Endocrine Unit Research Articles

Association of Increased Body Mass Index and Waist to Hip Ratio with Kidney Stone Disease: a prospective analysis of 493,410 UK Biobank participants

Catherine E Lovegrove1,2 – catherine.lovegrove@nds.ox.ac.ukThomas Littlejohns3- thomas.littlejohns@ndph.ox.ac.ukNaomi Allen3- naomi.allen@ndph.ox.ac.ukSarah A Howles1,4- sarah.bounds@doctors.org.ukBenjamin W Turney 1,2- ben.turney@nds.ox.ac.uk
 1 Department of Urology, Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, UK2 University of Oxford Nuffield Department of Surgical Sciences, Oxford, Oxfordshire, UK3 University of Oxford Nuffield Department of Public Health, Oxford, Oxfordshire, UK4 Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
 
 Objectives To investigate the relationship between measures of adiposity and risk of incident kidney stone disease.
 Patients and methods The UK Biobank is a prospective cohort study of ~500,000 participants whose height, weight, BMI, waist circumference, hip circumference, waist:hip ratio (WHR), total fat mass, fat-free mass, body-fat percentage and percentage truncal fat were measured at enrolment with linkage to medical records. ICD-10 and OPCS codes were used to identify individuals with a new diagnosis of nephrolithiasis from 2006-2010. Individuals with a history of kidney stones or incomplete data were excluded. Multivariate Cox-proportional hazard models were used to assess associations between anthropometric measures and incident kidney stones.
 Results From the UK Biobank, 493,410 individuals were identified for inclusion; 3,466 developed a kidney stone during the study period. Increasing weight, BMI, waist and hip circumferences, WHR, and body and truncal fat were associated with increased risk of incident kidney stone disease. However, after adjustment for BMI, only waist circumference and WHR remained significantly associated with risk of nephrolithiasis. In overweight patients, high (men 94-102cm, women 80-88cm) waist circumference or WHR (men >0.9, women >0.85) conferred >40% increased risk of stone formation.
 Conclusion This study indicates that android fat distribution is independently associated with increased risk of developing nephrolithiasis. Kidney stone disease is known to be associated with hypertension, cardiovascular disease, and diabetes, all of which are linked to android body shape. Our findings provide insight into anthropometric risk factors for stone disease, will facilitate identification of patients at greatest risk of stone recurrence, and will inform prevention strategies.

The role of biased calcium-sensing receptor signalling in urinary calcium excretion and kidney stone disease

Michelle Goldsworthy1,2, Asha Bayliss2, Anna Gluck2, Akira Wiberg3, Benjamin Turney1, DominicFurniss3, Rajesh Thakker2, Sarah Howles1,2
 1Nuffield Department of Surgical Sciences, University of Oxford, United Kingdom.2Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, UnitedKingdom.3Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Universityof Oxford, United Kingdom.
 
 Nephrolithiasis is a major health burden with a poorly understood pathogenesis. We conducted a genome-wide association study in British and Japanese populations identifying twenty nephrolithiasis-associated loci. Mutations in the calcium-sensing receptor (CaSR) cause disorders of calcium homeostasis and five identified loci (DGKD, DGKH, WDR72, GPIC1 and BCR) were predicted to influence CaSR-signalling.
 In a validation population, we demonstrated that genotype at the DGKD-associated locus correlated with urinary calcium excretion but not serum calcium concentration. In vitro studies demonstrated that knockdown and overexpression of DGKD resulted in biased CaSR-signalling. Thus, treatment of CaSR-expressing HEK cells with DGKD-targeted siRNA (DGKD-KD), resulted in decreased MAPK responses to alterations in extracellular calcium concentration [Ca2+]e, as assessed by SRE-reporter and ERK-phosphorylation (pERK) assays, when compared to cells treated with scrambled siRNA (WT) but without alteration in intracellular calcium responses [Ca2+]i as assessed by NFAT-reporter and Fluo-4 calcium assays (SRE maximal response DGKD-KD =5.28 fold change vs. WT=7.20 p=0.0065, pERK maximal response DGKD-KD=24.77, vs. WT= 39.46 fold change, p=0.0056). Conversely, DGKD overexpression (DGKD-OE) increased MAPK responses but suppressed [Ca2+]i responses to alterations in [Ca2+]e (SRE maximal response DGKD-OE =14.13 fold change vs. WT=9.06 fold change, p=0.01; NFAT maximal response DGKD-OE=13.67 fold change vs WT=59.16 fold change, p=0.0001).
 Our results demonstrate that alterations in DGKD expression cause biased CaSR-signalling. This biased signalling may provide an explanation for the correlation of genotype at the DGKD-associated locus with urinary calcium excretion but not serum calcium concentration. Our findings suggest that biased CaSR-signalling may be a common cause of nephrolithiasis.

