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Minimally invasive parathyroid carcinoma-A missing entity between parathyroid adenoma and carcinoma: Scintigraphic and histological features

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

Purpose Minimally invasive parathyroid carcinoma (MIPC) is clinically and biochemically comparable with parathyroid adenoma (PA) though histopathologically differ from PA. MIPC is an intermediate of PA and parathyroid carcinoma (PC). In literature, there is no definite criterion to diagnose MIPC. Our aim was to evaluate and characterize the imaging and biochemical parameters with histological characteristics of MIPC. Methodology Ten patients with MIPC were recruited from (single centre) Indian PHPT registry () from January 2014 to July 2018. Clinical, biochemical, imaging and histological features of MIPC patients were reviewed. Results The mean age of MIPC patients (n = 10; 3 males) was 39.9 +/- 11.3 years (range: 17-50). All patients had an elevated preoperative parathyroid hormone (iPTH) level ranging from 427 to 2138 pg/mL (median: 1328). MIBI scan showed intensely avid and enlarged parathyroid tumours in all patients; LIPT in 6, RIPT in 3 and ectopic mediastinal in 1 with mean size of the tumours was 2.8 +/- 1.1 cm. The mean of maximum standardized uptake value (SUVmax) of MIPC in F-18 fluorocholine PET/CT was 6.7 +/- 1.1 (range 6.0-8.3). The mean tumour weight was 12 +/- 9.5 g (range: 1.09-28). All MIPC patients had identified capsular invasion in 80% and vascular invasion in 50% only but there was no local invasion, lymph nodal or distant metastasis. The mean Ki-67 labelling index was 3.2 +/- 2.7 (range 1.1-10). Conclusion The study concluded that MIPC patients are less aggressive (on the basis of imaging and histopathological findings) and should be differentiated from parathyroid adenoma and carcinoma.

IF:2.9

Reduced uterine volume after induction of puberty in women with hypogonadism

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

Objective Adequate uterine growth is an essential component of pubertal induction with exogenous oestradiol in those with hypogonadism. Poor uterine development will render the individual vulnerable in the context of fertility. We assessed uterine size using ultrasound in those who had undergone pubertal induction treatment compared with a reference group who had experienced spontaneous puberty. Design This is a single-centre, retrospective, cross-sectional study of women who underwent pubertal induction compared with a reference group. Patients Ninety-five women with hypogonadism who had previously undergone pubertal induction and were receiving maintenance oestrogen replacement as adults were recruited: 48 women with Turner syndrome, 32 with premature ovarian insufficiency and 15 with gonadotrophin deficiency. The reference group consisted of 35 nulliparous women attending with male factor subfertility with a normal pelvis on ultrasonography. Measurements Pelvic ultrasound was performed by a single observer. Uterine dimensions (total length, anterior-posterior (AP), transverse, uterine volume and fundal cervical AP ratio (FCR) measurements) were recorded. Clinical details were also recorded. Results Those with hypogonadism had significantly reduced uterine dimensions compared with the reference group (uterine length 64 mm vs 71 mm P = <.05, uterine volume 28.9 mL vs 43.9 mL P = <.05). All women in the reference group attained a mature uterine configuration with a FCR >1, compared with 84% of those with hypogonadism (P = .01). A total of 24% and 48% of the diagnostic group had total uterine length and uterine volume measurements less than the 5th percentile of the reference group, respectively. In a subgroup of 22 women in whom serum oestradiol concentrations could be analysed, there was a positive correlation between this parameter and uterine volume. Conclusion Despite standard oestrogen therapy, uterine growth is often compromised in those with hypogonadism. Uterine health has historically been overlooked in pubertal induction protocols; however, with increasing options for fertility treatment, adequate uterine development is crucial. Given the variation in uterine size witnessed, a more tailored approach to treatment with regular monitoring of uterine dimensions should be advocated.

IF:2.9

Blood pressure in pregnancy-A stress test for hypertension? Five-year, prospective, follow-up of the ROLO study

