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The Journal of Clinical Endocrinology... Sep 2022Prenatal treatment with dexamethasone (DEX) has been used to prevent virilization in females at risk of congenital adrenal hyperplasia (CAH). Both affected and...
CONTEXT
Prenatal treatment with dexamethasone (DEX) has been used to prevent virilization in females at risk of congenital adrenal hyperplasia (CAH). Both affected and unaffected girls, as well boys, are treated until the genotype and sex of the fetus is known (gestational weeks 10-12). After that, only affected girls are treated until term. Exposure to a high synthetic glucocorticoid dosage may alter the developmental trajectory of the brain, with alterations in resting-state functional connectivity of the brain at adult age.
OBJECTIVE
To investigate resting-state functional connectivity in subjects at risk of having CAH, exposed to DEX treatment during the first trimester of fetal life, both in the whole brain and in 3 regions of interest (amygdala, hippocampus, and superior frontal gyrus).
DESIGN, SETTING, AND PARTICIPANTS
Eighteen participants (8 females) at risk of having CAH, exposed to DEX treatment, and 38 controls (24 females), age range 16 to 26 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. We used 2 different approaches: an exploratory whole-brain analysis and seed-based analysis. For seed-based analysis, we chose 3 different brain regions (amygdala, hippocampus, and superior frontal gyrus) based on our previous findings and literature evidence.
RESULTS
We did not observe any differences in functional connectivity during rest, either in the whole brain nor in seed-based connectivity analyses at this adolescent and young adult age.
CONCLUSIONS
Our results are reassuring; however, future studies on larger samples and with more sensitive methodologies are needed to confirm these findings.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adult; Dexamethasone; Female; Glucocorticoids; Humans; Magnetic Resonance Imaging; Male; Pregnancy; Pregnancy Trimester, First; Virilism; Young Adult
PubMed: 35882216
DOI: 10.1210/clinem/dgac426 -
Hormone and Metabolic Research =... Sep 2022Polycystic ovarian syndrome (PCOS) is a heterogenous condition accounting for serious health complications. The present study was conducted to assess the early clinical,...
Polycystic ovarian syndrome (PCOS) is a heterogenous condition accounting for serious health complications. The present study was conducted to assess the early clinical, biochemical, and radiological features in obese, non-obese young women with PCOS as compared to non-PCOS women. The study was conducted on 120 young women (18-22 years) with 80 having features of PCOS [40 obese (BMI≥25 kg/m2) and 40 non-obese (BMI<25 kg/m2) PCOS] as cases and 40 without PCOS as controls in a rural tertiary care center of Northern India over one year (2017-2018). After enrolment of cases and control, the anthropometric measurements, early clinical symptoms, and biochemical and ultrasonographic features were compared between the groups. Statistical analysis was done using SPSS software version 22.0 (p-value<0.05). A significant difference in anthropometric measurements were observed between obese and non-obese PCOS cases. Clinical features like acne, acanthosis nigricans, and hirsutism were more prevalent in obese PCOS as compared to non-obese and controls. On ultrasound, PCOS cases had a significantly increased number of peripherally arranged ovarian follicles, and ovarian volume. The LH: FSH ratio was significantly higher in cases as compared to controls. The levels of serum LH (10.04±1.60 vs. 8.93±2.40 mIU/ml) and total testosterone (2.71±0.39 vs. 2.21±0.39 pg/ml) were higher in obese PCOS as compared to non-obese PCOS cases. In conclusion, clinical, biochemical, and radiological features can be used in the early diagnosis of PCOS. Obesity is an independent risk factor for PCOS and is associated with an increased risk of complications.
Topics: Body Mass Index; Female; Hirsutism; Humans; Hyperandrogenism; Obesity; Polycystic Ovary Syndrome
PubMed: 35858631
DOI: 10.1055/a-1880-1264 -
The Journal of Clinical Endocrinology... Aug 2022Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face,...
CONTEXT
Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face, trunk, and extremities. Patients develop premature diabetes, hypertriglyceridemia, hepatic steatosis, and polycystic ovary syndrome. However, sparing of the facial fat and precocious pubertal development has not been previously reported in CGL1.
