Fifteen-minute consultation: Approach to the adolescent presenting with hirsutism.

Hirsutism, unwanted terminal hair growth in androgen-dependent areas, is a common presentation to general paediatricians, dermatologists and endocrinologists. Polycystic ovarian syndrome is the most common cause but can be challenging to diagnose in young people due to the significant overlap of features with the healthy adolescent population. There are other rare, but important, causes to consider such as non-classic congenital adrenal hyperplasia and androgen-secreting tumours. Hirsutism carries a significant psychological burden for those living with it. This 15 min consultation piece describes the causes of hirsutism, introduces a novel assessment tool and suggests an approach to investigations and management, including signposting to psychological support.

Real world evidence supports waking salivary cortisone as a screening test for adrenal insufficiency.

OBJECTIVE: 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. DESIGN, PATIENTS AND MEASUREMENTS: 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. RESULTS: 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 was 1 (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. CONCLUSIONS: 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.

Fifteen-minute consultation: The child with obesity.

Obesity is common among children and young people, with potential for significant clinical consequences. The physical and psychological comorbidities associated with childhood obesity persist into adult life, but many children do not have access to tailored obesity services. We present a framework for the identification, assessment and management of childhood obesity by the non-specialist. We also offer strategies to initiate discussions about weight and to communicate effectively with patients living with obesity.

How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey.

OBJECTIVE: We aimed to document current practice in the medical management of paediatric hyperthyroidism in the UK and compare to international recommendations. DESIGN: A 27-question online survey distributed via an electronic newsletter in August 2018. PARTICIPANTS: Responses from 48 members (11%) of the British Society for Paediatric Endocrinology and Diabetes. MEASUREMENTS: Information about antithyroid drug (ATD) preference, treatment duration, monitoring of full blood count (FBC), management of neutropaenia, agranulocytosis screening and patient education. RESULTS: Carbimazole is favoured by 98% of respondents and a "dose titration" regimen preferred over "block and replace" (65% vs 29%). TRAbs (thyroid-stimulating hormone receptor antibodies) are used for diagnostic purposes by 85% and by 33% to look for evidence of disease remission. The majority (81%) treat for a minimum of 2 years before considering a trial off ATD. All respondents reported that they "always/usually" warn their patients about the risk of agranulocytosis before starting ATD, but written information is "rarely/never" provided by 63%. Sore throat (98%) and fever (92%) are the most commonly cited symptoms used to alert a patient to possible agranulocytosis. FBC is measured prior to treatment by 65% and measured periodically during treatment by 70%. CONCLUSIONS: The management of paediatric hyperthyroidism with ATDs in the UK is not consistent with all international recommendations because a block and replace ATD regimen remains widely used. TRAbs are utilized at presentation, but underused for detecting disease remission. National consensus guidelines and written patient information may refine the management of paediatric patients on ATDs.

A simulation study assessing the accuracy and reliability of orchidometer estimation of testicular volume.

