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Endocrinology, Diabetes & Metabolism... Jan 2024Kabuki syndrome is a genetic disorder characterised by distinctive facial features, developmental delays, and multisystem congenital anomalies. Endocrine complications...
SUMMARY
Kabuki syndrome is a genetic disorder characterised by distinctive facial features, developmental delays, and multisystem congenital anomalies. Endocrine complications such as premature thelarche and short stature are common, whereas disorders of glycaemic control are less frequent. We describe a 23-year-old white female referred to the diabetes clinic for hyperglycaemia during haemodialysis. She was subsequently diagnosed with Kabuki syndrome based on characteristic clinical features, confirmed by detecting a heterozygous pathogenic variant in KMT2D. She was known to have had multiple congenital anomalies at birth, including complex congenital heart disease and a single dysplastic ectopic kidney, and received a cadaveric transplanted kidney at the age of 13. She had hyperglycaemia consistent with post-transplant diabetes mellitus (DM) and was started on insulin. Examination at the time revealed truncal obesity. She developed acute graft rejection and graft failure 14 months post-transplant and she was started on haemodialysis. Her blood glucose levels normalised post-graft explant, but she was hyperglycaemic again during haemodialysis at the age of 23. Given her clinical phenotype, negative diabetes antibodies and normal pancreas on ultrasound, she was assumed to have type 2 DM and achieved good glycaemic control with gliclazide.
LEARNING POINTS
Involve clinical genetics early in the investigative pathway of sick neonates born with multiple congenital anomalies to establish a diagnosis to direct medical care. Consider the possibility of Kabuki syndrome (KS) in the differential diagnoses in any neonate with normal karyotyping or microarray analysis and with multiple congenital anomalies (especially cardiac, renal, or skeletal), dysmorphic facial features, transient neonatal hypoglycaemia and failure to thrive. Consider the possibility of diabetes as an endocrine complication in KS patients who are obese or who have autoimmune disorders.
PubMed: 38290219
DOI: 10.1530/EDM-23-0133 -
TouchREVIEWS in Endocrinology Nov 2023Various studies, conducted since 2007, have reported a total of eight boys with prepubertal gynaecomastia and four girls with premature thelarche following exposure to... (Review)
Review
Various studies, conducted since 2007, have reported a total of eight boys with prepubertal gynaecomastia and four girls with premature thelarche following exposure to lavender and/or tree tea oil. All patients experienced regression of the breast tissue after they stopped using these oils. Both of these essential oils, and several of their constituents, have oestrogenic and antiandrogenic activity . However, limited dermal penetration of some of the components means that the findings cannot be extrapolated to the situation. There are unanswered questions as to how much lavender or tea tree oil was actually present in the skincare products used by the children and a lack of information about exposure to other agents. Furthermore, since both prepubertal gynaecomastia and premature thelarche often spontaneously regress, it cannot be concluded that the use of lavender and/or tree tea oil is the cause of the gynaecomastia and thelarche in these children.
PubMed: 38187077
DOI: 10.17925/EE.2023.19.2.9 -
Frontiers in Endocrinology 2023Girls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as...
INTRODUCTION
Girls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as "thelarche variant" (TV), characterized by an FSH-predominant response, although a univocal definition is lacking.
METHODS
Retrospective analysis on 91 girls with early thelarche (<8 years) and advanced bone age and/or accelerated growth who underwent 104 LHRH tests. Patients were classified into CPP (LH peak ≥5 IU/L; n = 28, 31%), TV (FSH peak ≥20 IU/L, LH peak <5 IU/L; n = 15, 16%), or PT (FSH peak <20 IU/L and LH peak <5 IU/L; n = 48, 53%).
RESULTS
TV patients were younger (5.51 years) and with less advanced bone age (+0.8 years). They had higher basal and peak FSH (2.5 and 26.6 IU/L) and lower basal and peak LH/FSH ratios (0.08 and 0.11). The prevalence of presence of ovarian follicles >5 mm in TV (42%) was similar to CPP but significantly higher than PT, whereas maximum ovarian volume was smaller in TV (1.0 cm). At the last follow-up visit (available in 60% of the cases), 44% of TV developed CPP compared with 14% of PT (p = 0.04). At first evaluation, those who progressed to CPP had a higher basal FSH (3.2 IU/L), lower LH/FSH ratio (0.07), and a higher peak LH (4.1 IU/L) compared with those who did not progress to CPP (basal FSH 1.9 IU/L, p < 0.01; basal LH/FSH ratio 0.12, p < 0.01; peak LH 2.8 IU/L, p = 0.02).
CONCLUSION
Using laboratory parameters only as a definition, we identified the clinical, laboratory, and imaging features of TV: these girls showed less advanced bone age and FSH predominance also at baseline, with smaller ovaries but with follicles >5 mm. Almost half of girls initially diagnosed as TV developed CPP at last follow-up visit, and these girls had higher baseline FSH, lower baseline LH/FSH ratio, and higher peak LH at first evaluation. Therefore, TV may represent a "precocious prepuberty" in which the FSH predominance may initially limit the progression into proper puberty, but it may eventually trigger full puberty (even CPP, depending on the girls' age).
Topics: Female; Humans; Infant; Luteinizing Hormone; Follicle Stimulating Hormone; Retrospective Studies; Prevalence; Puberty, Precocious
PubMed: 38107513
DOI: 10.3389/fendo.2023.1303989 -
Acta Bio-medica : Atenei Parmensis Dec 2023The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to...
BACKGROUND
The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors.
METHODS
We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk.
RESULTS
Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders.
CONCLUSION
Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
Topics: Female; Humans; Male; Child; Diabetes Mellitus, Type 2; Gonadotropin-Releasing Hormone; Puberty, Precocious; Obesity; Puberty
PubMed: 38054666
DOI: 10.23750/abm.v94i6.15316 -
Cureus Oct 2023Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls... (Review)
Review
Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls by the enlargement of the breasts (thelarche) in girls and in boys by the enlargement of the testes in either volume or length (testicular volume = 4 mL, testicular length = 25 mm, or both). Two types of PP are recognized - namely central PP (CPP) and peripheral PP (PPP). This paper aims to describe the clinical findings and laboratory workup of PP and to illustrate the new trends in the management of precocious sexual maturation. Gonadotropin-releasing hormone (GnRH)-independent type (PPP) refers to the development of early pubertal maturation not related to the central activation of the hypothalamic-pituitary-gonadal (HPG) axis. It is classified into genetic or acquired disorders. The most common forms of congenital or genetic causes involve McCune-Albright syndrome (MAS), familial male-limited PP, and congenital adrenal hyperplasia. The acquired causes include exogenous exposure to androgens, functioning tumors or cysts, and the pseudo-PP of profound primary hypothyroidism. On the other hand, CPP is the most common and it is a gonadotropin-dependent form. It is due to premature maturation of the HPG axis. CPP may occur as genetic alterations, such as MKRN3, DLK1, or KISS1;as a part of mutations in theepigenetic factors that regulate the HPG axis, such as Lin28b and let-7; or as a part of syndromes, central lesions such as hypothalamic hamartoma, and others. A full, detailed history and physical examination should be taken. Furthermore, several investigations should be conducted for both types of PP, including the estimation of serum gonadotropins such as luteinizing and follicle-stimulating hormones and sex steroids, in addition to a radiographic workup and thyroid function tests. Treatment depends on the type of PP: Long-acting GnRHa, either intramuscularly or implanted, is the norm of care for CPP management, while in PPP, especially in congenital adrenal hyperplasia, the goal of management is to suppress adrenal androgen secretion by glucocorticoids. In addition, anastrozole and letrozole - third-generation aromatase inhibitors - are more potent for MAS.
PubMed: 38021712
DOI: 10.7759/cureus.47485 -
Children (Basel, Switzerland) Nov 2023The gold standard gonadotropin-releasing hormone (GnRH) stimulation test uses the response to intravenously injected gonadorelin to diagnose central precocious puberty...
BACKGROUND
The gold standard gonadotropin-releasing hormone (GnRH) stimulation test uses the response to intravenously injected gonadorelin to diagnose central precocious puberty (CPP). However, gonadorelin is not always readily available.
OBJECTIVE
This study investigated the diagnostic efficacy of the subcutaneous triptorelin test and the optimal blood sampling time for diagnosis of CPP.
METHODS
This study retrospectively examined the medical records of 220 girls who had undergone either the triptorelin or gonadorelin test and compared their clinical characteristics. We retrospectively compared clinical parameters between girls diagnosed with CPP ( = 111) and idiopathic premature thelarche (IPT) ( = 109) using three different diagnostic methods: the gonadorelin, triptorelin 120 min, and triptorelin 180 min tests. The diagnostic ability of the stimulated luteinizing hormone (LH) concentration in the triptorelin test for CPP was evaluated using receiver operating characteristic (ROC) analysis.
RESULTS
The CPP group exhibited higher basal and peak gonadotropin levels, more advanced bone age, and a lower body mass index standard deviation score than the IPT group. In the gonadorelin test group, all girls with CPP exhibited a peak LH response 30-60 min after intravenous gonadorelin injection. In the triptorelin test group, most girls with CPP exhibited a peak LH response 60-180 min after subcutaneous triptorelin injection ( = 68). On the ROC curve, a peak LH concentration of ≥ 4.52 IU/L at 120 min had the highest CPP diagnostic accuracy, with sensitivity and specificity of 100% and 95.83%, respectively.
PubMed: 38002921
DOI: 10.3390/children10111830 -
Journal of Ovarian Research Nov 2023Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent.
OBJECTIVE
The aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls.
METHODS
PubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model.
RESULTS
A total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH.
CONCLUSION
Scientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.
Topics: Female; Humans; Anti-Mullerian Hormone; Follicle Stimulating Hormone; Inhibins; Observational Studies as Topic; Puberty, Precocious
PubMed: 37996919
DOI: 10.1186/s13048-023-01302-2 -
Archives of Toxicology Jan 2024The acyclic linear monoterpenes Linalool (Lin) and Linalyl acetate (LinAc) occur in nature as major constituents of various essential oils such as lavender oils. A...
