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5 Endocrinology
Diagnosis of diabetes mellitus (DM):
https://t.me/med1917
NICE
guidelines
Persistent hyperglycaemia is defined as:
• HbA1c of 48mmol/ mol (6.5%) or more.
• Fa st in g pl as ma g lu c os e l e ve l o f 7.0mmol/ L or more.
• Random plasma glucose of 11.1mmol/ L or more in the presence of symptoms or
signs of diabetes.
If the person is symptomatic (eg polyuria, polydipsia, unexplained weight loss),
a single abnormal Hb
repeat testing is sensible to confirm the diagnosis.
If the person is asymptomatic, do not diagnose diabetes on the basis of a single
abnormal Hb
with the same test, to confirm the diagnosis. If the repeat test result is normal,
A1
c or fasting plasma glucose level can be used, although
A1
c or plasma glucose result. Arrange repeat testing, preferably
arrange to monitor the person for the development of diabetes, the frequency
depending on clinical judgement.
201
Dierentiating type 1 and 2
Occasionally it may be dicult to dierentiate whether a patient has type 1 or
2
DM, although they can present dierently (table
weight loss; lean body habitus; acute presentation; persistent hyperglycaemia
despite diet and medications; presence of autoantibodies: islet cell antibodies
ICA
) and anti- glutamic acid decarboxylase (
(
Table 5.
1
Dierences between type 1 and type 2 diabetes
Epidemiology
Islet
autoantibodies
Cause
Presentation
Type 1
Often starts before puberty Older patients (usually)
>90% positive, eg
islet cell
Autoimmune - cell destruction Insulin resistance/ - cell
Usually acute with polydipsia,
polyuria, weight, ketosis
Not all new- onset DM in older people is type 2: if ketotic ± a poor response to
oral hypoglycaemics (and patient is slim or has a family or personal history of
autoimmunity), think of latent autoimmune diabetes in adults (
islet cell antibodies. There is also the entity of ketosis- prone diabetes which is a
heterogeneous syndrome characterized by patients who present with
provoked ketosis but who do not have the typical phenotype of autoimmune type
1
DM. They are usually obese, islet autoantibody negative, and have features of
both impaired insulin secretion and action.
Non- diabetic hyperglycaemia and diabetes prevention
High- risk individuals, including those with impaired fasting glucose, impaired glucose tolerance, obesity, family history of type
groups (Asian, Hispanic, black), should be targeted for preventative interventions.
Lifestyle modifications including healthy diet, regular exercise, weight loss, and
smoking cessation decrease the risk of future diabetes. For selected patients (eg
60
years and/ or
<
Overweight or obese individuals with prediabetes may benefit from semaglutide
BMI
>35), metformin may be useful for diabetes prevention.
which helps delay or prevent the onset of overt diabetes. In the
You programme identifies people with non- diabetic hyperglycaemia who are at
risk of developing type
style change programme (either face- to- face or digital). It has been shown to re-
2
duce the risk of developing type
DM
5.1
). Features of type 1 include
GAD
) antibodies; ketoacidosis.
DM
GAD, IA2
Type 2
DM
Negative
, ZnT8,
dysfunction
Asymptomatic/ complications,
MI
eg
LADA
) and measure
2
DM, or certain vulnerable ethnic
UK
, the Healthier
DKA
or un-
DM and refers them onto a 9- month, evidence- based life-
2
DM by >33%.
