Associations of health literacy with diabetic foot outcomes: a systematic review and meta-analysis.

BACKGROUND: People with diabetes have low health literacy, but the role of the latter in diabetic foot disease is unclear. AIM: To determine, through a systematic review and meta-analysis, if health literacy is associated with diabetic foot disease, its risk factors, or foot care. METHODS: We searched PubMed, EMBASE, CINAHL, Web of Science, Scopus and Science Direct. All studies were screened and data extracted by two independent reviewers. Studies in English with valid and reliable measures of health literacy and published tests of association were included. Data were extracted on the associations between the outcomes and health literacy. Meta-analyses were performed using random effects models. RESULTS: Sixteen articles were included in the systematic review, with 11 in the meta-analysis. In people with inadequate health literacy, the odds of having diabetic foot disease were twice those in people with adequate health literacy, but this was not statistically significant [odds ratio 1.99 (95% CI 0.83, 4.78); two studies in 1278 participants]. There was no statistically significant difference in health literacy levels between people with and without peripheral neuropathy [standardized mean difference -0.14 (95% CI -0.47, 0.18); two studies in 399 participants]. There was no association between health literacy and foot care [correlation coefficient 0.01 (95% CI -0.07, 0.10); seven studies in 1033 participants]. CONCLUSIONS: There were insufficient data to exclude associations between health literacy and diabetic foot disease and its risk factors, but health literacy appears unlikely to have a role in foot care. The contribution of low health literacy to diabetic foot disease requires definitive assessment through robust longitudinal studies.

Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.

BACKGROUND: Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. METHODS: A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. RESULTS: The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. CONCLUSION: This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. TRIAL REGISTRATION: ANZCTR 12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.

Novel approaches to the treatment of hyperglycaemia in type 2 diabetes mellitus.

Control of hyperglycaemia is a fundamental therapeutic goal in patients with type 2 diabetes. The progressive nature of ß-cell dysfunction in type 2 diabetes leads to the need for escalating anti-hyperglycaemic treatment, including insulin, in most patients. Given the prevalence of complications such as weight gain and hypoglycaemia associated with traditional anti-hyperglycaemic agents (AHA), including sulphonylureas and insulin, it is unsurprising that recent years have seen the development of novel agents to treat hyperglycaemia. With increasing evidence supporting the need for a multi-faceted approach to the prevention of adverse cardiovascular events in people with type 2 diabetes, a patient-centred and individualised management strategy addressing lifestyle, cardiovascular risk factor modification and glycaemic control remains critical in improving outcomes in these patients.

Admission blood glucose predicts mortality and length of stay in patients admitted through the emergency department.

BACKGROUND: Hyperglycaemia has been associated with adverse outcomes in several different hospital populations. AIM: The aim of this study was to investigate the relationship between admission blood glucose level (BGL) and outcomes in all patients admitted through the emergency department. METHODS: This study was a retrospective observational cohort study from an Australian tertiary referral hospital. Patients admitted in the first week of each month from April to October 2012 had demographic data, co-morbidities, BGL, intensive care unit admission, length of stay and dates of death recorded. Factors associated with outcomes were assessed by multi-level mixed-effects linear regression. RESULTS: Admission BGL was recorded for 601 admissions with no diagnosis of diabetes and for 219 admissions diagnosed with type 2 diabetes (T2DM). In patients with no diagnosis of diabetes, admission BGL was associated with in-hospital and 90-day mortality (P < 0.001). After multivariate analysis, BGL greater than 11.5 mmol/L was significantly associated with increased mortality at 90 days (P < 0.05). In patients with T2DM increased BGL on admission was not associated with in-hospital or 90-day mortality but was associated with length of hospital stay (ß: 0.22 days/mmol/L; 95% confidence interval 0.09-0.35; P < 0.001), although this association was lost on multivariable analysis. In patients with T2DM, increased coefficient of variation of BGL was also positively associated with length of hospital stay in an almost dose-dependent fashion (P < 0.001). CONCLUSION: Admission BGL was independently associated with increased mortality in patients with no diagnosis of diabetes. Glycaemic variability was associated with increased length of hospital stay in patients with T2DM.

Healthcare professional requirements for the care of adult diabetes patients managed with insulin pumps in Australia.

