A 12-year-old boy died from Addison’s disease after the chance of lifesaving treatment was ‘missed’

The death of a 12-year-old boy who was suffering from undiagnosed Addison’s disease was preventable, an inquest heard.

Ryan Lee Morse had been unwell from July 2012, with his parents noticing his skin darkening and him becoming lethargic and losing weight.

His condition worsened over the following months and he died during the early hours of December 8, 2012.

During the time he was unwell, Ryan’s mother, Carol Ann Morse, took him to Abernant Surgery in Abertillery several times.

She said: “Ryan was rarely ill as a child. In June 2012, which was towards the end of Ryan’s first comprehensive school year, I noticed his skin colour changing.

“His skin seemed to be getting darker.”

She said his joint areas, including elbows and knees, were getting darker. Under his eyes, it looked as if he had not slept for a month. I don’t suppose it worried me at the time because it was gradual.”

A post mortem was held on December 12 by Dr E. J. Lazda, a consultant pathologist at University Hospital of Wales in Cardiff who concluded that Ryan died as a result of Addison’s disease.

An inquest into Ryan’s death was held at Newport Coroner’s Court on Thursday.

Dr Yvette Cloette, a consultant paediatrician since 2004, was called during the early hours of December 8, 2012, by a registrar where she was told the details of Ryan’s death.

She said: “Ryan’s parents told me he had been unwell since July.

“It was thought Ryan had been particularly unwell since the Thursday before he passed away. He had to be collected from school that day. On (the) Friday morning, she said he hallucinated. His temperature did settle that afternoon but then he had diarrhoea.

“As his mum was cleaning him, she noticed his genitalia were black.

“I then examined Ryan. At this time I formed the opinion that Ryan may have had Addison’s disease. I didn’t share this with the family at the time because I didn’t have enough evidence.

“I believe that Ryan’s death was preventable. Addison’s is a disease which, once recognised, can be treated.”

She said it was easier to put things together retrospectively, as opposed to when treating an acute illness as a GP.

David Bowen, senior coroner for Gwent, paid tribute to Ryan’s family during the hearing.

“Before summing up, I think it’s right that I pay tribute to the dignity that has been shown by Mrs Morse and her family.

“It can’t have been easy for them to rehear events that took place over five years ago.

“Please accept my belated condolences.”

Mr Bowen told the inquest that Ryan had been fit and well up until July 2012.

“However at about that time, his parents began to notice a gradual change in his skin and a fluctuation in his general health.”

He had been diagnosed with a viral infection and prescribed Paracetamol, he said.

Over the next six to eight weeks, he did not improve.

Mr Bowen said: “Consequently, his mother took him back to the doctor. The GP was more concerned about the rash, it seems to me, than any of the other symptoms.

“He prescribed tablets and cream for that condition.”

Mr Bowen said that during October and November 2012, “Ryan’s health became much more of a concern for his parents.”

He suffered from headaches, pains in his legs, and occasional episodes of projectile vomiting.

On November 7, Mrs Morse took Ryan back to the GP surgery, where she described symptoms to Dr Rudling, who took samples of blood.

On November 21, they returned to receive the blood test results.

The results revealed a “slightly lower than normal” white blood cell count. The inquest heard Ryan was told he was still suffering from a viral infection that had been diagnosed some months earlier.

Mr Bowen said: “It appears that about this time, there was an outbreak of Norovirus or vomiting and sickness in the area that may have confused the diagnosis.”

Mrs Morse said: “I’d been told to bring Ryan back in January so I thought I would just get Christmas out of the way and take him back. I’d been a carer for 9-10 years but my job didn’t give me any insight into what Ryan had.”

On November 29, 2012, Ryan returned to school, but around a week later on December 6 he was so ill that his mum had to collect him early.

The following day, on December 7, Mrs Morse rang Abernant Surgery saying she needed to speak to a doctor.

Between 8.50am and 8.55am, she received a call from Dr Lyndsey Elizabeth Thomas.

Mrs Morse said: “She asked if he’d been given Paracetamol and I explained he wouldn’t take it. She asked what his temperature was like.

“I’d said Ryan was awake (that morning) and talking rubbish.”

The inquest heard Mrs Morse was asked to take Ryan to the surgery, but she said she was unable to.