5 Endocrinology
Treating diabetes mellitus
https://t.me/med1917
202
General Focus on education and lifestyle advice (eg exercise to insulin sensitivity),
p
238
healthy eating:
index sources of carbohydrate, and controlling intake of saturated and trans-fatty
acids. Consider referral for bariatric surgery if
DM
despite lifestyle interventions. Be prepared to negotiate HbA1c target and review
3– 6
every
atorvastatin as tolerated, control
care should be in a multidisciplinary clinic (
to drive if hypoglycaemic spells (
loss of licence; permanent if
— For patients with type 2 DM advise high fibre, low-glycaemic-
BMI
>35kg/m2 in patients with type 2
months. Assess global vascular risk; start a high- intensity statin (p
BP
(p
205
). Give foot care (p
OHCS
p
150
HGV
). More detailed guidance available at https://www.
p26). Advise informing
; loss of hypoglycaemia awareness may lead to
206
). (Pre- )pregnancy
gov.uk/guidance/diabetes-mellitus-assessing-fitness-to-drive
Type 1 DM Insulin (see
Type 2
DM
See fig
5.5
.
BOX
‘Using insulin’).
DVLA
107
), eg
and not
Fig 5.
5
Management of type 2 diabetes. Aim for HbA1c 48mmol/ mol or 53mmol/ mol if ≥2 agents.
Data from Algorithm for blood glucose lowering therapy in adults with type 2 diabetes,
Oral hypoglycaemic agents
Metformin A biguanide. insulin sensitivity and weight neutral. SE: nausea; diar-
rhoea (try modified- release version); abdominal pain; not hypoglycaemia. Avoid if
GFR
<30mL/ min (due to risk of lactic acidosis).
e
DPP4
inhibitors/ gliptins (Eg sitagliptin.) Weight neutral. Block the action of
an enzyme which destroys the hormone incretin.
Glitazone insulin sensitivity; SE: bone fractures, bladder cancer, weight gain,
fluid retention,
CI
: past or present
LFT
CCF
Sulfonylurea insulin secretion; eg gliclazide 40mg/ d. SE: hypoglycaemia (monitor
glucose); it weight .
SGLT2i
Selective sodium– glucose co- transporter- 2 inhibitor. Blocks the reabsorption
of glucose in the kidneys and promotes weight loss and excretion of excess glucose
in the urine (eg empagliflozin, shown to reduce mortality from cardiovascular dis-
CKD
ease and
progres sion in patients with type 2 DM, when compared to placebo).
https://www.nice.org.uk/guidance/ng28
(monitor
LFT
s periodically based on clinical judgement).
; osteoporosis; monitor weight, and stop if or oedema.
DPP 4
,
5 Endocrinology
Glucagon- like peptide (
DAFNE
https://t.me/med1917
liraglutide)
Incretin mimetics. Incretins are gut peptides that work by augmenting insulin release and reducing appetite and food intake. Given by subcutaneous injection. Used
2
diabetes as monotherapy, if metformin inappropriate, or in combination
for type
with other agents. May also be used to treat obesity in combination with lifestyle
measures, eg
referral for weight management. Generally leads to
BMI
>35 plu s 1 obe sity- relate d como rbidi ty, or 30–35 if needs specialist
Using insulin
Vital to educate to self- adjust doses in the light of exercise, finger- prick glucose,
calorie intake, and carbohydrate counting.
• Can modify diet wisely and avoid binge drinking (danger of delayed hypogly-
• Partner can abort hypoglycaemia: sugary drinks; GlucoGel® PO if coma
caemia).
(no risk of aspiration).
It is vital to write
• Dose titration to target— eg by 2– 4
UNITS
ation of U for zero!
Subcutaneous insulins Short- , medium- , or long- acting.
1
Rapid- acting insulin (eg Humalog®; Novorapid®)— prandial insulins to be in-
15
min before meals.
jected
2
Isophane insulin (variable peak at 4– 12
3
Pre- mixed insulins (eg NovoMix® 30 = 30% short- acting and 70% long- acting).
4
Long- acting recombinant human insulin analogues (insulin glargine) are used at
bedtime in type
1
or 2 DM. There is no awkward peak, so good if nocturnal hypoglycaemia is an issue.
regimens for overweight type
Common insulin regimens Plan the regimen to suit the lifestyle, not vice versa.
Disposable pens: dial dose; insert needle
thigh/ abdomen); change needle with each injection.
