The relationship between serum cobalamin concentration and mean red cell volume at varying concentrations of serum folate.

There is concern that exposure of patients to folic acid may prevent the development of the macrocytosis of cobalamin deficiency and thus delay the detection of the neurological complications. We examined the relationship between low cobalamin levels and mean cell volume (MCV) at different serum folate concentrations in 63,472 blood samples tested in a community pathology laboratory over 2 years. We found no evidence that high serum folate levels masked the macrocytosis of cobalamin deficiency in this population with similar increases in MCV regardless of whether the serum folate was low, normal or high. Macrocytosis appears to retain its value as a marker of cobalamin deficiency in people with serum folate concentrations above the population average.

Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial.

PURPOSE: Thiazide diuretics reduce urine calcium excretion and might therefore reduce postmenopausal bone loss. In some, but not all, case-control studies, their use has been associated with a reduced incidence of hip fractures. We studied the effects of hydrochlorothiazide on bone loss in normal postmenopausal women. SUBJECTS AND METHODS: We performed a randomized, double-blind, 2-year trial of the effects of hydrochlorothiazide (50 mg per day) and placebo on bone mineral density in normal postmenopausal women. Participants were not required to have either low bone mineral density or hypertension. Bone mineral density was measured using dual-energy x-ray absorptiometry. RESULTS: One hundred eighty-five women entered the study, of whom 138 completed 2 years of follow-up. In an intention-to-treat analysis, hydrochlorothiazide produced significant benefits on bone mineral density of the total body (between-group difference at 2 years of 0.8%, 95% confidence interval [CI]: 0.3% to 1.3%, P <0.0001), legs (0.9%, 95% CI: 0.2% to 1.7%, P <0.0001), mid-forearm (1.2%, 95% CI: 0.2% to 2.2%, P = 0.02), and ultradistal forearm (1.7%, 95% CI: 0.1% to 3.2%, P = 0.04). There was no effect in the lumbar spine (0.5%, 95% CI: -0.5% to 1.6%) or femoral neck (0.2%, 95% CI: 1.3% to 1.7%). The between-group changes tended to be greatest during the first 6 months, except in the mid-forearm where there appeared to be a progressive divergence. An as-treated analysis produced similar results. Urine calcium excretion and indices of bone turnover decreased in the thiazide group, but parathyroid hormone concentrations did not differ between the groups. Treatment was tolerated well. CONCLUSIONS: Hydrochlorothiazide (50 mg per day) slows cortical bone loss in normal postmenopausal women. It may act directly on bone as well as on the renal tubule. The small size of the effect suggests that thiazides may have a role in the prevention of postmenopausal bone loss, but that they are not an appropriate monotherapy for treating osteoporosis.

Characteristics of children with florid vitamin D deficient rickets in the Auckland region in 1998.

AIM: To describe the characteristics of children with vitamin D deficiency rickets and identify common features and predisposing factors. METHODS: A review of the clinical notes of all children less than five years of age with radiological evidence of rickets and serum 25-hydroxyvitamin D levels of less than 10 micrograms/L. Patients were identified by searching all low vitamin D levels performed at the Endocrinology laboratory at Auckland Hospital and children presenting to the Starship Childrens' Hospital with rickets in 1998. RESULTS: In 1998, there were eighteen children (ten males and eight females) with vitamin D deficient rickets. The age range was 3 to 36 months with a median of 12 months. There were twelve children of Indian ethnic origin, one Maori, one Tongan, one Western Samoan, one Ethiopian, one Moroccan and one Indonesian. All children had an elevated alkaline phosphatase level and most had very low serum 25-hydroxyvitamin D levels (< or = 5 micrograms/L), and over half were hypocalcaemic. The common presenting features were delayed walking and bowed legs, swollen wrists or ankles, hypocalcaemic seizure, incidental radiological abnormalities and failure to thrive. CONCLUSIONS: There are a significant number of children in Auckland presenting with florid clinical rickets. The majority with vitamin D deficient rickets in this survey were of Indian ethnic origin. Strategies are needed to detect children at risk of vitamin D deficiency and supplement them with vitamin D.

Relation between troponin T concentration and mortality in patients presenting with an acute stroke: observational study.

OBJECTIVE: To assess whether a raised serum troponin T concentration would be an independent predictor of death in patients with an acute ischaemic stroke. DESIGN: Observational study. SETTING: Auckland Hospital, Auckland, New Zealand. SUBJECTS: All 181 patients with an acute ischaemic stroke admitted over nine months in 1997-8, from a total of 8057 patients admitted to the acute medical service. MAIN OUTCOME MEASURES: Blood samples for measuring troponin T concentration were collected 12-72 hours after admission; other variables previously associated with severity of stroke were also recorded and assessed as independent predictors of inpatient mortality. RESULTS: Troponin T concentration was raised (>0.1 microgram/l) in 17% (30) of patients admitted with an acute ischaemic stroke. Thirty one patients died in hospital (12/30 (40%) patients with a raised troponin T concentration v 19/151 (13%) patients with a normal concentration (relative risk 3.2 (95% confidence 1.7 to 5. 8; P=0.0025)). Of 17 possible predictors of death, assessed in a multivariate stepwise model, only a raised troponin T concentration (P=0.0002), age (P=0.0008), and an altered level of consciousness at presentation (P=0.0074) independently predicted an adverse outcome. CONCLUSIONS: Serum troponin T concentration at hospital admission is a powerful predictor of mortality in patients admitted with an acute ischaemic stroke.