“She then told me to give Ryan some dissolvable Paracetamol and see how it goes until dinner. She said fetch him up if you need to.”

Dr Lyndsey Elizabeth Thomas said her contact with Ryan was limited to a single telephone conversation with his mother on December 7.

She said: “I considered whether Ryan needed to be seen or admitted to hospital.

“I clearly recall explaining that if she had any concerns or if Ryan’s delirium or temperature didn’t improve in two hours, he would need to be seen, I would be able to go and visit him at the end of the morning surgery if necessary.”

Mrs Morse said she later noticed that her son’s genitals were black.

She rang the surgery and was put her through to Dr Rudling.

Mrs Morse said: “She said ‘it’s all to do with his hormones’. Phone Monday and we’ll fit him in. At this point I didn’t know what to think.

“I was thinking I’ll take him in on Monday and see what they say. There was no more temperature, no more sickness and no more diarrhoea.”

The inquest heard Dr Joanne Louise Rudling, who qualified in 1993, joined Abernant in August 2011.

She said her first contact with Ryan was in November 2012.

On December 7, Dr Rudling said the receptionist took a call from Ryan’s mother while she was in reception.

Dr Rudling said: “I decided to speak to Ryan’s mother in reception there and then.

“She also asked if this could be age related, I said it could be but I would have to examine him first.

“The impression I got was Ryan was improving. His mother was concerned about the darkening of his genitalia.”

Ryan’s father said goodnight around 10.15pm and went to bed. At around 11.10pm Mrs Morse could see Ryan had fallen asleep, and went to sleep herself at around 11.30pm.

She said: “I woke up and saw it was 4.10am and then I looked at Ryan and looking at his chest could see he wasn’t breathing.

“I started to do chest compressions, dialled 999, continued chest compressions until the paramedics arrived. They took over. They told me Ryan had died.”

Mr Bowen said: “This is a rare but natural disease, one which apparently GPs will not normally encounter.

“Unfortunately, neither doctor nor parents thought it necessary to refer Ryan to hospital, where the true nature of his illness may have been diagnosed.”

Recording a narrative conclusion, Mr Bowen said Ryan died of natural causes.

He said: “The opportunity to administer life-saving treatment was missed.”

Speaking after the inquest, Ryan’s sister Christina Morse said: “First of all I would like to thank everyone involved with Ryan and Ryan’s case.

“Today, after five long years, the coroner has come to the conclusion that Ryan’s death was due to natural causes and that Ryan’s death was preventable.”

From http://www.walesonline.co.uk/news/wales-news/boy-died-addisons-disease-after-13687355

Yes, You Need a Medical Alert Bracelet!

Shared with permission from https://aiunited.org/medicalbracelets/

Advice from a Volunteer Firefighter with Adrenal Insufficiency

My name is Jeannie, and I have been diagnosed with Secondary AI since March of 2015. To make a long story short, I was diagnosed with a pituitary adenoma in Feb of 2015. It was apron 8mm x 10mm at the time wit was found. On April 25th, 2015 I was getting ready for work in the early morning hours.. I passed out in my bathroom and was immediately rushed to the hospital by my husband. They did a secondary MRI and found that the tumor had tripled in size to 23mm x almost 41mm. My Cortisol was also so low it was undetectable by the lab. I was taken by ambulance to Emory University hospital in Atlanta where the Neurosurgeon I had been in consult with was. I arrived there on Sunday and was in Surgery Wednesday Morning. The surgery took 9 hours and recovery was close to 6.

Prior to this all taking place I was a volunteer firefighter, and had worked EMS for almost 16 years. I have been in nearly every situation possible. I see so many people that have our condition asking about Medic Alert bracelets, What kind they should have, what it should say on it, etc. So I have put together a short list to help out a little bit. This is coming from both someone who has this extremely rare disease, and also from the Emergency Medical Side of me. Knowing what We as medics look for in the field, How quickly things move, what we ask or need to know, etc.

Please know that this IS NOT Professional Medical advice, But this is advice coming from someone who can shed some light on how to potentially save your life if you should ever be alone, or without anyone who knows your condition and you fall unconscious or are unable to the the responders what your condition is.

First off if you are looking for a medic alert bracelet or wondering if you should get one.

