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Open access

Teodoro Durá-Travé, Fidel Gallinas-Victoriano, María Malumbres-Chacon, Lotfi Ahmed-Mohamed, María Jesús Chueca Guindulain, and Sara Berrade-Zubiri


The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status.


Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- to 8- years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves.


There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (p<0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89% and 82% respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls.


Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, eliminating the need for GnRH stimulation testing.

Open access

Liubov G. Yanevskaya, Tatiana Karonova, Ilya V Sleptsov, Marina Evgenevna Boriskova, Aluza Ramilevna Bakhtiyarova, Roman A Chernikov, Karina Alexandrovna Pogosian, Alena Timurovna Andreeva, Denis Andreevich Lebedev, Elena Nikolaevna Grineva, and John P. Bilezikian

Objective. The aim of our study was to investigate the distribution of the PHPT clinical manifestations and biochemical features in patients who underwent parathyroidectomy.

Materials and methods. Medical records of 449 patients from three Medical Centers (Saint-Petersburg, Russia), hospitalized during a period from 2011 to 2018, were reviewed. History and anthropometric data, laboratory results (iPTH, total and  iCa, phosphorus, ALP, 24-h urinary calcium, 25(OH)D) and imaging data (ultrasonography, scintigraphy, CT/MRI scan, DXA) were analyzed.

Results. Three hundred ninety-four patients were included in the final analysis. Median age was 60 years with 94.2 % being women. Symptomatic disease was evident in 222 (56.4%) patients, asymptomatic in 172 (43.6%). Skeletal involvement was more common for women, while frequency of other manifestations did not differ in both genders. There was no difference between symptomatic and asymptomatic patients in age. Serum iPTH level was higher in symptomatic patients (202.9 and 181.0 pg/ml, p=0.022). Serum 25(OH)D level was estimated in few patients and negatively correlated with PTH (r= -0.294, p=0.005), iCa (r= -0.268, p=0.010) and total Ca (r= -0.284, p=0.014) levels. Manifestations of CVD were observed in 67.7% of cases and affected equally both symptomatic and asymptomatic patients (70.7% and 63.4%, p=0.076). Both age and BMI were higher in patients with CVD, whether or not they were symptomatic (62 and 53 years, p<0.0001; 30.4 vs 26.0 kg/m2, p<0.0001, respectively).

Conclusions. This experience illustrates that symptomatic phenotype is still the most common form of PHPT.

Open access

Jan Roar Mellembakken, Azita Mahmoudan, Lars Mørkrid, Inger Sundström-Poromaa, Laure Morin-Papunen, Juha S. Tapanainen, Terhi Piltonen, Angelica Linden Hirschberg, Elisabeth Stener-Victorin, Eszter Vanky, Pernille Ravn, Richard Christian Jensen, Marianne Skovsager Andersen, and Dorte Glintborg


Objective: Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) in normal weight women with PCOS and controls matched for age and BMI?

Methods: From a Nordic cross-sectional base of 2,615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI<25 kg/m2 (512 women with PCOS according to Rotterdam criteria and 281 age and BMI-matched controls). Participants underwent measurements of BP and body composition (BMI, waist-hip ratio), lipid status, and fasting BG. Data were presented as median (quartiles).

Results: The median age for women with PCOS were 28 (25; 32) years, and median BMI was 22.2 (20.7; 23.4) kg/m2. Systolic BP was 118 (109; 128) mmHg in women with PCOS compared to 110 (105; 120) mmHg in controls, and diastolic BP was 74 (67; 81) vs. 70 (64; 75) mmHg, both p<0.001. The prevalence of women with BP ≥140/90 mmHg was 11.1% (57/512) in women with PCOS vs. 1.8% (5/281) in controls, p<0.001. In women ≥ 35 years the prevalence of BP ≥140/90 mmHg was comparable in women with PCOS and controls (12.7% vs. 9.8%, p=0.6). Using multiple regression analyses, the strongest association with BP was found for waist circumference, fasting BG and total cholesterol in women with PCOS.

Conclusions: Normal weight women with PCOS have higher BP than controls. BP and metabolic screening are relevant also in young normal weight women with PCOS.

Open access

Stine Linding Andersen and Stig Andersen

The management of hyperthyroidism in pregnant patients has been a topic of raised clinical awareness for decades. It is a strong recommendation that overt hyperthyroidism of Graves’ disease in pregnant women should be treated to prevent complications. The consequences of hyperthyroidism in pregnancy are less studied than hypothyroidism, and a literature review illustrates that the main burden of evidence to support current clinical guidance emerges from early observations of severe complications in Graves’ disease patients suffering from untreated hyperthyroidism in the pregnancy. On the other hand, the more long-term consequences in children born to mothers with hyperthyroidism are less clear. A hypothesis of fetal programming by maternal hyperthyroidism implies that excessive levels of maternal thyroid hormones impair fetal growth and development. Evidence from experimental studies provides clues on such mechanisms and report adverse developmental abnormalities in the fetal brain and other organs. Only few human studies addressed developmental outcomes in children born to mothers with hyperthyroidism and did not consistently support an association. In contrast, large observational human studies performed within the last decade substantiate a risk of teratogenic side effects to the use of antithyroid drugs in early pregnancy. Thus, scientific and clinical practice are challenged by the distinct role of the various exposures associated with Graves’ disease including the hyperthyroidism per se, the treatment, and thyroid autoimmunity. More basic and clinical studies are needed to extend knowledge on the effects of each exposure, on the potential interaction between exposures and with other determinants, and on the underlying mechanisms.

Open access

Nardin Aslih, Mediea Michaeli, Diana Mashenko, Adrian Ellenbogon, Oshrit Lebovitz, Yuval Atzmon, and Einat Shalom-Paz

Aim: To find a cutoff ratio of estradiol/metaphase II oocyte (E2/M2) ratio and to evaluate the correlation with patients' characteristics, embryo morphokinetics using EmbryoScope™ and IVF cycle outcomes.

Material and Methods: For this retrospective cohort study, records of all fresh cycles that were cultured and scored by EmbryoScope™ were evaluated. The peak E2/M2 ratio was calculated on the day of human chorionic gonadotropin (hCG) administration and correlated to embryo morphokinetic quality and cycle outcomes. A receiver operating characteristics analysis was calculated for the E2/M2 ratio and clinical pregnancy rates.

Results: A total of 2461 oocytes were collected from 319 patients. Receiver operating characteristics analysis revealed a cut-off of 204 as a discriminative point to predict clinical pregnancy with a sensitivity of 69.5% and specificity of 62.1% (P<0.001). E2/M2 >204 group were older, had higher E2 concentration, fewer M2 oocytes despite elevated gonadotrophin doses. E2/M2 ratio ≤ 204 was correlated with higher fertilization rate, better embryo quality, higher pregnancy and live birth rates, and more frozen embryos.

Conclusion: E2/M2 ratio<204 yielded the best probability to achieve good quality embryos with good morphokinetic scores and better pregnancy outcomes and may be used to predict IVF cycle outcomes. Advanced maternal age and low ovarian response received higher concentrations of gonadotrophins, which resulted in higher E2/M2 ratio. Milder stimulation to those patients may improve their cycle outcomes.

Open access

Angelica Amorim Amato, Hailey Britt Wheeler, and Bruce Blumberg

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An Endocrine-Disrupting Chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens are chemicals, including some EDCs that promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This “generational toxicology” is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.

Open access

Karim Gariani and François R Jornayvaz

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. NAFLD encompasses a whole spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The latter can lead to hepatocellular carcinoma. Furthermore, NASH is the most rapidly increasing indication for liver transplantation in western countries and therefore represents a global health issue. The pathophysiology of NASH is complex and includes multiple parallel hits. NASH is notably characterized by steatosis as well as evidence of hepatocyte injury and inflammation, with or without fibrosis. NASH is frequently associated with type 2 diabetes and conditions associated with insulin resistance. Moreover, NASH may also be found in many other endocrine diseases such as polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or glucocorticoid excess, for example. In this review, we will discuss the pathophysiology of NASH associated with different endocrinopathies.