Redo in Thyroid Surgeries

Background: Revision of thyroid surgery is usually technically difficult because of anatomical changes and subsequent fibrosis after the primary surgery especially in the central neck. However, with experience and appropriate preparation, the risk of permanent hypoparathyroidism or recurrent laryngeal nerve injury after revision surgery is reduced. Objective: The aim of the study was to determine the causes of redo in thyroid surgeries, operative difficulties and postoperative complications. Patients and Methods: This prospective randomized controlled study included a total of 60 patients with primary total thyroidectomy and redo surgery, attending at Endocrine Surgery Unit, General Surgery Department, and Mansoura University Hospitals. This study was conducted between February 2018 and January 2019. The included subjects were randomly divided into three main groups: Group 1 (primary total thyroidectomy) consisted of 20 patients underwent total thyroidectomy, Group 2 (early redo surgery) consisted of 20 patients underwent completion thyroidectomy, and Group 3 (late redo surgery) consisted of 20 patients underwent recurrent thyroidectomy. Results: Compared to total thyroidectomy, early and late redo in thyroid surgeries gave better results regarding the recurrence and complications, which occurred in no one case 1 year later. Conclusion: From this study it is shown that total thyroidectomy is advised to be done in all patients with thyroid diseases as there were no recurrence detected and to avoid complications that may be present in redo surgery. To guard against performance of completion thyroidectomy, ultrasound examination and fine needle aspiration cytology (FNAC) should be taken from different sites.

Thyroidectomy for Cancer: The Surgeon and the Parathyroid Glands Sparing.

Background: The diagnosis of thyroid cancer is continuously increasing and consequently the amount of thyroidectomy. Notwithstanding the actual surgical skill, postoperative hypoparathyroidism still represents its most frequent complication. The aims of the present study are to analyze the rate of postoperative hypoparathyroidism after thyroidectomy, performed for cancer by a single first operator, without any technological aid, and to compare the data to those obtained adopting the most recent technological adjuncts developed to reduce the postoperative hypoparathyroidism. Methods: During the period 1997–2020 at the Endocrine Surgery Unit of the Department of Clinical and Experimental Medicine of the University of Florence, 1648 consecutive extracapsular thyroidectomies for cancer (401 with central compartment node dissection) were performed. The percentage of hypoparathyroidism, temporary or permanent, was recorded both in the first period (Group A) and in the second, most recent period (Group B). Total thyroidectomies were compared either with those with central compartment dissection and lobectomies. Minimally invasive procedures (MIT, MIVAT, some transoral) were also compared with conventional. Fisher’s exact and Chi-square tests were used for comparison of categorical variables. p < 0.01 was considered statistically significant. Furthermore, a literature research from PubMed® has been performed, considering the most available tools to better identify parathyroid glands during thyroidectomy, in order to reduce the postoperative hypoparathyroidism. We grouped and analyzed them by technological affinity. Results: On the 1648 thyroidectomies enrolled for the study, the histotype was differentiated in 93.93 % of cases, medullary in 4% and poorly differentiated in the remaining 2.06%. Total extracapsular thyroidectomy and lobectomy were performed respectively in 95.45% and 4.55%. We recorded a total of 318 (19.29%) cases of hypocalcemia, with permanent hypoparathyroidism in 11 (0.66%). In regard to the literature, four categories of tools to facilitate the identification of the parathyroids were identified: (a) vital dye; (b) optical devices; (c) autofluorescence of parathyroids; and (d) autofluorescence enhanced by contrast media. Postoperative hypoparathyroidism had a variable range in the different groups. Conclusions: Our data confirm that the incidence of post-surgical hypoparathyroidism is extremely low in the high volume centers. Its potential reduction adopting technological adjuncts is difficult to estimate, and their cost, together with complexity of application, do not allow immediate routine use. The trend towards increasingly unilateral surgery in thyroid carcinoma, as confirmed by our results in case of lobectomy, is expected to really contribute to a further reduction of postsurgical hypoparathyroidism.