CASE DESCRIPTION
We report a 21-year-old woman of European descent with CGL1 who had sparing of the facial fat and premature thelarche at birth with premature pubarche and menstrual bleeding at age 3 years. Her serum 17-OH progesterone level rose to 1000 ng/dL (30.26 nmol/L) after cosyntropin stimulation test, suggestive of nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. Hydrocortisone replacement therapy from age 3.5 to 10 years resulted in cessation of menstruation and growth of pubic hair, and a reduction of breast size. Sanger and whole-exome sequencing revealed compound heterozygous variants c.493-1G>C; p.(Leu165_Gln196del), and c.del366_588+534; p.(Leu123Cysfs*55) in AGPAT2 plus c.806G>C; p.(Ser269Thr) and c.844G>T; p.(Val282Leu) in CYP21A2. She developed diabetes at age 13 requiring high-dose insulin and had 7 episodes of acute pancreatitis due to extreme hypertriglyceridemia in the next 5 years. Metreleptin therapy was initiated at age 18 and after 3 years, she had remission of diabetes and hypertriglyceridemia; however, menstrual irregularity and severe hirsutism did not improve.
CONCLUSION
Concomitant NCAH in this CGL1 patient was associated with precocious pubertal development and sparing of facial fat. Metreleptin therapy drastically improved her hyperglycemia and hyperlipidemia but not menstrual irregularity and hirsutism.
Topics: Acute Disease; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Child; Child, Preschool; Female; Hirsutism; Humans; Hyperinsulinism; Hyperlipidemias; Hypertriglyceridemia; Infant, Newborn; Lipodystrophy, Congenital Generalized; Menstruation Disturbances; Pancreatitis; Puberty, Precocious; Steroid 21-Hydroxylase; Young Adult
PubMed: 35857714
DOI: 10.1210/clinem/dgac406 -
The American Journal of Case Reports May 2022BACKGROUND The immunomodulatory and pharmacokinetic effects of cyclosporine A are used to treat diverse disease entities in different medical fields, including organ...
BACKGROUND The immunomodulatory and pharmacokinetic effects of cyclosporine A are used to treat diverse disease entities in different medical fields, including organ transplantation and/or autoimmune diseases. It is also applied in patients with nephrotic range proteinuria as an adjunct to steroids and supportive antihypertensive/antiproteinuric medications. Cyclosporine has a small therapeutic window and is dosed with respect to the underlying disease entity and severity via trough level adaptations. Among its most frequent adverse effects are hypertension, nephrotoxicity, neurotoxicity, and electrolyte disturbances. Hypertrichosis and gingival hyperplasia are obvious and widely recognized adverse effects. CASE REPORT We report on a 66-year-old woman who was treated with cyclosporine A for primary membranous nephropathy. During treatment with cyclosporine, she developed hirsutism and gingival hyperplasia. Later, she reported having impaired nasal breathing and dyspnea on mild physical exercise. Clinical, rhinoscopic, and radiological evaluations showed marked conchal hyperplasia as a potential cause of her symptoms. An extensive medical work-up did not show evidence of allergic, immunologic, or other drug adverse effects, suggesting cyclosporine-induced hyperplasia of the turbinates as a hypothetical causative factor. Dose reductions did not lead to resolution of symptoms but resulted in increasing proteinuria. Therefore, cyclosporine was stopped, and the patient was treated with rituximab. Thereafter, hirsutism and gingival and conchal hyperplasia gradually regressed over 2-4 months, showing complete resolution of conchal hyperplasia on computed-tomography follow-up after 6 months. CONCLUSIONS Cyclosporine can not only result in gingival hyperplasia but also in hyperplasia of the turbinates leading to impaired nasal breathing and shortness of breath on exertion. An extensive search for many other known causes of conchal swelling is warranted to finally suggest an adverse effect of cyclosporine. Discontinuation of cyclosporine resulted in complete remission of conchal hyperplasia as well as other adverse effects.
Topics: Aged; Cyclosporine; Female; Gingival Hyperplasia; Glomerulonephritis, Membranous; Hirsutism; Humans; Hyperplasia; Immunosuppressive Agents; Nasal Obstruction; Proteinuria; Turbinates
PubMed: 35642551
DOI: 10.12659/AJCR.935362 -
Journal of Medical Case Reports May 2022Adrenocortical carcinoma is a rare malignancy (0.5-2 cases/million/year) with a poor prognosis. Hypercortisolism, virilization, and compressive features are among the...
BACKGROUND
Adrenocortical carcinoma is a rare malignancy (0.5-2 cases/million/year) with a poor prognosis. Hypercortisolism, virilization, and compressive features are among the common presentations of adrenocortical carcinoma. Hematuria is one of the rare initial presentations of adrenocortical carcinoma reported in the literature. We report a case of adrenal carcinoma presenting with microscopic hematuria.