CONTEXT: Measuring testicular volume (TV) by orchidometer is the standard method of male pubertal staging. A paucity of evidence exists as to its inter- and intra-observer reliability and the impact of clinicians' gender, training and experience on accuracy. OBJECTIVE: Prosthetic testicular models were engineered to investigate accuracy and reliability of TV estimation. DESIGN: Simulation study. SETTING: Conducted over three-day 2015 British Society for Paediatric Endocrinology and Diabetes (BSPED) meeting. PARTICIPANTS: Two hundred fifteen meeting delegates (161F, 54M): 50% consultants, 30% trainees, 9% clinical nurse specialists, 11% other professionals. INTERVENTION: Three child-sized mannequins displayed latex scrotum containing prosthetic testicles of 3, 4, 5, 10 and 20 mL. Demographic data, paediatric endocrinology experience, TV examination training, examination technique and TV estimations were collected. Delegates were asked to repeat their measurements later during the meeting. Scrotum order was changed daily. MAIN OUTCOME MEASURES: Accuracy by variance from the simulated TV. Inter- and intra-observer variability. RESULTS: One thousand two hundred eighty four individual estimations were obtained. Eighty-five participants repeated measurements. Delegates measured TV accurately on 33.4% (±2.6) of occasions: overestimations 37% (±2.3), underestimations 28% (±1.8) (Fleiss' Kappa score 0.04). The accuracy of assessing a 4 mL testis was 36%-39%. Observers underestimated the volume when paired with a 3 mL testis and overestimated when paired with a 5 mL testis demonstrating a tendency impose biological symmetry. Intra-observer reliability was lacking; individuals giving different estimations for the same size testicle on 61% (±4.2) of occasions, 20% (±3.5) of estimations were more than 1 size outside the previous measurement. On only 39% (±4.2) of occasions did individuals agree with their previous estimation (irrespective of whether or not it was initially accurate). Training did not impact on results but experience did improve accuracy. CONCLUSIONS: Overall TV estimation accuracy was poor. Considerable variation exists between and within subjects. Seniority slightly improved measurement estimation.

Use of salivary cortisol and cortisone in the high- and low-dose synacthen test.

CONTEXT: Salivary cortisone reflects serum cortisol levels, is more sensitive than salivary cortisol at lower values of serum cortisol and is noninvasive. OBJECTIVE: To investigate the relationship between serum cortisol and salivary cortisol and cortisone following low- and high-dose synacthen. DESIGN AND SETTING: Prospective pharmacodynamic studies in clinical research facilities. PARTICIPANTS AND INTERVENTION: Thirty-five dexamethasone-suppressed, healthy adult males underwent an intravenous synacthen test: N = 23 low-dose (1 mcg), N = 12 high-dose (250 mcg). Paired serum and salivary samples were taken at 15 sampling points over 120 minutes. MAIN OUTCOME MEASURE: Serum cortisol and salivary cortisol and cortisone were analysed for correlations and by a mixed-effects model. RESULTS: At baseline, the correlation between serum cortisol and salivary cortisol was weak with many samples undetectable (r = .45, NS), but there was a strong correlation with salivary cortisone (r = .94, P < .001). Up to 50 minutes following synacthen, the correlation coefficient between serum cortisol and salivary cortisol and cortisone was <0.8, but both had a stronger correlation at 60 minutes (salivary cortisol r = .89, P < .001, salivary cortisone r = .85, P < .001). The relationship was examined excluding samples in the dynamic phase (baseline to 60 minutes). Salivary cortisol and cortisone showed a close relationship to serum cortisol. Salivary cortisone showed the stronger correlation: salivary cortisol r = .82, P < .001, salivary cortisone r = .96, P < .001. CONCLUSION: Following synacthen, both salivary cortisol and cortisone reflect serum cortisol levels, but there is a lag in their rise up to 60 minutes. The results support further research for possible future use of a 60-minute salivary cortisone measurement during the synacthen test.

International survey on high- and low-dose synacthen test and assessment of accuracy in preparing low-dose synacthen.

OBJECTIVE: The short synacthen test (SST) is widely used to assess patients for adrenal insufficiency, but the frequency and protocols used across different centres for the low-dose test (LDT) are unknown. This study aimed to survey centres and test the accuracy of ten different synacthen preparation strategies used for the LDT. METHODS: Members of 6 international endocrine societies were surveyed regarding diagnostic tests used for adrenal insufficiency, and in particular the SST. Synacthen was diluted for the LDT and concentrations measured using a synacthen ELISA. RESULTS: Survey responses were received from 766 individuals across 60 countries (52% adult, 45% paediatric endocrinologists). The SST is used by 98% of centres: 92% using high-dose (250 µg), 43% low-dose and 37% both. Ten low-dose dilution methods were assessed and variation in synacthen concentration was demonstrated with intramethod coefficients of variation (CV) ranging from 2.1% to 109%. The method using 5% dextrose as a diluent was the least variable (CV of 2.1%). The variation in dilution methods means that the dose of synacthen administered in a LDT may vary between 0.16 and 0.81 µg. CONCLUSIONS: The high-dose SST is the most popular diagnostic test of adrenal insufficiency, but up to 72% of paediatric endocrinologists use a LDT. There is considerable variation observed both within and between low-dose synacthen dilution methods creating considerable risk of inaccurate dosing and thereby invalid results.