Total Thyroidectomy versus Total Thyroidectomy with Prophylactic Central Compartment Neck Dissection in Early Papillary Thyroid Cancer

Abstract Background: Thyroid cancer has the highest increase in incidence rate among all cancers, and this is largely but not full attributed to the increased detection of subclinical papillary carcinomas, the high incidence of occult nodal metastasis in PTC, advocating prophylactic central compartment neck dissection (pCCND) for the initial management of these tumors is, in theory, the ideal thing to do. Nevertheless, the role of pCCND in the management of PTC remains contro-versial regarding its benefits and risks. Aim of Study: The aim of this study is to compare between total thyroidectomy with or without prophylactic central compartment neck dissection in case of papillary thyroid cancer with clinically negative cervical LN metastasis, focusing mainly on the rate of complications and the risk of recurrence of the disease. Patients and Methods: This is a retrospective comparative study was conducted in the Department of Endocrine Surgery Unit, Ain Shams University hospitals and Shefa Elorman hospital, the study included 40 cases diagnosed with papillary thyroid cancer with clinical negative LNs, operated between March 2013 and March 2018. Sampling Method: we collected 40 cases of papillary thyroid cancer with clinical negative LNs operated in the department of endocrine surgery unit, Ain Shams University hospitals and Shefa Elorman hospital, between March 2013 and March 2018, 20 of them (group 1) underwent total thy-roidectomy and 20 cases (group 2) underwent total thyroid-ectomy and prophylactic central compartment neck dissection. Results: Females to male ratio was 17:3 in both groups with no statistical significant difference (p=1), the mean age of the participants in group (1) was 39.5±10.1 years while in group (2) was 37.5±7.4, with no statistical significant difference between both groups (p= 0.742), the mean operative time in group (1) patients was (122.1±19.1 min.) while in group (2) patients was (182.2±15.3 min.) with statistically significant relationship, only one case 5% in group (2) patients suffered hoarseness of voice.5% of group (1) patients and 10% of group (2) patients suffered from transient hypocalcemia, one patient (5%) in group (1) patients had recurrence and 4 patients (20%) of group (2) patients suffered from recurrence. Conclusion: Total thyroidectomy with prophylactic central LN dissection done in cases suffering from PTC with clinically negative cervical LNs increase operative time and post-operative hospital stay in comparison to total thyroidectomy with no statistical difference as regard to surgical complications and post-operative recurrence especially with presence of post-operative radioactive ablation.

Hypocalcemia following total thyroidectomy for benign goitre

Thyroidectomy has a complication rate lower than 5%. Most frequently, postoperative hypocalcemia has been observed. the aim of the present study was to assess Hypocalcemia following total thyroidectomy for benign goiter in head, neck, endocrine surgery unit at Alexandria main university hospital. Post-thyroidectomy hypocalcaemia (PTHC) is a recognised postoperative complication with potential wide-ranging implications and healthcare costs. Hypocalcaemia can be asymptomatic; however, clinical manifestations such as paraesthesia and muscle spasms can be distressing for the patient, while persistent untreated hypocalcaemia can be life threatening. Thyroid surgery (total or near total thyroidectomy) can lead to serious complications, including transient or permanent vocal cord palsy or severe bleeding. However, hypocalcemia is the most frequent complication after thyroid surgery. Transient hypocalcemia frequently complicates postoperative care of patients who have undergone thyroid surgery. Post-thyroidectomy hypocalcemia arises because of parathyroid removal, devascularization and damage which induce a state of transient (or permanent) hypoparathyroidism. Additional mechanisms, such as vitamin D deficiency, an acute increase in calcitonin serum levels (because of gland handling during surgery) or an “hungry bone syndrome” are believed to contribute to this process.

Factitious Cushing's syndrome, hypopituitarism, and self-provoked skin lesions: when the skin mirrors the soul.

