Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study.

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.

International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood.

This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.

Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity.

CONTEXT: Prader-Willi syndrome (PWS) is characterized by lack of appetite control and hyperphagia, leading to obesity. Pharmacological options for weight management are needed. OBJECTIVE: To determine whether liraglutide treatment for weight management is superior to placebo/no treatment in pediatric individuals with PWS. METHODS: This was a multicenter, 52-week, placebo-controlled trial with a 16-week double-blinded period. Adolescents (n = 31, aged 12-17 years; Tanner stage 2-5) and children (n = 24, aged 6-11 years; Tanner stage <2) with PWS and obesity were included. Patients were randomized 2:1 to liraglutide 3.0 mg (or maximum-tolerated dose) or placebo for 16 weeks, after which placebo was stopped. Liraglutide was continued for 52 weeks. All patients followed a structured diet and exercise program throughout the trial. The coprimary endpoints were change in body mass index (BMI) standard deviation score (SDS) from baseline to 16 and 52 weeks. Secondary endpoints included other weight-related parameters, hyperphagia, and safety. RESULTS: Change in BMI SDS from baseline to weeks 16 and 52 was not significantly different between treatments in adolescents (estimated treatment difference: -0.07 at week 16 and -0.14 at week 52) and children (-0.06 and -0.07, respectively). Changes in other weight-related parameters between treatments were not significant. At week 52, hyperphagia total and drive scores were lower in adolescents treated with liraglutide vs no treatment. The most common adverse events with liraglutide were gastrointestinal disorders. CONCLUSION: Although the coprimary endpoints were not met, changes in hyperphagia total and drive scores in adolescents warrant further studies on liraglutide in this population.

The SELFI Study: Iodine Excess and Thyroid Dysfunction in Women Undergoing Oil-Soluble Contrast Hysterosalpingography.

CONTEXT: Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates. However, OSCM has high iodine content and long half-life, leading to potential iodine excess. OBJECTIVE: This work aimed to determine the pattern of iodine excess after OSCM HSG and the effect on thyroid function. METHODS: A prospective cohort study was conducted of 196 consecutive consenting eligible women without overt hypothyroidism or hyperthyroidism. All completed the study with compliance greater than 95%. Participants underwent OSCM HSG (Auckland, 2019-2021) with serial monitoring of thyrotropin (TSH), free thyroxine (FT4), and urine iodine concentration (UIC) for 24 weeks. The main outcome measure was the development of subclinical hypothyroidism (SCH), defined as a nonpregnant TSH greater than 4 mIU/L with normal FT4 (11-22 pmol/L) in those with normal baseline thyroid function. RESULTS: Iodine excess (UIC ≥ 300 µg/L) was almost universal (98%) with UIC peaking usually by 4 weeks. There was marked iodine excess, with 90% and 17% of participants having UIC greater than or equal to 1000 µg/L and greater than 10 000 µg/L, respectively. Iodine excess was prolonged with 67% having a UIC greater than or equal to 1000 µg/L for at least 3 months. SCH developed in 38%; the majority (96%) were mild (TSH 4-10 mIU/L) and most developed SCH by week 4 (75%). Three participants met the current treatment guidelines (TSH > 10 mIU/L). Thyroxine treatment of mild SCH tended to improve pregnancy success (P = .063). Hyperthyroidism (TSH < 0.3 mIU/L) occurred in 9 participants (5%). CONCLUSION: OSCM HSG resulted in marked and prolonged iodine excess. SCH occurred frequently with late-onset hyperthyroidism occasionally. Regular thyroid function tests are required for 6 months following this procedure.

Hysterosalpingography with Oil-Soluble Contrast Medium Does Not Increase Newborn Hypothyroidism.

OBJECTIVE: Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates in women with idiopathic infertility. However, OSCM has high iodine content and slow clearance resulting in potential iodine excess. If pregnancy occurs, this could impact fetal thyroid gland development and function. We aim to determine the effect of a preconceptional OSCM HSG on the thyroid function of the neonate. Design and Patients. This was a retrospective analysis of newborn TSH data for a cohort of neonates conceived within six months of an OSCM HSG in the Auckland region, New Zealand, from the years 2000 to 2019. Thyroid-stimulating hormone (TSH) levels of these newborns were obtained from newborn screening, which is routinely performed for all children at 48-72 hours of life. The primary outcome was the incidence of permanent or transient congenital hypothyroidism in this cohort. RESULTS: Of 146 babies included, all had normal TSH levels with values ranging from 1 to 7 mIU/L on the whole blood analysis of a capillary heel sample using the Perkin-Elmer AutoDelfia assay. Conception during the first 3 cycles following an OSCM HSG was 76%; however, TSH levels in this group were not higher than those conceived in later cycles. CONCLUSION: Preconceptional OSCM HSG did not increase the risk of congenital hypothyroidism in the New Zealand scenario.

Therapeutic effects of hysterosalpingography contrast media in infertile women: what do we know about the H2O in the H2Oil trial and why does it matter?

Recent interest in the use of oil-soluble contrast media (OSCM) for hysterosalpingography (HSG) and other tubal flushing procedures is largely the result of publication of the large, multicentre, randomized controlled H2Oil trial in the New England Journal of Medicine in 2017, addressing the long-held suspicion that pregnancy rates following HSG with OSCM are higher than if a water-soluble contrast media (WSCM) is used. However, the findings of this trial have been compromised by the WSCM selected for comparison with OSCM. The chosen WSCM belongs to a superceded class of ionic media, with an iodine concentration, osmolality and viscosity all lying at the extreme end of the range for water-soluble radiographic contrast. The requirement for safe, cheap, versatile WSCM for intravascular use during computerized tomography, angiography and interventional procedures has resulted in considerable refinement of WSCM, with current widespread use of non-ionic, low osmolality or iso-osmolar WSCM in radiology, including for HSG. However, the use of the earlier ionic, high osmolality agents such as that selected for the H2Oil trial persists for HSG in some centres, despite potential adverse effects on the endometrium and fallopian tubal epithelium compared with more modern, less toxic WSCM. Knowledge of the variety of physical and chemical characteristics of the available WSCM is essential for interpretation of the current literature and establishing the most effective and safe water-soluble agent to use for HSG. Design of future clinical trials to establish the potential superiority of OSCM over WSCM for fertility enhancement must include the use of the readily available, inexpensive modern WSCM. While the fertility rates following OSCM HSG have been shown to be high in women with idiopathic infertility, more robust trials are required before the widespread use of OSCM for HSG or other modalities such as ultrasound and laparoscopy should be adopted.

A systematic review of gratitude interventions: Effects on physical health and health behaviors.

OBJECTIVE: Gratitude interventions are easy-to-deliver, offering promise for use in clinical-care. Although gratitude interventions have consistently shown benefits to psychological wellbeing, the effects on physical health outcomes are mixed. This systematic review aims to synthesize gratitude intervention studies which assessed physical health and health behavior outcomes, as well as evaluate study quality, comment on their efficacy, and provide directions for future research. METHODS: Relevant studies were identified through searches conducted in PsycINFO, MedLine, Embase and Cochrane Library databases, up until August 2019. Only studies that evaluated a gratitude intervention, randomly assigned participants to gratitude and control conditions, and assessed objective and subjective measures of physical health and health behaviors were included. The Revised Cochrane risk-of-bias (RoB2) tool was used to assess risk of bias. RESULTS: Of the 1433 articles found, 19 were included in the review. Subjective sleep quality was improved in 5/8 studies. Improvements in blood pressure, glycemic control, asthma control and eating behavior were understudied yet demonstrated improvements (all 1/1). Other outcome categories remain understudied and mixed, such as inflammation markers (1/2) and self-reported physical symptoms (2/8). The majority of studies showed some risk of bias concerns. CONCLUSIONS: Although it was suggested gratitude interventions may improve subjective sleep quality, more research is still needed to make firm conclusions on the efficacy of gratitude interventions on improving health outcomes. Further research focusing on gratitude's link with sleep and causal mechanisms is needed, especially in patient populations where more 'clinically-usable' psychosocial interventions are urgently needed.

Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor.

Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP. LEARNING POINTS: Adrenocortical carcinoma is an important differential diagnosis for virilization in young childrenMitotane is a chemotherapeutic agent that is used to treat adrenocortical carcinoma and causes adrenal necrosisMitotane is an endocrine disruptor. In addition to the intended effect of adrenal insufficiency, it can cause hypothyroidism, with gynecomastia also reported in adults.Patients taking mitotane require very high doses of hydrocortisone replacement therapy because mitotane interferes with steroid metabolism. This effect persists after mitotane therapy is completedIn our case, mitotane caused peripheral precocious puberty, possibly through its estrogenic effect.

Consensus guidelines on the use of bisphosphonate therapy in children and adolescents.

Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence-based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non-fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence-based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made.

Fish oil supplementation to rats fed high-fat diet during pregnancy prevents development of impaired insulin sensitivity in male adult offspring.

We examined whether maternal fish oil supplementation during pregnancy could prevent development of insulin resistance in adult male offspring of rat dams fed a high-fat diet. Time-mated Sprague-Dawley rat dams were randomised into four treatment groups: Con-Con, dams fed a control diet (fat: 15% kcal) and administered water by gavage; Con-FO, control diet with unoxidised fish oil by gavage; HF-Con, high-fat diet (fat: 45% kcal) and water by gavage; and HF-FO, high-fat diet and unoxidised fish oil by gavage. Dams were fed the allocated diet ad libitum during pregnancy and lactation, but daily gavage occurred only during pregnancy. After weaning, male offspring consumed a chow diet ad libitum until adulthood. Maternal high-fat diet led to increased food consumption, adiposity, systolic blood pressure, and triglycerides and plasma leptin in adult HF-Con offspring. HF-Con offspring also exhibited lower insulin sensitivity than Con-Con rats. Male offspring from HF-FO group were similar to HF-Con regarding food consumption and most metabolic parameters. However, insulin sensitivity in the HF-FO group was improved relative to the HF-Con offspring. Supplementation with unoxidised n-3 PUFA rich oils in the setting of a maternal obesogenic diet improved insulin sensitivity, but had no impact on body composition of adult male offspring.

Nulliparity is associated with subtle adverse metabolic outcomes in overweight/obese mothers and their offspring.

BACKGROUND: We aimed to evaluate metabolic outcomes in overweight/obese nulliparous and multiparous women and their offspring. STUDY DESIGN: Seventy-two overweight and obese women who participated in a randomized controlled trial of exercise in pregnancy were included in the study, comparing 18 nulliparous and 54 multiparous women and their singleton offspring. Women were assessed at 19 and 36 weeks of gestation. Fetal growth was measured using standard obstetric ultrasound techniques. Cord blood was collected at birth. Maternal and offspring body composition was assessed using DXA ~2 weeks after delivery. RESULTS: Nulliparous women had higher HbA1c in the third trimester of pregnancy than multiparous women (5.48% vs 5.29%; P=.002) and were more insulin-resistant based on the surrogate marker sex hormone-binding globulin (354 vs 408 nmol/L; P=.047). Nulliparous women also had higher levels of the inflammatory marker tumour necrosis factor-alpha (4.74 vs 3.62 pg/mL; P=.025). At birth, the offspring of nulliparous women were on average 340 g (P=.013) and 0.69 standard deviation scores (P=.026) lighter than those born of multiparous women. Cord blood data showed lower insulin-like growth factor-II (P=.026) and higher IGF binding protein-1 (P=.002) levels in the offspring of nulliparous women. In addition, a less favourable metabolic profile was observed in the offspring of nulliparous women, as indicated by higher triglyceride (P<.001) and interleukin-6 (P=.039) concentrations. CONCLUSIONS: Infants born of nulliparous overweight and obese women appear to be exposed to a less favourable metabolic environment in utero, with evidence of subtle adverse metabolic outcomes at birth compared to infants of overweight/obese multiparous women.

Dietary Intake and Eating Behaviours of Obese New Zealand Children and Adolescents Enrolled in a Community-Based Intervention Programme.

