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The Journal of Clinical Endocrinology... Feb 2024Adrenocortical carcinomas are very rare malignancies in childhood associated with poor outcome in advanced disease. Most adrenocortical tumours (ACT) are functional...
CONTEXT
Adrenocortical carcinomas are very rare malignancies in childhood associated with poor outcome in advanced disease. Most adrenocortical tumours (ACT) are functional causing signs and symptoms of adrenal hormone excess. In most studies, endocrine manifestations were reported 4-6 months prior to diagnosis.
OBJECTIVE
We seeked to extend our knowledge on endocrine manifestations with regard to age and sex to facilitate early diagnosis.
DESIGN/SETTINGS/PATIENTS
We retrospectively analysed features of adrenal hormone excess in children and adolescents with ACT registered with the GPOH-MET studies between 1997 and 2022. Stage of puberty was defined as `prepubertal` in females <8 years of age and males <9 years.
RESULTS
By December 2022, 155 patients (110 female, 45 male) with data on endocrine manifestations had been reported. Median age at ACT diagnosis was 4.2 years [0.1-17.8], median interval from first symptoms 4.2 months [0-90.7]. In 63 females of prepubertal age pubarche (68.3%), clitoral hypertrophy (49.2%), and weight gain (31.7%) were most frequently reported, in 47 pubertal female excessive pubic hair (46.8%), acne (36.2%), and hypertension (36.2%). Leading symptoms in 34 males of prepubertal age were pubarche (55.9%), penile growth (47.1%), and acne (32.4%) and in 11 pubertal males, weight gain (45.5%), hypertension (36.4%), excessive pubic hair (27.3%), and cushingoid appearance (27.3%). In pubertal patients, symptoms of androgen excess were mainly unrecognized as part of pubertal development while symptoms of Cushing's syndrome were more frequently apparent.
CONCLUSIONS
The endocrine phenotype induced by paediatric ACT is age- and sex-dependent.
PubMed: 38318871
DOI: 10.1210/clinem/dgae073 -
Cureus Jan 2024Abiraterone acetate causes an adrenocorticotropic hormone (ACTH)-mediated mineralocorticoid excess. We present a 77-year-old man with prostate adenocarcinoma who...
Abiraterone acetate causes an adrenocorticotropic hormone (ACTH)-mediated mineralocorticoid excess. We present a 77-year-old man with prostate adenocarcinoma who developed signs and symptoms of mineralocorticoid excess while on abiraterone and discuss its pathophysiology and treatment options. The patient developed hypokalemia, metabolic alkalosis, and hypertension, indicative of increased mineralocorticoid activity, confirmed by elevated ACTH, corticosterone, and deoxycorticosterone levels. Abiraterone inhibits cytochrome P450c17 (CYP17A1), thus inhibiting testosterone and cortisol synthesis. Diminished cortisol synthesis, in turn, leads to excessive mineralocorticoid precursor production mediated by ACTH, leading to enhanced sodium absorption and potassium excretion. Abiraterone is often prescribed with low-dose prednisone to suppress ACTH; however, this strategy may not provide physiological glucocorticoid levels, resulting in ACTH-mediated mineralocorticoid excess in some patients. High-dose steroids or mineralocorticoid antagonists may activate mutant androgen receptors in prostate cancer tissue; therefore, amiloride is suggested for managing residual mineralocorticoid activity. This case highlights the importance of being vigilant for the signs and symptoms of mineralocorticoid excess in patients on abiraterone.
PubMed: 38318572
DOI: 10.7759/cureus.51757 -
Expert Review of Endocrinology &... Mar 2024Hirsutism is a prevalent condition among women and represents a primary clinical feature of polycystic ovary syndrome (PCOS). (Review)
Review
INTRODUCTION
Hirsutism is a prevalent condition among women and represents a primary clinical feature of polycystic ovary syndrome (PCOS).
AREAS COVERED
Our study aims to address the principal challenges associated with this hyperandrogenic manifestation in PCOS women. Our narrative review based on the available indexed literature explored the complexities of establishing mFG cutoff values for various ethnic groups, investigated hirsutism during peri- and postmenopausal stages, and examined the role of oxyandrogens.
EXPERT OPINION
Hirsutism may have a negative impact on the quality of life and on the mental health, being associated with anxiety and depression. Future perspectives for its diagnosis include the use of artificial intelligence and the consideration of the distress caused by excessive hair growth.
