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John P H Wilding 1 Affiliations expand PMID: 32061161 DOI: 10.1530/EJE-20-0099 Abstract Endocrine disorders such as Cushing's syndrome and hypothyroidism may cause weight gain and exacerbate metabolic dysfunction in obesity. Other forms of endocrine dysfunction, particularly gonadal dysfunction (predominantly testosterone deficiency in men and polycystic ovarian syndrome in women), and abnormalities of the hypothalamic-pituitary-adrenal axis, the growth hormone-IGF-1 system and vitamin D deficiency are common in obesity. As a result, endocrinologists may be referred people with obesity for endocrine testing and asked to consider treatment with various hormones. A recent systematic review and associated guidance from the European Society of Endocrinology provide a useful evidence summary and clear guidelines on endocrine testing and treatment in people with obesity. With the exception of screening for hypothyroidism, most endocrine testing is not recommended in the absence of clinical features of endocrine syndromes in obesity, and likewise hormone treatment is rarely needed. These guidelines should help reduce unnecessary endocrine testing in those referred for assessment of obesity and encourage clinicians to support patients with their attempts at weight loss, which if successful has a good chance of correcting any endocrine dysfunction. Similar articles Classical endocrine diseases causing obesity. Weaver JU.Front Horm Res. 2008;36:212-228. doi: 10.1159/000115367.PMID: 18230905 Review. Is obesity an endocrine condition? Stocks AE.Aust Fam Physician. 1977 Feb;6(2):109-16.PMID: 558747 FPIN’s clinical inquiries. Secondary causes of obesity. Allen G, Safranek S.Am Fam Physician. 2011 Apr 15;83(8):972-3.PMID: 21524038 No abstract available. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease]. Hagymási K, Reismann P, Rácz K, Tulassay Z.Orv Hetil. 2009 Nov 29;150(48):2173-81. doi: 10.1556/OH.2009.28749.PMID: 19923096 Review. Hungarian. Obesity and endocrine disease. Kokkoris P, Pi-Sunyer FX.Endocrinol Metab Clin North Am. 2003 Dec;32(4):895-914. doi: 10.1016/s0889-8529(03)00078-1.PMID: 14711067 Review. From https://pubmed.ncbi.nlm.nih.gov/32061161/
Cases of adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome are often caused by unilateral tumors in the adrenal glands, but Indian researchers have now reported a rare case where the condition was caused by tumors in both adrenal glands. Fewer than 40 cases of bilateral tumors have been reported so far, but an accurate diagnosis is critical for adequate and prompt treatment. Sampling the veins draining the adrenal glands may be a good way to diagnose the condition, researchers said. The study, “Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing’s syndrome: A case report and review of the literature,” was published in the World Journal of Clinical Cases. Cushing’s syndrome, a condition characterized by excess cortisol in circulation, can be divided into two main forms, depending on ACTH status. Some patients have tumors that increase the amount of ACTH in the body, and this hormone will act on the adrenal glands to produce cortisol in excess. Others have tumors in the adrenal glands, which produce excess cortisol by themselves, without requiring ACTH activation. This is known as ACTH-independent Cushing’s syndrome. Among the latter, the disease is mostly caused by unilateral tumors — in one adrenal gland only — with cases of bilateral tumors being extremely rare in this population. Now, researchers reported the case of a 31-year-old Indian woman who developed ACTH-independent Cushing’s syndrome because of tumors in both adrenal glands. The patient complained of weight gain, red face, moon face, bruising, and menstrual irregularity for the past two years. She recently had been diagnosed with high blood pressure and had started treatment the month prior to the presentation. A physical examination confirmed obesity in her torso, moon face, buffalo hump, thin skin, excessive hair growth, acne, swollen legs and feet, and skin striae on her abdomen, arms, and legs. Laboratory examinations showed that the woman had an impaired tolerance to glucose, excess insulin, and elevated cortisol in both the blood and urine. Consistent with features of Cushing’s syndrome, cortisol levels had no circadian rhythm and were non-responsive to a dexamethasone test, which in normal circumstances lowers cortisol production. Because ACTH levels were within normal levels, researchers suspected an adrenal tumor, which led them to conduct imaging scans. An