Scientists Discover Biological Reason Why Women Are More Likely to Develop Adrenal Disorders

Scientists have discovered a potential biological reason why women are more likely to develop adrenal disorders, including cancer. According to the researchers, the answer could lie in the increased turnover of hormone-producing cells found in the adrenal glands of females.

The adrenal gland is a hormone producing organ that sits on top of the kidneys. The outer part, or cortex, is responsible for the production of several hormones, including the stress-related hormone cortisol and the blood pressure controlling aldosterone. Adrenal cancer is relatively rare but occurs approximately three times more in women than in men. The cellular basis for this difference has not been investigated in detail but uncovering it might lead to sex-specific treatments and has huge implications for many areas of research.

Dr Andreas Schedl, from INSERM, France, who led the study said:

To our surprise we found that adrenal cells in female mice show a much more rapid turnover compared to males, which we could trace back to a different behaviour of adrenal stem cells between the two sexes. Furthermore, we could show that the observed differences are due to hormones that are produced by testes that suppress cell division, thus slowing down renewal in the male adrenal.”

The scientists studied the adrenal cortex of male and female adult mice and found that female mice replace their entire set of hormone-producing cells within 3 months, while it takes male mice an entire 9 months. Using different techniques to label cells within the adrenal cortex, they established that females not only have a higher proliferation rate of cells, but also recruit stem cells from a different part of the adrenal gland.

The research has wide reaching implications, as it demonstrates the basic mechanism underlying the increased turnover of cells within the adrenal gland, providing a possible explanation for the increased incidence of adrenal disorders in women.

Dr Schedl explained: “It is early days and many more experiments will need to be performed before our research can directly benefit patients. However, we believe that our study teaches a number of important lessons that are of immediate relevance to scientists, pharmacologists and clinicians.”

This research might lead to sex-specific treatment options for diseases like adrenal cancer and, according to Dr Schedl, could have implications on a far wider field of disorders: “Importantly, while our study concentrated on the adrenals, we are convinced that similar differences may also be found in other organ systems.”

Dr Helen Rippon, Chief Executive of the charity Worldwide Cancer Research, whose supporters helped fund the study, said: “Sex differences are not necessarily the first thing that comes to mind when thinking about cancer research or treatments. But this study has shown that it is crucial to consider potential differences between male and female when trying to understand the basis of cancer biology. Most importantly, these findings could have implications for treatment options further down the line and highlight the importance of early-stage, discovery research. We are delighted to fund this kind of research, as we believe that these innovative approaches are ultimately going to lead to a world where no life is cut short by cancer.”

Worldwide Cancer Research, La Ligue Contre le Cancer and the ANR supported this research. The research was published in Cell Stem Cell.

Source:

Worldwide Cancer Research

Journal reference:

Grabek, A. et al. (2019) The Adult Adrenal Cortex Undergoes Rapid Tissue Renewal in a Sex-Specific MannerCell Stem Celldoi.org/10.1016/j.stem.2019.04.012.

From https://www.news-medical.net/news/20190522/Scientists-discover-biological-reason-why-women-are-more-likely-to-develop-adrenal-disorders.aspx

How to avoid pitfalls in interpretation of adrenal imaging

By Philip Ward, AuntMinnieEurope.com staff writer

January 15, 2019 — A clear understanding of the pitfalls in the performance and interpretation of adrenal CT can help prevent incorrect and inappropriate investigations, award-winning researchers from a top London facility have found. It’s essential to keep aware of the full range of pseudolesions and mimics, they said.

“Evaluation of adrenal tumor function is limited on imaging, but may be inferred from imaging findings,” noted Dr. Gurinder Nandra and colleagues from the department of radiology at St. George’s University Hospitals NHS Foundation Trust in an e-poster presentation that received a cum laude award at RSNA 2018 in Chicago.

Other adrenal pathology, including metastases and adrenocortical carcinoma, may be encountered, and this means it’s important to know about the imaging approaches to evaluate the adrenals, the authors pointed out.

Incidental adrenal nodules are identified in around 5% of patients who undergo CT. The prevalence of detecting incidentalomas increases with age, but most incidentally encountered adrenal pathology is benign and of little clinical relevance, they wrote. Adenomas are by far the most common adrenal pathology identified.

