The video version of this podcast can be found here:

·      https://youtu.be/BnwK2Vts3gY

This episode makes reference to guidelines produced by the "National Institute for Health and Care Excellence" in the UK, also referred to as "NICE". The content on this channel reflects my professional interpretation/summary of the guidance and I am in no way affiliated with, employed by or funded/sponsored by NICE.

My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode I go through new and updated recommendations published in September 2024 by the National Institute for Health and Care Excellence (NICE), focusing on those that are relevant to Primary Care only. I also cover the guideline on Adrenal insufficiency published on 28th August 2024.

 

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

 

There is a podcast version of this and other videos that you can access here:

 

Primary Care guidelines podcast:

 

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148

There is a YouTube version of this and other videos that you can access here: 

  • The Practical GP YouTube Channel: 

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk

The Full NICE News bulletin for September 2024 can be found here:

·      https://www.nice.org.uk/guidance/published?from=2024-09-01&to=2024-09-31&ndt=Guidance&ndt=Quality+standard

The links to the guidance covered in this episode can be found here:

Vibegron for treating symptoms of overactive bladder syndrome:

·      https://www.nice.org.uk/guidance/ta999

Adrenal insufficiency: identification and management:

·      https://www.nice.org.uk/guidance/ng243

The Imperial Centre for Endocrinology prednisolone withdrawal regimen can be found here:

·      https://www.impendo.co.uk/prednisolone/prednisolone-withdrawal

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release] 

 

Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I am Fernando, a GP in the UK. Today, we are looking at the NICE updates published in September 2024, focusing on what is relevant in Primary Care only.

 

We are going to cover just two areas, the treatment of overactive bladder and the guideline on adrenal insufficiency, which was published late in August 2024 and did not make it into last month’s episode.

 

Right, let’s get started.

 

The first area is a technology appraisal on Vibegron for treating the symptoms of overactive bladder syndrome in adults. It is very similar to the technology appraisal on mirabegron.

Before looking at the recommendation, let’s have a quick overview of Overactive bladder syndrome. It is a condition characterized by a frequent and urgent need to pass urine, sometimes with urinary incontinence. It is often caused by involuntary contractions of the bladder wall.

Treatment for OAB involves lifestyle changes, behavioural therapies, and medications. NICE recommends that bladder training and lifestyle advice should be offered as first-line treatments. Then an antimuscarinic drug should be offered second-line and beta 3 agonists should be offered third line.

So, let’s look at the two types of drug treatment:

  1. Antimuscarinic Agents (or Anticholinergics) are the most commonly prescribed drugs and they work by blocking muscarinic receptors in the bladder, reducing the involuntary contractions of the detrusor muscle.
  • Examples are:
  • Oxybutynin
  • Tolterodine
  • Solifenacin
  • Darifenacin and
  • Fesoterodine
  • Since muscarinic receptors are also found in other parts of the body (e.g., the salivary glands, eyes, and intestines), antimuscarinic agents can cause side effects such as dry mouth, constipation, blurred vision, and cognitive dysfunction, especially in elderly patients.
  1. Beta-3 Adrenergic Agonists are drugs like mirabegron and vibegron which offer an alternative to antimuscarinics. These drugs specifically stimulate beta-3 receptors on the detrusor muscle, causing the muscle to relax. This increases the bladder’s capacity and reduces the urgency and frequency of urination.
  • Beta-3 agonists tend to have fewer side effects compared to antimuscarinic agents. Some common side effects are mild increases in blood pressure, arrythmias, headache, and urinary tract infections.

So, in summary, the main difference between these Drug Classes are that Antimuscarinics work by reducing involuntary bladder contractions whereas Beta-3 agonists relax the bladder, improving bladder storage.

Vibegron, as a beta 3 agonist, works in a similar way to mirabegron and an indirect comparison suggests that it is equally effective at a lower cost. So, vibegron is recommended if antimuscarinic medicines are not suitable, do not work well enough or have unacceptable side effects.

The next section is a brand-new guideline on adrenal insufficiency.

And before we look into it, let’s give a very brief overview on the subject.

Adrenal insufficiency is a disorder where the adrenal glands do not produce sufficient amounts of cortisol, and sometimes aldosterone. It's classified into primary, secondary, and tertiary, each with different causes and pathophysiology.

  • Primary adrenal insufficiency is caused by a problem in the adrenal glands. Possible causes include autoimmune conditions, infection, and malignancy. The autoimmune condition Addison's disease is the most common cause in adults, and congenital adrenal hyperplasia is the most common cause in children
  • Secondary adrenal insufficiency is caused by a problem in the pituitary gland which limits the secretion of ACTH, leading to reduced adrenal stimulation. Possible causes include pituitary tumours, and damage to the pituitary gland secondary to trauma, surgery or radiation.
  • And Tertiary adrenal insufficiency is caused by a problem in the hypothalamus which reduces the levels of corticotropin-releasing hormone (or CRH). Possible causes include tumours in the hypothalamus or adjoining structures, or more commonly the use of prolonged glucocorticoids which suppress the hypothalamic-pituitary-adrenal axis.

