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Cureus Mar 2024Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including... (Review)
Review
Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.
PubMed: 38606228
DOI: 10.7759/cureus.56031 -
Molecular Human Reproduction Apr 2024Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, but its pathology has not been fully characterized and the...
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, but its pathology has not been fully characterized and the optimal treatment strategy remains unclear. Cellular senescence is a permanent state of cell-cycle arrest that can be induced by multiple stresses. Senescent cells contribute to the pathogenesis of various diseases, owing to an alteration in secretory profile, termed 'senescence-associated secretory phenotype' (SASP), including with respect to pro-inflammatory cytokines. Senolytics, a class of drugs that selectively eliminate senescent cells, are now being used clinically, and a combination of dasatinib and quercetin (DQ) has been extensively used as a senolytic. We aimed to investigate whether cellular senescence is involved in the pathology of PCOS and whether DQ treatment has beneficial effects in patients with PCOS. We obtained ovaries from patients with or without PCOS, and established a mouse model of PCOS by injecting dehydroepiandrosterone. The expression of the senescence markers p16INK4a, p21, p53, γH2AX, and senescence-associated β-galactosidase and the SASP-related factor interleukin-6 was significantly higher in the ovaries of patients with PCOS and PCOS mice than in controls. To evaluate the effects of hyperandrogenism and DQ on cellular senescence in vitro, we stimulated cultured human granulosa cells (GCs) with testosterone and treated them with DQ. The expression of markers of senescence and a SASP-related factor was increased by testosterone, and DQ reduced this increase. DQ reduced the expression of markers of senescence and a SASP-related factor in the ovaries of PCOS mice and improved their morphology. These results indicate that cellular senescence occurs in PCOS. Hyperandrogenism causes cellular senescence in GCs in PCOS, and senolytic treatment reduces the accumulation of senescent GCs and improves ovarian morphology under hyperandrogenism. Thus, DQ might represent a novel therapy for PCOS.
Topics: Polycystic Ovary Syndrome; Female; Cellular Senescence; Humans; Animals; Granulosa Cells; Quercetin; Mice; Senescence-Associated Secretory Phenotype; Adult; Dasatinib; Disease Models, Animal; Senotherapeutics; Hyperandrogenism; Interleukin-6; Dehydroepiandrosterone
PubMed: 38603629
DOI: 10.1093/molehr/gaae015 -
Internal Medicine (Tokyo, Japan) Apr 202417α-hydroxylase deficiency is a type of congenital adrenocortical hyperplasia that is typically diagnosed in childhood or adolescence. It manifests as hypertension with...
17α-hydroxylase deficiency is a type of congenital adrenocortical hyperplasia that is typically diagnosed in childhood or adolescence. It manifests as hypertension with gonadal dysfunction as the primary symptom. We herein report 17α-hydroxylase/17,20-lyase deficiency (17OHD) diagnosed at the age of 45 years. The patient presented with hypertension, irregular menstruation, and hyperaldosteronism. The clinical manifestations of 17OHD vary based on the specific variant pattern of CYP17A1. In this case, the variant was c.157_159 TCC del p. Phe53del, which has been frequently reported in Japan. The enzymatic deficiency due to this variant is partial, leading to a delay in making a correct diagnosis.
PubMed: 38599871
DOI: 10.2169/internalmedicine.3084-23 -
Giant Bilateral Adrenal Myelolipomas in a Non-Compliant Patient with Congenital Adrenal Hyperplasia.The American Journal of Case Reports Apr 2024BACKGROUND 21-hydroxylase deficiency, an essential enzyme for glucocorticoid and mineralocorticoid synthesis, is the cause of congenital adrenal hyperplasia (CAH) in...
