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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 -
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
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Children with Cushing’s syndrome are at risk of developing new autoimmune and related disorders after being cured of the disease, a new study shows. The study, “Incidence of Autoimmune and Related Disorders After Resolution of Endogenous Cushing Syndrome in Children,” was published in Hormone and Metabolic Research. Patients with Cushing’s syndrome have excess levels of the hormone cortisol, a corticosteroid that inhibits the effects of the immune system. As a result, these patients are protected from autoimmune and related diseases. But it is not known if the risk rises after their disease is resolved. To address this, researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) examined 127 children with Cushing’s syndrome at the National Institutes of Health from 1997 until 2017. Among the participants, 77.5 percent had a pituitary tumor causing the disease, 21.7 percent had ACTH-independent disease, and one patient had ectopic Cushing’s syndrome. All patients underwent surgery to treat their symptoms. After a mean follow-up of 31.2 months, 7.8 percent of patients developed a new autoimmune or related disorder. Researchers found no significant differences in age at diagnosis, gender, cortisol levels, and urinary-free cortisol at diagnosis, when comparing those who developed autoimmune disorders with those who didn’t. However, those who developed an immune disorder had a significantly shorter symptom duration of Cushing’s syndrome. This suggests that increased cortisol levels, even for a short period of time, may contribute to more reactivity of the immune system after treatment. The new disorder was diagnosed, on average, 9.8 months after Cushing’s treatment. The disorders reported were celiac disease, psoriasis, Hashimoto thyroiditis, Graves disease, optic nerve inflammation, skin hypopigmentation/vitiligo, allergic rhinitis/asthma, and nerve cell damage of unknown origin responsive to glucocorticoids. “Although the size of our cohort did not allow for comparison of the frequency with the general population, it seems that there was a higher frequency of optic neuritis than expected,” the researchers stated. It is still unclear why autoimmune disorders tend to develop after Cushing’s resolution, but the researchers hypothesized it could be a consequence of the impact of glucocorticoids on the immune system. Overall, the study shows that children with Cushing’s syndrome are at risk for autoimmune and related disorders after their condition is managed. “The presentation of new autoimmune diseases or recurrence of previously known autoimmune conditions should be considered when concerning symptoms arise,” the researchers stated. Additional studies are warranted to further explore this link and improve care of this specific population. From https://cushingsdiseasenews.com/2018/03/06/after-cushings-cured-autoimmune-disease-risk-looms-study/
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untilFirst In Human represents the first time cameras have embedded in Building 10 and followed first in human patients throughout their entire trial. This unique access is the product of Hoffman’s nearly twenty years of filmmaking in partnership with the NIH on projects such as The Alzheimer’s Project and The Weight of the Nation. This episode airs at 9:00 PM eastern More information at https://cushieblogger.com/2017/08/10/nih-discovery-channels-documentary-series-first-in-human/
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Researchers have determined mutations in the gene CABLES1 may lead to Cushing syndrome, a rare disorder in which the body overproduces the stress hormone cortisol. The National Institutes of Health study findings published in Endocrine-Related Cancer found four of the 181 children and adult patient examined had mutant forms of CABLES1 that do not respond to cortisol. The determination proved significant because normal functioning CABLES1 protein, expressed by the CABLES1 gene, slows the division and growth of pituitary cells that produce the hormone adrenocorticotropin (ACTH). Researchers