Spontaneous resolution of labial adhesions in pre-pubertal girls.

AIMS: This study sought to observe the rate and timing of spontaneous resolution of labial adhesions that had been diagnosed in pre-pubertal girls. The secondary aim was to evaluate the conservative approach to management of labial adhesions that has been advocated by the Gynaecology Department, by assessing the rates of concurrent uro-gynaecological symptoms in this population, as well as parent satisfaction with their child's management. METHODS: A retrospective chart review was performed of all patients diagnosed with labial adhesions in the Department of Paediatric and Adolescent Gynaecology between 2000 and 2017. Patients and their parents (depending on the age of the patient at the time of this study) were then invited to participate in follow-up surveys and questionnaires and clinical examination. RESULTS: Of 148 girls identified, the median age of the follow-up participants (n = 45) was 6.1 years (2.6-27.2 years), compared with that of the entire cohort of 7.4 years (1-27 years). After a median follow-up period of 2.6 years (0.4-20.7 years), 40% (18/45) of girls reported and/or had findings that supported resolution of labial adhesions without treatment. Two parents (4%) sought treatment elsewhere after their appointment. A history of UTI was reported in 30% (14/45) of patients, and 16% (7/45) had a known history of vulvovaginitis. CONCLUSIONS: Our findings support the natural history of spontaneous resolution of labial adhesions. Concurrent uro-gynaecological conditions that developed were successfully treated according to standard treatments. A conservative approach to the management of labial adhesions is associated with very low rates of parental concern and intervention.

Integrating teaching into everyday clinical practice.

The teaching and training of doctors-in-training in paediatrics has become increasingly challenging in recent times. All too often there is a perception that training must come second to service provision. In this article, the case of a child with community-acquired pneumonia is considered and used to illustrate how a culture of teaching can be embedded in everyday clinical practice.

Rickets.

Rickets, historically referred to as "the English disease", is common worldwide. Absence of phosphate at the growth plate and mineralising bone surfaces due to inadequate vitamin D supply either from sunlight exposure or diet is the main cause. Inherited disorders causing hypophosphataemia have shown the intricacies of phosphate metabolism. Present advice about the provision of vitamin D to young infants needs to be clarified; the existing guidance is fragmentary and contradictory, and will not help to eradicate the disease.

A retrospective study on weaning glucocorticoids and recovery of the hypothalamic-pituitary-adrenal axis.

CONTEXT: Glucocorticoids suppress the hypothalamic-pituitary-adrenal (HPA) axis resulting in tertiary adrenal insufficiency (AI). When weaning patients off glucocorticoids there is no consensus on whether to maintain patients on prednisolone or convert to hydrocortisone. OBJECTIVE: Investigate HPA axis recovery in patients on long-term prednisolone and assess outcome after hydrocortisone conversion. DESIGN: Retrospective cohort study. SETTING: Outpatient endocrine steroid clinic. PATIENTS: Patients on long-term prednisolone referred for HPA axis testing between 2015-2022. MAIN OUTCOMES MEASURED: 1) HPA axis recovery rate in patients on prednisolone demonstrated by normal ACTH stimulation test (AST).2) HPA axis recovery rate sub-analysis of dose-matched patients with confirmed tertiary AI on prednisolone or hydrocortisone. RESULTS: 206 patients on prednisolone were tested for tertiary AI. Of these 176 remained on prednisolone while 30 were converted to hydrocortisone. The overall HPA axis recovery rate for patients on prednisolone after interval testing was 137/206 (66.5%). HPA axis recovery rate in dose-matched prednisolone and hydrocortisone conversion groups was 7/10 (70%) and 2/13 (15%) (p=0.008), respectively. There was no difference in mean (SD) age (67.1(12.2) v 63.4(11.1) years; p=0.464) and baseline cortisol (5.3(4.2) v 4.6(3.1)µg/dL; p=0.648) and median [IQR] glucocorticoids duration (1213[1114] v 2316[4808] days; p=0.693) and baseline ACTH (20.5[29.0] v 16.3[14.8]ng/L; p=0.905) between dose-matched prednisolone and hydrocortisone groups. Follow-up duration in prednisolone group was significantly lower (median [IQR] 348[975] v 667[884] days; p=0.012). CONCLUSIONS: Patients with glucocorticoid induced AI maintained on once-daily prednisolone can recover HPA axis function when weaning. There is no apparent advantage to recover HPA axis function in converting to multiple dosing hydrocortisone.

