Temporal trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (ATPO) testing across two phases of iodine fortification in Tasmania (1995-2013).

CONTEXT: Tasmania is an island state of the Australian Commonwealth with a well-documented history of mild iodine deficiency. Between 2001 and 2009, Tasmania experienced two incremental phases of iodine fortification. OBJECTIVE: To examine trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (ATPO) testing and their relationship to different phases of iodine nutrition in the Tasmanian population between 1995 and 2013. DESIGN: Retrospective longitudinal study. SETTING AND PARTICIPANTS: The major primary care and largest public hospital pathology providers in Tasmania submitted data for all TSH and ATPO tests performed between 1995 and 2013. Data linkage methodology was used to determine trends in TSH and ATPO testing. RESULTS: A total of 1.66 million TSH assessments, involving 389,910 individual patients, were performed in Tasmania between 1995 and 2013. There was approximately a fourfold increase in the overall rate of TSH testing during this period with the rate of incident TSH assessment remaining relatively stable over the study period. The incidence of overt suppression and elevation of TSH (TSH≤0.1 mIU/L and ≥10 mIU/L) declined 62.3% and 59.7%, respectively, with a trend for increased incidence of borderline TSH elevation ≥4.0 mIU/L. The incidence of thyroid autoimmunity as determined by the proportion of abnormal ATPO results remained stable, with the absolute number of positive test results increasing during the study period. CONCLUSION: Iodine supplementation of this mildly iodine-deficient population was not associated with an obvious increase in incidence of overt thyroid dysfunction or autoimmunity. Whilst the volume of TSH testing increased over the study period, the increase was driven by patients undergoing follow-up TSH assessments.

Utility of FDG-PET imaging in screening for succinate dehydrogenase B and D mutation-related lesions.

OBJECTIVE: Mutations of the genes encoding succinate dehydrogenase B and D (SDHB, SDHD) are associated with highly penetrant phenotypes, including paragangliomas and phaeochromocytomas. Patients with these mutations require lifelong surveillance; however, there is currently ambiguity regarding the optimal screening regimen. We sought to determine the utility of fluorodeoxyglucose (18F) positron emission tomography (18F-FDG PET) imaging, compared to other modalities for detecting SDHB and SDHD mutation-related lesions. DESIGN: A retrospective audit of patients with SDHB or SDHD mutation. PATIENTS: All adult patients with confirmed SDHB and SDHD mutations who underwent 18F-FDG PET/CT at our institution between 1 July 2011 and 30 May 2015. MEASUREMENTS: 18F-FDG PET/computed tomography (CT) performed during surveillance of patients with SDHB and SDHD mutations. Lesion numbers and locations detected by 18F-FDG PET were compared to those identified on the CT component, as well as other imaging modalities and histology when available. RESULTS: Thirty-one 18F-FDG PET/CT studies were completed on 22 patients. For SDHB (20 patients), there were five positive and 21 negative studies. There were no false-negative 18F-FDG PET studies. Positive 18F-FDG PET findings correlated with magnetic resonance imaging (MRI), CT and [68 Ga]-DOTA(0)-Tyr(3)-octreotate (68 Ga DOTATATE PET/CT) imaging with no missed lesions; the only potential false-positive result relating to nonspecific postoperative changes (sensitivity 100·0%, specificity 95·5%). For SDHD (two patients), lesions were detected on 18F-FDG PET and correlated with other imaging in three of five studies. Metastatic lesions were incompletely visualized on 18F-FDG PET but were detected on the noncontrast fusion CT. CONCLUSIONS: 18F-FDG PET/CT is suitable for detecting SDHB and SDHD mutation-related lesions and may be considered effective for periodic surveillance of patients with these mutations.

Omega-3 fatty acid supplementation provides an additional benefit to a low-dust diet in the management of horses with chronic lower airway inflammatory disease.

BACKGROUND: Omega-3 polyunsaturated fatty acid (PUFA) may benefit humans and animals with chronic inflammatory diseases. HYPOTHESIS: Omega-3 PUFA supplementation improves clinical signs, lung function, and airway inflammation in horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD). ANIMALS: Eight research horses and 35 client-owned horses. METHODS: A pilot study examined the dose of PUFA that can alter plasma PUFA composition. Then, a randomized, controlled clinical trial was performed in horses with RAO and IAD. Horses were fed a complete pelleted diet with no hay and randomly assigned to 1 of 3 daily treatments for 2 months: 30 or 60 g of the supplement or 30 g of placebo. Clinical signs, lung function, plasma PUFA composition, and bronchoalveolar lavage fluid (BALF) cytology were evaluated. Data were expressed as median (25-75th percentiles). P < .05 was considered significant. RESULTS: Polyunsaturated fatty acid supplementation resulted in increased plasma docosahexaenoic acid (DHA) that peaked at 4 weeks. Clinical improvement was noted in all horses involved in the clinical trial, but the group that received PUFA had greater improvement in clinical signs (cough score improved 60%), lung function (respiratory effort decreased 48%), and BALF (neutrophils decreased from 23 to 9%) when compared to placebo (cough score improved 33%, respiratory effort decreased 27%, BALF neutrophils increased from 11 to 17%; P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding horses with RAO and IAD a PUFA supplement containing 1.5-3 g DHA for 2 months provides an additional benefit to low-dust diet.

Pre-operative embolisation of metastatic paraganglioma of the thoracic spine.

We report a 46-year-old male with metastatic functioning paraganglioma of the thoracic spine. Thoracic spine functioning paragangliomas are rare and we describe the benefits of embolisation of the lesion prior to surgical decompression.

Feeding conjugated linoleic acid partially recovers carcass quality in pigs fed dried corn distillers grains with solubles.

Dried corn distillers grains with solubles (DDGS) fed to swine may adversely affect carcass quality due to the high concentration of unsaturated fat. Feeding CLA enhances pork quality when unsaturated fat is contained in the diet. The effects of CLA on growth and pork quality were evaluated in pigs fed DDGS. Diets containing 0, 20, or 40% DDGS were fed to pigs beginning 30 d before slaughter. At 10 d before slaughter, one-half of each DDGS treatment group was fed 0.6% CLA or 1% choice white grease. Carcass data, liver- and backfat-samples were collected at slaughter. Longissimus muscle area, 10th-rib back-fat depth, last rib midline backfat depth, LM color, marbling, firmness and drip loss, and bacon collagen content were not altered by DDGS or CLA. Outer layer backfat iodine values were increased (P 0.05) for pigs fed DDGS. Feeding CLA decreased (P

Effects of temperature stress on growth performance and bacon quality in grow-finish pigs housed at two densities.

Managing stressors is essential for optimizing pig growth performance. To determine the effects of temperature and space allocation on growth performance and carcass characteristics, pigs were housed within their thermoneutral zone, at 23.9 degrees C, or above their thermoneutral zone, at 32.2 degrees C, and were provided either 0.66 or 0.93 m(2)/pig for the final 35 d of the grow-finish period. Individual BW were recorded on d 1, 10, 20, and 30. At slaughter, carcass measurements and samples of backfat and belly fat were collected. Final BW was decreased (P < or = 0.05) from 113 to 103 kg for pigs housed at 32.2 degrees C. The ADG was reduced (P < 0.05) for pigs housed at 32.2 degrees C (0.89 vs. 0.54 kg/d), as was G:F (0.28 vs. 0.24). Housing at 0.66 m(2)/pig resulted in pigs that were lighter (P < or = 0.05), at 106 compared with 110 kg, as a result of decreased (P < or = 0.05) ADG (0.78 to 0.65 kg/d) and decreased (P < or = 0.05) G:F (0.275 to 0.255) compared with pigs housed at 0.93 m(2)/pig. Pigs housed at a greater spatial allocation had elevated (P < or = 0.05) ADFI. The interaction of housing at 32.2 degrees C and decreasing spatial allocation increased (P < or = 0.05) the adipose iodine value from 66.8 to 70.4, decreased (P < or = 0.05) the saturated:unsaturated fatty acids ratio from 0.59 to 0.56, and increased (P < or = 0.05) the n-6:n-3 from 23.56 to 25.27. Decreased spatial allocation resulted in decreased (P < or = 0.05) belly weights. Although increased temperature did not affect belly weight, the 32.2 degrees C pigs had decreased (P < or = 0.05) raw and cooked slice weights, increased (P < or = 0.05) percentage lean of bacon, increased (P < or = 0.05) lean:fat ratio of bacon slices, increased (P < or = 0.05) raw slice scores, and increased (P < or = 0.05) quantity of collagen in belly fat. Some of these changes may have resulted from changes in lipid metabolism. Increasing spatial allocation in the 32.2 degrees C pigs decreased fatty acid synthase (P = 0.03) and stearoyl-CoA desaturase- 1 (P = 0.08) mRNA expression in adipose tissue. The results from this study demonstrated decreased growth, carcass lipid quality, and bacon quality in pigs housed at temperatures above the thermoneutral zone; however, increasing the spatial allocation for housing may be a means to ameliorate the negative effects of temperature stress.