at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) joined scientists from other institutions in the United States, France and Canada, in the evaluation. “The mutations we identified impair the tumor suppressor function in the pituitary gland,” Constantine A. Stratakis, the study’s senior author and director of the NICHD Division of Intramural Research, said. “This discovery could lead to the development of treatment strategies that simulate the function of the CABLES1 protein and prevent recurrence of pituitary tumors in people with Cushing syndrome.” Cushing syndrome symptoms include obesity, muscle weakness, fatigue, high blood pressure, high blood sugar, depression and anxiety, officials said, adding excess cortisol found in the disorder can result from certain steroid medications or from tumors of the pituitary or adrenal glands. Researchers maintain that more studies are needed to fully understand how CABLES1 suppresses tumor formation in the pituitary gland. From https://lifesciencedaily.com/stories/21624-study-links-genetic-mutations-cushing-syndrome/
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Finding may lead to therapies that prevent pituitary tumor recurrence. Read more: https://www.nih.gov/news-events/nih-researchers-find-potential-genetic-cause-cushing-syndrome
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Rank Status Study 1 Recruiting Study to Evaluate CORT125134 in Patients With Cushing's Syndrome Condition: Cushing's Syndrome Intervention: Drug: CORT125134 2 Recruiting Cushing's Disease Complications Condition: Cushing's Disease Intervention: Other: Exams and questionnaires 3 Recruiting The Accuracy of Late Night Urinary Free Cortisol/Creatinine and Hair Cortisol in Cushing's Syndrome Diagnosis Condition: Cushing Syndrome Intervention: 4 Recruiting Treatment for Endogenous Cushing's Syndrome Condition: Endogenous Cushing's Syndrome Intervention: Drug: COR-003 5 Recruiting Saliva Cortisol Measurement as a Screening Test for Suspicious Cushings Syndrome in Children. Condition: Cushings Syndrome Intervention: Other: Children refered to the obesity clinic 6 Recruiting Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease Condition: Cushing's Disease Intervention: Drug: LCI699 7 Recruiting Treatment of Cushing's Disease With R-roscovitine Condition: Cushings Disease Intervention: Drug: R-roscovitine 8 Recruiting A Study of ATR-101 for the Treatment of Endogenous Cushing's Syndrome Condition: Cushing Syndrome Interventions: Drug: ATR-101; Drug: Placebos 9 Recruiting Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Patients With Ectopic Cushing Syndrome Condition: Cushing Syndrome Interventions: Drug: F-DOPA PET Scan; Drug: Mifepristone; Drug: Ga-DOTATATE; Drug: Octreoscan; Other: CT, MRI 10 Not yet recruiting Endocrine Cardiomyopathy in Cushing Syndrome: Response to Cyclic GMP PDE5 inhibitOrs Condition: Cushing's Syndrome Cardiomyopathy Intervention: Drug: Tadalafil 11 Recruiting Long-term Beneficial Metabolic Effects of Adrenalectomy in Subclinical Cushing's Syndrome of Adrenal Incidentaloma Condition: Cushing Syndrome Intervention: Procedure: surgery 12 Recruiting Long Term Safety and Efficacy of Pasireotide s.c. in Patients With Cushing's Disease Condition: Cushings Disease Intervention: Drug: SOM230 13 Recruiting New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome Condition: Cushing Syndrome Interventions: Drug: Pentetreotide; Drug: 18-F-fluorodeoxyglucose; Drug: (18F)-L-3,4-dihydroxyophenylalanine (18F-DOPA) 14 Not yet recruiting Targeting Iatrogenic Cushing's Syndrome With 11β-hydroxysteroid Dehydrogenase Type 1 Inhibition Condition: Iatrogenic Cushing's Disease Interventions: Drug: AZD4017 and prednisolone; Drug: Placebo Oral Tablet and prednisolone 15 Not yet recruiting Assessment of Persistent Cognitive Impairment After Cure of Cushing's Disease Condition: Cushing's Disease Intervention: Device: Virtual radial task in 3D 16 Recruiting Biomarker Expression in Patients With ACTH-Dependent Cushing's Syndrome Before and After Surgery Condition: Cushing's Syndrome Intervention: 17 Recruiting Efficacy and Safety Evaluation of Osilodrostat in Cushing's Disease Condition: Cushing's Disease Interventions: Drug: osilodrostat; Drug: osilodrostat Placebo 18 Recruiting Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome Condition: Cushing's Syndrome Intervention: Drug: metyrapone 19 Recruiting Adrenal Venous Sampling in Patients With Overt or Subclinical Cushings Syndrome, and Bilateral Adrenal Tumors Condition: Cushing Syndrome Intervention: Radiation: Adrenal venous sampling 20 Recruiting Glycemic Fluctuations in Newly Diagnosed Growth Hormone-Secreting Pituitary Adenoma and Cushing Syndrome Subjects Condition: Pituitary Adenoma Intervention: Device: continuous glucose monitoring Rank Status Study 21 Recruiting Targeted Therapy With Gefitinib in Patients With USP8-mutated Cushing's Disease Conditions: Cushing's Disease; Corticotrophin Adenoma Intervention: Drug: Gefitinib 22 Recruiting Cardiac Steatosis in Cushing's Syndrome Conditions: Endocrine System Disease; Cardiovascular Imaging Intervention: Other: 1H magnetic resonance spectroscopy and CMRI 23 Recruiting Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly Conditions: Cushing's Disease; Acromegaly Interventions: Drug: Pasireotide s.c.; Drug: Sitagliptin; Drug: Liraglutide; Drug: Insulin; Drug: Pasireotide LAR; Drug: Metformin 24 Recruiting Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome Conditions: Cushing's Syndrome; Ectopic Corticotropin Syndrome; Adrenal Adenoma; Adrenal Carcinoma; AIMAH; PPNAD Intervention: Drug: Osilodrostat 25 Recruiting Effects of Hormone Stimulation on Brain Scans for Cushing s Disease Condition: Pituitary Neoplasm Intervention: Drug: Acthrel 26 Recruiting Does Serum-DXM Increase Diagnostic Accuracy of the Overnight DXM Suppression Test in the Work-up of Cushing's Syndrome? Conditions: Cushing's Syndrome; Adrenal Incidentalomas; Alcoholism; Obesity Intervention: 27 Recruiting Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome Condition: Adrenal Tumour With Mild Hypercortisolism Intervention: Procedure: Adrenalectomy 28 Recruiting Study of Adrenalectomy Versus Observation for Subclinical Hypercortisolism Conditions: Hypercortisolism; Cushing Syndrome Interventions: Procedure: Adrenalectomy; Other: Observation 29 Not yet recruiting Dynamic Hormone Diagnostics in Endocrine Disease Conditions: Adrenal Insufficiency; Congenital Adrenal Hyperplasia; Cushing Syndrome; Growth Hormone Deficiency; Acromegaly; Primary Hyperaldosteronism Intervention: Other: 27 hour subcutaneous fluid sampling 30 Recruiting An Investigation of Pituitary Tumors and Related Hypothalmic Disorders Conditions: Abnormalities; Craniopharyngioma; Cushing's Syndrome; Endocrine Disease; Pituitary Neoplasm Intervention: 31 Recruiting Ga-68-DOTATOC -PET in the Management of Pituitary Tumours Condition: Pituitary Tumours Intervention: Procedure: Gallium-68 DOTATOC PET 32 Recruiting Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus Conditions: Type 2 Diabetes Mellitus; Insulin Resistance Interventions: Drug: Mifepristone 600 mg daily; Drug: Placebo 33 Recruiting Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy Conditions: Pituitary Adenomas; Prolactinomas Intervention: Drug: Lapatinib 34 Recruiting Mutations of Glucocorticoid Receptor in Bilateral Adrenal Hyperplasia Condition: General Glucocorticoid Resistance Intervention: Genetic: blood collection for mutation characterization 35 Recruiting Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex Conditions: Cushing's Syndrome; Hereditary Neoplastic Syndrome; Lentigo; Neoplasm; Testicular Neoplasm Intervention: 36 Not yet recruiting Reduction by Pasireotide of the Effluent Volume in High-output Enterostomy in Patients Refractory to Usual Medical Treatment Condition: Enterostomy Interventions: Drug: Pasireotide; Drug: Placebo 37 Recruiting Mifepristone for Breast Cancer Patients With Higher Levels of Progesterone Receptor Isoform A Than Isoform B. Condition: Breast Cancer Intervention: Drug: Mifepristone 38 Recruiting SOM230 Ectopic ACTH-producing Tumors Condition: Ectopic ACTH Syndrome Intervention: Drug: Pasireotide 39 Recruiting Decreasing Rates of Intraurethral Catheterization Postoperatively in Spine Surgery Condition: Post-operative Urinary Retention Interventions: Drug: Tamsulosin; Drug: Placebo 40 Recruiting Adrenal Tumors - Pathogenesis and Therapy Conditions: Adrenal Tumors; Adrenocortical Carcinoma; Cushing Syndrome; Conn Syndrome; Pheochromocytoma Intervention:
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Diagnosing Cushing’s syndrome can take 24 hours of complicated and repeated analysis of blood and urine, brain imaging, and tissue samples from sinuses. But that may soon be in the past: National Institutes of Health (NIH) researchers have found that measuring cortisol levels in hair samples can do the same job faster. Patients with Cushing’s syndrome have a high level of cortisol, perhaps from a tumor of the pituitary or adrenal glands, or as a side effect from medications. In the study, 36 participants—30 with Cushing’s syndrome, six without—provided hair samples divided into three equal segments. The researchers found that the segments closest to the scalp had the most cortisol (96.6 ± 267.7 pg/mg for Cushing’s syndrome patients versus 14.1 ± 9.2 pg/mg in control patients). Those segments’ cortisol content correlated most closely with the majority of the initial biochemical tests, including in blood taken at night (when cortisol levels normally drop). The study was small; Cushing’s syndrome is rare, and it’s hard to recruit large numbers of patients. Still, the researchers believe it is the largest of its kind to compare hair cortisol levels to diagnostic tests in Cushing’s patients. “Our results are encouraging,” said Mihail Zilbermint, MD, the study’s senior author and an endocrinologist at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “We are hopeful that hair analysis may ultimately prove useful as a less-invasive screening test for Cushing’s syndrome or in helping to confirm the diagnosis.” The authors suggest the test is also a convenient alternative with the “unique ability” for retrospective evaluation of hypercortisolemia over months. Download PDF From https://www.ptcommunity.com/journal/article/full/2017/4/271/research-briefs-april-2017
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Early and midterm nonremission after transsphenoidal surgery in people with Cushing’s disease may be predicted by normalized early postoperative values for adrenocorticotropic hormone and cortisol, study data show. Prashant Chittiboina, MD, MPH, assistant clinical investigator in the neurosurgery unit for pituitary and inheritable diseases at the National Institute of Neurological Diseases and Stroke at the NIH, and colleagues evaluated 250 patients with Cushing’s disease who received 291 transsphenoidal surgery procedures during the study period to determine remission after the procedure. Patients were treated between December 2003 and July 2016. Early remission was assessed at 10 days and medium-term remission was assessed at 11 months. Early nonremission was predicted by normalized early postoperative values for cortisol (P = .016) and by normalized early postoperative values for adrenocorticotropic hormone (ACTH; P = .048). Early nonremission was further predicted with 100% sensitivity, 39% specificity, 100% negative predictive value and 18% positive predictive value for a cutoff of –12 µg/mL in normalized early postoperative values for cortisol and with 88% sensitivity, 41% specificity, 96% negative predictive value and 16% positive predictive value for a cutoff of –40 pg/mL in normalized early postoperative values for ACTH. Medium-term nonremission was also predicted by normalized early postoperative values for cortisol (P = .023) and ACTH (P = .025). “We evaluated the utility of early postoperative cortisol and ACTH levels for predicting nonremission after transsphenoidal adenomectomy for Cushing’s disease,” the researchers wrote. “Postoperative operative day 1 values at 6 a.m. performed best at predicting early nonremission, albeit with a lower [area under the receiver operating characteristic curve]. Normalizing early cortisol and ACTH values to post-[corticotropin-releasing hormone] values improved their prognostic value. Further prospective studies will explore the utility of normalized very early postoperative day 0 cortisol and ACTH levels in identifying patients at risk for nonremission following [transsphenoidal surgery] in patients with [Cushing’s disease].” – by Amber Cox Disclosure: The researchers report no relevant financial disclosures. From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B7de200ed-c667-4b48-ab19-256d90a7bbc5%7D/postoperative-acth-cortisol-levels-may-predict-cushings-disease-remission-rate
