Nordic questionnaire

Adrenal insufficiency

www.addison.dk

www.hypofyse.dk

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A THANK YOU TO OUR MEMBERS

The Nordic questionnaire that Addison Foreningen [The Danish Addison Association] and Hypofysenetværket [The Danish Pituitary Network] took part in is now officially concluded. We would like to take this opportunity to thank everybody who took the time to answer the questionnaire. It has been a supremely unique opportunity to collect information on adrenal insufficiency. All this data can provide us and others with a far better insight into the situation of patients with Addison disease and pituitary disease in the Nordic countries.

Addison Foreningen i Danmark Hypofysenetværket

INTRODUCTION

The survey was conducted in Denmark, Norway and Sweden at the end of 2012. Everybody who had an email address registered with the five Nordic patient support associations was sent a link to a page on the Internet. Morbus Addison Forening in Norway, Addison Foreningen in Denmark, Hypofysenetværket in Denmark, Stödföreningen Hypofysis and Svenska Addisonföreningen in Sweden. The members were extremely interested in answering the survey questions, beating many records. One hour after the questionnaire had been uploaded on the Internet, almost 50% had responded. The survey was sent out to 1,268 members of which 106 were either incorrectly addressed or could not receive the questionnaire. A total of 711 members responded within a month, giving a response rate of 62%. Denmark came out on top with a response rate of 75%, followed by Norway with 58% and Sweden with 53%. The response rates for all countries were higher than expected for comparable surveys.

The patient support associations own the data which are stored on an external web server. All data are completely anonymous, and it is not possible to link individuals to the answers. Viropharma (a part of Shire) has assisted the associations not only in preparing the questionnaire but also with the analyses and setting up the material.

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Adrenal insufficiency If untreated, adrenal insufficiency is a potentially fatal condition. Satisfactory treatment with medication is available; however, there is no cure. The disease is caused by either impaired or complete loss of adrenal cortex function or pituitary function. The most common cause of Addison's disease is the formation of antibodies against the adrenal glands, which is a so-called autoimmune disease. This autoimmune condition is the result of incorrect coding in the immune system that causes antibodies to attack the body's own cells. The antibodies affect production of cortisol, resulting in too little formation of this life-essential hormone. In primary adrenal insufficiency, another hormone is often also lacking. This is called aldosterone and is involved in the regulation of the salt and water balance. However, cortisol is the most important hormone that is replaced. It is essential for metabolism and replenishing our energy depots. Normally, cortisol is produced in the adrenal cortex in response to a signal from the pituitary. Therefore, disease not only in the adrenals but also in the pituitary can result in a lack of cortisol. In order to survive, life-long treatment with cortisol is necessary. The body cannot store cortisol, however, and the amount needed during the course of a day varies. Hydrocortisone, which is the synthetic form of cortisol, is normally used to replace the lost cortisol. The treatment objective in adrenal insufficiency is to provide the body with a sufficient dose of cortisone1 to meet the body's needs but not so much that there are side effects. If the adrenal glands are the cause of the adrenal insufficiency this is called Addison's disease or Primary Addison's. Secondary adrenal insufficiency is due to a disease of the pituitary that results in loss of the signals from the pituitary that tell the adrenal cortex to produce cortisol; it is called secondary Addison's because it gives the same symptoms as primary Addison's. Conditions other than Addison's that are treated with large amounts of cortisone over a long period of time can cause drug-induced Addison's disease. This is because the cortisone stops the adrenals' production of cortisol. Usually, the adrenal glands return to normal, but sometimes it can take a long time. The body normally produces cortisol continuously. This production is increased in response to stress or infection, for example. An inability to increase this production or inadequate function of the adrenal cortex can result in an Addisonian crisis. An Addisonian crisis is a potentially life-threatening condition that occurs when the cortisol drops to a dangerous level. It requires the immediate administration of hydrocortisone, SoluCortef, which is often given intravenously. The treatment of adrenal insufficiency has not changed noticeably over the last 60 years. Reports have shown that patients with adrenal insufficiency have a reduced level of functionality and reduced quality of life. Moreover, they have an increased risk of developing cardiac disease and osteoporosis, and they have a decreased life expectancy.

