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Flashcards in Endocrinology Deck (106):

What are the causes of hyerpnatraemia (name 5)?

1) Insensible loss in unconscious patient, e.g., sweating, vomiting, burns.
2) Diabetes Insipidus.
3)Osmotic coma, e.g., diabetic coma.
4) Conn's syndrome (hyperkalaemic acidosis)


What are the symptoms of hypernatraemia (4)?

-If severe, cerebral haemorrhage or thrombosis may occur.


How should hypernatraemia be Rx?

Dehydration and low sodium should be corrected slowly, over a 48 hr period at least. The more extreme the derangement, the slower this should be. Oral rehydration is preferable, but often has to be IV.


If IV fluids are used to correct a high sodium, what fluid should be used?

Ongoing debate! Some clinicians use 5% dextrose (guided by repeated sodium levels and urine output), others use 0.9% saline (as this is hypotonic in a hypernatraemic patient).


What is the result of excessively rapid rehydration of someone with hypernatraemia?

It can result in cerebral oedema.


What are the causes of cerebral oedema? (List 5)

1) Acute hepatic failure.
2) Benign intercranial hypertension.
3) Raye's syndrome.
4) Excessive fluid infusion in a dehydrated/hypernatraemic patient.
5) Poor fluid management in someone with hyponatraemia.


How does cerebral oedema appear on a CT?

As a hypodense area.


Different forms of cerebral oedema are described (not caused!) what are they?

1) Vasogenic - caused by excessive protein-rich fluid leaking into the extracellular space through damaged capillaries. It especially affects white matter. Sometimes it can be Rx with corticosteroids.
2) Cytotoxic - damage to neurones and glial cells leads to leakage.
3) Interstitial - CSF leaks into the extracellular space, e.g., non-communicating hydrocephalus.


At what pressure do clinical signs of cerebral oedema start to appear?

Around 30 mm Hg


What happens if the process of cerebral oedema is not arrested?

Respiratory arrest and death from brainstem coning occurs.


What device is sometimes used to anticipate and prevent the bad consequences of developing cerebral oedema?

ICP bolt - inserted by the neurosurgeons, and managed by ITU.


What is a normal cerebral pressure, i.e., when no cerebral oedema is present , if a bolt were inserted, what would the pressure be?

0-1mm Hg


Other than bolts, what treatments exist for cerebral oedema?

Mannitol used to be used. It is not routinely used anymore as it can possibly result in reduced cerebral perfusion. It is also potentially nephrotoxic, so UO must be monitored hourly.
Steroids are sometimes used in certain circumstances.
Barbituates (e.g., theiopentone) - however may cause haemodynamic disturbances and mask the clinical effects of cerebral oedema.


When might steroids be used to treat cerebral oedema?

Only if the cerebral oedema is secondary to tumour or abscess but never due to trauma.


How should patients with cerebral oedema be positioned?

Flat, or with the head raised no more than 30 degrees from the horizontal, as further elevation produces paradoxical elevation in ICP.


How can control of respiration be used to treat cerebral oedema?

Hyperventilation - reduces PCO2 to 3.5 Pa as this causes vasoconstriction and may reduce cerebral oedema.


What is galactosaemia?

A rare autosomal recessive condition caused by the absence of an enzyme, galactose-1-uridyl transferase. This results in the accumulation in cells of galactose-1-phosphate, which is highly toxic. The incidence in the UK is about 1/60,000.


If an infant is normal at birth, but on commencement of milk feeds they suffer from 4 complaints, what should be suspected? What are those 4 complaints?

Jaundice, vomiting, diarrhoea, and failure to thrive.
The condition is galacotsaemia.
It can result in cataract formation (it is one of the causes of bilateral cataracts in infants), psychomotor retardation, hepatosplenomegally, renal disease, increased susceptibility to infection, and hypoglycaemia after exposure to galactose in the diet.


If galacotsaemia is suspected in a newborn, what investigations would support the diagnosis?

Raised plasma galactose.


What proportion of premenopausal women have hirsuitism? What is the most common cause?

1 in 10!
Most common cause is PCOS, but there are lots of others, so important to stay alert to other possibilities.


What are the possible causes of hirsuitism? (12)

1) Idiopathic
2) PCOS (over 70% of cases)
3) Menopause/primary ovarian failure.
4) Congenital adrenal hyperplasia.
5) Pituitary tumours: Cushing's disease, acromegaly, hyperprolactinaemia.
6) Cushing's syndrome.
7) Androgen-secreting tumours: adrenal, ovarian.
8) Insulin resistance syndrome.
9) Hypothyroidism.
10) Obesity.
11) Porphyrias.
12) Medications, e.g., steroids, sodium valproate, phenytoin, danazol, minoxidil, progestogens.


