Wednesday, October 31, 2012

Adrenal Insufficiency - Female Patient found Unconscious with Syringe Nearby

Crew’s misdiagnosis of drug overdose could have cost patient her life

Kimberly Doran | From the October 2012 Issue |

A call comes in to 9-1-1 dispatch. “Help” is all that’s spoken before the operator hears the phone hit the floor. The 9-1-1 dispatcher calls back only to get a busy signal. Police and EMS are dispatched for a well-being call.

On arrival, the front door is found to be slightly ajar. The crew knocks, but there’s no reply. They find a young woman  lying on the floor, naked, and in a pool of vomit. A syringe with an unknown substance is on the ground nearby. Suspecting a drug overdose, the EMS crew begins treating the patient for this condition. The patient is unconscious with emesis around her head and face. Her vital signs are blood pressure 60/45, heart rate of 130 bpm and respiratory rate of 10.

The patient shows no signs of waking. The crew clears the airway and administers oxygen. An IV is established, and the patient is readied for transport. As the crew leaves the scene, one of the medics turns to shut the door and sees a vial under a chair. He retrieves it and notes that the label says Solu-Cortef (a glucocorticoid). He bags it for the emergency department (ED). Following his instinct, he looks around the area for medications and finds two bottles. One is labeled dexamethosone and the other is labeled fludrocortisone. He takes his findings and rushes out the door into the awaiting ambulance. During transport, the patient continues to deteriorate.

The medic administers 0.5 mg of narcan and a 500mL bolus of normal saline with no response. He radios ahead to let the hospital know that they’re en route. Now questioning the original diagnosis of drug overdose, he reports the medications he found on the scene in hopes it will help the receiving physician determine the cause of the patient’s condition.

Arrival at the ED
On arrival to the ED, the medic hands over the loaded syringe containing 2mL of unidentified solution, as well as the empty vial of Solu-Cortef and the bottles of dexamethosone and fludrocortisones.

As the crew arrives at the hospital, the ED physician meets the crew and informs them that he’s familiar with the medications. He says they're all used for people who have various forms of adrenal insufficiency (AI). The symptoms seen in this patient coincide with life-threatening adrenal crisis. The physician administers 100 mg of Solu-Cortef via IV and within minutes, the patient rouses. In 30 minutes, she can explain what happened in the desperate moments before her crisis.

Adrenal Insufficiency
Adrenal Insufficiency (AI) is a life-threatening in which the body is unable to produce enough cortisol to sustain life. In other words, their adrenal cortex is “asleep.” People suffering from AI take daily cortisol/glucocorticoid steroid replacement because whatever adrenal function is depleted. These patients are glucocorticoid dependent. In times of injury, dehydration, illness or surgery, they require an injection of Solu-Cortef. Solu-Cortef contains both glucocorticoid and mineralocorticoid properties, helping the body to compensate during a stress event.

The adrenal medulla (inside of the adrenal gland) secretes epinephrine and norepinephrine. The adrenal cortex (outer layer of the adrenal gland) secretes cortisol and aldosterone. Cortisol, a glucocorticoid, is often called the “stress” hormone. One of cortisol's functions is elevating blood glucose levels in times of stress. It also functions as a mediator for several inflammatory pathways.

Absence of cortisol can result in hypotension, hypoglycemia and death. Aldosterone, a mineralocorticoid, is responsible for the regulation of sodium and water. Absence of aldosterone can result in hypotension and electrolyte imbalance. AI in the prehospital setting may be difficult to recognize in the absence of a good history, including medications, to point providers in the cause of the problem. Two life-threatening conditions associated with AI include hypotension and hypoglycemia.

If not managed, these two conditions are life threatening. Prehospital treatment should include management of the patient’s airway, vascular access and fluid resuscitation. If blood glucose levels are low, the patient should receive dextrose per local protocol. It’s important to complete a thorough physical assessment and obtain a complete patient history before treating patients with this condition. Providers may confuse patients having an adrenal crisis with drug overdose patients because of their similar symptoms. Although AI is rare, it should still be considered as a potential diagnosis.

Authors’ noteParts of the above case are taken from a true story. However, the difference is that there was no syringe on the floor, no vial under the chair and no one found the medications. The patient was treated with charcoal and diagnosed as a drug-overdose patient. She likely would have died, but her mother charged into the ED and expressed the need for Solu-Cortef. Security was called, but luckily someone listened, researched and called the patient’s treating physician. The patient was treated and released. 

From Journal of Emergency Medical Services

Monday, October 29, 2012

Use of ketoconazole in the treatment of Cushing's syndrome

An older, but still useful, abstract:

J Clin Endocrinol Metab. 1986 Dec;63(6):1365-71.



The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period.

Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another.

The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.



Tuesday, October 9, 2012

Cushing's, The "Gift" that Keeps on Giving

I had an eye doctor appointment yesterday. No problems, just a routine check, maybe update my contacts to a newer version.

I was completely not ready when the doctor said "cataracts" to me. Say what? I'm not that old.  He mentioned a few other things like macular degeneration but that was less distressing to me somehow than the Cataract Word.

They're not bad yet.  They're slow growing.  I won't need to do anything about them for 7-8 years.  AARRGGHH!

My mother is waiting for her cataract surgery.  Maybe we can do this together, a bonding thing.

When I got home and all the eye drops had worn off, I looked at the brochures he had given me.  One of the symptoms was light insensitivity.  So that explains why I have trouble first thing in the morning and it hurts to open my eyes and other bright lights can be painful.  It's nice to be validated but...

Then, I turned the page to find contributing factors and came upon the word STEROIDS.  Not again!  Almost all the problems in my life start with the word steroids.  I did a search of the Cushing's Help boards for "Cataracts" and came up with 84 entries.  How could I have missed this?


The eye conditions glaucoma and cataracts also may occur in Cushing's syndrome. In Cushing's disease (tumors on the pituitary gland), your field of vision can be affected. You may have loss of side, or peripheral, vision.



Tuesday, October 2, 2012

Novartis launches pasireotide for Cushing’s disease

Cushing’s disease patients for whom surgery is not a viable option have a new treatment alternative, in the form of the orphan medicine pasireotide.

Launched by Novartis as Signifor, the drug is a somatostatin analogue that blocks the release of excessive adrenocorticotropic hormone, thus reducing cortisol levels.

Pasireotide is available as a solution for injection that should be self-administered by the patient twice a day. Patients should be informed how to inject the drug under the skin and that using the same injection site for two consecutive injections is not recommended.

After two months of treatment, patients’ blood cortisol levels are measured to determine whether treatment should continue, and at what dose (see Panel).

Patients who experience adverse reactions may need to temporarily lower their twice-daily dose, with decrements of 0.3mg suggested in the summary of product characteristics.

Pasireotide is indicated for adults only and is contraindicated for use by patients with severe liver impairment. It should be used with caution by patients who are taking medicines that prolong the QT interval, and clinical monitoring of heart rate is recommended for patients receiving pasireotide concomitantly with bradycardic drugs.

Dose adjustments of ciclosporin, insulin and antidiabetic medicines may be required if these are taken concomitantly with pasireotide.

The EMA granted marketing authorisation for pasireotide in April 2012 on the basis that, although the proportion of patients who responded to treatment in clinical trials was small (around 15 per cent), a partial response may be of benefit to patients whose condition cannot be managed with surgery.

Product information

Class: Somatostatin analogue

Dose: 0.6mg by subcutaneous injection twice daily. After two months of treatment, patients whose urinary free cortisol levels have reduced can continue treatment for as long as they experience a benefit. The dose can be increased to 0.9mg as long as the 0.6mg dose is well tolerated. Patients who have not responded after two months of treatment should be considered for discontinuation. The recommended twice-daily dose for patients with moderate liver impairment is 0.3mg initially, up to a maximum of 0.6mg.

NHS list price: 60 x 0.3mg/ml, £2,800; 60 x 0.6mg/ml, £3,240; 60 x 0.9mg/ml, £3,240

Legal category: POM 

From PJOnline


Interview with Dr. Amir H. Hamrahian

Amir H. Hamrahian, MD, is a Staff member in the Department of Endocrinology, Diabetes and Metabolism at Cleveland Clinic's main campus, having accepted that appointment in 2005. Prior to that appointment, he was also a clinical associate there for nearly five years. 

His clinical interests include pituitary and adrenal disorders.

Dr. Hamrahian received his medical degree from Hacettepe University in Ankara, Turkey, and upon graduation was a general practitioner in the provinces of Hamadan and Tehran, Iran. He completed an internal medicine residency at the University of North Dakota, Fargo, and an endocrinology fellowship at Case Western Reserve University and University Hospitals, Cleveland.

In 2003, he received the Teacher of the Year award from Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism. Dr. Hamrahian speaks three languages -- English, Turkish and Farsi -- and is board-certified in internal medicine as well as endocrinology, diabetes and metabolism. He is a member of the Endocrine Society, Pituitary Society and the American Association of Clinical Endocrinologists.

Some of the questions answered in this interview October 1, 2012 include (not in this order):


  • Can you tell me a little about you endocrine practice and your experience with Cushing’s as part of your practice?
  • What are some of biggest challenges you have in treating Cushing’s?
  • How do you test cyclical/episodic Cushing's?
  • Can someone with cyclical/episodic Cushing's take Korlym?
  • I know that Cushing's patients (those that currently have it and/or are cured/in remission can have healthy pregnancies with the right care. How do doctors support this process? Through an endocrinologist and a high-risk ob/gyn? And what sort of treatment is given throughout the pregnancy to prevent hypercortisolism.
  • While many patients have a successful long term result from surgery, there are just as many that don’t. Do you find that there are any particular challenges treating patients with Cushing’s disease when pituitary surgery has already failed?
  • As I understand, you were an investigator in the clinical trial for Korlym, and I think you treated 4 patients. Did these patients all have a previous surgery that had failed?
  • Many Cushing’s patients are trying to understand if they might be candidates for Korlym treatment, can you tell me a little history about the types of patients you treated with Korlym?  I hear that not all patients can take Korlym. Which type of patient should not take it?
  • Every past treatment for Cushing’s has always had the goal of lowering cortisol levels, but Korlym doesn’t lower cortisol levels, can you explain how it works?
  • So, how do you judge success for a Cushing’s patient on Korlym?
  • I lost copious amounts of hair while on Korlym, is this a known side effect?
  • Are there any long term reproductive implications due to use of Korlym?

Listen to this interview at or to the podcast by searching for Cushings in the iTunes podcast area or click here: