Lucy-Ann Behan

Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients

Background: Hyponatraemia is a well-recognised complication of neurosurgical conditions, but the incidence and implications have not been well documented. Objective: To define the incidence, pathophysiology and clinical implications of significant hyponatraemia in several neurosurgical conditions. Methods: All patients admitted to the Irish National Neurosciences Centre at Beaumont Hospital, Dublin with traumatic brain injury, subarachnoid haemorrhage, intracranial neoplasm, pituitary disorders and spinal disorders who developed significant hyponatraemia (plasma sodium <130 mmol/l) from January 2002 to September 2003 were identified from computerised laboratory records. Data were collected by retrospective case note analysis. Results: Hyponatraemia was more common in patients with pituitary disorders (5/81, 6.25%; p = 0.004), traumatic brain injury (44/457, 9.6%; p<0.001), intracranial neoplasm (56/355, 15.8%; p<0.001) and subarachnoid haemorrhage (62/316, 19.6%; p<0.001) than in those with spinal disorders (4/489, 0.81%). The pathophysiology of hyponatraemia was: syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 116 cases (62%) (31 (16.6%) drug-associated), hypovolaemic hyponatraemia in 50 cases (26.7%) (which included patients with insufficient data to assign to the cerebral salt-wasting group (CSWS)), CSWS in nine cases (4.8%), intravenous fluids in seven cases (3.7%) and mixed SIADH/CSWS in five cases (2.7%). Hyponatraemic patients with cerebral irritation had significantly lower plasma sodium concentrations (mean (SD) 124.8 (0.34) mmol/l) than asymptomatic patients (126.6 (0.29) mmol/l) (p<0.0001). Hyponatraemic patients had a significantly longer hospital stay (median 19 days (interquartile range (IQR) 12–28)) than normonatraemic patients (median 12 days (IQR 10.5–15)) (p<0.001). Conclusions: Hyponatraemia is common in intracerebral disorders and is associated with a longer hospital stay. Cerebral irritation is associated with more severe hyponatraemia. SIADH is the most common cause of hyponatraemia and is often drug-associated.

Acute Glucocorticoid Deficiency and Diabetes Insipidus Are Common After Acute Traumatic Brain Injury and Predict Mortality

CONTEXT Published data demonstrates that hypopituitarism is common after traumatic brain injury (TBI). Hormone deficiencies are transient in many, but the natural history of the acute changes after TBI has not been documented. In addition, it is not clear whether there are any early parameters that accurately predict the development of permanent hypopituitarism. OBJECTIVES There were 3 main objectives of this study: 1) to describe the natural history of plasma cortisol (PC) changes and sodium balance after TBI; 2) to identify whether acute hypocortisolemia or cranial diabetes insipidus (CDI) predict mortality; and 3) to identify whether the acute pituitary dysfunction predicts the development of chronic anterior hypopituitarism. DESIGN Each TBI patient underwent sequential measurement of PC, plasma sodium, urine osmolality, and fluid balance after TBI. All other anterior pituitary hormones were measured on day 10 after TBI. The results from 15 surgical comparisons defined a PC less than 300 nmol/L as inappropriately low for an acutely ill patient. CDI was diagnosed according to standard criteria. Surviving TBI patients underwent dynamic anterior pituitary testing at least 6 months after TBI. SETTING The patients were recruited from the Irish National Neurosurgery Centre. PATIENTS One hundred sequential TBI patients were recruited. Fifteen patients admitted to Intensive Therapy Unit (ITU) after major surgery were recruited as comparison patients. MAIN OUTCOME MEASURES PC in TBI patients was compared with that of comparison patients. The mortality rate was compared between TBI patients with and without acute hypocortisolemia. Results of follow-up dynamic pituitary testing were compared between those with and without acute hypocortisolemia. RESULTS Most of the TBI patients (78%) developed inappropriately low PC after TBI. Low PC and CDI were predictive of mortality. Thirty-nine percent of the patients who had follow-up testing had at least 1 pituitary hormone deficit, all of whom had had previous acute hypocortisolemia or CDI. CONCLUSIONS Acute hypocortisolemia and CDI are predictive of mortality and long-term pituitary deficits in TBI.

Morbidity and mortality in patients with craniopharyngioma after surgery.

Objective  Craniopharyngioma (CP) is a benign tumour of the suprasellar region that is associated with increased morbidity and mortality in comparison with other causes of hypopituitarism. We aimed to establish the rate and causes of mortality and morbidity in patients with CP who attended our centre.