The results of this interesting study are presented on the following pages.

1 In this report, cortisone is used as a general term for all steroid-containing preparations.

2

The survey

There was a quick and high response rate from all countries, but Denmark came out on top with regard to the number of responses. There was a large age difference among the responders, of which 58% had primary Addison’s and 26% had pituitary insufficiency. More than twice as many women as men responded.

Which country do you live in?

Sweden

Norway

Denmark

I am...

Woman

Man

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Which type of adrenal cortex insufficiency do you have?

Primary (Addison’s)

Pituitary insufficiency

CAH (AGS)

Other

Don’t know

Hypothyroidism

Do you have any other autoimmune disease(s)?

Diabetes Type 1

Vitamin B12 deficiency

Vitiligo

Autoimmune ovarian inflammation

Other

No

How old are you?

Over 80

51 - 60 41 - 50 31 - 40

21 - 30 10 - 20

Below 10

61 - 70 71 - 80

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Treatment of adrenal insufficiency

The treatment involves replacing the hormones that the adrenal glands should normally have produced. Cortisol is replaced with hydrocortisone, which is a synthetic form of our natural cortisol. In rare cases, it is replaced with other corticosteroids. The most common treatment consists of 20-30 mg hydrocortisone 2 or 3 times a day. This dosing schedule is intended to replicate the pattern of cortisol excretion in a healthy person. Sometimes, if the patient does not produce enough aldosterone, it can also be necessary to give a mineral corticoid, Florinef (generally only in primary Addison’s). The main contribution of this hormone is to normalise the salt-fluid balance and the blood pressure.

Treatment of adrenal insufficiency aims at achieving a physiological cortisol level not only under normal conditions but also during stress when extra cortisol is needed. It is recommended to give the lowest dose of hydrocortisone that maintains the balance between the risk of developing an Addison crisis and the risks associated with too much cortisol.

Both too much and too little cortisol is harmful to health. Forgotten doses, or too little cortisol during illness, can result in an Addison crisis with high fever, vomiting, diarrhoea, and a drop in blood pressure. Very high doses over a long period of time can result in obesity, high blood pressure, diabetes and osteoporosis. It is difficult to tell from blood tests, etc. whether the treatment is adequate/optimal. This means that the treating doctor must make a very careful clinical assessment.

In this survey, almost everybody in Denmark and Sweden was treated with hydrocortisone. In contrast, almost everybody in Norway was treated with cortisone acetate. A small majority, about 45%, take their medicine twice a day, and about 40% take their medicine 3 times a day. Almost 70% of the patients were satisfied or very satisfied with their treatment.

Are you being treated at a University hospital or a Regional hospital?

Don’t know

Regional hospital 10

University hospital

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Which type of cortisone do you take?

Cortisone acetate

Hydrocortisone

Sweden

Norway

Denmark

Dose

3 times a day Other Once a day Twice a day

What is your normal daily dose of cortisone?

>40 mg

35 mg 30 mg 25 mg 20 mg 15 mg

12.5 mg

10 mg 5 mg

Don’t know Other dose

37.5 mg 40 mg

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Do you take any other medicines?*

No

Don’t know

Diuretics

Sex hormones

Growth hormone

Thyroxine

Other

* Only patients who answered that they had pituitary insufficiency

Do you take Florinef?

No

Yes

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How satisfied are you with your cortisone treatment?

Very dissatisfied

Dissatisfied

Neither nor

Satisfied

Very satisfied

What would you like to change about your current treatment?

Nothing/everything’s fine Don’t know

Other Better follow-up/contact with hospitals/the same doctor

Better information and advice That the hospital sees the “whole” patient

That healthcare personnel listen/are more interested Tablets with lower strength/easier to divide

Hydrocortisone Not need medicine

Avoid Addison crisis Not awake at night

Less tired/more energy Lower dose without tiredness

Fewer side effects Better effect/dose without side effects

Better adjusted to my needs Sustained release pill/Once daily pill

Pump/plaster/other than tablets Effect when you wake up

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If you could change something in connection with your cortisone treatment, what would it be?

