MRI for Cushing Disease: A Systematic Review.

BACKGROUND: MR imaging is key in the diagnostic work-up of Cushing disease. The sensitivity of MR imaging in Cushing disease is not known nor is the prognostic significance of "MR imaging-negative" disease. PURPOSE: Our aim was to determine the overall sensitivity and prognostic significance of MR imaging localization of Cushing disease. DATA SOURCES: We performed a systematic review of the MEDLINE and PubMed databases for cohort studies reporting the sensitivity of MR imaging for the detection of adenomas in Cushing disease. STUDY SELECTION: This study included 57 studies, comprising 5651 patients. DATA ANALYSIS: Risk of bias was assessed using the methodological index for non-randomized studies criteria. Meta-analysis of proportions and pooled subgroup analysis were performed. DATA SYNTHESIS: Overall sensitivity was 73.4% (95% CI, 68.8%-77.7%), and the sensitivity for microadenomas was 70.6% (66.2%-74.6%). There was a trend toward greater sensitivity in more recent studies and with the use of higher-field-strength scanners. Thinner-section acquisitions and gadolinium-enhanced imaging, particularly dynamic sequences, also increased the sensitivity. The use of FLAIR and newer 3D spoiled gradient-echo and FSE sequences, such as spoiled gradient-echo sequences and sampling perfection with application-optimized contrasts by using different flip angle evolutions, may further increase the sensitivity but appear complementary to standard 2D spin-echo sequences. MR imaging detection conferred a 2.63-fold (95% CI, 2.06-3.35-fold) increase in remission for microadenomas compared with MR imaging-negative Cushing disease. LIMITATIONS: Pooled analysis is limited by heterogeneity among studies. We could not account for variation in image interpretation and tumor characteristics. CONCLUSIONS: Detection on MR imaging improves the chances of curative resection of adenomas in Cushing disease. The evolution of MR imaging technology has improved the sensitivity for adenoma detection. Given the prognostic importance of MR imaging localization, further effort should be made to improve MR imaging protocols for Cushing disease.

Robust impurity detection and tracking for tokamaks.

A robust impurity detection and tracking code, able to generate large sets of dust tracks from tokamak camera footage, is presented. This machine learning-based code is tested with cameras from the Joint European Torus, Doublet-III-D, and Magnum-PSI and is able to generate dust tracks with a 65-100% classification accuracy. Moreover, the number dust particles detected from a single camera shot can be up to the order of 1000. Several areas of improvement for the code are highlighted, such as generating more significant training data sets and accounting for selection biases. Although the code is tested with dust in single two-dimensional camera views, it could easily be applied to multiple-camera stereoscopic reconstruction or nondust impurities.

Trabecular bone score in adults with cerebral palsy.

CONTEXT: Bone fragility in cerebral palsy (CP) is secondary to a complex interplay of functional, hormonal, and nutritional factors that affect bone remodelling. A greater understanding of bone microarchitectural changes seen in CP should assist therapeutic decision making. OBJECTIVE: To examine the relationship between trabecular bone score (TBS), BMD and fractures in adults with CP; the influence of clinical factors and body composition on bone microarchitecture were explored. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: 43 adults (25 male) with CP of median age 25 years (interquartile range 21.4-33.9) who had evaluable dual-energy X-ray absorptiometry imaging of the lumbar spine from a single tertiary hospital between 2005-March 2018. RESULTS: 24/43 (55.8%) of patients had TBS values indicating intermediate or high risk of fracture (<1.31). TBS correlated with areal BMD at the lumbar spine, femoral neck and total body. TBS was significantly associated with arm and leg lean mass, with adjustment for age, gender and height (adjusted R2 = 0.18, p = 0.042 for arm lean mass; adjusted R2 = 0.19, p = 0.036 for leg lean mass). There was no difference in TBS when patients were grouped by fracture status, anticonvulsant use, gonadal status or use of PEG feeding. TBS was lower in non-ambulatory patients compared with ambulatory patients (1.28 vs 1.37, p = 0.019). CONCLUSIONS: Abnormal bone microarchitecture, as measured by TBS, was seen in >50% of young adults with CP. TBS correlated with both areal BMD and appendicular lean mass. Maintaining muscle function is likely to be important for bone health in young adults with CP and needs to be confirmed in further studies.