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

Objective To investigate whether maternal blood pressure (BP) below the diagnostic criteria of hypertensive disorders of pregnancy (HDP) is associated with maternal BP 5 years later. Design Prospective, observational study. Setting Dublin, Ireland (2007-2011). Sample Three hundred twenty-nine women from the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet to prevent the recurrence of macrosomia). Methods Maternal BP measurements were taken during pregnancy (13, 28 and 34 weeks' gestation and day 1 postpartum) and at the 5-year follow-up. Systolic BP (SBP) and diastolic BP (DBP) were categorized as normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP 120-129 and DBP < 80 mm Hg), HTN stage 1 (SBP 130-139 or DBP 80-89 mm Hg) or HTN stage 2 (SBP >= 140 or DBP >= 90 mm Hg) at each timepoint. Main Outcome Measures Maternal blood pressure at the 5-year follow-up. Results Women with elevated BP at 28 and 34 weeks' gestation had 2.68 (95% CI: 1.36-5.26) and 2.45-fold (95% CI: 1.22-4.95) increased odds of HTN stage 1 respectively, at the 5-year follow-up, compared to those with normal BP in pregnancy. Conclusion Elevated BP at 28 and 34 weeks' gestation was associated with an increased risk of HTN stage 1 at 5 years later. Thus, raised BP, below the diagnostic criteria of HDP, could be flagged for follow-up postpartum.

IF:2.9

'Peptide receptor radionuclide therapy in the management of advanced pheochromocytoma and paraganglioma: A systematic review and meta-analysis'

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

Objective Inoperable and metastatic pheochromocytomas and paragangliomas (PPGLs) present a therapeutic challenge with current treatment options being limited to radiolabelled meta-iodo-benzyl-guanidine (MIBG) and systemic chemotherapy. Peptide receptor radionuclide therapy (PRRT) seems to be a promising option for these patients with few studies reporting favourable response. This systematic review was conducted to evaluate the efficacy and safety of PRRT in patients with advanced PPGLs. Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in PubMed, Scopus and Embase were made using relevant keywords and articles up to May 2019 were included. Data on efficacy and toxicity were extracted from the individual articles, and pooled estimates were generated using meta-analysis. Results Twelve articles consisting of 201 patients with advanced PPGLs were included. Overall, treatment with PRRT achieved an objective response rate of 25% (95% CI: 19%-32%) and a disease control rate of 84% (95% CI: 77%-89%). Clinical and biochemical responses were seen in 61% and 64% of the patients, respectively. Among the PRRTs, similar tumour response rates were noted for Y-90-yttrium- and Lu-177-lutetium-based agents. Treatment-related adverse effects were minimal with grade 3/4 neutropenia, thrombocytopenia, lymphopenia and nephrotoxicity observed in 3%, 9%, 11% and 4% of the patients, respectively. Treatment discontinuation was noted in five out of 102 patients. Conclusions Peptide receptor radionuclide therapy is a safe and efficacious treatment option for advanced PPGLs and may be considered a viable alternative to chemotherapy and I-(131) MIBG.

IF:2.9

Genetic scores for BMI related to metabolically unhealthy obesity in an older Chinese population

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

Objective In this study, a genetic risk score (GRS) for the body mass index (BMI) tested and built using a large sample of Chinese individuals aged at least 50 years in southern China. We collected information regarding the participants' weights at 20 years of age and middle age and tested the BMI-GRS effect modes. Methods This study involved a prospective study design. The genetic data of the participants in from the Guangzhou Biobank Cohort Study and selected BMI-related single-nucleotide polymorphisms (SNPs) were used to establish the GRS. Results We included 13 597 participants with 12 SNPs. After adjusting for covariates, the high-GRS group was 36% (95% CI: 25%-48%) and 34% (95% CI: 23%-47%) more likely of being overweight at baseline and follow-up, respectively, and 56% (95% CI: 34%-82%) and 49% (95% CI: 29%-72%) more likely of being obese at baseline and follow-up, respectively, compared with the low-GRS group (P-value for all trends <.05). The RRs for the incidences of metabolically healthy and unhealthy obese (MHO and MUO, respectively) individuals in the high-GRS group were 0.94 (95% CI: 0.65-1.35) and 1.28 (95% CI: 1.00-1.63), respectively. Conclusion High-GRS participants were more likely to be overweight/obese at baseline and follow-up, and this relationship exhibited a dose-response relationship. The GRS was also associated with MUO.

IF:2.9

Primary adrenal insufficiency: New genetic causes and their long-term consequences

期刊: CLINICAL ENDOCRINOLOGY, 0; ()

Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that requires urgent diagnosis and treatment. Whilst the most common causes are congenital adrenal hyperplasia (CAH) in childhood and autoimmune adrenal insufficiency in adolescence and adulthood, more than 30 other physical and genetics cause of PAI have been reported. Reaching a specific diagnosis can have implications for management and for monitoring associated features, as well as for counselling families about recurrence risk in siblings and relatives. Here, we describe some recent insights into the genetics of adrenal insufficiency and associated molecular mechanisms. We discuss (a) the role of the nuclear receptors DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human adrenal and reproductive dysfunction; (b) multisystem growth restriction syndromes due to gain-of-function in the growth repressors CDKN1C (IMAGE syndrome) and SAMD9 (MIRAGE syndrome), or loss of POLE1; (c) nonclassic forms of STAR and P450scc/CYP11A1 insufficiency that present with a delayed-onset adrenal phenotype and represent a surprisingly prevalent cause of undiagnosed PAI; and (d) a new sphingolipidosis causing PAI due to defects in sphingosine-1-phosphate lyase-1 (SGPL1). Reaching a specific diagnosis can have life-long implications for management. In some situations, milder or nonclassic forms of these conditions can first present in adulthood and may have been labelled, "Addison's disease."