That I could take the morning dose without having to wake up :)

Auto-dose (surgically inserted)

The same doctor Another medicine that does not give so many

side effects That they develop

instruments so that we get a more accurate

dosage!!!

1 pill per day. I immediately feel unwell if I am an hour

late.

5 mg tablets. Difficult to divide 20 mg into

many parts

Better contact with the

endocrinologist.

Tablet that you take at night and which doesn’t begin to work before the

morning and which then gives less and less effect as the day passes!

Get a more precise reaction. Dose as needed.

Better follow-up from doctors and specialists I feel very

much alone.

The tablets work well.

Plasters instead of tablets or an injection once a week or once a month

One dose for the entire 24 hours. Have a

tendency to forget the afternoon dose.

Sustained release/long-acting/slow release/one dose instead of

two/being able to take medicine just once a day.

It would be really good if I could get down to 20-25 mg, and that I could

have fun without getting ill afterwards - or not be able to meet up for that reason. It is very tiresome and very

tedious.

Reduce the side effects such as stomach ache, weight increase,

hair loss, blisters and rash.

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If you could change something in connection with your cortisone treatment, what would it be?

Impact on quality of life

Several studies have shown that patients with adrenal insufficiency experience a reduced level of functionality and reduced quality of life. One German study shows that the quality of life is lower the higher the dose of hydrocortisone. Another study conducted in Germany with patients with adrenal insufficiency revealed that the most common symptoms are tiredness and lack of energy (84% of patients with primary adrenal insufficiency and 64% of those with secondary adrenal insufficiency). Several patients with adrenal insufficiency have reported a loss of appetite, nausea and vomiting. The non-specific symptoms associated with the disease means that it can take a long time before a diagnosis is made.

Even though in our study more than 70% were satisfied with their treatment, more than 88% believe that the disease affects their quality of life, and 41% have problems with depression. Most people think that the most difficult aspect is that that it is an invisible disease; that you are not able to do what you did before; and that you could experience an Addison crisis. More than half are worried about long-term effects.

From next year, I want to switch to hydrocortisone.

Difficult to answer, as I don’t know what is the “normal” condition with this diagnosis.

Cortisone pump. Have been given a cortisone

pump - it is heaven!!!!!!!

10

Does your disease (adrenal insufficiency) affect your quality of life?

Yes, a lot

Yes, quite a lot

Yes, a little

No, not at all

Do you have problems with depression?

No

Yes

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What do you think is the biggest problem with your disease?

Don’t know

Other

That I am not able to do what I did before

That I can have an Addison crisis

That it is invisible

What is your general state of health? (1 = very poor, 10 = very good)

Median 6.6

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Are you concerned about long-term effects of your treatment?

No

Yes, a little

Yes, a lot

Don’t know

Do you have problems with your teeth?

No, no problems

Yes, a little

Yes, a lot

Do you have problems with your weight?

Don’t know

No, not at all

Yes, a little

Yes, rather much

Yes, a lot

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Other offical studies have shown that many patients with adrenal insufficiency have had to make changes to their life. Many also experience that the disease affects their capacity to work or go to school. This study has also shown similar results. 35% of the respondents consider that they are healthy enough to work full time. Many have had to cut back on their level of activity, both at work and in sports and social activities.

Other

Which activities have you had to change because of your Addison’s/pituitary insufficiency

None

Family life

Physical activities

Social activities

Work

Do you feel well enough to work?

Yes, full-time

Yes, part-time

No, I am on sick leave

No, I have taken early retirement

I am unemployed

14

If yes, how many days have you been absent?

More than 16 days

11-15

6-10

1-5

In the last 3 months, have you been absent from school/work because of something related to your

illness (adrenal insufficiency)?

