuretic hormone. In all patients urea corrected the hyponatraemia despite a normal fluid intake. Five patients were controlled (serum sodium concentration greater than 128 mmol(mEq)/1) with a dose of 30 g urea daily, and two with 60 g daily. The patients who needed 30 g drank 1-2 1 of fluid daily, while those who needed 60 g drank up to 3.1 per day. No major side effects were noted, even after treatment periods of up to 270 days. These findings suggest that urea is a safe and efficacious treatment of the syndrome of inappropriate secretion of antidiuretic hormone.     

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.     

The Effects of Hyponatremia on Bone Density and Fractures: A Systematic Review and Meta-Analysis

Objective: Hyponatremia decreases bone mineral density and is a major risk factor for fragility fractures. Objectives of our systematic review and meta-analysis were to analyze the overall effects of hyponatremia on bone fractures, osteoporosis, and mortality.Methods: We extracted data from Medline, Cochrane Central, and EMBASE 1960–2017 and conference abstracts from 2007–2017. We included studies with data on serum sodium, fractures, bone density, or diagnoses of osteoporosis. Studies were independently reviewed by two authors and assessed for bias using the Newcastle-Ottawa scale. Random effect models meta-analysis was used when at least three studies reported the same outcome measures. We reported summary odds ratios (ORs) and 95% confidence intervals (CIs).Results: We included 26 studies for qualitative analysis. Fifteen studies were included in the meta-analysis to evaluate the effects of hyponatremia on fractures, four studies for bone mineral density changes, and six for mortality. Hyponatremia increased the odds of fractures at all sites (summary OR, 2.34 [95% CI, 1.86, 2.96]. There was an increase in the odds of osteoporosis (summary OR, 2.67 [95% CI, 2.07, 3.43]). Mortality risk among the included studies remained high (summary OR, 1.31 [95% CI, 1.16, 1.47]).Conclusion: Our meta-analysis confirms a statistically significant association of hyponatremia with bone fractures and osteoporosis along with higher mortality. Long-term prospective studies evaluating the impact of correcting hyponatremia on bone health, fractures, and mortality are required.Abbreviations: AVP = arginine vasopressin; CI = confidence interval; CKD = chronic kidney disease; OR = odds ratio; SIADH = syndrome of inappropriate antidiuretic hormone     

Sitagliptin in Glutamic Acid Decarboxylase Antibody-Positive Diabetes Mellitus

ObjectiveTo describe a case illustrating the use of sitagliptin, an inhibitor of dipeptidyl-peptidase-4 (DPP-4), in anti-glutamic acid decarboxylase antibody-positive diabetes mellitus in association with a rare ataxic variant of stiff person syndrome.MethodsWe present our experience with use of the DPP-4 inhibitor sitagliptin for management of autoimmune diabetes in a elderly woman and highlight the association of diabetes with other autoimmune conditions.ResultsA 68-year-old Japanese woman presented with poorly controlled “type 2” diabetes mellitus, cerebral palsy, cerebellar ataxia, and hypothyroidism. She complained of stiffness and spasms, which had resulted in multiple falls and immobility. Antidiabetic medications included gliclazide, rosiglitazone, and acarbose; various insulins had been tried but discontinued because they worsened her stiffness and spasms. Her hemoglobin A_1c values remained above 9% despite maximal doses of the aforementioned orally administered hypoglycemic agents. After sitagliptin therapy was initiated, her hemoglobin A_1c level decreased from 9.3% (78 mmol/mol) to 7.3% (56 mmol/mol) in 5 months. Investigations confirmed the presence of an ataxic variant of stiff person syndrome. On repeated testing 18 months later, her anti-glutamic acid decarboxylase antibody levels had declined by more than 85%.ConclusionApart from the well-known mechanism of an increase in glucagonlike peptide-1, sitagliptin may exert its glucose-lowering effect by other mechanisms in patients with autoimmune diabetes. Further studies should be undertaken to address the effectiveness of DPP-4 inhibitors in non-type 2 diabetes. (Endocr Pract. 2012;18: e65-e68)     

