To compare glycated hemoglobin (HbA1c) and the oral glucose tolerance test (OGTT) for the diagnosis of prediabetes and diabetes in young women with polycystic ovary syndrome (PCOS). This cross-sectional study included 154 women aged 20-40 years with a diagnosis of PCOS, who were screened for prediabetes and diabetes by the OGTT and HbA1c. Women with diabetes, hyperprolactinemia, thyroid or adrenal diseases, and anemia and users of hormonal contraception or corticosteroids were excluded. Clinical, biochemical and ultrasound data were collected from the electronic medical records. The women were classified as having normal glucose metabolism, prediabetes, or diabetes based on the diagnostic tests. Sensitivity and specificity were calculated and the Kappa method was used to assess agreement between the two methods. According to the OGTT and HbA1c values, 79.2% and 76% of the women were within the normal range, respectively, 16.8% and 19.5% had prediabetes, and 4% and 4.5% had diabetes (p > .05). The Kappa coefficient of 0.41 (95% confidence interval: 0.24-0.58) indicated medium agreement between methods. Considering the OGTT as the gold standard, the specificity of HbA1c was 89.5% and sensitivity was 85.7% in the diagnosis of prediabetes and 100% and 66.7%, respectively, in the diagnosis of diabetes. The HbA1c, when compared to the OGTT, showed high sensitivity and specificity in the diagnosis of prediabetes in young women with PCOS.

Worldwide, adults and children are at risk of adrenal insufficiency largely due to infectious diseases and adrenal suppression from use of anti-inflammatory glucocorticoids. Home waking salivary cortisone is an accurate screening test for adrenal insufficiency, it has potential to reduce costs, and patients prefer it to the adrenocorticotropin (ACTH) (synacthen) stimulation test. We carried out a service evaluation of home waking salivary cortisone in clinical care to identify implementation barriers. Service evaluation in a centre where 212 patients referred for adrenal insufficiency had a waking salivary cortisone. Problems encountered during testing were recorded and patient feedback, via focus groups,collected. From all patients providing a waking salivary cortisone 55% had a normal test, 23% adrenal suppression, and 22% an equivocal result requiring a clinical centre ACTH stimulation test. The median (interquartile range [IQR]) for the time of the saliva sample was 07:40 (07:00-08:40). The median (IQR) days between collection and (i) delivery to local laboratory was1 (0.25-2) day; (ii) reporting by local laboratory was 13 (11-18) days. Patients considered the test is "easy to do" and preferred it to the inpatient ACTH stimulation test. The principal challenge to clinical implementation was results reporting to clinicians due to delays at the local laboratory. This service evaluation provides real-world evidence that home waking salivary cortisone is an effective, practical screening test for adrenal insufficiency. It identified key barriers to testing implementation that need to be addressed when introducing the test to a health service.

Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. National, multicenter and retrospective study. All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017. Diagnostic tests of CD and tumour size. Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery.

The hypothalamic-pituitary-testicular axis is characterised by the existence of major functional changes from its establishment in fetal life until the end of puberty. The assessment of serum testosterone and gonadotrophins and semen analysis, typically used in the adult male, is not applicable during most of infancy and childhood. On the other hand, the disorders of gonadal axis have different clinical consequences depending on the developmental stage at which the dysfunction is established. This review addresses the approaches to evaluate the hypothalamic-pituitary-testicular axis in the newborn, during childhood and at pubertal age. We focused on the hormonal laboratory and genetic studies as well as on the clinical signs and imaging studies that guide the aetiological diagnosis and the functional status of the gonads. Serum gonadotrophin and testosterone determination is useful in the first 3-6 months after birth and at pubertal age, whereas AMH and inhibin B are useful biomarkers of testis function from birth until the end of puberty. Clinical and imaging signs are helpful to appraise testicular hormone actions during fetal and postnatal life. The interpretation of results derived from the assessment of hypothalamic-pituitary-testicular in paediatric patients requires a comprehensive knowledge of the developmental physiology of the axis to understand its pathophysiology and reach an accurate diagnosis of its disorders.