Pelvic pain in transmasculine adolescents receiving testosterone therapy.

Background: Pelvic pain is a common complaint among individuals assigned female at birth. However, few studies have explored pelvic pain among transmasculine patients on gender-affirming testosterone treatment, and most of these were performed in adult populations. Aims: The aim of our study was to investigate the prevalence, risk factors, nature and treatment of pelvic pain among trans adolescents on testosterone. Methods: A retrospective cohort study was performed on all trans adolescents started on gender-affirming testosterone treatment at our institution between 2007 and 2020. Results: Among 158 trans adolescents who were started on testosterone therapy and followed-up for at least six months, 37 (23.4%) reported pelvic pain, with a median interval between testosterone initiation and reported onset of pain of 1.6 months (range 0.3-6.4). The prevalence of pelvic pain was higher in patients who were receiving menstrual suppression (n = 36, 26.3%) compared to those who were not (n = 1, 4.8%), giving a risk difference of 21.5% (95% CI 9.8% to 33.2%, p = 0.028). The most common descriptive terms were "cramps" (n = 17, 45.9%) and "similar to previous period pain" (n = 8, 21.6%). A range of different pharmacological strategies were employed, including paracetamol, NSAIDs, danazol, norethisterone, medroxyprogesterone, etonogestrel implant, intra-uterine device, goserelin and pelvic floor physiotherapy, with variable outcomes. Conclusion: In conclusion, we report here - in what is to our knowledge the first time - the prevalence rate of pelvic pain in trans adolescents on gender-affirming testosterone treatment, and observe that a quarter of them described pelvic pain. Limitations of our study include its retrospective nature, which is likely to be associated with under-reporting of pelvic pain, and the limited documentation of the nature and likely causes of this pain within the medical records. Prospective longitudinal studies to better understand the nature, etiology and optimal management of testosterone-associated pelvic pain are therefore warranted.

Characteristics of Menstrual Suppression and Its Association With Mental Health in Transgender Adolescents.

OBJECTIVE: To investigate the prevalence, nature, and effectiveness of menstrual suppression in transgender and gender-diverse (TGD) adolescents, and to explore whether there is an association between menstrual suppression and mental health in this population. METHODS: A cross-sectional study was performed of TGD adolescents assigned female at birth attending their first appointment at a specialist pediatric gender service between February 2017 and December 2021. Demographic and mental health data were collected using a questionnaire at the time of first visit, and information regarding menstrual suppression at this time was retrieved from the medical record. RESULTS: A total of 530 TGD individuals were included; 131 (24.7%) were on menstrual suppression at their initial visit, mainly to help alleviate gender dysphoria. Combined oral contraceptive pills were the most common agent used (n=61, 46.6%), followed by norethindrone (n=39, 29.8%) and intramuscular medroxyprogesterone (n=19, 14.5%). Rates of effectiveness (in stopping menstruation) and patient satisfaction were high. Among the 399 individuals not on menstrual suppression, there was strong interest in starting this treatment. No differences in the risk of gender dysphoria, depression, or anxiety were observed between those who were receiving menstrual suppression and those who were not. CONCLUSION: Effectiveness of and satisfaction with menstrual suppression were high in TGD adolescents receiving this treatment. These findings support the routine exploration and management of menstrual health in TGD adolescents. However, menstrual suppression was not associated with any difference in gender dysphoria, depression, or anxiety symptoms in this cross-sectional study, and longitudinal studies are required to better investigate this.