Effect of dietary vitamin E supplementation and feeding period on pork quality.

Feeding increased levels of dietary vitamin E can inhibit lipid oxidation. The aim of this study was to investigate the effect of levels of dietary alpha-tocopherol acetate (VE) and feeding duration on meat quality and lipid oxidation. Eighty-one pigs were allocated to 1 of 3 diets containing 40, 200, or 400 IU of VE/kg of feed, and each diet group was divided into 3 feeding periods (3, 6, or 9 wk). Carcass characteristics and meat quality were evaluated. Oxidative stability of fresh and cooked pork patties and pork chops was determined after chilled or frozen storage. Increasing dietary concentrations of VE did not affect any growth performance parameter. Drip loss, however, decreased (P < 0.05) with increased dietary VE levels. Moreover, an increased duration of VE feeding improved (P < 0.05) pH and drip loss. Less lipid oxidation (P < 0.05) was detected in fresh ground pork from pigs fed greater concentrations of VE after 4 d of storage. A greater (P < 0.05) resistance to oxidation in cooked ground pork was observed in pigs fed 200 or 400 IU of VE/kg at 2 and 6 d of storage. Fresh and cooked pork patty oxidation decreased (P < 0.05) linearly as feeding duration increased from 3 to 9 wk. After 6 mo of freezer storage, lipid oxidation of pork chops from pigs fed 200 or 400 IU of VE/kg was lower (P < 0.05) than for pigs fed 40 IU of VE/kg. Likewise, lipid oxidation of pork chops of pigs fed VE for an extended period of time (6 wk) was lower (P < 0.05) after 9 mo of storage. Fatty acid profiles of neutral lipid fraction of the LM became more unsaturated (P < 0.05) with added VE to the feed. These results indicate an increased intake of dietary VE concentration, and prolonged feeding of VE can improve drip loss and reduce lipid oxidation in ground pork and pork chops. This study suggests that supplementation with 200 IU of VE/kg of feed for 6 wk before market is beneficial in improving lipid stability and pork quality.

Effects of dietary vitamin E and fat supplementation on pork quality.

The effects of dietary vitamin E (VE, alpha-tocopherol acetate) and fat supplementation on growth and carcass quality characteristics, oxidative stability of fresh and cooked pork patty in storage, fatty acid profiles of muscle and adipose tissue, and VE concentrations of plasma, muscle, and adipose tissue were studied. Six hundred pigs were allocated to 1 of 6 diets and fed for 63 d in a 3 x 2 factorial design. The dietary treatments included 3 fat levels (normal corn, high oil corn, high oil corn plus added beef tallow) and 2 levels of VE supplementation (40 IU/kg, normal VE supplementation; and 200 IU/kg, high VE supplementation). At 113 kg of BW, 54 pigs were slaughtered as a subsample to evaluate dietary effects on pork quality. Growth performance and meat quality characteristics did not differ (P > 0.05) among treatment groups. The high level of VE supplementation had a beneficial effect on the oxidative stability of pork as indicated by thiobarbituric acid reactive substance (TBARS) values. Lean tissue had lower (P < 0.05) TBARS in the group fed the high VE than in those fed the normal VE level. The TBARS values differed among storage periods (0 to 6 d) and also between fresh and cooked ground ham. Fat type did not significantly affect total saturated and unsaturated fatty acids proportions in the neutral and polar fraction of muscle. Adding VE acetate led to greater (P < 0.05) monounsaturated and total unsaturated fatty acid proportions in neutral lipids of muscle and adipose tissues. Increasing dietary levels of VE acetate increased the concentration of VE in plasma and muscle. These results indicate that dietary VE acetate supplementation increased (P < 0.05) lipid stability and the VE concentration of muscle.