**The answer is yes, If you have been diagnosed ANY TYPE of adrenal insufficient or are on replacement medication.. YES. you need one.**

Here are some of those reasons and some pointers on what they should look like / what they should say.

#1– If you are found unconscious, and there are not bystanders around to tell emergency crews what is wrong with you, You will go longer without your steroids. If we see on your bracelet that you are steroid dependent, it dissolves the ENTIRE guessing game of why you’re unconscious.

#2– It should have on there your emergency contact and a GOOD telephone number. That way if nothing else. We can call them. NOT EVERY EMS AGENCY HAS ACCESS TO THE “CLOUD” BASED SYSTEMS THAT STORE YOUR INFO. Please be sure that if your emergency contacts number changes.. You change it on your bracelet. There is nothing worse than wasted time calling a number that doesn’t belong to the person we NEED to talk to.

#3– DO NOT MAKE IT “PRETTY” OR “NOT SO OBVIOUS”. I can not stress this enough. Ladies I know that you want the cute ones that look like normal bracelets, and have pretty charms, etc on them… THE ENTIRE point of a medical alert bracelet is that someone needs to see it and know that they should look at it. If it looks like a regular bracelet or regular necklace and it isn’t obvious within the first 3 seconds once we get to you and look in the obvious places (neck/wrist). it will NOT get seen. I promise you, we are too busy trying to play the guessing game of why you are not responding, than to take a look at every single piece of regular jewelry and see if it might have a really small inscribing of what is wrong with you. Once again. Make it noticeable. We will see that we need to look at it. Once we do. The guessing game is more than likely OVER. and we can begin to treat you appropriately.

#4– Most EMT’s and Paramedics Don’t Understand or know about Addisons or the treatment involved. If nothing else, carry a letter from your doctor explaining what is wrong with you, etc. It is very rare, and NOT covered in most Paramedic courses. So please, for those of you that put “ADRENAL INSUFFICIENT” on your bracelet and NOT “STEROID DEPENDENT” please keep in mind that you may end up with the Paramedic that just graduated, is nervous, and will mistake adrenal insufficiency for Adrenaline insufficiency.. and try to give you epinephrine. Please understand that I have seen this almost happen. It is something that is easily misunderstood in the heat of the moment.

#5– If you have an emergency injection that you carry with you all the time, on your person, or somewhere close. PUT ON THERE THAT YOU HAVE IT! MOST ems agencies have standing protocol that they can assist with emergency medications (Don’t jump in here if you are one of those states that doesn’t allow it.. I said most) That way if we find you down, and look at your bracelet, AND see that you have emergency meds with you… guess what now, not only is the guessing game over, You’re ALSO getting the RIGHT EMERGENCY MEDS, instead of us having to either give you what we carry, or you having to wait until you get to the ER and the ER doc has to go through your file and figure out that you need the medication that’s been in your pocketbook the ENTIRE TIME.If you are unsure if your state allows this, or if you Local EMS agency can do this. Contact their local medical control and ask. If they do, Please offer to give a small talk on what the disease is and how to use the emergency kit. Most will know once they see the acto-vial, but if they do not, Please educate them. Explain to them that it can be the only thing that could save your life.

Please take the time and make sure that you have correct information on your bracelet. Secondary or Primary, the treatment in an Emergency situation is the same. So there is NO need for you to spell out if you are secondary or primary. Both get the emergency injection in case of a crisis. Both get fluid bolus, heart and blood pressure monitoring. Nothing is different when it comes to an emergency situation. If you have any questions on the wording or what to get on it. Be sure you at least have an emergency contact, That you are steroid dependent, and where your emergency injection is located.

IF you know that your local EMS agency uses the “cloud” for stored emergency info, you can spend the money to get it. But I worked for service that covered a county with over 100 sq miles, and we didn’t use it. It is unreliable and takes too much time to log in to the system, try to read the small number on your band, type it in, etc. When you can simply put the information on the band itself.

If you have any other further questions, You can refer to AIU’s emergency page.