Fractures in spina bifida from childhood to young adulthood.

This study assessed the prevalence and types of fractures in spina bifida and examined risk factors for fracture. Fracture prevalence was highest in childhood and reduced in adolescence and young adulthood. The importance of maintaining mobility is highlighted by the increased risk of fracture in those who are non-ambulatory. INTRODUCTION: The aims of this study are to study the prevalence and types of fractures according to age group in spina bifida and examine risk factors associated with fracture. METHODS: This is a retrospective cohort study of 146 individuals with spina bifida aged 2 years or older who attended the paediatric or adult spina bifida multidisciplinary clinic at a single tertiary hospital. RESULTS: Median age at which first fracture occurred was 7 years (interquartile range 4-13 years). Fracture rates in children (ages 2-10), adolescents (ages 11-18) and adults (age > 18) were 10.9/1000 (95 % confidence interval 5.9-18.3), 5.4/1000 (95 % CI 1.5-13.8) and 2.9/1000 (95 % CI 0.6-8.1) patient years respectively. Childhood fractures predominantly involved the distal femur and femoral shaft; these fractures were rarely seen in adulthood. Non-ambulatory status was associated with a 9.8 times higher risk of fracture compared with ambulatory patients (odds ratio 9.8, p = 0.016, 95 % CI 1.5-63.0). Relative risk of re-fracture was 3.1 (95 % CI 1.4-6.8). Urological intervention with intestinal segments was associated with renal calculi (p = 0.037) but neither was associated with fracture. CONCLUSIONS: The risk of fracture is lower in adults compared with children with spina bifida. The predominant childhood fracture affects the distal femur, and immobility is the most significant risk factor for fracture. Clinical factors contributing to fracture risk need to be elucidated to enable selection of patients who require investigation and treatment of osteoporosis.

Genetics and genomics of ovarian sex cord-stromal tumors.

Ovarian sex cord-stromal tumors (SCST) represent approximately 8% of malignant ovarian tumors. The most common are granulosa cell tumors (GCT) which account for approximately 90% of malignant SCST. Recent studies have unraveled the key genomic and genetic events contributing to their pathogenesis. SCST are found in the hereditary syndromes: Peutz-Jeghers syndrome, Ollier disease and Maffucci syndrome, and DICER1 syndrome. Genomic studies have largely been limited to GCT where a number of recurring chromosomal abnormalities (monsomy and trisomy) have been identified although their contribution to pathogenesis remains unclear. In addition to the recurrent DICER1 mutations reported in non-hereditary cases of Sertoli cell and Sertoli-Leydig cell tumors, recurrent somatic mutations in both the juvenile (j) and adult (a) forms of GCT have been reported. Approximately 30% of jGCT contain a somatic mutation, the gsp oncogene, while a further 60% have an activating mutation in the AKT gene. In the case of aGCT, a well characterized mutation in the FOXL2 transcription factor (FOXL2 C134W) is found in almost all cases, which arguably defines the disease, although the molecular events that determine the stage, behavior and prognosis of aGCT remain to be determined.

Review: The role of multiple placental glucocorticoid receptor isoforms in adapting to the maternal environment and regulating fetal growth.