To determine all-cause in-hospital mortality associated with severe hypernatraemia and the causes, comorbidities, time to treatment, discharge destination and postdischarge mortality. Retrospective observational cohort study. Severe hypernatraemia, (sodium concentration ≥ 155 mmol/L), at any time during a tertiary hospital admission in Melbourne, Australia, 1 January 2019 to 31 December 2019 (pre-COVID19). Deaths, Charlson Comorbidity Index (CCI), hypernatraemia causes, time to treatment, discharge destination. One hundred and one inpatients: 64 community-acquired, 37 hospital-acquired. In-hospital mortality was 38%, but cumulative mortality was 65% by 1 month after discharge, with only a minor further increase at 6 and 12 months. After adjusting for peak sodium concentration, the community acquired group had significantly reduced odds of in-hospital mortality (odds ratio 0.15, 95% confidence interval [0.04-0.54], p = .003). Iatrogenic factors were present in 57% (21/37) of the hospital-acquired group. Only 55% of all cases received active sodium directed treatment. Time to start treatment did not affect outcomes. High levels of comorbidity were present, median CCI (IQR) was 6 (5-8) in the community and 5 (4-7) in the hospital group. Dementia prevalence was higher in the community group, 66% (42/64) versus 19% (7/37) (p = .001). Infection was the most common precipitant with 52% (33/64) in the community and 32% (12/37) in the hospital group. Of the survivors, 32% who had been living independently required residential care after discharge. Mortality was high and loss of independence in survivors common. To potentially improve outcomes, hypernatraemia-specific guidelines should be formulated and efforts made to reduce system and iatrogenic factors.

We designed a longitudinal study to investigate the association between the ages of central pubertal activation and the appearance of clinical signs of puberty and determined total luteinizing hormone (LH) immunoreactivity in daytime- and nocturnal sleeptime-excreted urine samples. Thirty healthy volunteers (17 boys and 13 girls, aged 3.4-15.2years and 4.3-14.3years, respectively, at the beginning of the study) were included. Male and female subjects were followed for an average of 15 visits during 5.5 and 5.8 years on average, respectively. At each visit, subjects provided 24-h urine samples divided into nocturnal sleeptime and waketime portions according to the participant's sleep-and-wake rhythm. Total urinary LH (U-LH) concentrations were measured in duplicate by Delfia® IFMA (Wallac), which has been designed specifically to detect intact LH as well as the beta subunit and its core fragment, but not the human chorionic gonadotropin. The initial increases in nocturnal sleeptime total U-LH concentrations over the cutoff value of 0.7 IU/L occurred at around the same time (around 9-10 years of age) in both sexes, which could not be detected in waketime urine samples. The mean first age for the nocturnal sleeptime total U-LH concentrations to reach or surpass the cutoff was 10.7 years (range: 10.2-11.6years) in boys and 11.8 years (range: 10.7-13.4years) in girls, showing no statistically significant difference between the sexes (p = .15). The mean time span from the age at which sleeptime total U-LH concentration first exceeded the 0.7 IU/L level to observing pubertal stage 2 was 1.5years in boys and 0.1years in girls. Findings in our population with a limited sample size suggest that the timing of central pubertal activation is a sex-independent phenomenon, which can be observed by monitoring the nocturnal sleeptime total LH concentrations in urine. The lag time from central pubertal activation of gonadotropin secretion to the clinical onset of puberty is significantly longer in boys.

The sun imposes a 24-h periodicity to life and circadian rhythms have evolved to maintain homoeostasis through the day/night cycle. In humans, there is a central clock that controls the sleep/wake cycle which is paralleled metabolically by a fast/feed cycle. The clock maintains homoeostasis by synchronising metabolism to the time of feeding. Loss of synchrony between the clock and hormonal rhythms results in loss of homoeostasis as evidenced by obesity, depression, and diabetes in people undertaking shift work. Cortisol has a distinct circadian rhythm; peaking on waking and low at sleep onset. Loss of this rhythm in adrenal insufficiency is associated with a poor quality of life and increased mortality. To replace the cortisol rhythm requires chronotherapy and for this you need to define the key parameters of the target rhythm, create a formulation to replicate that rhythm, and then prove clinical benefit. The physiology of hormones is more complex than that of nonnative drugs. Hormones are secreted with varied rhythms, bound to multiple cognate binding proteins, and actively transported and cleared through enzymatic pathways in multiple organs. We have examined the diurnal rhythm of cortisol in healthy volunteers, created physiologically-based pharmacokinetic models, and tested various oral delayed and sustained formulations of hydrocortisone (development name, Chronocort) in clinical trials. The outcome from this work was the manufacture of modified-release hydrocortisone hard capsules (tradename Efmody, Diurnal Ltd), that replicate the cortisol diurnal rhythm and improve the disease control of congenital adrenal hyperplasia the commonest hereditary form of adrenal insufficiency.