Reasons You Have Flab Around Your Abdomen

Some diseases and conditions could be responsible for your abdominal fat.
Mita Majumdar | Updated: April 24, 2017 6:15 pm

Visceral fat or unhealthy belly fat that surrounds the liver and other organs in the abdomen puts you at risk for serious health problems, such as, metabolic syndrome, heart disease, and type 2 diabetes. But, what causes your pot belly or beer fat in the first place? The most obvious answers you will get is – ‘You are not exercising enough’, or, ‘you are eating too much of fatty foods or sugary foods’, or ‘you are not eating the right foods’, or ultimately, ‘It’s genetics! You got it from your parents’. All of these reasons are true, of course. However, some diseases/ disorders and conditions, too, could be responsible for your abdominal fat and these have nothing to do with not exercising or not eating right. Following are some of these disorders.

Cushing’s Syndrome

Cushing’s syndrome, also called hypercortisolism, is an endocrine disorder that occurs when your body is exposed to high cortisol levels over a long period of time. It is a treatable disorder, however, if it is chronic, the symptoms can last lifelong.

Symptoms: Symptoms vary according to the severity of the disorder. The characteristic symptoms include –

  • Fatty tissue deposits in the midsection
  • Fatty deposits in the upper back, especially between the shoulders, so that it resembles a hump
  • Puffy face
  • Violaceous stretch marks (pink or purple) on the arms, breast, stomach, and thighs that are more than 1 cm wide. [1]
  • Easy bruising
  • Fatigue
  • Hirsutism and irregularity in menstruation in women
  • Loss of libido and erectile dysfunction in men
  • Cognitive dysfunction, depression, unpredictable emotional outbursts, irritability is present in 70-85 percent of people with Cushing’s syndrome.[1]

Causes:

  • Overuse of corticosteroids
  • Overproduction of cortisol by the adrenal glands

Management:

  • Surgery is the first line of treatment for Cushing’s syndrome.
  • Medication include: [2]

a.Pituitary gland directed therapy

b.Adrenal-blocking drugs

c.Glucocorticoid receptor-antagonizing drugs

  • Pituitary radiotherapy

Addison’s disease

Addison’s disease, also called adrenal insufficiency, is a disorder where your adrenal glands produce insufficient hormones, especially, glucocorticoids including cortisol and aldosterone. It is a life-threatening disease that can affect anyone irrespective of their gender or age.

How do glucocorticoids influence abdominal fats? Glucocorticoids including cortisol convert the fats into energy in the liver. They also help your body respond to stress. When sufficient amount of glucocorticoids are not produced by the adrenal glands, the fats accumulate in the abdominal area, and you see it as flab around your middle.

Symptoms:

  • Hyperpigmentation
  • Extreme fatigue
  • Low blood sugar and low blood pressure
  • Salt craving as one of the functions of adrenal glands is to maintain the sodium-potassium balance in the body
  • Nausea, vomiting, abdominal pain
  • Weight loss but gain in abdominal fat

Causes:

  • Insufficient production of adrenal cortex hormones
  • Stopping of prescribed corticosteroids
  • Tuberculosis and other infections of adrenal glands
  • Spread of cancer to the adrenal glands

Management:

  • Oral corticosteroids or corticosteroid injections
  • Intravenous injections of hydrocortisone, saline solution, and dextrose in case of Addisonian crisis

Stress

Chronic stress is a very big cause of belly fat. When you are exposed to stress, a chain reaction starts in the body because of the dysregulation of HPA axis of the neuroendocrine system. HPA axis is a complex interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus produces a corticotropin releasing hormone (CRH) and vasopressin. These together stimulate the secretion of adrenocorticotropic hormone (ACTH). ACTH is transported by the blood to the adrenal glands, which then produces corticosteroids, mainly, cortisol from cholesterol. One of the functions of cortisol is to signal the body to store fat, and specifically, the fat storage occurs in the abdominal area, where the cortisol receptors are greater. Researchers have found that stress causes hyperactivation of HPA axis, leading to accumulation of fat tissue, especially in the abdomen region.

So, the more and longer you are stressed (or if you are chronically stressed), chances are that you will be carrying more belly fat!

Ascites

Ascites is the buildup of fluid in the abdominal space. Ascites usually occurs in people with cancer, and it is then called malignant ascites. Onset of ascites is generally the terminal phase in cancer. Ascites also occurs in patients with liver cirrhosis, kidney failure, or heart disease.

Symptoms:

The first sign of ascites is an increase in abdominal girth accompanied by weight gain. [4] Although it looks like it is belly fat, it is actually the fluid that causes the bulging.