The physiopathology in each case is also different:

  • In primary adrenal insufficiency, the adrenal cortex is unable to produce both glucocorticoids, and mineralocorticoids, leading to cortisol and aldosterone deficiency.
  • In secondary and tertiary adrenal insufficiency, the adrenal glands themselves are functional, but low levels of ACTH and / or corticotropin-releasing hormone (or CRH) impair the production of cortisol. However, mineralocorticoid production is usually preserved because it is regulated primarily by the renin-angiotensin system, not ACTH.

Adrenal insufficiency requires treatment with glucocorticoids and, in primary adrenal insufficiency, mineralocorticoids too. Failure to manage it can lead to life-threatening adrenal crises, especially during stress.

NICE states that we should suspect adrenal insufficiency when there are unexplained suggestive symptoms, bearing in mind that many of these symptoms are non-specific. They include:

  • weight loss and lack of appetite
  • nausea, vomiting or diarrhoea
  • dizziness, hypoglycaemia and hypotension
  • salt craving, hyponatraemia and hyperkalaemia and
  • lethargy, and muscle weakness

We should also suspect adrenal insufficiency in people with unexplained hyperpigmentation, although hyperpigmentation may not be seen on black or brown skin. In these cases, we should ask the person if they have noticed a change in their skin colour and we should assess the buccal mucosa or any surgical scars.

When do we get this hyperpigmentation? This only happens in the case of primary adrenal insufficiency, when ACTH levels are high. ACTH and melanocyte-stimulating hormone (of MSH) share the same precursor, so when ACTH levels are high, MSH levels also increase with the subsequent increase in melanin.

One common cause of adrenal insufficiency occurs due to adrenal suppression in people who have recently stopped prolonged glucocorticoids by any route. Prolonged means 4 weeks in adults and 3 weeks in children.  However, it can also happen to those who are still taking steroids and have had an episode of physiological stress

Considering this, how should we taper off steroids to prevent adrenal insufficiency?

Well, the first thing that we need to understand is the concept of physiological equivalent dose, which is the dose of glucocorticoid that is equivalent to the amount that a healthy adrenal gland would normally produce. For adults this is a total daily dose of 3 mg to 5 mg of prednisolone, or of 0.5 mg of dexamethasone. In children the calculation requires the use of a complex formula.

So, for someone taking steroids for more than 4 weeks (or 3 weeks in the case of children), in order to taper off the dose safely, we should first reduce the dose gradually to a daily physiological equivalent dose. Then, we should give that dose every other day for 2 weeks, then then twice a week for 2 weeks and then stop, always taking into account that this decision should be made by the clinical team who initiated the treatment for whichever condition the steroids were prescribed for.

However, for people taking steroids for more than 12 weeks, a slower dose-tapering regimen is recommended. For example, for people taking prednisolone, once the daily dose is 3 mg, we are advised to follow the Imperial Centre for Endocrinology prednisolone withdrawal regimen. I have put the link to this in the episode description but the regimen looks like this, where we give patients, a schedule indicating what dose to take each day of the week depending on whether they are in week 1, 2, 3, etc. It takes 7 weeks to reduce the dose from 3 mg to 2 mg using this schedule and, similarly, thereafter, so a total of 21 weeks to reduce from 3 mg to zero. If the starting dose is 5 mg of prednisolone, then a slightly different regimen is followed where the reduction of the dose to zero is over 24 weeks.

As the initial investigations for adrenal insufficiency, we will offer an 8 am to 9 am serum cortisol test, bearing in mind that we should not do this test if taking oral glucocorticoids at physiological equivalent doses or above, because the cortisol levels will be suppressed.

In addition, other routes such as inhaled, intramuscular or topical steroids, may also cause a low cortisol level.

People taking oral oestrogen will have a falsely elevated cortisol so we should stop oral oestrogens for 6 weeks before checking it. If the oral oestrogen is taken for HRT, we will be able to switch to a transdermal preparation.

Once we get the results, if the cortisol level is:

Below 150 nmol/L, then the person may have adrenal insufficiency and we should refer them to endocrinology, urgently in the case of children.

If it is between 150 nmol/L and 300 nmol/L, then the probability of adrenal insufficiency is uncertain and we should repeat the test. If it remains at this level, we will seek specialist advice.

If it is above 300 nmol/L then adrenal insufficiency is very unlikely

The Routine pharmacological management is with Corticosteroid replacement, offering hydrocortisone or prednisolone, and we will add a mineralocorticoid like fludrocortisone for people with primary adrenal insufficiency or congenital adrenal hyperplasia. We will be seeking specialist advice so I will not cover any more of the treatment here.

If there are symptoms of adrenal insufficiency while tapering the dose below a physiological equivalent dose, we will prescribe double the physiological equivalent glucocorticoid dose daily until symptoms resolve, then we will reduce to a daily physiological equivalent dose for 1 week and then use a slower tapering regimen. If symptoms still develop using this slower regimen, then we will need further investigations such as checking serum cortisol levels.

Patients with adrenal insufficiency should be given an emergency kit containing an intramuscular hydrocortisone injection for emergency use in the case of a suspected adrenal crisis.

People having an adrenal crisis should immediately go to hospital by ambulance without needing a referral.

So that is it, a review of the NICE updates relevant to primary care.

We have come to the end of this episode. Remember that this is not medical advice and it is only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.

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