Cushing’s Syndrome is Hazardous to Your Health

Posted on July 3, 2013 by MaryO

morbidity

People with Cushing’s syndrome, even when treated, have higher morbidity and mortality rates that comparable controls. That is the conclusion of a new study published in the June issue of the Journal of Clinical Endocrinology Metabolism. The study by Olaf Dekkers et al, examined data records from the Danish National Registry of Patients and the Danish Civil Registration System of 343 patients with benign Cushing’s syndrome of adrenal or pituitary origin (i.e., Cushing’s disease) and a matched population comparison cohort (n=34,300).  Due to the lengthy delay of many patients being diagnosed with Cushing’s syndrome, morbidity was investigated in the 3 years before diagnosis while  morbidity and mortality were assessed during complete follow-up after diagnosis and treatment.

The study found that mortality was twice as high in Cushing’s syndrome patients (HR 2.3, 95% CI 1.8-2.9) compared with controls over a mean follow-up period of 12.1 years. Furthermore, patients with Cushing’s syndrome were at increased risk for:

  • venous thromboembolism (HR 2.6, 95% CI 1.5-4.7)
  • myocardial infarction (HR 3.7, 95% CI 2.4-5.5)
  • stroke (HR 2.0, 95% CI 1.3-3.2)
  • peptic ulcers (HR 2.0, 95% CI 1.1-3.6)
  • fractures (HR 1.4, 95% CI 1.0-1.9)
  • infections (HR 4.9, 95% CI 3.7-6.4).

The study also found that this increased multimorbidity risk was present before diagnosis indicating that it was due to cortisol overproduction rather than treatment.

Many of the Cushing’s syndrome patients underwent surgery to remove the benign tumor. For this group, the investigators performed a sensitivity analysis of the  long-term mortality and cardiovascular risk in this  subgroup (n=186)  considered to be cured after operation (adrenal surgery and patients with pituitary surgery in combination with a diagnosis of hypopituitarism in the first 6 months after operation).  The risk estimates for mortality (HR 2.31, 95% CI 1.62-3.28), venous thromboembolism (HR 2.03, 95% CI 0.75-5.48), stroke (HR 1.91, 95% CI 0.90-4.05), and acute myocardial infarction (HR 4.38, 95% CI 2.31-8.28) were also increased in this subgroup one year after the operation.

The standard treatment for endogenous Cushing’s syndrome is surgery. This past year, Signifor (pasireotide) was approved for treatment of adults patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.  Cushing’s disease, which accounts for the majority of Cushing’s syndrome patients, is defined as the presence of an ACTH producing tumor on the pituitary grand. In the study by Dekker’s et al, the percentage of patients with Cushing’s disease is not known. We look forward to reexamination of this dataset in a few years following the introduction of more treatment options for Cushing’s disease as well as an analysis that explores the differences in mortality/morbidity rates in the different subsets of patients that make of Cushing’s syndrome (Cushing’s disease, ectopic Cushing’s syndrome, Exogenous Cyshing’s syndrome).

References

Dekkers OM, Horvath-Pujo, Jorgensen JOL, et al, Multisystem morbidity and mortality in Cushing’s syndrome: a cohort study. J Clin Endocrinol Metab 2013 98(6): 2277–2284. doi: 10.1210/jc.2012-3582

– See more at: http://www.raredr.com/medicine/articles/cushing%E2%80%99s-syndrome-hazardous-your-health-0

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Have You Gone to the ER With an Adrenal Crisis?

Posted on June 23, 2013 by MaryO

This Survey is to gather information for the Adrenal Insufficiency Awareness Organization’s grant project to create educational materials for ER personnel.

The survey is for those of you who have been to the ER during an impending or full blown Adrenal Crisis. (you may fill it out for a child or yourself)

Your help is appreciated!

At the end of the survey you will have the chance to enter for a chance to win an Adrenal Insufficiency Awareness Pin.

https://www.surveymonkey.com/s/ERcare

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From the CushieWiki: Personal Stories

Posted on May 23, 2013 by MaryO

Cushie Warriors

Personal Stories – Autumn

Personal Stories – Deb

Personal Stories – HockeyGirl

Personal Stories – Jessica

Personal Stories – Kate

Personal Stories – MaryO

Personal Stories – Staticnrg

All Personal experiences

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Classifying hypertension

Posted on May 19, 2013 by MaryO

HYPERTENSION is classified into two categories according to its cause: essential and secondary.

The vast majority of patients have essential or primary hypertension, while only about 5-10% of patients have secondary hypertension, which are mainly caused by kidney and hormonal conditions like renal artery stenosis, hyperthyroidism, Cushing’s syndrome, and even pregnancy, among others.

The exact cause of essential hypertension is still unknown, although it is certainly the result of a combination of factors, including increasing age, having relatives with high blood pressure (ie family history), a sedentary lifestyle, a poor diet with too much salt, drinking too much alcohol, smoking and too much stress.

Says Malaysian Society of Hypertension president and Universiti Malaya Department of Primary Care Medicine senior consultant Prof Datin Dr Chia Yook Chin: “Each factor increases blood pressure by just a little, but when you add them all together little by little, it raises it by quite a lot.”

Despite not knowing the root cause of hypertension, it has been established that there is overstimulation of the sympathetic nerves in people with this condition.

This in turn increases the secretion of certain hormones involved in the regulation of sodium and fluids in the body, called renin, angiotensin, and aldosterone.

The amount of salt and water in our body affects our blood pressure – the more salt and water present, the higher our blood pressure.

These two elements are regulated by our kidneys through the three hormones mentioned above, which are produced by the adrenal glands located on top of the kidneys.

The overstimulation of the sympathetic nerves also results in increased vascular tone, which causes our arteries to become constricted, thus, also raising blood pressure.

From The Star

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Cushing’s Syndrome, Prostate Cancer and Adrenocortical Carcinoma

Posted on March 11, 2013 by MaryO

Orphagen has identified and characterized small molecule antagonists to steroidogenic factor-1 (SF-1). SF-1 binds to and regulates DNA promoter elements in the major transporters and enzymes required for adrenal steroid synthesis. It is also required for development of the adrenal gland. SF-1 antagonists inhibit cortisol secretion in adrenal cells and have potential application in two orphan indications, Cushing’s syndrome and adrenocortical carcinoma. In addition, SF-1 appears to have an important role in the progression of advanced prostate cancer.

 

cushings-adrenocortical-crop

 

Cushing’s syndrome:
An estimated 20,000 people in the US have Cushing’s, with more than 3,000 new cases diagnosed each year. The incidence is similar in Europe. Cushing’s syndrome disproportionately affects females, who make up about 75% of the diagnosed cases. Symptoms of Cushing’s syndrome can include obesity, diabetes, psychiatric disorders, osteoporosis and immune suppression. Cushing’s syndrome is caused by elevated secretion of cortisol from the adrenal gland, in association with pituitary, adrenal or other cancers.

Orphagen has identified small molecule antagonists to SF-1 that have the potential to suppress cortisol levels in all Cushing’s patients without serious side effects.

Adrenocortical carcinoma (ACC):
ACC is a rare malignancy with an extremely poor prognosis (5-year overall survival: 37-47%). Complete surgical resection offers hope for long-term survival but surgery is not an option in up to two-thirds of patients because metastasis has usually occurred by the time of diagnosis.

SF-1 is recognized as a potential mechanism-based therapeutic target for control of ACC and an SF-1 antagonist could be used in the treatment of ACC.

Pediatric ACC:
Pediatric ACC is a very rare but aggressive cancer with a long-term survival rate of about 50%. Approximately 60% of children with adrenocortical tumors are diagnosed before the age of four. The SF-1 gene is amplified and SF-1 protein is overexpressed in the vast majority of childhood adrenocortical tumors strongly implicating SF-1 in pediatric adrenocortical tumorigenesis.

Castration resistant prostate cancer (CRPC):
CRPC is the most common cancer in males. Surgery is not an option if the cancer has spread beyond the prostate gland, at which point patients typically receive hormonal therapy, essentially chemical castration. This course of therapy usually fails within two years, resulting in castration resistant prostate cancer (CRPC). Most patients eventually succumb to CRPC, which is the second leading cause of cancer deaths in men.
SF-1 antagonists may: (1) block the adrenal androgens that circumvent chemical castration, and are a primary cause of CRPC; and (2) inhibit synthesis of androgens within the prostate tumor itself, where SF-1 may control induction of enzymes for de novo androgen synthesis in treatment-resistant cancers.

From http://www.orphagen.com/research_cushings.html

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