SummaryFactitious Cushing’s syndrome (CS) is a very rare form of Münchausen syndrome. Its presentation and course are extremely heterogeneous, and diagnosis is generally challenging. We report the case of a 52-year-old woman who was initially investigated because of the occurrence of cushingoid features. Nevertheless, endocrine work-up showed very low morning plasma ACTH and serum cortisol levels. In addition, it also demonstrated central hypopituitarism and hypogonadotropic hypogonadism. Head MRI showed a small pituitary mass. Based on these results, and probably overlooking the initial clinical suspicion, general practitioner (GP) referred the patient to our Endocrine Unit for hypopituitarism. At inspection, moon face, central obesity, and bruising were evident. Multiple ulcerative skin lesions were also concentrated in the right arm and leg. Dermatology evaluation suggested that the lesions were self-provoked. For several days, the patient denied the assumption of corticosteroids, but we finally discovered that the GP’ nurse had prescribed betamethasone without the GP’s knowledge for about 2 years. In conclusion, the surreptitious assumption of corticosteroids is very rare, but the physicians should be aware that pituitary function could be impaired by high doses of corticosteroids, mimicking hypopituitarism. In these patients, a multidisciplinary approach and environmental investigation can be useful to diagnose factitious CS.Learning pointsSurreptitious assumption of corticosteroids can cause heterogeneous presentation, ranging from Cushing’s syndrome to multiple hypopituitarism.Suppression of ACTH and cortisol levels in a patient with cushingoid features firstly suggests surreptitious assumption of corticosteroids.A multidisciplinary approach can be extremely useful in patients with suspected factitious Cushing’s syndrome.Sometimes, to prove surreptitious assumption of corticosteroids needs environmental investigation.

Mapping the journey of transition: a single-center study of 170 childhood-onset GH deficiency patients.

ObjectiveTo analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP).DesignSingle- center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP.ResultsCOGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%).ConclusionThe effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD.

Aldosterone signaling defect in young infants: single-center report and review

BackgroundAldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases.MethodsA combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020.ResultsA total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240–1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene.ConclusionEtiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency.

Effects of Varicocele on Serum Testosterone Levels and Changes of Testosterone Levels after Varicocelectomy among Infertile Men: A Prospective Controlled Study

Background: Varicocele repair has been advocated as an option to prevent and treat low serum testosterone, even in men with normal semen quality. The association between clinical varicocele and impaired testosterone production is less clearly understood. Although, the conceptions of the negative impact of clinical varicocele on Leydig cell functions and the beneficial effect of varicocele repair on testosterone production have been proposed for decades. Objective: To examine the hypotheses that clinical varicoceles affect baseline serum total testosterone levels and to study the effects of varicocelectomy on serum testosterone levels and semen quality in infertile men who suffer from varicocele. Patients and Methods: This study included 100 patients (50 control and 50 cases) presented to the General Surgery and Endocrine Surgery Unit Outpatient Clinic at Mansoura University Hospitals with clinical varicocele for primary infertility. The study was conducted during the period between 1st April 2020 and end of March 2021. Results: Regarding preoperative and postoperative testosterone level among the intervention group, there were highly statistically significant increases in total testosterone as well as significant improvement in gonadal functions (significant increase in number of cases with euogonadism) after the operation among the intervention group (P < 0.001). however the percent of improvement was more than among hypogonadal compared to euogonadal. Conclusion: Varicocelectomy was demonstrated to significantly improve both sperm quality (in terms of volume, count, motility and morphology) as well as serum testosterone in infertile men, especially in cases with hypogonadism.

Less extensive surgery for low-risk papillary thyroid cancers post 2015 American Thyroid Association guidelines in an Australian tertiary centre

IntroductionThe 2015 American Thyroid Association guidelines (ATA15) consider hemithyroidectomy (HT) a viable treatment option for low-risk papillary thyroid cancers (PTCs) between 1 and 4 cm. We aimed to examine the impact of ATA15 in a high-volume Australian endocrine surgery unit. MethodsA retrospective study of all patients undergoing thyroidectomy from January 2010 to December 2019. Inclusion criteria: PTC histopathology, Bethesda V-VI, size 1–4 cm, and absence of clinical evidence of lymph node or distant metastases pre-operatively. Primary outcome was rate of HT before and after ATA15. ResultsOf 5408 thyroidectomy patients, 339 (6.3%) met the inclusion criteria – 186 (54.9%) pre-ATA15 (2010–2015) and 153 (45.1%) post-ATA15 (2016–2019). The patient groups were similar; there were no significant differences between groups in age, sex, tumour size, proportion with Bethesda VI cytology, compressive symptoms, or thyrotoxicosis. Post-ATA15, there was a significant increase in HT rate from 5.4% to 19.6% (P = 0.0001). However, there was no corresponding increase in completion thyroidectomy (CT) rate (50.0% versus 27.6%, P = 0.2). The proportion managed with prophylactic central neck dissection (pCND) fell from 80.5% to 10.8% (P < 0.0001). Pre-ATA15, the only factor significantly associated with HT was Bethesda V. In contrast, post-ATA15, HT was more likely in patients with younger age, smaller tumours, and Bethesda V. ConclusionAfter the release of 2015 ATA guidelines, we observed a significant increase in HT rate and a significant decrease in pCND rate for low-risk PTCs in our specialised thyroid cancer unit. This reflects a growing clinician uptake of a more conservative approach as recommended by ATA15.