The physiological mechanisms that confer different outcomes in morbidity and mortality of the fetus exposed to stressful environments may be driven by significant differences in the expression and function of the placental glucocorticoid receptor (GR). The recent discovery that the placenta contains at least 8 different isoforms of the GR raises questions about the regulation and physiological relevance of the many GR variants expressed in the placenta. The current data also highlights that individual differences in glucocorticoid sensitivity, variations in the effect of different complications of pregnancy on birth outcomes and sex differences in the response to stress, may all be dependent on a specific GR isoform expression profile. This review will investigate the current state of knowledge of GR isoforms in the placenta and discuss the potential role of these multiple isoforms in regulating glucocorticoid sensitivity.

Musculoskeletal and Endocrine Health in Adults With Cerebral Palsy: New Opportunities for Intervention.

CONTEXT: Cerebral palsy (CP) increases fracture risk through diminished ambulation, nutritional deficiencies, and anticonvulsant medication use. Studies examining bone mineral density (BMD) in adults with CP are limited. OBJECTIVE: To examine the relationship between body composition, BMD, and fractures in adults with CP. The effect of functional, nutritional, and endocrine factors on BMD and body composition is also explored. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: Forty-five adults with CP (mean age, 28.3 ± 11.0 years) who had dual-energy x-ray absorptiometry imaging at a single tertiary hospital between 2005 and 2015. RESULTS: Seventeen (38%) had a past history of fragility fracture; 43% had a Z-score of ≤ -2.0 at the lumbar spine (LS) and 41% at the femoral neck (FN). In nonambulatory patients, every one unit decrease in FN Z-score increased the risk of fracture 3.2-fold (95% confidence interval, 1.07-9.70; P = .044). Stepwise linear regression revealed that the Gross Motor Function Classification System was the best predictor of LS Z-score (R(2) = 0.550; ß = -0.582; P = .002) and FN Z-score (R(2) = 0.428; ß = -0.494; P = .004); 35.7% of the variance in BMD was accounted for by lean tissue mass. Hypogonadism, present in 20% of patients, was associated with reduced lean tissue mass and reduced LS BMD. Lean tissue mass positively correlated with BMD in eugonadal patients, but not in hypogonadal patients. CONCLUSIONS: Low BMD and fractures are common in adults with CP. This is the first study to document hypogonadism in adults with CP with detrimental changes in body composition and BMD.

Role of adrenal vein sampling in primary aldosteronism: the Monash Health experience.

BACKGROUND: Adrenal vein sampling (AVS) is useful for distinguishing unilateral versus bilateral hypersecretion in primary aldosteronism (PA), but is technically challenging. Furthermore, the use of adrenocorticotropic hormone (ACTH)-stimulation in AVS is controversial. We implemented a Monash Health-specific AVS protocol in 2010. AIM: The audit aimed to: (i) examine the impact of a dedicated protocol on success rates of AVS at a tertiary referral centre; (ii) evaluate the impact of AVS on sub-typing of PA; and (iii) assess the utility of ACTH stimulation in AVS. METHODS: AVS was performed on patients with PA confirmed by positive saline suppression testing (aldosterone level >140 pmol/L post-saline infusion), with sequential sampling of adrenal and peripheral veins, pre- and post-ACTH infusion. Patients with unilateral aldosterone-producing adenoma diagnosed on successful AVS were referred for adrenalectomy. RESULTS: Between 2010 and 2014 inclusive, a total of 28 AVS procedures was performed, with complete pre- and post-ACTH data for 19 procedures. Bilateral successful cannulation rates improved post-implementation of our protocol (61% vs 41%). Of the patients, 32% had discordant imaging and AVS results: four patients with unilateral adenomas did not lateralise on AVS and were managed medically; four patients with bilateral or no adenomas on imaging, lateralised on AVS and had surgery. Overall, use of ACTH did not increase successful cannulation and tended to mask lateralisation. CONCLUSION: AVS is crucial in subtype classification of PA and should be performed by a dedicated radiologist with a standardised protocol. AVS outcomes were not improved with the use of ACTH stimulation.

Expression of eight glucocorticoid receptor isoforms in the human preterm placenta vary with fetal sex and birthweight.