OBJECTIVES: The aim of this study was to describe dietary intake and eating behaviours of obese children and adolescents, and also to determine how these differ in Indigenous versus non-Indigenous children at enrolment in an obesity programme. METHODS: Baseline dietary intake and eating behaviour records were assessed from those enrolled in a clinical unblinded randomised controlled trial of a multi-disciplinary intervention. The setting was a community-based obesity programme in Taranaki, New Zealand. Children or adolescents who were enrolled from January 2012 to August 2014, with a BMI ≥98th percentile or >91st centile with weight-related comorbidities were eligible. RESULTS: 239 participants (45% Maori, 45% NZ Europeans, 10% other ethnicities), aged 5-17 years were assessed. Two-thirds of participants experienced hyperphagia and half were not satiated after a meal. Comfort eating was reported by 62% of participants, and daily energy intake was above the recommended guidelines for 54%. Fruit and vegetable intake was suboptimal compared with the recommended 5 servings per day (mean 3.5 [SD = 1.9] servings per day), and the mean weekly breakfasts were less than the national average (5.9 vs 6.5; p<0.0001). Median sweet drink intake amongst Maori was twice that of NZ Europeans (250 vs 125 ml per day; p = 0.0002). CONCLUSIONS: There was a concerning prevalence of abnormal eating behaviours and significant differences in dietary intake between obese participants and their national counterparts. Ethnic differences between Indigenous and non-Indigenous participants were also present, especially in relation to sweet drink consumption. Eating behaviours, especially sweet drink consumption and fruit/vegetable intake need to be addressed.

Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance.

Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring.

Adrenal insufficiency in a child following unilateral excision of a dual-hormone secreting phaeochromocytoma.

UNLABELLED: Phaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion. LEARNING POINTS: Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.Serial/diurnal cortisol levels, ACTH measurement +/- low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.

Supplementation with a blend of krill and salmon oil is associated with increased metabolic risk in overweight men.

BACKGROUND: Krill is an increasingly popular source of marine n-3 (ω-3) PUFA that is seen as a premium product. However, to our knowledge, the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported. OBJECTIVE: We assessed whether supplementation with a blend of krill and salmon (KS) oil [which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] affects insulin sensitivity in overweight men. DESIGN: The design was a randomized, double-blind, controlled crossover trial. A total of 47 men with a mean ± SD age of 46.5 ± 5.1 y, who were overweight [body mass index (in kg/m(2)) from 25 to 30] but otherwise healthy, received 5 1-g capsules of KS oil or a control (canola oil) for 8 wk and crossed over to another treatment after an 8-wk washout period. The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test. Secondary outcomes included lipid profiles, inflammatory markers, 24-h ambulatory blood pressure, and carotid artery intimamedia thickness. RESULTS: Unexpectedly, insulin sensitivity (per the Matsuda index) was 14% lower with the KS oil than with the control oil (P = 0.049). A mediation analysis showed that, after controlling for the likely positive effects of blood EPA and DHA (i.e., the omega-3 index), the reduction in insulin sensitivity after KS-oil supplementation was more marked [27% lower than with the control oil (P = 0.009)]. CONCLUSIONS: Supplementation with a blend of KS oil is associated with decreased insulin sensitivity. Thus, krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease. This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000602921.

Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA.

We evaluated the quality and content of fish oil supplements in New Zealand. All encapsulated fish oil supplements marketed in New Zealand were eligible for inclusion. Fatty acid content was measured by gas chromatography. Peroxide values (PV) and anisidine values (AV) were measured, and total oxidation values (Totox) calculated. Only 3 of 32 fish oil supplements contained quantities of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that were equal or higher than labelled content, with most products tested (69%) containing <67%. The vast majority of supplements exceeded recommended levels of oxidation markers. 83% products exceeded the recommended PV levels, 25% exceeded AV thresholds, and 50% exceeded recommended Totox levels. Only 8% met the international recommendations, not exceeding any of these indices. Almost all fish oil supplements available in the New Zealand market contain concentrations of EPA and DHA considerably lower than claimed by labels. Importantly, the majority of supplements tested exceeded the recommended indices of oxidative markers. Surprisingly, best-before date, cost, country of origin, and exclusivity were all poor markers of supplement quality.

An unusual cause of growth failure in cystic fibrosis: A salutary reminder of the interaction between glucocorticoids and cytochrome P450 inhibiting medication.

A 12 ½ year old male with cystic fibrosis presented with growth failure after itraconazole was added to a treatment regimen including inhaled and intranasal glucocorticoids. Investigations showed severe adrenal suppression. This case demonstrates the potential for exogenous glucocorticoids to accumulate when their degradation is inhibited by a CYP3A4 inhibitor.