Endocrine and metabolic Flashcards
Conditions and presentations
What is the minimum HbA1c that would be diagnostic of type 2 diabetes mellitus?
6.5%
48 mmol/mol
Secondary hyperparathyroidism
PTH (Elevated)
Ca2+ (Low or normal)
Phosphate (Elevated)
Vitamin D levels (Low)
May have few symptoms
Eventually may develop bone disease, osteitis fibrosa cystica and soft tissue calcifications
Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in a setting of chronic renal failure
Secondary hyperparathyroidism management
Usually managed with medical therapy.
Indications for surgery in secondary (renal) hyperparathyroidism:
- Bone pain
- Persistent pruritus
- Soft tissue calcifications
Tertiary hyperparathyroidism management
- Allow 12 months to elapse following transplant as many cases will resolve
- The presence of an autonomously functioning parathyroid gland may require surgery.
- If the culprit gland can be identified then it should be excised.
- Otherwise total parathyroidectomy and re-implantation of part of the gland may be required.
Primary amenorrhoea
Failure to establish menstruation by 15 in girls
Normal secondary sexual characteristics
such as breast development
Or
Age of 13 girls with no secondary sexual characteristics
Secondary amenorrhoea definition
Cessation of menstruation for 3-6 months in women with prev normal and regular menses
6-12 months in women with previous oligomenorrhoea
Primary causes of Amenorrhoea (6)
gonadal dysgenesis (e.g. Turner’s syndrome) - the most common causes
testicular feminisation
congenital malformations of the genital tract
functional hypothalamic amenorrhoea (e.g. secondary to anorexia)
congenital adrenal hyperplasia
imperforate hymen
Secondary causes of amenorrhoea (8)
hypothalamic amenorrhoea (e.g. secondary stress, excessive exercise)
polycystic ovarian syndrome (PCOS)
hyperprolactinaemia
premature ovarian failure
thyrotoxicosis (hypothyroidism)
Sheehan’s syndrome
Asherman’s syndrome (intrauterine adhesions)
Pregnancy
Investigations for amenorrhoea
exclude pregnancy with urinary or serum bHCG
full blood count, urea & electrolytes, coeliac screen, thyroid function tests
gonadotrophins
low levels indicate a hypothalamic cause where as raised levels suggest an ovarian problem (e.g. Premature ovarian failure)
raised if gonadal dysgenesis (e.g. Turner’s syndrome)
prolactin
androgen levels
raised levels may be seen in PCOS
oestradiol
Management of primary amenorrhoea
investigate and treat any underlying cause
with primary ovarian insufficiency due to gonadal dysgenesis (e.g. Turner’s syndrome) are likely to benefit from hormone replacement therapy (e.g. to prevent osteoporosis etC)
Secondary amenorrhoea investigations
exclude pregnancy, lactation, and menopause (in women 40 years of age or older)
treat the underlying cause
What is ectopic pregnancy?
Implantation of a fertilized ovum outside the uterus results in an ectopic pregnancy
27 year old woman who presents to the emergency department with a history female with a history of 6-8 weeks amenorrhoea who presents with lower abdominal pain and later develops vaginal bleeding
Ectopic pregnancy
Ectopic pregnancy symptoms
lower abdominal pain
due to tubal spasm
typically the first symptom
pain is usually constant and may be unilateral.
vaginal bleeding
usually less than a normal period
may be dark brown in colour
history of recent amenorrhoea
typically 6-8 weeks from the start of last period
if longer (e.g. 10 wks) this suggest another causes e.g. inevitable abortion
peritoneal bleeding can cause shoulder tip pain and pain on defecation / urination
dizziness, fainting or syncope may be seen
symptoms of pregnancy such as breast tenderness may also be reported
Signs of ectopic pregnancy
abdominal tenderness
cervical excitation (also known as cervical motion tenderness)
adnexal mass: NICE advise NOT to examine for an adnexal mass due to an increased risk of rupturing the pregnancy. A pelvic examination to check for cervical excitation is however recommended
Pregnancy of unknown location investigation
case of pregnancy of unknown location, serum bHCG levels >1,500 points toward a diagnosis of an ectopic pregnancy
Osteomalacia
softening of the bones secondary to low vitamin D levels that in turn lead to decreased bone mineral content. If this occurs in growing children it is referred to as rickets, with the term osteomalacia preferred for adults.
Causes of osteomalacia (9)
vitamin D deficiency
malabsorption
lack of sunlight
diet
chronic kidney disease
drug induced e.g. anticonvulsants
inherited: hypophosphatemic rickets (previously called vitamin D-resistant rickets)
liver disease: e.g. cirrhosis
coeliac disease
Features of Osteomalacia
bone pain
bone/muscle tenderness
fractures: especially femoral neck
proximal myopathy: may lead to a waddling gait
Investigations of osteomalacia
bloods
low vitamin D levels
low calcium, phosphate (in around 30%)
raised alkaline phosphatase (in 95-100% of patients)
x-ray
translucent bands (Looser’s zones or pseudofractures)
Treatment of osteomalacia
- vitamin D supplementation
A loading dose is often needed initially
calcium supplementation if dietary calcium is inadequate
Paget’s disease of the bone
primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity. Paget’s disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients.
Which bones are commonly affected by Paget’s disease?
The skull, spine/pelvis, and long bones of the lower extremities are most commonly affected.
Predisposing factors for Paget’s’s disease
increasing age
male sex
northern latitude
family history
Clinical features of Paget’s disease?
only 5% of patients are symptomatic
the stereotypical presentation is an older male with bone pain and an isolated raised ALP
bone pain (e.g. pelvis, lumbar spine, femur)
classical, untreated features: bowing of tibia, bossing of skull
Investigations for Paget’s disease
- bloods
- other markers of bone turnover
- X-rays
- bone scintigraphy
Paget’s disease blood findings
raised alkaline phosphatase (ALP)
calcium and phosphate are typically normal. Hypercalcaemia may occasionally occur with prolonged immobilisation
Other markers of bone turnover in Paget’s disease
procollagen type I N-terminal propeptide (PINP)
serum C-telopeptide (CTx)
urinary N-telopeptide (NTx)
urinary hydroxyproline
X-rays Paget’s disease
osteolysis in early disease → mixed lytic/sclerotic lesions later
skull x-ray: thickened vault, osteoporosis circumscripta
Bone scintigraphy Paget’s disease
Increased uptake is seen focally at the sites of active bone lesion
Management of Paget’s disease
indications for treatment include
bone pain
skull or long bone deformity
fracture
periarticular Paget’s
bisphosphonate (either oral risedronate or IV zoledronate)
calcitonin is less commonly used now
Complications of bone disease
deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure
Primary hyperparathyroidism
excess secretion of PTH resulting in hypercalcaemia. It is the most common cause of hypercalcaemia in outpatients and is often diagnosed following an incidental finding of an elevated serum calcium concentration.
In 85% of cases a parathyroid adenoma is responsible.
Causes of primary hyperparathyroidism
85%: solitary adenoma
10%: hyperplasia
4%: multiple adenoma
1%: carcinoma
Symptomatic features of primary hyperparathyroidism
- 80% of patients may asymptomatic
polydipsia, polyuria
depression
anorexia, nausea, constipation
peptic ulceration
pancreatitis
bone pain/fracture
renal stones
hypertension
Primary hyperparathyroidism mnemonic
`Bones, groans, abdominal groans and psychic moans
Associations of primary hyperparathyroidism
- hypertension
- mutiple endocrine neoplasia: Men I and Men II
Treatment of primary hyperparathyroidism
the definitive management is total parathyroidectomy
conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage
patients not suitable for surgery may be treated with cinacalcet, a calcimimetic
a calcimimetic ‘mimics’ the action of calcium on tissues by allosteric activation of the calcium-sensing receptor
Investigations of primary hyperparathyroidism
bloods
raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan
x-ray findings
pepperpot skull
osteitis fibrosa cystica
Gynaecomastia
abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia
Causes of gynaecomastia (9)
physiological: normal in puberty
syndromes with androgen deficiency: Kallman’s, Klinefelter’s
testicular failure: e.g. mumps
liver disease
testicular cancer e.g. seminoma secreting hCG
ectopic tumour secretion
hyperthyroidism
haemodialysis
drugs
Drugs which cause gynaecomastia (7)
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids
Very rare drugs which cause gynaecomastia (6)
tricyclics
isoniazid
calcium channel blockers
heroin
busulfan
methyldopa
Hypertension
a clinic reading persistently above >= 140/90 mmHg, or:
a 24 hour blood pressure average reading >= 135/85 mmHg
Primary hypertension
This is where there is no single disease causing the rise in blood pressure but rather a series of complex physiological changes which occur as we get older.
Secondary hypertension
caused by a wide variety of endocrine, renal and other causes.
Renal disease secondary hypertension
Glomerulonephritis
• Chronic pyelonephritis
• Adult polycystic kidney disease
• Renal artery stenosis
Endocrine disorders secondary hypertension (5’
Primary hyperaldosteronism
• Phaeochromocytoma
• Cushing’s syndrome
• Liddle’s syndrome
• Congenital adrenal hyperplasia (11-beta hydroxylase deficiency)
• Acromegaly
Other causes of Secondary hypertension
Glucocorticoids
• NSAIDs
• Pregnancy
• Coarctation of the aorta
• Combined oral contraceptive pill
Signs and symptoms of hypertension
Typically asymptomatic
If above 200/120 patients may experience
headaches
visual disturbance
seizures
What else to check when suspecting hypertension
fundoscopy: to check for hypertensive retinopathy
urine dipstick: to check for renal disease, either as a cause or consequence of hypertension
ECG: to check for left ventricular hypertrophy or ischaemic heart disease
Investigation of 24hr blood pressure
- 24 hour reasoning
-24 hour blood pressure monitoring is not available then home readings using an automated sphygmomanometer are useful.
urea and electrolytes: check for renal disease, either as a cause or consequence of hypertension
HbA1c: check for co-existing diabetes mellitus, another important risk factor for cardiovascular disease
lipids: check for hyperlipidaemia, again another important risk factor for cardiovascular disease
ECG
urine dipstick
Management of hypertension
drug therapy using antihypertensives
modification of other risk factors to reduce the overall risk of cardiovascular disease
monitoring the patient for the development of complications of hypertension
Angiotensin-converting enzyme (ACE) inhibitor
Inhibit the conversion angiotensin I to angiotensin II
Associated with cough, angioedema, hyperkalaemia
Calcium channel blockers
Block voltage-gated calcium channels relaxing vascular smooth muscle and force of myocardial contraction
Flushing
Ankle swelling
Headache
Thiazide type diuretics
Inhibit sodium absorption at the beginning of the distal convoluted tubule
Hyponatraemia
Hypokalaemia
Dehydration
Angiotensin II receptor blockers (A2RB)
Block effects of angiotensin II at the AT1 receptor
Hyperkalaemia
Stage 1 hypertension
Clinic BP >= 140/90 mmHg and subsequent ABPM daytime average or HBPM average BP >= 135/85 mmHg
Stage 2 hypertension
Clinic BP >= 160/100 mmHg and subsequent ABPM daytime average or HBPM average BP >= 150/95 mmHg
Severe hypertension
Clinic systolic BP >= 180 mmHg, or clinic diastolic BP >= 120 mmHg
the blood pressure is >= 180/120 mmHg:
Immediate referral for:
Retinal haemorrhage or papilloedema (accelerated hypertension).
Life-threatening symptoms: new confusion, chest pain, heart failure, or acute kidney injury.
Suspected phaeochromocytoma (e.g., labile/postural hypotension, headache, palpitations, pallor, sweating).
If none of the above:
Urgent investigations for end-organ damage (e.g., bloods, urine ACR, ECG).
If target organ damage is found:
Start antihypertensive treatment immediately (don’t wait for ABPM or HBPM).
If no target organ damage:
Repeat clinic BP measurement.
Amubulatory blood pressure
at least 2 measurements per hour during the person’s usual waking hours (for example, between 08:00 and 22:00)
use the average value of at least 14 measurements
If ABPM not tolerated, consider HBPM
HBPM
for each BP recording, two consecutive measurements need to be taken, at least 1 minute apart and with the person seated
BP should be recorded twice daily, ideally in the morning and evening
BP should be recorded for at least 4 days, ideally for 7 days
discard the measurements taken on the first day and use the average value of all the remaining measurements
ABPM/HBPM >= 135/85 mmHg (i.e. stage 1 hypertension)
treat if < 80 years of age AND any of the following apply; target organ damage, established cardiovascular disease, renal disease, diabetes or a 10-year cardiovascular risk equivalent to 10% or greater
in 2019, NICE made a further recommendation, suggesting that we should ‘consider antihypertensive drug treatment in addition to lifestyle advice for adults aged under 60 with stage 1 hypertension and an estimated 10-year risk below 10%. ‘. This seems to be due to evidence that QRISK may underestimate the lifetime probability of developing cardiovascular disease
ABPM/HBPM >= 150/95 mmHg (i.e. stage 2 hypertension)
OFFER DRUG REGARDLESS OF AGE
Mittelschmerz
translates to ‘middle pain’ and refers to abdominal pain associated with ovulation. This mid-cyclical pain is experienced by 20% of women and there are several theories as to why it occurs
occurs due to a leakage of follicular fluid containing prostaglandins at the time of ovulation, which causes the pain. Another explanation is that the growth of the follicle stretches the surface of the ovary, causing pain.
Presentation of Mittelschmerz
Sudden onset of pain in either iliac fossa which then manifests as a generalised pelvic pain.
Typically, the pain is not severe and varies in duration, lasting from minutes to hours.
It is self-limiting and resolves within 24 hours of onset.
Pain may switch side from month to month, depending on the site of ovulation
Investigation of Mittelschmerz
There is no specific test to confirm Mittelschmerz and it diagnosed clinically, after taking a full history and examination to exclude other conditions
No abnormal signs on abdominal or pelvic examination.
Management of Mittelschmerz
Mittelschmerz is not harmful and can be controlled with simple analgesia.
Dysmenorrhoea
excessive pain during the menstrual period. It is traditionally divided into primary and secondary dysmenorrhoea.
Primary dysmenorrhoea
underlying pelvic pathology. It affects up to 50% of menstruating women and usually appears within 1-2 years of the menarche. Excessive endometrial prostaglandin production is thought to be partially responsible.
Features of primary dysmenorrhea
pain typically starts just before or within a few hours of the period starting
suprapubic cramping pains which may radiate to the back or down the thigh
Management of primary dysmenorrhea
NSAIDs such as mefenamic acid and ibuprofen are effective in up to 80% of women. They work by inhibiting prostaglandin production
combined oral contraceptive pills are used second line
Secondary dysmenorrhea
develops many years after the menarche and is the result of an underlying pathology. In contrast to primary dysmenorrhoea the pain usually starts 3-4 days before the onset of the period.
Causes of secondary dysmenorrhea
endometriosis
adenomyosis
pelvic inflammatory disease
intrauterine devices- copper coil
fibroids
Heavy bleeding management
management has shifted towards what the woman considers to be excessive.
Treatment based on whether woman needs contraception
Investigations of heavy bleeding
a full blood count should be performed in all women
NICE recommend arranging a routine transvaginal ultrasound scan if symptoms (for example, intermenstrual or postcoital bleeding, pelvic pain and/or pressure symptoms) suggest a structural or histological abnormality. Other indications include abnormal pelvic exam findings.