INTRODUCTION: Administration of betamethasone to women at risk of preterm delivery is known to be associated with reduced fetal growth via alterations in placental function and possibly direct effects on the fetus. The placental glucocorticoid receptor (GR) is central to this response and recent evidence suggests there are numerous isoforms for GR in term placentae. In this study we have questioned whether GR isoform expression varies in preterm placentae in relation to betamethasone exposure, fetal sex and birthweight. METHODS: Preterm (24-36 completed weeks of gestation, n = 55) and term placentae (>37 completed weeks of gestation, n = 56) were collected at delivery. Placental GR expression was examined using Western Blot and analysed in relation to gestational age at delivery, fetal sex, birthweight and betamethasone exposure. Data was analysed using non-parametric tests. RESULTS: Eight known isoforms of the GR were detected in the preterm placenta and include GRα (94 kDa), GRß (91 kDa), GRα C (81 kDa) GR P (74 kDa) GR A (65 kDa), GRα D1-3 (50-55 kDa). Expression varied between preterm and term placentae with a greater expression of GRα C in preterm placentae relative to term placentae. The only sex differences in preterm placentae was that GRα D2 expression was higher in males than females. There were no alterations in preterm placental GR expression in association with betamethasone exposure. DISCUSSION: GRα C is the isoform involved in glucocorticoid induced apoptosis and suggests that its predominance in preterm placentae may contribute to the pathophysiology of preterm birth.

Management of hypoparathyroidism in pregnancy and lactation - A report of 10 cases.

INTRODUCTION: Hypoparathyroidism in pregnancy is rare, but important, as it is associated with maternal morbidity and foetal loss. There are limited case reports and no established management guidelines. Optimal maintenance of calcium levels during pregnancy is required to minimise the risk of related complications. This study aims to identify causes and examine outcomes of hypoparathyroidism in pregnancy in a cohort of women delivering at a large referral centre. DESIGN AND METHOD: The Monash Health maternity service database captures pregnancy and birthing outcomes in over 9000 women each year. We audited this database between 2000 and 2014 to examine the clinical course, treatment and outcomes of pregnant women with hypoparathyroidism. RESULTS: We identified 10 pregnancies from 6 women with pre-existing hypoparathyroidism secondary to idiopathic hypoparathyroidism (n = 3), autosomal dominant branchial arch disorder with hypoparathyroidism (n = 3) and autosomal dominant hypocalcaemia (n = 1), surgery for thyroid cancer (n = 2) and Graves' disease (n = 1). Maternal calcium levels were monitored through pregnancy and management adjusted to maintain normocalcaemia. One woman was delivered by caesarean section at 34 weeks' gestation because of intrauterine growth restriction, and oligohydramnios complicated two other pregnancies. The postpartum period was complicated by severe hypercalcaemia in one woman and by symptomatic, labile serum calcium levels during lactation in another woman, requiring close monitoring over a 6 month period. CONCLUSION: Although rare, hypoparathyroidism in pregnancy poses a management challenge for clinicians, and co-ordinated care is required by obstetricians and endocrinologists to ensure optimal outcomes for both mother and baby. Continued monitoring of maternal calcium levels during lactation and weaning is essential to avoid the potential complications of either hypercalcaemia or hypocalcaemia.

Mutation profile of differentiated thyroid tumours in an Australian urban population.

BACKGROUND: The majority of differentiated thyroid cancers are characterised by one of several point mutations or gene rearrangements. Limited data are available on the prevalence and clinical correlations of these mutations in the Australian population. AIMS: The aim of the present study was to characterise the mutation profile of differentiated thyroid tumours in the local population. METHODS: The study involved 148 patients with differentiated thyroid cancer. The following tumours were examined: 109 papillary carcinomas (PTC), 27 follicular carcinomas (FC) and 12 Hurthle cell carcinomas (HCC). Polymerase chain reaction (PCR) was performed for BRAF and RAS mutations (RNA and DNA) as well as for RET/PTC rearrangements and PAX8-PPARγ translocations (RNA). Clinicopathological parameters and outcome data were analysed according to BRAFV600E status in PTC and RAS mutation status in FC. RESULTS: BRAFV600E was identified in 74/109 (68%) PTC. BRAFV600E was not significantly correlated with clinicopathological features of aggressive disease. At a median follow up of 48 months, there was no significant difference between BRAFV600E and wild-type BRAF PTC with respect to the rates of nodal recurrence, distant metastases or disease-specific death. In FC, RAS mutations (five NRAS and three HRAS) were present in 8/27 (30%) tumours. RAS mutation was significantly associated with widely invasive histology (P = 0.01) and distant metastases (P = 0.01) on follow up. CONCLUSION: In the present study, BRAF mutation was not associated with negative prognostic indicators or adverse outcomes in PTC. RAS mutation was positively correlated with aggressive features in FC suggesting potential prognostic utility, although confirmation is required from larger studies.

CCL2-dependent macrophage recruitment is critical for mineralocorticoid receptor-mediated cardiac fibrosis, inflammation, and blood pressure responses in male mice.

Recent studies show that mice with selective deletion of the mineralocorticoid receptor (MR) in macrophages are protected from mineralocorticoid-induced cardiac fibrosis and hypertension without altering cardiac macrophage accumulation. However, it is unclear whether preventing macrophages from entering cardiac tissue would provide similar or additional protection in this disease setting. Therefore, we examined mineralocorticoid-induced cardiovascular disease in mice lacking the CCL2 gene (encoding monocyte chemoattractant protein-1), which have a markedly reduced capacity to recruit proinflammatory tissue macrophages. Male wild-type (WT) and CCL2-null mice were treated for 8 days or 8 weeks with either vehicle (control, CON) or deoxycorticosterone (DOC). At both time points, there was a significant reduction in DOC-induced macrophage recruitment (50% at 8 d and 75% at 8 wk) in the heart with a corresponding suppression of cardiac inflammatory markers in the CCL2-null mice. CCL2-null mice given DOC/salt also displayed 35% less cardiac fibrosis at 8 weeks vs WT DOC. Absence of recruited macrophages in CCL2-null mice promotes greater collagen breakdown by matrix metalloproteinase-9 in the heart and also leads to significantly reduced cardiac fibroblast and myofibroblast numbers. Systolic blood pressure (BP) after DOC/salt was significantly lower in CCL2-null than for WT mice. In the aorta at 8 weeks, MR-responsive gene expression remained intact. However, macrophage-mediated proinflammatory gene expression was reduced in the CCL2-null mice and may account for differential regulation of BP. Our data thus demonstrate an important role for CCL2-dependent macrophage recruitment in MR-dependent cardiac inflammation and remodeling and in the regulation of systolic BP.

The effect of gonadal status on body composition and bone mineral density in transfusion-dependent thalassemia.