Among the technical aspects that deserve special attention are the following:

  • The region of interest (ROI): Changing the size of the ROI can alter the perceived attenuation of the nodule. The ROI should cover at least two-thirds of the circumference of the nodule, and exclude tiny areas of heterogeneity from the ROI (e.g., flecks of calcification) that are not representative of the adrenal pathology. Unenhanced attenuation of less than 10 Hounsfield units (HU) can be used to diagnose lipid-rich adrenal adenoma (sensitivity 71%, specificity of 98%).
  • Attenuation values on unenhanced CT: A homogenously dense lesion on unenhanced CT suggests a lack of microscopic lipid content. If attenuation on unenhanced CT is greater than 20 to 30 HU, evaluate the enhancement kinetics with CT.
  • Effect of kVp on attenuation values in a dual energy study: To use threshold of less than 10 HU to diagnose a lipid-rich adrenal adenoma, the kVp should be 120. Changing kVp can alter the attenuation values of soft tissues and adrenal glands.
  • Timing of post-contrast acquisitions: “Imaging needs to be performed at the correct times to allow sufficient time for enhancement and washout of contrast. Post-contrast images should be obtained at 60 to 75 seconds and 15 minutes,” the authors stated.
  • Assessment of washout on nondedicated studies: Relative washout can be calculated on nondedicated studies if more than one acquisition is made within 15 minutes post-intravenous contrast.
  • Suspicious attenuation: Attenuation of more than 43 HU on noncontrast CT is suspicious for malignancy, regardless of washout characteristics. PET/CT is of more use than CT and MRI in such cases, and adrenal hemorrhage also is a consideration at this attenuation.
  • Evaluation of small nodules: Minor nodularity of less than 1 cm in diameter does not require further radiological investigation. Also, CT evaluation of small adrenal nodules is limited by partial volume artifacts. MRI evaluation of small adrenal nodules is limited by the India ink artifact, or black boundary artifact, on an out-of-phase sequence. This artifact may give the impression of signal loss and lead to an incorrect diagnosis of a lipid-rich adenoma.
  • Evaluation of large adrenal masses: Malignancy risk increases with size (over 4 cm, 70%; over 6 cm, 85%) when excluding myelolipoma. In the absence of known malignancy, an adrenal lesion of less than 4 cm with indeterminate imaging features is likely to be benign.
  • Enhancement characteristics of metastases: Enhancement/washout characteristics of adrenal metastases are variable, and they can be confused with pheochromocytoma.
  • Adrenal calcification: Calcification is seen in benign adrenal pathology, but also can be seen in cases of malignancy, including adrenocortical carcinoma. “Look for ancillary features of malignancy including size, heterogeneity and invasion,” the authors recommended. “Evaluation of a predominantly calcified adrenal lesion will be limited with chemical shift MRI.”
  • Heterogeneous signal loss: Heterogeneous signal loss is not typical for a small lipid-rich adenoma and raises the possibility of malignant pathology. It also can be seen in larger adenomas because of calcification/cystic change/myelolipomatous metaplasia.

In their RSNA 2018 exhibit, Nandra and colleagues also identified the following list of mimics that can crop up:

  • Mimics arising from gastrointestinal tract: Gastric pathology can extend into the left suprarenal space and mimic adrenal pathology. The most common mimics include gastrointestinal stromal tumors and gastric diverticula. Pathology elsewhere in the gastrointestinal tract can mimic adrenal pathology (e.g., a fluid-filled colon).
  • Mimics arising from solid viscera: Pathology from the spleen, pancreas, liver, and kidneys can extend into the suprarenal space and mimic adrenal pathology. This includes splenic lobulation, splenunculi, upper pole renal pathology, pancreatic tail pathology, and exophytic hepatic lesions.
  • Mimics arising from vessels: Dilated, tortuous, or aneurysmal vessels may extend into the suprarenal space and mimic adrenal pathology. The most common mimics include splenic varices and splenic artery pseudoaneurysms.
  • Mimics arising from retroperitoneal tissues: Various retroperitoneal lesions can extend into the suprarenal space and mimic adrenal pathology, and normal anatomy in the retroperitoneum also can mimic adrenal pathology (e.g., a thickened diaphragmatic crus).

From https://www.auntminnieeurope.com/index.aspx?sec=ser&sub=def&pag=dis&ItemID=616803

Vision Loss The First Sign Of Adrenal Tumour In 42-Year-Old Patient

A 42-year-old woman who presented to hospital with acute vision loss in her right eye was diagnosed with a benign tumour in her adrenal gland.

Writing in BMJ Case Reports, clinicians described how the patient presented with a visual acuity of 6/36 in her right eye and 6/6 in her left eye.

Investigations revealed an exudative retinal detachment in her right eye as well as a pigment epithelial detachment.

The patient had multifocal central serous retinopathy in both eyes.

The woman, who had hypertension and diabetes, was diagnosed with Cushing syndrome and a right adrenal adenoma was also discovered.

During a treatment period that spanned several years, the patient received an adrenalectomy followed by a maintenance dose of steroids.

The patient subsequently developed central serous retinopathy again which the clinicians believe might be related to steroid use.

The authors advised “careful deliberation” in prescribing a maintenance dose of steroids following removal of the adrenal glands because of the potential link to retinopathy.

From https://www.aop.org.uk/ot/science-and-vision/research/2018/12/17/vision-loss-the-first-sign-of-adrenal-tumour-in-42-year-old-patient

Mutations in Two Genes, USP48 and BRAF, Linked to Cushing’s Disease

Mutations in USP48 and BRAF genes contribute to the overproduction of adrenocorticotropin (ACTH) hormone by the pituitary gland and consequent development of Cushing’s disease, a study shows, linking these genes to the disease for a first time.

The study, “Identification of recurrent USP48 and BRAF mutations in Cushing’s disease,” published in the journal Nature Communications, also identified a possible treatment for patients with BRAF-related mutations.

Cushing’s disease is a condition characterized by excessive cortisol levels that, if left untreated, can lead to serious cardiovascular problems, infections, and mood disorders. It usually arises from benign pituitary tumors that produce too much of ACTH hormone, which in turn stimulates the adrenal glands to secrete cortisol.

It is still not clear why some people develop these tumors, but studies have pointed to mutations in the USP8 gene as a possible cause. They are present in 35%–62% of all tumor cases, and influence treatment response and long-term outcomes.

But major disease drivers in people whose tumors have no evidence of  USP8 mutations are unknown. Recognizing this gap, researchers in China examined tumor tissue samples from 22 patients with pituitary ademonas but a normal USP8 gene.

Their analysis revealed four genes that were recurrently mutated, including two — BRAF and USP48 — never before reported in this disease setting. Then, looking at 91 samples from patients, researchers found BRAF mutations in 17% of cases and USP48 mutations in 23% of patients.

These mutations were also found in patients with USP8-mutant pituitary tumors, but at a much lower rate — 5.1% for BRAF and 1.2% for USP48 mutations.

However, mutations in these two genes were not seen in patients with pituitary tumors producing other hormones, suggesting they are “unique genetic signatures of [ACTH-producing] adenomas,” the researchers wrote.

The team also found that BRAF and USP48 mutations activate signaling pathways that lead to the production of proopiomelanocortin (POMC), which is the precursor of ACTH.

“ACTH overproduction is a hallmark of Cushing’s disease and appears to be frequently induced by mutations in genes that tightly regulate POMC gene transcription in the pathogenesis of this disease,” investigators wrote.

Patients with BRAF and USP48 mutations had significantly higher levels of midnight plasma ACTH and midnight serum cortisol, compared to patients without these mutations. Tumor size, however, was similar among the two groups.

Interestingly, the team found that the BRAF inhibitor Zelboraf (vemurafenib) effectively reduced ACTH production in cells from ACTH-producing pituitary tumors. Zelboraf, marketed by Genentech, is approved in the U.S. and Europe to treat cancers with BRAF mutations, and findings suggest it may be a good therapeutic candidate for some people with Cushing’s disease.

“The mutational status of BRAFUSP8, and USP48 in corticotroph adenomas may be used in the future to characterize the molecular subtypes and guide targeted molecular therapy,” the researchers suggested.

From https://cushingsdiseasenews.com/2018/11/20/mutations-in-usp48-braf-genes-contribute-for-cushings-disease-study-finds/

8 medical conditions that could cause sudden weight gain

Weight gain can be associated with hormonal conditions, mood disorders, or other physiological factors. A sudden and unexplained weight gain could be your body’s way of signalling an underlying medical issue that needs to be addressed. For the sake of health and long-term well-being, it is important to differentiate between a few harmless extra kilos and a fluctuation that could be hiding a bigger problem. You can only be certain after consulting a healthcare practitioner.