Heavy bleeding does not require contraception
either mefenamic acid 500 mg tds (particularly if there is dysmenorrhoea as well) or tranexamic acid 1 g tds. Both are started on the first day of the period
if no improvement then try other drug whilst awaiting referral
Require contraception heavy bleeding
intrauterine system (Mirena) should be considered first-line
combined oral contraceptive pill
long-acting progestogens
Norethisterone 5 mg tds can be used as a short-term option to rapidly stop heavy menstrual bleeding.
PCOS
complex condition of ovarian dysfunction thought to affect between 5-20% of women of reproductive age.
The aetiology of PCOS is not fully understood. Both hyperinsulinaemia and high levels of luteinizing hormone are seen in PCOS and there appears to be some overlap with the metabolic syndrome.
Features of PCOS
subfertility and infertility
menstrual disturbances: oligomenorrhoea and amenorrhoea
hirsutism, acne (due to hyperandrogenism)
obesity
acanthosis nigricans (due to insulin resistance)
Investigations of PCOS
pelvic ultrasound: multiple cysts on the ovaries
NICE Clinical Knowledge Summaries recommend the following baseline investigatons: FSH, LH, prolactin, TSH, testosterone, sex hormone-binding globulin (SHBG) are useful investigations
raised LH:FSH ratio is a ‘classical’ feature but is no longer thought to be useful in diagnosis
prolactin may be normal or mildly elevated
testosterone may be normal or mildly elevated - however, if markedly raised consider other causes
SHBG is normal to low in women with PCOS
check for impaired glucose tolerance
Diagnostic criteria of PCOS
a formal diagnosis should only be made after performing investigations to exclude other conditions
the Rotterdam criteria state that a diagnosis of PCOS can be made if 2 of the following 3 are present:
infrequent or no ovulation (usually manifested as infrequent or no menstruation)
clinical and/or biochemical signs of hyperandrogenism (such as hirsutism, acne, or elevated levels of total or free testosterone)
polycystic ovaries on ultrasound scan (defined as the presence of ≥ 12 follicles (measuring 2-9 mm in diameter) in one or both ovaries and/or increased ovarian volume > 10 cm³)
General managment of PCOS
weight reduction if appropriate
if a women requires contraception then a combined oral contraceptive (COC) pill may help regulate her cycle and induce a monthly bleed (see below)
Hirsutism and acne general management of PCOS
a COC pill may be used help manage hirsutism. Possible options include a third generation COC which has fewer androgenic effects or co-cyprindiol which has an anti-androgen action. Both of these types of COC may carry an increased risk of venous thromboembolism
if doesn’t respond to COC then topical eflornithine may be tried
spironolactone, flutamide and finasteride may be used under specialist supervision
Infertility management of PCOS
weight reduction if appropriate
the management of infertility in patients with PCOS should be supervised by a specialist. There is an ongoing debate as to whether metformin, clomifene or a combination should be used to stimulate ovulation
a 2007 trial published in the New England Journal of Medicine suggested clomifene was the most effective treatment. There is a potential risk of multiple pregnancies with anti-oestrogen therapies such as clomifene. The RCOG published an opinion paper in 2008 and concluded that on current evidence metformin is not a first line treatment of choice in the management of PCOS
metformin is also used, either combined with clomifene or alone, particularly in patients who are obese
gonadotrophins
Premenstrual syndrome
Premenstrual syndrome (PMS) describes the emotional and physical symptoms that women may experience in the luteal phase of the normal menstrual cycle.
PMS only occurs in the presence of ovulatory menstrual cycles - it doesn’t occur prior to puberty, during pregnancy or after the menopause.
Emotional symptoms of PMS
anxiety
stress
fatigue
mood swings
Physical symptoms of PMS
- bloating
- breast pain
PMS mild symptom managment
apart from the usual advice on sleep, exercise, smoking and alcohol, specific advice includes regular, frequent (2-3 hourly), small, balanced meals rich in complex carbohydrates
Moderate symptom managment of PMS
new-generation combined oral contraceptive pill (COCP)
examples include Yasminµ (drospirenone 3 mg and ethinylestradiol 0.030 mg)
Severe symptom managment of PMS
selective serotonin reuptake inhibitor (SSRI)
this may be taken continuously or just during the luteal phase (for example days 15-28 of the menstrual cycle, depending on its length)
Addisons disease
Autoimmune destruction of the adrenal glands is the most common cause of primary hypoadrenalism in the UK, accounting for 80% of cases. This is termed Addison’s disease and results in reduced cortisol and aldosterone being produced
Features of Addison’s disease
lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
hyperpigmentation (especially palmar creases)
vitiligo
loss of pubic hair in women
hypotension
hypoglycaemia
hyponatraemia and hyperkalaemia may be seen
crisis: collapse, shock, pyrexia
Hyperpigmentation in Addison’s disease
ACTH is derived from a larger precursor molecule called proopiomelanocortin (POMC). When POMC is cleaved to produce ACTH, other melanocyte-stimulating hormones (MSH) are also produced. These MSHs have the effect of stimulating melanocytes in the skin to produce more melanin, the pigment responsible for skin colour
primary Addison’s is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
Primary causes of hypoadrenalism
tuberculosis
metastases (e.g. bronchial carcinoma)
meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
antiphospholipid syndrome
Secondary causes of hypoadrenalism
pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
Addison’s disease Associated electrolyte abnormalities are seen in around one-third of undiagnosed patients (4)
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
Definite investigation for Addison’s disease
ACTH stimulation test (short Synacthen test).
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
If ACTH simulation is not available
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
Management of Addison’s disease
glucocorticoid and mineralocorticoid replacement therapy.
hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the first half of the day
fludrocortisone
Patient education on Addison’s disease
emphasise the importance of not missing glucocorticoid doses
consider MedicAlert bracelets and steroid cards
patients should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis
discuss how to adjust the glucocorticoid dose during an intercurrent illness (see below)
Management of intercurrent illness in Addison’s disease
in simple terms the glucocorticoid dose should be doubled, with the fludrocortisone dose staying the same
the Addison’s Clinical Advisory Panel have produced guidelines detailing particular scenarios - please see the CKS link for more details
Addisonian crisis causes
sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
Management of Addisonian crisis
hydrocortisone 100 mg im or iv
1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
DKA
complication of existing type 1 diabetes mellitus or be the first presentation, accounting for around 6% of cases. Rarely, under conditions of extreme stress, patients with type 2 diabetes mellitus may also develop DKA.
Pathophysiology of DKA
DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies
Features of DKA
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (‘pear drops’ smell
American Diabetes Association (2009) diagnostic criteria DKA
glucose > 13.8 mmol/l
pH < 7.30
serum bicarbonate <18 mmol/l
anion gap > 10
ketonaemia
Joint British Diabetes Societies (2013) diagnostic criteria
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick
Management of DKA
-fluid replacement
- insulin
-correction of electrolytes disturbance
-long-acting insulin should be continued, short-acting insulin should be stopped
Fluid replacement of DKA
most patients with DKA are deplete around 5-8 litres
isotonic saline is used initially, even if the patient is severely acidotic
Insulin management of DKA
an intravenous infusion should be started at 0.1 unit/kg/hour
once blood glucose is < 14 mmol/l an infusion of 10% dextrose should be started at 125 mls/hr in addition to the 0.9% sodium chloride regime
Correction of DKA electrolyte disturbance
serum potassium is often high on admission despite total body potassium being low
this often falls quickly following treatment with insulin resulting in hypokalaemia
potassium may therefore need to be added to the replacement fluids
if the rate of potassium infusion is greater than 20 mmol/hour then cardiac monitoring may be required
DKA resolution
pH >7.3 and
blood ketones < 0.6 mmol/L and
bicarbonate > 15.0mmol/L
Further points include
both the ketonaemia and acidosis should have been resolved within 24 hours. If this hasn’t happened the patient requires senior review from an endocrinologist
if the above criteria are met and the patient is eating and drinking switch to subcutaneous insulin
the patient should be reviewed by the diabetes specialist nurse prior to discharge
Complications of DKA or the treatment
gastric stasis
thromboembolism
arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
iatrogenic due to incorrect fluid therapy: cerebral oedema hypokalaemia, hypoglycaemia
acute respiratory distress syndrome
acute kidney injury
Cerebral oedema, children and DKA
children/young adults are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology etc. It usually occurs 4-12 hours following commencement of treatment but can present at any time. If there is any suspicion a CT head and senior review should be sought
Features of head and neck cancer (4)
neck lump
hoarseness
persistent sore throat
persistent mouth ulcer
Laryngeal cancer
Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for laryngeal cancer in people aged 45 and over with:
persistent unexplained hoarseness or
an unexplained lump in the neck
Oral cancer
Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for oral cancer in people with either:
unexplained ulceration in the oral cavity lasting for more than 3 weeks or
a persistent and unexplained lump in the neck.
Consider an urgent referral (for an appointment within 2 weeks) for assessment for possible oral cancer by a dentist in people who have either:
a lump on the lip or in the oral cavity or
a red or red and white patch in the oral cavity consistent with erythroplakia or erythroleukoplakia.
Thyroid cancer
Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for thyroid cancer in people with an unexplained thyroid lump.
Reactive lymphadenopathy
By far the most common cause of neck swellings. There may be a history of local infection or a generalised viral illness
Lymphoma
Rubbery, painless lymphadenopathy
The phenomenon of pain whilst drinking alcohol is very uncommon
There may be associated night sweats and splenomegaly
Thyroid swelling
May be hypo-, eu- or hyperthyroid symptomatically
Moves upwards on swallowing
Thyroglossal cyst
More common in patients < 20 years old
Usually midline, between the isthmus of the thyroid and the hyoid bone
Moves upwards with protrusion of the tongue
May be painful if infected
Pharyngeal pouch
More common in older men
Represents a posteromedial herniation between thyropharyngeus and cricopharyngeus muscles
Usually not seen but if large then a midline lump in the neck that gurgles on palpation
Typical symptoms are dysphagia, regurgitation, aspiration and chronic cough
Cystic hygroma
A congenital lymphatic lesion (lymphangioma) typically found in the neck, classically on the left side
Most are evident at birth, around 90% present before 2 years of age
Branchial cyst
An oval, mobile cystic mass that develops between the sternocleidomastoid muscle and the pharynx
Develop due to failure of obliteration of the second branchial cleft in embryonic development
Usually present in early adulthood
Cervical rib
More common in adult females
Around 10% develop thoracic outlet syndrome
Carotid aneurysm
Pulsatile lateral neck mass which doesn’t move on swallowing
Nipple discharge - physiological
During breast feeding
Galactorrhoea
Commonest cause may be response to emotional events, drugs such as histamine receptor antagonists are also implicated
Hyperprolactinaemia
Commonest type of pituitary tumour
Microadenomas <1cm in diameter
Macroadenomas >1cm in diameter
Pressure on optic chiasm may cause bitemporal hemianopia
Mammary duct ectasia
Dilatation breast ducts.
Most common in menopausal women
Discharge typically thick and green in colour
Most common in smokers
Carcinoma
Often blood stained
May be underlying mass or axillary lymphadenopathy
Intraductal papilloma
Commoner in younger patients
May cause blood stained discharge
There is usually no palpable lump
Assessment of nipple discharge
Examine breast and determine whether there is mass lesion present
All mass lesions should undergo Triple assessment.
Elements of triple assessments
- bi manual assessment
- mammogram
- needle biopsy
reporting of investigations
1 No abnormality
2 Abnormality with benign features
3 Indeterminate probably benign
4 Indeterminate probably malignant
5 Malignant
Management of non-malignant nipple discharge
Exclude endocrine disease
Nipple cytology unhelpful
Smoking cessation advice for duct ectasia
For duct ectasia with severe symptoms, total duct excision may be warranted.
Cushing syndrome independent causes
iatrogenic: steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)
Pseudo-Cushing’s
mimics Cushing’s
often due to alcohol excess or severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
insulin stress test may be used to differentiate
ACTH dependent causes of Cushing
Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes
Epidemiology of Cushing
exogenous causes of Cushing’s syndrome (e.g. glucocorticoid therapy) are far more common than endogenous ones.
Cushing ABG findings
hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance.
Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically associated with very low potassium levels.
What three tests are used to confirm Cushing’s
overnight (low-dose) dexamethasone suppression test
24 hr urinary free cortisol
Bedtime salivary cortisol
overnight (low-dose) dexamethasone suppression test
this is the most sensitive test and is now used first-line to test for Cushing’s syndrome
patients with Cushing’s syndrome do not have their morning cortisol spike suppressed
24 hr urinary free cortisol
two measurements are required
Bedtime salivary cortisol
two measurements are required
Cortisol ACTH
Not suppressed Suppressed
Cushing’s syndrome due to other causes (e.g. adrenal adenomas)
Cortisol suppresses and ACTH not suppressed
Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)
Cortisol and ACTH not suppressed
Ectopic ACTH syndrome
Other tests for cushings
CRH stimulation
if pituitary source then cortisol rises
if ectopic/adrenal then no change in cortisol
Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion.
An insulin stress test is used to differentiate between true Cushing’s and pseudo-Cushing’s.
Managment of Cushing’s syndrome
Primary treatment is surgical removal of the underlying cause (e.g., adrenal tumor, pituitary adenoma).
If surgery isn’t feasible or unsuccessful, medical therapy may include adrenal enzyme inhibitors (e.g., ketoconazole, metyrapone), cortisol receptor blockers (e.g., mifepristone), or pituitary-directed drugs (e.g., pasireotide).
Close monitoring of symptoms, cortisol levels, and potential complications (e.g., osteoporosis, hypertension) is crucial.
Lifestyle modifications such as dietary changes and exercise may be recommended to manage weight gain and other associated symptoms
Complications of Cushing’s syndrome”
Hypertension
Osteoporosis
Diabetes mellitus
Muscle weakness
Skin changes
Mood disturbances
Menstrual irregularities and infertility
CVD
Increased susceptibility to infection
Acromegaly
- Rare conditon which is caused by growth hormone-secreting pituitary adenoma
Growth hormone releasing hormone (GHRH) independent acromegaly
- ** Pituitary adenoma: **
- Primary pituitary hyperplasia:
Growth hormone releasing hormone (GHRH) dependent acromegaly
- Hypothalamic source
- Ectopic GHRH release
Pathophysiology of acromegaly
Excess growth hormone (GH) results in excess production of insulin-like growth factor 1 (IGF-1)
gigantism vs acromegaly
- gigantism occurs before epiphyseal plate closure, leading to excessive linear growth.
- Acromegaly occurs after plate closure, causing enlargement of bones and soft tissues.