UNLABELLED: Patients with transfusion-dependent thalassemia have abnormal growth, hormonal deficits, and increased bone loss. We investigated the relationship between skeletal muscle mass, fat mass, and bone mineral density in adult subjects with transfusion-dependent thalassemia based on their gonadal status. Our findings show that hypogonadism attenuates the strength of the muscle-bone relationship in males but strengthens the positive correlation of skeletal muscle mass and fat mass in female subjects. INTRODUCTION: Transfusion-dependent thalassemia is associated with a high prevalence of fractures. Multiple hormonal complications, in particular hypogonadism, can lead to changes in body composition and bone mineral density (BMD). We investigated for the first time the relationship between skeletal muscle mass (SMM), fat mass, and BMD in adult subjects with transfusion-dependent thalassemia based on their gonadal status. METHODS: A retrospective cohort study of 186 adults with transfusion-dependent thalassemia was analyzed. Body composition and BMD were measured using dual energy X-ray absorptiometry. The association between skeletal muscle, fat, and BMD was investigated through uni-, multi-, and stepwise regression analyses after adjusting for multicollinearity. SMM was derived using the formula, SMM = 1.19 × ALST-1.65, where ALST is equivalent to the sum of both arm and leg lean tissue mass. RESULTS: There were 186 subjects, males (43.5 %) and females (56.5 %), with a median age of 36.5. Hypogonadism was reported in 44.4 % of males and 44.7 % of females. SMM and BMD were positively correlated and strongest in eugonadal males (0.36 ≤ R (2) ≤ 0.59), but the association was attenuated in hypogonadal males. SMM (0.27 ≤ R (2) ≤ 0.69) and total fat mass (0.26 ≤ R (2) ≤ 0.55) were positively correlated with BMD in hypogonadal females, but the correlation was less pronounced in eugonadal females. Leg lean tissue mass and arm lean tissue mass in males and females, respectively, were most highly correlated to BMD in the stepwise regression analysis. CONCLUSION: Hypogonadism attenuates the strength of the muscle-bone relationship in males but strengthens the positive correlation of skeletal muscle mass and fat mass in female subjects. This study supports the notion that exercise is important for maintaining BMD and the need to optimize treatment of hypogonadism in patients with transfusion-dependent thalassemia.

Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer.

Prostate cancer is a leading cause of cancer death, frequently associated with widespread bone metastases. We report two cases of hypocalcemia following the first dose of denosumab in metastatic hormone refractory prostate cancer, the first case requiring 26 days of intravenous calcium therapy. This is the first report of prolonged hypocalcemia following denosumab in a patient with normal renal function.

Thalassemia bone disease: the association between nephrolithiasis, bone mineral density and fractures.

UNLABELLED: Thalassemia bone disease is well described, but the prevalence of nephrolithiasis has not been characterized. The association between nephrolithiasis, reduced bone density, and increased fractures has been demonstrated through this retrospective study of 166 participants with transfusion-dependent thalassemia. The findings support the need for increased vigilance of kidney and bone disease in this cohort. INTRODUCTION: Previous studies have revealed that thalassemia is associated with reduced bone mineral density (BMD) and fractures. Many causes are implicated including hypogonadism, growth hormone deficiency, marrow expansion, and iron overload. Nephrolithiasis is associated with reduced BMD and increased fractures in the general population. However, the prevalence of nephrolithiasis and its association with bone density and fractures have not been characterized in thalassemia. METHODS: We have addressed this question by performing a retrospective cohort study of 166 participants with transfusion-dependent thalassemia who had undergone dual-energy X-ray absorptiometry between 2009 and 2011. Logistic regression modeling was used to adjust for potential confounders. RESULTS: We found a high prevalence of kidney stones (18.1 %) which was greater in males compared to females (28.7 vs 9.7 %, respectively). Renal stones were associated with reduced femoral neck Z-score and fractures in men after adjusting for potential confounders. These results indicate that nephrolithiasis is highly prevalent in patients with transfusion-dependent thalassemia and is significantly associated with reduced BMD and increased fractures. CONCLUSIONS: The findings from this study strongly support the need for ongoing surveillance of BMD, fractures, and nephrolithiasis in the management of transfusion-dependent thalassemia.

Movement- and behavioral state-dependent activity of pontine reticulospinal neurons.

