-
Journal of Eating Disorders Aug 2021Childhood-onset Anorexia Nervosa (AN) is recognised to be atypical in presentation, both in terms of extent and nature of eating pathology, exercise and compensatory...
BACKGROUND
Childhood-onset Anorexia Nervosa (AN) is recognised to be atypical in presentation, both in terms of extent and nature of eating pathology, exercise and compensatory behaviours with many falling short of full diagnostic criteria. Failure to consider an eating disorder diagnosis in youth who present with extreme weight loss may have serious immediate and long term implications. However, failure to consider other non-organic causes of weight loss may be equally detrimental to the child's health.
CASE PRESENTATION
This case reports on the acute presentation of a 12-year old boy, who presented to hospital in a severely malnourished state eight weeks into lockdown. To compensate for Covid-19 induced restrictions on sporting activity, this boy had followed a self-imposed daily schedule of arduous exercise, without increasing his nutritional intake. This report examines the clinical features suggestive of AN and other differential diagnosis. A discussion on the specific diagnostic differential of exercise addiction and challenges faced by youth during Covid-19 restrictions are presented.
CONCLUSION
Accepting that AN may present atypically in pre-pubertal youth, it is important that clinicians maintain an open mind in youth presenting without goal directed weight loss. Although weight loss was significant in this case, it was due to an excessive exercise regime. This may have commenced as a coping strategy in response to Covid-19 restrictions but subsequently became excessive and impairing in nature. The collateral damage of Covid-19 mandated restrictions, aimed at containing the spread of the virus, are evident in this case. Clinicians need to be alert to potentially maladaptive coping strategies and unusual or altered pathways of presentation, especially in younger children during these challenging times.
PubMed: 34372925
DOI: 10.1186/s40337-021-00450-4 -
Wellcome Open Research 2022Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in...
Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was different by foetal kidney size. Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m , 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty.
PubMed: 37274450
DOI: 10.12688/wellcomeopenres.17796.1 -
Molecular Genetics & Genomic Medicine Aug 2020Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility...
BACKGROUND
Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highlighted that these abnormalities are widespread among children and adults with FA. To date there has been no systematic study that has evaluated the endocrine abnormalities in a cohort of patients with FA, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG. The objectives of the study were to evaluate endocrine gland function in patients with FA of a single FA genotype, and to determine the frequency and nature of endocrine abnormalities in this group.
METHODS
Cross-sectional, descriptive study of 24 South African patients of African ancestry with FA (homozygous for a FANCG founder mutation). Outcomes measured included growth, pubertal status, growth hormone axis screening, thyroid gland function, glucose and insulin metabolism and bone age (BA).
RESULTS
Endocrine dysfunction was present in 70.8% (17 of 24), including abnormal insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 3 (IGFBP-3) in 25.0% (6 of 24), insulin resistance in 41.7% (10 of 24), abnormal thyroid function in 16.7% (4 of 24) and short stature in 45.8% (11 of 24). No abnormalities of glucose metabolism were identified. Abnormal pubertal status was seen in three males (12.5%). Abnormal BAs were present in 34.8% (8 of 23).
CONCLUSION
Endocrine abnormalities occur at a high frequency in patients with FA, homozygous for a FANCG founder mutation, similar to other FA cohorts. Our data are specific to FA patients with a single genotype, and therefore provide the first genotype-phenotype information on endocrine abnormalities in South African patients, homozygous for a FANCG founder mutation. Recommendations regarding endocrine screening in this patient subgroup are made, including, but not limited to, baseline testing of thyroid function, fasted insulin and glucose, and IGF-1 and IGFBP-3.
Topics: Adolescent; Black People; Blood Glucose; Child; Child, Preschool; Fanconi Anemia; Fanconi Anemia Complementation Group G Protein; Female; Founder Effect; Homozygote; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Mutation; Puberty; South Africa; Thyroid Hormones
PubMed: 32529760
DOI: 10.1002/mgg3.1351 -
Case Reports in Pediatrics 2021. Griscelli syndrome (GS) is a rare disorder characterized by partial albinism and silver hair with alteration in genes necessary for melanin transport. Type 2 GS is...
. Griscelli syndrome (GS) is a rare disorder characterized by partial albinism and silver hair with alteration in genes necessary for melanin transport. Type 2 GS is fatal due to severe immunodeficiency without curative stem cell transplant (SCT). Late endocrinopathies are quite common in other disorders after SCT. These complications have not been reported in GS. . A 7-year-old female presented for growth failure with a history of GS status post curative SCT and consequently developed graft-versus-host disease (GvHD). She also had a history of eosinophilic enterocolitis, for which she was taking supraphysiologic glucocorticoids for the past year. She presented with severe short stature along with mild hyperthyroxinemia with subsequent diagnosis of Graves' disease, which was treated with methimazole. GH therapy was commenced due to persistent growth failure, with a robust increase in growth parameters. She started spontaneous puberty; however, initial biochemical evaluation revealed hypergonadotropic hypogonadism with undetectable anti-Mullerian hormone (AMH) consistent with low ovarian reserve and premature ovarian failure. . Growth failure was multifactorial due to her inflammatory condition and poor weight gain from multiple underlying illnesses, including hyperthyroidism, as well as chronic supraphysiologic glucocorticoid use. Although hypothyroidism is more commonly seen after SCT, rare cases of hyperthyroidism have been reported. In addition to SCTs, GvHD and GS have been associated with autoimmune conditions. It is important to monitor pubertal progression as the majority of those treated with alkylating agents prior to SCT have pubertal and ovarian failure and remain at risk for premature menopause.
