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MaryO

~Chief Cushie~
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  1. Biomarkers in a majority of Cushing’s syndrome patients with surgically induced disease remission showed a high rate of bone turnover and greater bone mineral density one and two years later, a study reports. Before treatment, these patients were found to have greater bone degradation and poorer bone formation, as can be common to disease-related bone disorders. Researchers believe their work is the first study of its kind, “and the data obtained will be instrumental for clinicians who care for patients with Cushing’s syndrome.” The study, “The Effect of Biochemical Remission on Bone Metabolism in Cushing’s Syndrome: A 2‐Year Follow‐Up Study,” was published in the Journal of Bone and Mineral Research. Two common co-conditions of Cushing’s syndrome are osteopenia, a loss of bone mass, and osteoporosis, in which the body makes too little bone, loses too much bone, or both. Studies suggest up to 80% of people with Cushing’s have evidence of reduced bone mineral density affecting the entire skeleton. However, few risk factors to predict bone health have been identified so far, and guidelines for osteoporosis management due to Cushing’s are lacking. Uncertainty as to the natural course of osteoporosis once a diagnosis of Cushing’s syndrome has been made is also still evident. Investigators at the University of Munich, reportedly for a first time, analyzed the natural course of bone mineral density and bone turnover (recycling) in a group of people with endogenous Cushing’s syndrome — which refers to the disease caused by excess cortisol in the bloodstream, often due to a tumor in the adrenal or pituitary glands. They examined medical records of 89 Cushing syndrome patients with a mean age of 44, of which 74% were women. Of these, 65% had pituitary Cushing’s (Cushing’s disease), 28% had adrenal, and 7% had ectopic Cushing’s, which is caused by tumors outside the adrenal or pituitary glands. A group of 71 age- and sex-matched healthy participants were included as controls. In all patients, blood samples were collected at the time of diagnosis (baseline) and one and two years after removing one or both adrenal glands or moving tumors affecting the pituitary gland. Blood samples were analyzed for biomarkers related to bone formation and degradation (resorption). At the study’s beginning, the mean levels of two bone formation markers, osteocalcin and intact PINP, were significantly decreased in patients compared with controls, whereas the bone formation marker alkaline phosphatase was increased. Both markers for bone degradation — called CTX and TrAcP — were also high, which demonstrated “increased bone resorption and decreased bone formation in [Cushing’s syndrome],” the team wrote. While bone markers were similar in participants with a reduced bone mass relative to those with a normal bone mass, bone mineral density was lower overall. Bone mineral density was significantly lower in the neck and spine compared with the femur (thigh bone). Normal bone mineral density was reported in 28 (32%) patients, while 46 (52%) had osteopenia, and the remaining 15 (17%) lived with osteoporosis. A history of low-trauma bone fractures due to osteoporosis occurred in 17 (19%) patients, taking place shortly before diagnosis in more than half of these (58%) people, and more than two years before a Cushing’s diagnosis in the remaining group (42%). Compared to patients without fractures, those with fractures had a significantly lower T‐score, a bone density measure that represents how close a person is to average peak bone density. While Cushing’s subtype, age, or body mass index (BMI, body fat based on height) did not differ between groups, men had a significantly higher risk of fractures than women (35% of men vs. 14% of women). Both disease severity and duration did not contribute to fractures rates, but urinary free cortisol (a circulating cortisol measure) was significantly higher in patients with a low T‐score. At the one year after tumor removal, which led to Cushing’s remission based on blood tests, a significant increase in bone formation markers was reported. These biomarkers decreased slightly at two years post-surgery, but remained elevated. At the beginning of the study, bone resorption markers were mildly increased, which rose further one year after surgery before returning almost to normal levels by two years. In parallel, bone density measures conducted in 40 patients showed a matching increase in T-score, particularly in the spine. After two years, bone mineral density improved in 78% of patients, and T-scores improved in 45% of them. No fractures occurred after Cushing’s treatment, and there was no significant correlation between bone turnover markers and better bone mineral density. “This study analyzes for the first time in a comprehensive way bone turnover markers during the course of [Cushing’s syndrome],” the researchers wrote. “Our data suggest that the phase immediately after remission from [Cushing’s syndrome] is characterized by a high rate of bone turnover, resulting in a spontaneous net increase in bone mineral density in the majority of patients.” These results “will influence future therapeutic strategies in patients” with Cushing’s syndrome, they added. Steve Bryson PhD Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone. From https://cushingsdiseasenews.com/2021/02/19/successful-cushings-surgery-leads-to-better-bone-density-study-finds/
  2. Novel genetic associations could pave the way for early interventions and personalized treatment of an incurable condition. Scientists from the University of Bergen (Norway) and Karolinska Institutet (Sweden) have discovered the genes involved in autoimmune Addison's disease, a condition where the body's immune systems destroys the adrenal cortex leading to a life-threatening hormonal deficiency of cortisol and aldosterone. Groundbreaking study The rarity of Addison's disease has until now made scanning of the whole genome for clues to the disease's genetic origins difficult, as this method normally requires many thousands of study participants. However, by combining the world's two largest Addison's disease registries, Prof. Eystein Husebye and his team at the University of Bergen and collaborators at Karolinska Institutet in Sweden (prof. Kämpe) were able to identify strong genetic signals associated with the disease. Most of them are directly involved in the development and functioning of the human immune system including specific molecular types in the so-called HLA-region (this is what makes matching donors and recipients in organ transplants necessary) and two different types of a gene called AIRE (which stands for AutoImmune REgulator). AIRE is a key factor in shaping the immune system by removing self-reacting immune cells. Variants of AIRE, such as the ones identified in this study, could compromise this elimination of self-reacting cells, which could lead to an autoimmune attack later in life. Knowing what predisposes people to develop Addison's disease opens up the possibilities of determining the molecular repercussions of the predisposing genetic variation (currently ongoing in Prof. Husebye's lab). The fact that it is now feasible to map the genetic risk profile of an individual also means that personalised treatment aimed at stopping and even reversing the autoimmune adrenal destruction can become a feasible option in the future. ### Contact information: Professor at the University of Bergen, Eystein Husebye - Eystein.Husebye@uib.no - cell phone +47 99 40 47 88 Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system. From https://www.eurekalert.org/pub_releases/2021-02/tuob-nsi021221.php