BACKGROUND 21-hydroxylase deficiency, an essential enzyme for glucocorticoid and mineralocorticoid synthesis, is the cause of congenital adrenal hyperplasia (CAH) in more than 95% of cases. It is an autosomal recessive disorder encoded by the CYP21A2 gene, categorized into classical forms, which encompass the salt-wasting (SW) and simple virilizing (SV) forms, as well as the nonclassical form (NC). The aim of medical treatment is to replace missing glucocorticoids and, if necessary, mineralocorticoids, while also reducing elevated adrenal androgens. CASE REPORT We present the case of a 42-year-old woman with CAH who discontinued therapy during adolescence and was admitted to hospital with fatigue, nausea, and severe abdominal pain. A CT scan showed an extreme enlargement of the adrenal glands. Laboratory tests revealed elevated levels of 17-hydroxyprogesterone and other adrenal androgens, along with normal plasma metanephrine levels. Decreased morning cortisol levels suggested partial adrenal insufficiency requiring glucocorticoid replacement therapy. Due to the development of several serious complications and clinical deterioration, the multidisciplinary team recommended bilateral removal of masses measuring 300×250×200 mm on the right side and 250×200×200 mm on the left side. Histological and immunochemical examination confirmed the presence of giant myelolipomas with adrenal cortex hyperplasia. CONCLUSIONS Adrenal tumors, particularly myelolipomas, have a higher prevalence in patients with CAH. Our case report provides further evidence of the suspected link between non-compliant CAH therapy and the development of myelolipomas, along with promotion of their pronounced growth.
Topics: Adult; Female; Humans; Adrenal Gland Neoplasms; Adrenal Glands; Adrenal Hyperplasia, Congenital; Glucocorticoids; Lipoma; Myelolipoma; Steroid 21-Hydroxylase
PubMed: 38582958
DOI: 10.12659/AJCR.943005 -
Anales de Pediatria May 2024
Topics: Humans; Adrenal Gland Neoplasms; Virilism; Female; Diagnosis, Differential; Adrenal Hyperplasia, Congenital
PubMed: 38580598
DOI: 10.1016/j.anpede.2024.03.019 -
Molecular Therapy. Methods & Clinical... Jun 2024Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol...
Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia; however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex. One strategy to overcome this technological limitation is to deliver the relevant adrenocortical gene to a currently targetable organ outside of the adrenal cortex. To explore this possibility, we developed a vector encoding human 21-hydroxylase and directed expression to the liver in a mouse model of congenital adrenal hyperplasia. This extra-adrenal expression resulted in reconstitution of the steroidogenic pathway. Aldosterone and renin levels normalized, and corticosterone levels improved sufficiently to reduce adrenal hyperplasia. This strategy could provide an alternative treatment option for monogenic adrenal disorders, particularly for mineralocorticoid defects. These findings also demonstrate, when targeting the adrenal gland, that inadvertent liver transduction should be precluded as it may confound data interpretation.
PubMed: 38558568
DOI: 10.1016/j.omtm.2024.101232 -
Gynecological Endocrinology : the... Mar 2024To highlight the challenges in diagnosing 46, XY disorder of sex development related to mutation. (Review)
Review
OBJECTIVE
To highlight the challenges in diagnosing 46, XY disorder of sex development related to mutation.
METHODS
We present an unusual case of a 12-year-old female child came for enlargement of clitoris and initially diagnosed as partial androgen insensitivity syndrome (AIS).
RESULTS
On examination, the patient's vulva was found virilized with 3cm-long clitoris. Her peripheral blood karyotype was 46, XY. The ultrasound showed an empty pelvis and hormone results confirmed hyperandrogenism. Therefore, the partial AIS was suspected, but the following whole exon sequencing indicates a pathological missense mutation in . Further investigation and surgery did not reveal any brain, heart, lung or diaphragm lesions related to MYRF, but only maldeveloped internal genitalia and a persistent urachus. Her serum testosterone dropped to normal after surgical removal of the remaining ipsilateral testis and epididymitis without spermatogenesis as shown by pathology.
CONCLUSION
Due to the karyotype, hyperandrogenism, empty pelvis but a virilism after puberty, the patient was initially diagnosed as partial AIS. This misleading clinical diagnose will not be verified as the mutation if without the whole exon sequencing, particularly in the absence of obvious brain, heart, lung and diaphragm lesions as in this case.