PubMed: 34987878
DOI: 10.1155/2021/9981306 -
Current Issues in Molecular Biology May 2024Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic,... (Review)
Review
Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic, gonadal, or phenotypic sex accompanied by abnormal development of internal and/or external genitalia. gene mutation is one of the principal genetic alterations implicated in causing DSD. This review outlines the role of gene during the process of gonadal development in humans, provides an overview of the molecular and functional characteristics of gene, and discusses potential clinical phenotypes and additional organ diseases due to mutations. mutations were analyzed in patients with 46,XY DSD and 46,XX DSD both during the neonatal and pubertal periods. Loss of function of the gene causes several different phenotypes, including some associated with disease in additional organs. Clinical phenotypes may vary, even among patients carrying the same variant, indicating that there is no specific genotype-phenotype correlation. Genetic tests are crucial diagnostic tools that should be used early in the diagnostic pathway, as early as the neonatal period, when gonadal dysgenesis is the main manifestation of mutation. gene mutations could be mainly associated with amenorrhea, ovarian failure, hypogonadism, and infertility during puberty. Fertility preservation techniques should be considered as early as possible.
PubMed: 38785542
DOI: 10.3390/cimb46050274 -
Trials Jan 2022Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several...
Vitamin D and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial.
BACKGROUND
Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV.
METHODS/DESIGN
We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMC) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMC Z-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function.
DISCUSSION
This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings.
TRIAL REGISTRATION
Pan African Clinical Trials Registry PACTR20200989766029 . Registered on 3 September 2020.
Topics: Adolescent; Bone Density; Calcium Carbonate; Child; Cholecalciferol; Dietary Supplements; Double-Blind Method; HIV Infections; Humans; Morbidity; Randomized Controlled Trials as Topic; Vitamin D; Young Adult
PubMed: 35081986
DOI: 10.1186/s13063-021-05985-0 -
Journal of the Endocrine Society May 2021Severe prolonged hypothyroidism due to Hashimoto thyroiditis may lead to rapid pubertal progression and compromised adult height after initiation of levothyroxine (LT4)...
Severe prolonged hypothyroidism due to Hashimoto thyroiditis may lead to rapid pubertal progression and compromised adult height after initiation of levothyroxine (LT4) therapy. There are no reports of aromatase inhibitor use to augment height in these patients. We describe a patient with severe hypothyroidism and growth failure who experienced rapid pubertal and bone age maturation on initiation of LT4 therapy. Anastrozole was added after 2 years to delay epiphyseal fusion. A boy aged 12 years and 1 month presented to the endocrine clinic with short stature and a markedly delayed bone age of 6 years. Brain magnetic resonance imaging showed a 1.5 × 1.0 × 1.2-cm enlarged lobular anterior pituitary. On examination, his height was -3.5 SD score (SDS) and weight was -2.87 SDS. Laboratory studies showed elevated thyrotropin (TSH) 850.6 μIU/mL, low free thyroxine 0.25 ng/dL, and elevated antithyroid antibodies. LT4 was initiated with normalization of TSH after 6 months. After 2 years of treatment he demonstrated catch-up growth with rapid bone age maturation, and his predicted adult height was compromised at 164.6 cm vs a midparental target height of 175.4 cm. Anastrozole 1 mg once daily was initiated. After 1.5 years of anastrozole treatment, the rate of his bone age advancement had slowed and his linear growth remained robust. The patient's near-final height (167 cm) was 2.4 cm taller than his height prediction prior to starting anastrozole. Anastrozole slowed the rate of bone age advancement in a patient with severe hypothyroidism and rapidly progressive puberty during treatment with LT4, leading to improvement in near-final height.
PubMed: 33928201
DOI: 10.1210/jendso/bvab025 -
BioRxiv : the Preprint Server For... Nov 2023Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia...
Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation, however contribution of uterine gland structure to gland secretions such as LIF is not known. Here we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma and muscle using the progesterone receptor causes a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a mullerian duct Cre line - , displays gland bud elongation but a failure in gland branching. Surprisingly, adult uterine epithelial deletion of ESR1 using the lactoferrin-Cre () displays normally branched uterine glands. Intriguingly, unbranched glands from uteri fail to express glandular pre-implantation , preventing implantation chamber formation and embryo alignment along the uterine mesometrial-antimesometrial axis. In contrast, branched glands from uteri display reduced expression of glandular resulting in delayed implantation chamber formation and embryo-uterine axes alignment but deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice express in the luminal epithelium but fail to express in the glandular epithelium even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandular expression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure-function contributes to pregnancy success.