BACKGROUND: Healthcare professional (HCP) time supporting insulin pump therapy (IPT) has not been documented, yet it is important in planning and allocating resources for effective care. AIM: This study aims to determine HCP time spent in IPT patient care to inform resource planning for optimal IPT delivery. METHODS: Twenty-four Australian adult IPT-experienced institutions (14 government funded, seven private, three both) collected data between April 2012 and January 2013 prospectively, including: patient demographics, HCP classification, purpose of HCP-patient interaction, interaction mode and HCP time with the patient. A subset of patients was tracked from pre-pump education until stable on IPT. RESULTS: Data on 2577 HCP-adult patient interactions (62% face-to-face, 29% remote, 9% administrative) were collected over 12.2 ± 6.4 weeks for 895 patients; age 35.4 ± 14.2 years; 67% female; 99% type 1 diabetes, representing 25% of all IPT patients of the institutions. Time (hours) spent on IPT interactions per centre per week were: nurses 5.4 ± 2.8, dietitians 0.4 ± 0.2 and doctors 1.0 ± 0.5. IPT starts accounted for 48% of IPT interaction time. The percentage of available diabetes clinic time spent on outpatient IPT interactions was 20.4%, 4.6% and 2.7% for nurses, dietitians and doctors respectively. Fifteen patients tracked from pre-pump to stabilisation over 11.8 ± 4.5 weeks, required a median (range) of 9.2 (3.0-20.9), 2.4 (0.5-6.0) and 1.8 (0.5-5.4) hours per patient from nurses, dietitians and doctors respectively. CONCLUSIONS: IPT patient care represents a substantial investment in HCP time, particularly for nurses. Funding models for IPT care need urgent review to ensure this now mainstream therapy integrates well into healthcare resources.

22q11.2 deletion presenting with severe hypocalcaemia, seizure and basal ganglia calcification in an adult man.

We report a 40-year-old man who was found to have profound hypocalcaemia and hypoparathyroidism when investigated for multiple, generalized, tonic/clonic seizures and a chest infection. Computed tomography scan of the brain revealed extensive symmetric bilateral calcification within the cerebellum, thalamus and basal ganglia. Molecular cytogenetic testing by fluorescent in situ hybridization using the commercial Vysis LSI DiGeorge/VCFS dual colour probe set showed a deletion of 22q11.2. The extraordinary feature of this case is the adult presentation of hypocalcaemia, hypoparathyroidism and basal ganglia calcification due to 22q11.2 deletion.

Prolactinomas in a large kindred with multiple endocrine neoplasia type 1: clinical features and inheritance pattern.

Multiple endocrine neoplasia type 1 (MEN 1) is associated with neoplasia and hyperfunction of the parathyroid and pituitary glands, pancreatic islet cells, and neuroendocrine cells of the gut. The inheritance pattern is autosomal dominant, and the underlying genetic defect is situated at chromosome 11q13. The MEN 1 gene behaves as a defective copy of a normally constitutive tumor suppressor gene. Development of the MEN 1 phenotype, however, is a multistep and multifactorial process. The Tasman 1 genealogy is the largest MEN 1 pedigree detected to date. Thus far, 90 related members with MEN 1 have been screened for evidence of prolactinoma. Prolactinomas were found in 18 patients (20%). Prolactinomas were not evenly distributed in the genealogy; in 2 branches of the overall genealogy prolactinomas were present in 50% or more of MEN 1-affected members. The familial distribution of prolactinomas in these branches was consistent with an autosomal dominant mode of inheritance. In the remainder of the pedigree, prolactinomas were uncommon and did not display this inheritance pattern. This pedigree represents one of the largest published MEN 1 genealogies in which the risk of developing prolactinoma follows an autosomal dominant pattern of transmission. It is the first to demonstrate an inheritance pattern for prolactinomas acting in addition to, yet distinct from, the inheritance of the underlying MEN 1 gene defect. These findings are consistent with the existence of an undefined second genetic defect involved in the pathogenesis of prolactinoma in MEN 1.

Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred.