Topics: Female; Humans; Hirsutism; Polycystic Ovary Syndrome; Quality of Life; Artificial Intelligence
PubMed: 38305206
DOI: 10.1080/17446651.2024.2310558 -
European Journal of Obstetrics,... Mar 2024Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is...
OBJECTIVE
Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation.
STUDY DESIGN
STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation.
RESULT
STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs.
CONCLUSION
Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.
Topics: Female; Humans; Endometriosis; Matrix Metalloproteinase 2; STAT3 Transcription Factor; Interleukin-6; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Stromal Cells; Endometrium; Nandrolone
PubMed: 38301500
DOI: 10.1016/j.ejogrb.2024.01.013 -
Pediatrics in Review Feb 2024We describe congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, which is the most common primary adrenal insufficiency in children and adolescents. In... (Review)
Review
We describe congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, which is the most common primary adrenal insufficiency in children and adolescents. In this comprehensive review of CAH, we describe presentations at different life stages depending on disease severity. CAH is characterized by androgen excess secondary to impaired steroidogenesis in the adrenal glands. Diagnosis of CAH is most common during infancy with elevated 17-hydroxyprogesterone levels on the newborn screen in the United States. However, CAH can also present in childhood, with late-onset symptoms such as premature adrenarche, growth acceleration, hirsutism, and irregular menses. The growing child with CAH is treated with hydrocortisone for glucocorticoid replacement, along with increased stress doses for acute illness, trauma, and procedures. Mineralocorticoid and salt replacement may also be necessary. Although 21-hydroxylase deficiency is the most common type of CAH, there are other rare types, such as 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase deficiency. In addition, classic CAH is associated with long-term comorbidities, including cardiometabolic risk factors, impaired cognitive function, adrenal rest tumors, and bone health effects. Overall, early identification and treatment of CAH is important for the pediatric patient.
Topics: Infant, Newborn; Adolescent; Child; Humans; Adrenal Hyperplasia, Congenital; Glucocorticoids; Hydrocortisone; Puberty, Precocious
PubMed: 38296783
DOI: 10.1542/pir.2022-005617 -
JNMA; Journal of the Nepal Medical... Dec 2023Congenital adrenal hyperplasia occurs due to enzymatic defects in the adrenocortical steroidogenesis. 11β hydroxylase deficiency is the second most common cause of...
UNLABELLED
Congenital adrenal hyperplasia occurs due to enzymatic defects in the adrenocortical steroidogenesis. 11β hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia which presents with hypertension and features of androgen excess. Hypertension has also been found to cause end-organ damage in children with 11β hydroxylase deficiency. We report a case of a 10-year-old male child with hypothyroidism under thyroid replacement therapy, presenting with features of severe hypertension and androgen excess, later on, diagnosed as congenital adrenal hyperplasia due to 11β hydroxylase deficiency.
KEYWORDS
case reports; congenital adrenal hyperplasia; hypertension; hypothyroidism.
Topics: Male; Child; Humans; Adrenal Hyperplasia, Congenital; Steroid 11-beta-Hydroxylase; Androgens; Mutation; Hypertension; Hypothyroidism
PubMed: 38289749
DOI: 10.31729/jnma.8378 -
Cureus Dec 2023Menopause, when menstrual cycles stop, is brought on by a decline in the level of the hormones progesterone and oestrogen synthesised by the ovaries. Menopause is an... (Review)
Review
Menopause, when menstrual cycles stop, is brought on by a decline in the level of the hormones progesterone and oestrogen synthesised by the ovaries. Menopause is an unavoidable stage of a female's lifecycle, but because experiences differ for every woman, several women require health care aid to manage their health problems. The physiological variations that take place at various periods of the reproducing age, along with the kind and timing of menopause, are components that are frequently associated with a greater threat of cardiometabolic illness. The most researched associations between menopause and cardiometabolic health are reduced levels of ovarian estrogen synthesis and excessive amounts of androgen during the onset of menopause. Although testosterone and oestrogens have differing effects on adipocyte physiology, it is debatable how important oestrogens are for the emergence of metabolic disorders following menopause. The control of adipocyte differentiation by the brain as well as potential roles of oestrogen and endocrine disruptors chemicals are reviewed in this systematic review of the subject. In general, women had a greater frequency of metabolic syndrome compared to men. Female metabolism was significantly impacted by overt hyperthyroidism and subclinical hypothyroidism. Osteoporosis is another medical condition that menopausal women may experience. Estrogen deprivation is the main contributor to osteoporosis in menopausal women. The regular cycle of bone turnover is disrupted by the decrease in estrogen secretion, which boosts osteoclastic resorption activity while decreasing osteoblastic activity. The entire article assesses and provides information on all the changes in a woman's life after menopause.
