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Eyelid Edema Due to Cushing's Syndrome
MaryO posted a topic in News Items and ResearchAbstract Cushing's syndrome (CS) shows diverse signs such as centripetal obesity, moon face, and buffalo hump, which can complicate the diagnosis. Facial features including eyelid edema, as an underrecognized sign, can be diagnostic clues for an excess of corticoids in a CS patient. A 49-year-old woman presented with amenorrhea and weight gain that had continued for 2 years. Her medical history was dyslipidemia, hypertension, and osteoporosis. Physical examination revealed eyelid edemas (Figure 1A), moon face, buffalo hump, abdominal purple striae, and centripetal obesity (body mass index (BMI), 30.8 kg/m2). Basal plasma adrenocorticotropin was undetectable and serum cortisol level was high (16.9 μg/dl) without circadian rhythms. Free cortisol level in a 24-h urine collection was elevated (158.7 μg/day). Overnight administration of dexamethasone (1 mg) did not reduce serum cortisol level (17.4 μg/dl). Magnetic resonance imaging suggested bilateral adenomas. We made a diagnosis of adrenal Cushing's syndrome (CS). Since 131l-adosterol scintigraphy showed specific uptake in the left adrenal gland, left adrenalectomy was laparoscopically performed. Histopathology of the tumor was compatible with adrenocortical adenoma. Three months after surgery, her BMI decreased to 25.0 kg/m2 and eyelid edemas were ameliorated (Figure 1B). FIGURE 1 Open in figure viewerPowerPoint (A) Bilateral eyelid edemas due to Cushing's syndrome are shown. (B) These findings were improved three months after surgery for left adrenal adenomas Eyelid edema, in addition to centripetal obesity, moon face, and buffalo hump, is also a significant sign of CS; however, it has scarcely been reported in countries other than Japan.1, 2 Increased capillary permeability, insufficient venous return due to muscle atrophy, and sodium retention due to mineralocorticoid actions conceivably cause edema in CS. AUTHORS’ CONTRIBUTIONS KY wrote the first draft and managed all the submission processes. KO and KH contributed to the clinical management of the patient. FO organized the writing the manuscript. ACKNOWLEDGMENT None. CONFLICT OF INTEREST The authors declare no conflicts of interest. ETHICAL APPROVAL Written informed consent was obtained from the patient to publish this case report. 1Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing's syndrome. Lancet. 2015; 386: 913- 927. CrossrefCASPubMedWeb of Science®Google Scholar 2Komiya I, Takasu N, Ohara N, et al. Forty-one cases of Cushing's syndrome: a comparison between Cushing's syndrome (adrenal adenoma) and Cushing's disease (adrenal hyperplasia). Nihon Naibunpi Gakkai Zasshi. 1992; 68: 607- 622. CASPubMedGoogle Scholar https://doi.org/10.1002/ccr3.5940 From https://onlinelibrary.wiley.com/doi/10.1002/ccr3.5940
By Ed Miseta, Chief Editor, Clinical Leader Follow Me On Twitter @EdClinical Sparrow Pharmaceuticals is an emerging biopharma company on a mission to help patients suffering from an excess of corticosteroids, with a focus on Cushing’s syndrome, autonomous cortisol secretion (ACS), and polymyalgia rheumatica (PMR). Cushing’s and ACS are both caused by an excess of cortisol produced by tumors. Patients with Cushing’s can present physically with a fatty hump between their shoulders, a rounded face, and pink or purple stretch marks on their skin. Cushing’s syndrome and ACS can both result in high blood pressure, bone loss, type 2 diabetes, weight gain, and mood, cognition, and sleep disorders. Any of those symptoms may be side effects for patients with conditions such as PMR who rely on long-term treatment with corticosteroid medications such as prednisone. “Cushing’s syndrome impacts around 20,000 patients in the U.S. alone,” says David Katz, Chief Scientific Officer for Sparrow. “Approximately 50% of those patients can be cured by surgery, but some will develop another tumor years later. ACS is an under-recognized condition, but it may affect up to 3 million patients in the U.S. There are also around 2 million people in the U.S. who rely on long-term use of corticosteroid medications to control autoimmune diseases and other conditions.” The treatments being developed by Sparrow are based on recognition that cortisol and corticosteroid medications are activated in certain tissues such as the liver, bone, fat, and brain, where in excess they act to cause toxicity. The company’s investigational drugs inhibit HSD-1, the enzyme responsible for that activation. Sparrow is about to launch a Phase 2 trial for Cushing’s syndrome. In early 2022 the company will also begin two additional Phase 2 trials for ACS and PMR, a common autoimmune disease in elderly patients. PMR is an arthritic syndrome characterized by a phenomenon known as claudication, which means the more you use a limb, the more it hurts and the harder it is to use. “For example, the more a PMR patient walks, the more painful and stiff their legs will become,” says Katz. “If they're trying to do anything with their arms, the arms will get stiffer and more painful. The disease is pretty debilitating in terms of physical function. The only approved treatment for PMR is steroids, which have side effects such as diabetes, hypertension, osteoporosis, and fractures.” Unknown Clinical Challenges Katz is excited about the clinical trials for ACS and PMR because no sizable interventional trials have been reported in either of those conditions. “We're going into a completely new area, and we don't know what we're going to encounter in terms of patient recruitment and retention,” says Katz. “There is also no strong precedent for how to get approval for a drug in these conditions. The only treatment indicated for PMR is steroids, and that came without any efficacy clinical trials. There are no drugs approved for ACS. It’s hard to anticipate the challenges we will face when we are in an area that is very new.” Patient centricity is a topic that is very important to