CASE PRESENTATION
A 67-year-old Sri Lankan patient with diabetes, hypertension, and ischemic heart disease presented with an acute coronary event. During the routine evaluation, microscopic hematuria was detected without proteinuria or active sediments. She denied any painful micturition, previous similar episodes, or abdominal pain. Further evaluation revealed a hypokalemia with biochemical evidence of hypercortisolism and high testosterone levels with suppressed adrenocorticotropic hormone levels. On imaging, there was evidence of a right suprarenal mass 7 cm × 3 cm × 6 cm in size that was hypoechoic and lobulated and suggestive of a lipid-poor tumor. She underwent adrenalectomy. By the time of surgery 3 weeks later, significant weight gain with features of Cushing syndrome, including hirsutism, skin atrophy, easy bruising without virilization, and proximal myopathy, were noted. Histology identified a right-sided adrenal tumor with capsular and vascular invasion. Hypercortisolism and hematuria disappeared after surgery. The patient was referred for further oncological management.
CONCLUSION
This case illustrates a rare presentation of adrenal carcinoma. Awareness of this presentation may facilitate early evaluation and management.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Aged; Cushing Syndrome; Female; Hematuria; Humans; Virilism
PubMed: 35637536
DOI: 10.1186/s13256-022-03398-4 -
Journal of Investigative Medicine High... 2022Androgen-producing steroid cell ovarian tumors are rare, comprising less than 1% of ovarian neoplasms, and can present with infertility and rapid virilization. Here we...
Androgen-producing steroid cell ovarian tumors are rare, comprising less than 1% of ovarian neoplasms, and can present with infertility and rapid virilization. Here we discuss the case of a 28-year-old woman who presented with an unusually insidious 2-year history of infertility, hirsutism, and clitoromegaly who was found to have an elevated serum testosterone and a left ovarian mass. She underwent oophorectomy and pathology revealed a steroid cell tumor, not otherwise specified (NOS), with no malignant features. Following surgery, the patient's hyperandrogenic symptoms resolved with normalization of testosterone within 6 months, and she was able to conceive spontaneously. In reproductive-aged women with progressive hyperandrogenic symptoms, androgen-producing tumors, including those of ovarian origin, should be suspected. Thorough investigation, including plasma hormone levels and tumor histology, can lead to accurate diagnosis and management. Treatment should be guided by histology and surgical staging, with consideration for future fertility desires. Women who have not completed childbearing can undergo unilateral oophorectomy or tumor resection for benign tumors, with close monitoring of sex hormone levels postoperatively.
Topics: Adult; Androgens; Female; Humans; Infertility; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; Testosterone; Virilism
PubMed: 35596563
DOI: 10.1177/23247096211056494 -
Clinica Chimica Acta; International... Jun 2022A polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting females. Furthermore, it is a heterogeneous disease with a variety of etiologies and... (Review)
Review
A polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting females. Furthermore, it is a heterogeneous disease with a variety of etiologies and outcomes. Patients frequently complain about infertility, irregular menstruation, acne, seborrheic dermatitis, hirsutism, and obesity. PCOS can be caused by hypothalamic-pituitary-ovarian axis dysfunction, heredity, or metabolic abnormalities. PCOS is characterized by chronic low-level inflammation, which includes an imbalance in pro-inflammatory factor secretion, endothelial cell dysfunction, and leukocytosis. PCOS is also distinguished by hormonal and immune dysregulation. During PCOS, immune cells and immune regulatory molecules play critical roles in maintaining metabolic homeostasis and regulating immune responses. Because of oligo/anovulation, patients with PCOS have low progesterone levels. Therefore, low progesterone levels in PCOS overstimulate the immune system, causing it to produce more estrogen, which leads to a variety of autoantibodies. This review aims to summarize the immune regulation involved in the pathogenesis of PCOS and pave the way for the development of better PCOS treatment options in the near future.
Topics: Anovulation; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Progesterone
PubMed: 35447143
DOI: 10.1016/j.cca.2022.04.234 -
BMJ Case Reports Apr 2022Hyperandrogenism with virilisation de novo in postmenopausal women is exceedingly rare, with aetiology oscillating between ovarian tumours, adrenal tumours, ovarian...
Hyperandrogenism with virilisation de novo in postmenopausal women is exceedingly rare, with aetiology oscillating between ovarian tumours, adrenal tumours, ovarian hyperthecosis and, less frequently, Cushing's syndrome. We report a case of a postmenopausal woman in her late 60s, referred from her primary healthcare physician to a gynaecology appointment due to hirsutism and vasomotor symptoms. At physical examination, clitoromegaly was also identified. Blood tests revealed severe hyperandrogenemia, with total testosterone above 200 ng/dL, but transvaginal ultrasound and abdominal CT were unremarkable. Three months later, abdominal CT was repeated, revealing a moderate heterogeneous enhancement with 18 mm on the left ovary, which was confirmed by transvaginal ultrasound. Total laparoscopic hysterectomy with bilateral adnexectomy was performed. Histopathological examination reported an ovarian steroid cell tumour not otherwise specified on the left ovary and bilateral ovarian hyperthecosis. Two months later, the patient had normal total testosterone and the hirsutism complaints were completely absent.