  3. Central hypothyroidism is prevalent in about 1 in 2 adults with Cushing’s syndrome, and thyroid function can be restored after curative surgery for most patients, according to study findings. “Our study findings have confirmed and greatly extended previous smaller studies that suggested a link between hypercortisolism and thyroid dysfunction but were inconclusive due to smaller sample size and short follow-up,” Skand Shekhar, MD, an endocrinologist and clinical investigator in the reproductive physiology and pathophysiology group at the National Institute of Environmental Health Sciences, NIH, told Healio. “Due to our large sample and longer follow-up, we firmly established a significant negative correlation between hypercortisolemia measures — serum and urinary cortisol, serum adrenocorticotropic hormone — and thyroid hormones triiodothyronine, free thyroxine and thyrotropin.” Shekhar and colleagues conducted a retrospective review of two groups of adults aged 18 to 60 years with Cushing’s syndrome. The first group was evaluated at the NIH Clinical Center from 2005 to 2018 (n = 68; mean age, 43.8 years; 62% white), and the second group was evaluated from 1985 to 1994 (n = 55; mean age, 37.2 years; 89% white). The first cohort was followed for 6 to 12 months to observe the pattern of thyroid hormone changes after surgical cure of adrenocorticotropic hormone-dependent Cushing’s syndrome. The second group underwent diurnal thyroid-stimulating hormone evaluation before treatment and during remission for some cases. Urinary free cortisol and morning thyroid hormone levels were collected for all participants. In the second group, researchers evaluated diurnal patterns of TSH concentrations with hourly measurements from 3 to 7 p.m. and midnight to 4 p.m. In the first group, adrenocorticotropic hormone and serum cortisol were measured. In the first cohort, seven participants were receiving levothyroxine for previously diagnosed primary or central hypothyroidism. Of the remaining 61 adults, 32 had untreated central hypothyroidism. Thirteen participants had free T4 at the lower limit of normal, and 19 had subnormal levels. There were 29 adults with subnormal levels of T3 and seven with subnormal TSH. Before surgery, 36 participants in the first group had central hypothyroidism. Six months after surgery, central hypothyroidism remained for 10 participants. After 12 months, the number of adults with central hypothyroidism dropped to six. Preoperative T3 and TSH levels were negatively associated with morning and midnight cortisol, adrenocorticotropic hormone and urinary free cortisol. In post hoc analysis, a baseline urinary free cortisol of more than 1,000 g per day was adversely associated with baseline and 6-month T3 and free T4 levels. In the second group, there were 51 participants not on thyroid-modifying drugs who had a thyroid function test 6 or 12 months after surgery. Before surgery, free T4 levels were subnormal in 17 participants, T3 levels were subnormal in 22, and TSH levels were in the lower half of the reference range or below in all but one participant. After surgery, two participants had below normal free T4, one had subnormal T3, and TSH levels were in the lower half of the reference range or below in 23 of 48 participants. Before surgery, there was no difference in mean TSH between daytime and nighttime. A mean 8 months after surgery, the second group had a normal nocturnal TSH surge from 1.3 mIU/L during the day to 2.17 mIU/L at night (P = .01). The nocturnal TSH increase persisted as long as 3 years in participants who had follow-up evaluations. “We found a very high prevalence of thyroid hormone deficiency that appears to start at the level of the hypothalamus-pituitary gland and extend to the tissue level,” Shekhar said. “Some of these patients may experience thyroid hormone deficiency symptoms, such as fatigue, depression, cold intolerance, weight gain, etc, as a result of systematic and tissue-level thyroid hormone deficiency. We also noted a strong correlation between hypothyroidism and hypogonadism, which implies that hypothyroid patients are also likely to suffer adverse reproductive effects. Thus, it is imperative to perform thorough thyroid hormone assessment in patients with Cushing’s syndrome, and thyroid hormone supplementation should be considered for these patients unless cure of Cushing’s syndrome is imminent.” Researchers said providers should routinely screen for hypothyroidism in adults with Cushing’s syndrome. Even after thyroid function is restored, regular follow-up should also be conducted. Further research is needed to investigate thyroid dysfunction in iatrogenic Cushing’s syndrome and the impact of these findings on euthyroid sick syndrome, Shekhar said. For more information: Skand Shekhar, MD, can be reached at skand.shekhar@nih.gov. From https://www.healio.com/news/endocrinology/20210208/thyroid-dysfunction-highly-prevalent-in-cushings-syndrome
  4. The cancer medicine bexarotene may hold promise for treating Cushing’s disease, a study suggests. The study, “Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT‐20 cells,” was published in the Journal of Cellular and Molecular Medicine. Cushing’s disease is caused by a tumor on the pituitary gland, leading this gland to produce too much adrenocorticotropic hormone (ACTH). Excess ACTH causes the adrenal glands to release too much of the stress hormone cortisol; abnormally high cortisol levels are primarily responsible for the symptoms of Cushing’s. Typically, first-line treatment is surgical removal of the pituitary tumor. But surgery, while effective in the majority of cases, does not help all. Additional treatment with medications or radiation therapy (radiotherapy) works for some, but not others, and these treatments often have substantial side effects. “Thus, the development of new drugs for CD [Cushing’s disease] treatment is extremely urgent especially for patients who have low tolerance for surgery and radiotherapy,” the researchers wrote. Recent research has shown that a protein called testicular receptor 4 (TR4) helps to drive ACTH production in pituitary cancers. Thus, blocking the activity of TR4 could be therapeutic in Cushing’s disease. Researchers conducted computer simulations to screen for compounds that could block TR4. This revealed bexarotene as a potential inhibitor. Further biochemical tests confirmed that bexarotene could bind to, and block the activity of, TR4. Bexarotene is a type of medication called a retinoid. It is approved to treat cutaneous T-cell lymphoma, a rare cancer that affects the skin, and available under the brand name Targretin. When pituitary cancer cells in dishes were treated with bexarotene, the cells’ growth was impaired, and apoptosis (a type of programmed cell death) was triggered. Bexarotene treatment also reduced the secretion of ACTH from these cells. In mice with ACTH-secreting pituitary tumors, bexarotene’s use significantly reduced tumor size, and lowered levels of ACTH and cortisol. Cushing’s-like symptoms also eased; for example, bexarotene treatment reduced the accumulation of fat around the abdomen in these mice. Additional cellular experiments suggested that bexarotene specifically works on TR4 by changing the location of the protein. Normally, TR4 is present in the nucleus — the cellular compartment that houses DNA — where it helps to control the production of ACTH. But with bexarotene treatment, TR4 tended to go outside of the nucleus, leading to lower ACTH production. The researchers noted that other mechanisms may also be involved in the observed effects of bexarotene. “In summary, our work demonstrates that bexarotene is a potential inhibitor for TR4. Importantly, bexarotene may represent a new drug candidate to treat CD,” the researchers concluded. From https://cushingsdiseasenews.com/2021/02/05/bexarotene-cancer-drug-t-cell-lymphoma-acth-production/?preview_id=39289
  5. Abstract Cushing's syndrome is a rare entity in children. Adrenal tumour is the common cause of this syndrome in young children, whereas, iatrogenic causes are more common among older children. We report a 4 year old male child diagnosed with Cushing syndrome due to a right adrenal adenoma; the child presented with obesity and increase distribution of body hair. After thorough investigation and control of hypertension and dyselectrolytemia, right adrenalectomy was performed. The patient had good clinical recovery with weight loss and biochemical resolution of Cushing's syndrome. 1. Introduction Cushing's syndrome (CS) is rarely encountered in children. The overall incidence of Cushing syndrome is approximately 2–5 new cases per million people per year. Only approximately 10% of the new cases each year occur in children [1]. Unlike in adults, a male-to-female predominance have been observed in infants and young toddlers [[1], [2], [3]]. Although iatrogenic causes are common in children above seven years of age, adrenal causes (adenoma, carcinoma or hyperplasia) are common in children of younger age [4]. We report a 4 year old boy diagnosed with Cushing syndrome caused by a right adrenal adenoma, who had presented with obesity and increase distribution of body hair. Right adrenalectomy was performed and clinical stabilization resulted in weight loss and biochemical resolution of Cushing's syndrome. (see Fig. 5) 2. Case report A 4 years old boy presented with complaints of excessive weight gain of 5 months duration and increase frequency of micturition and appearance of body hair for 4 months. There was no history of any other illness, medication or steroid intake. The child was first born at term by normal vaginal delivery and birth weight of 3 kg. Physical examination revealed a chubby boy with moon face, buffalo hump, protruding abdomen, increase body hair and appearance of coarse pubic hair (Fig. 1). His intelligent quotient (IQ) was appropriate for his age and sex. His younger sibling was in good health and other family members did not have any metabolic or similar problems. Download : Download high-res image (710KB) Download : Download full-size image Fig. 1. The child with moon face, protruded abdomen and coarse body hair. The patient's body length was 92cm (between -2SD to -3SD), weight 20kg (between 1 SD and 2 SD), weight for height >3SD, and BMI was 23.6 (BMI for age >3 SD). His blood pressure on right arm in lying position was 138/76 mm Hg (above 99th percentile for height and age). Investigations: Morning 8am serum cortisol level - 27.3 μg/dl (normal: 6–23 μg/dl). with a concurrent plasma ACTH level of < 5 pg/ml (n value < 46 pg/ml). His serum cortisol following low dose dexamethasone suppression test (1mg dexamethasone at 11pm) at 8 am next morning was 22.1 μug/dl and his 24 hours urine catecholamine fraction was within normal limit. HB % -- 10.3 gm/dl; LDDST -- 25 μg/dl; FBS -- 106 mg/dl. Serum Na+ - 140.6mmol/l; K+ - 2.83mmol/l; Ca+ - 8.7 mg/dl. S. Creatinine −0.3 mg/dl. Ultrasonography of abdomen revealed a heterogenous predominantly hypoechoic right supra renal mass. Contrast enhanced CT abdomen revealed well defined soft tissue density lesion (size −5.2 cm × 5.2 cm x 5.7cm) in right adrenal gland with calcifications and fat attenuations showing mild attenuation on post contrast study (Fig. 2). Download : Download high-res image (703KB) Download : Download full-size image Fig. 2. CECT shows right adrenal mass with calcification and mild attenuation on post-contrast study. The child was started on oral amlodipine 2.5mg 12hourly; after 5days blood pressure became normal. For hypokalemia oral potassium was given @20 meq 8 hourly and serum potassium value became normal after 4 days. Right laparoscopic adrenalectomy was planned. but due to intra operative technical problems it was converted to an open adrenalectomy with right subcostal incision. A lobulated mass of size 9 cm × 5 cm x 4 cm with intact capsule was excised. The tumour weighed 230 gm. There was no adhesion with adjacent organs, three regional nodes were enlarged but without any tumour tissue. Inferior vena cava was spared. Histopathology report was consistent with adrenal adenoma (Fig. 3) (see Fig. 4). Download : Download high-res image (427KB) Download : Download full-size image Fig. 3. Cut section of tumour shows fleshy mass with fatty tissue. Download : Download high-res image (618KB) Download : Download full-size image Fig. 4. Microphotograph (100 × 10) showing intact capsule and adrenal tumour cells, which are larger in size with nuclear pleomorphism, inconspicuous nucleoli, cytoplasm of the tumour cells are abundant, eosinophilic and vacuolated. Download : Download high-res image (593KB) Download : Download full-size image Fig. 5. Physical appearance 4 months after adrenalectomy. Post operative management: during post operative period hypokalemia and flaxuating blood sugar level was managed with oral potassium and oral glucose supplement. patient developed mild cough and respiratory distress on post op day 2, it was managed with salbutamol nebulization and respiratory physio therapy. Patient developed minor ssi and discharged on 10 th post operative day with oral prednisolone supplementation. Follow up: the patient was followed up 2week after discharge and then every monthly, the oral prednisolone was gradually tapered and completely withdrawn on 2nd month after surgery.The patient experienced no post-surgical complications. After 4 months of surgery he reduces 6 kgs of his body weight with BMI of 16.5 (between median and 1SD) & BP 100/74 mm hg (within normal range), the moon face, buffalo hump, central obesity disappeared, morning 8am serum cortisol level was found within normal range 14 μg/dl (n value 6–23 μg/dl). 