Liver lipid accumulation in duck embryos and hatchlings change with parental age.

The purpose of this study was to investigate the effects of duck breeder age on liver lipid accumulation and yolk absorption and utilization in duck embryos (day 25 of incubation) and newly hatched ducklings. One breeder flock was monitored at 24 (young breeders), 31 (mature breeders and near peak egg production) and 47 (post peak egg production) weeks of age. Electron microscopy images of duck embryo liver slices revealed a significant change in hepatic lipid accumulation as a function of breeder age. More specifically, as breeder age increased both the relative number of liver lipid droplets as well as the size of the lipid droplets increased in duck embryos (day 25 of incubation). At hatch, however, newly hatched ducklings from 31-week-old breeders exhibited the lowest number as well as the smallest sized lipid droplets when compared to ducklings from 24 or 47-week-old breeders. The trend in yolk absorption at day 25 as a function of breeder age paralleled that in liver lipid accumulation. That is, day 25 maintained a higher percentage of unabsorbed yolk when compared to embryos from 31- or 47-week-old breeders. In contrast to breeder age, time of incubation (day 25 vs. day 28 or hatch) had little effect on yolk fatty acid profiles when compared to breeder age. Although there were no clear trends in yolk fatty acid usage among the various ages of breeders, newly hatched ducklings from 31-week-old breeders did have a significantly higher proportion of 18:2 n6 compared to those from breeders at 24 or 47 weeks of age. These data would suggest that breeder age subsequently affects the relative number and size of liver lipid droplets in embryos and newly hatched ducklings.

Malignant thymic carcinoid is not prevented by transcervical thymectomy in multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant tumour syndrome. It is characterized by primary hyperparathyroidism, pituitary neoplasia and foregut lineage neuroendocrine neoplasia. Malignant thymic carcinoid tumours are an uncommon but important manifestation of MEN 1. Transcervical thymectomy is often advocated as prophylaxis against thymic carcinoids, although there is a paucity of evidence to support the efficacy of this procedure. This is the first report of a malignant thymic carcinoid occurring in an MEN 1 patient following prior parathyroidectomy and transcervical thymectomy. It is concluded that transcervical thymectomy does not reliably provide prophylaxis against thymic carcinoid.

Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1).

BACKGROUND: The majority of reports describing the natural history and prognosis of multiple endocrine neoplasia type 1 (MEN 1) utilize phenotypic rather than molecular genetic criteria to establish a diagnosis of MEN 1. OBJECTIVES AND PATIENTS: We sought to determine the spectrum of endocrine abnormality amongst 152 members (64 gene carriers and 88 noncarriers) of a large MEN 1 family in whom a determination of MEN 1 status had previously been made by phenotype screening. The predictive utility of both clinical and molecular screening techniques are described. RESULTS: A novel IVS2-3 (C-G) MEN1 mutation was identified in affected members of this family. Seven (10%) of 71 individuals satisfying clinical diagnostic criteria for MEN 1 were found to be genetically negative (excluded by mutation analysis and haplotyping) for MEN 1. These cases of MEN 1 phenocopy comprised four cases of primary hyperparathyroidism, two 'nonsecretory' pituitary adenoma and one case of coincident prolactinoma and hyperparathyroidism. Three of the patients with hyperparathyroidism had previously required parathyroidectomy and each had achieved normocalcaemia following parathyroid resection. Predictive genetic testing prospectively identified three children with the MEN 1 genotype. Serum calcium was normal at the time of their initial molecular genetic diagnosis. In each case hyperparathyroidism subsequently developed during adolescence. CONCLUSION: Multiple endocrine neoplasia type 1 phenocopy is an important differential diagnosis in patients exhibiting an multiple endocrine neoplasia type 1 phenotype. This is a relevant consideration, particularly when the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but nonspecific, criteria such as mild hyperparathyroidism, pituitary micoadenoma, and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to confirm clinical diagnoses of multiple endocrine neoplasia type 1.