If the weighing scale says your numbers are up but you haven’t changed your eating and exercise habits, you might consider any of the 8 medical conditions:

1.     Hypothyroidism The American Thyroid Association reveals that one in eight women will develop a thyroid disorder during her lifetime. Hypothyroidism refers to an underactive thyroid. The thyroid controls several body functions and your metabolism is one of them. If you’re not producing enough thyroid hormone your body can’t burn as much energy. Symptoms appear throughout your system. They include: weight gain, exhaustion, drier skin, thinner hair, bloating, muscle weakness, constantly feeling cold, and constipation. Once diagnosis is confirmed a doctor can prescribe an oral replacement for thyroid hormone that can relieve symptoms within weeks.

2.     Polycystic ovary syndrome (PCOS) One in 10 women of childbearing age undergoes PCOS. It is an endocrine disorder characterised by an imbalance in the sex hormones oestrogen and testosterone.  This results in irregular periods, acne and even facial hair growth. The disorder also disrupts the way the body uses insulin — which is the hormone responsible for converting carbohydrates into energy. As a result the sugars and starches you consume are stored as fat instead of energy, thus, weight gain. PCOS has no cure but women who have it can manage their symptoms with lifestyle changes and medication. A doctor’s consultation will help you find an appropriate method.

3. Insomnia Avoid fake news! Subscribe to the Standard SMS service and receive factual, verified breaking news as it happens. Text the word ‘NEWS’ to 22840 Sleep deprivation can negatively impact both your metabolism and your hunger hormones. Sleeping too little increases ghrelin, the hormone that signals the body that it’s time to eat, while lowering leptin, the hormone that says you are full. The result: increased cravings and snacking to get more energy through the day. Insomnia increases impulsive eating. A 2018 study published in the American Journal of Clinical Nutrition found that the right amount of sleep could mean consuming up to 10 fewer grams of sugar throughout the day.

4.     Tumours Weight gain around your belly as opposed to your lower body or other areas can be more dangerous to your health. Large pelvic area tumours like uterine or ovarian tumours can inflate the abdomen the way excess fat does. In some cases they can also be cancerous. In addition to weight gain, symptoms of ovarian or uterine tumours include vaginal bleeding, lower back pain, constipation and painful intercourse. But these signs are common for other conditions as well so it‘s worth confirming with a doctor to rule out any possible complications.

5. Peri menopause and menopause Perimenopause -the transition period to menopause can start as early as a woman’s mid-thirties, but usually starts in their forties. This period triggers hormones like oestrogen to rise and fall unevenly, which can cue weight gain in some women. Genetics are a good starting point on how your body experiences these changes, so it would be helpful to look into how it affected your mother and other older women in your family. Other signs of perimenopause are mood swings, irregular periods, hot flashes, and changes in libido. Age also contributes to loss of muscle mass and increase in body fat. An Ob-Gyn should be able to talk you through these changes and recommend management options.

6.     Mood disorders Depression and anxiety can result in fatigue, lack of focus and irritability. Some people cope with anxious or sad feelings by mindlessly munching on food they don’t really need. Additionally chronic stress throws your body into fight-or-flight mode, leading to a surge of adrenaline, as well as a heavy dose of the hormone cortisol –responsible for restoring energy reserves and storing fat.

7. Cushing syndrome Sometimes tumours on the pituitary or adrenal glands can contribute to a condition known as Cushing’s disease which is characterised by high levels of cortisol in the blood. Taking long term steroids could also result in this disease. Patients with Cushing syndrome will experience rapid weight gain in the face, abdomen and chest. They also display slender arms and legs compared to the heavy weight in the core of the body. Other symptoms include: high blood pressure, mood swings, osteoporosis, discoloured stretch marks, acne, and fragile skin. Depending on the cause, Cushing‘s disease can be treated in a different ways.

8. New medication Before starting on any new prescription medication, ask your doctor if weight gain is a possible side effect. Birth control pills may lead to weight gain depending on the brand, dosage, and the person’s hormonal levels. Psychiatric medications, especially for depression and bipolar disorder, have been known to cause weight gain, as they target the brain. Similarly, taking insulin to manage diabetes or medications that treat high blood pressure can also lead to extra kilos, so staying active and sticking to a strict meal plan can help you take insulin without unnecessarily weight gain.

Adapted from https://www.standardmedia.co.ke/lifestyle/article/2001297348/8-medical-conditions-that-could-cause-sudden-weight-gain

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