3. Discussion Cushing's syndrome is caused by prolonged exposure to supraphysiological levels of circulating glucocorticoids, which may be endogenously or exogenously derived. During infancy, CS is usually associated with McCune-Albright syndrome; adrenocortical tumours most commonly occur in children under four years of age and Cushing's disease (ACTH dependent) is the commonest cause of CS after five years of age [5]. Primary adrenocortical tumours (ACTs) account for only 0.3–0.4% of all childhood neoplasms. Almost a third of these tumours manifests as Cushing syndrome and over 70% of the unilateral tumours in young children are often malignant [2,3,6,7]. There seems to be a bimodal incidence of these tumours, with one peak at under 5 years of age and the second one in the fourth or fifth decades of life. ACTs may be associated with other syndromes, such as, Li-Fraumeni syndrome, Beckwith-wiedemann syndrome, isolated hemihypertrophy, or even a germline point mutation of P53 tumour suppressor gene as reported in a series from Brazil [8]. In comparison to adult CS, growth failure with associated weight gain is one of the most reliable indicators of hypercortisolaemia in pediatric CS. The parents often fail to notice facial changes and growth failure and hence the diagnosis is often delayed. In one study, the mean time from appearing symptoms to diagnosis in 33 children with Cushing's disease was 2.5 years [5]. More recently the comparison of height and BMI SDS measurements provided a sensitive diagnostic discriminator in pediatric patients with CD and those with simple obesity [9]. In the present case, the parents observed noticeable changes in his face and presence of body hair, which made them to bring the child to medical attention. A review of 254 children on the International Pediatric Adrenocortical Tumour Registry identified virilization as the most common manifestation [10]. About 10% of the tumours can be non-functional at presentation, and approximately one third of pediatric patients present with hypertension. Majority of patients (192/254) in the Registry had localized disease and metastatic disease was found in less than 5% of cases. Older children with CS or mixed androgen and cortisol secreting adrenocortical tumours had a worse prognosis compared to younger children [10]. The present case had mild hypertension as well as dyselectrolytemia at presentation, which could be controlled with medication. He had a single adenoma confined to the adrenal gland and there was no evidence of malignancy. After surgical excision of the tumour and the right adrenal gland, the patient made rapid improvement in clinical condition and has been on follow up for last 7 months. 4. Conclusion Pediatric adrenocortical tumours (ACTs) are most commonly encountered in females and in children less than four years. But our case being an 4-year-old boy forms a rare presentation of endogenous Cushing's syndrome due to adrenal adenoma. Cushing's syndrome in this child was controlled after right adrenalectomy. Patient consent Informed written consent was taken. Funding No funding or grant support. Authorship All authors attest that they meet the current ICMJE criteria for authorship. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References [1] M.A. Magiakou, G. Mastorakos, E.H. Oldfield, et al. Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy N Engl J Med, 331 (10) (1994), pp. 629-636 [PubMed: 8052272] [2] C. Tsigos, G.P. Chrousos Differential diagnosis and management of Cushing's syndrome Annu Rev Med, 47 (1996), pp. 443-461 [PubMed: 8712794] [3] D.N. Orth Cushing's syndrome N Engl J Med, 332 (12) (1995), pp. 791-803 [PubMed: 7862184] [4] C.J. Migeon, R. Lanes (fifth ed.)F. Lifshitz (Ed.), “Adrenal cortex: hypo and hyper_x0002_function,” in Pediatric Endocrinology, vol. 8, Informa Healthcare, London, UK (2007), p. 214 [5] L.F. Chan, H.L. Storr, A.B. Grossman, M.O. Savage Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment Arq Bras Endocrinol Metabol, 51 (8) (2007), pp. 1261-1271, 10.1590/S0004-273 [6] C.A. Stratakis, L.S. Kirschner Clinical and genetic analysis of primary bilateral adrenal diseases(micro- and macronodular disease) leading to Cushing syndrome Horm Metab Res, 30 (6–7) (1998), pp. 456-463 [PubMed: 9694579] [7] W.L. Miller, J.J. Townsend, M.M. Grumbach, S.L. Kaplan An infant with Cushing's disease due to anadrenocorticotropin-producing pituitary adenoma J Clin Endocrinol Metabol, 48 (6) (1979), pp. 1017-1025 [8] R.C. Ribeiro, F. Sandrini, B. Figueiredo, G.P. Zambetti, E. Michalkiewicz, A.R. Lafferty, et al. An inherited P53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma Proc Natl Acad Sci U S A, 98 (16) (2001), pp. 9330-9335 [9] J.E. Greening, H.L. Storr, S.A. McKenzie, K.M. Davies, L. Martin, A.B. Grossman, et al. Linear growth and body mass index in pediatric patients with Cushing's disease or simple obesity J Endocrinol Invest, 29 (10) (2006), pp. 885-887 [10] E. Michalkiewicz, R. Sandrini, B. Figueiredo, E.C. Miranda, E. Caran, A.G. Oliveira-Filho, et al. Clinical and outcome characteristics of children with adrenocortical tumors: a report from the international pediatric adrenocortical tumor Registry J Clin Oncol, 22 (5) (2004), pp. 838-845 From https://www.sciencedirect.com/science/article/pii/S2213576620303833
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  7. Researchers conducted this retrospective cohort study to investigate acute and life-threatening complications in patients with active Cushing syndrome (CS). Participants in the study were 242 patients with CS, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. In patients with benign pituitary CS, the prevalence of acute complications was 62%, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Infections, thromboembolic events, hypokalemia, hypertensive crises, cardiac arrhythmias and acute coronary events were complications reported in patients with benign CS. The whole spectrum of acute and life-threatening complications in CS and their high prevalence was illustrated in this study both before disease diagnosis and after successful surgery. Read the full article on Journal of Clinical Endocrinology and Metabolism.