Pelvic Pain in Transgender People Using Testosterone Therapy.

Purpose: This descriptive study aimed to assess the characteristics of pelvic pain and explore predictive factors for pelvic pain in transgender (trans) individuals using testosterone therapy. Methods: An online cross-sectional survey was open between August 28, 2020, and December 31, 2020, to trans people presumed female at birth, using testosterone for gender affirmation, living in Australia, and >16 years of age. The survey explored characteristics of pelvic pain following initiation of testosterone therapy, type and length of testosterone therapy, menstruation history, and relevant sexual, gynecological, and mental health experiences. Logistic regression was applied to estimate the effect size of possible factors contributing to pain after starting testosterone. Results: Among 486 participants (median age = 27 years), 351 (72.2%)* reported experiencing pelvic pain following initiation of testosterone therapy, described most commonly as in the suprapubic region and as "cramping." Median duration of testosterone therapy was 32 months. Persistent menstruation, current or previous history of post-traumatic stress disorder, and experiences of pain with orgasm were associated with higher odds of pelvic pain after testosterone therapy. No association was observed with genital dryness, intrauterine device use, previous pregnancy, penetrative sexual activities, touching external genitalia, or known diagnoses of endometriosis, vulvodynia, vaginismus, depression, anxiety, or obesity. Conclusions: Pelvic pain is frequently reported in trans people following initiation of testosterone therapy. Given the association with persistent menstruation and orgasm, as well as the known androgen sensitivity of the pelvic floor musculature, further research into pelvic floor muscle dysfunction as a contributor is warranted.

Multivariable Model to Predict an ACTH Stimulation Test to Diagnose Adrenal Insufficiency Using Previous Test Results.

Context: The adrenocorticotropin hormone stimulation test (AST) is used to diagnose adrenal insufficiency, and is often repeated in patients when monitoring recovery of the hypothalamo-pituitary-adrenal axis. Objective: To develop and validate a prediction model that uses previous AST results with new baseline cortisol to predict the result of a new AST. Methods: This was a retrospective, longitudinal cohort study in patients who had undergone at least 2 ASTs, using polynomial regression with backwards variable selection, at a Tertiary UK adult endocrinology center. Model was developed from 258 paired ASTs over 5 years in 175 adults (mean age 52.4 years, SD 16.4), then validated on data from 111 patients over 1 year (51.8, 17.5) from the same center, data collected after model development. Candidate prediction variables included previous test baseline adrenocorticotropin hormone (ACTH), previous test baseline and 30-minute cortisol, days between tests, and new baseline ACTH and cortisol used with calculated cortisol/ACTH ratios to assess 8 candidate predictors. The main outcome measure was a new test cortisol measured 30 minutes after Synacthen administration. Results: Using 258 sequential ASTs from 175 patients for model development and 111 patient tests for model validation, previous baseline cortisol, previous 30-minute cortisol and new baseline cortisol were superior at predicting new 30-minute cortisol (R2 = 0.71 [0.49-0.93], area under the curve [AUC] = 0.97 [0.94-1.0]) than new baseline cortisol alone (R2 = 0.53 [0.22-0.84], AUC = 0.88 [0.81-0.95]). Conclusion: Results of a previous AST can be objectively combined with new early-morning cortisol to predict the results of a new AST better than new early-morning cortisol alone. An online calculator is available at https://endocrinology.shinyapps.io/sheffield_sst_calculator/ for external validation.

Home Waking Salivary Cortisone to Screen for Adrenal Insufficiency.

BACKGROUND: Worldwide, adults and children are at risk of adrenal insufficiency as a result of adrenal suppression from use of anti-inflammatory glucocorticoids and opiates, as well as infectious diseases. The adrenocorticotropin (ACTH) stimulation test is the reference standard for diagnosis of adrenal insufficiency but requires clinic attendance and venesection. Salivary cortisone reflects free serum cortisol, and samples can be collected at home and posted to a laboratory. We tested whether home waking salivary cortisone level could be used to screen for adrenal insufficiency. METHODS: A prospective, diagnostic accuracy study was performed in patients at high risk of adrenal insufficiency. Patients collected a home salivary sample on waking and then attended the clinical facility for an ACTH stimulation test. Salivary cortisone was measured by liquid chromatography­tandem mass spectrometry. Receiver-operating characteristic curves were computed, and positive and negative predictive values were calculated. RESULTS: Two hundred twenty patients were recruited. As measured by an ACTH stimulation test, the prevalence of adrenal insufficiency was 44%. The area under the receiver-operating characteristic curve for waking salivary cortisone as a predictor of adrenal insufficiency was 0.95 (95% confidence interval [CI], 0.92 to 0.97). Cutoffs to ensure a minimum of 95% sensitivity and specificity gave a negative predictive value of 96% (95% CI, 90 to 99) and a positive predictive value of 95% (95% CI, 87 to 99) to exclude and confirm adrenal insufficiency, respectively. Waking salivary cortisone data provided information similar to that of an ACTH stimulation test in 70% of participants. Eighty-three percent of patients preferred home salivary collection to clinic attendance. CONCLUSIONS: Home waking salivary cortisone sampling has accuracy for the diagnosis of adrenal insufficiency similar to that of a standard ACTH stimulation test. Patients found the at-home test to be more convenient than the hospital-based test. (Funded by the National Institute for Health Research.)

Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance.

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery, there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death. There are no unified guidelines for those <18 years old in the UK, leading to substantial variation in the management of AI. This paper sets out guidance for intercurrent illness, medical, dental and surgical procedures to allow timely and appropriate recognition and treatment of AI and adrenal crisis for children and young people.

Salivary Steroid Collection in Children Under Conditions Replicating Home Sampling.

CONTEXT: Measurement of salivary glucocorticoids is an accepted method for testing adrenal function but there are few data on stability during home collection. Current salivary collection techniques require active participation or present a choking hazard and are unsuitable for young children. OBJECTIVE: We sought to compare different salivary collection methods; assess the stability of salivary glucocorticoids under conditions replicating home collection; and assess patient tolerability and caregiver acceptability of a salivary collection device for young children, a swab encased in an infant pacifier (SaliPac). METHODS: Six healthy adults collected salivary samples using a Salivette Cortisol, passive drool, and SalivaBio at night, waking, and 3 Pm for five days. Time to collect 1-mL saliva using the SalivaBio and SaliPac and caregiver acceptability were assessed in 30 children younger than 6 years. Saliva was stored at 4 °C, room temperature (RT), and 50 °C for 24, 48, 72 hours and 1 week to replicate potential postage conditions. Salivary cortisol and cortisone concentrations were measured by mass spectrometry. RESULTS: There was no difference in salivary glucocorticoid concentrations using the 3 collection methods. Salivary cortisol and cortisone were stable for 72 hours at RT and 4 °C, and repeated freeze-thaw cycles did not cause significant degradation. In children younger than 6 years the SalivaBio and SaliPac were well tolerated and collected sufficient saliva for salivary steroid analysis in less than 4 minutes. CONCLUSION: Salivette, passive drool, and SalivaBio collect samples with comparable salivary cortisol and cortisone concentrations, which are stable under conditions replicating home collection. SaliPac is an acceptable device for salivary sampling in young children.