Isolated biochemical central hypothyroidism is a presentation we are experiencing more frequently as endocrinologists, with variation in levels of investigation between physicians. We therefore conducted research to investigate the final diagnosis and clinical outcome of patients across multiple hospitals in South Wales with biochemical isolated central hypothyroidism; namely to establish whether this isolated biochemical picture was clinically significant. We also analysed whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications, and how common this is. We performed a retrospective observational study of patients across nine different hospitals in South Wales. We analysed patients referred to endocrinology at each site over a 6-year period with unexplained isolated biochemical central hypothyroidism. 1022 individual patients' thyroid function test results were identified from our biochemical database using our inclusion criteria. After exclusion criteria were applied, 71 patients' results were analysed as to the final pathophysiology of their central hypothyroidism. Of the 71 patients included in the study, none were found to have any clinically significant pathology on pituitary imaging. On reviewing their medications, 46/71 (65%) were found to be taking psychotropic medications. Our study strongly suggests isolated central hypothyroidism, in the absence of other pituitary hormone dysfunction or visual field defect, does not require further investigation, saving resources as well as sparing patients unnecessary anxiety. It also strongly supports a relationship between patients taking psychotropic medications and biochemical isolated central hypothyroidism, an association only described in a very limited amount of literature before this, and further supporting our previous single-centre study findings. The mechanism behind this is likely to be the suppression of thyrotropin secretion via antagonism of the dopamine-serotoninergic pathway. In our opinion, patients found to have isolated biochemical central hypothyroidism who are taking psychotropic medications can therefore be regarded to have a recognised cause for this biochemical finding and do not require further radiological investigation.

Interpreting thyroid function tests can be challenging due to inherent variation, and the need for tests rises with age. While age-related changes in thyrotropin (TSH) levels are known, the biological variation in older adults remains unclear. We recruited nineteen 65-99-year-old (older adults) without thyroid disease for monthly blood sampling for 1 year. Serum was stored at -20C°, and TSH, total thyroxine (TT4) and total triiodothyronine (TT3) were analysed in random order in a single batch for each participant. Results were compared to test results from 15 euthyroid men aged 24-53 years (younger adults) collected previously using a similar methodology. Interindividual coefficients of variation in older/younger adults were 46.7%/44.0% for TSH, 12.7%/19.5% for TT4 and 14.6%/22.4% for TT3. Intraindividual coefficients of variation (CVI ) were 19.0%/25.4% for TSH, 5.5%/10.8% for TT4 and 6.9%/13.2% for TT3. The index of individuality was below 0.6 for all hormones in all age groups. The number of samples required to determine the homoeostatic set-point at 10% precision in older adults was 14-21 for TSH and 2 for TT4 and TT3. TT4 in older adults was the only parameter in any group with comparable CVI between individuals (p = .22). CVI for TT4 and TT3 was halved in older compared to younger adults with two tests of TT4 needed to describe the individual set-point. Similar CVI between older adults caused TT4 to provide a reliable estimate of thyroid function, and the added value of measuring thyroxine could improve clinical practice.

Duncan et al. reviewed the response to growth hormone stimulation testing after priming in peripubertal children. The concern is that there is little research documenting the response to growth hormone treatment in patients with sex hormone primed growth hormone stimulation testing and those unprimed. The controversy about priming or not can be summarized as follows: if one wants to know if the production of growth hormone during puberty will be adequate in terms of peak growth hormone responses then stimulation with priming should be done.