Other symptoms include:

  • Shortness of breath
  • Nausea and vomiting
  • Swelling in the feet and ankle
  • Decreased appetite, sense of fullness, bloating
  • Fatigue
  • Haemorrhoids

Management:

If the ascites is not causing any discomfort, it may not require any treatment. Treatment of ascites can have many side effects. Talk to your doctor before you go in for management/ treatment.

Abdominal hernia

Abdominal hernia is a swelling or a bulge in the abdominal area where an organ or fatty tissue pushes through a weak spot in the abdominal wall. The abdominal wall is made up of tough connective tissue and tendons that stretch from the ribs to the groin. Depending on the position of the weakness in your abdominal wall, the hernia can be inguinal (groin), femoral (upper thigh), umbilical (belly button), hiatal (upper stomach), or even incisional. Incisional hernia can occur when the intestine pushes through a weak spot at the site of abdominal surgery.

Symptoms:

  • Visible bulge that may or may not cause discomfort
  • Feeling of heaviness in the abdomen
  • Sharp pain when you strain or lift objects

Causes:

  • Constipation and diarrhoea
  • Persistent coughing and sneezing
  • Straining or suddenly lifting a heavy object

Management:

  • Umbilical hernia, common in young children, mostly resolves by itself as the abdominal muscles get stronger.
  • Other abdominal hernia normally do not resolve by themselves. Doctors suggest waiting and watching.
  • If treatment is required, surgery is the only option. Surgery involves pushing the hernia back into the abdomen and repairing the abdominal wall.

Menopause

Menopause is certainly not a disease or a disorder. It is the time in a woman’s life when she stops menstruating and cannot become pregnant because her ovaries stop producing the required amounts of hormones oestrogen and progesterone. A woman reaches menopause when she has not had her periods for 12 months.

Symptoms:

  • Hot flashes and/ or night sweats
  • Vaginal dryness
  • Mood swings
  • Sleep disturbances

It is very common to gain belly fat during menopause. This is because of the low oestrogen levels. Oestrogen seems to influence the distribution of fat in the body, in a way that the fat is redistributed from the hips, buttocks, and thighs to the belly. However, a study published in the journal Metabolism reported that though women did significantly gain belly fat, especially deep inside the belly, relative fat distribution is not significantly different after menopause. [5] But the fact remains that women do gain flab in the abdomen after menopause.

Belly fat can be seriously harmful. If your belly fat is not because of the above-mentioned conditions, you can lose it by adopting a healthy lifestyle that includes sleeping enough, exercising regularly, eating right, and reducing stress.

Reference

  1. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clinical Epidemiology. 2015;7:281-293. doi:10.2147/CLEP.S44336.
  1. Feelders RA, Hofland LJ. Medical treatment of Cushing’s disease. J Clin Endocrinol Metab. 2013;98:425–438.
  1. Kyrou I, Chrousos GP, Tsigos C. Stress, visceral obesity, and metabolic complications. Ann N Y Acad Sci. 2006 Nov;1083:77-110.
  1. Sinicrope FA. Ascites. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.
  2. Franklin RM, Ploutz-Snyder L, Kanaley JA. Longitudinal changes in abdominal fat distribution with menopause. Metabolism. 2009 Mar;58(3):311-5. doi: 10.1016/j.metabol.2008.09.030.

Adapted from http://www.thehealthsite.com/diseases-conditions/reasons-you-have-flab-around-your-abdomen-f0417/

 

Lower health-related quality of life observed in patients with Addison’s disease, Cushing’s syndrome

Patients with hypothalamic-pituitary-adrenal axis dysregulations report health-related quality of life that is far lower than that of the general population, according to findings of a prospective study.

“In most centers, both patients with adrenal deficiency and patients with Cushing’s syndrome are managed by the same team,” Charlotte DeBucy, of the Center for Rare Adrenal Diseases at Cochin Hospital in Paris, and colleagues wrote. “Despite the usual perception that both types of diseases alter quality of life, few studies have similarly investigated the impact of cortisol dysregulations on [health-related quality of life]. Such studies are important, however, to identify meaningful differences that would be important to consider to improve management and outcome.”

