IRISH DERM TUTOR

Introduction

Management

General advice

Topical

Antibiotics

Combined oral contraceptive pill

Spironolactone

Isotretinoin

Acne variants

Acne conglobata

Acne fulminans

SAPHO (and other syndromes)

Gram negative folliculitis

Pyoderma faciale

Acne associated with endocrine issues

Androgen production females

Causes hyperandrogenism

Baseline investigations hyperandrogenism

PCOS

Acne is a chronic disorder of the pilosebaceous apparatus

Greater than 90% of adolescents will get some form of acne with 10% being classed as severe

Peak age onset: 14-17 girls, 16-19 males

It mainly resolves by the mid-20s but about 10-20% persist into adulthood

Is more prevalent and more severe in male teenagers

But can be more frequent and persistent in adult females

Acne is characterised clinically in increasing severity by:

1/Commedones (whiteheads and blackheads)- dilated pores with blockage of openings by hyperplasia of cells

 2/Papules and pustules (papulopustular acne)

 3/Cysts and nodules (nodulocystic acne)

4/Scarring

4 main pathogeneic factors:

Hypercornification of pilosebaceous unit

Increased sebum production (high levels androgens aid in stimulating the sebaceous gland)

Dysbiosis in the pilosebaceous follicle with activation and thriving of Propionibacterium Acne

Increased inflammation (both an innate and cellular inflammatory response)

Hypercornification of the pilosebaceous unit:

• The skin cells in the infundibulum proliferate too quickly and are sticky so they don’t slough off as they should. This causes a blockage of the pores.

At the same time get increased sebum production:

• Androgen secretion is under hormonal control

• Androgen receptors are located on the sebaceous gland in the outer root sheath

• Androgens (like the potent DHT) binds to these receptors to stimulate sebum production

• This increased sebum gets trapped under the clogged pores and plays a key role in acne and is why acne tends to occur in sebaceous areas of the face, cheset and back

The combination of abnormal keratinisation and increased sebum leads to the formation of the commedone

The increased sebum and hypekeratosis is a perfect reservoir for Proprionibacterium acnes proliferation

Inflammation occurs as the body responds to the P acnes and you get inflammatory appearing papules and cysts

This can lead to marked inflammation with rupture of the apparatus leading to the formation of nodules and cysts and increased chance of scar formation

Scarring is the end result of acne that we would like to avoid

Post-inflammatory hyperpigmentation or post-inflammatory erythema is often seen after an acne lesion is resolved and is not true scarring. Appearance often improves with time once inflammation is settled

Atrophic Scars: Depressed scars due to collagen loss.

• Ice Pick: Deep, very narrow scars that extend into the dermis. They look like small, narrow holes, similar to puncture wounds, and are usually less than 2mm wide

• Boxcar: Wider, U-shaped scars with sharp edges. They can be shallow or deep

• Rolling: Wide scars but edges are not sharp giving the skin a wave-like or rolling appearance.

Hypertrophic and Keloid scars: Raised scars due to excess collagen.

• Hypertrophic: Raised but confined to the original wound

• Keloid: Larger and extending beyond the area of the initial injury

  • Hypertrophic: Raised but confined to the original wound

  • Keloids: Larger, extending beyond the initial injury

Should wash face with an appropriate cleanser twice daily rather then soap as soap can be irritating - patients can ask pharmacist for advice on an appropriate cleanser to use for acne. The cleansers should be non-alkaline.

Minimise application oils and cosmetics to affected skin which can create blockages in the skin’s hair follicles (if using make up use ‘non comedogenic’ make up)

Remove makeup at the end of the day

Avoid picking/scratching spots

Point them towards helpful websites about how to look after acne prone skin:

Acnesupport.org.uk (in association with the BAD)

AAD website: Skin care for acne prone skin (https://www.aad.org/public/diseases/acne/skin-care - can ask them to google ‘AAD skin care for acne prone skin’

For mild acne may get away with just a topical agent or in moderate acne you should continue to use a topical agent while using a systemic agent

Topical agents are most suitable for facial acne

Often advise to use at night to affected areas

Counsel patients it will take 4-6 weeks to start to work and they should have at least a 3-month trial

Adherence can often be a reason for lack of effect

All treatments can be irritant so if it is too irritating could consider using it only a few times a week and build it up to daily as tolerated or washing the cream off after an hour and gradually increase the exposure time

If you are using another product after applying the acne treatment wait 15 minutes to give time for your skin to absorb the treatment

Benzoyl peroxide:

Peeling action to relieve and release blackheads (keratolytic), also some mild antibacterial effects

Start at 5% and increase to 10% if needed

Warn patient it can bleach bedding and clothing so should use white sheets, towel etc to avoid this

Topical retinoids:

Aid expulsion of existing comedones and prevents formation of new commedones

Eg Adapalene (aka differin)

Is less likely to cause harm to an unborn child then oral retinoids but as a precaution must not be used during pregnancy and by women planning to have a baby

Warn regarding irritancy, photosensitivity (perhaps use at night), peeling/dryness and need to moisturise

Topical antibiotics:

Anti-inflammatory effects and antibacterial effects (should combine topical antibiotics with benzoyl peroxide to decrease antibiotic resistance)

Also should avoid concomitant use with oral antibiotics

Topical azelaic acid (15% or 20% twice daily):

Is another topical agent that can be used if considering using an oral tetracycline in moderate to severe acne (I haven’t used this too much in practice)

If using a single topical agent consider a topical retinoid (good if commedonal only) or benzoyl peroxide (patient can get without script)

Combination topical treatments are useful:

Epiduo (BPO and Adapalene) once daily in evening

or

Duac (BPO and Clindamycin) once daily

or

Treclin (Tretinoin and topical Clindamycin) once daily

When the patient has not responded to topical agents, if the acne is moderate to severe or the acne is widely distributed to involve back, neck and chest you may then consider an oral antibiotic

Course of oral antibiotics should be at least 3-4 months as it takes time for medication to have an effect

Stop if clear after this course and just use a topical treatment

Otherwise can repeat up to 6 months with oral antibiotics

Ideally would stop treatment after 6 months but there are some cases where people remain on them for longer

You should always combine oral antibiotics with topical treatment (benzoyl peroxide or topical retinoid) to improve efficacy

1st line: Tetracyclines

Lymecycline (aka tetralysal) 408mg od often a good first line drug- very tolerable medicaton

Doxycycline 100mg od (but warn of increased risk of photosensitivity and advise non-commedogenic sunscreen)

Oxytetracycline 500mg bd (once daily dosing of others more convenient)

Minocycline effective but no longer considered a 1st line therapy as can have more serious side effects- hypersensitivity, hepatic dysfunction, lupus like syndromes

The tetracyclines can rarely cause benign intracranial hypertension. This is also a potential side effect of isotretinoin you need a 2-week wash out period between stopping the tetracycline and starting isotretinoin

Don’t give tetracyclines until the age of 12 (when permanent teeth should be in) as if given before can cause permanent staining of these teeth

Tetracycline absorption is affected by antacids so take them with food

2nd line: Macrolides

Erythromycin 500mg bd (less often clarithromycin 250mg bd)

1st line in pregnancy and in children under age of 12

Can sometimes be used if tetracyclines not effective

Some strains P acnes have now been found to be resistant to erythromycin

Others antibiotics:

Trimethoprim 300mg bd (unlicensed) - this antibiotic of course can be associated with significant side effects including severe drug rashes so often caution is used when considering this

Can be useful in the treatment of acne based on their anti-androgenic properties but their are risks associated with the use of the COCP

MoA COCP acne:

The combined oral contraceptive pill (COCP) contains an oestrogen (ethinylestradiol) and a progestin

Its MoA is based on the COCPs overall anti-androgenic properties (all OCPs are overall anti-androgenic regardless of how androgenic the progestin is)

Oestrogens:

• Decrease the formation of ovarian and adrenal androgens (ovaries sense increased oestrogen in so reduce production of sex hormones)

• Increase sex hormone binding globulin (sHBG) which (reduces free androgens in the serum)

• Reduce 5-alpha reductase activity and blocks the androgen receptor

The progesterone-only pill can actually make acne worse so is not good for the management of acne

Classes of COCP:

Based on the type of progestin used

2nd generation (More androgenic, decreased risk of thromboembolism)