Focused parathyroidectomy without intraoperative parathyroid hormone measurement in primary hyperparathyroidism: Still a valid approach?

BackgroundConcern regarding suboptimal cure rates has led to some endocrine surgery units abandoning focused parathyroidectomy for primary hyperparathyroidism in favor of open bilateral neck exploration or making intraoperative parathyroid hormone estimation mandatory in focused parathyroidectomy. This study explores whether focused parathyroidectomy for radiologically localized primary hyperparathyroidism without intraoperative parathyroid hormone is still a valid approach. MethodsRetrospective review of a tertiary referral endocrine surgery unit database. All parathyroidectomies for primary hyperparathyroidism over 6 years (2013–2019) were included. Lithium-induced hyperparathyroidism, reoperations, familial disease, and concurrent thyroid surgery were excluded. Characteristics and outcomes for focused parathyroidectomy and open bilateral neck exploration were compared by intention-to-treat and treatment delivered. Persistence and recurrence, conversions and complications were analyzed as endpoints. ResultsA total of 2,828 parathyroidectomies were performed and 2,421 analyzed. By intention to treat there were 1,409 focused parathyroidectomies and 1,012 open bilateral neck explorations. Focused parathyroidectomy patients were younger: 63 vs 66 years (P < .01); however, gender (77%, 79% female), preoperative peak serum calcium (2.72, 2.70 mmol/L [P = .23]), and serum parathyroid hormone (11.5, 11.0 pmol/L [P = .52]) did not differ. In total, 229 (16.3%) focused parathyroidectomies were converted to open bilateral neck exploration. Multiple gland disease was confirmed in 54.5% of converted patients. Median follow-up was 41 months (3–60 months). Persistence or recurrence requiring reoperation totaled 2.2% and did not differ between focused parathyroidectomy and open bilateral neck exploration in either intention to treat or final treatment analyses. Complications occurred in 1.2% of focused parathyroidectomy and 3.2% open bilateral neck exploration (P < .01). ConclusionsIn experienced hands and with a ready-selective approach to conversion, focused parathyroidectomy based on concordant imaging and without intraoperative parathyroid hormone may deliver equivalent cure rates to open bilateral neck exploration with significantly fewer complications. Focused parathyroidectomy without intraoperative parathyroid hormone should therefore be maintained in the endocrine surgeon’s armamentarium.

Clinical significance of serum gonadotropin and androgen levels among Egyptian overweight/obese pubertal girls.

Evaluate the association between overweight/obesity with serum gonadotropin and androgen levels in Egyptian pubertal girls. A case-control study carried out in "Obesity Clinic" of "Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU)", Pediatric Hospital, Cairo University. It included 40 overweight and obese girls and 40 age-matching normal weight (control) ones, aged 12-18 years. Anthropometric assessment (weight, height and hip and waist circumferences) was done, and waist/hip and BMI were calculated. Laboratory investigations: lipid profile, serum gonadotropin (LH, FSH), androgen (free and total testosterone), estradiol, insulin, and FBG were quantified, while insulin resistance (IR) was calculated. Hypogonadotropins (FSH and LH) and hyperandrogenaemia (total and free testosterone) were significantly prominent among obese girls. Correlation between gonadotropin, androgen and all of the studied variables, for the three studied groups (obese, overweight and control) revealed constant relations. Gonadotropin and androgens showed opposing correlations. Gonadotropin had significant negativ e correlations with the anthropometric parameters of obesity (BMI, Waist C, and W/H ratio), insulin, insulin resistance and lipid profile (triglycerides, total cholesterol and LDL), whereas androgens had significant positiv e ones. In addition, gonadotropin showed significant positiv e correlations with estradiol and HDL, while androgens showed significant negative ones. Overweight/obesity had no effect on the correlations between gonadotropin and androgen on one side, with the anthropometric measurements and laboratory investigations on the other one. Alterations in androgen levels occur at earlier ages than gonadotropin, among both overweight and obese girls.

Thyroid nodules with indeterminate cytology: association between nodule size, histopathological characteristics and clinical outcome in differentiated thyroid carcinomas\xa0\u2014\xa0a multicenter retrospective cohort study on 761 patients

A great number of surgical diagnostic procedures are performed every year for thyroid nodules that are included in undetermined cytological classes that reveal to be malignant thyroid carcinomas in one-third of cases. In the most recent guidelines, lobectomy is the most recommended surgical approach for this classes of nodules, but total thyroidectomy is the recommended treatment for undetermined nodules larger than 4 cm. The main study aim is to support or question the dimensional criteria as an independent clinical decision element for undetermined thyroid nodules management. We examined data regarding 761 patients undergoing thyroid surgery for undetermined thyroid nodules at two high-volume endocrine surgery units in Italy. Patients were divided into three groups based on the preoperative size of the nodules (N < 1, 1 < N < 4, N > 4 cm). Among the patients belonging to the different groups, we analyzed: differences in malignancy rate, histological characteristics of invasiveness and neoplastic aggressiveness, rates of recurrence and response to therapy. Nodule size (evaluated as a categorical variable and as a continuous variable) did not show any statistically significant correlation with the rate of malignancy, histopathological characteristics of tumor aggressiveness and the patient’s clinical outcome. Most of the tumors found were included in the low risk class (79.2%) and only one was classified as high risk. Follow up of cancer cases showed excellent results in terms of survival, response to therapy and disease recurrence. Malignant thyroid tumors of any size resulting from a nodule identified as cytologically indeterminate are usually characterized by a low risk follicular pattern, well-differentiated and with an excellent outcome. As a result, preferring an extended surgical attitude for undetermined nodules based on tumor size, in absence of other risk factors, can lead to overtreatment in a significant percentage of cases.

Management of NAFLD patients with advanced fibrosis.

The prevalence of non alcoholic fatty liver disease (NAFLD) has increased to 25% in the general population and could double by 2030. Liver fibrosis is the main indicator of morbidity and mortality and recent estimations suggest a substantial number of individuals with undiagnosed advanced liver disease. Strategies to monitor advanced fibrosis are essential for early detection, referral, diagnosis and treatment in primary care and endocrine units, where NAFLD and consequently liver fibrosis are more prevalent. Blood-based non-invasive methods could be used to stratify patients according to the risk of the progression of fibrosis and combined with imaging techniques to improve stratification. Powerful new diagnostic tools such as MRE and PDFF are emerging and might prevent the need for liver biopsy in the near future. The current therapeutic landscape of NAFLD is rapidly evolving with an increasing number of molecules that treat key factors involved in its progression, but that still have a limited or no ability to effectively reverse fibrosis. Management of this disease will probably require a combination of sequential and personalized treatments as a result of its complex and dynamic pathophysiology. Lifestyle interventions are still the most effective therapeutic option and should be better integrated into patient management together with specific programs of bariatric endoscopy/surgery for morbidly obese patients.

CD4 CD25 T Cells in Children with Recent Onset Type 1 Diabetes

Abstract Background: Type 1 diabetes (T1D) results from T-cell-mediated autoimmune destruction of the insulin-producing pancreatic islet Beta cells. This breakdown of immunological self-tolerance results in auto reactivity to islet self-antigens. This requires genetic susceptibility as well as environmental factors (gene environmental interaction). It is believed that numerical and functional balance between killer cells (CD4+ and CD8+) and regulatory T-cells in the pancreatic infiltrate determines the extent of Beta cell destruction. Aim of Study: To study the number and function of Treg CD4+ CD25+ T-cells in infants and children with recent onset type 1 diabetes and to compare the results with the Treg CD4+ CD25+ T-cells in the siblings of the diabetic child and control subjects. Patients and Methods: This study was performed on60 patients meeting the diagnostic criteria of type I diabetes, together with 20 children of their non diabetic siblings were recruited at the Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU) at Cairo University Children’s Hospital in the period from December 2011 to October 2012. In addition to 20 children with age and sex-matched, none of whom had either a personal or family history of diabetes or other autoim-mune pathologies as control were included in the study. Results: Show no statistically significant relation of CD4 CD25 T-lymphocytes to age, anthropometric measures (weight & height), laboratory data including HBA1C, lipid profile or thyroid function tests, the insulin dose and the severity of the case presentation (whether classic onset or DKA). Also there was no statistically significant difference between the 3 groups (diabetic – non diabetic siblings – controls) regarding CD4CD25 T- lymphocytes levels by the one-way ANOVA test. Conclusion: The sensitivity of CD4 CD25 T-lymphocytes in case of type 1 diabetes was 60% and the specificity was 47%. The PPV (positive predictive value) and the NPV (neg-ative predictive value) were 55% and 67% respectively. Such results conclude that CD4 CD25 T-lymphocytes cannot be taken as a valid marker in case of type I diabetes.

Improved Glycemic Outcomes with Early Initiation of Insulin Pump Therapy in Pediatric Postoperative Total Pancreatectomy with Islet Autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis and poor quality of life. Euglycemia is critical for islet cell survival and engraftment. We reviewed clinical care practice and hypothesized that early in-hospital transition from intravenous insulin to insulin pump therapy, managed by an endocrine unit trained on post-surgical care, would improve glucose control and impact the length of hospital stay. We completed a retrospective analysis of 40 pediatric patients who underwent TPIAT. Comparative hospitalized postoperative groups included those who received insulin intravenously, followed by multiple daily injections, subsequently managed by pump therapy (n = 14), versus those who received insulin intravenously followed by early pump therapy provided on the endocrine unit trained to manage post-surgical patients (n = 26). The outcomes analyzed included percentage of blood glucoses in target (4.44–6.66 mmol/L (80–120 mg/dL)), hypoglycemia (<3.33 mmol/L (<60 mg/dL)) and hyperglycemia (>7.77 mmol/L (>140 mg/dL)), blood glucose variability, and length of hospital unit stay post-ICU. Hospitalized patients with early transition to pump therapy on a specialized endocrine unit had a higher proportion of glucose values in the target range (61% vs. 51%, p = 0.0003), a lower proportion of hyperglycemia (15% vs. 19%, p = 0.04), and a lower proportion of hypoglycemia, though not statistically significant (3.4% vs. 4.4%, p = 0.33). Early pump users also had lower variability in glucose values over 10 days post-intravenous insulin (p = 0.001), and the post-transition median length of stay was shorter by 5 days (median: 11.5 vs. 16.5 days, p = 0.005). Early in-hospital pump therapy managed by the specialized endocrine unit improved glucose outcomes and reduced the duration of in-unit stay.

The heritability of body composition

BackgroundPhysical growth during childhood and adolescence is influenced by both genetic and environmental factors. Heritability, the proportion of phenotypic variance explained by genetic factors, has been demonstrated for stature and weight status. The aim of this study was to explore the heritability of body composition.MethodsA real-life, observational study of the children and adolescents referred to the Endocrine Unit in a tertiary medical center. In January 2018, body composition by means of bioimpedance analysis (BIA) was implemented as part of the standard intake assessment of subjects referred for endocrine consultation. The clinic BIA database was searched for subjects with the term “observation of growth” as the sole reason for referral. BIA of 114 triads of healthy subjects aged 5–18 years and their parents were analyzed. The BIA report included the following data: fat mass, fat percentage, truncal fat percentage and muscle mass. Calculated variables included: appendicular skeletal muscle mass (ASMM = the sum of muscle mass of four limbs), muscle-to-fat ratio [MFR = ASMM (kg)/fat mass (kg)] and sarcopenic index [(SI = ASMM(kg)/height (meter)²]. Data collection from medical files included pubertal stage and home address for socioeconomic position grading.ResultsThere were sex differences in body composition parameters in both the prepubertal and pubertal subjects. The boys among the prepubertal subjects had a lower fat percentage on average than girls (p = 0.020). Among the adolescents, boys on average had lower fat percentage (p = 0.011), higher sarcopenic index (p = 0.021), and higher muscle-to-fat ratio (p < 0.001), than adolescent girls. Correlation analyses between body composition parameters of all participants revealed significant correlations in the sarcopenic index of prepubertal children and their parents (boys-fathers: r = 0.380, p = 0.050; boys-mothers: r = 0.435, p = 0.026; girls-fathers: r = 0.462, p = 0.012; girls-mothers: r = 0.365, p = 0.050) and adiposity indices (fat percentage, truncal fat percentage and muscle-to-fat ratio) of prepubertal boys and their mothers (r = 0.438, p = 0.025; r = 0.420, p = 0.033, and r = 0.478, p = 0.014, respectively). There were no associations between body composition parameters of adolescents and their parents. Socioeconomic position adversely affected fat percentage in adolescent girls and mothers.ConclusionsHeritable body composition traits were demonstrated in childhood but not in adolescence, suggesting that environmental influence has a more telling effect during teenage years.

Health Status of Children and Young Persons With Congenital Adrenal Hyperplasia in the United Kingdom: Results of a Multi-Center Cohort Study

Introduction: The association between congenital adrenal hyperplasia (CAH) and increased morbidity and mortality in adult life has been well established, however, limited knowledge exists regarding the onset of co-morbidities during childhood. Objective: To establish the health status of children and young persons (CYP) with CAH in the United Kingdom. Methods: This cross-sectional multi-center study involved 14 tertiary endocrine units across the United Kingdom. We recruited 107 patients aged 8-18 years with 21-hydroxylase deficiency and 83 matched controls. We collected and analyzed demographic, clinical, and metabolic data, as well as psychological questionnaires (Strengths and Difficulties [SDQ], Paediatric Quality of Life [PedsQL]and Self-Image Profile [SIP]). Results: The majority of patients (62.2%) were diagnosed within the first month of life, most commonly presenting with ambiguous genitalia (32.7%) or salt losing crisis (25.2%). After diagnosis, 37.3% of patients required admission for adrenal crisis, 11.2% presenting three or more episodes. Of the female patients, 57.6% had undergone urogenital examination under anesthesia and 35.5% had genital surgery. Most CAH patients received glucocorticoid (GC) replacement therapy with hydrocortisone (HC) (94.3%) and the rest with prednisolone, with a mean for relative GC doses of 13.3 (±3.7) mg/m2 per day HC-equivalent. 76.6% of patients received treatment with fludrocortisone, with a mean dose of 105.0 (±50.2) µg/m2 per day. Comparing height-Standard Deviation Score (SDS), patients under 12 years were taller (p=0.011) and patients aged 12-18 years shorter (p=0.031) than controls. Bone age was advanced in patients, with a mean difference from the chronological age of 1.9 (±2.2) years. CAH patients were more frequently overweight (26.4%) or obese (22.6%) compared to controls (10.8% and 10.8% respectively, p<0.001). Five patients had high blood pressure. A small number of patients had abnormal lipid profiles: raised total cholesterol (7%), low HDL (13%), raised LDL (4%) and triglycerides (15%). Insulin resistance as defined by HOMA-IR was found in 53.8% of patients with CAH, which was comparable to healthy controls (56.3%). 15.8% of patients had SDQ scores within the “high” and “very high” categories of concern. In the PedsQL questionnaires, ‘school functioning’ was the lowest scoring dimension with a median (IQR) of 70 (55 - 80), followed by ‘emotional functioning’ with a median score of 75 (65 - 85). The SIP scores were comparable to normative values, for all age and gender groups. Conclusion: Children with CAH have increased prevalence of growth and weight gain problems, metabolic co-morbidities, as well as reduced quality of life and mental wellbeing. There is a pressing need to optimize management and monitoring strategies in CYP with CAH order to improve long-term health outcomes.

Patient Reported Experience on Consenting for Surgery – Elective Versus Emergency Patients

IntroductionInformed consent for surgery is a medical and legal requirement, but completing these does not necessarily translate to high patient satisfaction. This patient-reported experience study aimed to examine the surgical consent process, comparing the patients’ experience in elective and emergency settings. MethodsOver a 6-mo period, postoperative patients at The Alfred Hospital Breast and Endocrine Surgical Unit were invited to participate in a survey on the surgical consent process – including perceived priorities, information provided and overall experience. Standard statistical techniques were used, with a significant P-value of < 0.05. ResultsA total of 412 patients were invited, with 130 (32%) responses. More patients underwent elective surgery (N= 90, 69%) than emergency surgery (N = 40, 31%). Emergency patients were more likely to sign the consent form regardless of its contents (93% versus 39%, P < 0.001) and more likely to be influenced by external pressures (63% versus 1%, P < 0.001). Elective patients were more likely to want to discuss their surgery with a senior surgeon (74% versus 23%, P < 0.001) and more likely to seek advice from external sources (83% versus 10%, P < 0.001). Both groups highly valued the opportunity to ask questions (67% versus 63%, P = 0.65). ConclusionThis study shows patients have a range of different priorities in preparation for surgery. Therefore, each consent process should be patient-specific, and focus on providing the patient with quality resources that inform decision-making.