Prolactinomas and somatotropinomas are reported to be the pituitary lesions most frequently associated with multiple endocrine neoplasia type 1 (MEN 1). However, few reports have documented the full spectrum of pituitary disease in this condition. We report herein the clinical, biochemical (PRL, alpha-subunit, insulin-like growth factor-I, cortisol, and thyroid function), and radiological (magnetic resonance imaging and computerized tomography scan) characteristics of pituitary disease occurring in a single MEN 1 pedigree containing 165 MEN 1-affected members. Pituitary lesions were detected in 30 (18%) of 165 patients overall. In the subgroup of MEN 1 patients (n = 131) living after recognition of MEN 1 in the kindred, pituitary lesions were detected in 25 (19%). In 76% of patients with pituitary lesions, the diagnosis was made by prospective screening; the remainder sought medical attention for symptomatic pituitary disease. Prolactinomas accounted for 76%, and nonfunctioning adenomas accounted for the remaining 24%. alpha-Subunit elevation was observed in 29% of 41 patients tested, and an aggressive alpha-subunit secreting macroadenoma developed in 1 subject with a previously documented prolactinoma. Progression of pituitary disease occurred in 47% of patients with prolactinoma. There were no cases of Cushing's disease, thyrotropinoma, or somatotropinoma. We conclude that 1) in addition to prolactinomas, nonfunctioning pituitary tumors are common in MEN 1; 2) alpha-subunit hypersecretion is frequent in MEN 1; 3) comprehensive screening may identify many clinically significant but asymptomatic pituitary lesions; and 4) prolactinomas occurring in MEN 1 may behave more aggressively than sporadic prolactinomas.

Two families with an autosomal dominant inheritance pattern for papillary carcinoma of the thyroid.

BACKGROUND: Papillary carcinoma of the thyroid (PTC) is the most prevalent malignancy of the thyroid gland. Although the majority of lesions are sporadic tumors, an established relationship exists between familial adenomatous polyposis (FAP) and PTC. Moreover, some authors postulate the existence of familial PTC as a distinct entity. Evidence for this is limited, however, there being few well characterized descriptions of pedigrees with high prevalence of PTC. AIMS: The objective of the present study was to examine an apparent heritable predisposition to PTC occurring in two Tasmanian families in which PTC occurs commonly. METHODS: Pedigree charts were constructed for both families and the medical records of the members reviewed. RESULTS: In Pedigree I, 7 of 25 members had PTC (6 of these had coexisting multinodular goiter (MNG), and 11 others had MNG. In Pedigree II, identical male twins and their daughters had PTC. CONCLUSIONS: In both families there is evidence of autosomal dominant inheritance of PTC. The association of PTC with MNG suggests a possible role for MNG in tumor pathogenesis in hereditary PTC. The majority of the patients were diagnosed with PTC before commencement of prospective screening, indicating clinically relevant disease in the families described.

Somatotrophinomas in multiple endocrine neoplasia type 1: a review of clinical phenotype and insulin-like growth factor-1 levels in a large multiple endocrine neoplasia type 1 kindred.

PURPOSE: Within the spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN-1), widely disparate prevalence rates for somatotrophinomas have been described. Studies that combine multiple, small MEN-1 kindreds report pituitary disease in 60% to 65% of patients, somatotrophinomas accounting for 27% to 37% of total pituitary lesions. However, reports based on large MEN-1 family screening programs have produced lower prevalence rates for pituitary adenomas (9% to 40%), of which somatotrophinomas comprise up to 14%. We sought to determine the prevalence of both biochemical and clinically overt growth hormone (GH) hypersecretion in the largest reported MEN-1 genealogy, the Tasman 1 kindred. PATIENTS AND METHODS: The Tasman 1 MEN-1 kindred contains 165 members with established MEN-1. We reviewed the records of 124 MEN-1 patients for evidence of acromegaly or gigantism. To determine if clinical criteria underestimate the occurrence of biochemical GH hypersecretion, a subset of 33 patients was assessed for elevated levels of serum insulin-like growth factor-1 (IGF-1). RESULTS: No cases of acromegaly or gigantism were detected in the 124 patients reviewed. Of the 33 patients screened with IGF-1, 13 had previously diagnosed pituitary lesions--11 prolactinomas and 2 nonsecretory lesions. The IGF-1 levels were normal in all patients studied. There were no significant differences in mean IGF-1 values between patients with and without pituitary lesions. CONCLUSIONS: This report represents the largest study of growth hormone secretion patterns thus far described in MEN-1. The apparent absence of somatotrophinomas in a kindred of this size is unexpected. These results support the existence of kindred-specific MEN-1 phenotypes. We conclude that the pathogenesis of GH-secreting adenomas in MEN-1 is influenced by secondary factors acting in synergy with the well-documented primary MEN-1 gene defect on chromosome 11q13.