abdominal computed tomography (CT) scan showed adrenal adenomas in both adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). A magnetic resonance imaging (MRI) scan showed that the pituitary gland (which normally produces ACTH) was normal. To determine whether both adrenal tumors were producing cortisol, researchers sampled the adrenal veins and compared their cortisol levels to those of peripheral veins. They found that the left adrenal gland was producing higher amounts of cortisol, thought the right adrenal gland was also producing cortisol in excess. “Our case indicates that adrenal vein [blood] sampling might be useful for obtaining differential diagnoses” in cases of Cushing’s syndrome, researchers stated. Also, they may help design a surgical plan that makes much more sense.” The tumors were surgically removed — first the left, and three months later the right — which alleviated many of her symptoms. She also started prednisolone treatment, which helped resolve many disease symptoms. “Bilateral cortisol-secreting tumors are a rare cause of Cushing’s syndrome,” researchers said. So when patients present bilateral adrenal lesions, “it is crucial to make a definitive diagnosis before operation since various treatments are prescribed for different causes,” they said. The team recommends that in such cases the two tumors should not be removed at the same time, as this approach may cause adrenal insufficiency and the need for glucocorticoid replacement therapy. From https://cushingsdiseasenews.com/2019/06/27/rare-case-of-cs-due-to-bilateral-tumors-in-the-adrenal-glands/
The oral chemotherapy temozolomide might be an effective treatment for Cushing’s disease caused by aggressive tumors in the pituitary gland that continue to grow after surgery and taking other medications, a case report suggests. The study, “Successful reduction of ACTH secretion in a case of intractable Cushing’s disease with pituitary Crooke’s cell adenoma by combined modality therapy including temozolomide,” was published in the journal J-Stage. Cushing’s disease is often caused by a tumor in the pituitary gland that secretes high levels of adrenocorticotropic hormone (ACTH), leading to high levels of cortisol and other symptoms. Macroadenomas are aggressive, fast-growing tumors that reach sizes larger than 10 millimeters. Crooke’s cell adenoma is a type of macroadenoma that does not respond to conventional therapies, but has deficient mechanisms of DNA repair. That is why chemotherapeutic agents that damage the DNA, such as temozolomide, might be potential treatments. Researchers in Japan reported the case of a 56-year-old woman with Cushing’s disease caused by a Crooke’s cell adenoma in the pituitary gland who responded positively to temozolomide. The patient was diagnosed with Cushing’s disease at age 39 when she went to the hospital complaining of continuous weight gain. She also had excessive production of urine and a loss of vision in the right eye. The lab tests showed high levels of cortisol and ACTH, and the MRI detected a tumor of 4.5 centimeters in the pituitary gland. The doctors removed a part of the tumor surgically, which initially reduced the levels of ACTH and cortisol. However, the hormone levels and the size of the residual tumor started to increase gradually after the surgery, despite treatment with several medications. By the time the patient was 56 years old, she went to the hospital complaining of general fatigue, leg edema (swelling from fluid), high blood pressure, and central obesity (belly fat). Further examination showed a 5.7 cm tumor, identified as a Crooke’s cell macroadenoma. The patient underwent a second surgery to remove as much tumor as possible, but the levels of ACTH remained high. She took temozolomide for nine months, which normalized the levels of ACTH and cortisol. After the treatment, the patient no longer had high blood pressure or leg edema. The tumor shrunk considerably in the year following temozolomide treatment. The patient started radiation therapy to control tumor growth. The levels of cortisol and ACHT remained normal, and the tumor did not grow in the seven years following temozolomide treatment. “These clinical findings suggest that [temozolomide] treatment to patients with Crooke’s cell adenoma accompanied with elevated ACTH may be a good indication to induce lowering ACTH levels and tumor shrinkage,” researchers wrote. Other cases of Cushing’s disease caused by aggressive macroadenomas showed positive results, such as reduction of tumor size and decrease in plasma ACTH, after temozolomide treatment. However, more studies are needed to establish the ideal course of chemotherapy to treat these tumors, the researchers noted. From https://cushingsdiseasenews.com/2019/06/18/temozolomide-effective-cushings-disease-aggressive-tumors-case-report/