Signs and symptoms of acromegaly
Investigations of acromegaly
-
Bedside tests
* urine dip
* ecg
* fundoscopy +perimertry
2.** Bloods**
* IGF1
* oral glucose tolerance test
* anterior pituitary profile
3.** Radiology**
* CXR (cardiomegaly)
* MRI Pituitary (adenoma)
* If considering an ectopic source, can do CTCAP
-
Specialty tests
* Sleep studies
* colonoscopy
anterior pituitary profile- what tests (8)
- TFT
- LH
- FSH
- Prolactin
- Oestrogen
- Testosterone
- Cortisol
- HBA1c
Acromegaly managment
1.Surgery
Transphenoidal (first line)/transfrontal resection of the pituitary +/-radiotherapy
- **Drug managment **
* octreotide, lanreorid
* Growth hormone antagonists (pegvisomant)
* Dopamine agonists (bromocriptine, cabergoline) -
follow up
* monitor for bowel changes
* blood tests to make sure no reoccurance
Complications of acromegaly
Clinical features of Addison’s disease
- Hypotension
- Fatigue and weakness
- Gastrointestinal symptoms
- Syncope
- Skin pigmentation due to increased ACTH which stimulates production of alpha melanocyte stimulating hormone (MSH).
Investigations for Addison’s disease
- U+E and serum cortisol
- ACTH
- Renin
- aldosterone
- Testing for adrenal auto-antibodies
- Chest X-ray
- CT scan of the adrenal glands
- MRI of the brain
Blood gas findings in Addison’s
- hyperkalaemic
- hyponatraemic,
- hypoglycaemic metabolic acidosis
gold standard investigation to confirm the addison’s.
ACTH (Short Synacthen) test
Addison’s sick day rules?
Doubling the regular steroid medication dose during any intercurrent illness
Managment of Addison’s crisis
- Aggressive fluid resuscitation
- Administration of intravenous/IM (if no access) steroids STAT
- Glucose administration if hypoglycaemia is present
What is Addison’s crisis
life-threatening condition that occurs when the body experiences a severe deficiency in cortisol
Signs and symptoms of Addison’s crisis
Sudden and severe weakness
Fatigue
Nausea and vomiting
Abdominal pain
Low blood pressure
Dehydration
Confusion or loss of consciousness
Causes of Addison’s crisis
Inadequate cortisol production due to adrenal gland dysfunction
Stressful events such as infections, trauma, or surgery
Sudden withdrawal of corticosteroid medications
Adrenal hemorrhage or infarction
Addison’s crisis prevention
Proper adherence to corticosteroid replacement therapy in individuals with Addison’s disease
Awareness of stressors that may precipitate a crisis and proactive management
Carrying medical identification indicating adrenal insufficiency status
Education of family members and caregivers regarding signs and management of Addison’s crisis
Complications of Addison’s disease
- Addisonian crisis (life-threatening adrenal crisis)
- Severe electrolyte imbalances
- Cardiovascular collapse
- Hypoglycemia
- Side effects of long term corticosteroid use e.g. osteoporosis
Diabetes insipidus
condition characterized by the reduced production or response to antidiuretic hormone (ADH), resulting in excessive urination and thirst.
Types of DI
- Cranial
- Nephrogenic
cranial DI
- Head trauma
- Inflammatory conditions (e.g., sarcoidosis)
- Cranial infections such as meningitis
- Vascular conditions such as sickle cell disease
- Rare genetic causes
Nephrogenic DI causes
- Drugs (e.g., lithium)
- Metabolic disturbances (e.g., hypercalcaemia, hypokalaemia, hyperglycaemia)
- Chronic renal disease
- Rare genetic causes (e.g., Wolfram’s syndrome)
Drugs which cause DI
- Lithium:
- Tetracyclines:
- Antifungals: Medications like amphotericin B.
- Antivirals:
- Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Such as ibuprofen.
Features of DI
Large volumes of dilute urine (>3 litres in 24 hours and a urine osmolality of <300 mOsm/kg)
Nocturia
Excessive thirst
——————————————
In childten
Failure to thrive
Enuresis
DI investigations
- Urea and electrolytes (sodium may be raised)
- Blood glucose (to rule out diabetes mellitus)
- Urine dip
- Paired serum and urine osmolality measurements
Serum osmolality DI
serum osmolality is raised** (>295 mOsm/kg) with inappropriately dilute urine (urine osmolality < 300 mOsm/kg).**
If the diagnosis remains uncertain then water deprivation
Cranial DI managment
- Cranial diabetes insipidus can be managed with desmopressin
- Sodium levels should be monitored routinely due to the risk of hyponatraemia.
Nephrogenic Diabetes Insipidus
- Correcting any underlying metabolic abnormalities
- discontinuing any offending drugs.
- High dose desmopressin (meh)
- Thiazide diuretic
- non-steroidal anti-inflammatory drug to reduce urine volume.
Amiodarone- induced thyroxicosis
- Recognized adverse effect of the anti-arrhythmic agent.
- Amiodarone is rich in iodine,
Types of amiodarone induced thyrotoxicosis
- AIT type 1 - direct toxic effect of amiodarone on the thyroid gland causing thyroiditis,
- AIT type 2-amiodarone triggers underlying thyroid autoimmunity.
AIT side effects
Weight loss
Tremors
Palpitations
Nervousness
Fatigue
hyperprolactinemia symptoms in women
- galactorrhea
- menstruation issues
side effects of Amiodarone (8)
- hypothyroidism
- hyperthyroidism/thyrotoxicosis
- corneal deposits
- Stevens-Johnson syndrome
- skin discoloration
- liver failure
- pneumonitis
- pulmonary fibrosis.
Monitoring on Amiodarone
- Thyroid function tests: Monitoring for hypothyroidism and hyperthyroidism.
- Liver function tests: To monitor for hepatic toxicity.
- Pulmonary function tests and chest radiography: To monitor for pulmonary toxicity.
- Ophthalmologic examination: To monitor for corneal deposits and optic neuropathy.
SULFONYLUREAS
- stimulate the pancreatic beta cells, promoting the release of insulin
- 40-80mg daily max 320mg daily.
Sulfonylureas side effects
Hypoglycemia is a significant risk with sulfonylureas.
Weight gain
Nausea
Diarrhoea
Allergic reactions
contradictions of Sulfoylurea
- Type 1 diabetes
- Diabetic ketoacidosis
- Severe renal or hepatic impairment
THIAZOLIDINEDIONES
- increasing peripheral insulin sensitivity, thus lowering blood glucose levels.
- 15-30mg once daily Max 45mg once daily.
side effects of THIAZOLIDINEDIONES
Weight gain
Fluid retention leading to heart failure
Increased risk of fractures
Potentially an increased risk of bladder cancer.
SGLT2 INHIBITORS
nhibitors increase urinary glucose excretion, thus reducing blood glucose levels.
Dose: The usual dose for dapagliflozin is 10mg once daily.
SGLT2 INHIBITORS side effects
- Genital mycotic infections
- Urinary tract infections
- Euglycemic diabetic ketoacidosis
- Increased risk of lower limb amputation
SGLT2 INHIBITORS contradictions
Severe renal impairment or end-stage renal disease
DPP4-INHIBITORS side effects (4)
Nasopharyngitis
Upper respiratory tract infection
Headache
Pancreatitis
DPP4-INHIBITORS contradictions
Sitagliptin should be used with caution in patients with a history of pancreatitis.
The dose should be adjusted in patients with renal impairment.
What is the primary cause of acromegaly in over 95% of cases?
Excess growth hormone secondary to a pituitary adenoma
A minority of cases are caused by ectopic GHRH or GH production by tumors, such as pancreatic tumors.
What are the characteristic features of acromegaly? (10)
- Coarse facial appearance
- Spade-like hands
- Increase in shoe size
- Large tongue
- Prognathism
- Interdental spaces
- Excessive sweating and oily skin
- Features of pituitary tumor (hypopituitarism, headaches, bitemporal hemianopia)
- Raised prolactin in 1/3 of cases leading to galactorrhoea
- 6% of patients have MEN-1
These features arise due to the effects of excess growth hormone.
Which condition may result from raised prolactin levels in acromegaly?
Galactorrhoea
This occurs in approximately 1/3 of cases.
What is a common complication of acromegaly related to metabolic health?
Diabetes (>10%)
Diabetes is one of the significant complications associated with acromegaly.
List three complications of acromegaly.
- Hypertension
- Diabetes
- Cardiomyopathy
- Colorectal cancer
These complications are important to monitor in patients with acromegaly.
True or False: Acromegaly can be caused by ectopic GHRH or GH production.
True
This is a minority of cases compared to pituitary adenoma.
Fill in the blank: The presence of a pituitary tumor can lead to _______ symptoms in acromegaly.
hypopituitarism
Hypopituitarism can occur due to the pressure effects of the tumor.
What appearance do patients with acromegaly typically exhibit?
Coarse facial appearance
This is one of the hallmark features of the condition.
What percentage of acromegaly patients may have MEN-1?
6%
MEN-1 (Multiple Endocrine Neoplasia type 1) is a genetic syndrome that can be associated with acromegaly.
What is the first-line treatment for acromegaly in the majority of patients?
Trans-sphenoidal surgery
This surgical approach is typically the preferred method for managing acromegaly caused by pituitary tumors.
What is indicated if a pituitary tumour is inoperable or surgery is unsuccessful?
Medication
Various medications may be considered to manage acromegaly when surgical options are limited.
What is a somatostatin analogue?
A medication that directly inhibits the release of growth hormone
An example is octreotide, which is effective in 50-70% of patients.
What is the effectiveness of octreotide in treating acromegaly?
50-70% of patients
Octreotide is a somatostatin analogue used to inhibit growth hormone release.
What is pegvisomant?
A GH receptor antagonist that prevents dimerization of the GH receptor
It is administered once daily via subcutaneous injection and decreases IGF-1 levels in 90% of patients to normal.
What percentage of patients does pegvisomant decrease IGF-1 levels to normal?
90%
Pegvisomant is effective in normalizing IGF-1 levels, but does not reduce tumor volume.
Why is surgery still needed after pegvisomant treatment?
It doesn’t reduce tumour volume
Surgery may still be necessary if there is a mass effect from the tumor.
What is the role of dopamine agonists in acromegaly treatment?
They are the first effective medical treatment for acromegaly
An example is bromocriptine, but their use is now largely superseded by somatostatin analogues.
True or False: Dopamine agonists are effective in the majority of patients with acromegaly.
False
Dopamine agonists are effective only in a minority of patients.
When is external irradiation used in acromegaly management?
For older patients or following failed surgical/medical treatment
This approach is considered when other treatment options have not been successful.
What is Bartter’s syndrome?
An inherited cause of severe hypokalaemia due to defective chloride absorption at the NKCC2 in the ascending loop of Henle
Usually autosomal recessive
What is the genetic inheritance pattern of Bartter’s syndrome?
Usually autosomal recessive
This means that two copies of the mutated gene are required for the syndrome to manifest
What is the primary physiological defect in Bartter’s syndrome?
Defective chloride absorption at the NKCC2 in the ascending loop of Henle
This leads to severe hypokalaemia
How does Bartter’s syndrome differ from other causes of hypokalaemia?
It is associated with normotension
Other causes like Conn’s, Cushing’s, and Liddle’s syndrome are associated with hypertension
What is the effect of loop diuretics on NKCC2?
They inhibit NKCC2
Bartter’s syndrome can be thought of as similar to taking large doses of furosemide
At what age does Bartter’s syndrome usually present?
Usually presents in childhood
Symptoms can include failure to thrive
List three clinical features of Bartter’s syndrome.
- Failure to thrive
- Polyuria
- Polydipsia
- Hypokalaemia
- Normotension
- Weakness
These features can vary in presentation
True or False: Bartter’s syndrome is associated with hypertension.
False
It is associated with normotension
What does congenital adrenal hyperplasia (CAH) refer to?
A group of autosomal recessive disorders that impair adrenal steroid biosynthesis
What is the primary consequence of cortisol production deficiency in CAH?
Compensatory overproduction of adrenocorticotropic hormone (ACTH) by the anterior pituitary
What effect do elevated ACTH levels have in CAH?
Increase the production of adrenal androgens
What can excessive adrenal androgens result in for female infants?
Virilization and ambiguous genitalia
What is the most common cause of CAH?
21-hydroxylase deficiency (90%)
What is impaired in 21-hydroxylase deficiency?
Conversion of 17-hydroxyprogesterone to 11-deoxycortisol
What are the consequences of 21-hydroxylase deficiency?
Cortisol deficiency and excess androgen production
What is the second most common cause of CAH?
11-beta hydroxylase deficiency (5%)
What is a clinical consequence of 11-beta hydroxylase deficiency?
Hypertension due to excess deoxycorticosterone
What is the rarest form of CAH?
17-hydroxylase deficiency
What does 17-hydroxylase deficiency lead to?
Mineralocorticoid excess with low androgen and estrogen levels
How do the symptoms of CAH vary?
Depending on the specific enzyme deficiency and the severity of the disorder
What is a common clinical presentation in female infants with CAH?
Ambiguous genitalia due to excessive androgen exposure in utero
How do male infants typically present at birth with CAH?
Appear normal, which can delay diagnosis
What is the effect of androgen exposure in utero on male infants?
Male infants appear normal at birth, which can delay diagnosis
What is a salt-wasting crisis in the context of CAH?
A severe form occurring in about 75% of cases with 21-hydroxylase deficiency, characterized by dehydration, hypotension, and electrolyte imbalances
What are the potential consequences of a salt-wasting crisis if not treated promptly?
It can be life-threatening
What is precocious puberty and how is it related to CAH?
Excess androgens can lead to early development of secondary sexual characteristics in both males and females
What fertility issues may adults with untreated CAH experience?
Infertility due to hormonal imbalances
What growth abnormalities are associated with children who have CAH?
Accelerated growth rates initially but may have a shorter adult stature due to early epiphyseal closure
What is the screening method for diagnosing CAH in newborns?
Looking for elevated levels of serum concentration of 17-hydroxyprogesterone (17OHP)
Is newborn screening for CAH done in the UK?
No, it is not yet done in the UK
What is ACTH stimulation testing used for in diagnosing CAH?
To evaluate the adrenal gland’s response to ACTH, with abnormal increases in 17OHP indicating CAH
What is the primary management strategy for CAH?
Glucocorticoid replacement to reduce ACTH levels and minimize adrenal androgen production
In cases of mineralocorticoid deficiency, what medication is prescribed?
Fludrocortisone
Fill in the blank: CAH can lead to _______ in both males and females due to excess androgens.
precocious puberty
True or False: Children with CAH typically have normal growth patterns throughout their development.
False
What is a feature of 21-hydroxylase deficiency?
Virilisation of female genitalia
This condition leads to the development of male characteristics in genetically female infants.
What percentage of patients with 21-hydroxylase deficiency experience a salt-losing crisis?
60-70%
A salt-losing crisis typically occurs at 1-3 weeks of age in affected infants.
What is a feature of 11-beta hydroxylase deficiency?
Hypertension
This condition can lead to high blood pressure due to adrenal hormone imbalances.
What are two features of 11-beta hydroxylase deficiency?
- Virilisation of female genitalia
- Hypokalaemia
Hypokalaemia refers to low potassium levels in the blood.
What is a feature of 17-hydroxylase deficiency in females?
Non-virilising
This means that females do not develop male characteristics.
What is a feature of 17-hydroxylase deficiency in boys?
Inter-sex
This condition can result in ambiguous genitalia in male infants.
What is a common feature of both 21-hydroxylase and 11-beta hydroxylase deficiencies?
Virilisation of female genitalia
Both conditions lead to the development of male characteristics in genetically female infants.
