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
Primary hyperparathyroidism
PTH (Elevated)
Ca2+ (Elevated)
Phosphate (Low)
Urine calcium : creatinine clearance ratio > 0.01
May be asymptomatic if mild
Recurrent abdominal pain (pancreatitis, renal colic)
Changes to emotional or cognitive state
Most cases due to solitary adenoma (80%), multifocal disease occurs in 10-15% and parathyroid carcinoma in 1% or less
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
Tertiary hyperparathyroidism
Ca2+ (Normal or high)
PTH (Elevated)
Phosphate levels (Decreased or Normal)
Vitamin D (Normal or decreased)
Alkaline phosphatase (Elevated) Metastatic calcification
Bone pain and / or fracture
Nephrolithiasis
Pancreatitis
Occurs as a result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, hyperplasia of all 4 glands is usually the cause
Treatment of primary hyperparathyroidism
Indications for surgery
* Elevated serum Calcium > 1mg/dL above normal
* Hypercalciuria > 400mg/day
* Creatinine clearance < 30% compared with normal
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Episode of life threatening hypercalcaemia
Nephrolithiasis
Age < 50 years
Neuromuscular symptoms
Reduction in bone mineral density of the femoral neck, lumbar spine, or distal radius of more than 2.5 standard deviations below peak bone mass (T score lower than -2.5)
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
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
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
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
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
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
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: see below
Drugs which cause gynaecomastia
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids
Very rare drugs which cause gynaecomastia
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
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:
admit for specialist assessment if:
signs of retinal haemorrhage or papilloedema (accelerated hypertension) or
life-threatening symptoms such as new-onset confusion, chest pain, signs of heart failure, or acute kidney injury
NICE also recommend referral if a phaeochromocytoma is suspected (labile or postural hypotension, headache, palpitations, pallor and diaphoresis)
if none of the above then arrange urgent investigations for end-organ damage (e.g. bloods, urine ACR, ECG)
if target organ damage is identified, consider starting antihypertensive drug treatment immediately, without waiting for the results of ABPM or HBPM.
if no target organ damage is identified, repeat clinic blood pressure measurement within 7 days
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)
Several 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:
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
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
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
- 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
Managment of Addison’s crisis
Immediate administration of intravenous hydrocortisone
Fluid replacement to address dehydration and low blood pressure
Correction of electrolyte imbalances, particularly sodium and potassium levels
Management of any underlying causes or triggers
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
- 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
- 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.
THIAZOLIDINEDIONES contradicitons
Heart failure
Hepatic impairment
Bladder cancer or uninvestigated macroscopic haematuria
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
DPP4-INHIBITORS side effects
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?
- 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?
• 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 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 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)
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
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 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