When we become stressed out bodies release cortisol – the stress hormone – which helps us cope with challenges. Cortisol’s role is to convert protein into energy by releasing glycogen and counteract inflammation. When cortisol is released in the body temporarily, this is okay and won’t have long-lasting detrimental effects to health as it is a natural response to a stressor. But when cortisol levels remain high chronically it can eventually begin to tear your body down thus causing health complications. This is why numerous health experts recommend the reduction of stress as much as possible because in the long run it can harm our health. High cortisol levels over the long term can destroy healthy muscle and bone, slow down healing, impair digestion, metabolism and mental function, and weaken the immune system. Additionally, adrenal fatigue has been linked to numerous other health conditions including fibromyalgia, hypothyroidism, chronic fatigue syndrome, arthritis, premature menopause, and many others. High cortisol levels are also associated with many unwanted symptoms which we will outline below. High cortisol symptoms If you’re concerned about your cortisol levels, the following signs and symptoms associated with high cortisol levels can alert you and prompt you to make the necessary changes in order to reduce cortisol levels. Unexplained weight gain Skin symptoms including acne, skin infections, lesions, thin-appearing skin, bruising, growing facial hair, and reddish purple streaks on skin Muscle and bone symptoms like a deep pain in the bones, weak muscles, chronic backaches, increased risk of bone fractures Gender specific changes such as women developing male-pattern hair growth, irregular menstrual cycles, low libido, infertility Neurological symptoms such as depression, irritability, headaches, chronic fatigue, and anxiety High blood pressure (hypertension) Poor sleep or lack of sleep Swelling of hands and feet If you notice any of the above symptoms, you may want to have your cortisol levels checked to confirm diagnosis. Living with high cortisol levels over the long term can have detrimental effects on a person’s health. Treating high cortisol as soon as possible can lower the risk of long-term health problems. Causes of high cortisol There are two main causes of high cortisol: Chronic stress and more rarely, Cushing’s disease. Cushing’s disease is caused by a hormone-secreting tumor on the adrenal gland which results in the release more cortisol than required. Living with chronic stress also leads to high cortisol because the release of cortisol is a natural response from the body when it is stressed. The hypothalamic–pituitary-adrenal [HPA] axis is what regulates the timely release of cortisol during acute stress, but when stress becomes chronic the feedback from the HPA becomes damaged and so cortisol continues to be released. Conditions that can contribute to chronic stress and high cortisol include: Depression Panic disorder Generalized anxiety disorder Post traumatic stress disorder (PTSD) Anorexia nervosa Bulimia nervosa Alcoholism Diabetes Severe obesity Metabolic syndrome Polycystic ovary syndrome (PCOS) Obstructive sleep apnea Working in shifts End-stage kidney disease Chronic pain Tips to lower high cortisol Here are some tips that can help you lower your high cortisol levels and thus prevent long-term health problems associated with high cortisol. [MaryO'Note: These will not work if you have active Cushing's! You must remove the source of your Cushing's first.] Eat a well balanced meal with plenty of fruits and vegetables, avoid sugars, consume low glycemic index foods, avoid processed foods, eat a wide variety of health foods to ensure you receive all essential vitamins and nutrients Exercise on a regular basis Take time out of each day to relax – listen to music, meditate, pray, perform your favorite hobby, anything that promotes relaxation Take up yoga or tai chi Ensure you are getting adequate sleep Drink tea Watch funny videos or hang out with a funny friend Go for a massage Do something spiritual – attend a service Chew gum Limit caffeine intake Stretch By incorporating these helpful tips into your life you will find that your high cortisol symptoms begin to diminish and your overall health begins to improve. From http://www.belmarrahealth.com/high-cortisol-symptoms-signs-look/