Topics: Child; Female; Humans; Male; Androgen-Insensitivity Syndrome; Hyperandrogenism; Mutation; Receptors, Androgen; Sexual Development; Transcription Factors; Membrane Proteins
PubMed: 38547923
DOI: 10.1080/09513590.2024.2331072 -
Pakistan Journal of Medical Sciences 2024Hirsutism is a common endocrine disorder and its etiology varies from benign and idiopathic disorders to serious malignant diseases. Hirsutism creates negative impact on...
BACKGROUND AND OBJECTIVE
Hirsutism is a common endocrine disorder and its etiology varies from benign and idiopathic disorders to serious malignant diseases. Hirsutism creates negative impact on quality of life and considerable effects on fertility. Our objective was to determine the various causes of hirsutism in women presenting at two endocrine clinics.
METHOD
This cross-sectional study was conducted at Baqai Institute of Diabetology and Endocrinology, Karachi and at Jinnah hospital, Lahore from August 2020 to December 2021 women between 12-45 years of age with complains of hirsutism were included in the study. Severity of Hirsutism was evaluated using modified Ferriman-Gallwey score (FG). Patients with modified FG score of 8 or more were considered having hirsutism.
RESULTS
The study had 113 patients with a mean age of 15.50+7.29 years with 89% having moderate hirsutism (FG score 16-25). Polycystic ovaries was the most common cause of hirsutism. Common sites for hirsutism included back (83%), arms (74%), buttocks (70%), and upper abdomen (47%). High BMI (p-value <0.01) and high Dehydroepiandrosterone levels were positively associated with the severity of hirsutism (p-value of 0.006.).
CONCLUSION
The various causes of hirsutism identified were polycystic ovaries, followed by idiopathic, thyroid dysfunction, congenital adrenal hyperplasia, and hyperprolactinemia; therefore, all women presenting with hirsutism should be evaluated for potential serious and curable etiologies, before embarking on a treatment plan.
PubMed: 38545015
DOI: 10.12669/pjms.40.4.8271 -
International Journal of Molecular... Mar 2024MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a post-transcriptional level. Observational studies suggest an association of...
MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a post-transcriptional level. Observational studies suggest an association of serum miRNAs and polycystic ovary syndrome (PCOS), a common heterogeneous endocrinopathy characterized by hyperandrogenism (HA), oligo- or amenorrhea (OM) and polycystic ovaries. It is not known whether these miRNA profiles also differ between PCOS phenotypes. In this pilot study, we compared serum expression profiles between the four PCOS phenotypes (A-D) and analyzed them both in PCOS (all phenotypes) and in phenotypes with HA by quantitative-real-time PCR (qRT-PCR). The serum expression of miR-23a-3p was upregulated in phenotype B ( = 10) and discriminated it from phenotypes A ( = 11), C ( = 11) and D ( = 11, AUC = 0.837; 95%CI, 0.706-0.968; = 0.006). The expression of miR-424-5p was downregulated in phenotype C ( = 11) and discriminated it from phenotypes A, B and D (AUC = 0.801; 95%CI, 0.591-1.000; = 0.007). MiR-93-5p expression was downregulated in women with PCOS (all phenotypes, = 42) compared to controls ( = 8; = 0.042). Phenotypes with HA (A, B, C; = 32) did not show differences in the analyzed expression pattern. Our data provide new insights into phenotype-specific miRNA alterations in the serum of women with PCOS. Understanding the differential hormonal and miRNA profiles across PCOS phenotypes is important to improve the pathophysiological understanding of PCOS heterogeneity.
Topics: Humans; Female; Polycystic Ovary Syndrome; Pilot Projects; Hyperandrogenism; MicroRNAs; Phenotype
PubMed: 38542179
DOI: 10.3390/ijms25063205 -
Journal of Ovarian Research Mar 2024Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The... (Review)
Review
Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Gastrointestinal Microbiome; Polyphenols; Dysbiosis; Hyperandrogenism; Insulin Resistance; Inflammation
PubMed: 38539230
DOI: 10.1186/s13048-024-01354-y