Katz, and he spends a lot of time thinking about how to make trials a more pleasant experience for patients by limiting the burden placed on them. He notes that can sometimes be a difficult trade-off because of the procedures that must be performed to meet regulatory standards. “In Cushing’s syndrome clinical care and clinical trials, the standard way for someone's cortisol level to be measured is a 24-hour urine collection,” states Katz. “That involves looking at the amount of cortisol in the urine over a 24-hour period. That collection is inconvenient and burdensome, and the patient must then carry it somewhere to be analyzed.” Sparrow hopes to shift that collection to a spot urine sample, like what patients would experience during a physical. The patient would urinate into a cup and hand it off to a clinic employee for analysis. The process would be much simpler and less burdensome for the patient. Sparrow will first need to prove that in a clinical trial the spot sample will work as well or better than the 24-hour collection. Subjects in the initial clinical trials will have to contribute the 24-hour collections so that Sparrow can demonstrate that future patients will not need to do so. The Future of Endocrinology Katz has a positive outlook on the future of endocrinology. Sparrow’s leading drug candidate, SPI-62, is an oral, small-molecule HSD-1 inhibitor. In four clinical trials, it demonstrated potent targeting of HSD-1 in both the brain and liver, and significantly lowered cortisol levels in the liver. The studies also showed a favorable safety and tolerability profile. “If we are successful at developing SPI-62, I believe it will change the field of endocrinology,” says Katz. “We aim to shift the focus in Cushing’s syndrome to intracellular cortisol as the main driver of symptoms. What I mean by that is if we find that SPI-62 substantially reduces symptoms and that the degree of inhibition of our target HSD-1 correlates well with clinical improvement, then we can get to a new standard of care. We can potentially get rid of the 24-hour urine collections, which will be a big relief to patients. Additionally, many of today's drugs have a side effect called adrenal insufficiency, which results when the drugs either reduce cortisol too much or completely block activity. Many of today's drugs also require frequent monitoring and dose titration to prevent adrenal insufficiency. We believe that with HSD-1 inhibition we might avoid adrenal insufficiency as well.” Katz is hopeful patients treated with SPI-62 will not require monitoring and dose titration. That proof will take years and lots of clinical trials. Sparrow may also produce the first targeted therapy for ACS. That could improve the recognition of ACS as a prevalent form of hypercortisolism and a substantial cause of morbidity and mortality. “ACS is probably the most under-recognized condition in endocrinology based on recent epidemiological studies,” adds Katz. “It's possible that as few as 3% of patients who have ACS actually have a diagnosis. That is shocking for a condition that is associated with a lot of cardiometabolic and bone morbidity, negative effects on mood and cognition, sleep, and muscle strength, and is associated with excess mortality. We want to bring attention to this condition by bringing out a targeted therapy to treat a spectrum of symptoms by getting to the root cause of them.” From https://www.clinicalleader.com/doc/sparrow-pharmaceuticals-hopes-to-change-the-future-of-endocrinology-0001
Low TSH, Low FT4, buffalo hump and many other symptoms
Guest posted a question in Guest QuestionsI have been struggling with progressive symptoms of extreme fatigue, muscle weakness, increased anxiety and depression, rage, acne, weight gain, and sweating just doing small tasks over the last 3 to 4 years. I also have a very hard time controlling my body temperature. I get really cold, turn the heat up, get really hot, turn the heat down, over and over throughout the day. (I’m 36 years old) If I’m sitting I’m freezing. If I’m up moving I’m on fire and sweating. Just such dramatic ends of the spectrum. Anyway, for a long time my GP was only checking my TSH. (Hypothyroidism runs strong in my family). My TSH has always been on the low end of normal. I was feeling so awful, I insisted they were missing something and asked them to check my FT4. That has also always ran at the lower end of normal. They treat me with Levothyroxine to try to increase my FT4, but in doing so, cause my TSH to go even lower. I googled what it meant to have a Low TSH with a low FT4 and it said it could be hypothyroidism caused by a pituitary tumor. I then came across Cushing’s which started showing pictures of the classic “buffalo hump” and my jaw hit the floor. About a month ago, I caught myself in profile in my mirror and was completely taken aback by my appearance. My husband and I aren’t sure how long my neck has looked this way. Either way I was just wondering what others thoughts were. My GP has ordered some kind of cortisol test thus far that I’ll go for tomorrow. I would also like an MRI of my pituitary and possibly adrenals. I’m just tired of sleeping my life away and have been searching for answers for so long. Please let me know what you think of the hump. Are there other causes for this appearance? Thanks
Guest posted a question in Guest QuestionsI've been searching every possible alternative explanation. I really hoped I just had a Lipoma but GP was pretty confident no. I've gained about 40lbs in the past year, I bruise easily and I have a Buffalo Hump. Cycle is regular, my mood is good, well ya know pandemic, home schooling, owning a business ... Lol I don't think I'm suffering any unusual stress or anxiety though. I am anxious over the time it's taking to get any info. I had blood drawn and an upcoming sono, date TBD, but don't see my GP for 5 wks! Can I get blood results over ph and skip right to Endocrinologist if Cortisol is high? Any input of speeding this along? Anyone else with only a few symptoms? Thanks!