Preoperative sestamibi scanning and surgical findings at bilateral, unilateral, or minimal reoperation for recurrent hyperparathyroidism after subtotal parathyroidectomy in patients with multiple endocrine neoplasia type 1.

HYPOTHESES: Preoperative parathyroid radioisotope scanning is of little or no value in patients with multiple endocrine neoplasia type 1 when 4 or more hypertrophied glands are present. Scanning using technetium Tc 99m sestamibi and single photon emission computed tomography will achieve a high level of sensitivity and specificity after 3 or more glands have previously been removed, justifying limited surgical reexploration. DESIGN: In a prospective study, the preoperative documented report of the predicted site of residual parathyroid was compared with the surgical findings in 13 patients having 19 scans and 17 reoperations. SETTING: All patients belonged to one family, previously described as Tasman family 1, and were confirmed by genetic testing as having multiple endocrine neoplasia type 1. In 10 of 13 patients, reexploration was being undertaken more than 10 years after the first operation. MAIN OUTCOME MEASURES: Scanning was regarded as successful when the documented preoperative report correctly predicted the side and quadrant in which a gland was found at surgery. Surgery was regarded as successful when calcium levels decreased to or below normal levels and were maintained. RESULTS: All 13 scans before first reexploration were successful in identifying the location of a residual parathyroid. From a statistical viewpoint, this equates to 100% sensitivity and 92% specificity. However, despite accurate localization of 1 residual gland in every patient, 7 supernumerary glands in 4 patients and 1 parathyroid remnant in a fifth patient were not localized so that sensitivity in locating all glands in every patient was only 61%. Scans performed for persistent hypercalcemia 48 to 72 hours after reexploration in 2 patients were unsuccessful in demonstrating any residual parathyroid. Scans performed 3 months after surgery in the same 2 patients and a third patient were successful, with sensitivity and specificity of 100%. Apart from patient 11, who awaits reexploration, normocalcemia was eventually achieved in every patient, with 11 of 12 having an initial period of hypocalcemia. CONCLUSIONS: Three months after reexploration and trimming or resection with transplant of half a gland left at first operation, sestamibi scanning achieved sensitivity and specificity of 100% in locating supernumerary parathyroids in patients with multiple endocrine neoplasia type 1 and persistent hypercalcemia. Before first reexploration, however, scans rarely provided new information, predominantly showing only the hypertrophied half-gland remnant.

The outcome of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1.

BACKGROUND: The efficacy of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is unclear. The long-term outcome and optimal timing of operation remain controversial. OBJECTIVE: To determine the long-term outcome of parathyroidectomy for primary hyperparathyroidism in the presence of MEN 1. DESIGN: Case series and retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Patients with MEN 1 from 2 families. INTERVENTIONS: Subtotal parathyroidectomy, ie, resection of 3 1/2 parathyroid glands from each patient. MAIN OUTCOME MEASURES: Recurrence of hyperparathyroidism. RESULTS: Thirty-seven patients underwent subtotal parathyroidectomy. Overall, persistent postoperative hypoparathyroidism developed in 24%, normocalcemia was maintained in 46%, and hyperparathyroidism recurred in 30%. However, after adjustment for the duration of follow-up (by using the Kaplan-Meier method), the cumulative recurrence rates for hyperparathyroidism were 15% at 2 years, 23% at 4 years, 55% at 8 years, and 67% after 8 years. Early recurrence of hyperparathyroidism (within 5 years of operation) was less likely to develop in patients in whom ionized calcium levels of 1.00 mmol/L (4.00 mg/dL) or less were achieved during the perioperative period than in patients in whom this degree of hypocalcemia failed to develop (P=.01). CONCLUSIONS: While relatively long periods of disease remission are possible after subtotal parathyroidectomy, our results indicate that recurrent hyperparathyroidism eventually develops in most patients with MEN 1.

Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy.

