Monday, June 28, 2010

Adrenal incidentaloma: Does an adequate workup rule out surprises?

Raymon H. Grogan, MD, Elliot Mitmaker, MD, Menno R. Vriens, MD, PhD, Avital Harari, MD, Jessica E. Gosnell, MD, Wen T. Shen, MD, Orlo H. Clark, MD, Quan-Yang Duh, MDCorresponding Author Informationemail address

Accepted 14 May 2010. published online 24 June 2010.
Corrected Proof

Background

Adrenal incidentaloma remains a diagnostic challenge. Despite well-established management guidelines, the long-term results of following these guidelines are unknown. We sought to determine how accurately these guidelines identify functioning incidentalomas and how often these guidelines result in adrenalectomy for benign tumors.

Methods

We catalogued adrenal incidentalomas from a retrospective review of 500 consecutive adrenalectomies at a single institution. The outcome measures studied were patient demographics, preoperative biochemical analysis, imaging characteristics, tumor size, type of operation performed, and postoperative histologic diagnosis.

Results

Eighty-one of the 500 adrenalectomies performed were for incidentalomas. Size was the only significant characteristic that distinguished cortical cancers from benign adenomas. Only 1 out of 26 functioning tumors was incorrectly identified on preoperative workup. We also found that 25% of cortisol-secreting incidentalomas were cystic, and that benign adenomas accounted for 42% of all tumors resected.

Conclusion

Current guidelines accurately predict the functional status of adrenal incidentalomas. Some cystic lesions may be functioning and should therefore be screened for hormonal hypersecretion. However, even with the most up-to-date diagnostic tools available, most adrenal incidentalomas resected are benign tumors.

 

Department of Endocrine Surgery, University of California San Francisco, San Francisco, CA

Corresponding Author InformationReprint requests: Quan-Yang Duh, MD, UCSF Department of Endocrine Surgery, 1600 Divisadero Street C-347, Box 1674, San Francisco, CA 94143.

PII: S0039-6060(10)00261-8

doi:10.1016/j.surg.2010.05.001

© 2010 Mosby, Inc. All rights reserved.

 

From http://www.surgjournal.com/article/PIIS0039606010002618/abstract?rss=yes

Saturday, June 26, 2010

Adrenal Disorders: Cushing's Disease & Cushing's Syndrome

The production of cortisol by the adrenal glands is stimulated by ACTH (Adrenal Cortical Tropic Hormone), which is produced by the pituitary gland in the brain. Thus, overproduction of cortisol can be caused by either a tumor in the pituitary gland (Cushing's disease), or in the adrenal glands (Cushing's syndrome). Less commonly, a tumor producing too much ACTH may be found outside of the pituitary gland. In patients with Cushing's disease, the blood levels of both ACTH and cortisol are elevated. In patients with Cushing's syndrome, the blood level of cortisol is increased in the setting of a low level of ACTH. Rarely, adrenocortical cancers may cause Cushing's syndrome.

Diagnosis

There is a great deal of variability throughout the day in the amounts of cortisol produced by the adrenal glands. For this reason, the most sensitive test measures the amount of cortisol excreted in the urine over a 24-hour period. A 24 hour free cortisol level greater than 100 µg is diagnostic of Cushing's syndrome. Patients suspected of having Cushing's syndrome will also undergo a dexamethasone suppression test which helps to determine the cause of the increased cortisol production. A CT or MRI scan is used to determine the location of the tumor.

Treatment

Patients with Cushing's disease typically have benign tumors of the pituitary gland in the brain. These patients are referred to a neurosurgeon for removal of the tumors. If removal of the pituitary tumor and medications fail to control Cushing's disease, removing both adrenal glands may be indicated. In patients with Cushing's syndrome, an adrenalectomy—surgical removal of the adrenal gland—is curative. This operation is usually performed laparoscopically, through several very small incisions.

From http://www.columbiasurgery.org/pat/adrenal/cushing.html

Friday, June 25, 2010

Adrenal Alerts ~ June 25, 2010

Day 175 in the life of a (former) Cushing's patient - 365 days ...
My adrenal glands were "generous", for sure, especially after being on keto for so long. Of course, no one was surprised. The left, after fat removal, was 13.5 grams. The right was 11.6 grams. The fat removed around it is removed before ...
365 days with Cushing's Disease - http://cushings365.posterous.com/

 

Crazy Happy Thyroid Dance | Dear Thyroid™
By Dear Thyroid
Another key aspect of interdependence is the dance between PCOS, your adrenals and your thyroid. While the cause isn't well-delineated, I believe most of PCOS begins with the stress cascade of overtaxed adrenals and too much cortisol in ...
Dear Thyroid™ - http://dearthyroid.org/

 

Journal of Clinical Investigation -- Adrenal glucocorticoids have ...
Manipulation of the adrenal circadian clock, in particular phase-shifting of adrenal glucocorticoid rhythms, regulated the speed of behavioral reentrainment ...
www.jci.org/articles/view/41192

 

What Are the Causes of Secondary Adrenal Insufficiency
What Are the Causes of Secondary Adrenal Insufficiency news, info, articles, and resources shared by health experts on OrganizedWisdom Health.
http://organizedwisdom.com/What-Are-the-Causes-of-Secondary-Adrenal-Insufficiency/wt/med

 

Adrenal cortical insufficiency medications - eHealthMe.com
Performance of 1 Adrenal cortical insufficiency drug in real world: hydrocortisone, and more. Long term effects of Adrenal cortical insufficiency drug are ...
www.ehealthme.com/condition/adrenal+cortical+insufficiency

Thursday, June 24, 2010

CAH (congenital adrenal hyperplasia) and Prenatal Dexamethasone

MountainQueen posted this on the Cushing's Help Boards.  She said:

I came across this article about the clinical use of Dex for CAH carriers. After reading this article I remembered that NO ONE asked me if I was pregnant before I took the Dex test. What would have happened if I had been?
Very interesting article for CAH gene carriers: From Time Magazine on line

Medical Ethics: Prenatal Dexamethasone Use Questioned


By CATHERINE ELTON Catherine Elton Mon Jun 21, 11:45 pm ET


When Marisa Langford found out she was pregnant again, she called Dr. Maria New, a total stranger, before calling her own mother. New, a prominent pediatric endocrinologist and researcher at Mount Sinai Medical Center in New York City, is one of the world's foremost experts in congenital adrenal hyperplasia, or CAH, a group of inherited disorders of the adrenal gland.


Langford and her husband learned they were silent carriers of the genetic variation that causes CAH when their son was diagnosed with the condition after birth. Their son - like the 1 in 16,000 babies born with CAH each year in the U.S. - faces a lifetime of taking powerful steroid medications to compensate for his faulty adrenal glands. When Langford contacted New about her second pregnancy, New, who was not Langford's regular doctor, called a local pediatric endocrinologist. That doctor prescribed Langford a commonly used medication for CAH. "Dr. New told me I had to start taking dexamethasone immediately," says Langford, 30, who lives in Tampa. "We felt very confident in someone of her stature and that what she was telling us was the right thing to do."(See the most common hospital mishaps.)


The early prenatal use of dexamethasone, or dex, has been shown to prevent some of the symptoms of CAH in girls, namely ambiguous genitalia. Because the condition causes overproduction of male hormones in the womb, girls who are affected tend to have genitals that look more male than female, though internal sex organs are normal. (In boys, in contrast, the condition leads to early signs of puberty, such as deep voice, body hair and enlarged penis by age 2 or 3.) But while the prenatal treatment may address girls' physical symptoms, it does not prevent the underlying, medical condition, which in some severe cases can be life-threatening, nor does it preclude the need for medication throughout life.


Langford says also that neither New nor her prescribing physician mentioned that prenatal dexamethasone treatment is an off-label use of the drug (an application for which it was not specifically approved by the government) or that the medical community is sharply divided over whether dexamethasone should be used during pregnancy at all.


Is It Safe - or Even Necessary?

To date, there has been just one controlled, prospective, long-term trial of prenatal dexamethasone for the prevention of ambiguous genitalia, conducted in Sweden. The results, published in 2007 in the Journal of Clinical Endocrinology & Metabolism - more than two decades after doctors began using the medication in pregnant patients - found some mild behavioral and cognitive deficits in children whose mothers had been treated. But the study, with just 26 participants, was too small to be definitive. "We just don't know what we are doing to these kids," says Dr. Walter Miller, the chief of endocrinology at University of California, San Francisco. "It's not sufficient to say, The baby was born and had all fingers and toes, so it's fine."(See the top 10 medical breakthroughs of 2009.)


In animal studies, dexamethasone has been shown to cause birth defects, but proponents of the treatment note that no human birth defects have ever been associated with the treatment, and that it is uncertain whether findings in lab animals translate to humans. Meanwhile, the possible benefits are clear: the treatment can spare young girls the potential psychosocial problems associated with having ambiguous genitalia as well as the ordeal of surgery to correct deformities later. "I see potential for benefits and I don't see evidence there's any negatives to this. There are lots of risks associated with surgery, and if this can prevent surgery, then it's a good thing," says Dr. Ingrid Holm, a pediatric endocrinologist at Children's Hospital in Boston.


Research has also suggested that affected women who were treated with dex in the womb show more typical gender behavior than other women with CAH; the latter group tends to behave more tomboyishly and express little interest in having children. New told the Wall Street Journal in 2009 that the treatment further spares parents the "terrifying prospect" of not knowing whether their newborn is a boy or a girl. (Comment on this story.)


It is these very benefits, however, that lead some researchers to question what, exactly, doctors are treating - and whether it needs to be treated at all. Miller believes that prenatal dex is being used to alleviate "parental anxiety," rather than the child's condition. Other doctors and researchers have criticized New for introducing gender behavior into the medical prognosis - in two recent presentations on CAH at medical conferences, New offered medical outcome data on prenatal dex alongside data on typical gender behavior. "Maybe this gives clinicians the idea that the treatment goal is normalizing behavior. To say you want a girl to be less masculine is not a reasonable goal of clinical care," says David E. Sandberg, a University of Michigan pediatric psychologist who treats and conducts research on children with CAH.(Read how postpartum depression can strike fathers.)


Perhaps most controversially, prenatal dex must be given as soon as a woman learns she is pregnant, which is usually several weeks before genetic tests can determine if the fetus is in fact a female affected with CAH - the chance of which is 1 in 8 for parents who already have an affected child or know they are carriers of the genetic disorder. If the baby is healthy, treatment is stopped, but at that point, the fetus has been exposed to the steroid drug for weeks. There is no data on how many mothers receive prenatal dex, but according to the odds, 7 of 8 may be taking medication unnecessarily.


Concerns over Patient Consent

Some critics strongly oppose prenatal dex in large part because of the way it is presented to patients. Guidelines issued by pediatric endocrine societies in Europe and North America recommend that doctors obtain written informed consent from the patient as well as ethics-committee oversight for the treatment, but it is not known how many physicians adhere to these guidelines. Langford says she was not made aware of them. In addition, 2010 practice guidelines from the international Endocrine Society suggest that prenatal dex be administered as part of clinical research, which requires informed consent and ethics-committee oversight.


However, prenatal dex is routinely given outside the research setting, as an off-label treatment. It is common - and perfectly legal - for doctors to use their own discretion when prescribing drugs off-label. Antiseizure drugs like topiramate are commonly prescribed to treat migraine headache pain, for example. The practice allows patients to receive valuable treatment for which the drug may not have been expressly approved and may never be - it takes money and drug-company interest, which are hard to come by, to conduct the large randomized controlled trials required for a new-use the Food and Drug Administration (FDA) approval of a drug that is already on the market.


But as doctors share information about a drug's perceived off-label benefits and lack of harm, it gets even harder to take a step back and launch a formal randomized controlled trial - considered the gold standard in medical research - because patients demand the treatment, and doctors say it would be unethical to withhold it from them or from control groups in clinical trials. "It's a risky and dangerous way to innovate," says prominent University of Pennsylvania bioethicist Arthur Caplan. "There's no systematic collection of information. So, yes, things do get proven this way, and it is a way to innovate, but it also can come at a cost of unnecessary expense and, sometimes, bad side effects."


It also enables doctors to do human research without gaining proper approval. All participants in human medical research are, by law, entitled to the protective oversight of an institutional review board (IRB), a committee that safeguards the interests of research volunteers and ensures they have been fully informed about the potential risks and benefits of an experimental treatment. If doctors are simply treating a patient with an off-label drug, they are not required to obtain written informed consent from patients. But if doctors give treatment with the intent to gain knowledge, they are technically doing research, which must receive IRB approval.


Ethicists say physicians may sometimes treat patients off-label, then decide later to launch a follow-up study; or, they do follow-up research on patients who have been treated by other doctors. In the process, they have converted these patients into unwitting research volunteers. Some doctors game the system this way, Caplan says, to avoid battles with IRBs.


Critics suspect that Mount Sinai's New, who has long championed prenatal dex and bills it as safe on her foundation website, has gamed the system. In a letter dated Feb. 2, 2010, a group of 36 bioethicists, including Alice Dreger, a professor of bioethics at Northwestern University, asked the FDA and the federal Office for Human Research Protections to investigate New's practices; the authors contend that the doctor has conducted follow-up studies on prenatal dex patients without receiving IRB approval for treatment trials. Dreger says she has also asked Weill Cornell Medical College, where New previously worked, and Mount Sinai Medical Center to investigate the matter.


New, who declined to be interviewed for this article, does not administer the treatment in her current practice - according to Mount Sinai Medical Center, she has prescribed it only once since joining the hospital in 2004 - but ethical concerns remain, Dreger says, if the doctor consults with patients, resulting in their being prescribed dex elsewhere, then follows up with them for research purposes. At a medical conference in January, where New presented data from her research on prenatal dex, the doctor refused to answer a fellow researcher's questions regarding her process of informed consent.


Clinical Trials vs. Legal Trials

For Langford's part, she says she is grateful to New for her help, even though her daughter, now 4 and healthy, was found not to have CAH.


But Jenny Westphal, 24, who took dexamethasone throughout her pregnancy at the recommendation of another doctor, says she feels misled. Like Langford she was not asked to give informed consent. Unlike Langford, however, her daughter, now 3, who has CAH, has also had serious and mysterious health problems since birth, including feeding disorders, that are not commonly associated with her adrenal-gland disorder.


In April, Westphal, who lives in Wisconsin, started doing research online and discovered there was some controversy over the treatment. "I was outraged, frustrated and confused. Confused, because no one had ever warned me about this. I wasn't given the chance to decide for myself, based on the risks and benefits, if I wanted the treatment or not," she says.


Westphal may never know whether her daughter's problems were caused by dexamethasone, though she will likely always believe they were. That is why so many similar situations, in which experimental drugs are prescribed off-label without informed consent rather than in clinical trials, wind up becoming case studies - not in scientific journals, but exactly where Westphal and her husband are considering taking theirs: to court.


Originally from http://news.yahoo.com/s/time/20100622/hl_time/08599199645300