• Levonorgesterol

• Norethisterone

3rd generation (Less androgenic, increased risk of thrombembolism)

• Desogestrel

• Gestodene

• Norgestimate

4th generation (Less androgenic, increased risk thromboembolism)

• Drosperinone (an anti-androgenic progestin)

Co-cyrpindol (aka dianette): An oestrogen combined with the anti-androgen cyproterone acetate is often used

Due to limited evidence it can be difficult to make recommendations on the most effective choice of contraception in acne

A 2012 Cochrane meta-analysis found few important differences between the different COCPs in their effectiveness for treating acne

Although some studies have suggested the more anti-androgenic COCPs are more effective in treating acne then levonorgesterol (2nd generation)

How they compare with alternative acne treatments is not clear

FDA approval for all combined OCPs for acne specifies that they are only approved for the treatment of acne in women who also desire contraception

NICE guidelines:

‘If a person receiving treatment for acne wishes to use hormonal contraception, consider using the combined oral contraceptive pill in preference to the progestogen-only pill’

NICE CKS (clinical knowledge summaries) - updated May 2023

‘Co-cyprindiol (Dianette®) or other ethinylestradiol/cyproterone acetate-containing products may be considered in moderate to severe acne where other treatments have failed but require careful discussion of the risks and benefits with the patient’

‘Use should be discontinued 3 months after acne has been controlled’

In general in the dermatology clinic we will ask the patient to discuss with their GP the most appropriate choice of combined OCP for them

Adverse effects:
All combined OCPs are associated with with an increased risk of VTE

The size of the risk is highest during the first year of treatment or when switching/starting after a pill free period of at least 1 month

Studies have shown that the incidence of VTE for combined OCPs containing 30-35ug ethinyloestradiol and the progestin cyproterone acetate, desogesterl/gestodene (3rd gen) or drosperinone (4th gen) are similar

The risk with the above is about 50-80% higher compared to the combined OCP with levonorgesterol (1st gen)

Other cardiovascular risk (generally uncommon in women of reproductive age):

• Myocardial infarction (risk only increased if have risk factors like smoking, DM, Hypertension)

• Stroke (smoking, hypertension, increased age increase risk)

May be slight increased risk of breast cancer +/- cervical cancer

Cases where it is deemed risks outweigh benefits include:

Patients aged ≥ 35 who smoke ≥ 15 cigarettes a day

Patients with cardiovascular risk factors such as Hypertension, DM, Smoking, Older age

History of hypertension

History of DVT/PE

History of IHD, CVA

Current breast cancer, hepatocellular carcinoma or malignant hepatoma

Severe cirrhosis

Aldosterone antogonist

Works on acne due to its anti-androgenic properties

It inhibits 5a reductase which normally converts testosterone to its more potent DHT

Like the OCPs it is also anti-androgenic by increasing sHBG

Is generally well tolerated

Dose: 50-200mg per day

CI:

Renal insufficiency

Hyperkalaemia

Pregnancy

Abnormal uterine bleeding that has not been worked up

Black box warning: Strong family or personal history breast cancer

Adverse effects:

Hormonal

• Menstrual irregularities

• Gynaecomastia

• Breast tenderness (not good for males)

Diuretic effects

• Dizziness

• Headaches

• Frequent urination

• Hyperkalaemia

For patients should probably do a baseline U&E looking at kidney function and potassium and consider a blood pressure

For the hyperkalaemia there is variation about how often to screen.

Recent literature has suggested no need to monitor if are 18-45 years old, has no known renal disease, has no congestive cardiac failure and is on no medications affecting the RAA system

In scenarios where patients are not monitoring bloods - screen and warn against high potassium diets (bananaas, coconut water, potatoes, salt substitutes)

Should also warn patients about potential drop in blood pressure so if getting dizzy on the current dose consider decreasing it

If monitored - often checked every 3-6 months and with dosing changes

(aka roaccutane)

Oral retinoid

Vitamin A derivative

Targets all major pathogenic processes in acne

Comes in 5mg, 10mg, 20mg, 40mg depending on manufacturers

Soya oil is in some brands of isotretinoin so soya allergy can be considered a contraindication (also be cautious with peanut allergies) and if patients report peanut or soya allergy check with local department if they have guidelines in place for this

Indications:

• Severe acne with nodulocystic acne

• Acne with scarring

• Persistent acne that has failed to respond to antibiotic therapy

• Acne associated with psychosocial disability

Dosing regimes can vary between prescribers so should check with your own department if their is a isotretinoin prescribing protocol

One such regime could be a starting dose of 0.5mg/kg for 4 weeks followed by 1mg/kg for 12 weeks

Usual course is about 4-6 months but may be longer if particularly difficult to treat acne or if have started at a lower dose then above

Patient should be given a BAD isotretinoin leaflet and also the Isotretinoin information package insert when considering isotretinoin and this should be documented

Dosing:

Again this will be depending on the department - some people will go with the above regime or some people will aim for target dosing as below

Target dose usually 120-150mg/kg (although in some instances may need to go above this eg 180mg/kg)

So for instance in a 60kg patient the maximum target dose in one course would be 150 x 60 = 9000mg

So in regime noted above:

1st 4 weeks at 30mg (0.5mg/kg) - 30 x 28 = 840mg

Following 12 weeks 60mg (1mg/kg) - 5040mg

So with this course it means they would have had 5880mg

Therefore could potentially have another 2 months of the medication before gets to 150mg/kg (9000 - 5880 = 3120mg)

Adverse effects:

Potent teratogen:

• Most important consideration in female patients is its teratogenicity

• Counsel them regarding the potent teratogenicity and document it clearly in the patient letter and at each visit

• They should be advised to use an effective method of contraception (OCP, implant, coil, injection) PLUS a barrier method

• Contraception should start 1 month before treatment and continue till at least 1 month after stopping treatment (ideally start it on 2-3rd day of menstrual cycle but if have irregular periods not always easy to achieve)

• They need to come in for a pregnancy test every month before they are given the next monthly prescription and come in 5 weeks after treatment cessation for a final pregnancy test

• In the UK get them to sign a ‘Pregnancy Prevention Programme’ certificate which states all the above considerations

Mood issues (and sexual dysfunction)

• Link between depression and suicide is unclear despite multiple systematic reviews

• Many systematic reviews fail to identify correlation between isotretinoin use and suicidal behaviour

• Other studies (eg Bremener et al, 2005) suggest there is a link

• In fact, a patient’s mood can often improve post roaccutane as their acne is clear and their self esteem improves

• In general it is important to ask about symptoms of depression prior to starting

• If there is any significant history of mood issues (eg prior self harm, thoughts of self harms, suicidal ideation or a significant personal history of depression or severe family history of depression) you may want to liaise with psychiatry prior to commencing treatment

• It is important to inform them of the potential association and ask the patient (and perhaps parents) to be mindful of this association and if there are any concerns about mood changes or the patient becoming withdrawn that they should stop the isotretinoin immediately and contact the department

• Isotretinoin package leaflet states risk as:

  • 1/1,000 - depression, existing depression worsening, increased violence aggression

  • 1/10,000 - thoughts of self harm, suicidal ideation, attempted suicide, suicide

• EADV Dermatology forum acne guidelines state:

  ‘In light of continued uncertainty with respect to isotretinoin depression and suicidal behaviour, caution and giving patient information appear reasonable’

• See recent report from commision on human medicines below for more recent evidence

However, it is the evidence is not well defined report was released by the commission on ‘human medicines isotretinoin expert working group in April 2023 may change practice.

The group were tasked to look further into reporting and estimated side effects of isotretinoin and in particular the effects on mental health and sexual dysfunction.

In essence they felt the risks of psychiatric and sexual side effects were currently unclear but may be greater than previously estimated, highlighting the need for better information and monitoring of patients. Frequencies are now listed as "not known" until more research provides robust data.

Here is a of the key points regarding the risks of depression and sexual side effects associated with isotretinoin:

Depression Risk

• The current product information states depression may occur as a rare side effect (up to 1 in 1000 patients).

• However, the expert working group felt this underestimates the risk, as depression is more common in the general population.

• They recommended changing the frequency to "not known" as there is insufficient data to accurately estimate the risk.

• This does not mean the risk is higher or lower than stated before, just that the true risk is unclear.

• The risk could potentially be greater than previously thought, especially in younger patients.

Sexual Side Effects

• Patients reported erectile dysfunction, reduced libido, vaginal dryness and other sexual problems during and after isotretinoin treatment.

• The product information will now include warnings these may persist after stopping treatment.

• Specific side effects to be listed are erectile dysfunction, reduced libido, vaginal dryness, orgasm difficulties and genital numbness.

• Frequencies are not known for these side effects.

• Under-reporting is likely due to the sensitive nature of sexual side effects.

• More research is needed to accurately establish the risk of sexual side effects in both males and females.

An additional recommendation from the group was that two different prescribers should confirm treatment is apporpirate before it is started in people under the age of 18

Also, there needs to be more consistent monitoring of all patient’s psychitric and sexual health

They also recommended further research is required to look at these side effects

Raised LFTs or Lipids

• Reversible on stopping

• Should do FBC, U&E, LFT, Lipids at baseline and repeat at 6-8 weeks

• If normal no need to do thereafter

Other side effects:

Marked dryness of skin,mucous membranes (especially lips) and increased risk nose bleeds

Contact lens issues (due to dryness of eyes)

Increased photosensitivity

Fragile skin - advise against waxing, piercing, tattooing, chemical dermabrasion or cutaneous laser treatment during treatment for at least 6 months after treatment (risk of epidermal stripping, hypertrophic scarring or post-inflammatory pigmentation issues)

Risk of paronychia (infection at base of nail)

Muscle aches and pains (may affect performance if doing sports at an elite level)

Hair thinning (usually reversible)

Decreased libido and impotence in men

Need to avoid Vitamin A supplements (risk of Vitamin A toxicity)

Mild headache

Benign intracranial hypertension

• Rare

• Get persistent headache (unresponsive to simple analgesia), nausea, vomiting and visual disturbance

• Should be examined for papilloedema and referred for urgent neurological advice

• Tetracyclines also have increased risk of this so need a 2 week wash out period from when they stopped a tetracycline to when they start isotretinoin

Night blindness

• Can develop a form of night blindness

• Regarding pilots:

  • They cannot be certified while on treatment with isotreitnoin and they are made unfit to fly until they are off treatment for 2 weeks. At that stage they will need reassesment prior to certification

  • Dark adaptation may be affected permanently in some individuals so might jeopardise career choice if any patient may be considering to become a pilot

• Regarding HGV drivers:

  • There is no legal requirement for people in driving profession to inform the DVLA while they are being treated with isotretinoin

  • However need to make these patients aware about the possibility of night blindness and reduced dark vision adaptation

  • If they develop night vision problems they need to stop driving, inform the dermatologist and arrange formal testing of vision

  • If night blindness is confirmed they then must inform the DVLA

A recent report (April 2023) from the commission on human medicines (Isotretinoin expert safety review) has reviewed the available scientific data and safety information related to suspected psychiatric and sexual side effects associated with isotretinoin

The working group concluded that the balance between benefits and risks of isotretinoin remains favourable but better information, monitroing and additional oversight of the start of treatment for patients under 18 would help minimise further risk

Recommendations include:

1. Better information Patients and their families should receive better information about the risks of isotretinoin so that they can make an informed decision before using this medicine.

2. Better monitoring There should be more consistent monitoring of a patient’s psychiatric and sexual health so that any problems are spotted earlier and there are defined routes for patients to receive help.

3. Better checks There should be tighter controls on first prescribing isotretinoin to young people (aged 12 to 18) so that it is only started when doctors agree the acne is severe enough to justify it and that other standard treatments have been sufficiently tried and haven't worked.

4. Better communication Patients should receive information about the risks of isotretinoin earlier, before they have a full discussion with a specialist dermatologist (an acne specialist). Patients and their families will then have more time to fully consider the benefits and risks of isotretinoin.

All healthcare professionals involved in the care of patients should keep each other informed about any suspected side effects they become aware of in a particular patient.

Form of severe nodulocystic acne with interconnecting abscesses and sinuses which result in hypertrophic (thick) and atrophic (thin) scars.

Do not get systemic symptoms in acne conglobata

Can be associated with follicular occlusion tetrad

1. Acne conglobata

2. Hidradenitis suppurativa

3. Dissecting cellulitis of the scalp

4. Pilonidal sinus

To treat acne conglobata you: may give the patient a short course of oral steroids (eg 0.5mg/kg) when starting/prior to starting the isotretinoin to prevent a flare up which could lead to acne fulminans

You may also consider starting with a lower dose of isotretinoin and using erythromycin at the same time

Remember you can’t use tetracyclines with isotretinoin due to risk of benign intracranial hypertension

Severe form of acne conglobata associated with systemic symptoms

Nearly always in adult adolescent males

Get severe acne with nodules and scarring, fluctuating fever, joint pains, malaise, and lymphadenopathy

Can even get osteolytic bone lesions of the sternum and clavicle

Can get elevated WCC and inflamm markers

Again you will need prednisolone to get it under control and you usually start with a low dose of isotretinoin which you slowly increase the dose of

SAPHO:

Suspect in people who have a pustular skin condition and rhumatic pain

• Synovitis (inflammation of the joints)

• Acne (conglobata or fulminans)

• Pustulosis (thick yellow blisters often on palms and soles much like palmoplantar pustulosis)

• Hyperostosis (increase in bone substance)

• Osteitis (Bone inflammation)

  Other skin problems - Hidradentitis suppurative, dissecting cellulitis scalp

  Bone issues:

  • Often get pain, swelling and tenderness of the sternum

  • Clavicles frequently enlarged on X-ray

  • Bone biopsy can reaveal abscesses (sterile osteomyelitis)

Other syndromes with acronyms:

PAPA - Pyogenic arthritis, Pyoderma gangrenosum and Acne

PAPASH - Pyogenic arthritis, Pyoderma gangrenosum, Acne and HS

Acne can be complicated by a gram negative folliculitis

Affects patients that have been on long term broad-spectrum antibiotics

Typically a patient is on oral antibiotics for the acne that has been recently discontinued after resoultion or switched to a different antibiotic

Get centrofacial pustules (especially perinasal pustules

• Can get superficial pustules (type 1 > 80%) due to klebsiella, e coli, serrataia and citrobacter species or

• Deep-seated nodules and suppurating abscesses (type 2) due proteus species (motile and can invade deeply)

In part due to the change in balance between the gram +ve and -ve bacteria in the nose after prolonged broad-spectrum antibiotic therapy

Diagnosis: Bacterial swab of the new pustules looking for gram negative bacteria

Treatment:

Isotretinoin (reducing seborrhoea reduces the counts of gram-negative organisms colonising the nose)

Can resemble severe acne or rosacea

Tends to occur in young, adult women

It starts abruptly and rarely persists much more then a year

Does not arise fro comedones and is confined to the face

Get unsightly pustules and nodules on red areas of cheeks, chin and/or forhead. May scar.

Treatment may include  antibiotics, isotretinoin, systemic steriods

Only investigate for endocrine abnormalities in certain cases

Primarily indicated for patients with clinical features or a history of hyperandrogenism

Growth charts and a hand film for bone age are good screening tools in prepubertal children

Androgens can be produced in the skin but most circulating androgens are produced elsewhere (mainly the ovary and adrenal gland)

The major androgens in the serum of normoandrogenic women (in descending order are):

• DHEAS

• DHEA

• Androstenedione

• Testosterone

• Dihydrotestosterone

Adrenal gland:

Hypothalamus secretes CRH

Then the pituitary secretes ACTH which stimulates the production of the androgens DHEA, DHEAS and Androstenedione by the below pathway

As you can see the androgens are on the right

Notice that if have a 21a hydroxylase deficiency you cannot make as much aldosterone (mineralocorticoid) or corisol (corticosteroid) and as a result you make more androgens

This is seen in adult onset congenital adrenal hyperplasia

Also note that 5a reductase converts testosterone to the more potent dihydrotestosterone

Ovaries:

Hypothalamus secretes GnRH

Then the pituitary secretes LH and FSH

LH stimulates ovarian theca cells to convert cholesterol into testosterone

Some of this is released into the circulation

The rest if converted to oestrogens in the ovarian granulosa cells

• High levels of cicrulating androgens

• Low levels of SHBG

• Increaed conversion of weak androgens to DHT by type 1 5a reductase in the sebaceous gland

• Higher sensitivity of skin to DHT

• Effects of insulin and IGF-1

High circulating androgens due to:

Ovarian source

• PCOS

• Benign or malignant ovarian tumours

Adrenal source

• Congenital adrenal hyperplasia (most commonly the late onset variant due to deficiency of 21a hydroxylase)

• Benign or malignant adrenal tumours

Pituitary source:

• Cushing syndrome (increased ACTH)

• Acromegaly (increased GH and IGF-1)

• Prolactinoma (prolactin can stimulate adrenal gland)

Obesity and the metabolic syndrome:

• More androgens are made by the adrenals and body fat in response to the release of insulin and IGF-1
  
  
  

Hirsutism is more closely associated with elevated androgen levels than acne or FPHL and may warrant additional evaluation in absence of other signs of androgen excess

Best time to test is within first 7 days of menses (when androgens are highest)

Can’t be on hormonal treatment when doing investigations - would need to stop oral contraceptive pill 6 weeks before testing

LH/FSH

• Elevated LH and LH:FSH ratio traditionally considered as important in diagnosis of PCOS

• But not part of diagnostic criteria

• Also significant proportion of women with PCOS don’t have this abnormality

Oestradiol

Total Testosterone

• If very elevated need to consider androgen secreting tumour

SHBG

Free testosterone (free androgen index)

• Calculated from total testosterone and SHBG levels (100 x total testosterone/SHBG)

• Most sensitive means to measure free testosterone (better marker then total testosterone)

DHEA-S

• Represent reservoir of ciculating testosterone and DHT

• Little diurnal variation

• Useful in evaluating adrenal androgen production

17a hydroxyprogesterone

• Raised in late onset congenital adrenal hyperplasia

Prolactin

TFT (rule out hypohtyroidism as a mimic)

Consider:

Growth hormone, Insulin-like growth factor (but probably should involve endocrine if considering as is complex area)

Pelvic US (evaluate ovarian cysts)

When to test:

It can sometimes be difficult to know when to do a hormonal workup as acne is such a common sign

Some times to consider it:

• If have ance and another cutaneous sign of hyperandrogenism (eg hirsutism, female patter hair loss)

• Acne and associated menstrual issues

• Resistance to isotretinoin therapy

• Frank virilisation

Occurs in 6% of females of reproductive age

Get elevated androgens of ovarian origin

Diagnosis requires 2 of 3 of the following:

1. Androgen excess (clinical or biochemical)

2. Ovulatory dysfunction (oligo- or anovulation)

3. Polycystic ovaries (ultrasound findings)

   So technically in adolescents a diagnosis may be made based on hyperandrogenism (clinical or biochemical) and the presence of persistent oligomenorrhoea without US findings

There is also an association with PCOS and obesity and insulin resistance

Biochemical abnormalities PCOS:

Total testosterone - normal to moderately elevated

sHBG - normal to low

Free testosterone - normal or elevated women

LH:FSH ratio may be raised (but not always)

When diagnosing PCOS should exclude:

Other entitites that cause oligomenorrhoea/amenorrhoea:

• Premature ovarian failure - LH and FSH may be raised

• Hyperprolactinaemia - can cause a syndrome with irregular periods and polycystic ovaries so should be excluded

• Hypothyroidism - so may do TFT

  
  
  
  
  
  

Other causes of hyperandrogenism:

• Congenital adrenal hyperplasia

  • Inherited disorder adrenal steroidogeneis

  • Can’t produce as much cortisol or mineralocorticoids due to enzyme deficiency (eg 21a hydroxylase)

  • Get increased compensatory ACTH leading to increased steroid precurors (17a hydroxyprogesterone) which leading to increased androgens

• Androgen-secreting tumour

  • Worrying signs are signs of virilisation such as deep voice, reduced breast size, increased muscle bulk, clitoral hypertrophy

  • Total testosterone will be significantly raised > 5.2mmol/l

• Cushings syndrome

  • Myopathy, striae, bruising

  • Consider screening if concerned