Topics: Female; Hirsutism; Humans; Hyperandrogenism; Ovarian Neoplasms; Polycystic Ovary Syndrome; Postmenopause; Sex Cord-Gonadal Stromal Tumors; Testosterone; Virilism
PubMed: 35444026
DOI: 10.1136/bcr-2022-249907 -
Metabolic Surgery on Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.Frontiers in Endocrinology 2022Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease that is closely related to obesity. Metabolic surgery ameliorates a series of clinical... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease that is closely related to obesity. Metabolic surgery ameliorates a series of clinical manifestations and related comorbidities of PCOS. However, the overall efficacy of metabolic surgery on PCOS remains uncertain. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of metabolic surgery on obese patients with PCOS. A systematic literature search for relevant studies was conducted on PubMed, Embase, Web of Science, and the Cochrane Library from inception to June 2021. Data extraction and quality evaluation were performed by three researchers, and RevMan 5.4 software was used to conduct the meta-analysis. A total of 14 studies involving 501 obese patients with PCOS were included. Incidence of PCOS in obese women ranged from 5.5% to 63.5% among the included studies. The results showed the incidence of abnormal menstruation decreased from 81% to 15% (OR=0.03, 95% confidence interval (CI): 0.01-0.08), while the incidence of hirsutism dropped from 71% to 38% (OR=0.21, 95% CI: 0.06-0.74). Serum total testosterone and free testosterone levels decreased by 25.92 ng/dL (MD = -25.92, 95% CI: -28.90- -22.93) and 2.28 ng/dL (SMD = -2.28, 95% CI: -3.67- -0.89), respectively. Sex hormone-binding globulin (SHBG) levels increased by 26.46 nmol/L (MD = 26.46, 95% CI: 12.97-39.95). Serum anti-Mullerian hormone (AMH) levels decreased by 1.29 ng/mL (MD = -1.29, 95% CI: -1.92- -0.66). Small sample size studies revealed that pregnancy rates ranged from 95.2% to 100% postoperatively. Metabolic surgery contributed to marked improvement of abnormal menstruation, hirsutism, and levels of free testosterone, total testosterone, SHBG, and AMH in patients with PCOS. Our findings indicate that patients with PCOS are expected to benefit from metabolic surgery, and could help potentially improve their reproductive outcomes. Metabolic surgery could thus be a new viable option for the clinical treatment of PCOS.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021251524.
Topics: Anti-Mullerian Hormone; Bariatric Surgery; Female; Hirsutism; Humans; Obesity; Polycystic Ovary Syndrome
PubMed: 35360056
DOI: 10.3389/fendo.2022.848947 -
Clinical Endocrinology Aug 2022Androgen excess in women typically presents clinically with hirsutism, acne or androgenic alopecia. In the vast majority of cases, the underlying aetiology is polycystic... (Review)
Review
Androgen excess in women typically presents clinically with hirsutism, acne or androgenic alopecia. In the vast majority of cases, the underlying aetiology is polycystic ovary syndrome (PCOS), a common chronic condition that affects up to 10% of all women. Identification of women with non-PCOS pathology within large cohorts of patients presenting with androgen excess represents a diagnostic challenge for the endocrinologist, and rare pathology including nonclassic congenital adrenal hyperplasia, severe insulin resistance syndromes, Cushing's disease or androgen-secreting tumours of the ovary or adrenal gland may be missed in the absence of a pragmatic screening approach. Detailed clinical history, physical examination and biochemical phenotyping are critical in risk-stratifying women who are at the highest risk of non-PCOS disorders. Red flag features such as rapid onset symptoms, overt virilization, postmenopausal onset or severe biochemical disturbances should prompt investigations for underlying neoplastic pathology, including dynamic testing and imaging where appropriate. This review will outline a proposed diagnostic approach to androgen excess in women, including an introduction to androgen metabolism and provision of a suggested algorithmic strategy to identify non-PCOS pathology according to clinical and biochemical phenotype.
Topics: Adrenal Hyperplasia, Congenital; Androgens; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Virilism
PubMed: 35349173
DOI: 10.1111/cen.14710