Yes

No

Don’t know

15

An Addison crisis is very serious and requires immediate treatment at a hospital’s emergency department with administration of cortisol directly into the blood stream. The condition can occur in various phases of the disease. It can be the first symptom of Addison’s disease, but an Addison crisis can also occur in connection with an accident or an infection. Diarrhoea and vomiting can also trigger an Addison crisis. It is important that all patients with Addison’s disease carry an information card in their wallet which states that immediate adminstration of cortisone is life-essential in cases of accident or serious disease.

In order to avoid a life-threatening lack of cortisol it is important that the treating doctor provides clear information to the patient on appropriate measures in case of fever or other illness. Verbal and written information should be given at the onset of the disease and repeated at routine follow-up appointments.

Most people who answered the questionnaire carry either the cortisol card or a medallion. About 40% were not satisfied with the information they received when they were diagnosed, but 70% were satisfied with the information they are given when visiting the doctor and when they contact the hospital or doctor between appointments. About half of the patients had been prescribed Solu-Cortef. A quarter of those who responded have had to go to the Emergency department at least once during the last year because of an Addison crisis. Of those who had an Addison crisis, about 7% received a cortisone injection in the ambulance, and 53% had to wait longer than 1 hour before being given the cortisone injection at the hospital. 15% had to wait more than 4 hours before they received an injection. 57% believe that nurses do not have adequate knowledge of Addison’s disease.

Which symptoms do you experience when your cortisol level is low?

Don’t know

Other

Dizziness

Stomach ache

Pain in the joints

Feeling unwell

Headache

16

What do you do when you discover your cortisol level is low?

Increase the dose

Wait and rest

Nothing

Other

Do you yourself notice when your cortisol level is low?

Never

Rarely

Sometimes/Occassionally

Always

17

Did you receive adequate information when you were diagnosed?

Yes

No

Don’t know

Do you carry a medallion/medical alert or emergency card?

Yes, the card

Yes, the medallion

Yes, both the card and medallion

No

In which of the following situations do you increase your cortisone dose?

Fever

In hot weather

Mental stress

Physical stress

Infection

Other

18

Have you been given a prescription for Solu-Cortef?

Yes

No

Yes

No

Yes

No

Has your doctor told you about Solu-Cortef?

Do you feel you are given adequate information when you ask questions during or in between

appointments?

19

If you have Solu-Cortef: Have you or your close family given you an injection?

Yourself, yes

Yourself, no

Close family, yes

Close family, no

Have you received training in how to give an injection?

Yes

No

Have you been denied a prescription for Solu-Cortef?

Yes

No

20

If you have been transported by ambulance in an Addison crisis, were you given a cortisone injection in the ambulance?

No

Yes

What was the most frequent cause of your Addison crisis?

Gastroenteritis

Influenza

Other infection

Other

How many times within the last year have you been to the Emergency department

with an Addison crisis?

None

Once

Less than 5 times

5 or more times

21

Which information/service would you like your patient association to provide?

Don’t know

Information about the disease

Information about the treatment

Medical alert/crisis card Opportunity to meet others with the

same disease Telephone service with the

opportunity to ask questions Access to a mentor/helper

Other

I do not need more information

Do you think that the nursing staff know a lot about Addison’s disease?

Yes

No

Don’t know

How quickly were you given a cortisone injection at the hospital?

It took more than 4 hours

Don’t know

Within 0-1 hour

Within 1-2 hours

Within 2-4 hours

22

Which information/service would you like your patient association to provide?

Would you like to have received/receive further information about your disease or your medicine?

Positive stories

Emergency card in English

That one should not only focus on the disease itself, but what we can do to improve things, e.g. sport. Feel that there is a lot of focus on everything being negative; it doesn’t have to be.

Opportunity to buy a medallion

Dietary advice

Telephone service

Online chat

A FACEBOOK page

International research and groups; opportunity for follow-up abroad, not only in little Denmark

Am satisfied with the info we are given. It is up to oneself how you use it. Thanks.

Better information on hydrocortisone

Better information about the medicine and its effects and side effects; information on where I should go if I have an illness and need help. Information on what I can do if I my cortisol gets too low, and information on the possibility of getting emergency medicine and if I can keep it at home. Information on precautions when travelling, etc.

That I should increase the dose if I have a fever