PubMed: 37961508
DOI: 10.1101/2023.11.01.565233 -
Medicine Dec 202317α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to...
RATIONALE
17α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to synthesize cortisol, adrenal androgens and gonadal steroids. However, it is rare in clinic combining with type 2 diabetes mellitus (T2DM).
PATIENT CONCERNS
A 21-year-old woman was transferred to an endocrinology clinic because of paroxysmal paralysis. In addition, she presented with hypertension, primary amenorrhea and lack of pubertal development. Blood evaluation revealed hypokalemia, and a low cortisol level with an increased adrenocorticotropic hormone concentration. The renin activity and testosterone and estrogen levels were suppressed, and the gonadotropin levels were high. CT scan showed bilateral adrenal hyperplasia. Besides, this patient had hyperglycemia, hyperinsulinism and negative diabetes type 1 related antibodies. A homozygous mutation c. 985 to 987delinsAA in exon 6 was found in the patient which caused the missense mutation (p.Y329fs).
DIAGNOSES
17α-hydroxylase/17, 20-lyase deficiency combined with T2DM was considered.
INTERVENTIONS
The patient received dexamethasone, estradiol valerate, metformin, amlodipine besylate and D3 calcium carbonate tablets. The doses of dexamethasone was changed according to her blood potassium levels.
OUTCOMES
After treatment, the blood pressure, blood potassium and blood glucose returned to normal range. Besides, she had restored her menstrual cycle.
LESSONS
For patients with hypertension, hypokalemia and lack of pubertal development, the possibility of 17OHD should be considered. The subsequent treatment would be challenging in patients with combined 17OHD and T2DM, considering the potential contribution of glucocorticoids to diabetic balance and osteoporosis.
Topics: Female; Humans; Young Adult; Adrenal Hyperplasia, Congenital; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone; Hypertension; Hypokalemia; Lyases; Mixed Function Oxygenases; Mutation; Potassium; Steroid 17-alpha-Hydroxylase
PubMed: 38206738
DOI: 10.1097/MD.0000000000036727 -
Antimicrobial Agents and Chemotherapy Feb 2022This phase 2 study investigated long-term safety and efficacy of rilpivirine (RPV) plus two investigator-selected nucleos(t)ide reverse transcriptase inhibitors (NRTIs)...
This phase 2 study investigated long-term safety and efficacy of rilpivirine (RPV) plus two investigator-selected nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in HIV-1-infected antiviral therapy-naive adolescents. Participants (≥12 to <18 years of age) were treated with RPV at 25 mg once daily (q.d.) plus 2 NRTIs and entered the treatment extension period for up to 240 weeks, with visits every 3 months. Long-term safety (analysis of adverse events [AEs] and laboratory results), efficacy (virologic response and outcome for patients with viral loads of <50 and <400 by time to loss of virologic response [TLOVR] and FDA Snapshot methods, as well as CD4 cell count), and adherence (by pill count) for up to 240 weeks are presented. Twenty-four of 36 participants entered the treatment extension period, and 21 completed week 240. At week 240, a viral load of <50 copies/mL was achieved by 14/32 (43.8%) participants; virologic response by TLOVR was higher in participants with a baseline viral load of ≤100,000 copies/mL (48.0%) versus a viral load of >100,000 copies/mL (28.6%). By FDA Snapshot, a viral load of <50 copies/mL at week 240 was found in 53.1% (17/32) of participants with a baseline viral load of ≤100,000 copies/mL. Higher response was observed in participants with adherence of >95% and a baseline viral load of ≤100,000 copies/mL. Through week 240, 16/32 participants (50.0%) experienced virologic failure, including seven who developed treatment-emergent RPV resistance-associated mutations (RAMs [frequently E138K]): all 7 had ≥1 treatment-emergent NRTI RAM. No serious AEs after week 48, no discontinuations due to AEs between week 48 and week 240, and no new safety signals were observed. RPV did not affect pubertal development or adolescent growth. At the 5-year follow-up, efficacy was low in adolescents, particularly those with poor adherence and/or a high baseline viral load of >100,000 copies/mL. To limit the risk of virologic failure, RPV is restricted to patients with a baseline VL of ≤100,000 copies/mL in most countries. In addition, adequate treatment adherence to RPV treatment is imperative for long-term viral suppression and should be emphasized in the management of adolescents living with HIV. RPV exhibited a favorable long-term safety profile for adolescents living with HIV-1 with adequate adherence. (This study has been registered at ClinicalTrials.gov under identifier NCT00799864.).
Topics: Adolescent; Anti-HIV Agents; Anti-Retroviral Agents; HIV Infections; HIV-1; Humans; Rilpivirine; Treatment Outcome; Viral Load
PubMed: 34871089
DOI: 10.1128/AAC.00916-21