De Bucy and colleagues analyzed data from 343 patients with Addison’s disease or Cushing’s syndrome followed in routine practice at a single center in France between September 2007 and April 2014 (78% women; mean age, 48 years; mean length of time since diagnosis, 7.8 years; 61% married). All participants completed the short-form health survey (SF-36), a survey of health-related quality-of-life measures and the 12-item general health questionnaire (GHQ-12), a measure of psychological well-being or distress. Questionnaires were completed at baseline and at 6, 12, 24 and 36 months. Patients with Cushing’s syndrome were also assessed for cortisol status at baseline and at follow-up evaluations.

Within the cohort, 206 had Cushing’s syndrome of pituitary origin, 91 had Cushing’s syndrome of adrenal origin and 46 patients had Addison’s disease; 16% were included in the study before any treatment was initiated.

Researchers found that mean standard deviation scores for psychological and physical dimensions of the SF-36 were “well below” those of the general population, but diagnosis, cortisol status and time since treatment initiation all influenced individual scores. Cushing’s syndrome of pituitary origin was associated with worse health-related quality of life, especially for physical functioning, social functioning and mental health. In Cushing’s syndrome, health-related quality of life was generally worse during periods of hypercortisolism, but scores for these patients were lower than those of patients with Addison’s disease even during periods of hypocortisolism or eucortisolism, according to the researchers.

“The differences were particularly large for physical functioning and role-physical subscales,” the researchers wrote.

They also found that mental health scores for patients with Cushing’s syndrome decreased during periods of hypocortisolism, whereas other adrenal conditions were associated with higher mental health scores.

More than half of patients, regardless of diagnosis and cortisol status, had psychological distress requiring attention, according to the GHQ-12 survey.

“Our findings are important for clinical practice,” the researchers wrote. “The consequences of cortisol dysregulation on [health-related quality of life] should be considered in the management of adrenal insufficiency and even more (in) Cushing’s syndrome patients, and these consequences can be long term, affecting apparently cured patients. Early information on these consequences might be helpful for patients who often perceive a poor quality of life as the result of inadequate disease control or treatment. Even if this possibility exists, knowing that adrenal diseases have long-lasting effects on [health-related quality of life] may be helpful for patients to cope with them.” – by Regina Schaffer

Disclosure: L’association Surrénales supported this study. The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B842655ce-e710-4476-a3c2-2909b06434ed%7D/lower-health-related-quality-of-life-observed-in-patients-with-addisons-disease-cushings-syndrome

History of Cortisone’s Discovery

It was Christmas Day in 1914 when the Mayo Clinic chemist Edward C. Kendall, PhD, first succeeded in isolating pure crystalline thyroxin using 6,500 pounds of hog thyroid glands, a success that would set him on the course for making one of the greatest discoveries in medicine in the last century.

His pivotal discovery, according to William F. Young, Jr., MD, MSc, chair of the division of endocrinology, diabetes, metabolism and nutrition at the Mayo Clinic College of Medicine, would lead Kendall, a self-described “hormone hunter,” to conduct adrenal experiments that would eventually change the course of medicine in ways he couldn’t have imagined. Kendall and his team’s discovery of cortisone would lead not only to a breakthrough treatment, Young said, but a Nobel Prize and international acclaim.

In an interview prior to presenting the Clark T. Swain Memorial History of Endocrinology Lecture at ENDO 2017, Young said that understanding the history behind such a monumental discovery can help endocrinologists see how hormone research has evolved, and provides insight into how to make advances in basic science and improve patient care. In preparing to tell Kendall’s story, Young completed archival research at Mayo and uncovered information that has not previously been published, he said.

“The cortisone story originated at Mayo Clinic, where I have been on staff for 33 years,” Young told Endocrine Today. “Although much of this story is not new information, it is not familiar to the current generations of endocrine scientists and clinical endocrinologists. It is a story of discovery science, clinical intuition, persistence, team science, patient volunteerism and sacrifice, hopes, and dreams.”

‘A big oak tree’

When Kendall first took on the project of preparing better adrenal extracts to potentially treat Addison’s disease in 1930, he was already thinking bigger, Young said.

“He once said, ‘I want to grow a great big oak tree … I am not interested in a bunch of blackberry bushes,’” Young said.

During his experiments at Mayo Clinic, the cost of bovine adrenals rose from 0.20 cents a pound to $3 per pound, equivalent to $42 per pound today. In 1934, Kendall struck a deal with Parke Davis Co., were he would extract “adrenalin” at no cost for the company if it would, in turn, deliver to him 600 pounds of bovine adrenals each week, Young said. He would then use the adrenal cortex for his studies.

