High Cortisol Levels, as Seen in Cushing’s, Can Lead to Greater Risk of Heart Disease, Study Finds

People with high cortisol levels have lower muscle mass and higher visceral fat deposits, putting them at a greater risk for cardiovascular disease, new research shows.

High levels of cortisol can result from a variety of reasons, including Cushing’s disease and adrenal tumors. Most adrenal tumors are found to be non-functioning, meaning they do not produce excess hormones. However, up to 47 percent of patients have mild autonomous cortisol excess (MACE).

The study, “Impact of hypercortisolism on skeletal muscle mass and adipose tissue mass in patients with adrenal adenomas,” was published in the journal Clinical Endocrinology.

Long-term studies have shown that as a group, patients with MACE tend to have increased cardiovascular risk factors, such as hypertension, type 2 diabetes mellitus (DM2), obesity, and high lipid levels, which are associated with higher cardiovascular death rates.

Abdominal adiposity, which refers to fat deposits around the abdomen and stomach, and central sarcopenia, referring to loss of skeletal muscle mass, are both known to be linked to higher cardiovascular risk and increased mortality.

Overt hypercortisolism is known to lead to increased visceral adiposity (body fat stored within the abdominal cavity) and muscle loss. However, little is known about the body composition of patients with adrenal adenomas and MACE.

Therefore, researchers set out to determine whether central sarcopenia and adiposity are present in patients with MACE, and whether they can be markers of disease severity in patients with adrenal adenomas. To determine this, researchers used body composition measurements of 25 patients with Cushing’s disease, 48 patients with MACE, and 32 patients with non-functioning adrenal tumors (NFAT) using abdominal CTs.

Specifically, researchers looked at visceral fat, subcutaneous fat, and total abdominal muscle mass. Visceral fat refers to fat around organs, and it is “deeper” than subcutaneous fat, which is closer to the skin.

Results showed that, compared to patients with non-functional tumors, those with Cushing’s disease had a higher visceral to total (V/T) fat ratio but a lower visceral to subcutaneous (V/S) fat ratio. In MACE patients, however, both ratios were decreased compared to patients with non-functional tumors.

Cushing’s disease patients also had 10 cm2  less total muscle mass, compared to patients with non-functional tumors.

An overnight dexamethasone suppression test was conducted in these patients to determine levels of cortisol in the blood. The next morning, cortisol levels were checked. High levels of cortisol indicate the presence of a disease, such as MACE or Cushing’s disease.

After administering the test, researchers determined that for an increase in cortisol in the morning, there was a correlating increase in the V/T ratio and the V/S fat ratio, and a decrease in the mean total muscle mass.

Therefore, the higher the degree of hypercortisolism, the lower the muscle mass and the higher the visceral adiposity.

These results could prove to be clinically useful as both visceral adiposity and low muscle mass are risk factors of a number of diseases, including cardiovascular disease.

“Body composition measurement may provide an additive value in making a diagnosis of clinically important MACE and aid in individualizing management of patients with ACAs and MACE,” the researchers concluded.

From https://cushingsdiseasenews.com/2017/11/30/cushings-disease-high-cortisol-levels-leads-to-greater-risk-heart-disease/

Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and Subclinical Cushing Syndrome

Eur J Endocrinol. 2016 Jul 22. pii: EJE-16-0465. [Epub ahead of print]

Abstract

OBJECTIVE:

Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with Subclinical Cushing Syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: 1) determine the effect of adrenalectomy compared to conservative management on cardiovascular risk factors in patients with SCS and 2) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS versus those with a non-functioning (NF) adrenal tumor.

METHODS:

Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched on November 17th, 2015. Reviewers extracted data and assessed methodological quality in duplicate.

RESULTS:

We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared to conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI 4.3 – 27.8) and diabetes mellitus (RR 3.9, 95%CI 1.5- 9.9), but not dyslipidemia (RR 2.6, 95%CI 0.97 -7.2) or obesity (RR 3.4 (95%CI 0.95-12)). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients), however, insufficient data exist for comparison to patients with SCS.

CONCLUSIONS:

Available low to moderate quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and as compared to conservative management.

[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/27450696

If One Partner Has Cushing’s Syndrome, Can The Couple Still Get Pregnant?

Cushing’s syndrome can affect fertility in both men and women.

Women

The high levels of cortisol in Cushing’s syndrome disrupt a woman’s ovaries. Her menstrual periods may stop completely or become irregular. As a result, women with Cushing’s syndrome almost always have difficulty becoming pregnant.5,6,7 For those who do become pregnant, the risk of miscarriage is high.5,6,7

In rare cases, usually when a woman’s Cushing’s syndrome is caused by a benign adrenal tumor, pregnancy can occur, but it brings high risk for the mother and fetus.5,6,7

After a woman is treated for Cushing’s syndrome, her ovaries often recover from the effects of too much cortisol. Her regular menstrual cycles will return, and she can become pregnant.8

In some women, regular periods do not return after they are treated for Cushing’s syndrome. This occurs if surgery removes the part of the pituitary gland involved in reproduction.4 An infertility specialist can prescribe hormone therapy to bring back regular periods, ovulation, and fertility.8

Men

A man diagnosed with Cushing’s syndrome may have a decline in sperm production and could have reduced fertility.9 He also might experience a lowered sex drive as well as impotence (pronounced IM-puh-tuhns). In addition, some medications used to treat Cushing’s syndrome can reduce fertility.10 However, fertility usually recovers after Cushing’s syndrome is cured and treatment has stopped.9

Does Cushing’s syndrome affect pregnancy?

Cushing’s syndrome can cause serious and potentially life-threatening effects for the mother and the fetus during pregnancy.11,12 For example, Cushing’s syndrome raises a woman’s risk of developing pregnancy-related high blood pressure (called preeclampsia, pronounced pree-i-KLAMP-see-uh, or eclampsia) and/or pregnancy diabetes, which also is called gestational (pronounced je-STEY-shuhn-ul) diabetes). Infection and slow healing of any wounds are more likely, as is heart failure. When the syndrome is caused by a tumor, it will be surgically removed as early as possible to reduce any threat.13


  1. Margulies, P. (n.d.). Adrenal diseases—Cushing’s syndrome: The facts you need to know. Retrieved May 21, 2012, from National Adrenal Diseases Foundation website http://www.nadf.us/adrenal-diseases/cushings-syndrome/ External Web Site Policy
  2. Nieman, L. K., & Ilias, I. (2005). Evaluation and treatment of Cushing’s syndrome. Journal of American Medicine, 118(12), 1340-1346. PMID 16378774.
  3. American Cancer Society. (n.d.). Fact sheet on pituitary tumors. Retrieved May 19, 2012, fromhttp://documents.cancer.org/acs/groups/cid/documents/webcontent/003133-pdf.pdf (PDF – 171 KB). External Web Site Policy
  4. Biddie, S. C., Conway-Campbell, B. L, & Lightman, S. L. (2012). Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology, 51(3), 4034-4112. Retrieved May 19, 2012, from PMID: 3281495.
  5. Abraham, M. R., & Smith, C. V. (n.d.). Adrenal disease and pregnancy.Retrieved April 8, 2012, fromhttp://emedicine.medscape.com/article/127772-overview – aw2aab6b6. External Web Site Policy
  6. Pickard, J., Jochen, A. L., Sadur, C. N., & Hofeldt, F. D. (1990). Cushing’s syndrome in pregnancy. Obstetrical & Gynecological Survey, 45(2), 87-93.PMID 2405312.
  7. Lindsay, J. R., Jonklaas, J., Oldfield, E. H., & Nieman, L. K. (2005). Cushing’s syndrome during pregnancy: Personal experience and review of the literature. Journal of Clinical Endocrinology and Metabolism, 90(5), 3077.PMID 15705919.
  8. Klibansky, A. (n.d.). Pregnancy after cure of Cushing’s disease. Retrieved April 27, 2012, fromhttp://03342db.netsolhost.com/page/pregnancy_after_cure_of_cushings_disease.php. External Web Site Policy
  9. Jequier, A.M. Endocrine infertility. In Male infertility: A clinical guide (2nd ed.). Cambridge University Press, 2011: chap 20, pages 187-188. Retrieved May 19, 2012, from http://books.google.com/books?id=DQL0YC79uCMC&pg=PA188&lpg=PA188&dq=male+infertility+causes+and+treatment+Cushing&source=bl&ots=k1Ah5tVJC7&sig=WJR4N0wUawlh0Rant31QMPq6ufs&hl=en&sa=X&ei=hGe5T-LrHYSX6AHgrvmzCw&ved=0CGoQ6AEwAQ#v=onepage&q=male%20infertility%20causes%20and%20treatment%20Cushing&f=false. External Web Site Policy
  10. Stewart, P. M., & Krone, N. P. (2011). The adrenal cortex. In Kronenberg, H. M., Shlomo, M., Polonsky, K. S., Larsen P. R. (Eds.). Williams textbook of endocrinology (12th ed.). (chap. 15). Philadelphia, PA: Saunders Elsevier.
  11. Abraham, M. R., & Smith, C. V. Adrenal disease and pregnancy. Retrieved April 8, 2012, from http://emedicine.medscape.com/article/127772-overview – aw2aab6b6. External Web Site Policy
  12. Buescher, M. A. (1996). Cushing’s syndrome in pregnancy. Endocrinologist, 6, 357-361.
  13. Ezzat, S., Asa, S. L., Couldwell, W. T., Barr, C. E., Dodge, W. E., Vance M. L., et al. (2004). The prevalence of pituitary adenomas: A systematic review.Cancer, 101(3), 613-619. PMID 15274075.

From https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/faqs.aspx

Day 2 Coverage of ENDO 2015

ENDO_2015

 

OR22-Osteoporosis–Winner: Outstanding Abstract Award

Effects of teriparatide on bone microarchitecture in postmenopausal women with osteoporosis
S Orlov, R Ridout, L Tile, M Kapral, S Cardew, MR Werb, SD Sandler, J Chang, H Hu, E Szabo, C Derzko, A Cheung


FRI 224-247-Metabolic and Genetic Bone Disorders

The effect of vitamin D supplementation on falls and physical performance in elderly women. A randomized clinical trial
S Yousefian, JC Gallagher, SH Tella


The etiology and risk factors analysis in hypercalcemic crisis
H Liao, DL Lorber, E Cohen


LBF 001-014-Late-breaking Thyroid/HPT Axis II

Diagnostic lobectomy for thyroid nodules >4 cm with benign cytology after fine-needle aspiration is associated with improved outcomes at an acceptable cost compared to observation: …
L Lee, E Theodosopoulos, EJ Mitmaker, JA Lee, J Chabot, JH Kuo


LBF 015-023-Late-breaking Reproductive Endocrinology II

Effect of testosterone treatment on cardiac biomarkers in a randomized controlled trial of men with type 2 diabetes
EJ Gianatti, R Hoermann, Q Lam, P Dupuis, JD Zajac, M Grossmann


OR17-Novel Aspects of Adrenal Tumors and the HPA Axis

Epigenetic modulation of DNA Is associated with fatigue, depression and anxiety in patients with Cushing’s syndrome in remission: A genome-wide methylation study
CAM Glad, JC Andersson-Assarsson, P Berglund, R Bergthorsdottir, O Ragnarsson, G Johannsson


Pharmacogenetic analysis of glucocorticoid gene polymorphisms and prediction of daily dexamethasone doses in adults with congenital adrenal hyperplasia
JS Frassei, LG Gomes, RP Moreira, G Madureira, BB Mendonca, TA Bachega


OR20-Pituitary Tumors-New Clinical Considerations

Reduced mortality in patients with GH replacement therapy – a Swedish study based on more than 4,000 patient-years
DS Olsson, AG Nilsson, P Trimpou, B-A Bengtsson, E Andersson, G Johannsson


OR22-Osteoporosis

Denosumab restores cortical bone loss at the 1/3 radius associated with aging and reduces wrist fracture risk: Analyses from the Freedom extension cross-over group
JP Bilezikian, CL Benhamou, CJF Lin, JP Brown, NS Daizadeh, PR Ebeling, A Fahrleitner-Pammer, E Franek, N Gilchrist, PD Miller, JA Simon1, I Valter, AF Zerbini, C Libanati


OR22-Osteoporosis–Winner Clinical Fellows Abstract Award Travel Grants in Womens Health

Estrone may be more important than testosterone and estradiol for bone health and prevention of fractures in post-menopausal women
G Toraldo, TG Travison, X Zhang, KE Broe, S Bhasin, DP Kiel, AD Coviello

Cushing Syndrome in Children: Growth after Surgical Cure

Cushing syndrome (CS) occurs only rarely in children, but when it does, it causes weight gain and stunting. In young children, adrenal tumors are usually the cause while in adolescents, pituitary tumors are more likely.

The September 2014 issue of Endocrine-Related Cancer examines growth patterns in 19 pediatric patients with ACTH-dependent CS (CD) and 18 patients with a form of ACTH-independent CS, micronodular adrenal hyperplasia (MAH). The researchers gathered data at the time of surgery and also followed up one year later.

Patients in the CD and the MAH groups had similar demographic characteristics, baseline heights and BMI scores before surgery. All patients experienced significant improvements in height and BMI after surgery. Patients with MAH, however, fared significantly better than those with CD and had better post-operative growth.

The researchers propose several reasons:

  • When ACTH-secreting pituitary adenoma requires extensive surgical exploration, remaining pituitary cells often lose some of their function.
  • CD patients tend to be older and have consistent and increased glucocorticoid exposure; they develop vertebral fractures more often leading to compromised skeletal and overall growth potential. MAH patients often have cyclical CS, with intermittent hypercortisolism and an overall milder CS.
  • CD patients often need a longer-than-expected course of therapy with steroids after surgery, which alters metabolism and growth.
  • CD patients have been shown to have advance bone age because of ACTH-induced metabolic changes.

The authors indicate that CS patients are often considered for growth hormone therapy once the underlying problem is corrected. They remind clinicians that MAH patients are less likely to need growth hormone. They recommend close monitoring for CD patients, and early intervention with growth hormone if growth does not meet expectation. –

See more at: http://www.hcplive.com/articles/Cushing-Syndrome-in-Children-Growth-after-Surgical-Cure

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