Forty-five years ago Shik and colleagues were the first to demonstrate that electrical stimulation of the dorsal pontine reticular formation induced fictive locomotion in decerebrate cats. This supraspinal motor site was subsequently termed the "mesencephalic locomotor region (MLR)". Cholinergic neurons of the pedunculopontine tegmental nucleus (PPT) have been suggested to form, or at least comprise in part, the neuroanatomical basis for the MLR, but direct evidence is lacking. In an effort to clarify the location and activity profiles of pontine reticulospinal neurons supporting locomotor behaviors, we employed in the present study a retrograde tracing method in combination with single-unit recordings and antidromic spinal cord stimulation as well as characterized the locomotor- and behavioral state-dependent activities of both reticulospinal and non-reticulospinal neurons. The retrograde labeling and antidromic stimulation responses suggested a candidate group of reticulospinal neurons that were non-cholinergic and located just medial to the PPT cholinergic neurons and ventral to the cuneiform nucleus (CnF). Unit recordings from these reticulospinal neurons in freely behaving animals revealed that the preponderance of neurons fired in relation to motor behaviors and that some of these neurons were also active during rapid eye movement sleep. By contrast, non-reticulospinal neurons, which likely included cholinergic neurons, did not exhibit firing activity in relation to motor behaviors. In summary, the present study provides neuroanatomical and electrophysiological evidence that non-cholinergic, pontine reticulospinal neurons may constitute the major component of the long-sought neuroanatomic MLR in mammals.

A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration.

UNLABELLED: This study evaluates the effect of zoledronic acid (ZOL) on the osseointegration of titanium implants in rabbits with glucocorticoid (GC)-induced bone loss, and our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of GCs on the osseointegration of titanium implants. INTRODUCTION: The purpose of this study is to evaluate the effect of ZOL on the osseointegration of titanium implants in rabbits with GC-induced bone loss. METHODS: Three groups of six NZW rabbits were treated for 18 weeks with saline (SALINE), GC (methylprednisolone, 0.35 mg/kg three times a week), or GC + ZOL (methylprednisolone + single dose of ZOL, 0.1 mg/kg). The animals received a titanium implant in the left tibia after 6 weeks and were killed at the 18th week. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at baseline, eighth week (W8), and 18th week (W18) after treatment to determine the change upon treatment (BMD). Histomorphometric and serum bone alkaline phosphatase analysis (BAP) were also performed. RESULTS: At W8, GC group had a significant reduction in lumbar spine and tibia BMD compared with SALINE (p = 0.003 and p = 0.000), as also observed for GC + ZOL group (p = 0.014 and p = 0.003) just 2 weeks after ZOL treatment. In contrast, at W18, the GC + ZOL had an evident BMD rescue with similar lumbar spine and tibia BMD compared with SALINE (0.043 +/- 0.006 vs. 0.055 +/- 0.009 g/cm(2), p = 0.457 and 0.027 +/- 0.003 vs. 0.041 +/- 0.011 g/cm(2), p = 0.232) and a significantly higher BMD compared with the GC (p = 0.024 and p = 0.001). Histomorphometry revealed that osseointegration was significantly reduced in GC (tibia cortical thickness and diameter, bone-implant contact, total and peri-implant bone area) whereas GC + ZOL had these parameters similar to SALINE (p > 0.05). Likewise, ZOL reversed the BAP alteration induced by GC. CONCLUSIONS: Our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of glucocorticoids on the osseointegration of titanium implants, suggesting that ZOL therapy may improve the outcome of bone implants in patients with glucocorticoid-induced osteoporosis.

Lessons from a review of thyroglobulin assays in the management of thyroid cancer.

Thyroglobulin (Tg) measurement has become increasingly an important and integral part of the follow up and management of patients with differentiated thyroid cancer. Clinicians predominantly rely on Tg for decision-making for surveillance of patients with differentiated thyroid cancer, but despite this new reliance, issues regarding Tg measurement have not been appropriately addressed especially within a local context. In the process of developing an institutional protocol we have identified that there are significant clinical and technical issues regarding Tg measurement, and surprisingly Tg assessment is currently not part of an external quality control programme. We conducted a small pilot study to specifically emphasize some of the assay issues. We aim to inform endocrinologists, pathologists and nuclear medicine physicians, the need and urgency for these issues to be addressed to improve the ongoing surveillance of differentiated thyroid cancer.