In addition, Kendall struck a side deal with Wilson Labs, Young said, for an additional 300 pounds of bovine adrenals per week, to produce a cortical extract for them. He would in turn use the adrenal medullas to boost his production of adrenalin for the Park Davis deal.

“From 1934 to 1949, virtually all of the adrenaline used in North America was manufactured at Mayo Clinic in the small town of in Rochester, Minnesota,” Young said. “This lab ran 24 hours a day, in three shifts. By 1949, over 150 tons of adrenal glands had been processed at Mayo Clinic … $12.4 million in research supply dollars.”

A new discovery

In 1934, Kendall recognized through his work that the adrenal cortex produced more than one hormone, Young said. Over the next year, Kendall’s group isolated five crystalline compounds, naming them compounds “A” through “E” based on their order of identification. Compound “E” — what would later be named cortisone — was found to be biologically active, Young said.

Interest in synthesizing the active hormone from the adrenal cortex grew as part of the American war effort in the 1940s, Young said, and the U.S. National Research Council made it a priority. By 1948, 9,000 mg of “compound E” had been synthesized for clinical study; 2,000 mg were given to each of three investigators at Mayo Clinic for studies in patients with Addison’s disease and the remaining 3,000 mg were saved for future study.

In 1948, a patient known as H.G., a 28-year-old women with progressive inflammatory arthritis, presented to the clinic, Young said. After an unsuccessful treatment with the Swedish hepatoxin lactophenin — a therapy used at the time that induced jaundice in some patients, leading to remission — her physician, Philip Hench, went to Kendall for help. Kendall agreed to give Hench some of the remaining 3,000 mg of “compound E,” if Hench could convince Merck to grant permission.

The clinicians did get permission, and H.G. began treatment. Within days, Young said, the improvement was remarkable. Reading from the original, handwritten notes of Hench and his colleagues in rheumatology, , Young detailed the patient’s progress:

“Rolled over and turned off the radio with ease for the first time in weeks,” the notes said from “day 3.” “No more trembling of knees when moving.”

The clinicians were so amazed, Young said, that they filmed H.G’s progress. Young, who obtained the original films from the Mayo Clinic archives, showed footage of a crippled H.G. struggling to stand, only to be walking normally.

“They started taking videos because they realized no one would believe them,” Young said as the video played. “That they actually had something that could affect, up until this point, a crippling disorder.”

Hench came up with the acronym “cortisone,” adapted from corticosterone.

The discovery became international news. In December 1950, Kendall, Hench along with Tadeus Reichstein, received the 1950 Nobel Prize in Physiology and Medicine — just 27 months after H.G. received her first dose of “compound E.”

The future of corticosteroids

Today, Young said, corticosteroids are used for their anti-inflammatory and immunosuppressive properties across the field of medicine. Natural and synthetic glucocorticoids are used to treat a wide variety of non-adrenal diseases, from allergies, to gastrointestinal disorders and infectious diseases.

The important story of patient H.G. — and the scientific journey of Kendall and his colleagues — still resonates, Young said.

“My hope is that this story will remind us of our endocrine heritage and give us an opportunity to recognize the unlimited potential for discovery, research and clinical investigation that is taking place in research laboratories and clinical endocrine centers across the globe,” Young said in an interview. “In the current environment in the U.S., where federal research funds are being cut back, it is important to recall where the major advances in research and public health have come from.”

“There are many other messages in the presentation,” Young said. “For example, the importance of ‘team science’— a phrase only recently coined — has been in place for decades. It is team science that has led to many of the major advances in medicine, including the therapeutic use of corticosteroids.” – by Regina Schaffer

Reference:

Young WF. A Chemist, a Patient and the 1950 Nobel Prize in Physiology and Medicine: The Stories Behind the Stories on Cortisone. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2017; Orlando, Fla.

Disclosures: Young reports no relevant financial disclosures.

 

From http://www.healio.com/endocrinology/adrenal/news/online/%7Bd8d71bcc-a981-418e-9d41-af4b2dcaa48f%7D/history-of-cortisones-discovery-offers-lessons-in-team-science-persistence

%d bloggers like this: