Journal of Reproductive Endocrinology & Infertility

Description

A group of genetic disorders known as Congenital Adrenal Hyperplasia (CAH) affect cortisol biosynthesis and necessitate lifelong treatment with glucocorticoids. Teenage life and the transition from pediatric to adult care can be significantly impacted by the complexity of CAH. The objective was to determine the rates of medication adherence and transition readiness among adolescents and young adults with CAH. Due to its occult manifestations, diagnosing Neoclassic Adrenal Hyperplasia (NCAH) caused by 21-Hydroxylase Deficiency (21-HD) can be challenging. We retrospectively included 78 NCAH patients to characterize the clinical and molecular characteristics of NCAH patients with 21-hydroxylase deficiency. They were shown and compared in terms of their genotype and phenotype. Using a dual-reporter luciferase assay system, the transcriptional activities of novel CYP21A2 promoter variants were investigated. There were 53 (68%) females and 25 (32%) males in this cohort. The average age of onset was 13 (female: 13 are between 7 and 38; male: 11 are between 6 and 71). The most common complaint among females was menstrual cycle disorder (62%, n=33), while adrenal incidentalomas (52%, n=13) were the most common complaint among males.

Recessive Condition

Infertility was mentioned by 17 patients, or 22% of the total. The variant p was used the most often. Ile173Asn (n=31) (20%) Importantly, 21 patients (27 percent) had five promoter region variants; including 103/126 and 196/296.2 Patients with promoter variants had higher levels of progesterone, androstenedione, 17-hydroxyprogesterone, and ACTH, as well as older onset age. The basic transcription activity of the 103/126 and 196/296 promoter variants was reduced by 57% and 25%, respectively, when compared to the wild-type promoter. As a result, males with adrenal incidentaloma and females with menstrual cycle disorders or infertility should be considered for NCAH due to 21-HD. The CYP21A2 promoter region ought to also be investigated when genotyping NCAH patients. An autosomal recessive condition known as congenital adrenal hyperplasia is typically linked to a lack of the enzyme 21-hydroxylase, which is necessary for the biosynthesis of mineralocorticoids and glucocorticoids. A 49-year-old male with congenital adrenal hyperplasia, adrenal myelolipoma, testicular adrenal rest tumors, and primary pigmented nodular adrenocortical disease are the subjects of our case study. In the context of congenital adrenal hyperplasia, exogenous steroid treatment noncompliance is associated with adrenal myelolipoma, a rare benign disease process. The benign testicular tumors known as testicular adrenal rest tumors are associated with congenital adrenal hyperplasia. An ACTH-independent cortisol-producing disease is primary pigmented nodular adrenocortical disease. The connection between congenital adrenal hyperplasia, adrenal myelolipoma, and testicular adrenal rest tumors is emphasized in our case, as is the significance of being familiar with these connections for patient management.

Cortisol overproduction, including neuropsychological symptoms, is frequently associated with Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH). A patient with PBMAH who presented with manic symptoms and underwent unilateral adrenalectomy is the subject of our report. The most prevalent condition that results in congenital adrenal hyperplasia is 21-hydroxylase deficiency (21HD). Depending on the severity of the disease, 21HD women's increased production of adrenal-derived androgens and progesterone affects their reproductive function and fertility in a variety of ways. A number of factors, including an overproduction of androgen and progesterone that disrupts the gonadotropic axis and mechanical and psychological factors related to genital surgery, impair sexuality and fertility in women with classic 21OHD. These women's fertility and fecundity improve over time. Contrarily, non-classic 21OHD women appear to have relative subfertility. Genetic counseling and partner genotyping are required prior to pregnancy. A rare condition known as Macronodular Hyperplasia (MH) of the adrenal gland typically presents as Cushing Syndrome. A renal tumor may be mistaken for an adrenal tumor in an asymptomatic patient, despite being typically readily apparent on imaging. A patient with combined macro- and micro-nodular adrenal hyperplasia that appears to be an upper pole renal mass is the subject of our report. The robotic partial nephrectomy and partial adrenalectomy were performed on the patient without incident. One of the major complications that can lead to infertility in male patients with Congenital Adrenal Hyperplasia (CAH), Testicular Adrenal Rest Tumor (TART) should be diagnosed and treated early. It is unclear exactly what causes CAH patients to develop TART.

Adrenalectomy

The correlation between genotype and phenotype in CAH patients receiving TART is the focus of this study. Pituitary ACTH-independent Cushing's Syndrome (CS) is rare and is characterized by primary bilateral adrenocortical hyperplasia. Micro nodular Adrenal Hyperplasia (MiAH), which is subdivided into Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and Isolated Micro Nodular Adrenocortical Disease (i-MAD), and Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) are the two main subtypes. The most effective treatment for these entities is a topic of heated debate. Recent studies have shown that Unilateral Adrenalectomy (UA) can be effective in patients with PBMAH and some patients with MiBAH with fewer long-term side effects. Bilateral Adrenalectomy (BA) was once the treatment of choice for patients with overt CS. For these patients, medical therapies can also be used as a bridge to surgery or rarely in the long run. Taking into account the most recent findings in pathophysiology and genetics, we examine the various degrees of CS that result from PBMAH and MiBAH, with a special focus on their respective therapies, which include UA. Mutations in the CYP21A2 gene are the root cause of the autosomal-recessive disorder known as congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Computational structural modeling suggested that these brand-new variants probably have an impact on structural stability. Prenatal counseling and precise diagnosis are aided by our findings, which contribute to a deeper comprehension of the CYP21A2 mutational spectrum.

Adrenal masses are more likely to occur in people with congenital adrenal hyperplasia. It is still unknown whether CAH patients have a higher risk of adrenal carcinoma or a higher frequency of incidentalomas. As a result, the management CAH subjects whose adrenal masses appear suspicious continue to be problematic. A group of monogenic, autosomal recessive disorders known as Congenital Adrenal Hyperplasia (CAH) is typically diagnosed in childhood. Cortisol biosynthesis is disrupted as a result of enzyme deficiencies in the adrenal steroid genesis pathways, leading to clinical manifestations of CAH. Despite not being a primary hypertensive disorder, classical forms of CAH have a higher prevalence of hypertension due to difficulties in glucocorticoid and mineralocorticoid therapy dose adjustments. Rare forms of CAH that are associated with endocrine hypertension include P450 oxidoreductase deficiency, 17-hydroxylase deficiency, and 11-hydroxylase deficiency. These deficiencies may be the only presenting symptom in late childhood and early adulthood. Due to the excessive secretion of the mineralocorticoid deoxycorticosterone in these patients with CAH, hypokalemia, low aldosterone and renin levels, and hypertension are frequently accompanied by these conditions. Hyperpigmentation, hirsutism, short stature, irregular menstruation, and other physical examination findings may direct the CAH diagnosis. Molecular genetic analysis is used to confirm the diagnosis made by measuring the steroid hormone profile in individuals who are suspected of having the condition. Cortisol must be replaced throughout a patient's life for congenital adrenal hyperplasia (CAH). While issues with cognitive function, particularly working memory, have previously been identified, the disease's long-term effects on brain function remain a mystery.