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.

Refractory amiodarone-associated thyrotoxicosis: an indication for thyroidectomy.

BACKGROUND: Tasmania is an area of endemic iodine deficiency. Amiodarone is a class III anti-arrhythmic drug that is widely used for the management of ventricular and supraventricular tachydysrhythmias. Individuals from areas of endemic iodine deficiency appear more likely to manifest hyperthyroidism following amiodarone therapy, whereas hypothyroidism is a more frequent complication in iodine-replete communities. METHODS: Cases series. The clinical and biochemical response to medical and surgical management of five consecutive Tasmanian patients presenting with severe type-II amiodarone-associated thyrotoxicosis was reviewed. RESULTS: Five patients were identified. Combinations of antithyroid therapy including propylthiouracil, lithium carbonate, dexamethasone and cholestyramine were used. Thyroidectomy was required in two cases (40%) due to severe unremitting thyrotoxicosis despite combined drug regimens. Anaesthesia and total thyroidectomy were undertaken without complication despite the presence of severe hyperthyroidism at the time of surgery. In both cases thyroid histopathology demonstrated degenerative and destructive follicular lesions with multinuclear cell infiltrate and focal fibrosis. CONCLUSION: Amiodarone-associated thyrotoxicosis may be severe and refractory to medical therapy. Despite the potential risks of anaesthesia associated with uncontrolled thyrotoxicosis, thyroidectomy should be considered in the setting of life-threatening thyrotoxicosis.

The changing incidence and spectrum of thyroid carcinoma in Tasmania (1978-1998) during a transition from iodine sufficiency to iodine deficiency.

Exposure to ionizing radiation, changing levels of iodine nutrition, and increased pathologic diagnosis of clinically unimportant thyroid neoplasia have all been proposed as explanations for a worldwide rise in the incidence of thyroid carcinoma (TC) over the past 6 decades. Tasmania is geographically an area of endemic iodine deficiency. In this report, we describe the spectrum of TC in a population averaging 450,000 persons during a 21-yr period that spans the communities transition from iodine sufficiency to iodine deficiency after discontinuation of universal iodine prophylaxis in the mid 1980s. The Tasmanian Cancer Register was used to ascertain all cases of TC diagnosed in Tasmania between 1978 and 1998. Histopathological and demographic data were reviewed. A total of 289 cases of TC were identified. Papillary TC (PTC), follicular TC, medullary TC, and other species accounted for 62%, 23%, 4%, and 11% of cases, respectively. The age standardized incidence rate for total TC increased from 2.45 to 5.33 per 100,000 for females and 0.75 to 1.76 per 100,000 for males between 1978 and 1984 and 1992 and 1998, respectively. A rise in the incidence of PTC by 4.5-fold (P < 0.05) in females and 2.1-fold in males (not significant) was the dominant change over this period. In parallel, the proportion of follicular TC relative to PTC fell from 0.35 to 0.17 during these years (P < 0.05). The rise in PTC incidence was, in part, due to an increase in the occurrence of tumors 1cm or less in diameter. Nonetheless, a 3-fold rise in incidence of larger lesions was also observed during the study period. Forty-three (24%) PTC cases had multifocal disease, 17 (40%) of whom had bilateral tumors. Familial (autosomal dominant) PTC was identified in nine (5%) total PTC cases. Prior studies have linked iodine prophylaxis to a rise in the proportion of differentiated TC, particularly PTC. Our data suggest a complex relationship between iodine nutrition and thyroid tumorigenesis. Factors such as a long latency between changes in iodine nutrition and thyroid tumorigenesis, a dose threshold for the effect of iodine nutrition on thyroid tumorigenesis, and an interaction between iodine nutrition and thyroidal sensitivity to ionizing radiation may all play a role.

Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is the diagnosis used to describe children who are inattentive, impulsive, and hyperactive. ADHD is a widespread condition that is of public health concern. In most children with ADHD the cause is unknown, but is thought to be biological and multifactorial. Several previous studies indicated that some physical symptoms reported in ADHD are similar to symptoms observed in essential fatty acid (EFA) deficiency in animals and humans deprived of EFAs. We reported previously that a subgroup of ADHD subjects reporting many symptoms indicative of EFA deficiency (L-ADHD) had significantly lower proportions of plasma arachidonic acid and docosahexaenoic acid than did ADHD subjects with few such symptoms or control subjects. In another study using contrast analysis of the plasma polar lipid data, subjects with lower compositions of total n-3 fatty acids had significantly more behavioral problems, temper tantrums, and learning, health, and sleep problems than did those with high proportions of n-3 fatty acids. The reasons for the lower proportions of long-chain polyunsaturated fatty acids (LCPUFAs) in these children are not clear; however, factors involving fatty acid intake, conversion of EFAs to LCPUFA products, and enhanced metabolism are discussed. The relation between LCPUFA status and the behavior problems that the children exhibited is also unclear. We are currently testing this relation in a double-blind, placebo-controlled intervention in a population of children with clinically diagnosed ADHD who exhibit symptoms of EFA deficiency.

NADH and NADPH-dependent reduction of coenzyme Q at the plasma membrane.

High affinity for NADH, and low affinity for NADPH, for reduction of endogenous coenzyme Q10 (CoQ10) by pig liver plasma membrane is reported in the present work. CoQ reduction in plasma membrane is carried out, in addition to other mechanisms, by plasma membrane coenzyme Q reductase (PMQR). We show that PMQR-catalyzed reduction of CoQ0 by both NADH and NADPH is accompanied by generation of CoQ0 semiquinone radicals in a superoxide-dependent reaction. In the presence of a water-soluble vitamin E homologue, Trolox, this reduction leads to quenching of the Trolox phenoxyl radicals. The involvement of PMQR versus DT-diaphorase under the conditions of vitamin E and selenium sufficiency and deficiency was evaluated for CoQ reduction by plasma membranes. The data presented here suggest that both nucleotides (NADH and NADPH) can be accountable for CoQ reduction by PMQR on the basis of their physiological concentrations within the cell. The enzyme is primarily responsible for CoQ reduction in plasma membrane under normal (nonoxidative stress-associated) conditions.

Octreotide improves biochemical, radiologic, and symptomatic indices of gastroenteropancreatic neoplasia in patients with multiple endocrine neoplasia type 1 (MEN-1). Implications for an integrated model of MEN-1 tumorigenesis.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant tumor syndrome associated with parathyroid, gastroenteropancreatic (GEP), and pituitary neoplasia. Gastrinoma and GEP malignancy are common life-threatening endocrine complications of MEN-1. An effective management strategy for these disorders remains to be determined. The authors attempted to determine the role of the somatostatin analogue, octreotide, in ameliorating features of hypergastrinemic GEP neoplasia associated with MEN-1. METHODS: Five MEN-1 patients with hypergastrinemia and either symptoms of GEP neoplasia or hepatic metastases received a trial of octreotide, 100 microg subcutaneously, three times daily for 3 months. RESULTS: Treatment with octreotide was associated with a rapid symptomatic and biochemical response. In all patients serum gastrin fell to < 25% of the pretreatment value. The serum glycoprotein-alphasubunit (a marker of enterochromaffin-like [ECL] cell hyperplasia, gastric carcinoidosis, and disseminated enteropancreatic malignancy) was elevated at baseline in three patients. In each case the serum glycoprotein-alphasubunit normalized after treatment with octreotide. Hepatic metastases were present in two patients at baseline. The size of the metastases diminished by up to 15% during the period of octreotide treatment. Four patients reported symptoms prior to treatment: lethargy, easy fatigability, and generalized musculoskeletal discomfort. A marked symptomatic improvement occurred in each case. No patient experienced side effects related to octreotide therapy and all elected to remain on treatment after completion of the trial. CONCLUSIONS: Octreotide is a safe and effective adjunct to surgical strategies for the management of GEP neoplasia in hypergastrinemic MEN-1 patients.

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.