PubMed: 38288203
DOI: 10.7759/cureus.51287 -
Fluids and Barriers of the CNS Jan 2024Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects...
BACKGROUND
Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved.
METHODS
We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics.
RESULTS
Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats.
CONCLUSIONS
Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target.
Topics: Humans; Female; Rats; Animals; Pseudotumor Cerebri; Androgens; Rats, Zucker; Obesity; Testosterone
PubMed: 38273331
DOI: 10.1186/s12987-024-00511-1 -
International Journal of Molecular... Jan 2024Metabolic preconditioning, characterized by conditions like obesity and insulin resistance syndrome, disrupts hormonal balance. Elevated androgen levels stimulate...
Metabolic preconditioning, characterized by conditions like obesity and insulin resistance syndrome, disrupts hormonal balance. Elevated androgen levels stimulate excessive sebum production and follicular cell proliferation, leading to acne lesions. Similarly, thyroid hormone imbalances affect sebaceous gland activity, epidermal lipid composition, and skin cell turnover, impacting acne occurrence and severity. This study aimed to assess the potential contribution of metabolic and endocrine preconditions to acne development. A total of 389 patients diagnosed with acne were included and divided into three groups: the metabolic precondition group (MPG, N = 163, 41.9%), the endocrine precondition group (EPG, N = 162, 41.65%), and the control group (CG, N = 89, 22.88%). Data related to the degree of acne severity and comorbidities of interest were collected from the patients' medical records. In the groups with concomitant diseases, moderate and severe acne were significantly more prevalent (56.44% and 41.10% in MPG, and 35.80% and 61.11% in EPG) compared to the control group (5.61% and 4.89%). The most prevalent preconditions observed were insulin resistance syndrome in MPG (63.8%) and autoimmune thyroiditis in EPG (95.06%). Significant age-related differences in acne severity were found across all study groups ( < 0.05). In MPG, the age variable was significantly higher in the presence of mild acne, while in EPG, the age variable was significantly lower for the mild acne group. A positive association was observed between the severity of acne and insulin resistance syndrome, obesity, autoimmune thyroiditis, and hypothyroidism ( < 0.05). Risk analysis indicated a significantly higher risk (RR > 1, 95% CI RR > 1, < 0.001) of developing moderate and severe acne in the presence of these preconditions. The presence of both metabolic and endocrine preconditions significantly increased the likelihood of developing severe acne, leading to the hypothesis that both conditions may be contributing factors to the development of acne.
Topics: Humans; Insulin Resistance; Thyroid Diseases; Metabolic Syndrome; Acne Vulgaris; Hashimoto Disease; Thyroiditis, Autoimmune; Risk Assessment; Obesity
PubMed: 38255795
DOI: 10.3390/ijms25020721 -
Frontiers in Cell and Developmental... 2023Embryonic development and adult physiology are dependent on the action of steroid hormones. In particular, the reproductive system is reliant on hormonal signaling to... (Review)
Review
Embryonic development and adult physiology are dependent on the action of steroid hormones. In particular, the reproductive system is reliant on hormonal signaling to promote gonadal function and to ensure fertility. Here we will describe hormone receptor functions and their impacts on testicular function, focusing on a specific group of essential hormones: androgens, estrogens, progesterone, cortisol, and aldosterone. In addition to focusing on hormone receptor function and localization within the testis, we will highlight the effects of altered receptor signaling, including the consequences of reduced and excess signaling activity. These hormones act through various cellular pathways and receptor types, emphasizing the need for a multifaceted research approach to understand their critical roles in testicular function. Hormones exhibit intricate interactions with each other, as evidenced, for example, by the antagonistic effects of progesterone on mineralocorticoid receptors and cortisol's impact on androgens. In light of research findings in the field demonstrating an intricate interplay between hormones, a systems biology approach is crucial for a nuanced understanding of this complex hormonal network. This review can serve as a resource for further investigation into hormonal support of male reproductive health.
PubMed: 38250327
DOI: 10.3389/fcell.2023.1339385