Male sickle cell patients, compensated transpubertal hypogonadism and normal final growth

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (5)

Objective Investigate the gonadal hormonal function in sickle cell individuals. Context Sickle cell disease (SCD) is associated with delayed physical and sexual development, and it has been related to both primary testicular failure and hypothalamo-pituitary-gonadal axis abnormalities. Design The study of the pituitary gonadotrophin reserve was done evaluating the hormonal levels before and after stimulation by gonadoliberin. Patients Male patients with homozygous SCD (18-39 years, median = 29.5 years). Measurements Gonadal function was evaluated through clinical parameters and the hormonal quantification. Results Although low body weight and other clinical signs of undernutrition such as clinical hypoandrogenism and the extreme retardation of puberty were seen in these patients, final stature and hormonal testicular reserve to hCG stimulation were proved to be normal according to our previous data. In the present investigation, the basal luteotropic gonadotropin (LH), follicle-stimulating hormone (FSH) and testosterone (T) levels were similar between the patients and controls. Prostate-specific antigen (PSA) levels-used as a biochemical marker of androgenicity, mainly in puberty-were lower in the patients than in the controls and were only correlated with T. A subtle abnormality in the pituitary responsivity to gonadotropin-releasing hormone (GnRH) was disclosed, with a higher response to LH 60 minutes after stimulation in patients than in controls. Conclusions These data, in addition to both the clinical and biochemical signs of hypoandrogenism associated with normal to elevated T levels strongly suggest a peripheral origin of hypogonadism, which is probably due to androgen resistance in the patients with SCD.

IF:2.9

Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (5)

Objective To investigate the impact of mandatory iodine fortification (IF) on the incidence of nosological subtypes of overt thyrotoxicosis and hypothyroidism. Design We identified and scrutinized all possible new cases of overt thyrotoxicosis and hypothyroidism in an open cohort in Northern Jutland (n = 309 434; 1 January 1997) during the years 2014-2016. Individual medical history was evaluated to verify and detail the incidence of overt thyroid dysfunction and for classification into nosological subtypes. A number of cases were excluded during final verification due to spontaneous normalization of thyroid function, as they had no medical history suggesting a known condition, which could transiently affect thyroid function (subacute/silent thyroiditis, PPTD and iatrogenic thyroid dysfunction). An identical survey was conducted in 1997-2000 prior to mandatory IF of salt (13 mu g/g) that was in effect from year 2001. Results The standardized incidence rate (SIR) of verified overt thyrotoxicosis decreased markedly from 97.5/100 000/year in 1997-2000 to 48.8 in 2014-2016 (SIRR: 0.50 [95% CI: 0.45-0.56]). This was due to a distinct decrease in the SIR of multinodular toxic goitre (SIRR: 0.18 [0.15-0.23]), solitary toxic adenoma (SIRR: 0.26 [0.16-0.43]) and to a lesser degree Graves' disease (SIRR: 0.67 [0.56-0.79]). SIR for overt hypothyroidism was unaltered by 2014-2016 (SIRR: 1.03 [0.87-1.22]). However, age distribution shifted with more young and fewer elderly cases of verified overt hypothyroidism. Conclusion Mandatory IF caused a substantial reduction in SIR of verified overt thyrotoxicosis (especially of nodular origin) while avoiding an increase in SIR of verified overt hypothyroidism.