What is minoxidil?

Topical minoxidil is used sometimes in the treatment of androgenic alopecia. It causes hair growth. (It is one of the causes of hirsuitism).
It mode of action involves dilation of arterioles.
Results of the use of the drug are variable, and it often has to be continued for long periods.


What is danazol? What is it used for? (2 main uses)

A testosterone derivative which suppresses the LH surge, inhibits ovarian steroid genesis, reduces plasma levels of sex hormone binding globulin (and therefore increases levels of free, unbound testosterone).
The main use is in endometriosis, where it creates a high androgen, low oestrogen environment which does not support the growth of endometriosis. Usually used for 6-9/12.
The other use is in the prophylaxis of hereditary angioneurotic oedema


What are the characteristics of idiopathic hirsutism?
What is it thought to be caused by?
What ethnicities are most effected?

Regular menstrual cycles are maintained, and there are no other features of androgen excess.
It is thought to be due to an increased sensitivity to androgens.
This type of hirsutism has been reported within families (I.e., likely a genetic element), and is more common in South Asian and Mediterranean ethnicities.


What is the most common cause of hirsutism?
What percentage of hirsutism does it account for?
What percentage of the population does it affect?

It affects 5-10% of premenopausal women.
It accounts for 70% of hirsutism.


What criteria is used to diagnose PCOS, and what are the criteria?

Although there are several criteria, the system that seems most widely adopted is the Rotterdam Criteria.
To qualify as having PCOS, a women must have two out of three of:
1) Ultrasound evidence of polycystic ovaries.
2) Oligomenorrhea (cycle length of 35 days or more) and/or presence of anovulation (for 6 months or more).
3) Clinical and/or biochemical signs of hyperandrogenism.


Other than hirsutism, what are the features of hyperandrogenism? (6)

1) Deep voice.
2) Frontal balding.
3) Cliteromegally.
4) Acne.
5) Increased libido.
6) Malodorous perspiration.


When taking a history of someone with hirsutism, what points should be covered? (9)

1) When the symptoms were first noticed, and age of onset.
2) Features of hyperandrogenism.
3) Areas where hair growth has been noted.
4) How quickly the hair growth has progressed.
5) What methods have been used to control hair growth.
6) Obstetric history (e.g., previous pregnancies, infertility).
7) Menstrual history (age of menarchy, regularity of cycle, possibility of pregnancy, last menstrual period).
8) Any recent change in weight.
9) Medications.


Why does obesity implicated in PCOS - I.e., making it worse, or maybe even triggering it?

Obesity leads to increased insulin resistance, which in turn leads to hyperinsulinaemia.
High levels of insulin have two relevant consequences in this context:
1) High insulin levels encourage the theca cells of the ovaries to produce more androgens.
2) They also cause the liver to produce lower amounts of sex hormone binding globulin-this leads to increased levels of free testosterone (though total levels of testosterone may in fact stay the same).


When considering a diagnosis of hirsutism, what alternative diagnosis should be considered and rejected before beginning to go down the "hirsuitism" path?
How can you differentiate the two?
What, in a general sense, causes hirsutism? (Although, of course, there are many possible sub-causes).

Hirsutism (in general terms) is caused by either an over-production of androgens or an increased sensitivity to them, causing MALE PATTERN HAIR GROWTH.
It should NOT be confused with hypertrichosis, which involves a general excess of hair in a non-androgen distribution, and has a different aetiology.


What is the typical age of onset of hirsuitism?
If it occurs in an infant or a pre-pubescent, is this potentially more or less serious? And what possible causes should be considered in this case?

The typical age of onset can vary from 15-35; it often first appears at the time of puberty and tends to worsen gradually over time.
In an infant or prepubescent, it should be taken MORE seriously; possible causes include hypothyroidism, congenital adrenal hyperplasia, or precocious pubity.


What are the two types of human hair and where are they found?
In hirsutism, which type shows excessive growth.

1) Terminal - dark, course, and thick - typically found on the scalp, eyebrows, eyelashes, and - after puberty - around the groin and axilary areas areas.
2) Vellous hair - soft and brown - covers the rest of the body, except for the palms of hands, soles of fees, and lips.
Hirsutism is the excessive growth of the terminal hair type in females.


Where does hirsutism typically affect, I.e., what areas of the body?

It follows an androgen-dependant (I.e., male) distribution pattern. Face, upper list, chin, chest (including areola), lower abdomen (including linea alba). Also the anterior thighs and buttocks.
Amount of hair depends on the individual and their family, and their ethnic group.


What ethnic groups tend to be more or less affected by hirsutism?

More common - South Asia and Mediterranean ethnicities.
Rarer in - East Asia and sub-Saharan Africa.


What is congenital adrenal hyperplasia (CAH)?

It is an autosomal recessive disorder in which cortisol production is impaired.


How does congenital adrenal hyperplasia present classically and non-classically?

Classical presentation is in childhood with - ambiguous genitalia in girls or precocious pubity.
Non-classic or adult onset CAH is milder - it tends to be picked up in adults, with symptoms of glucocorticoid deficiency and is often noted due to hirsutism. It often mimic PCOS. It is a milder phenotype.


What is the risk of Caucasians developing CAH? What ethnic groups have a higher risk, and by how much?

The risk generally is low - about 0.2-0.3%.
However some populations have a tenfold increased risk these are Ashkenazi Jews, Southern Meddetarranians, and Eastern Europaeans.


In what group of women may identifying Congenital Adrenal Hyperplasia be of especial use, and why?

Women who are trying to get pregnant; this is because treatment with glucocorticoids can reduced the chance of miscarriage.
As this is a genetic condition, pre-conception genetic councils sling Maui be appropriate.


What are androgen secreting tumours, and where do they arise?
Common or rare?
Why is it important to rule out this diagnosis?

It is a tumour of the ovary or testes that secretes androgen.
A cause of hirsutism in women.
It is rare - only about 0.2% of androgen disorders in women - but important to rule out as HALF these tumour are malignant.


What features would make me think, "hang on one damn second - what is this lovely patient sitting on front of me has an androgen secreting tumour?"
What initial hormonal investigation would add weight to this diagnosis?

You should consider it in people presenting with a RAPID ONSET of hirsutism or virilisation, especially just after puberty.
Initially, test FSH and LH - they are both low in CAH.
In AST, testosterone levels are high at 1.5-2x the normal level. Other androgens in the sex steroid genesis pathway are used to help distinguish between CAH and AST.


Why does hypothyroidism lead to hirsutism?

1) It can cause dry, brittle hair that snaps easily.
2) It can include the ratio of anagen to telogen phases (telogen is the phase in hair growth where there is resting of hair production)! While anagen is the active, hair-growing phase)
3) It can reduce the production of SHBG and therefore increase the level of circulating free testosterone.


What is hyperandrogenic insulin resistant acanthosis nigricans (HAIR-AN) syndrome?

It is a inherited condition that may present with features of PCOS.
Severe insulin resistance causes high circulating levels of androgens, which in turn causes acanthosis nigricans. Virilisation may be a feature.
Both insulin resistance and hirsutism may occur and be very difficult to treat in this group.


What is acanthosis nigricans?
Where is it most notable?

A rare condition characterised by brown to black velvety papillomatous hyperplasia of the epidermis with intense hyper pigmentation most prominent in the axilary, infra-mammary, inguinal, and neck creases.
There may also be veruccous patches on the knuckles and other extensor surfaces, and hyperkeratosis of the palms and soles.


How is acanthosis nigricans distributed in contrast to other forms of hyperpigmentation? What other conditions might involve hyperpigmentation?

In acanthosis nigricans, the areas of hyperpigmentation are discrete, which is in contrast with other diseases that cause hyperpigmentation such as Addison's disease.


What life event can occasionally trigger a rare form of hirsutism and why? (2)

1) Pregnancy - transient luteomas or thecomas increase circulating levels of androgens by in erasing ovarian production.
2) Menopause - oestrogen levels tend to fall faster than androgen levels during this time. Also, separately, the rise in LH during this time causes a rise in testosterone levels.


What system is used to attempt to score hirsutism objectively? What areas are looked at? What do different scores mean?

The Modified Ferryman-Gallwey score (FGS).
Scores 9 areas of the body 1-4 based on hairiness.
The nine areas are the upper lip, the chin, the chest, the upper abdomen, the lower abdomen, the upper arms, the thighs, and the buttocks.
A cumulative score above 8 counts as hirsuitism, with a score of 8-15 equalling mild disease, and more than 15 meaning moderate or severe disease.


Before asking about hair/assessing hairiness of a women using the Modified FGS, what should you ask/check first?

The patient may have already tried some method of hair removal; therefore ask about this, and take it into account when scoring, I.e., score as I've the removed hair were present.


When taking a history of someone with hirsuitism, what areas should be covered?

1) Menstrual history.
2) Drug Hx
3) Family Hx.
4) Obviously, all the questions about wheee the hairiness is and when it started.
5) Psychological impact.


What sort of psychological impact can hirsutism have on a women?

It can cause decreased self-confidence, decreased self perception of femininity, anxiety, social withdrawal, and depression.
Negative body image may be present.


When examining someone with hirsutism, as well as checking out exactly how hairy they are and where (I.e., doing a Modified Ferryman-Gallway Scale) what else should be looked for?

Other signs suggestive of conditions that may cause hirsutism.
PCOS is the most obvious; but other signs include:
1) Acne.
2) Acanthosis nigricans.
3) Frontal baldness.
4) Signs of hypothyroidism.
5) Acromegally.
6) Signs of Cushing's disease.


In someone presenting with hirsutism, when and why would a pelvic and/or abdominal examination be appropriate?

Only appropriate if symptoms have developed over the last 6 months or less.
The examination is performed in an attempt to identify if there is any palpable pelvic tumour.
Examination of the external genitalia is NOT indicted UNLESS a patient describes cliteromegally or other virilising features are see.


When should women with hirsutism be investigated further?

1) If the Modified Ferryman-Gallway Scale is more than 15.
2) if there has been rapid symptom onset.
3) If there is menstrual irregularity.
4) Infertility.
5) Acanthosis nigricans.
6) Signs of virilisation.
7) In African or East Asian women, wheee body hair is uncommon, and should be investigated even with a low Modified Ferryman-Gallway Scale score.


What is the most likely diagnosis in most women with mild hirsutism, no other symptoms, and a regularly menstrual cycle?

The most likely diagnosis is idiopathic hirsutism, and in this case no further investigation is usually required.


What is the first line investigation usually performed for hirsutism?

Free testosterone is usually the first Ix performed. This should be taken between day 4-10 of the cycle, as an early morning cycle.
Note though that levels of free testosterone varies thought the menstrual cycle, being highest at the mid-cycle.
They also reduce pre-menopause.
A free testosterone on its own is enough to distinguish a hyperandrogenic cause.


In hirsutism if free testosterone levels are normal, what might be done next?

If free testosterone and SHBG should be measured as this could show a relatively elevated free testosterone. When interpreting these realists care should be take when interpreting patients who are on combined hormonal contraception as this reduced free testosterone by increasing levels of SHBG.


If a patient presents with symptoms other than simple hirsuitism, apart from free testosterone, what other hormonal tests might be appropriate to help find a cause?

Prolactin, FSH, LH, and TSH.
Although FSH/PH ratios re not used routinely in PCOS screening, it can be useful as the result helps eliminate premature ovarian failure as a potential menstrual disturbance.
A pelvic US may be arranged if PCOS is suspected.


If clinically adult-onset CAH is suspected, what test can be done to confirm this diagnosis?

An early morning, morning follicular phase (1-14) serum 17-alpha hydroxyprogesterone - in the this condition this enzyme is substantially elevated as well as testosterone.


What level of testosterone might raise suspicion of a tumour? (especially in hirsuitism). What type of tumour?

The tumour that would be suspected would be an androgen genie tumour.
The level to raise suspicion would be 1.5-2x the upper limit of normal, or levels about 5nmol/l


What would be the reason for looking for an elevated dehydroiandrosterone in distinguishing tumours?

DHEAS is not produced by the ovaries - therefore if it's raised, then we are looking at a testicular tumour.


I what tests might be requested if either metabolic syndrome or HAIR-AN is suspected, what tests mig be reasonable?

Blood tests for fasting glucose and lids is appropriate.


When should a patient with hirsutism be referred onwards? Note that endocrinology, gynecology, or dermatology may be appropriate, depending on the suspected cause? (5)

1) Seen in a pre-pubertal girl.
2) Fast onset and rapid hair growth occurring after puberty (6-12 months).
3) Virilising features.
4) No improvement after 6-12/12 of lifestyle and first line drug medications, and considering anti-androgen therapy.
5) Serum testosterone is approaching double the reference range.


If treatable causes of hirsutism have been excluded, management strategies are available; how long is it common to take before any benefit is seen?

6-9 months.


What lifestyle measures may help people with hirsutism? (3)

1) Weight loss is often appropriate. If patient overweight/obese, encourage to eat better and exercise more, maybe involve dietician, one study found a 50% hair loss in people over 6 months who lost 5-10% of their body weight.
2) Though study evidence is weak, spearmint tea drinking may help!
3) According to a small, recent study, in patients with PCOS, omega-3 fish oils taken for 6 months improved their hirsutism including objectively using MFGS. Also increased sex-hormone binding globulin and decreased androgen levels.