Critical assessment of the endocrine potential of Linalool and Linalyl acetate: proactive testing strategy assessing estrogenic and androgenic activity of Lavender oil main components.
The acyclic linear monoterpenes Linalool (Lin) and Linalyl acetate (LinAc) occur in nature as major constituents of various essential oils such as lavender oils. A potential endocrine activity of these compounds was discussed in literature including premature thelarche and prepubertal gynecomastia due to lavender product use. This study aims to follow-up on these critical findings reported by testing Lin and LinAc in several studies in line with current guidance and regulatory framework. No relevant anti-/ER and AR-mediated activity was observed in recombinant yeast cell-based screening tests and guideline reporter gene in vitro assays in mammalian cells. Findings in the screening test suggested an anti-androgenic activity, which could not be confirmed in the respective mammalian cell guideline assay. Mechanistic guideline in vivo studies (Uterotrophic and Hershberger assays) with Lin did not show significant dose related changes in estrogen or androgen sensitive organ weights and a guideline reproductive toxicity screening study did not reveal evident effects on sex steroid hormone sensitive organ weights, associated histopathological findings and altered sperm parameters. Estrous cycling and mating/fertility indices were not affected and no evident Lin-related steroid hormone dependent effects were found in the offspring. Overall, the initial concerns from literature were not confirmed. Findings in the yeast screening test were aberrant from follow-up guideline in vitro and in vivo studies, which underlines the need to apply careful interpretation of single in vitro test results to support a respective line of evidence and to establish a biologically plausible link to an adverse outcome.
Topics: Animals; Male; Allergens; Androgens; Estrone; Mammals; Monoterpenes; Oils, Volatile; Plant Oils; Saccharomyces cerevisiae; Seeds
PubMed: 37906319
DOI: 10.1007/s00204-023-03623-z -
European Review For Medical and... Oct 2023Although there is a relationship between earlier onset of puberty and increased adiposity tissue. Publications in the literature on adiposis in patients with central...
OBJECTIVE
Although there is a relationship between earlier onset of puberty and increased adiposity tissue. Publications in the literature on adiposis in patients with central precocious puberty (CPP) and visceral fat thickness (VFT) have conflicting results. So, in this study, we aimed to evaluate the relationship between sexual maturation and obesity in the development of early puberty and to examine their relationship with pelvic sonographic parameters.
PATIENTS AND METHODS
A total of 126 girls [patients - premature thelarche (PT) and CPP - and controls] were included in this study. Anthropometric and ultrasonographic evaluations were made by the same pediatric endocrinologist and pediatric radiologist, respectively. Pubertal stages were made according to the Tanner stages. Height, weight, and body mass index were measured as anthropometric measurements, and visceral, subcutaneous, and transabdominal fat thicknesses were measured in sonographic evaluation.
RESULTS
The study population was divided into three groups: 44 healthy subjects to Group 1, 23 patients with PT to Group 2, and 59 patients with CPP to Group 3. When we evaluated the anthropometric and ultrasonographic parameters according to pubertal status, significant differences, especially between Group 1 and Group 3, were observed in all data. In the multiple logistic regression analysis, the endometrial thickness (OR = 7.521, p < 0.001) and VFT (OR = 1.530, p < 0.001) were found to be independent predictors of precocious puberty.
CONCLUSIONS
It has been found that VFT and endometrial thickness measurements, which are evaluated quickly and accurately by USG, are important predictors of prepubertal precociousness.
Topics: Child; Female; Humans; Puberty, Precocious; Intra-Abdominal Fat; Puberty; Anthropometry; Obesity
PubMed: 37843336
DOI: 10.26355/eurrev_202310_33950 -
Nutrients Oct 2023The prevalence of central precocious puberty (CPP) in girls has increased worldwide and is often associated with obesity in childhood as well as high fat/high glycemic... (Review)
Review
The prevalence of central precocious puberty (CPP) in girls has increased worldwide and is often associated with obesity in childhood as well as high fat/high glycemic index diets. Evidence suggests that subjects with obesity present with alterations in appetite-regulating hormones. The arcuate and paraventricular nuclei of the hypothalamus are the centers of action of appetite hormones, as well as the location of gonadotropin-releasing hormone (GnRH) neurons, the activation of which results in the onset of puberty. This anatomical proximity raises the question of possible alterations in appetite-regulating hormones in patients with CPP. Furthermore, diet-induced hypothalamic inflammation constitutes a probable mechanism of the pathophysiology of CPP, as well as alterations in appetite-regulating hormones in young children. In this article, we summarize the evidence investigating whether girls with CPP present with alterations in appetite-regulating hormones. We present evidence that leptin concentrations are elevated in girls with CPP, ghrelin concentrations are lower in girls with CPP, nesfatin-1 and orexin-A concentrations are elevated among girls with premature thelarche, and insulin concentrations are increased in girls with early menarche.
Topics: Female; Child; Humans; Child, Preschool; Puberty, Precocious; Luteinizing Hormone; Appetite; Pediatric Obesity; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone
PubMed: 37836591
DOI: 10.3390/nu15194306