Recombinant Human Parathyroid Hormone Therapy (1-34) In an Adult Patient with a Gain-of-Function Mutation in the Calcium-Sensing Receptor-a Case Report

ObjectiveTo describe a case of hypocalcemia in a patient with a gain-of-function mutation in the calcium-sensing receptor that was undetected until adulthood and successfully treated with recombinant parathyroid hormone.MethodsThe clinical findings, laboratory data, and a review of the pertinent literature are presented.ResultsA 55-year-old woman was hospitalized and seen by the endocrinology consult service for hypocalcemia that was refractory to repeated doses of intravenous calcium gluconate. She expressed concern about chronic leg muscle cramps and paresthesias of the lips and fingertips. In addition, she had no history of neck surgery, neck irradiation, or any autoimmune disease. She was a well-appearing female with no dysmorphic features or skin changes. Laboratory tests revealed hypocalcemia, hyperphosphatemia, hypomagnesemia, and hypovitamino-sis D. Her parathyroid hormone concentration (PTH) was low at 14.2 pg/mL. Her PTH and calcium concentrations remained low despite repletion of magnesium and treatment with calcitriol and oral calcium replacement. A 24-hour collection for urinary calcium showed inappropriate hypercalciuria. Medical records showed her hypocalcemia to be chronic. Additionally, several family members had also complained of muscle cramps. A congenital cause of her hypoparathyroidism was considered, and genetic testing confirmed heterozygosity for a gain-of-function mutation in the calcium-sensing receptor gene associated with autosomal dominant familial isolated hypoparathyroidism (ADH). Treatment with subcutaneous recombinant human parathyroid hormone teriparatide (rhPTH [1-34]) 20 mcg twice daily for three days normalized her calcium and phosphorus concentrations.ConclusionrhPTH (1-34) is an effective treatment for patients with hypoparathyroidism due to gain-of-function mutations in the calcium-sensing receptor. ADH can be insidious in presentation and the diagnosis can be missed unless there is a high index of suspicion. (Endocr Pract. 2013;19:e24-e28)     

Clinical Practice Patterns for Postoperative Water Balance After Pituitary Surgery

Objective: Abnormalities of water and sodium balance, including diabetes insipidus and the syndrome of inappropriate antidiuretic hormone (SIADH), are common complications of transsphenoidal surgery. Postoperative practice patterns vary among clinicians, and no consensus guidelines exist to direct their monitoring and management. We aimed to identify and compare practice patterns regarding the evaluation and management to these postoperative complications.Methods: A questionnaire was utilized to capture demographic data and practice habits in the postoperative setting. Respondents were members of the Pituitary Society, an international organization comprised of clinicians and researchers dedicated to the study of pituitary disease.Results: Eighty-six respondents completed at least part of the survey. The geographic distribution of respondents was roughly even between American and non-American practitioners. The majority of respondents practiced at academic institutions (67.4%), worked in multidisciplinary teams (88.4%), and possessed significantly greater than 10 years of clinical experience (71%). Compared to non-American practitioners, American practitioners described a shorter length of stay postoperatively (P<.001) and prescribed more restrictive volume recommendations for postoperative SIADH (P = .0035). Early career clinicians (less than 10 years in practice) checked first postoperative sodium level earlier than later career clinicians (P = .010).Conclusion: Water and sodium dysregulation are common following transsphenoidal surgery, but their management is not well-standardized in clinical practice. We created a questionnaire to define and compare practice patterns. Most respondents practice in academic settings in multidisciplinary teams. The length of clinical experience did not significantly impact practice habits. Practice location influenced length of stay postoperatively and fluid restriction in SIADH.Abbreviations: AVP = arginine vasopressin; DI = diabetes insipidus; LOS = length of stay; SIADH = syndrome of inappropriate antidiuretic hormone     

Do the etiology of hyponatremia and serum sodium levels affect the length of hospital stay in geriatric patients with hyponatremia?