What method of hair removal are their for women with hirsutism IF THEY CHOOSE TO GO DOWN THIS ROUTE? Note this is only. Temporary removal of hair. What problems with them? (6)

1) Waxing. (Can lead to in growing hair, folliculitis, and scarring of the skin)
2) Shaving. (Can cause stubble).
3) Plucking. (Can lead to in growing hair, folliculitis, and scarring of the skin)
4) Depilitory/ bleaching creams. (Risk skin irritation, especially more sensitive areas of body e.g., face).
5) Epiliation. (Can lead to in growing hair, folliculitis, and scarring of the skin)
6) Waxing.


What methods of per entrant hair reduction are there for people with hirsutism?

1) Electrolysis.
2) Laser therapy.
Should not be used if the hirsutism is associated with hyperandrogenism - this should be tackled first.
In both cases, avoid waxing or plucking hair between Rx, in the hope that hair can be Rx in the growing phase of the cycle.


Does the NHS find Rx for electrolysis or laser Rx for hirsutism?
If not, then who? And if these people are used, what should the patient make sure of first?

Rarely! Where available, it is limited to patients with hormone imbalance causing hirsutism, and can only be accessed via secondary care specialists.
Private Rx may be avialiable, but advise patients to always use a fully trained professional, registered with a recognised regulatory body and holding professional indemnity insurance!


What is the process of electrophoresis as used in hirsutism for hair removal?
Is it comfortable?
Can everywhere be Rx by this method?
Any side effects?
Does it always work first time?

But, if done, it involves putting a small sterile needle in each individual hair follicle and running a small current through it, causing the destruction of the hair follicle.
Can cause discomfort, with a sensation similar to that of hair plucking.
All hairs apart from those in the nose or ear canal can be treated in this way.
Inflammation of the treated areas often develops immediately after treatment, but often subsides within a few hours; the next day, small scabs may be present which will drop of naturally in about a week, but may cause scarring if picked off early.
As each hair follicle is treated individually this can take some time and be expensive.
For permanent results, multiple Rx of the same area may be required.


Laser therapy is often used to treat hirsutism - it is generally NOT available on the NHS - what does it involve?
What is it also own as?
How many sessions are required?
Is it painless?
Are there any side effects, and if so what, and who gets them the worse.

Also known as photoepilation, causes destruction of the hair follicle itself without the surrounding skin.
Often 6-10 sessions are required PER AREA to see the desired result.
The process is not painless, but is usually well tolerated.
Side effects are rare, but include depigmentation of the skin, burns, and scarring.
They are more common in people with a darker skin colour.


What topical Rx is available for hirsutism?

Eflorinthine hydrochloride - (Vaniqua) can be used for facial hirsutism. It irreversibly inhibits an enzyme involved in hair growth. The effects last only while the treatment is being taken. (Note that it is often combined with laser therapy). It should be applied bd to the affected area and rubbed in completely. Other skin products can be used, but you have to wait 5 minutes after applying Vaniqua before doing so. However, don't wash the Rx area for 4 hours. Side effects include tingling, rashes, and in some cases acne. It can take up to 8 weeks to work! So warn people about this and not to give up if it doesn't work straight away! However, if no improvement after 4/12 of correct use, then stop.
This drug IS available through the NHS, but depending on local guidelines, may or may not be initiated in primary care - it is expensive, and local prescribing guidelines may restrict it's availability.


Are there any systemic medications that can be used to treat someone with hirsutism? (One main one)
How long do they last?

1) for premenopausal women with problematic hair growth, COC (if not contraindicated) is recommended as first line treatment.
2) there are other oral medications for hirsutism (see later) but they are prescribed off licence and usually initiated by secondary care specialists. Also see previous slide about Eflornium hydrochloride (Vaniqua) and why it is limited.
Note also that again they do not offer a permanent solution - the hair comes back when the treatment is stopped!


In which group is COC treatment less effective for treating hirsutism?

Women with PCOS who are obese. (They should be encouraged to lose weight!)


How does the COCP work to treat hirsutism?

It works by several mechanisms to reduce circulating testosterone:
1) LH production is suppressed, reducing ovarian testosterone production and increasing SHBG production.
2) A slight drop in adrenal production of testosterone and and a mild effect on testosterone binding also occur.
3) Lower testosterone means a reversion of terminal hair back to vellous type.
Note that this does NOT stop/even technically TREAT hirsuitism, it can just make it more manageable and slow or stop the progression of the condition.
It can take 6-12 months before effects are seen.