Hyponatremia Following Mild/Moderate Subarachnoid Hemorrhage Is Due To SIAD and Glucocorticoid Deficiency and not Cerebral Salt Wasting

CONTEXT Hyponatremia is common after acute subarachnoid hemorrhage (SAH) but the etiology is unclear and there is a paucity of prospective data in the field. The cause of hyponatremia is variously attributed to the syndrome of inappropriate antidiuresis (SIAD), acute glucocorticoid insufficiency, and the cerebral salt wasting syndrome (CSWS). OBJECTIVE The objective was to prospectively determine the etiology of hyponatremia after SAH using sequential clinical examination and biochemical measurement of plasma cortisol, arginine vasopressin (AVP), and brain natriuretic peptide (BNP). DESIGN This was a prospective cohort study. SETTING The setting was the National Neurosurgery Centre in a tertiary referral centre in Dublin, Ireland. PATIENTS One hundred patients with acute nontraumatic aneurysmal SAH were recruited on presentation. INTERVENTIONS Clinical examination and basic biochemical evaluation were performed daily. Plasma cortisol at 0900 hours, AVP, and BNP concentrations were measured on days 1, 2, 3, 4, 6, 8, 10, and 12 following SAH. Those with 0900 hours plasma cortisol<300 nmol/L were empirically treated with iv hydrocortisone. MAIN OUTCOME MEASURES Plasma sodium concentration was recorded daily along with a variety of clinical and biochemical criteria. The cause of hyponatremia was determined clinically. Later measurement of plasma AVP and BNP concentrations enabled a firm biochemical diagnosis of the cause of hyponatremia to be made. RESULTS Forty-nine of 100 developed hyponatremia<135 mmol/L, including 14/100<130 mmol/L. The cause of hyponatremia, and determined by both clinical examination and biochemical hormone measurement, was SIAD in 36/49 (71.4%), acute glucocorticoid insufficiency in 4/49 (8.2%), incorrect iv fluids in 5/49 (10.2%), and hypovolemia in 5/49 (10.2%). There were no cases of CSWS. CONCLUSIONS The most common cause of hyponatremia after acute nontraumatic aneurysmal SAH is SIAD. Acute glucocorticoid insufficiency accounts for a small but significant number of cases. We found no cases of CSWS.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage

The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long‐term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients’ acute admission with SAH could predict the occurrence of long‐term hypopituitarism.

Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

Background  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15–30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens.

Somnolence in adult craniopharyngioma patients is a common, heterogeneous condition that is potentially treatable

Context and Objective  Somnolence and obesity are prevalent in craniopharyngioma patients.

Thyrotoxic periodic paralysis due to excessive L-thyroxine replacement in a Caucasian man

Thyrotoxic periodic paralysis is a potentially fatal complication of hyperthyroidism, more common in Asian races, which is defined by a massive intracellular flux of potassium. This leads to profound hypokalaemia and muscle paralysis. Although the paralysis is temporary, it may be lethal if not diagnosed and treated rapidly, as profound hypokalaemia may induce respiratory muscle paralysis or cardiac arrest. The condition is often misdiagnosed in the west due to its comparative rarity in Caucasians; however it is now increasingly described in Caucasians and is also being seen with increasing frequency in western hospitals due to increasing immigration and population mobility. Here we describe the case of a patient with panhypopituitarism due to a craniopharyngioma, who developed thyrotoxic periodic paralysis due to excessive L-thyroxine replacement. This disorder has been described in Asian subjects but, to our knowledge, thyrotoxic periodic paralysis secondary to excessive L-thyroxine replacement has never been described in Caucasians.

Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus

Objective  Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood‐onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus.

Low-dose hydrocortisone replacement therapy is associated with improved bone remodelling balance in hypopituitary male patients.

OBJECTIVE Glucocorticoid (GC) therapy is associated with adverse effects on bone metabolism, yet the effects of different GC physiological replacement regimens in hypopituitarism are not well characterised. We aimed to assess the effect of three hydrocortisone (HC) replacement dose regimens on bone turnover. STUDY DESIGN An open cross-over study randomising ten hypopituitary men with severe acth deficiency to three commonly used HC dose regimens: dose A (20 mg mane and 10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg tarde). METHODS Following 6 weeks of each regimen, the participants underwent 24-h serum cortisol sampling and measurement of bone turnover markers: bone-specific alkaline phosphatase, procollagen type I N-propeptide (PINP), intact osteocalcin (OC(1-49)), C-terminal cross-linking telopeptide (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Bone remodelling balance was estimated as an absolute ratio (PINP:CTX-I) and as an index using standardised scores derived from the matched controls. RESULTS There were significant increases in the concentrations of the formation markers PINP (P=0.045) and OC(1-49) (P=0.006) and in the PINP:CTX-I ratio (P=0.015), and a more positive bone remodelling balance index (P=0.03) was observed in patients on the lowest dose C than in those on the highest dose A. Mean 24-h cortisol concentrations correlated negatively with CTX-I (r=-0.66 and P=0.04) and TRACP5b (r=-0.74 and P=0.01) in patients on dose B and with OC(1-49) (r=-0.66 and P=0.04) and CTX-I (r=-0.81 and P<0.01) in patients on dose C. In patients receiving the lower-dose regimen, trough cortisol concentrations correlated with increased bone formation and resorption. CONCLUSION Low-dose HC replacement (10 mg mane and 5 mg tarde) is associated with increased bone formation and a positive bone remodelling balance. This may have a long-term beneficial effect on bone health.