BACKGROUND: Sporadic primary hyperparathyroidism (PHPT) occurs most frequently in postmenopausal women. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal-dominant disease in which mild to moderate PHPT develops in most gene carriers by 20 years of age. Primary hyperparathyroidism associated with MEN 1 is typically recurrent, despite initially successful subtotal parathyroidectomy. Osteoporosis is considered a complication of sporadic PHPT and an indication for parathyroidectomy. In the setting of MEN 1, however, the relationship of bone mass to PHPT, fracture risk, and parathyroidectomy is unknown. HYPOTHESIS: Parathyroidectomy improves bone mineral density for patients with primary hyperparathyroidism in the setting of MEN 1. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Twenty-nine women with MEN 1 belonging to a single family with a history of MEN 1. INTERVENTIONS: Parathyroidectomy. MAIN OUTCOME MEASURES: Bone mineral density (BMD) and history of skeletal fracture. RESULTS: Osteopenia and osteoporosis were diagnosed in 41% and 45% of patients, respectively. Forty-four percent of patients with uncontrolled PHPT had severe osteopenia (T score, <-2.0) by 35 years of age. Reduction in BMD was greatest at the femoral neck. Reduced BMD was associated with an increased likelihood of skeletal fracture (P = .05). Patients with uncontrolled PHPT had lower femoral neck and lumbar spine BMDs than those in whom PHPT was controlled by parathyroidectomy (P = .005 and .02, respectively). Successful parathyroidectomy improved femoral neck and lumbar spine BMDs by a mean +/- SEM of 5.2% +/- 2.5% and 3.2% +/- 2.9%, respectively. CONCLUSIONS: Osteoporosis is a frequent and early complication of PHPT in MEN 1. Despite difficulty in achieving a cure of PHPT in MEN 1, parathyroidectomy has an important role in the optimization of BMD for patients with MEN 1.

Adrenal lesions in a large kindred with multiple endocrine neoplasia type 1.

OBJECTIVE: To review the prevalence and natural history of adrenal lesions occurring in patients from a single kindred with multiple endocrine neoplasia type 1 (MEN-1). DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Medical records of 33 patients from the Tasman 1 MEN-1 kindred who had undergone abdominal computed tomographic (CT) scanning were reviewed. In 30 patients, the results of abdominal ultrasonographic examinations were available for correlation with CT scan. Computed tomographic and ultrasound scans of 18 patients were reviewed by a radiologist blinded to the patients' clinical details. Three patients underwent adrenalectomy, and the histopathologic material was reviewed. MAIN OUTCOME MEASURES: Computed tomographic and ultrasound scans. RESULTS: Adrenal lesions were detected in 12 patients (36%) by CT scan examination. Ultrasound imaged 58% of these lesions. Pancreatic lesions were present in all cases of adrenal disease. Follow-up was available for 8 patients with adrenal disease. Over 5.5 years, 6 patients (75%) had stable disease, 1 patient had an adrenal lesion that enlarged by 5 mm, and 1 patient had a lesion that enlarged by 50 mm. Adrenal histopathologic material was available in 3 patients. Macronodular cortical hyperplasia was present in 2 patients and a cortical adenoma present in 1 patient. Another kindred had bilateral macronodular cortical hyperplasia at autopsy. CONCLUSIONS: Adrenal lesions are common in MEN-1 and occur in association with pancreatic disease. Abdominal CT scan is more sensitive than ultrasonographic examination in detecting adrenal disease. Primary hypersecretory syndromes of the adrenal glands appear to be rare, and the majority of lesions follow an indolent clinical course.

A population-based study of the relationship between salt intake, bone resorption and bone mass.

OBJECTIVE: To explore the relationship between urinary sodium (the best measure of salt intake), urinary calcium, urinary deoxypyridinoline (DPYR) and bone mass. DESIGN: Cross-sectional study. SETTING: Population based sample of healthy Hobart residents. SUBJECTS: One hundred and fifty-four (M = 34, F = 120) subjects invited to take part from a systematic sample of the electoral roll and a single newspaper advertisement. RESULTS: In both sexes, urinary sodium correlated moderately with urinary DPYR (r = 0.32, P < 0.0001) and urinary calcium (r = 0.37, P < 0.0001). In multivariate analysis, the combination of urinary sodium, total body bone area, age and sex explained 22% of the variation in log-transformed DPYR (P < 0.00001). In univariate analysis, both urinary sodium and urinary DPYR were strongly associated with bone mineral content and bone mineral density at all sites but this association disappeared after adjustment for confounders particularly body weight. CONCLUSIONS: This study has shown that salt intake is associated with markers of bone resorption in a population-based sample of males and females and appears likely to be a risk factor for osteoporosis despite the lack of a demonstrable association between bone mass and a single measure of urinary sodium excretion. Further studies are needed to define the effect of salt intake on bone mass and fractures more clearly. These studies will need to be either longitudinal or interventional in design with repeated measures of urinary sodium so that habitual sodium intake can be accurately assessed and regression dilution bias can be minimised.