  8. Thyroid cancer survival rates are 84 percent for 10 years or more if diagnosed early. Early diagnosis is crucial therefore and spotting the unusual signs could be a matter of life and death. A sign your thyroid cancer has advanced includes Cushing syndrome. What is it? What is Cushing syndrome? Cushing syndrome occurs when your body is exposed to high levels of the hormone cortisol for a long time, said the Mayo Clinic. The health site continued: “Cushing syndrome, sometimes called hypercortisolism, may be caused by the use of oral corticosteroid medication. “The condition can also occur when your body makes too much cortisol on its own. “Too much cortisol can produce some of the hallmark signs of Cushing syndrome — a fatty hump between your shoulders, a rounded face, and pink or purple stretch marks on your skin.” In a study published in the US National Library of Medicine National Institutes of Health, thyroid carcinoma and Cushing’s syndrome was further investigated. The study noted: “Two cases of thyroid carcinoma and Cushing's syndrome are reported. “Both of our own cases were medullary carcinomas of the thyroid, and on reviewing the histology of five of the other cases all proved to be medullary carcinoma with identifiable amyloid in the stroma. “A consideration of the temporal relationships of the development of the carcinoma and of Cushing's syndrome suggested that in the two cases with papillary carcinoma these conditions could have been unrelated, but that in eight of the nine cases with medullary carcinoma there was evidence that thyroid carcinoma was present at the time of diagnosis of Cushing's syndrome. “Medullary carcinoma of the thyroid is also probably related to this group of tumours. It is suggested that the great majority of the tumours associated with Cushing's syndrome are derived from cells of foregut origin which are endocrine in nature.” In rare cases, adrenal tumours can cause Cushing syndrome a condition arising when a tumour secretes hormones the thyroid wouldn’t normally create. Cushing syndrome associated with medullary thyroid cancer is uncommon. The syndrome is more commonly caused by the pituitary gland overproducing adrenocorticotropic hormone (ACTH), or by taking oral corticosteroid medication. See a GP if you have symptoms of thyroid cancer, warns the NHS. The national health body added: “The symptoms may be caused by less serious conditions, such as an enlarged thyroid, so it's important to get them checked. “A GP will examine your neck and can organise a blood test to check how well your thyroid is working. “If they think you could have cancer or they're not sure what's causing your symptoms, you'll be referred to a hospital specialist for more tests.” Adapted from https://www.express.co.uk/life-style/health/1351753/thyroid-cancer-signs-symptoms-cushing-syndrome
  9. A young healthcare worker who contracted COVID-19 shortly after being diagnosed with Cushing’s disease was detailed in a case report from Japan. While the woman was successfully treated for both conditions, Cushing’s may worsen a COVID-19 infection. Prompt treatment and multidisciplinary care is required for Cushing’s patients who get COVID-19, its researchers said. The report, “Successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia,” was published in Endocrine Journal. Cushing’s disease is caused by a tumor on the pituitary gland, which results in abnormally high levels of the stress hormone cortisol (hypercortisolism). Since COVID-19 is still a fairly new disease, and Cushing’s is rare, there is scant data on how COVID-19 tends to affect Cushing’s patients. In the report, researchers described the case of a 27-year-old Japanese female healthcare worker with active Cushing’s disease who contracted COVID-19. The patient had a six-year-long history of amenorrhea (missed periods) and dyslipidemia (abnormal fat levels in the body). She had also experienced weight gain, a rounding face, and acne. After transferring to a new workplace, the woman visited a new gynecologist, who checked her hormonal status. Abnormal findings prompted a visit to the endocrinology department. Clinical examination revealed features indicative of Cushing’s syndrome, such as a round face with acne, central obesity, and buffalo hump. Laboratory testing confirmed hypercortisolism, and MRI revealed a tumor in the patient’s pituitary gland. She was scheduled for surgery to remove the tumor, and treated with metyrapone, a medication that can decrease cortisol production in the body. Shortly thereafter, she had close contact with a patient she was helping to care for, who was infected with COVID-19 but not yet diagnosed. A few days later, the woman experienced a fever, nausea, and headache. These persisted for a few days, and then she started having difficulty breathing. Imaging of her lungs revealed a fluid buildup (pneumonia), and a test for SARS-CoV-2 — the virus that causes COVID-19 — came back positive. A week after symptoms developed, the patient required supplemental oxygen. Her condition worsened 10 days later, and laboratory tests were indicative of increased inflammation. To control the patient’s Cushing’s disease, she was treated with increasing doses of metyrapone and similar medications to decrease cortisol production; she was also administered cortisol — this “block and replace” approach aims to maintain cortisol levels within the normal range. The patient experienced metyrapone side effects that included stomach upset, nausea, dizziness, swelling, increased acne, and hypokalemia (low potassium levels). She was given antiviral therapies (e.g., favipiravir) to help manage the COVID-19. Additional medications to prevent opportunistic fungal infections were also administered. From the next day onward, her symptoms eased, and the woman was eventually discharged from the hospital. A month after being discharged, she tested negative for SARS-CoV-2. Surgery for the pituitary tumor was then again possible. Appropriate safeguards were put in place to protect the medical team caring for her from infection, during and after the surgery. The patient didn’t have any noteworthy complications from the surgery, and her cortisol levels soon dropped to within normal limits. She was considered to be in remission. Although broad conclusions cannot be reliably drawn from a single case, the researchers suggested that the patient’s underlying Cushing’s disease may have made her more susceptible to severe pneumonia due to COVID-19. “Since hypercortisolism due to active Cushing’s disease may enhance the severity of COVID-19 infection, it is necessary to provide appropriate, multidisciplinary and prompt treatment,” the researchers wrote. From https://cushingsdiseasenews.com/2021/01/15/covid-19-may-be-severe-cushings-patients-case-report-suggests/?cn-reloaded=1
  10. Dr. Theodore Friedman will host a webinar on COVID-19 Vaccines for Endocrine Patients Dr. Friedman will discuss topics including: How do the vaccines work? What did the New England Journal of Medicine article say about the Pfizer vaccine? What are the different vaccine options? What are the side effects? Who should and shouldn’t get a vaccine? What about Dr. Friedman’s vaccine studies? Sunday • December 27 • 6 PM PST Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m5085619c25d8a2417d9316b56fe7830b OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 177 542 2496 Your phone/computer will be muted on entry. Slides will be available on the day of the talk here There will be plenty of time for questions using the chat button. Meeting Password: pcos For more information, email us at mail@goodhormonehealth.com
  11. Dr. Theodore Friedman will host a webinar on COVID-19 Vaccines for Endocrine Patients Dr. Friedman will discuss topics including: How do the vaccines work? What did the New England Journal of Medicine article say about the Pfizer vaccine? What are the different vaccine options? What are the side effects? Who should and shouldn’t get a vaccine? What about Dr. Friedman’s vaccine studies? Sunday • December 27 • 6 PM PST Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m5085619c25d8a2417d9316b56fe7830b OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 177 542 2496 Your phone/computer will be muted on entry. Slides will be available on the day of the talk here There will be plenty of time for questions using the chat button. Meeting Password: pcos For more information, email us at mail@goodhormonehealth.com
  12. Update November 22, 2020 I have not updated my patients on the COVID-19 pandemic since March. Since the last update and as of today’s date, 12.2 million Americans have been infected with COVID-19 and 256,000 Americans have died. Several of Dr. Friedman’s patients have been infected with COVID-19. Many businesses have closed and there have been major economic loses. The response to the pandemic has unfortunately been politicized and I say unfortunately because the virus doesn’t distinguish based on victim’s political party. Please see Dr. Friedman’s Letter in the Los Angeles Jewish Journal https://jewishjournal.com/letters_to_the_editor/316110/letters-lockdown-vs-no-lockdown/. Dr. Friedman completely supports efforts to limit the spread of the virus, including wearing masks, social distancing, handwashing and staying at home. Listening to government officials including the CDC is crucial. Dr. Friedman agrees with data showing gatherings are much safer outside and encourages his patients to err on the side of safety and caution. Dr. Friedman is spearheading efforts at Charles R. Drew University to be a site for a vaccine study and after some delays, it looks like his University will be a site for the Sanofi vaccine in December 2020. Dr. Friedman is very excited about the promising results from the Moderna and Pfizer trials and thinks vaccines along with mask-wearing and social distancing will curtail the pandemic, hopefully in the latter half of 2021. He does think that COVID-19 will be with us for a long time. Dr. Friedman anticipates that changes due to COVID-19, including telemedicine and working from home will remain with us after the pandemic subsides. As mentioned in the March update, patients with endocrine problems such as Cushing’s syndrome, Addison’s Disease, hypopituitarism and diabetes have slightly impaired immune systems, making them potentially susceptible for a more severe infection by COVID-19. He would recommend those patients to be especially vigilant about mask-wearing/social distancing and to get a vaccine when it comes out. He advices his patients the following: Wear masks, social distancing, handwashing and staying at home as much as possible Use delivery services for groceries, food and medications. Wash hands frequently for 20 seconds and/or use hand sanitizer several times a day Avoid air travel, public gatherings and other public places as guided by local officials Quarantine if sick or exposed. Labcorp and Quest both introduced testing for COVID-19 using nasal swabs. Several other laboratories are also performing tests. Dr. Friedman recommends PCR testing and not rapid antigen testing. For those with symptoms of Coronavirus, he recommends seeing your primary care doctor for testing. Dr. Friedman is unable to provide requisitions or swabs for this testing that should be done by their primary doctor. While Dr. Friedman was initially enthusiastic about antibody testing, he is concerned about the quality of the tests and no longer recommends it. Labcorp and Quest are both still open and Quest has a new Peace of Mind program for lab services not related to COVID-19 and for patients who are 60 years of age or older, or have other conditions that put them at greater risk for COVID-19, in which patients can come to their nearby Quest location during the first hour of each day for VIP care. Dr. Friedman encourages people to get their hormone testing done and make their followup appointments. Many patients have requested extra supply of their medications. However, most insurances do not allow this and carefully monitor medication use. Dr. Friedman recommends patients to use a mail-order pharmacy and sign up for auto-refills so that they get a consistent supply of their medications. Except for patients sick with COVID-19, patients should not up-dose hydrocortisone Dr. Friedman has restarting in person visits on the last Tuesday of each month and continues to see patients via telemedicine on the other Tuesday nights. Please visit goodhormonehealth.com for more information or to schedule an appointment. Dr. Friedman’s staff will still be doing in person growth hormone stimulation tests on Tuesday night in an isolated and sanitized clinic setting. Dr. Friedman especially encourages patients to eat healthy and exercise (especially being outside) including walking, hiking, biking, aerobic videos yoga or pilates at home, during this stressful period. Dr. Friedman encourages patients to get their flu vaccine and the COVID-19 vaccine when available. Everyone should pray that the pandemic ends soon. Dr. Friedman wishes everyone to stay healthy
  13. From message board member @sharm - Sharmyn McGraw: Hi All, I hope you can join us on Zoom this Saturday, Nov. 14, 2020 starting at 9:00 a.m. (PST). For those that can't make it, I will record the meeting and post it later on our Facebook page. I look forward to seeing you! Contact @sharm if you have questions or email her here: pituitarybuddy@hotmail.com
  14. From message board member @sharm - Sharmyn McGraw: Hi All, I hope you can join us on Zoom this Saturday, Nov. 14, 2020 starting at 9:00 a.m. (PST). For those that can't make it, I will record the meeting and post it later on our Facebook page. I look forward to seeing you! Contact @sharm if you have questions or email her here: pituitarybuddy@hotmail.com
  15. How stressed are you? Your earwax could hold the answer. A new method of collecting and analyzing earwax for levels of the stress hormone cortisol may be a simple and cheap way to track the mental health of people with depression and anxiety. Cortisol is a crucial hormone that spikes when a person is stressed and declines when they're relaxed. In the short-term, the hormone is responsible for the "fight or flight" response, so it's important for survival. But cortisol is often consistently elevated in people with depression and anxiety, and persistent high levels of cortisol can have negative effects on the immune system, blood pressure and other bodily functions. There are other disorders which involve abnormal cortisol, including Cushing's disease (caused by the overproduction of cortisol) and Addison's disease (caused by the underproduction of cortisol). People with Cushing's disease have abnormal fat deposits, weakened immune systems and brittle bones. People with Addison's disease have dangerously low blood pressure. There are a lot of ways to measure cortisol: in saliva, in blood, even in hair. But saliva and blood samples capture only a moment in time, and cortisol fluctuates significantly throughout the day. Even the experience of getting a needle stick to draw blood can increase stress, and thus cortisol levels. Hair samples can provide a snapshot of cortisol over several months instead of several minutes, but hair can be expensive to analyze — and some people don't have much of it. Andrés Herane-Vives, a lecturer at University College London's Institute of Cognitive Neuroscience and Institute of Psychiatry, and his colleagues instead turned to the ear. Earwax is stable and resistant to bacterial contamination, so it can be shipped to a laboratory easily for analysis. It also can hold a record of cortisol levels stretching over weeks. But previous methods of harvesting earwax involved sticking a syringe into the ear and flushing it out with water, which can be slightly painful and stressful. So Herane-Vives and his colleagues developed a swab that, when used, would be no more stressful than a Q-tip. The swab has a shield around the handle, so that people can't stick it too far into their ear and damage their eardrum, and a sponge at the end to collect the wax. In a small pilot study, researchers collected blood, hair and earwax from 37 participants at two different time points. At each collection point, they sampled earwax using a syringe from one ear, and using the new self-swab method from the other. The researchers then compared the reliability of the cortisol measurements from the self-swab earwax with that of the other methods. They found that cortisol was more concentrated in earwax than in hair, making for easier analysis. Analyzing the self-swabbed earwax was also faster and more efficient than analyzing the earwax from the syringe, which had to be dried out before using. Finally, the earwax showed more consistency in cortisol levels compared with the other methods, which were more sensitive to fluctuations caused by things like recent alcohol consumption. Participants also said that self-swabbing was more comfortable than the syringe method. The researchers reported their findings Nov. 2 in the journal Heliyon. Herane-Vives is also starting a company called Trears to market the new method. In the future, he hopes that earwax could also be used to monitor other hormones. The researchers also need to follow up with studies of Asian individuals, who were left out of this pilot study because a significant number only produce dry, flaky earwax as opposed to wet, waxy earwax. "After this successful pilot study, if our device holds up to further scrutiny in larger trials, we hope to transform diagnostics and care for millions of people with depression or cortisol-related conditions such as Addison's disease and Cushing syndrome, and potentially numerous other conditions," he said in a statement. Originally published in Live Science.
  16. We have an opportunity for you to take part in a Cushing's Disease study(IPS_4636) for Patients. Our project number for this study is IPS_4636. Project Details: Web- Camera Interview There is a homework component Interview is 75-minutes long 125 Reward + 100 homework Things to Note: Patient study only, Caregivers please pass the link along Unique links, please do not pass along for 2nd use One Participant per household Want to share this opportunity? Let us know and we can provide a new link Preliminary questions are Mobile Friendly! Save this email to reference if you have any questions about the study! If you have any problems, email pm3@rarepatientvoice.com and reference the project number. If you hit reply, you will get an auto do-not-reply email. If you are interested in this study, please click the link below to answer a few questions to see if you qualify. Study Link: Link OR if the Study Hyperlink is not clickable above, please copy/paste this URL below. https://panel.rarepatientvoice.com/newdesign/site/rarepatientvoice/surveystart.php?surveyID=hld5jbejublj&panelMemberID=trfnbc7mvduh1gseff1h&invite=email Thanks as always for your participation! Please be aware that by entering this information you are not guaranteed that you will be selected to participate. As always, we do not share any of your contact information without your permission.
  17. The treatment of adrenal insufficiency with hydrocortisone granules in children with congenital adrenal hyperplasia (CAH) was associated with an absence of adrenal crises and normal growth patterns over a 2-year period, according to study findings published in The Journal of Clinical Endocrinology and Metabolism. The study included a total of 17 children with CAH and 1 child with hypopituitarism. All included participants were <6 years old who were receiving current adrenocortical replacement therapy, including hydrocortisone with or without fludrocortisone. Hydrocortisone medications used in this population were converted from pharmacy compounded capsules to hydrocortisone granules without changing the dose. These study participants were followed by study investigators for 2 years. Glucocorticoid replacement therapy was given three times a day for a median treatment duration of 795 days. Treatment was adjusted by 3 monthly 17-hydroxyprogesterone (17-OHP) profiles in children with CAH. There were a 150 follow-up visits throughout the study. At each visit, participants underwent assessments that measured hydrocortisone dose, height, weight, pubertal status, adverse events, and incidence of adrenal crisis. A total of 40 follow-up visits had changes in hydrocortisone doses based on salivary measurements (n=32) and serum 17-OHP levels (n=8). At time of study entry, the median daily doses of hydrocortisone were 11.9 mg/m2 for children between the ages of 2 to 8 years, 9.9 mg/m2 for children between 1 month and 2 years, and 12.0 mg/m2 for children <28 days of age. At the end of the study, the respective doses for the 3 age groups were 10.2, 9.8, and 8.6. The investigators observed no trends in either accelerated growth or reduced growth; however, 1 patient with congenital renal hypoplasia and CAH did show reduced growth. While 193 treatment-emergent adverse events, including pyrexia, gastroenteritis, and viral upper respiratory tract infection, were reported in 14 patients, there were no observed adrenal crises. Limitations of this study included the small sample size as well as the relatively high drop-out rate of the initial sample. The researchers concluded that “hydrocortisone granules are an effective treatment for childhood adrenal insufficiency providing the ability to accurately prescribe pediatric appropriate doses.” Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures. Reference Neumann U, Braune K, Whitaker MJ, et al. A prospective study of children 0-7 years with CAH and adrenal insufficiency treated with hydrocortisone granules. Published online September 4, 2020. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa626
  18. Generally overweight people have weight everywhere and don't get a buffalo hump. Please don't give up! I know it's hard to get a diagnosis but definitely worthwhile.
  19. Dr. Friedman wants to update his patients about natural desiccated thyroid (NDT) recalls based on new information from the FDA. Dr. Friedman prescribes various thyroid hormone preparations to his patients with hypothyroidism. This includes natural desiccated thyroid (NDT) of which two preparations are WP Thyroid and Nature-Throid, both made by RLC Labs. On August 25, 2020, RLC Labs announced a voluntary, consumer-level recall of all lots of Nature-Throid and WP Thyroid tablets because some lots contain less than the required 90% of the active ingredient as determined by the FDA. The RLC spokesperson said to Dr. Friedman that one lot of WP Thyroid and 5 lots of Nature-Throid contained between 87% and 90% of the labeled amount of levothyroxine (T4) or liothyronine (T3). Recently the FDA announced which lots are recalled that are listed below. According to the recall, if a patient receives a sub-potent tablet, hypothyroid symptoms may not be controlled. To date, there have been no reports of adverse events related to this recall. Patients who have had an adverse event should contact RLC Labs. The lot numbers are listed on the bottles of Nature-Throid and WP Thyroid. With this information about which lots are recalled, Dr. Friedman is only recommended those taking the effective lots to discontinue them. Currently no lots of Nature-Throid and WP Thyroid tablets are commercially available, so a replacement with the same product is not an option. It is unknown how long it will be before Nature-Throid and WP Thyroid become commercially available. In September 2020, the FDA also announced that two lots (one of 15 mg and one of 120 mg) (see table) of NP Thyroid made by Acella Pharamceuticals were also recalled due to reduced potency between 87% and 90% of the labeled amount of levothyroxine (T4) or liothyronine (T3). Other lots are currently available. The lot numbers are not listed on the Acella product bottles, but the expiration dates are. If patient has one of the products with the expiration date listed, they can ask their pharmacy for the lot number. Dr. Friedman has several comments about these recalls. Dr. Friedman sees them as unfortunate, but still believes NDT is a good option for patients with hypothyroidism. The “subpotent” Nature-Throid, WP Thyroid and NP Thyroid pills are only slightly less potent than stated in that only the effective lots are between 87% and 90% of the T4 and T3 levels. For most patients, they will not have symptoms from these subpotent pills and if they are taking a lot that is subpotent, the dose can be adjusted based on laboratory levels at your next appointment with Dr. Friedman. According to Dr. Friedman, patients taking Nature-Throid and WP Thyroid with the subpotent lots have three options: 1) they can continue taking Nature-Throid and WP Thyroid knowing they may have a subpotent lot and knowing that they may not be able to get a refill at least temporarily. 2) patients can be switched to Armour thyroid, NP thyroid or have a compounding pharmacy compound the equivalent dose using USP grade porcine powder. Please let Dr. Friedman’s office know if you would like to go on a different desiccated thyroid product (and which one) and what pharmacy you would like to use, 3) Dr. Friedman has a small supply of desiccated thyroid with no reclled lots that is available at his clinic for those in Los Angeles on the last Tuesday night of each month. He will not be able to mail desiccated thyroid. Please contact his office about this option. Patients with a subpotent lot of NP thyroid can have their pharmacy switch them to an unaffected lot at no charge. Patients do not need to contact Dr. Friedman, but if you have any questions or need to schedule an appointment with Dr. Friedman, please email us at mail@goodhormonehealth.com or schedule an appointment on his website at www.goodhormonehealth.com.
  20. Presented by Dr. Magge, Assistant Professor of Neurology at Weill Cornell Medical College and an Assistant Attending Neurologist at New York-Presbyterian Hospital. Dr. Ranakrishna, Chief of Neurological Surgery at NewYork-Presbyterian Brooklyn Methodist Hospital, Associate Professor of Neurological Surgery at Avina and Willis Murphy at Weill Cornell Medicine Click here to attend. Date: Tuesday, October 13, 2020 Time: 10:00 AM Eastern Daylight Time Learning objectives: - the basic characteristics of the different types of pituitary adenomas - the potential predictors of recurrence and aggressiveness in pituitary adenomas - the surgical and radiotherapy options for recurrent pituitary adenomas - the potential medical interventions, including chemotherapy, for recurrent pituitary adenomas
  21. Presented by Dr. Magge, Assistant Professor of Neurology at Weill Cornell Medical College and an Assistant Attending Neurologist at New York-Presbyterian Hospital. Dr. Ranakrishna, Chief of Neurological Surgery at NewYork-Presbyterian Brooklyn Methodist Hospital, Associate Professor of Neurological Surgery at Avina and Willis Murphy at Weill Cornell Medicine Click here to attend. Date: Tuesday, October 13, 2020 Time: 10:00 AM Eastern Daylight Time Learning objectives: - the basic characteristics of the different types of pituitary adenomas - the potential predictors of recurrence and aggressiveness in pituitary adenomas - the surgical and radiotherapy options for recurrent pituitary adenomas - the potential medical interventions, including chemotherapy, for recurrent pituitary adenomas
  22. Bettye passed away due to complications of Cushing’s disease. Once she was finally diagnosed, a decision was made against surgery and Bettye was put on the cortisol-lowering medication Korlym. Though she had initially gained weight from Cushing’s disease, as many patients do, she rapidly lost weight and was admitted into hospice care soon after. Read more at https://cushingsbios.com/2017/09/28/in-memory-bettye-jean-douglas-september-28-2016/
  23. Health Condition: All Conditions Demographics: Ages 18+, United States Resident Special Request(s): Everyone who has taken part in a clinical trial is asked to share. We are interested in learning why you decided to take part in a clinical trial and how your experience went. Honoraria: Some respondents may be asked to participate in a clinical trial awareness network where there are paid opportunities to tell their stories. Apply to learn more.
  24. Michael P Catalino 1 2, David M Meredith 3 4, Umberto De Girolami 3 4, Sherwin Tavakol 1 5, Le Min 6, Edward R Laws 1 4 Affiliations expand PMID: 32886921 DOI: 10.3171/2020.5.JNS201514 Abstract Objective: This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes. Methods: Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups. Results: The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke's hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7-7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4-2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups. Conclusions: This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar. Keywords: ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; Cushing disease; HPA = hypothalamic-pituitary-adrenal; HR = hazard ratio; IPSS = inferior petrosal sinus sampling; ROC = receiver operating characteristic; UFC = urinary free cortisol; corticotroph adenoma; corticotroph hyperplasia; diagnosis; pathology; pituitary surgery; surgical outcomes. From https://pubmed.ncbi.nlm.nih.gov/32886921/
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