Open access

Fizzah Iqbal, William Adams, Ioannis Dimitropoulos, Samiul Muquit, and Daniel Flanagan


Pituitary apoplexy is an acute syndrome of haemorrhage or infarction into the pituitary. The condition is relatively well described. Less well described is sub-acute presentation of the same condition


To compare the clinical presentation and natural history of subacute pituitary haemorrhage/ infarction with pituitary apoplexy (acute).


Retrospective analysis of a consecutive cohort of 55 patients (33 with pituitary apoplexy, 22 with subacute disease) presenting to University Hospital Plymouth between 1994 and 2019. Comparison of the clinical, endocrinological and radiological features at presentation. Comparison of clinical treatment and subsequent outcomes for the two groups


There were no significant differences in predisposing factors for the two groups. Acute headache was more frequent in the acute group. Chronic headache was common in both groups prior to presentation. Low sodium was more common at presentation in the acute group (11/26 vs 2/19 p= 0.02) otherwise there were no differences in endocrine deficit at presentation. A significant proportion showed an improvement in endocrine function at follow up (acute 8/31, subacute 5/21 p = 1.0). MRI characteristics were variable at presentation and follow up in both groups. Ring enhancement with contrast was more frequent in acute (14/20 vs 3/11 p= 0.03). This appearance resolved at follow up in the majority.


Pituitary apoplexy has a characteristic and dramatic presentation. Subacute pituitary haemorrhage/ infarction shows similar natural history and outcome. These would appear to represent a spectrum of the same condition.

Open access

Sirazum Choudhury, Tricia Tan, Katharine Lazarus, and Karim Meeran

The introduction of adrenocortical extract in 1930, improved life expectancy to between two and five years with further increases seen with the introduction of cortisone acetate from 1948. Most patients are now treated with synthetic hydrocortisone, and incremental advances have been made with optimisation of daily dosing and the introduction of multi-dose regimens. Today there remains a significant mortality gap between individuals with treated hypoadrenalism and the general population. It is unclear whether this gap is a result of glucocorticoid over-replacement, under-replacement or loss of the circadian and ultradian rhythm of cortisol secretion, with detrimental risk of excess glucocorticoid at later times in the day. The way forwards involves replacement of the diurnal cortisol rhythm with better glucocorticoid replacement regimens. The steroid profile produced by both prednisolone and dual-release hydrocortisone (Plenadren), provide a smoother glucocorticoid profile than standard oral multidose regimens of hydrocortisone and cortisone acetate. The individualisation of prednisolone doses and lower bioavailability of Plenadren offer reductions in total steroid exposure. Although there is emerging evidence of both treatments offering better cardiometabolic outcomes than standard glucocorticoid replacement regimens, there is a paucity of evidence involving very low dose prednisolone (2-4 mg daily) compared to the larger doses (~7.5 mg) historically used. Data from upcoming clinical studies on prednisolone will therefore be of key importance in informing future practice.

Open access

Satoshi Higuchi, Hideki Ota, Yuta Tezuka, Kazumasa Seiji, Hidenobu Takagi, Jognmin Lee, Yi-Wei Lee, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Masataka Kudo, Fumitoshi Satoh, and Kei Takase

Objectives: This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner.

Design: A retrospective, single center, observational study.

Methods: We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and post-contrast myocardial T1-mapping images.

Results: PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio [aOR] = 1.06 [95% CI: 1.030–1.096], p<0.01), end-systolic volume index (ESVI: 1.06 [1.017–1.113], p<0.01), stroke index (SI: 1.07 [1.020–1.121], p<0.01), cardiac index (CI: 1.001 [1.000–1.001], p<0.01), and native T1 (1.01 [1.000–1.019], p = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, p<p0.01), ESVI (0.26, p<p0.01), and SI (0.18, p=0.03); and between ARR and EDVI (0.25, p<0.01), ESVI (0.24, p<0.01), and native T1 (0.17, p = 0.047).

Conclusions: APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting higher risk of volume overload and myocardial damage.