Vitamin D levels in prepubertal children in Southern Tasmania: prevalence and determinants.

OBJECTIVE: To describe the prevalence and determinants of 25-hydroxy D3(25(OH)D) in children. DESIGN: Cross-sectional study. SETTING: Southern Tasmania between June and November 1997. SUBJECTS: Two hundred and one 8-y old male and female children taking part in a cohort study whose principal endpoints were blood pressure and high-density lipoprotein (HDL) cholesterol. RESULTS: The mean 25(OH)D level was 79 nmol/l (s.d. 29.5, median 73, range 12-222). Boys had higher levels than girls (82.1 vs 72.8 nmol/l, P=0.02). 25(OH)D was associated with sunlight exposure in winter school holidays (r=0.20, P=0.005) and winter weekends (r=0.16, P=0.02), the month after school holidays (87.5 vs 69.5 nmol, P<0.0001) and body mass index (r=-0.23, P=0.001). Dietary intake of vitamin D was low (mean 40 IU/day, range 5.2-384) and was not associated with 25(OH)D levels (r=0.01, P=0.91). Variation in skin melanin density was weakly associated with 25(OH)D (r=0.09, P=0.19). CONCLUSIONS: Sunlight is the major determinant of vitamin D stores in our population. Neither variation in skin type within Caucasians nor diet modified this association to any significant extent. Extrapolation of these findings to sunlight bone mass associations in a very similar population suggests that a minimum level of around 50 nmol/l in the population is required for optimal bone development in prepubertal children but this needs to be confirmed with further controlled trials of vitamin D supplementation and bone mass. SPONSORSHIP: Arthritis Foundation of Australia, Roche Pharmaceuticals.

A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males.

OBJECTIVE: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Single school in northwest Tasmania. PARTICIPANTS: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y). INTERVENTIONS: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. RESULTS: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. CONCLUSIONS: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.

Hypercalcemia and lipoid pneumonia.

A 49-year-old man with an 11 year history of NIDDM presented hypercalcemic and with acute on chronic renal failure. His only symptoms were mild anorexia and nausea. Four years previously he had been diagnosed as having lipoid pneumonia, with classical histological findings. On this admission, serum parathyroid hormone was suppressed and 1,25 dihydroxyvitamin D levels elevated. The cause of his hypercalcemia presumably was ectopic 1 hydroxylation of 25 hydroxyvitamin D in the chronic granulomata in his lungs. It should be emphasised that any chronic granulomatous disease, and not just sarcoidosis, may be a cause of hypercalcemia.

Expression of the MEN-1 gene in a large kindred with multiple endocrine neoplasia type 1.

In 1983 a large family with MEN-1 (designated Tasman 1) was identified in Tasmania. Kindred screening and case follow-up over the subsequent 15 years has yielded data on over 160 MEN-1-affected patients. Hyperparathyroidism is present in over 60% of gene carriers by age 20 years and 95% by age 30 years. Hyperplasia is the characteristic pathological finding. Kaplan-Meier analysis indicates hyperparathyroidism recurs in the majority of patients despite near-total parathyroidectomy. Gastrinoma, 'nonfunctioning' pancreatic adenoma and insulinoma occur in up to 60, 50 and 10% of patients, respectively. Metastatic gastroenteropancreatic (GEP) tumours develop in up to 35% of family members, being frequent in some branches of Tasman 1, whilst rare in others. Pituitary disease developed in 19% of patients. Prolactinoma and 'nonfunctioning' adenoma account for 76 and 24%, respectively, of pituitary abnormalities. Prolactinomas exhibit clustering within branches of the Tasman 1 kindred. Adrenal adenomas occur in 36% of patients. The majority of adrenal lesions are benign and nonsecretory and develop in association with pancreatic neoplasia. Carcinoid tumours are uncommon but important malignancies. Malignant thymic carcinoid occurs in male patients, whereas bronchial carcinoid occurs predominantly in women. Prior to recognition of MEN-1 in Tasman 1, complications of hyperparathyroidism and malignancy accounted for the majority of patient mortality. Since commencement of prospective screening, malignant GEP tumours and cardiovascular disease have become the most prevalent causes of death amongst MEN-1-affected patients.