Please help, confused over blood tests
Guest posted a question in Guest QuestionsCan someone please offer help, ive been suffering for a year and just got blood results today with a high cortisol reading. My doctor said that my contraceptive pill could have caused this, however, I am not on the regular pill but on the POP progesteron only pill. Is anyone aware of if this raises cortisol levels the same way the regular combined pill does? Any help would be so very much appreciated!
Bill's Reign of Terror, Part I: The Sneak AttackI first became aware of Bill on November 6, but now that I know about him, I am pretty sure he officially arrived during the summer of 2012. Since then, I suffered from depression, acne, menstrual problems, 30lb weight gain (while training for a marathon), and high blood pressure. Best of all, Bill has taken up residence on the back of my neck and created a little colony on my belly too. I always been pretty healthy (except for hypothyroidism) but in the last year, I had seen several different doctors for all of the weird things that have been happening to me. A gynecologist and dermatologist both suggested my menstrual and acne problems were likely hormonal and happening because I was probably going through perimenopause (I was 40 at the time). A psychiatrist put me on Effexor for depression and a beta-blocker for anxiety (I jump a foot when the phone would ring or someone would knock on my office door). All of these treatments seemed completely reasonable to me and they helped. It never occurred to me or anyone else they could be related. And all potentially explained why I kept gaining weight, despite not changing my diet and exercise (5-6 days a week) regime. Who knew hitting your 40s was going to be this rough? I started to really slow down on my runs - 2 to 3 minutes per mile slower than before. Maybe it was the weight gain that was making running harder, maybe it was the unusually hot and humid summer. I kept waiting for my running to get back to normal. But it never did. Every day it was a struggle to run. It was something I used to love so much - it was my way of working through stress. Now, it just made me feel bad. When I went to my regular endocrinologist in July for my annual thyroid check-up, he discovered my TSH was "way off" - and a little light went on. That's why I felt so crappy this year! I recounted my symptoms to Endo 1 (whom I had been seeing for 7 years). He thought I must be "very sensitive" to changes in hormones to have such a large reaction to the drop in TSH but hey, you never know. My Synthroid does was adjusted and I kept waiting to feel better. But I just kept getting worse. At my follow-up appointment in October, Endo 1 (who was with a medical student) told me my hormone levels were perfect and my face fell. He said I looked like I wanted a different answer. I explained that I felt worse and was having very troubling symptoms now. I run the week before and two miles in developed an excruciating headache, blurry vision and unsteadiness that stopped me in my tracks. I had to sit down for 30 minutes before the symptoms subsided and I could walk back to my car. I haven't run since. He started standing up, with the medical student in tow, and told me "this is not an endocrine problem - you should talk to your PCP and go see a cardiologist." That was that. I found a great cardiologist that deals with athletes, Dr. B. I was supposed to run the Philly marathon in November and so I tried to get his nurse to squeeze me onto his schedule in early November so I could figure out if there was something wrong with my heart. I had a stress test at his lab which came out completely normal. However, my blood pressure was very high. He told me that my heart was fine but something was very wrong for my blood pressure to be so high. I had mentioned to him that I had high BP readings at the various doctor's offices I had visited over the year - but I was always told "you are young and healthy, your BP is just high because you are in seeing the doctor today" (which for the record is ridiculous - it is hard to stress me out and a visit to the doctor is certainly not enough to do it). After reviewing my records and giving me a physical exam, he came back and told me he suspected I had Cushing's. He started some lab work to try and test for it too - two 24 hour UFC's and a dexamethasone suppression test. I had never heard of Cushing's, but my symptoms fit to a T. And as I read about "buffalo humps" and reached up to feel my neck, I realized I had known about Bill for some time. The cardiologist was so wonderful. He told me. "This is an endocrine issue, not a cardiac issue. But I am going to keep seeing you until you are better and I am going to help you navigate through the system." I felt very happy and relieved when I left his office. There was something wrong and it had a name. Now, I would just have a couple of tests, see my endocrinologist and go back to my normal life. If only life were so easy....