Fill in the blank: A feature of 11-beta hydroxylase deficiency is _______.
Hypertension
What is congenital hypothyroidism?
A condition affecting around 1 in 4000 babies that, if not diagnosed and treated within the first four weeks, causes irreversible cognitive impairment
Congenital hypothyroidism is a serious condition that can have lasting effects on a child’s development.
What are the features of congenital hypothyroidism?
• Prolonged neonatal jaundice
• Delayed mental & physical milestones
• Short stature
• Puffy face
• Macroglossia
• Hypotonia
These features can help in early identification of the condition.
At what age are children screened for congenital hypothyroidism?
5-7 days
Screening is typically done using the heel prick test.
True or False: Congenital hypothyroidism can be treated effectively if diagnosed after four weeks.
False
Diagnosis and treatment must occur within the first four weeks to prevent irreversible cognitive impairment.
Fill in the blank: Congenital hypothyroidism affects approximately 1 in ______ babies.
4000
This statistic highlights the rarity of the condition.
What are the diagnostic criteria for type 2 diabetes mellitus in symptomatic patients?
• Fasting glucose ≥ 7.0 mmol/l
• Random glucose ≥ 11.1 mmol/l (or after 75g oral glucose tolerance test)
Symptoms may include polyuria and polydipsia.
What additional requirement must be met for diagnosing type 2 diabetes in asymptomatic patients?
The criteria must be demonstrated on two separate occasions.
This ensures the accuracy of the diagnosis.
What is the HbA1c threshold for diagnosing diabetes mellitus?
HbA1c ≥ 48 mmol/mol (6.5%)
Values below this do not exclude diabetes.
Under what circumstances should the HbA1c test be repeated to confirm diabetes diagnosis?
In patients without symptoms.
This helps ensure the reliability of the diagnosis.
What conditions may lead to misleading HbA1c results? (9)
• Increased red cell turnover
• Haemoglobinopathies
• Haemolytic anaemia
• Untreated iron deficiency anaemia
• Suspected gestational diabetes
• Children
• HIV
• Chronic kidney disease
• Medications causing hyperglycaemia (e.g., corticosteroids)
These conditions can affect the accuracy of HbA1c measurements.
What is considered normal glycaemic control for HbA1c?
HbA1c <= 41 mmol/mol (5.9%)
Values above this indicate prediabetes or diabetes.
What HbA1c range indicates prediabetes?
HbA1c 42-47 mmol/mol (6.0-6.4%)
Fasting glucose levels can also indicate prediabetes.
Fill in the blank: In diabetes mellitus, fasting glucose is ≥ _______.
7.0 mmol/l
This is a key diagnostic threshold.
True or False: A random glucose test of 10.0 mmol/l can diagnose type 2 diabetes.
False
The threshold for random glucose is ≥ 11.1 mmol/l.
What is the diagnostic threshold for diabetes based on fasting glucose?
Fasting glucose ≥ 7.0 mmol/l
This is a critical value for diagnosis.
What are the two types of impaired glucose conditions?
• Impaired fasting glucose
• Impaired glucose tolerance
These conditions are precursors to diabetes.
What fasting glucose level indicates impaired fasting glucose (IFG)?
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l
Define impaired glucose tolerance (IGT).
Fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
What action should be taken for people with impaired fasting glucose (IFG) according to Diabetes UK?
Offer an oral glucose tolerance test to rule out a diagnosis of diabetes
What OGTT result indicates that a person does not have diabetes but has impaired glucose tolerance (IGT)?
A result below 11.1 mmol/l but above 7.8 mmol/l
What fasting glucose level indicates impaired fasting glucose (IFG)?
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l
Define impaired glucose tolerance (IGT).
Fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
What action should be taken for people with impaired fasting glucose (IFG) according to Diabetes UK?
Offer an oral glucose tolerance test to rule out a diagnosis of diabetes
What are the 4 main ways to check blood glucose?
- Finger-prick bedside glucose monitor
- One-off blood glucose (fasting or non-fasting)
- HbA1c (measures average glucose over 2-3 months)
- Glucose tolerance test (fasting glucose followed by 75g glucose load and a second reading after 2 hours)
What fasting glucose level indicates diabetes in symptomatic patients?
Greater than or equal to 7.0 mmol/l
What random glucose level indicates diabetes in symptomatic patients?
Greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
What is required for diagnosing diabetes in asymptomatic patients?
Criteria must be demonstrated on two separate occasions
What HbA1c level is diagnostic of diabetes mellitus according to WHO?
Greater than or equal to 6.5% (48 mmol/mol)
What HbA1c level is diagnostic of diabetes mellitus according to WHO?
Greater than or equal to 6.5% (48 mmol/mol)
True or False: An HbA1c value of less than 6.5% excludes diabetes.
False
What must be done to confirm a diabetes diagnosis in asymptomatic patients with HbA1c?
The test must be repeated
What can cause misleading HbA1c results?
Increased red cell turnover
Fill in the blank: A glucose tolerance test involves a fasting blood glucose followed by a _______ glucose load.
75g
What are the 4 main ways to check blood glucose?
- Finger-prick bedside glucose monitor
- One-off blood glucose (fasting or non-fasting)
- HbA1c (measures average glucose over 2-3 months)
- Glucose tolerance test (fasting glucose followed by 75g glucose load and a second reading after 2 hours)
What fasting glucose level indicates diabetes in symptomatic patients?
Greater than or equal to 7.0 mmol/l
What random glucose level indicates diabetes in symptomatic patients?
Greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
What is required for diagnosing diabetes in asymptomatic patients?
Criteria must be demonstrated on two separate occasions
True or False: An HbA1c value of less than 6.5% excludes diabetes.
False
What must be done to confirm a diabetes diagnosis in asymptomatic patients with HbA1c?
The test must be repeated
Fill in the blank: A glucose tolerance test involves a fasting blood glucose followed by a _______ glucose load.
75g
What is Type 1 diabetes mellitus (T1DM)?
An autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system
What results from the destruction of beta cells in T1DM?
An absolute deficiency of insulin resulting in raised glucose levels
When do patients typically develop Type 1 diabetes mellitus?
In childhood/early adult life
What is a common presentation of T1DM?
Patients may present unwell, possibly in diabetic ketoacidosis
What is Type 2 diabetes mellitus (T2DM)?
The most common cause of diabetes in the developed world caused by a relative deficiency of insulin due to an excess of adipose tissue
What leads to the development of T2DM?
Not enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up
What is prediabetes?
A term for patients who don’t yet meet the criteria for a formal diagnosis of T2DM but are likely to develop the condition over the next few years
What interventions are recommended for patients with prediabetes?
Closer monitoring and lifestyle interventions such as weight loss
What is gestational diabetes?
A condition where some pregnant women develop raised glucose levels during pregnancy
Why is it important to detect gestational diabetes?
Untreated gestational diabetes may lead to complications
What is Type 1 diabetes mellitus (T1DM)?
An autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system
What results from the destruction of beta cells in T1DM?
An absolute deficiency of insulin resulting in raised glucose levels
When do patients typically develop Type 1 diabetes mellitus?
In childhood/early adult life
What is a common presentation of T1DM?
Patients may present unwell, possibly in diabetic ketoacidosis
What is Type 2 diabetes mellitus (T2DM)?
The most common cause of diabetes in the developed world caused by a relative deficiency of insulin due to an excess of adipose tissue
What leads to the development of T2DM?
Not enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up
What interventions are recommended for patients with prediabetes?
Closer monitoring and lifestyle interventions such as weight loss
What is gestational diabetes?
A condition where some pregnant women develop raised glucose levels during pregnancy
What does MODY stand for?
Maturity onset diabetes of the young
What type of disorders does MODY represent?
Inherited genetic disorders affecting the production of insulin
What are common symptoms of MODY?
Asymptomatic hyperglycaemia with progression to more severe complications such as diabetic ketoacidosis
What is LADA?
Latent autoimmune diabetes in adults
How do the majority of patients with autoimmune-related diabetes present?
Younger in life
What is a common misdiagnosis for patients with LADA?
Type 2 diabetes mellitus (T2DM)
What can cause diabetes to develop aside from genetic factors?
Any pathological process which damages the insulin-producing cells of the pancreas
Name two examples of conditions that may lead to diabetes.
- Chronic pancreatitis
- Haemochromatosis
What type of drugs may cause raised glucose levels?
Glucocorticoids
True or False: LADA is commonly diagnosed in older adults.
False
Fill in the blank: MODY results in younger patients developing symptoms similar to those with _______.
T2DM
What type of disorders does MODY represent?
Inherited genetic disorders affecting the production of insulin
What are common symptoms of MODY?
Asymptomatic hyperglycaemia with progression to more severe complications such as diabetic ketoacidosis
How do the majority of patients with autoimmune-related diabetes present?
Younger in life
What is a common misdiagnosis for patients with LADA?
Type 2 diabetes mellitus (T2DM)
What can cause diabetes to develop aside from genetic factors?
Any pathological process which damages the insulin-producing cells of the pancreas
Name two examples of conditions that may lead to diabetes.
- Chronic pancreatitis
- Haemochromatosis
True or False: LADA is commonly diagnosed in older adults.
False
What is the primary mechanism of action of insulin?
Direct replacement for endogenous insulin
What is the primary route of administration for insulin?
Subcutaneous
What are the main side effects of insulin?
- Hypoglycaemia
- Weight gain
- Lipodystrophy
What is the primary mechanism of action of Metformin?
- Increases insulin sensitivity
- Decreases hepatic gluconeogenesis
What is the route of administration for Metformin?
Oral
What are the main side effects of Metformin?
- Gastrointestinal upset
- Lactic acidosis
Fill in the blank: The main side effect of insulin is _______.
Hypoglycaemia
Fill in the blank: Metformin is administered via _______.
Oral
True or False: Insulin decreases hepatic gluconeogenesis.
False
True or False: Lactic acidosis is a side effect of Metformin.
True
What is the primary mechanism of action of insulin?
Direct replacement for endogenous insulin
What is the primary mechanism of action of Metformin?
- Increases insulin sensitivity
- Decreases hepatic gluconeogenesis
What is the route of administration for Metformin?
Oral
What are the main side effects of Metformin?
- Gastrointestinal upset
- Lactic acidosis
Fill in the blank: The main side effect of insulin is _______.
Hypoglycaemia
What do sulfonylureas do?
Stimulate pancreatic beta cells to secrete insulin
What is the primary action of thiazolidinediones?
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
What is the mechanism of action for DPP-4 inhibitors?
Increases incretin levels which inhibit glucagon secretion
What do SGLT-2 inhibitors do?
Inhibits reabsorption of glucose in the kidney
What is the function of GLP-1 agonists?
Incretin mimetic which inhibits glucagon secretion
What is the administration route for sulfonylureas?
Oral
What is the administration route for thiazolidinediones?
Oral
What is the administration route for DPP-4 inhibitors?
Oral
What is the administration route for SGLT-2 inhibitors?
Oral
What is the administration route for GLP-1 agonists?
Subcutaneous
What is a common side effect of sulfonylureas?
Hypoglycaemia
What is a common side effect of thiazolidinediones?
Weight gain
What is a potential side effect of DPP-4 inhibitors?
Hyponatraemia
What is a side effect of SGLT-2 inhibitors?
Urinary tract infection
What is a common side effect of GLP-1 agonists?
Nausea and vomiting
What risk is associated with the use of thiazolidinediones?
Fluid retention
What increased risk is associated with GLP-1 agonists?
Increased risk of pancreatitis
True or False: NICE provides guidelines on how drug therapy should be used in T2DM.
True
What is the primary goal of managing diabetes mellitus?
The principle of managing diabetes mellitus includes:
* Drug therapy to normalise blood glucose levels
* Monitoring for and treating any complications related to diabetes
* Modifying any other risk factors for other conditions such as cardiovascular disease
These principles ensure comprehensive care for diabetes patients.
What is required for patients with Type 1 diabetes to control blood sugar levels?
Patients with Type 1 diabetes always require insulin to control blood sugar levels due to an absolute deficiency of insulin.
There is no pancreatic tissue left to stimulate with drugs.
What are the different types of insulin based on?
Different types of insulin are available according to their duration of action.
This affects how quickly and how long insulin works in the body.
How is Type 2 diabetes primarily managed?
The majority of patients with Type 2 diabetes are controlled using oral medication.
This includes lifestyle modifications alongside medication.
What is the first-line drug for the vast majority of Type 2 diabetes patients?
The first-line drug for the vast majority of patients with Type 2 diabetes is metformin.
Metformin helps to lower blood sugar levels and improve insulin sensitivity.
Name some second-line drugs for Type 2 diabetes management.
Second-line drugs include:
* Sulfonylureas
* Gliptins
* Pioglitazone
These are used when metformin alone is insufficient.
What happens if oral medication is not sufficiently controlling blood glucose in Type 2 diabetes?
If oral medication is not controlling the blood glucose to a sufficient degree, then insulin is used.
This indicates a progression in treatment strategies for diabetes management.
What is diabetic foot disease?
An important complication of diabetes mellitus that should be screened for regularly
NICE produced guidelines relating to diabetic foot disease in 2015.
What are the two main factors that lead to diabetic foot disease?
- Neuropathy
- Peripheral arterial disease
What is one consequence of neuropathy in diabetic foot disease?
Loss of protective sensation
Example: not noticing a stone in the shoe
What is Charcot’s arthropathy?
A condition that can occur due to neuropathy in diabetic foot disease
What are some presentations of diabetic foot disease related to neuropathy?
- Loss of sensation
What are some presentations of diabetic foot disease related to ischaemia?
- Absent foot pulses
- Reduced ankle-brachial pressure index (ABPI)
- Intermittent claudication
What are some complications of diabetic foot disease?
- Calluses
- Ulceration
- Charcot’s arthropathy
- Cellulitis
- Osteomyelitis
- Gangrene
How often should patients with diabetes be screened for diabetic foot disease?
At least annually
What is one method for screening ischaemia in diabetic foot disease?
Palpating for both the dorsalis pedis pulse and posterior tibial artery pulse
What tool is used to screen for neuropathy in diabetic foot disease?
A 10 g monofilament
What does NICE recommend for patients with diabetes regarding diabetic foot disease?
To risk stratify patients
What defines low risk in diabetic foot assessment?
No risk factors except callus
This includes no deformity or previous ulceration.
What are the characteristics of moderate risk in diabetic foot assessment?
• Deformity or previous ulceration
• Neuropathy
• Non-critical limb ischaemia
• Neuropathy and non-critical limb ischaemia together
Patients with moderate risk should be monitored regularly.
What factors indicate high risk in diabetic foot assessment?
• Previous amputation
• On renal replacement therapy
• Neuropathy in combination with callus and/or deformity
• Non-critical limb ischaemia in combination with callus and/or deformity
High-risk patients require regular follow-up.
What is the follow-up recommendation for patients at moderate or high risk?
Regular follow-up by the local diabetic foot centre
This applies to any problems other than simple calluses.
True or False: Simple calluses are considered a risk factor in diabetic foot assessment.
False
Simple calluses alone do not classify a patient as at risk.
Fill in the blank: Patients with _______ should be followed up regularly by the local diabetic foot centre.
moderate or high risk
This includes those with any problems other than simple calluses.
What is androgen insensitivity syndrome?
An X-linked recessive condition resulting in end-organ resistance to testosterone, causing genotypically male children (46XY) to have a female phenotype.
Affected individuals have a rudimentary vagina and testes but no uterus.
What karyotype is associated with androgen insensitivity syndrome?
46 XY
What is the defect in androgen insensitivity syndrome?
Defect in androgen receptor
What are the hormone levels in individuals with androgen insensitivity syndrome?
Elevated testosterone, oestrogen, and LH levels
What is 5-a reductase deficiency?
An autosomal recessive condition resulting in the inability of males to convert testosterone to dihydrotestosterone (DHT).
This condition leads to ambiguous genitalia in the newborn period.
What karyotype is associated with 5-a reductase deficiency?
46 XY
What common condition is associated with 5-a reductase deficiency in newborns?
Ambiguous genitalia
What is a common feature seen in individuals with 5-a reductase deficiency?
Hypospadias
What happens at puberty for individuals with 5-a reductase deficiency?
Virilization occurs
In 5-a reductase deficiency, what is the status of the external genitalia?
External genitalia are female or ambiguous
What is male pseudohermaphroditism?
A condition where individuals have testes but external genitalia are female or ambiguous, which may be secondary to androgen insensitivity syndrome.
This term encompasses various conditions, including androgen insensitivity and 5-a reductase deficiency.
What is female pseudohermaphroditism?
An individual has ovaries but external genitalia that are male (virilized) or ambiguous
May be secondary to congenital adrenal hyperplasia
What is the chromosomal makeup associated with female pseudohermaphroditism?
46 XX
What is true hermaphroditism?
A condition where both ovarian and testicular tissue are present
Very rare
What are the possible chromosomal makeups for true hermaphroditism?
46 XX or 47 XXY
True or False: Female pseudohermaphroditism can occur in individuals with 47 XXY chromosomes.
False
What is female pseudohermaphroditism?
An individual has ovaries but external genitalia that are male (virilized) or ambiguous
May be secondary to congenital adrenal hyperplasia
What is the chromosomal makeup associated with female pseudohermaphroditism?
46 XX
What are the possible chromosomal makeups for true hermaphroditism?
46 XX or 47 XXY
True or False: Female pseudohermaphroditism can occur in individuals with 47 XXY chromosomes.
False
What is Kallman’s syndrome?
A cause of delayed puberty secondary to hypogonadotrophic hypogonadism
It is usually inherited as an X-linked recessive trait.
What is a key clinical clue for Kallman’s syndrome?
Lack of smell (anosmia) in a boy with delayed puberty
List the features of Kallman’s syndrome.
- Delayed puberty
- Hypogonadism
- Cryptorchidism
- Anosmia
- Low sex hormone levels
- Inappropriately low/normal LH and FSH levels
- Typically normal or above average height
What additional defects may be seen in some patients with Kallman’s syndrome?
Cleft lip/palate and visual/hearing defects
What is Androgen insensitivity syndrome?
An X-linked recessive condition due to end-organ resistance to testosterone
What is the phenotype of genotypically male children (46XY) with complete androgen insensitivity syndrome?
Female phenotype
What is the new term for testicular feminisation syndrome?
Complete androgen insensitivity syndrome
What is Kallman’s syndrome?
A cause of delayed puberty secondary to hypogonadotrophic hypogonadism
It is usually inherited as an X-linked recessive trait.
What causes Kallman’s syndrome?
Failure of GnRH-secreting neurons to migrate to the hypothalamus
List the features of Kallman’s syndrome.
- Delayed puberty
- Hypogonadism
- Cryptorchidism
- Anosmia
- Low sex hormone levels
- Inappropriately low/normal LH and FSH levels
- Typically normal or above average height
What additional defects may be seen in some patients with Kallman’s syndrome?
Cleft lip/palate and visual/hearing defects
What is Androgen insensitivity syndrome?
An X-linked recessive condition due to end-organ resistance to testosterone
What is the new term for testicular feminisation syndrome?
Complete androgen insensitivity syndrome
What is androgen insensitivity syndrome?
An X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype
Complete androgen insensitivity syndrome is also known as testicular feminisation syndrome.
What are the key features of complete androgen insensitivity syndrome?
• Primary amenorrhoea
• Undescended testes causing groin swellings
• Breast development may occur as a result of conversion of testosterone to oestradiol
How is androgen insensitivity syndrome diagnosed?
Buccal smear or chromosomal analysis to reveal 46XY genotype
What is the management approach for androgen insensitivity syndrome?
• Counselling - raise child as female
• Bilateral orchidectomy
• Oestrogen therapy
True or False: Androgen insensitivity syndrome can lead to testicular cancer due to undescended testes.
True
Fill in the blank: Complete androgen insensitivity syndrome is also known as _______.
testicular feminisation syndrome
What is Gitelman’s syndrome?
A defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
Gitelman’s syndrome is characterized by metabolic abnormalities, including hypomagnesaemia and hypokalaemia.
Which electrolyte imbalances are associated with Gitelman’s syndrome?
- Hypokalaemia
- Hypomagnesaemia
- Hypocalciuria
- Metabolic alkalosis
These imbalances result from the defect in the Na+ Cl- transporter.
What is the bp in hyperosmolar hyperglycaemic state?
Normotension
This condition is characterized by elevated blood glucose levels without significant ketoacidosis.
True or False: Hypercalcaemia can have multiple causes.
True
Causes of hypercalcaemia include primary hyperparathyroidism, malignancy, and vitamin D intoxication.
What are the features of hypoglycaemia?
- Sweating
- Hunger
- Palpitations
- Confusion
Hypoglycaemia symptoms can vary and may include neuroglycopenic symptoms as well.
What is a common feature of Graves’ disease?
- Hyperthyroidism
- Goiter
- Eye changes (exophthalmos)
Graves’ disease is an autoimmune disorder that leads to excessive thyroid hormone production.
Fill in the blank: Gitelman’s syndrome is characterized by _______.
[hypokalaemia]
Hypokalaemia is a defining feature of Gitelman’s syndrome due to the renal losses.
What is the primary defect in Gitelman’s syndrome?
Thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
This defect leads to electrolyte imbalances and metabolic issues.
What is the relationship between metabolic alkalosis and Gitelman’s syndrome?
It is a result of the renal loss of potassium and hydrogen ions.
Metabolic alkalosis occurs due to the body’s compensatory mechanisms in response to hypokalaemia.
What are glucagonomas?
Glucagonomas are small tumours, almost always found in the pancreas, and frequently malignant.
From which cells do glucagonomas arise?
They arise from the alpha cells of the pancreas.
What are the common presentations of glucagonoma?
They present with diabetes mellitus, venous thrombo-embolism, and the classical rash of necrolytic migratory erythema - a red, blistering rash.
What serum level of glucagon suggests a diagnosis of glucagonoma?
A serum level of glucagon > 1000pg/ml usually suggests the diagnosis.
What imaging technique is required for diagnosing glucagonoma?
Imaging with CT scanning is also required.
What are the treatment options for glucagonoma?
Treatment options include surgical resection and octreotide.
What is Graves’ disease?
An autoimmune thyroid disease where the body produces IgG antibodies to the TSH receptor
It is the most common cause of thyrotoxicosis.
What age group is typically affected by Graves’ disease?
Women aged 30-50 years
What are the typical features of thyrotoxicosis?
Increased metabolism, weight loss, heat intolerance, palpitations, and anxiety
Specific features may vary among patients.
What are the eye signs associated with Graves’ disease?
Exophthalmos and ophthalmoplegia
Eye signs occur in 30% of patients.
What is pretibial myxoedema?
A skin condition seen in Graves’ disease characterized by swelling on the shins
What is thyroid acropachy?
A triad of digital clubbing, soft tissue swelling of hands and feet, and periosteal new bone formation
What percentage of patients with Graves’ disease have TSH receptor stimulating antibodies?
90%
What percentage of patients with Graves’ disease have anti-thyroid peroxidase antibodies?
75%
What does thyroid scintigraphy show in Graves’ disease?
Diffuse, homogenous, increased uptake of radioactive iodine
True or False: Graves’ disease is the most common cause of hypothyroidism.
False
Fill in the blank: Graves’ disease is characterized by the production of _______ antibodies to the TSH receptor.
[IgG]
What is Graves’ disease?
An autoimmune thyroid disease where the body produces IgG antibodies to the TSH receptor
It is the most common cause of thyrotoxicosis.
What age group is typically affected by Graves’ disease?
Women aged 30-50 years
What are the typical features of thyrotoxicosis?
Increased metabolism, weight loss, heat intolerance, palpitations, and anxiety
Specific features may vary among patients.
What is pretibial myxoedema?
A skin condition seen in Graves’ disease characterized by swelling on the shins
What is thyroid acropachy?
A triad of digital clubbing, soft tissue swelling of hands and feet, and periosteal new bone formation
What percentage of patients with Graves’ disease have TSH receptor stimulating antibodies?
90%
What does thyroid scintigraphy show in Graves’ disease?
Diffuse, homogenous, increased uptake of radioactive iodine
True or False: Graves’ disease is the most common cause of hypothyroidism.
False
Fill in the blank: Graves’ disease is characterized by the production of _______ antibodies to the TSH receptor.
[IgG]
What are the three types of growth?
- Infancy (birth to 2-years-old)
- Childhood (3 to 11-years-old)
- Puberty (12 to 18-years-old)
What is the most important factor affecting fetal growth?
Environmental factors, such as maternal nutrition and uterine capacity
What are the factors that affect fetal growth?
- Environmental
- Placental
- Hormonal
- Genetic (predominately maternal)
What drives growth in infancy?
Nutrition and insulin
How does poorly controlled maternal diabetes affect fetal growth?
It leads to high fetal insulin production, resulting in hypoglycaemia and macrosomia
In infancy, what is the role of growth hormone?
Growth isn’t affected by growth hormone due to low receptor amounts
What drives growth during childhood?
Growth hormone and thyroxine
What hormones are primarily responsible for growth during puberty?
Growth hormone and sex steroids
What is the significance of high amounts of growth hormone during puberty?
It is important for growth spurts
What is the most important determinant of final adult height?
Genetic factors
Fill in the blank: In infancy, growth is driven by _______.
[Nutrition and insulin]
True or False: Growth during infancy is significantly affected by thyroid hormones.
False
What is the age range for childhood growth?
3 to 11-years-old
What are the effects of hypopituitarism on growth in infancy?
There is no effect on growth
What are the three types of growth?
- Infancy (birth to 2-years-old)
- Childhood (3 to 11-years-old)
- Puberty (12 to 18-years-old)
What is the most important factor affecting fetal growth?
Environmental factors, such as maternal nutrition and uterine capacity
What are the factors that affect fetal growth?
- Environmental
- Placental
- Hormonal
- Genetic (predominately maternal)
What drives growth in infancy?
Nutrition and insulin
How does poorly controlled maternal diabetes affect fetal growth?
It leads to high fetal insulin production, resulting in hypoglycaemia and macrosomia
In infancy, what is the role of growth hormone?
Growth isn’t affected by growth hormone due to low receptor amounts
What drives growth during childhood?
Growth hormone and thyroxine
What hormones are primarily responsible for growth during puberty?
Growth hormone and sex steroids
What is the significance of high amounts of growth hormone during puberty?
It is important for growth spurts
What is the most important determinant of final adult height?
Genetic factors
Fill in the blank: In infancy, growth is driven by _______.
[Nutrition and insulin]
True or False: Growth during infancy is significantly affected by thyroid hormones.
False
What is the age range for childhood growth?
3 to 11-years-old
What are the effects of hypopituitarism on growth in infancy?
There is no effect on growth
Fill in the blank: _______ is a GnRH agonist that can cause gynaecomastia.
Goserelin
Goserelin is used in hormone-sensitive conditions and can lead to changes in estrogen levels.
Name two very rare drug causes of gynaecomastia.
- Tricyclics
- Isoniazid
These drugs are less commonly associated with the development of gynaecomastia compared to others.
What type of medications are known to cause gynaecomastia aside from hormonal treatments?
- Calcium channel blockers
- Heroin
- Busulfan
- Methyldopa
These medications have been reported to cause gynaecomastia, although they are considered very rare causes.
What are the effects of estrogens and anabolic steroids on gynaecomastia?
They can cause gynaecomastia
Both estrogens and anabolic steroids can increase breast tissue due to their hormonal effects.
List two drug classes that can lead to gynaecomastia.
- Hormonal agents
- Psychotropic medications
Hormonal agents directly affect estrogen levels, while psychotropic medications can have indirect effects.
What is the most common drug cause of gynaecomastia?
Spironolactone
Spironolactone is a diuretic that can cause breast tissue enlargement in males.
List three common drugs that can cause gynaecomastia.
- Spironolactone
- Cimetidine
- Digoxin
These drugs are known to have hormonal effects that may lead to breast tissue development.
True or False: Cannabis is a drug that can cause gynaecomastia.
True
Cannabis has been associated with hormonal changes that may contribute to gynaecomastia.
What type of medications are known to cause gynaecomastia aside from hormonal treatments?
- Calcium channel blockers
- Heroin
- Busulfan
- Methyldopa
These medications have been reported to cause gynaecomastia, although they are considered very rare causes.
What are the effects of estrogens and anabolic steroids on gynaecomastia?
They can cause gynaecomastia
Both estrogens and anabolic steroids can increase breast tissue due to their hormonal effects.
List two drug classes that can lead to gynaecomastia.
- Hormonal agents
- Psychotropic medications
Hormonal agents directly affect estrogen levels, while psychotropic medications can have indirect effects.
What is gynaecomastia?
An abnormal amount of breast tissue in males, usually caused by an increased oestrogen:androgen ratio.
It is important to differentiate the causes of galactorrhoea from those of gynaecomastia.
What are the physiological causes of gynaecomastia?
Normal in puberty.
Gynaecomastia can be a common occurrence during puberty due to hormonal changes.
Name a syndrome associated with androgen deficiency that can cause gynaecomastia.
Kallmann’s syndrome, Klinefelter’s syndrome.
These syndromes are characterized by various hormonal imbalances.
What testicular condition can lead to gynaecomastia?
Testicular failure, e.g., mumps.
Mumps can lead to orchitis, affecting testicular function.
How can liver disease contribute to gynaecomastia?
Liver disease can disrupt hormone metabolism, leading to an increased oestrogen level.
Liver dysfunction affects the clearance of hormones.
What type of cancer can cause gynaecomastia?
Testicular cancer, e.g., seminoma secreting hCG.
Certain testicular tumors can secrete hormones that increase oestrogen levels.
What is ectopic tumour secretion?
Hormonal secretion from tumours located outside the usual endocrine glands, which can lead to gynaecomastia.
Ectopic secretion can mimic normal hormone levels.
Name a metabolic condition that can lead to gynaecomastia.
Hyperthyroidism.
Increased thyroid hormone levels can alter the balance of sex hormones.
What is the effect of haemodialysis on gynaecomastia?
Haemodialysis can lead to hormonal imbalances that may result in gynaecomastia.
The process can affect kidney function and hormone excretion.
What is the most common drug cause of gynaecomastia?
Spironolactone.
Spironolactone is a potassium-sparing diuretic that can increase oestrogen levels.
List two other drugs that can cause gynaecomastia.
- Cimetidine
- Digoxin
Both medications have been associated with hormonal changes leading to gynaecomastia.
What recreational drug is known to cause gynaecomastia?
Cannabis.
Cannabis use can lead to hormonal imbalances affecting breast tissue.
What medication used for hair loss can cause gynaecomastia?
Finasteride.
Finasteride affects hormone levels and can lead to breast tissue development.
What type of agonists can lead to gynaecomastia?
GnRH agonists, e.g., goserelin, buserelin.
These drugs influence the hormonal axis, potentially increasing oestrogen levels.
Fill in the blank: Gynaecomastia can also be caused by _______.
Oestrogens, anabolic steroids.
Exogenous hormones can disrupt the natural balance of sex hormones.
What is gynaecomastia?
An abnormal amount of breast tissue in males, usually caused by an increased oestrogen:androgen ratio.
It is important to differentiate the causes of galactorrhoea from those of gynaecomastia.
What are the physiological causes of gynaecomastia?
Normal in puberty.
Gynaecomastia can be a common occurrence during puberty due to hormonal changes.
Name a syndrome associated with androgen deficiency that can cause gynaecomastia.
Kallmann’s syndrome, Klinefelter’s syndrome.
These syndromes are characterized by various hormonal imbalances.
What testicular condition can lead to gynaecomastia?
Testicular failure, e.g., mumps.
Mumps can lead to orchitis, affecting testicular function.
How can liver disease contribute to gynaecomastia?
Liver disease can disrupt hormone metabolism, leading to an increased oestrogen level.
Liver dysfunction affects the clearance of hormones.
What type of cancer can cause gynaecomastia?
Testicular cancer, e.g., seminoma secreting hCG.
Certain testicular tumors can secrete hormones that increase oestrogen levels.
What is ectopic tumour secretion?
Hormonal secretion from tumours located outside the usual endocrine glands, which can lead to gynaecomastia.
Ectopic secretion can mimic normal hormone levels.
Name a metabolic condition that can lead to gynaecomastia.
Hyperthyroidism.
Increased thyroid hormone levels can alter the balance of sex hormones.
What is the effect of haemodialysis on gynaecomastia?
Haemodialysis can lead to hormonal imbalances that may result in gynaecomastia.
The process can affect kidney function and hormone excretion.
What is the most common drug cause of gynaecomastia?
Spironolactone.
Spironolactone is a potassium-sparing diuretic that can increase oestrogen levels.
List two other drugs that can cause gynaecomastia.
- Cimetidine
- Digoxin
Both medications have been associated with hormonal changes leading to gynaecomastia.
What recreational drug is known to cause gynaecomastia?
Cannabis.
Cannabis use can lead to hormonal imbalances affecting breast tissue.
What medication used for hair loss can cause gynaecomastia?
Finasteride.
Finasteride affects hormone levels and can lead to breast tissue development.
What type of agonists can lead to gynaecomastia?
GnRH agonists, e.g., goserelin, buserelin.
These drugs influence the hormonal axis, potentially increasing oestrogen levels.
Fill in the blank: Gynaecomastia can also be caused by _______.
Oestrogens, anabolic steroids.
Exogenous hormones can disrupt the natural balance of sex hormones.
What is Hashimoto’s thyroiditis?
An autoimmune disorder of the thyroid gland typically associated with hypothyroidism.
It may have a transient thyrotoxicosis in the acute phase.
How much more common is Hashimoto’s thyroiditis in women compared to men?
10 times more common
This prevalence highlights the gender disparity in autoimmune disorders.
What are the key features of Hashimoto’s thyroiditis?
- Features of hypothyroidism
- Firm, non-tender goitre
- Presence of anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) antibodies
These features are critical for diagnosis.
What other autoimmune conditions are associated with Hashimoto’s thyroiditis?
- Coeliac disease
- Type 1 diabetes mellitus
- Vitiligo
The association with other autoimmune diseases is significant for patient management.
What type of lymphoma is associated with Hashimoto’s thyroiditis?
MALT lymphoma
MALT lymphoma is a type of cancer that affects the mucosa-associated lymphoid tissue.
What is the primary cause of hypothyroidism related to Hashimoto’s thyroiditis?
Hashimoto’s thyroiditis
Other causes include iodine deficiency and subacute thyroiditis.
Fill in the blank: Hashimoto’s thyroiditis is typically associated with _______.
hypothyroidism
True or False: Hashimoto’s thyroiditis can cause transient thyrotoxicosis.
True
What is the characteristic texture of the goitre in Hashimoto’s thyroiditis?
Firm and non-tender
The goitre may vary in size and tenderness depending on the phase of the disease.
What antibodies are commonly found in Hashimoto’s thyroiditis?
- Anti-thyroid peroxidase (TPO)
- Anti-thyroglobulin (Tg)
The presence of these antibodies is crucial for diagnosis.
What is the commonest cause of hypercalcaemia in hospitalised patients?
Malignancy
Malignancy may involve processes such as PTHrP secretion from tumors and bone metastases.
What are two processes by which malignancy can cause hypercalcaemia?
- PTHrP from the tumour (e.g., squamous cell lung cancer)
- Bone metastases
What is the role of myeloma in hypercalcaemia?
Increased osteoclastic bone resorption due to local cytokines
Cytokines such as IL-1 and tumour necrosis factor are released by myeloma cells.
What is the key investigation for patients with hypercalcaemia?
Measuring parathyroid hormone levels
Name two granulomatous diseases that can lead to hypercalcaemia.
- Sarcoidosis
- Tuberculosis
What is a possible cause of hypercalcaemia related to vitamin D?
Vitamin D intoxication
Fill in the blank: Milk-______ syndrome can cause hypercalcaemia.
alkali
What types of drugs can contribute to hypercalcaemia?
- Thiazides
- Calcium-containing antacids
What condition is usually normal but may cause hypercalcaemia with prolonged immobilisation?
Paget’s disease of the bone
True or False: Hypercalcaemia can be caused by thyrotoxicosis.
True
What are some causes of hypercalcaemia listed in the document?
- Malignancy
- Sarcoidosis
- Vitamin D intoxication
- Thyrotoxicosis
- Milk-alkali syndrome
- Thiazides
- Calcium-containing antacids
- Paget’s disease of the bone
What is sick euthyroid syndrome also referred to as?
Non-thyroidal illness
This term reflects the condition’s association with systemic illness rather than primary thyroid disease.
In sick euthyroid syndrome, what is often said about the levels of TSH, thyroxine, and T3?
Everything is low
This statement is a simplification; in many cases, TSH remains within the normal range despite low levels of thyroxine and T3.
What is the typical TSH level in sick euthyroid syndrome?
Within the normal range
This is considered inappropriately normal given the low levels of thyroxine and T3.
What happens to the changes in hormone levels upon recovery from the systemic illness in sick euthyroid syndrome?
Changes are reversible
This characteristic underscores that no treatment is usually needed.
Is treatment usually needed for sick euthyroid syndrome?
No
Treatment is typically unnecessary as the condition resolves with recovery from the underlying systemic illness.
What does Waterhouse-Friderichsen syndrome describe?
Adrenal gland failure secondary to a previous adrenal haemorrhage caused by severe bacterial infection
This syndrome is associated with severe infections leading to adrenal insufficiency.
What is the most common cause of Waterhouse-Friderichsen syndrome?
Neisseria meningitidis
Other causes include Haemophilus influenzae, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus pneumoniae.
List some features of hypoadrenalism associated with Waterhouse-Friderichsen syndrome.
- Lethargy
- Weakness
- Anorexia
- Nausea & vomiting
- Weight loss
- Hyperpigmentation (especially palmar creases)
- Vitiligo
- Loss of pubic hair in women
These symptoms reflect the adrenal insufficiency present in the syndrome.
What crisis symptoms are associated with Waterhouse-Friderichsen syndrome?
- Collapse
- Shock
- Pyrexia
These crisis symptoms indicate severe adrenal crisis due to the syndrome.
What does Waterhouse-Friderichsen syndrome describe?
Adrenal gland failure secondary to a previous adrenal haemorrhage caused by severe bacterial infection
This syndrome is associated with severe infections leading to adrenal insufficiency.
What crisis symptoms are associated with Waterhouse-Friderichsen syndrome?
- Collapse
- Shock
- Pyrexia
These crisis symptoms indicate severe adrenal crisis due to the syndrome.
What is the purpose of the water deprivation test?
To evaluate patients who have polydipsia
Polydipsia is excessive thirst, which often leads to increased fluid intake.
What is the first step in conducting a water deprivation test?
Prevent the patient from drinking water
This is essential to assess the body’s ability to concentrate urine under conditions of dehydration.
What should the patient do after being instructed not to drink water during the test?
Empty their bladder
This allows for accurate measurement of urine osmolality.
How frequently should urine and plasma osmolalities be measured during the water deprivation test?
Hourly
This regular monitoring helps track changes in osmolality as dehydration progresses.
What is the expected starting plasma osmolarity in a normal individual?
Normal
Normal plasma osmolarity typically ranges between 275 and 295 mOsm/kg.
What urine osmolarity indicates normal kidney function after water deprivation?
> 600
This suggests that the kidneys are able to concentrate urine effectively.
What urine osmolarity is observed in psychogenic polydipsia?
> 400
In psychogenic polydipsia, the body still retains some ability to concentrate urine despite excessive fluid intake.
What is the urine osmolarity result for cranial diabetes insipidus after the water deprivation test?
> 600
This indicates that the kidneys can concentrate urine when stimulated with DDAVP (desmopressin).
What urine osmolarity is characteristic of nephrogenic diabetes insipidus?
< 300
Nephrogenic diabetes insipidus occurs when the kidneys are unable to respond to antidiuretic hormone (ADH).
True or False: In nephrogenic diabetes insipidus, urine osmolarity can exceed 600 mOsm/kg.
False
Nephrogenic diabetes insipidus is characterized by the inability to concentrate urine, resulting in low urine osmolarity.
What accounts for around 50-60% of cases of thyrotoxicosis?
Graves’ disease
Graves’ disease is an autoimmune disorder that leads to hyperthyroidism.
List three causes of thyrotoxicosis.
- Toxic nodular goitre
- Acute phase of subacute (De Quervain’s) thyroiditis
- Acute phase of post-partum thyroiditis
True or False: Patients with existing thyrotoxicosis should receive iodinated contrast medium.
False
Administration of iodinated contrast can lead to hyperthyroidism in these patients.
What occurs as a result of administering iodinated contrast to patients with existing thyrotoxicosis?
Hyperthyroidism developing over 2-12 weeks
This is due to a large iodine load to the thyroid.
What are the typical laboratory findings in thyrotoxicosis?
- TSH down
- T4 and T3 up
- Thyroid autoantibodies
Fill in the blank: The acute phase of _______ thyroiditis may lead to thyrotoxicosis.
Post-partum
What type of thyroiditis can present with an initial thyrotoxic phase?
Hashimoto’s thyroiditis
Hashimoto’s thyroiditis typically leads to hypothyroidism but may have an initial thyrotoxic phase.
What is a common complication of amiodarone therapy related to the thyroid?
Thyrotoxicosis
Amiodarone can cause thyroid dysfunction due to its high iodine content.
What is the effect of iodine deficiency on thyroid function?
It is better
Iodine deficiency can lead to hypothyroidism, but the body often compensates initially.
What is the definition of hyperthyroidism?
A condition where the thyroid gland produces excess thyroid hormones
Hyperthyroidism can lead to symptoms such as weight loss, heat intolerance, and increased heart rate.
What is the major hormone active in target cells produced by the thyroid gland?
Triiodothyronine (T3)
T3 is the most biologically active form of thyroid hormone.
Which thyroid hormone is the most prevalent form in plasma but less biologically active than T3?
Thyroxine (T4)
T4 is converted to T3 in target tissues.
What is the function of calcitonin?
Lowers plasma calcium
Calcitonin is secreted by parafollicular cells of the thyroid gland.
What is the process by which thyroid hormones are synthesized?
Thyroid actively concentrates iodide to twenty-five times the plasma concentration
This process is crucial for the production of T3 and T4.
What stimulates the secretion of thyroid hormones?
Thyroid Stimulating Hormone (TSH)
TSH is released from the anterior pituitary gland.
How long are the normal reserves of thyroid hormones in the thyroid gland?
Approximately 3 months
This reserve allows for consistent hormone levels in the body.
In Graves’ disease, what do patients develop antibodies against?
TSH receptors on the thyroid gland
This leads to chronic stimulation of the thyroid gland.
What is typically observed in individuals with Graves’ disease regarding thyroid hormones and TSH levels?
Raised thyroid hormones and low TSH
This pattern is due to the negative feedback mechanism.
What should be checked in individuals presenting with hyperthyroidism?
Thyroid receptor autoantibodies
These are present in up to 85% of cases of Graves’ disease.
Fill in the blank: Iodide is oxidized by _______ in the follicular cells to atomic iodine.
peroxidase
This is a crucial step in the synthesis of thyroid hormones.
What are the two main types of thyroid hormones synthesized from iodinated tyrosine residues?
T3 and T4
These hormones are formed through the coupling of iodinated tyrosine residues.
What percentage of insulinomas are malignant?
10% malignant
Additionally, 10% are multiple insulinomas.
What condition is often associated with multiple insulinomas?
Multiple Endocrine Neoplasia type 1 (MEN-1)
50% of patients with multiple tumours have MEN-1.
What are common features of hypoglycemia in insulinoma patients?
Symptoms typically occur early in the morning or just before a meal, including:
* diplopia
* weakness
Rapid weight gain may also be seen.
What laboratory findings are associated with insulinoma?
High insulin, raised proinsulin:insulin ratio, and high C-peptide
These findings are indicative of insulinoma.
What is the primary diagnostic method for insulinoma?
Supervised, prolonged fasting (up to 72 hours)
CT pancreas may also be used.
What is the main management strategy for insulinomas?
Surgery
Diazoxide and somatostatin are alternatives for patients not candidates for surgery.
Fill in the blank: The most common pancreatic endocrine tumour is _______.
[insulinoma]
What is hypospadias characterized by?
- A ventral urethral meatus
- A hooded prepuce
- Chordee (ventral curvature of the penis) in more severe forms
- The urethral meatus may open more proximally in more severe variants
75% of the openings are distally located.
What is the most common occurrence of hypospadias?
Hypospadias most commonly occurs as an isolated disorder
Associated conditions include cryptorchidism (present in 10%) and inguinal hernia.
What should be done once hypospadias has been identified?
Infants should be referred to specialist services.
At what age is corrective surgery for hypospadias typically performed?
Around 12 months of age.
Why is it essential that a child is not circumcised prior to hypospadias surgery?
The foreskin may be used in the corrective procedure.
In boys with very distal disease, what may be needed?
No treatment may be needed.
What is the primary cause of primary hypoparathyroidism?
Decrease PTH secretion
Commonly secondary to thyroid surgery.
What are the main symptoms of hypoparathyroidism secondary to hypocalcaemia?
- Tetany: muscle twitching, cramping and spasm
- Chvostek’s sign: facial muscle twitching when tapping over the parotid
- Chronic symptoms: depression, cataracts
- ECG changes: prolonged QT interval
What is Chvostek’s sign?
Tapping over the parotid causes facial muscles to twitch
What is the relationship between hypoparathyroidism and calcium levels?
Low calcium levels lead to symptoms of hypoparathyroidism
What is pseudohypoparathyroidism?
Target cells being insensitive to PTH
Associated with short stature and shortened 4th and 5th metacarpals.
How do cAMP and phosphate levels change in hypoparathyroidism following PTH infusion?
Both cAMP and phosphate levels increase
What happens to cAMP and phosphate levels in pseudohypoparathyroidism type I after PTH infusion?
Neither cAMP nor phosphate levels are increased
In pseudohypoparathyroidism type II, how do cAMP levels respond to PTH infusion?
Only cAMP levels rise
What is pseudopseudohypoparathyroidism?
Similar phenotype to pseudohypoparathyroidism but with normal biochemistry
What is the effect of inflating a blood pressure cuff above systolic on the brachial artery in relation to tetany?
Causes carpal spasm
True or False: Primary hypoparathyroidism is classified as being secondary to surgery in most medical textbooks.
True
What is the primary cause of primary hypoparathyroidism?
Decrease PTH secretion
Commonly secondary to thyroid surgery.
What are the main symptoms of hypoparathyroidism secondary to hypocalcaemia?
- Tetany: muscle twitching, cramping and spasm
- Chvostek’s sign: facial muscle twitching when tapping over the parotid
- Chronic symptoms: depression, cataracts
- ECG changes: prolonged QT interval
What is Chvostek’s sign?
Tapping over the parotid causes facial muscles to twitch
What is the relationship between hypoparathyroidism and calcium levels?
Low calcium levels lead to symptoms of hypoparathyroidism
What is pseudohypoparathyroidism?
Target cells being insensitive to PTH
Associated with short stature and shortened 4th and 5th metacarpals.
How do cAMP and phosphate levels change in hypoparathyroidism following PTH infusion?
Both cAMP and phosphate levels increase
What happens to cAMP and phosphate levels in pseudohypoparathyroidism type I after PTH infusion?
Neither cAMP nor phosphate levels are increased
In pseudohypoparathyroidism type II, how do cAMP levels respond to PTH infusion?
Only cAMP levels rise
What is pseudopseudohypoparathyroidism?
Similar phenotype to pseudohypoparathyroidism but with normal biochemistry
What is the effect of inflating a blood pressure cuff above systolic on the brachial artery in relation to tetany?
Causes carpal spasm
True or False: Primary hypoparathyroidism is classified as being secondary to surgery in most medical textbooks.
True
What is the inheritance pattern of multiple endocrine neoplasia (MEN)?
Autosomal dominant disorder
What are the three main types of multiple endocrine neoplasia (MEN)?
MEN type I, MEN type IIa, MEN type IIb
What are the three P’s associated with MEN type I?
- Parathyroid
- Pituitary
- Pancreas
What is the most common presentation of MEN type I?
Hypercalcaemia
What percentage of patients with MEN type I have parathyroid hyperplasia?
95%
What is a common pancreatic tumor associated with MEN type I?
Insulinoma, gastrinoma
What is the primary genetic mutation associated with MEN type I?
MEN1 gene
What are the two P’s associated with MEN type IIa?
- Parathyroid
- Phaeochromocytoma
What percentage of patients with MEN type IIa have medullary thyroid cancer?
70%
What is the primary genetic mutation associated with MEN type IIa?
RET oncogene
What are the features of MEN type IIb?
- Medullary thyroid cancer
- Phaeochromocytoma
- Marfanoid body habitus
- Neuromas
What is the percentage of patients with MEN type IIb that have medullary thyroid cancer?
100%
What is the primary genetic mutation associated with MEN type IIb?
RET oncogene
What is a common complication of gastrinoma in MEN type I?
Recurrent peptic ulceration
Fill in the blank: MEN type I is characterized by three P’s: Parathyroid, Pituitary, and _______.
Pancreas
True or False: MEN type IIa is associated with a higher incidence of parathyroid disease than MEN type IIb.
True
What is neuroblastoma?
A type of cancer that arises from neural crest tissue, primarily affecting children
Neuroblastoma is one of the top five causes of cancer in children, accounting for around 7-8% of childhood malignancies.
What is the most common site for neuroblastoma tumors?
Adrenal medulla
Neuroblastoma can also arise from the sympathetic nervous system.
What is the median age of onset for neuroblastoma?
Around 20 months
List some common features of neuroblastoma. (8)
- Abdominal mass
- Pallor
- Weight loss
- Bone pain
- Limp
- Hepatomegaly
- Paraplegia
- Proptosis
What investigations are used for diagnosing neuroblastoma?
- Biopsy
- Raised urinary vanillylmandelic acid (VMA)
- Raised homovanillic acid (HVA)
- Calcification on abdominal x-ray
True or False: Neuroblastoma is a common malignancy in adults.
False
Fill in the blank: Neuroblastoma accounts for around _______ of childhood malignancies.
7-8%
What is the formula for calculating BMI?
BMI = weight (kg) / height (m) squared
What BMI range is classified as underweight?
< 18.49
What BMI range is classified as normal weight?
18.5 - 25
What BMI range is classified as overweight?
25 - 30
What BMI range is classified as Obese class 1?
30 - 35
What BMI range is classified as Obese class 2?
35 - 40
What BMI range is classified as Obese class 3?
> 40
What is the first step in the management of obesity?
Conservative: diet, exercise
What is a medical management option for obesity?
Orlistat
What is Orlistat’s mechanism of action?
Pancreatic lipase inhibitor
What are some adverse effects of Orlistat?
- Faecal urgency/incontinence
- Flatulence
What is the lower dose version of Orlistat available without prescription?
‘Alli’
According to NICE, when should Orlistat be prescribed?
- BMI of 28 kg/m^2 or more with associated risk factors
- BMI of 30 kg/m^2 or more
- Continued weight loss e.g. 5% at 3 months
How long is Orlistat normally used for?
< 1 year
What type of drug is Liraglutide?
A glucagon-like peptide-1 (GLP-1) mimetic
What is the administration route for Liraglutide?
Once daily subcutaneous injection
What condition is Liraglutide primarily used to manage?
Type 2 diabetes mellitus (T2DM)
What effect did Liraglutide have when used for managing T2DM?
Caused weight loss in a significant proportion
What is the current NICE criteria for Liraglutide use in obesity?
Person has a BMI of at least 35 kg/m^2
What hormone is produced by adipose tissue and plays a key role in the regulation of body weight?
Leptin
Leptin acts on satiety centres in the hypothalamus and decreases appetite.
What effect does increased adipose tissue have on leptin levels?
Increases leptin levels
More adipose tissue, as seen in obesity, results in higher levels of leptin.
What hormones are stimulated by leptin?
Melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH)
Leptin stimulates their release to help regulate appetite.
What hormone is released when leptin levels are low?
Neuropeptide Y (NPY)
Low levels of leptin trigger the release of NPY, which stimulates appetite.
What is the primary function of ghrelin?
Stimulates hunger
Ghrelin is known as the hunger hormone.
Where is ghrelin primarily produced?
P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas
These locations are crucial for ghrelin secretion.
How do ghrelin levels change in relation to meal times?
Increase before meals and decrease after meals
This pattern helps regulate hunger and satiety.
True or False: Leptin induces hunger.
False
Leptin induces satiety, while ghrelin stimulates hunger.
What effect does increased adipose tissue have on leptin levels?
Increases leptin levels
More adipose tissue, as seen in obesity, results in higher levels of leptin.
What hormones are stimulated by leptin?
Melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH)
Leptin stimulates their release to help regulate appetite.
What hormone is released when leptin levels are low?
Neuropeptide Y (NPY)
Low levels of leptin trigger the release of NPY, which stimulates appetite.
What is the primary function of ghrelin?
Stimulates hunger
Ghrelin is known as the hunger hormone.
Where is ghrelin primarily produced?
P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas
These locations are crucial for ghrelin secretion.
How do ghrelin levels change in relation to meal times?
Increase before meals and decrease after meals
This pattern helps regulate hunger and satiety.
True or False: Leptin induces hunger.
False
Leptin induces satiety, while ghrelin stimulates hunger.
What is phaeochromocytoma?
A rare catecholamine secreting tumour
What percentage of phaeochromocytomas are familial?
About 10%
Which syndromes may be associated with phaeochromocytoma?
- MEN type II
- Neurofibromatosis
- Von Hippel-Lindau syndrome
What percentage of phaeochromocytomas are bilateral?
10%
What is the most common site for extra-adrenal phaeochromocytomas?
Organ of Zuckerkandl, adjacent to the bifurcation of the aorta
What are typical features of phaeochromocytoma?
- Hypertension (around 90% of cases, may be sustained)
- Headaches
- Palpitations
- Sweating
- Anxiety
What test has a sensitivity of 97% for diagnosing phaeochromocytoma?
24 hr urinary collection of metanephrines
What test has been replaced by the 24 hr urinary collection of metanephrines?
24 hr urinary collection of catecholamines
What is the definitive management for phaeochromocytoma?
Surgery
What medical management should stabilize a patient before surgery?
- Alpha-blocker (e.g. phenoxybenzamine)
- Beta-blocker (e.g. propranolol)
True or False: Hypertension is present in around 90% of phaeochromocytoma cases.
True
What is phaeochromocytoma?
A rare catecholamine secreting tumour
What percentage of phaeochromocytomas are familial?
About 10%
Which syndromes may be associated with phaeochromocytoma?
- MEN type II
- Neurofibromatosis
- Von Hippel-Lindau syndrome
What percentage of phaeochromocytomas are bilateral?
10%
What percentage of phaeochromocytomas are malignant?
10%
What is the most common site for extra-adrenal phaeochromocytomas?
Organ of Zuckerkandl, adjacent to the bifurcation of the aorta
What are typical features of phaeochromocytoma?
- Hypertension (around 90% of cases, may be sustained)
- Headaches
- Palpitations
- Sweating
- Anxiety
What test has a sensitivity of 97% for diagnosing phaeochromocytoma?
24 hr urinary collection of metanephrines
What test has been replaced by the 24 hr urinary collection of metanephrines?
24 hr urinary collection of catecholamines
What is the definitive management for phaeochromocytoma?
Surgery
What medical management should stabilize a patient before surgery?
- Alpha-blocker (e.g. phenoxybenzamine)
- Beta-blocker (e.g. propranolol)
True or False: Hypertension is present in around 90% of phaeochromocytoma cases.
True
What is Diabetes Insipidus (DI)?
A condition characterised by decreased secretion of antidiuretic hormone (ADH) or insensitivity to ADH
What are the two types of Diabetes Insipidus?
Cranial DI and Nephrogenic DI
What are common causes of cranial Diabetes Insipidus?
- Idiopathic
- Post head injury
- Pituitary surgery
- Craniopharyngiomas
- Infiltrative diseases (e.g., histiocytosis X, sarcoidosis)
- DIDMOAD syndrome
- Haemochromatosis
What genetic factors can cause nephrogenic Diabetes Insipidus?
- Vasopressin receptor mutation
- Mutation in aquaporin 2 channel
What are the main features of Diabetes Insipidus?
- Polyuria
- Polydipsia
What laboratory findings are typical in Diabetes Insipidus?
High plasma osmolality, low urine osmolality
What urine osmolality value excludes diabetes insipidus?
A urine osmolality of >700 mOsm/kg
What is the water deprivation test used for?
To evaluate patients who have polydipsia
What are the main management strategies for nephrogenic diabetes insipidus?
- Thiazides
- Low salt/protein diet
What is the primary treatment for central diabetes insipidus?
Desmopressin
What is diabetic ketoacidosis (DKA)?
A complication of diabetes characterized by uncontrolled lipolysis leading to ketone body formation
What are common precipitating factors for DKA?
- Infection
- Missed insulin doses
- Myocardial infarction
What are the key diagnostic criteria for DKA according to the American Diabetes Association?
- Glucose > 13.8 mmol/l
- pH < 7.30
- Serum bicarbonate < 18 mmol/l
- Anion gap > 10
- Ketonaemia
What are the main principles of DKA management?
- Fluid replacement
- Insulin therapy
- Correction of electrolyte disturbances
What is the typical fluid replacement protocol in DKA?
0.9% sodium chloride solution given in progressively decreasing volumes over several hours
What defines resolution of DKA?
- pH > 7.3
- Blood ketones < 0.6 mmol/L
- Bicarbonate > 15.0 mmol/L
What are common complications of DKA? (8)
- Gastric stasis
- Thromboembolism
- Arrhythmias
- Cerebral oedema
- Hypokalaemia
- Hypoglycaemia
- Acute respiratory distress syndrome
- Acute kidney injury
What is Hyperosmolar Hyperglycaemic State (HHS)?
A medical emergency characterized by severe hyperglycaemia and dehydration, typically in elderly patients with type 2 diabetes
What are the pathophysiological changes in HHS?
Hyperglycaemia leads to increased serum osmolality and osmotic diuresis resulting in severe volume depletion
What are the typical clinical features of HHS?
- Clinical signs of dehydration
- Polyuria
- Polydipsia
- Lethargy
- Altered level of consciousness
What laboratory findings are indicative of HHS?
- Marked hyperglycaemia (>30 mmol/L)
- Significantly raised serum osmolarity (> 320 mosmol/kg)
- No significant hyperketonaemia (<3 mmol/L)
- No significant acidosis (bicarbonate > 15 mmol/l or pH > 7.3)
What is the most common cause of hypercalcaemia in outpatients?
Primary hyperparathyroidism
What are the causes of primary hyperparathyroidism?
- Solitary adenoma (85%)
- Hyperplasia (10%)
- Multiple adenoma (4%)
- Carcinoma (1%)
What mnemonic can help remember the symptomatic features of primary hyperparathyroidism?
‘Bones, stones, abdominal groans and psychic moans’
What are the key investigations for primary hyperparathyroidism?
- Raised calcium
- Low phosphate
- PTH may be raised or normal
- Technetium-MIBI subtraction scan
- X-ray findings (e.g., pepperpot skull)
What is the definitive treatment for primary hyperparathyroidism?
Total parathyroidectomy
What is the water deprivation test result for normal individuals?
Starting plasma osmolality normal, final urine osmolality normal
What are some features of chronic kidney disease?
- Oedema
- Polyuria
- Lethargy
- Pruritus
- Anorexia
- Insomnia
- Nausea and vomiting
- Hypertension
What is the typical sensory loss distribution in diabetic peripheral neuropathy?
‘Glove and stocking’ distribution
What is the first-line treatment for diabetic neuropathy?
- Amitriptyline
- Duloxetine
- Gabapentin
- Pregabalin
What are the symptoms of gastroparesis in diabetic autonomic neuropathy?
- Erratic blood glucose control
- Bloating
- Vomiting
What is a common gastrointestinal issue associated with diabetic autonomic neuropathy?
Chronic diarrhoea
What does the term ‘gastroparesis’ refer to?
Delayed gastric emptying
What is the primary aim of investigating thyroid nodules?
To exclude thyroid cancer, which accounts for around 5% of all nodules, depending on patient demographic.
Name four benign causes of thyroid nodules.
- Multinodular goitre
- Thyroid adenoma
- Hashimoto’s thyroiditis
- Cysts (colloid, simple, or hemorrhagic)
What are the malignant causes of thyroid nodules?
- Papillary carcinoma
- Follicular carcinoma
- Medullary carcinoma
- Anaplastic carcinoma
- Lymphoma
What is the first-line imaging of choice for investigating thyroid nodules?
Ultrasonography
What is the most common cause of primary hyperparathyroidism?
A parathyroid adenoma, responsible in 85% of cases.
List the causes of primary hyperparathyroidism by percentage.
- 85%: solitary adenoma
- 10%: hyperplasia
- 4%: multiple adenoma
- 1%: carcinoma
What mnemonic can be used to remember the symptoms of primary hyperparathyroidism?
‘Bones, stones, abdominal groans and psychic moans’
What are the investigations for primary hyperparathyroidism?
- Blood tests showing raised calcium and low phosphate
- PTH may be raised or normal
- Technetium-MIBI subtraction scan
- X-ray findings (e.g., pepperpot skull, osteitis fibrosa cystica)
What is the definitive treatment for primary hyperparathyroidism?
Total parathyroidectomy
True or False: Patients not suitable for surgery may be treated with cinacalcet.
True
What is a pituitary adenoma?
A benign tumour of the pituitary gland.
What are the classifications of pituitary adenomas?
- Size: microadenoma (<1cm) and macroadenoma (≥1cm)
- Hormonal status: secretory/functioning and non-secretory/functioning
Which type of pituitary adenoma is the most common?
Prolactinomas
What symptoms can pituitary adenomas cause?
- Excess of a hormone
- Depletion of a hormone(s)
- Non-functioning tumors leading to generalised hypopituitarism
- Headaches from stretching of the dura
- Bitemporal hemianopia from optic chiasm compression
What is the initial investigation for pituitary adenomas?
- Pituitary blood profile (GH, prolactin, ACTH, FSH, LSH, TFTs)
- Formal visual field testing
- MRI brain with contrast
What is the first-line treatment for most pituitary adenomas?
Transsphenoidal surgery
What are the types of bariatric surgery?
- Primarily restrictive operations
- Primarily malabsorptive operations
- Mixed operations
What is the classification of BMI?
- Underweight: < 18.49
- Normal: 18.5 - 25
- Overweight: 25 - 30
- Obese class 1: 30 - 35
- Obese class 2: 35 - 40
- Obese class 3: > 40
What is orlistat used for?
A pancreatic lipase inhibitor used in the management of obesity.
What are the main symptoms of hypoparathyroidism?
- Tetany (muscle twitching, cramping, spasm)
- Perioral paraesthesia
- Trousseau’s sign
- Chvostek’s sign
- Chronic symptoms: depression, cataracts
What are the signs of hypothermia?
- Shivering
- Cold and pale skin
- Slurred speech
- Confusion/impaired mental state
What is the core temperature range for mild hypothermia?
32-35°C
What are the initial management steps for hypothermia?
- Remove from cold environment
- Warm with blankets
- Secure airway and monitor breathing
- Consider warm IV fluids if needed
What is hyperosmolar hyperglycaemic state (HHS)?
A medical emergency characterized by hyperglycaemia, osmotic diuresis, severe dehydration, and electrolyte deficiencies.
What are the clinical features of HHS?
- Polyuria
- Polydipsia
- Lethargy
- Nausea and vomiting
- Altered level of consciousness
What is a key feature of the management of HHS?
Fluid replacement with IV 0.9% sodium chloride solution.
What is ketonaemia?
Ketonaemia is defined as having a level of ketones less than 3 mmol/L.
What bicarbonate level indicates no significant acidosis?
Bicarbonate level greater than 15 mmol/L or pH greater than 7.3.
What is the estimated fluid loss in HHS?
Fluid losses in HHS are estimated to be between 100 - 220 ml/kg.
What is the typical administration rate for IV 0.9% sodium chloride solution?
Typically given at 0.5 - 1 L/hour depending on clinical assessment.
When should insulin be given during treatment?
Insulin should not be given unless blood glucose stops falling while giving IV fluids.
What are patients at risk of due to hyperviscosity?
Patients are at risk of thrombosis.
Name two vascular complications that may occur due to hyperviscosity.
- Myocardial infarction
- Stroke
What is the QRISK2 CVD risk assessment tool used for?
It is used to assess cardiovascular disease risk in patients aged <= 84 years.
In which situations should QRISK2 not be used?
- Type 1 diabetics
- Patients with eGFR less than 60 ml/min and/or albuminuria
- Patients with a history of familial hyperlipidaemia
What lipid levels should be checked before starting a statin?
Total cholesterol, HDL, and a full lipid profile including triglycerides.
What is the new cut-off for 10-year CVD risk according to 2014 guidelines?
The new cut-off is a 10-year CVD risk of 10% or greater.
What is the first-line statin recommended for primary prevention?
Atorvastatin 20mg.
What should be considered for all adults with type 1 diabetes regarding statin treatment?
Consider statin treatment for primary prevention of CVD.
What is the recommended statin dosage for patients with chronic kidney disease (CKD)?
Atorvastatin 20mg should be offered.
What should patients with established cardiovascular disease (CVD) be prescribed?
All patients with CVD should be taking a statin.
When should patients started on statins be followed up?
Patients should be followed up at 3 months.
What dietary fat intake is recommended for a cardioprotective diet?
Total fat intake should be <= 30% of total energy intake.
What is the recommended weekly intake of fish for a cardioprotective diet?
At least 2 portions of fish per week, including a portion of oily fish.
What is the recommended physical activity for cardiovascular health?
At least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic activity each week.
What are the characteristics of palmar xanthoma?
Palmar xanthoma is associated with remnant hyperlipidaemia and may less commonly be seen in familial hypercholesterolaemia.
What are eruptive xanthomas associated with?
Eruptive xanthomas are due to high triglyceride levels.
What are the management options for xanthelasma?
- Surgical excision
- Topical trichloroacetic acid
- Laser therapy
- Electrodesiccation
What is the primary action of statins?
Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis.
What are the adverse effects associated with statins?
- Myopathy
- Liver impairment
- Potential increased risk of intracerebral hemorrhage
What are key contraindications for statin use?
- Macrolides (e.g. erythromycin)
- Pregnancy
Who should receive a statin according to NICE guidelines?
- All people with established cardiovascular disease
- Anyone with a 10-year cardiovascular risk >= 10%
- Patients with type 2 diabetes mellitus
- Patients with type 1 diabetes mellitus diagnosed more than 10 years ago or aged over 40 or with established nephropathy
When should statins be taken for optimal effectiveness?
Statins should be taken at night.
What is the primary aim of investigating thyroid nodules?
To exclude thyroid cancer, which accounts for around 5% of all nodules, depending on patient demographic.
Name four benign causes of thyroid nodules.
- Multinodular goitre
- Thyroid adenoma
- Hashimoto’s thyroiditis
- Cysts (colloid, simple, or hemorrhagic)
What are the malignant causes of thyroid nodules?
- Papillary carcinoma
- Follicular carcinoma
- Medullary carcinoma
- Anaplastic carcinoma
- Lymphoma
What is the first-line imaging of choice for investigating thyroid nodules?
Ultrasonography
What is the most common cause of primary hyperparathyroidism?
A parathyroid adenoma, responsible in 85% of cases.
List the causes of primary hyperparathyroidism by percentage.
- 85%: solitary adenoma
- 10%: hyperplasia
- 4%: multiple adenoma
- 1%: carcinoma
What mnemonic can be used to remember the symptoms of primary hyperparathyroidism?
‘Bones, stones, abdominal groans and psychic moans’
What are the investigations for primary hyperparathyroidism?
- Blood tests showing raised calcium and low phosphate
- PTH may be raised or normal
- Technetium-MIBI subtraction scan
- X-ray findings (e.g., pepperpot skull, osteitis fibrosa cystica)
What is the definitive treatment for primary hyperparathyroidism?
Total parathyroidectomy
True or False: Patients not suitable for surgery may be treated with cinacalcet.
True
What is a pituitary adenoma?
A benign tumour of the pituitary gland.
What are the classifications of pituitary adenomas?
- Size: microadenoma (<1cm) and macroadenoma (≥1cm)
- Hormonal status: secretory/functioning and non-secretory/functioning
Which type of pituitary adenoma is the most common?
Prolactinomas
What symptoms can pituitary adenomas cause?
- Excess of a hormone
- Depletion of a hormone(s)
- Non-functioning tumors leading to generalised hypopituitarism
- Headaches from stretching of the dura
- Bitemporal hemianopia from optic chiasm compression
What is the initial investigation for pituitary adenomas?
- Pituitary blood profile (GH, prolactin, ACTH, FSH, LSH, TFTs)
- Formal visual field testing
- MRI brain with contrast
What is the first-line treatment for most pituitary adenomas?
Transsphenoidal surgery
What are the types of bariatric surgery? (3)
- Primarily restrictive operations
- Primarily malabsorptive operations
- Mixed operations
What is the classification of BMI?
- Underweight: < 18.49
- Normal: 18.5 - 25
- Overweight: 25 - 30
- Obese class 1: 30 - 35
- Obese class 2: 35 - 40
- Obese class 3: > 40
What is orlistat used for?
A pancreatic lipase inhibitor used in the management of obesity.
What are the main symptoms of hypoparathyroidism?
- Tetany (muscle twitching, cramping, spasm)
- Perioral paraesthesia
- Trousseau’s sign
- Chvostek’s sign
- Chronic symptoms: depression, cataracts
What are the signs of hypothermia?
- Shivering
- Cold and pale skin
- Slurred speech
- Confusion/impaired mental state
What is the core temperature range for mild hypothermia?
32-35°C
What are the initial management steps for hypothermia?
- Remove from cold environment
- Warm with blankets
- Secure airway and monitor breathing
- Consider warm IV fluids if needed
What is hyperosmolar hyperglycaemic state (HHS)?
A medical emergency characterized by hyperglycaemia, osmotic diuresis, severe dehydration, and electrolyte deficiencies.
What are the clinical features of HHS?
- Polyuria
- Polydipsia
- Lethargy
- Nausea and vomiting
- Altered level of consciousness
What is a key feature of the management of HHS?
Fluid replacement with IV 0.9% sodium chloride solution.
What is ketonaemia?
Ketonaemia is defined as having a level of ketones less than 3 mmol/L.
What bicarbonate level indicates no significant acidosis?
Bicarbonate level greater than 15 mmol/L or pH greater than 7.3.
What is the estimated fluid loss in HHS?
Fluid losses in HHS are estimated to be between 100 - 220 ml/kg.
What is the typical administration rate for IV 0.9% sodium chloride solution?
Typically given at 0.5 - 1 L/hour depending on clinical assessment.
When should insulin be given during treatment?
Insulin should not be given unless blood glucose stops falling while giving IV fluids.
What are patients at risk of due to hyperviscosity?
Patients are at risk of thrombosis.
Name two vascular complications that may occur due to hyperviscosity.
- Myocardial infarction
- Stroke
What is the QRISK2 CVD risk assessment tool used for?
It is used to assess cardiovascular disease risk in patients aged <= 84 years.
In which situations should QRISK2 not be used?
- Type 1 diabetics
- Patients with eGFR less than 60 ml/min and/or albuminuria
- Patients with a history of familial hyperlipidaemia
What lipid levels should be checked before starting a statin?
Total cholesterol, HDL, and a full lipid profile including triglycerides.
What is the new cut-off for 10-year CVD risk according to 2014 guidelines?
The new cut-off is a 10-year CVD risk of 10% or greater.
What is the first-line statin recommended for primary prevention?
Atorvastatin 20mg.
What should be considered for all adults with type 1 diabetes regarding statin treatment?
Consider statin treatment for primary prevention of CVD.
What is the recommended statin dosage for patients with chronic kidney disease (CKD)?
Atorvastatin 20mg should be offered.
What should patients with established cardiovascular disease (CVD) be prescribed?
All patients with CVD should be taking a statin.
When should patients started on statins be followed up?
Patients should be followed up at 3 months.
What dietary fat intake is recommended for a cardioprotective diet?
Total fat intake should be <= 30% of total energy intake.
What is the recommended weekly intake of fish for a cardioprotective diet?
At least 2 portions of fish per week, including a portion of oily fish.
What is the recommended physical activity for cardiovascular health?
At least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic activity each week.
What are the characteristics of palmar xanthoma?
Palmar xanthoma is associated with remnant hyperlipidaemia and may less commonly be seen in familial hypercholesterolaemia.
What are eruptive xanthomas associated with?
Eruptive xanthomas are due to high triglyceride levels.
What are the management options for xanthelasma?
- Surgical excision
- Topical trichloroacetic acid
- Laser therapy
- Electrodesiccation
What is the primary action of statins?
Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis.
What are the adverse effects associated with statins?
- Myopathy
- Liver impairment
- Potential increased risk of intracerebral hemorrhage
What are key contraindications for statin use?
- Macrolides (e.g. erythromycin)
- Pregnancy
Who should receive a statin according to NICE guidelines?
- All people with established cardiovascular disease
- Anyone with a 10-year cardiovascular risk >= 10%
- Patients with type 2 diabetes mellitus
- Patients with type 1 diabetes mellitus diagnosed more than 10 years ago or aged over 40 or with established nephropathy
When should statins be taken for optimal effectiveness?
Statins should be taken at night.
What is the most common cause of primary hyperaldosteronism?
Bilateral idiopathic adrenal hyperplasia
This accounts for around 60-70% of cases.
What condition was previously thought to be the most common cause of primary hyperaldosteronism?
Adrenal adenoma (Conn’s syndrome)
This was believed to be the most common cause before recent studies.
What are the causes of primary hyperaldosteronism?
- Bilateral idiopathic adrenal hyperplasia
- Adrenal adenoma
- Unilateral hyperplasia
- Familial hyperaldosteronism
- Adrenal carcinoma
These causes vary in prevalence among patients.
What is a classical feature of primary hyperaldosteronism often seen in exams?
Hypokalaemia
This feature is reported in only 10-40% of patients and is more common with adrenal adenomas.
What are the common features of primary hyperaldosteronism?
- Hypertension
- Hypokalaemia
- Metabolic alkalosis
Hypertension is increasingly recognized but still underdiagnosed as a cause of hypertension.
What is the first-line investigation recommended for suspected primary hyperaldosteronism?
Plasma aldosterone/renin ratio
This should show high aldosterone levels alongside low renin levels due to negative feedback.
What conditions warrant screening for primary hyperaldosteronism?
- Hypertension with hypokalemia
- Treatment-resistant hypertension
These conditions indicate a need for further investigation.
What imaging technique is used after the plasma aldosterone/renin ratio test to differentiate sources of aldosterone excess?
High-resolution CT abdomen
This imaging is followed by adrenal vein sampling if needed.
What is the management for adrenal adenoma in primary hyperaldosteronism?
Surgery (laparoscopic adrenalectomy)
This is the recommended treatment for adrenal adenomas.
What treatment is recommended for bilateral adrenocortical hyperplasia?
Aldosterone antagonist (e.g., spironolactone)
This is used for managing bilateral hyperplasia cases.
True or False: Hypokalaemia is seen in all patients with primary hyperaldosteronism.
False
Hypokalaemia is a classical feature but only seen in 10-40% of patients.