IF:2.9

Fracture rate in women with oestrogen deficiency - Comparison of Turner syndrome and premature ovarian insufficiency

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

Objective Women with early-onset oestrogen deficiency are at risk of reduced bone mineral density (BMD). We sought to assess fracture history and BMD in women with Turner syndrome (TS) and premature ovarian insufficiency (POI). Design A cross-sectional observational study. Patients Two hundred and sixty seven women with TS (median age 34.3 years) and 67 women with POI (median age 28.1 years). Measurements A questionnaire was used to collect data on fracture history, co-morbidities and drug history including age at first oestrogen exposure. Clinical data included height, weight, serum vitamin D and hip and spine T-scores, which were adjusted for height and age. Fractures were subdivided into major osteoporotic fractures (MOF) and 'other' fracture types. Results Overall fracture rate was similar in women with TS and POI (82 [30.5%] vs 22 [32.8%] respectively, P = .74). Compared to women with POI, those with TS had more fractures at MOF sites (30.2% vs 52.7%, P = .012) and fewer phalangeal fractures (27.9% vs 9.8%, P = .005). There was no difference in BMD between women who sustained a fracture compared to those who did not. Women with TS who fractured were more likely to suffer from hearing impairment compared to those with no fracture (62.2% vs 48.1%, P = .045). Conclusions TS is not associated with an overall excess risk of bone fracture. The higher rate of fractures at MOF sites in women with TS may be secondary to hearing impairment, thin cortical bone and abnormal bone remodelling.

IF:2.9

Seated saline infusion test in predicting subtype diagnosis of primary aldosteronism

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

Context Although saline infusion test is widely used as a confirmatory test for primary aldosteronism (PA), it is reportedly less sensitive in patients in whom aldosterone is responsive to the upright position by performing it in recumbent position. Based on a single-centre experience, seated saline infusion test (SSIT) has been reported to be highly sensitive and superior to recumbent testing in identifying both unilateral and bilateral forms of PA. However, due to limited participants number, the utility of SSIT needs to be validated in other series. Objective This study aimed to evaluate the accuracy of SSIT in determining the PA subtypes compared with adrenocorticotropic hormone stimulation test under dexamethasone suppression (Dex-AT). Patients and Setting Sixty-four patients with PA who underwent both SSIT and Dex-AT were included. Subtype diagnosis of PA was determined by adrenal venous sampling (AVS) (16 unilateral and 48 bilateral forms). Main Outcome Measure Plasma aldosterone concentrations (PACs) were measured after SSIT and Dex-AT. Results The area under the receiver operating characteristic (ROC) curve for diagnosing unilateral PA was greater in SSIT than that in Dex-AT (0.907 vs. 0.755; P = .023). ROC curve analysis predicted optimal cut-off PACs of 13.1 ng/dL (sensitivity, 93.8%; specificity, 79.2%) for SSIT and 34.2 ng/dL (sensitivity, 75.0%; specificity, 68.8%) for Dex-AT. Conclusions Seated saline infusion test has superior accuracy in subtype diagnosis of PA compared with Dex-AT. SSIT can be a sensitive test for determining patients who require AVS prior to surgery.

IF:2.9

Maternal cognitive function during pregnancy in relation to hypo- and hyperthyroxinemia

期刊: CLINICAL ENDOCRINOLOGY, 2019; 91 (6)

ObjectiveTo assess a possible relationship between maternal cognitive dysfunction during pregnancy and hypothyroxinemia, adjusted for major confounders. BackgroundThyroid dysfunction in general is associated with cognitive dysfunction. Cognitive dysfunction is common during pregnancy. DesignProspective follow-up study from 12 to 32 weeks of pregnancy. Participants2082 healthy pregnant women. MeasurementsCognitive function, depression and sleeping problems were assessed by self-report questionnaires at 12, 22 and 32 weeks of gestation, higher scores reflecting more symptoms. FT4, TSH and TPO-Ab were assessed at 12 weeks of gestation. Definitions: healthy (euthyroxinemia) control group: FT4 within 10-90th percentiles, without elevated TPO-Ab titres and TSH within first trimester-specific reference range (0.23-4.0 mU/L). Hypothyroxinemia: FT4 <2.5th percentile with TSH within first trimester-specific reference range. Poor cognitive function: a score >1 SD > mean on the cognitive function scale. ResultsA total of 54 women showed hypothyroxinemia and 1476 women had euthyroxinemia. At 12 weeks, multiple logistic regression showed that poor cognitive function was independently related to hypothyroxinemia: OR: 2.9 (95% CI: 1.6-5.4), adjusted for depression (OR: 3.1; 95% CI: 2.7-4.6) and sleeping problems (OR: 2.8, 95% CI: 1.9-3.9). TPO-Ab + women with hypothyroxinemia had the highest levels of cognitive dysfunction. Other cut-offs of hypothyroxinemia (<5th or <10th percentile with normal TSH) showed similar results. GLM-ANOVA showed that throughout pregnancy women with hypothyroxinemia at 12 weeks had significantly higher cognitive dysfunction scores compared with the healthy controls: F = 12.1, P = .001. ConclusionsWomen with hypothyroxinemia during early gestation are at risk for poor cognitive function throughout gestation, adjusted for depression and sleeping problems.

IF:2.9

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