BackgroundHyponatremia can lead to a prolonged hospital stay and increased morbidity and mortality rates in geriatric patients. This study aimed to evaluate the effects of hyponatremia etiology and serum sodium (Na) levels on hospitalisation time in geriatric patients hospitalised due to hyponatremia.MethodsThe demographic characteristics, laboratory data, etiology of hyponatremia, and length of hospital stay were retrospectively recorded for 132 patients over 65 years of age who were hospitalised for hyponatremia.ResultsOf the 132 patients, 90 were female (68.2%), and 42 were male (31.8%). The serum Na levels of 66 (50%) patients were <120 mmol/L, those of 64 (48.5%) patients were 120-129 mmol/L, and those of two (1.5%) patients were >130 mmol/L. One hundred nine (82.6%) patients had hypoosmolar hyponatremia, 14 (10.6%) patients had isoosmolar hyponatremia, and nine (6.8%) patients had hyperosmolar hyponatremia. Also, 19.7% of the patients were hypovolemic, 37.9% were euvolemic, and 42.4% were hypervolemic. Hyponatremia etiology was congestive heart failure in 38 (28.8%) patients, syndrome of inappropriate antidiuretic hormone in 29 (22.0%) patients, gastrointestinal fluid loss in 24 (18.2%) patients, renal pathologies in 20 (15.2%) patients, the presence of drugs in 20 (15.2%) patients, and hypocortisolemia in one (0.8%) patient. The mean length of hospital stay for the patients was five (1-60) days. There was no statistically significant difference between the lengths of hospital stay based on hyponatremia etiology and serum Na levels (p=0.861 and p=0.076). It was observed that the lengths of stay for patients who developed hyponatremia during their hospitalisation in various clinics were longer than those for patients who presented to the emergency department (p<0.001).ConclusionsIn this study, it was determined that the length of hospital stay did not change with the etiology of hyponatremia and serum Na level at the time of admission, but patients who developed hyponatremia during their hospitalisation had longer hospitalisation times.     

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.     

The hyponatremic patient: a systematic approach to laboratory diagnosis

HYPONATREMIA (SERUM SODIUM LEVEL LESS THAN 134 MMOL/L) is a common electrolyte disturbance. Its high prevalence and potential neurologic sequelae make a logical and rigorous differential diagnosis mandatory before any therapeutic intervention. A history of concurrent illness and medication use as well as the assessment of extracellular volume status on physical examination may provide useful clues as to the pathogenesis of hyponatremia. Measurement of the effective serum tonicity (serum osmolality less serum urea level) is the first step in the laboratory evaluation. In patients with normal or elevated effective serum osmolality (280 mOsm/kg or greater), pseudohyponatremia should be excluded. In the hypo-osmolar state (serum osmolality less than 280 mOsm/kg), urine osmolality is used to determine whether water excretion is normal or impaired. A urine osmolality value of less than 100 mOsm/kg indicates complete and appropriate suppression of antidiuretic hormone secretion. A urine sodium level less than 20 mmol/L is indicative of hypovolemia, whereas a level greater than 40 mmol/L is suggestive of the syndrome of inappropriate antidiuretic hormone secretion. Levels of hormones (thyroid-stimulating hormone and cortisol) and arterial blood gases should be determined in difficult cases of hyponatremia.Hyponatremia (serum sodium level less than 134 mmol/L) is a common electrolyte disturbance occurring in a broad spectrum of patients, from asymptomatic to critically ill.^1,2 There are serious neurologic sequelae associated with hyponatremia and its treatment. Therefore, a logical, rigorous differential diagnosis is mandatory before therapy can be begun.^3,4 Since hyponatremia is caused primarily by the retention of solute-free water, its cause encompasses disorders associated with limitation in water excretion.⁵ The principal causes of hyponatremia are summarized in Open in a separate windowAs with other electrolyte abnormalities, the history and physical examination can provide important clues toward the correct diagnosis. In most cases the initial laboratory evaluation includes measurement of serum osmolality and urine osmolality (by osmometer if available), urine sodium concentration and serum levels of other electrolytes (potassium, chloride and bicarbonate) as well as serum concentrations of urea, glucose, uric acid, total proteins and triglycerides. In addition, determination of serum levels of thyroid-stimulating hormone and cortisol is important to exclude any associated endocrinopathy (Fig. 1). Measurement of arterial blood gases is also useful in the differential diagnosis of hyponatremia, particularly in patients with abnormal serum bicarbonate concentrations.Open in a separate windowFig. 1: Clinical diagnostic algorithm for hyponatremia. TSH = thyroid-stimulating hormone, EABV = effective arterial blood volume, SIADH = syndrome of inappropriate secretion of antidiuretic hormone, FE = fractional excretion.Table 2Open in a separate windowThe step-by-step diagnostic evaluation of hyponatremia is shown in Fig. 1.     

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.     

Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss

Our recent animal and human studies revealed that chronic hyponatremia is a previously unrecognized cause of osteoporosis that is associated with increased osteoclast numbers in a rat model of the human disease of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We used cellular and molecular approaches to demonstrate that sustained low extracellular sodium ion concentrations ([Na(+)]) directly stimulate osteoclastogenesis and resorptive activity and to explore the mechanisms underlying this effect. Assays on murine preosteoclastic RAW 264.7 cells and on primary bone marrow monocytes both indicated that lowering the medium [Na(+)] dose-dependently increased osteoclast formation and resorptive activity. Low [Na(+)], rather than low osmolality, triggered these effects. Chronic reduction of [Na(+)] dose-dependently decreased intracellular calcium without depleting endoplasmic reticulum calcium stores. Moreover, we found that reduction of [Na(+)] dose-dependently decreased cellular uptake of radiolabeled ascorbic acid, and reduction of ascorbic acid in the culture medium mimicked the osteoclastogenic effect of low [Na(+)]. We also detected downstream effects of reduced ascorbic acid uptake, namely evidence of hyponatremia-induced oxidative stress. This was manifested by increased intracellular free oxygen radical accumulation and proportional changes in protein expression and phosphorylation, as indicated by Western blot analysis from cellular extracts and by increased serum 8-hydroxy-2'-deoxyguanosine levels in vivo in rats. Our results therefore reveal novel sodium signaling mechanisms in osteoclasts that may serve to mobilize sodium from bone stores during prolonged hyponatremia, thereby leading to a resorptive osteoporosis in patients with SIADH.     

The Clinical Physiology of Water Metabolism: Part III: The Water Depletion (Hyperosmolar) and Water Excess (Hyposmolar) Syndromes

Hyperosmolality occurs when there are defects in the two major homeostatic mechanisms required for water balance—thirst and arginine vasopressin (AVP) release. In this situation hypotonic fluids are lost in substantial quantities causing depletion of both intracellular and extracellular fluid compartments. Patients with essential hypernatremia have defective osmotically stimulated AVP release and thirst but may have intact mechanisms for AVP release following hypovolemia. Hyperosmolality can also be seen in circumstances in which impermeable solutes are present in excessive quantities in extracellular fluid. Under these conditions there is cellular dehydration and the serum sodium may actually be reduced by water drawn out of cells along an osmotic gradient.Hyposmolality and hyponatremia may be seen in a variety of clinical conditions. Salt depletion, states in which edema occurs and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may all produce severe dilution of body fluids resulting in serious neurologic disturbances. The differential diagnosis of these states is greatly facilitated by careful clinical assessment of extracellular fluid volume and by determination of urine sodium concentration. Treatment of the hyposmolar syndromes is contingent on the pathophysiology of the underlying disorder; hyponatremia due to salt depletion is treated with infusions of isotonic saline whereas mild hyponatremia in cirrhosis and ascites is best treated with water restriction. Severe symptomatic hyponatremia due to SIADH is treated with hypertonic saline therapy, sometimes in association with intravenous administration of furosemide. Less severe, chronic cases may be treated with dichlormethyltetracycline which blocks the action of AVP on the collecting duct.     

Exacerbation of Underlying Hypothyroidism Caused by Proteinuria and Induction of Urinary Thyroxine Loss: Case Report and Subsequent Investigation

ObjectiveTo describe a patient with excess urinary thyroxine (T₄) excretion and worsening of preexisting hypothyroidism in the setting of nephrotic syndrome and to determine whether excess urinary T₄ excretion is present in other patients with proteinuria.MethodsWe present data regarding the patient’s initial presentation, diagnostic studies, and course of her illness. We suspected urinary T₄ loss to be the cause of her presentation and analyzed her urine sample for total T₄. We also analyzed differences in urinary T₄ excretion in 22 patients with proteinuria and 16 control patients without proteinuria. Relevant medical literature is reviewed.ResultsA 44-year-old woman presented with a 3-month history of increasing fluid retention, weight gain, and fatigue. She had long-standing hypothyroidism on a stable levothyroxine dosage, 125 mcg/d. She had gained 27 kg and had developed significant edema. She had a grossly elevated thyroid-stimulating hormone level of 91 mIU/L. Her condition worsened, and a urinary protein measurement was 14.06 g/24 h—diagnostic of nephrotic syndrome. The levothyroxine dosage was increased to 225 mcg/d. Urinary total T₄ concentration in a 24-hour sample was 59.0 μg/L (83.1 μg/24 h), indicating that a substantial fraction of her orally ingested T₄ was lost in urine. Urinary total T₄ excretion was significantly higher in patients with proteinuria (mean ± standard deviation, 18.0 ± 18.2 μg/L) vs control patients without proteinuria (mean, 3.8 ± 1.8 μg/L) (P = .0014).ConclusionIn the patient described, urinary T₄ loss due to proteinuria and nephrotic syndrome resulted in a severe exacerbation of underlying hypothyroidism. (Endocr Pract. 2008;14:97-103)     

Outcome Of Implementation Of A Multidisciplinary Team Approach To The Care Of Patients After Transsphenoidal Surgery

Objective: Transsphenoidal surgery (TS) for sellar lesions is an established and safe procedure, but complications can occur, particularly involving the neuroendocrine system. We hypothesized that postoperative care of TS patients would be optimized when performed by a coordinated team including a pituitary neurosurgeon, endocrinologists, and a specialty nurse.Methods: We implemented a formalized, multidisciplinary team approach and standardized postoperative protocols for the care of adult patients undergoing TS by a single surgeon (J.N.B.) at our institution beginning in July 2009. We retrospectively compared the outcomes of 214 consecutive TS-treated cases: 113 cases prior to and 101 following the initiation of the team approach and protocol implementation. Outcomes assessed included the incidence of neurosurgical and endocrine complications, length of stay (LOS), and rates of hospital readmission and unscheduled clinical visits.Results: The median LOS decreased from 3 days preteam to 2 days postteam (P<.01). Discharge occurred on postoperative day 2 in 46% of the preteam group patients compared to 69% of the postteam group (P<.01). Rates of early postoperative diabetes insipidus (DI) and readmissions within 30 days for syndrome of inappropriate antidiuretic hormone (SIADH) or other complications did not differ between groups.Conclusion: Implementation of a multidisciplinary team approach was associated with a reduction of LOS. Despite earlier discharge, postoperative outcomes were not compromised. The endocrinologist is central to the success of this team approach, which could be successfully applied to care of patients undergoing TS, as well as other types of endocrine surgery at other centers.Abbreviations:CSF = cerebrospinal fluidDDAVP = desmopressinDI = diabetes insipidusLOS = length of stayPOD = postoperative daySIADH = syndrome of inappropriate antidiuretic hormoneTS = transsphenoidal surgery