Phaeochromocytomas discovered during coronial autopsies in Sydney, Melbourne and Auckland.

BACKGROUND: The diagnosis of phaeochromocytoma can be difficult and previous autopsy studies have found that many of these tumours are not recognised during life. AIM: To determine the incidence of phaeochromocytoma during coronial autopsies and the characteristics of the individuals concerned. METHOD: Review of coronial autopsy records from Auckland (1981-97), Melbourne (1991-97) and Sydney (1991-97). RESULTS: Twenty-two patients were found giving an incidence of 0.05% (one tumour per 2031 autopsies) with similar figures in each centre. Thirteen of the patients were men, 12 were overweight (body mass index >25 kg/m2) and three of the seven Auckland patients were Maori. Fourteen of the tumours were left-sided, one was extra-adrenal and none had metastasised. The one patient with bilateral tumours had multiple endocrine neoplasia syndrome type 2 (MEN-2) which had not been recognised during life. The heart weight was increased in 95% of the patients. The tumour may have contributed to the patient's death in up to 50% of the cases, although the true significance of these lesions as a cause of death remains unclear. Three patients died soon after general anaesthetics had been given for unrelated reasons. CONCLUSIONS: Even though phaeochromocytomas are uncommon, we fail to diagnose a significant number of these tumours during life. Methods are needed to increase the detection of phaeochromocytoma and to distinguish functional and non-functional tumours.

Hormone replacement therapy causes a respiratory alkalosis in normal postmenopausal women.

Menopause is associated with an increase in venous bicarbonate concentrations that is reversible with hormone replacement therapy (HRT). However, the mechanism underlying this effect is not known. To address this question, we studied the changes in acid-base indexes in the arterialized venous blood of normal postmenopausal women commencing conjugated equine estrogen (0.625 mg/day), medroxyprogesterone acetate (MPA; 5 mg/day), their combination, or placebo, in a double blind randomized controlled study over 3 months. Serum bicarbonate concentrations decreased significantly in the groups receiving either MPA or estrogen plus MPA (P = 0.008). This trend was apparent as early as 2 days and reached 2.7 and 2.3 mmol/L in the respective groups by 3 months. Similar changes were seen with partial pressure of carbon dioxide (P = 0.04); a change of -0.7 kPa occurred in the estrogen plus MPA group at 3 months. There were no changes in bicarbonate concentrations or partial pressure of carbon dioxide in those receiving estrogen alone or placebo. Accompanying changes in blood pH were apparent in the estrogen plus MPA group, where there was an upward trend at 1 week (P = 0.056) and a significant change from baseline (+0.013) at 3 months (P = 0.03). In the whole group, the changes in pH were inversely correlated with those in urinary excretion of hydroxyproline (r = -0.44; P = 0.01). We conclude that HRT using conjugated estrogens and MPA produces small, but sustained, changes in acid-base status. These may contribute to the effects of HRT and menopause on many tissues and disease processes, including the development of osteoporosis.

Urinary catecholamines and the diagnosis of phaeochromocytoma in Auckland.

AIM: To review the experience in Auckland with the use of urinary catecholamine measurements in the diagnosis of phaeochromocytoma. METHODS: Review of the test results of patients with proven phaeochromocytoma and retrospective analysis of the outcome of patients with increased 24-hour urinary excretion of the catecholamines noradrenaline, adrenaline and dopamine. RESULTS: Over six years the majority (16/18) of patients with proven phaeochromocytoma had raised urinary noradrenaline excretion either alone (3/16) or with raised adrenaline and/or dopamine (13/16). One phaeochromocytoma secreted adrenaline alone, none secreted dopamine alone and one had urinary catecholamine levels that were normal. Urinary adrenaline excretion was unexpectedly elevated in two patients with extra-adrenal phaeochromocytomas. Approximately 10% of 2590 24 hour urine specimens analysed over a 14 month period had an elevation of one or more catecholamine. Forty-six patients had urinary catecholamine excretion greater than twice the upper limit of normal. This group contained five of the six phaeochromocytomas diagnosed during this period. The other patients were normal (35/46, 76%) or were lost to follow up (6/46, 13%). CONCLUSIONS: In this series most patients with phaeochromocytoma (89%) had increases in the 24-hour urinary excretion of one or more than one catecholamine which exceeded twice the upper limit of normal for our laboratory with noradrenaline being most commonly affected. Increased catecholamine excretion was often seen in patients without phaeochromocytoma.