So the COC can be used to treat hirsutism. If the COC is contraindicated, can the POP be used instead?
If so, which ones should be used?
If not, which COP progesterone should be avoided? Which should be used?

No! The POP cannot be used to treat hirsutism, as many progesterone actually can demonstrate androgenic features and CAUSE hirsutism!
If the COC is used in this capacity, then don't use a COC containing norethistrone or levonorgestrel as they are highly androgenic.
The ones that should be used contain norgestimate, desorgestrel, or gestone.
COCS that contain progesterone with anti-androgenic properties include Yasmin (drospirenone) and Diannette (cyproterone acetate).


There is a COC that is licensed in the UK for people with moderately server hirsutism and/or severe acne - what is it?
If it is used for acne, what has to have been tried and failed first?
What are the common side effects (4). What is the one rare but serious side effect?

Co-cyprindiol (35 micrograms ethinylestradiol and 2mg cypretone acetate) is used.
If used for acne, then antibiotics have to have been tried and have failed first.
Common side effects include headaches, weight gain, depression, and fatigue. The rare bust serious side effect is liver dysfunction.


If used in hirsutism, how long should co-cymbridiol be used for?
What is co-cymbridiol contraindicated in?
What should it NOT be used for?

It should be used for 3-4/12 after complete resolution of symptoms.
It can be restarted if symptoms recur.
If there is no benefit after 6/12, then instead of this drug a COC or drospirenone should be tried instead.
Co-cymbridiol should not be used for contraception alone; it is absolutely contraindicated in a patient with a history of thromboembolism.


If systemic therapies used in primary care have little or no effect on hirsutism, are there any options available to secondary care? (6).
What specifically are the good and bad points of these treatments?

Although none of these drugs are licenced, they can be initiated in secondary care. The main drugs are:
1) Spironolactone! No, seriously! It is not used for its diuretic effect (in fact this is not seem clinically in this context); but a typical dose of 100mg OD is surprisingly well tolerated; after 6 months, FGS score is often improved by 15-40%, which is comparable to co-cymbridiol.
2) Flutamide (a drug used to treat prostate cancer!) is also sometimes used. It works as well as Spironolactone for prostate cancer, but is less widely used as it has the potential to cause liver failure.
3) Finasteride at 5mg/day can also work well. Although study quality in this area is currently weak, there appears to be no major side effects EXCEPT feminisation of the male foetus can occur on this medication if the woman taking it is pregnant - therefore give advice and make sure contraception is being used!!
4) Metformin USED to be used for hirsutism in PCOS; but recently a meta-analysis seemed to say other methods were better. Watch this space...
5) Gondaotrophins are occasionally used, basically as a last ditch effort to curb hirsutism. They are used when there is severe hyperandrogenism typically when associated with ovarian tumours. Sub optimal response to both the COC and anti-androgens have to have been reported before this can be used, as thee medicines have limited therapeutic ability (usually) over these medicines, but can additionally cause bone demineralisation and other related mentrual type symptoms.
6) In adult patients with CAH, steroid therapy is an option. However, there is little evidence that this is more edit I've than other treatments, and sometimes it can even make the hirsutism worse!


What is the annual incidence of hypothyroidism?

3.5/1000 in women, 0.6/1000 in men.


What is the communist cause of hypothyroidism?

In developed countries - autoimmune thyroiditis. In non-developed countries, iodine deficiency.


If autoimmune hypothyroidism is associated with goitre, what is it called?

Hashimoto's thyroiditis.


Is hypothyroidism associated with other disease?

Other autoimmune disease - including vitiligo, pernicious anaemia, type I diabetes mellitus, and Addision's disease.


Causes of hypothyroidism can be broadly divided into three groups - what are these groups?

Primary, secondary, and transient.


What are primary causes of hypothyroidism? (6)

1) Autoimmune: a) Hashimoto's thyroiditis, b) atrophic thyroiditis.
2) Infiltrative: a) sarcoidosis, b) haemochromatosis, c) scleroderma, d) amyloidosis
3) Drugs: a) Iodine, b) carbimazole, c) propylthiouracil , d) interferons, e) amiodarone, f) rifampacin.
4) Iodine deficiency.
5) Iatrogenic: a) thyroidectomy, b) radioiodine treatment.
6) Congenital: a) thyroid aplasia or hypoplasia, b) defective biosynthesis of thyroid hormones.


What are secondary causes of hypothyroidism? (3, 10)

1) Hypopituitarism: a) tumour, b) trauma, c) infiltrative, d) Sheehan's syndrome, e) pituitary surgery or irradiation.
2) Isolated TSH deficiency or inactivity.
3) Hypothalamic disease: a) tumours, b) traumas, c) infiltrative, d) idiopathic.


What are causes of transient hypothyroidism? (3)

Thyroiditis, including:
1) Postpartum.
2) Withdrawal of T4 in patients with intact thyroid.
3) Subacute thyroiditis.


When considering a diagnosis of hypothyroidism, what areas should be addressed in the history? Why? (5) (Excluding direct questions about symptoms of hypothyroidism).

1) Any family history of thyroid disease? In view of the genetic association with hypothyroidism
2) If female, is the patient in the postnatal period? To screen for postpartum thyroiditis or Sheehan’s syndrome
3) Has the patient had previous thyroid surgery or therapy? To indicate those suffering from iatrogenic hypothyroidism
4) Any use of anti-thyroid drugs?
5) Any symptoms or signs of a pituitary mass? Examples include headache and bitemporal hemianopia. This is to pick up potential secondary hypothyroidism


What symptoms from the systems enquiry are most discriminatory for hypothyroidism? (5)

Constipation, hoarse voice, feeling colder, puffiness of eyes and muscle weakness.


In hypothyroidism, what neurological and muscular assessment should take place?

Testing reflexes, sensation as directed by the history (for example, symptoms of carpal tunnel) and testing for proximal myopathy. To test for proximal myopathy, ask patients to slowly rise from seated with their arms crossed over the chest to demonstrate this problem.


In hypothyroidism, what general assessment should take place? What cardiovascular assessment?

The patient’s weight should be recorded and the general appearance should be assessed noting skin, hair and eyes (eye signs include periorbital oedema and proptosis - the distance between the lateral angle of the bony orbit and the cornea should be less than 22 mm).
It may also be relevant to examine for evidence of associated conditions, for example, vitiligo and xanthelasma.
Cardiovascular examination includes documenting the heart rate, blood pressure and listening to heart sounds; these may be muffled if a pericardial effusion is present.


Describe the steps in examination of the thyroid gland itself?

1) Inspect the neck for any evidence of scars. While
facing the front ask the patient to swallow – this reveals the shape of the thyroid and allows for visual assessment of goitre and any associated nodules
2. Examination of the thyroid gland itself is best done from behind. Ask the patient to slightly flex their neck to relax the sternocleidomastoid muscles:
a) Size – estimate the size and feel for the lower
b) Shape – nodular, multinodular, diffuse
c) Consistency – soft is normal; firm - simple goitre or
Hashimoto’s disease; stony hard – carcinoma,
fibrosis, Hashimoto’s disease
d) Tenderness – suggests thyroiditis
e) Mobility – carcinoma may tether the gland
3. Percussion – percuss the chest to indicate the presence of retrosternal goitre. On rare occasions a Pemberton’s test may be done: patients are asked to lift both their arms and if positive their face becomes swollen due to a retrosternal goitre occluding the neck veins
4. Auscultation – auscultate for a thyroid bruit over the thyroid lobes


How would TFT's differ for primary and secondary hypothyroidism, subclinical hypothyroidism, poor peripheral T4-->T3 conversion, and poor compliance?

Primary: TSH up; T4 low; T3 low.
Secondary: all down.
Subclinical: TSH up; T3&T4 normal.
Poor conversion: TSH & T4 normal, T3 down.
Poor compliance: all up.


What pieces of information might be good to tell a patient newly diagnosed with hypothyroidism? (7)

1) Levothyroxine has a half-life of 7 days in the bloodstream and it will take a week or more to start to feel better.
2) Conversely, if one tablet is missed out there will be no noticeable effect.
3) If muscle weakness, stiffness or cognitive defects are present these may take up to 6 months to fully resolve.
4) Levothyroxine should be taken on an empty stomach to maximise absorption
5) Treatment is generally lifelong and only small changes in levothyroxine dosage are likely over that time, as determined by yearly measurements of TSH levels.
6) In the UK, patients with hypothyroidism are eligible for a medical exemption certificate for pre- scription charges.
7) Explain TSH/T4/negative feedback.


What would be good stating doses of levothyroxine for different subgroups with hypothyroidism? How should that then be titrated?

Otherwise healthy adults - 100ug/day.
Over 60 - 25ug/day.
Previous ischaemic heart disease - 25ug/day.
Subclinical hypothyroidism - 75ug/day.
Adjustments to dose of 25-50ug/day should be made every 4 weeks according to response.


Why should care be taken when starting levothyroxine in a patient with existing ishaemic heart disease?

Bradycardia of hypothyroidism can mask underlying coronary disease. Be careful with titration, also.


Based on differing TSH and T4 results, which patients should be started on levothyroxine?

1) TSH 5-10 and low free serum thyroxine --> lifelong thyroxine.
2) TSH >10 with or without low free serum thyroxine --> lifelong thyroxine.
3) TSH 5-10 with normal thyroxine --> check for SYMPTOMS of hypothyroidism --> if symptomatic, give a trial of thyroxine for 3-6/12; if symptoms resolves --> lifelong treatment; if symptoms not resolved --> consider alternative diagnosis, including check for thyroid peroxide antibody.
4) 3) TSH 5-10 with normal thyroxine --> check for SYMPTOMS of hypothyroidism --> if asymptotic, check thyroid peroxide antibodies. If negative, recheck TSH every 3 yrs, if +ive, recheck TSH annually.


After starting thyroxine, when should the first TSH monitoring check be made? How long should it take TSH to fall within the reference range?

Make first test in 8-12 weeks. TSH reference ranges may take 3-6/12 to fall.


Why should a fully suppressed TSH (i.e., less than 0.1) always be avoided when treating hypothyroidism? (2)

1) Increased risk of osteoporosis in those aged >60.
2) AF increased by factor of 3.


If someone being monitored for hypothyroidism had a normal or high T4 and a elevated TSH, what might this represent?

Poor compliance - patient could be taking the levothyroxine in just the few days leading up to the test.


What might cause a persistently raised TSH and a normal T4? What might be worth testing for in this case?

Could be other drugs or malabsorption. Might be worth testing for coeliac's disease and autoimmune gastritis.


What drugs can prevent absorption of levothyroxine?

Calcium salts, ferrous sulphate, aluminium hydroxide and cholestyramine.


What drugs can increase the absorption of levothyroxine?

The epilepsy drugs! (As bloody usual!): phenytoin, carbamazepine, phenobarbitone and rifampicin. (Oh, and the TB drug).


What three important drugs can hypothyroidism affect?

Hypothyroidism can affect:
1) Digoxin - can cause higher serum digoxin level.
2) Warfarin - can cause decreased sensitivity to warfarin due to decreased metabolism of vitamin K dependent clotting factor.
3) Statins - more likely to cause rhabdomyolysis.
Therefore delay starting statins until patient euthyroid.
As patients become euthyroid, they are likely to need higher doses of digoxin and lower doses of warfarin.


What is the name for severe hypothyroidism? What is it?

Myxoedema is used to describe severe hypothyroidism; it specifically describes the situation where mucinous substances are deposited resulting in thickening of the skin and subcutaneous tissues – non-pitting oedema.


What is THE MOST severe form of hypothyroidism? What can ppt it? How do patients present? How is it Rx?

The most severe form of hypothyroidism is myxoedema Most often seen in elderly patients and is associated with a high mortality rate of 50%, even if promptly treated. It usually presents in patients with long-standing hypothyroidism, which may be undiagnosed or inadequately treated due to insufficient monitoring or poor compliance.
Ppt include sedative drugs and anything that impairs the respiratory system, including chest infections, heart failure and MI.
Patients present with reduced consciousness, psychosis (myxoedema madness), seizures, hypothermia (as low as 23


When should patients with hypothyroidism be referred to specialists? (7)

1) Patients less than 16 years old.
2) If subacute thyroiditis is suspected (fever and painful goitre).
3) Evidence of pituitary disease.
4) Significant co-morbidities such as ischaemic heart
5) Pregnant women.
6) Persistently raised TSH despite adequate treatment.
7) Non-responsive or worsening symptoms despite


Why is hypothyroidism in pregnancy worrying and important to manage properly?

Maternal hypothyroidism is associated with both obstetric and long-term developmental problems. These include psychomotor and cognitive impairment in the infant and an increased risk of miscarriage, stillbirth and pre-eclampsia.


If a patient with known hypothyroidism is planning pregnancy, how should this be managed? And if hypothyroidism develops? And after delivery?

Their TSH should be kept below 2.5 mU/L in order to reduce the risk of it rising during the first trimester.
All pregnant patients should be referred to secondary care as soon as notifying any healthcare professional that they are pregnant. While awaiting outpatient review, the TSH should be checked when pregnancy is confirmed and the T4 dose increased by 30% from 4–6 weeks gestation.
The TSH and free-T4 should be checked every 4 weeks until levels have stabilised aiming for a TSH in the low-normal range (0.4–2.0 mU/L) and subsequently every 4 weeks during the first trimester and again at 16 and 28 weeks gestation if stable. After delivery the woman’s T4 dose should be reduced to pre-pregnancy levels and TSH rechecked 6 to 8 weeks post- partum.