• ‘BD biphasic regimen’: twice- daily premixed insulins by pen (eg NovoMix 30®)—
useful in type
• ‘
QDS
logue: useful in type
with size of meals, or exercise).
• Once- daily before- bed long- acting insulin: a good initial insulin regimen when
intensifying treatment in type
2
DM.
regimen’: before meals rapid- acting insulin + bedtime long- acting ana-
1
DM for achieving a flexible lifestyle (eg for adjusting doses
units/ kg— and uptitrate as needed.
Dose adjustment for normal eating (
autonomy can save lives.
dosing improved glycaemic control as well as wellbeing. It is resource intensive.
Subcutaneous insulin dosing during intercurrent illnesses (eg influenza)
(Advice leaflets with sick day rules for patients with type 1 a n d 2 diabetes available at
https://trenddiabetes.online/trend-uk-releases-updated-sick-day-rules-leaflets/)
Advise patients to avoid stopping insulin during acute illness.
• Illness often increases insulin requirements despite reduced food intake.
• Maintain calorie intake, eg using milk.
• Check blood glucose ≥4 times a day and look for ketonuria. Increase insulin doses if
glucose rising. Advise to get help from a specialist diabetes nurse or
(esp. if glucose levels are rising or ketonuria). One option is
6– 8U) preceded by a fingerprick glucose check.
insulin (eg
• Admit if vomiting, dehydrated, ketotic (p
• Stop
SGLT2
• Metformin should be stopped in acute illness if diarrhoea and vomiting or
inh ibito rs in t ype 2 DM during acute illness or pre-surgery to avoid risk of
euglycaemic ketoacidosis. Check ketone levels in such cases.
sent (due to greater risk of lactic acidosis).
Insulin pumps (continuous subcutaneous insulin) Consider on ly in type 1 DM when at-
A1
tempts to reach Hb
caemia or person has been unable to achieve target Hb
c with multiple daily injections have resulted in disabling hypogly-
GLP
) analogues (semaglutide, dulaglutide,
5–15
% weight loss.
• Phone support (trained nurse 7/ 24).
UNIT
steps.
in full when prescribing insulin to avoid misinterpret-
h): favoured by
NICE
(it’s cheap!).
Insulin detemir is similar and has a role in intensive insulin
2
DM.
90
° to skin. Vary injection site (outer
2
DM, eg initial starting dose of 10 units or 0.2
DAFNE
found that training in flexible, intensive insulin
) multidisciplinary teams promoting
GP
2
816
), a child, or pregnant.
A1
c despite careful management.
if concerned
- hourly ultra fast- acting
AKI
pre-
203
5 Endocrinology
Complications of established diabetes
https://t.me/med1917
204
Prospective studies show that good control of hyperglycaemia is key to preventing
1
microvascular complications in type
and 2 DM.8 Find out what problems are
being experienced (eg glycaemic control, morale, erectile dysfunction—
Assess vascular risk BP control (see
is crucial for preventing macrovascular disease and mortality. Refer to
cessation services. Check plasma lipids.
BOX
‘Controlling blood pressure in diabetes’)
Look for complications • Check injection sites for infection or lipohypertrophy
(fatty change): advise on rotating sites of injection if present.
• Vascular disease Chief cause of death. MI is 4- fold commoner in DM and is more
likely to be ‘silent’. Stroke is twice as common. Women are at high risk—
moves the vascular advantage conferred by the female sex. Address other risk
factors— diet, smoking, hypertension (
20
mg daily for primary prevention in
have had diabetes >
factors), even if no overt
reduces vascular events (in context of secondary prevention). Safe to use in diabetic retinopathy.
secondary prevention. Oer atorvastatin
QRISK
>10%, or in
if
if established nephropathy or other
• Nephropathy (p
10
yrs, age >40yrs, established nephropathy or other
IHD,
9
Aspirin is not indicated for primary prevention; only used for
T1D
if they have had diabetes >10 years, or if age >40 years, or
310
) Microalbuminuria is when urine dipstick is −ve for protein
but the urine albumin:creatinine ratio (u
lab) reflecting early kidney disease and vascular risk. If u
renin– angiotensin system with an
ated), even if
ated dose. Consider referral to renal team if progressive in e
in a year, e
30
<
betic kidney disease progression.
• Diabetic retinopathy Blin dnes s is preventable. Annual retinal screening mandatory
for all patients. Most referrals to ophthalmologists now come from the retinopathy
BP
is normal, protects the kidneys. Titrate
GFR
of ≥25% + change in e
, or if marked albuminuria, eg u
p85). Suggest a statin (eg oer atorvastatin
T2D
if
QRISK
>10%, or in type 1 DM if they
vascular disease, or microalbuminuria. Aspirin 75mg
20
mg daily for primary prevention in
CVD
risk factors.
ACR
) is 3mg/ mmol (units vary, check
ACE
- i or
ARA
(titrate the max dose as toler-
GFR
category within 12mths, when e
ACR
>70mg/ mmol.
ACR
>3, inhibiting the
ACE
- i to maximum toler-
GFR
SGLT2
inhibitors reduce dia-
screening service. Refer to an ophthalmologist if any evidence of diabetic retinopathy
or if any uncertainty at or near the macula (the only place capable of
Pre- symptomatic screening enables laser photocoagulation to be used, aimed to stop
production of angiogenic factors from the ischaemic retina. Indications: maculopathy
or proliferative retinopathy. See
6.5
%, BP <
130/ 80
• Background retinopathy Microaneurysms (dots), haemorrhages (blots), and hard
exudates (lipid deposits). Refer if near the macula, eg for intravitreal triamcinolone.
• Pre- proliferative retinopathy
multiple blot haemorrhages are features of pre- proliferative retinopathy. Refer to
a specialist.
• Proliferative retinopathy New vesse ls form . Need s urgent re ferral .
• Maculopathy (Hard to see in early stages.) Suspect if acuity. Prompt laser,
intravitreal steroids, or anti- angiogenic agents may be needed in macular
oedema.
• Cataracts May be juvenile ‘snowflake’ form, or ‘senile’— which occur earlier in
mmHg, and possibly consider fibrate therapy.
2
figs
5.6– 5.9
. Support treatment by aiming for HbA1c
IRMA
S, venous beading, venous reduplication, and
diabetic subjects. Osmotic changes in the lens induced in acute hyperglycaemia
reverse with normoglycaemia (so wait before buying glasses).
• Rubeosis iridis New vessels on iris: occurs late and may lead to glaucoma.
• Metabolic complications See p
• Diabetic feet See p
• Neuropathy See p
206
206
816
.
.
.
p
224
).
smoking
DM
re-
CVD
risk
T2D
by >15mL/ min
GFR
6/ 6
vision).
5 Endocrinology
Controlling blood pressure in diabetes
https://t.me/med1917
Type 1 DM Treat BP if >
of metabolic syndrome, in which case it should be
ACE
- i 1st line or
an
ment, see local guidance,
Type 2 DM Target BP <
cular damage.
tients with
T2D
may be less eective, and may need to progress to Step
of diuretic or
ACE
-i in people of African-Caribbean origin as
to
of angioedema in this population.
switching to alternate agents pre- pregnancy, eg labetalol,
ACE
- i with an angiotensin receptor antagonist.
an
Fig 5.
6
Background retinopathy, with micro-
aneurysms and hard exudates.
135/ 85
mmHg, unless albuminuria or two or more features
130/ 80
ARA
if intolerant. If hypertensive and underlying renal involve-
p
300
.
135/ 85
1
st- line drug treatment should be an
are also oered
CCB
) if initial treatment less eective.
Courtesy of Prof J Trobe.
mmHg or <
130/ 80
mmHg kidney, eye, or cerebrovas-
ACE
-i/
ARB
S first line but with the caveat that they
ACE
- i contraindicated in pregnancy. Consider
ACE
ARB
ACE
inhibitors have a higher risk
Fig 5.
7
Pre- proliferative retinopathy, with
haemorrhages and a cotton- wool spot.
Reproduced from Warrell et al., Oxford Textbook
of Medicine,
mmHg (
NICE
2015
). Use
- i. African-Caribbean pa-
2
treatment (ie addition
S are generally preferred
CCB
S. Do not combine
2010
, with permission from
Oxford University Press.
205
Fig 5.
8
Proliferative retinopathy, with new
vessel formation and haemorrhages.
Courtesy of Prof J Trobe.
Fig 5.
9
Scars from previous laser photo-
coagulation.
Courtesy of Prof J Trobe.
5 Endocrinology
Diabetic neuropathy and diabetic foot care
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206
Refer early to foot services (podiatry, imaging, vascular surgery). Multidisciplinary
input essential.
Amputations are common (
Examine feet regularly. Distinguish between ischaemia (critical toes ± absent foot
pulses and worse outcome) and peripheral neuropathy (injury or infection over
pressure points, eg the metatarsal heads). In practice, many have both.
filament fibre (sensory loss is patchy so examine all areas), absent ankle jerks, neuropathic deformity (Charcot joint,
arch, rocker- bottom sole. Caused by loss of pain sensation, leading to mechanical
stress and repeated joint injury. Swelling, instability, and deformity.
tion is vital (cellulitis or osteomyelitis are often misdiagnosed).
Ischaemia If the foot pulses cannot be felt, do Doppler pressure measurements.
Any evidence of neuropathy or vascular disease raises risk of foot ulceration.
Educate (daily foot inspection— eg with a mirror for the sole; comfortable shoes).
Regular podiatry to remove callus, as haemorrhage and tissue necrosis may occur
below, leading to ulceration. Treat fungal infections (
endovascular angioplasty balloons, stents, and subintimal recanalization) has a role.
Foot ulceration Typically painless, punched- out ulcer (fig
callus ± superadded infection. Causes cellulitis, abscess ± osteomyelitis.
Assess degree of
1 Neuropathy (clinically).
2
Ischaemia (clinically + Doppler ± angiography).
3
Bony deformity, eg Charcot joint (clinically + X- ray). See fig
4
Infection (swabs, blood culture, X- ray, and
reveal depth).
Management Multidisciplinary approach required, involving podiatrist, diabeto-
logists, diabetes specialist nurses, vascular surgeons, orthopaedic surgeons, microbiologists. Management principles are:
podiatry for wound care, regular debridement of callus and dead tissue,
the wound—consider therapeutic shoes,
local infection guidance,
eg angioplasty, vascular bypass grafting. Diabetic foot infections: include a drug
predictably active against
Strep but, if severe limb and/or life-threatening infection, will need broader cover
against Gram +ve cocci, coliforms and other aerobic Gram –ve rods and anaerobes
(eg vancomyin + piperacillin-tazobactam). Oral augmentin may be reasonable if
superficial infection (eg ulcer with superficial inflammation). Risk of osteomyelitis
increased if ulcer area >
Consider admission if failing oral antibiotic therapy, scoring for sepsis markers, evidence for urgent surgery, eg abscess, deep or spreading infection, wet gangrene.
Absolute indications for surgery Abscess or deep infection; osteomyelitis;
spreading anaerobic infection; gangrene/ rest pain; suppurative arthritis.
Diabetic neuropathies Symmetric sensory polyneuropathy (‘Glove & stocking’
numbness, tingling, and pain, eg worse at night.) : first- line pharmacotherapy options for painful diabetic neuropathy include duloxetine, amitriptyline, pregabalin, and
gabapentin, eg amitriptyline
duloxetine commence at
to gauge response to treatment. If inadequate eect, consider switching or adding in
a second- line agent. Consider referral to pain specialist. Avoid use of opioids to treat
painful diabetic neuropathy because of lack of evidence of long- term ecacy and concern about addiction.
autoregulation; loss of respiratory sinus arrhythmia (vagal neuropathy); gastroparesis;
urine retention; erectile dysfunction; gustatory sweating; diarrhoea (may respond to
codeine phosphate). Gastroparesis (see
fludrocortisone (
SE:
oed ema, BP)/ midodrine (- agonist; SE: BP).
135
/ week)— and preventable: good care saves legs.
fig
5.11
): pes cavus, claw toes, loss of transverse
Early recogni-
p
404
). Surgery (including
5.10
) in an area of thick
5.11
MRI
for osteomyelitis, probe ulcer to
1
optimizing diabetes control, 2 ongoing
4
5
consider whether revascularization procedures required,
MRSA
2
cm2, positive probe to bone,
10
mg nocte— titrating in steps of 10– 25mg up to 75mg; eg
30
mg daily and uptitrate to 60–
Autonomic neuropathy (p
treat any superadded infection—refer to
. Empiric drug regimes should cover both Staph and
ESR
120
501
) Postural BP dro p; cerebrovascular
p
264
). Postural hypotension may respond to
.
>70 or abnormal X-ray.
mg daily. May take 2– 3mths
10
g mono-
3
o-loading
5 Endocrinology
Preventing loss of limbs: primary or secondary prevention?
https://t.me/med1917
Traditionally prevention involves foot care advice in diabetic clinics (eg ‘Don’t go
bare- foot’), promoting euglycaemia and normotension. But despite this, the sight
of a diabetic patient minus one limb is not rare, and must prompt us to redouble
our commitment to primary prevention, ie stopping those at risk from ever getting diabetes. The sequelae of diabetic neuropathy can lead to gangrene, amputation, and the impact on quality of life can be profound. As one patient post
amputation said, ‘I begin again to walk, on crutches. What nuisance, what fatigue, what sadness, when I think about all my ancient travels, and how active
I was just
the deserts, the rivers, and the seas? And now, the life of a legless cripple. For
5
months ago! Where are the runnings across mountains, the walks,
I begin to understand that crutches, wooden and articulated legs, are a pack of
jokes . . . Goodbye to family, goodbye to future! My life is gone, I’m no more than
an immobile trunk’ (Arthur Rimbaud. Letter to his sister Isabelle,
Fig 5.
11
Fig 5.
10
Gangrene (toes 2, 4, and 5).
Reproduced from Warrell et al.,
Oxford Textbook of Medicine,
with permission from Oxford
2010
University Press.
,
Charcot (neuropathic) joint.
Reproduced from Warrell et al.,
Oxford Textbook of Medicine,
with permission from Oxford
10
July
1891
2010
University Press.
).
,
Special situations in diabetes
Pregnancy (
new- onset gestational diabetes (
• All forms carry an increased risk to mother and fetus: miscarriage, pre- term labour,
OHCS
p26) 4% are complicated by DM: either pre- existing (<0.5%), or
GDM
) (>3.5%).
pre- eclampsia, congenital malformations, macrosomia, and a worsening of diabetic
complications, eg retinopathy, nephropathy.
• Risk of
GDM
previous gestational
• Pre- conception: oer general advice and discuss risks. Control/ reduce weight, aim
for Hb
• Screen for
• Oral hypoglycaemics other than metformin should be discontinued. Metformin may
be used as an adjunct or alternative to insulin in type
6
wks postpartum with
if: aged over 25; family history; + ve; weight; non- Caucasian;
DM
.
A1
c 6.5%, oer folic acid 5mg/ d until 12 wee ks.
GDM
wit h
OGTT
if r isk fac tors a t book ing (16– 18 wee ks if p reviou s
2
DM or
GDM
, do a fasting glucose. Even if −ve, 50% go on to develop DM.
GDM.
HIV
GDM)
Surgery Optimal blood sugar control pre- , peri- , and post- operatively is im-
portant to minimize risk of infection and balance catabolic response to surgery.
1
diabetics should ideally be first on the list and blood glucose levels should
Type
have been stabilized
1– 2
days pre major surgery. Consult local policy for how to
manage insulin- treated/ non- insulin- treated patients on morning of surgery (eg
setting up glucose/ insulin infusion).
207
+ ve;
.
5 Endocrinology
Hypoglycaemia
EXPLAIN
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208
Hypoglycaemia Commonest endocrine emergency— see p
&
nosis and treatment essential— brain damage
death can occur if severe or
818
prolonged.
Definition Blood glucose level <
viduals. However, some guidelines use <
3.9
mmol/L = hypoglycaemia in non-diabetic indi-
3.3
mmol/L. Severe hypoglycaemia indicates
severe cognitive impairment requiring external assistance for recovery. See
Symptoms Autonomic Sweating, anxiety, hunger, tremor, palpitations, dizziness.
Neuroglycopenic Confusion, drowsiness, visual trouble, seizures, coma. Rarely
focal symptoms, eg transient hemiplegia. Mutism, personality change, restlessness, and incoherence may lead to misdiagnosis of alcohol intoxication or even
psychosis.
Fas t in g h yp og ly ca e mi a Causes The chief cause is insulin or sulfonylurea treat-
ment in a diabetic, eg activity, missed meal, accidental or non- accidental overdose (check for circulating oral hypoglycaemics). In diabetic patients, you can
assess awareness of hypoglycaemia with scoring systems like the
non- diabetics you must
hypoglycaemics (
may misuse insulin to help stamina. Also: alcohol, eg a binge with no food; aspirin
poisoning;
insulin- like growth factor.
inherited enzyme defects.
immune hypoglycaemia (eg anti- insulin receptor antibodies in Hodgkin’s disease).
•Non- pancreatic neoplasms due to overproduction of
p
202
ACE
- i; - blockers; pentamidine; quinine sulfate; aminoglutethamide;
mechanism: •Exogenous drugs, eg insulin, oral
)? Access through diabetic in the family? Body- builders
10
•Pituitary insuciency. •Liver failure, plus some rare
•Addison’s disease. •Islet cell tumours (insulinoma) and
IGF- 2
, eg fibrosarcomas and
haemangiopericytomas.
When to investigate
• Whipple answered this (Whipple’s triad): symptoms or signs of hypoglycaemia
IGF-2
(due to overproduction of
signs post glucose rise.
• Document blood glucose levels during attack and lab glucose if in hospital (moni-
tors often not reliable at low readings).
• Take a drug history and exclude liver failure and adrenal insuciency. Consider
assay for presence of sulfonylureas.
• 72h fasting may be needed (monitor closely). Bloods: glucose, insulin, C- peptide,
and plasma ketones if symptomatic. If endogenous hyperinsulinism suspected, do
C
- peptide, proinsulin, - hydroxybutyrate. Consider measuring
insulin,
sulin antibodies.
) + plasma glucose + resolution of symptoms or
Interpreting results
• Hypoglycaemic hyperinsulinaemia (HH). Causes: insulinoma, sulfonylureas, in-
C
sulin injection (no detectable
non- insulinoma pancreatogenous hypoglycaemia syndrome, mutation in the
insulin- receptor gene. Congenital
ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A, ABCC8, & KCNJ11)
secretion (
• Insulin low or undetectable, no excess ketones. Causes: non- pancreatic neoplasm;
anti- insulin receptor antibodies.
• Insulin, ketones. Causes: alcohol, pituitary insuciency, Addison’s disease.
- peptide— only released with endogenous insulin);
HH
follows mutations in genes involved in insulin
Post- prandial hypoglycaemia May occur after gastric/ bariatric surgery (‘dumping’,
p
618
), and in type 2 DM. Inve stigat ion Mi xed mea l test.
Treatment See p
818
. If episodes are often, advise many small high- starch
meals. If post- prandial glucose, give slowly absorbed carbohydrate (high fibre).
Consider acarbose—sometimes used in post-prandial hypoglycaemia. In diabetics, rationalize hypoglycaemic agents (
p
203
).
. Prompt diag-
BOX
.
GOLD
score. In
IGF- 2
and in-
.
11
5 Endocrinology
The definition of hypoglycaemia is context dependent
https://t.me/med1917
The brain stops working if plasma glucose levels get too low, so we are nervous of
3
mmol/ L. But some are asymptomatic at this level. So what is definitely ab-
levels
normal? The answer may be
glucose levels (
patient when can I be sure that a low glucose is not contributing to their illness?’ If
4
mmol/ L, you may be wise to treat (p
<
hypoglycaemics, have they binged on alcohol
an underlying illness, eg insulinoma? Unlikely, but possible. Keep an open mind; let
the
more inclined to investigate if the eects of even mild hypoglycaemia might be disas-
NB
: whole blood glucose is 10– 15% < plasma glucose.) Think: ‘In this ill
GP
know. Counsel patient and relative about warning signs of hypoglycaemia. Be
4
mmol/ L, allowing for inaccuracies in fingerprick blood
818
)— just in case. Consider, is the patient on
24
h pre- test? Skipped meals? Is there
trous (eg in pilots) or if there are unexplained symptoms.
Insulinoma
This often benign (90– 95%) pancreatic islet cell tumour is sporadic or seen with
MEN- 1
(p
217
). It presents as fasting hypoglycaemia, with Whipple’s triad:
1
Symptoms associated with fasting or exercise.
2
Recorded hypoglycaemia with symptoms.
3
Symptoms relieved with glucose.
Screening test Hypoglycaemia + plasma insulin with C- peptide/ proinsulin and
negative sulfonylurea screen.
Imaging
CT/ MRI
test with hepatic venous sampling (
± endoscopic pancreatic US ± intra- arterial calcium stimulation
much time before proceeding to intra- operative visualization ± intra- operative
ultrasound).
surgery. Somatostatin receptor scintigraphy (gallium
18
F- L- 3,4
- dihydroxyphenylalanine
shown to be useful in detecting insulinomas when conventional imaging studies do
not identify them.
Treatment Excision. Medical treatment to control symptoms for insulinoma, eg
diazoxide, octreotide in those pending surgery.
Pursuing a voyage to the islets of Langerhans to the bitter end
A 50- year- old had episodic early- morning sweats and tremors and was found
to have hyperinsulinaemic hypoglycaemia (a rare condition known as nesidioblastosis). Selective
sion of the splenic and superior mesenteric arteries, so setting the stage for ‘hunt
IACS
showed a 2- fold increase in insulin secretion after infu-
the insulinoma’.
But cross- sectional imaging and endoscopic ultrasound were normal. At
laparotomy, no lesion was found despite mobilization of the pancreas, or during
intra- operative ultrasound. ‘Time to sew up and go home?’ ‘No!’ said the surgeon, ‘I’m going to do a distal pancreatectomy’. Histology showed no discrete
insulinoma, but diuse islet cell hyperplasia (nesidioblastosis). How much
pancreas to resect? Too little and nothing is gained: too much spells pancreatic endocrine disaster. Luckily the surgeon guessed right, and the patient was
cured by the procedure.
12
IACS
) (see
BOX
; all fallible, so don’t waste too
PET- CT
can help guide laparoscopic
DOTATATE
scans) have been
209
5 Endocrinology
Thyroid function tests (
TFT
TSH
https://t.me/med1917
210
Physiology
Thyroid- stimulating hormone (
the anterior pituitary (
active than
T
4
portion is the active part.
T
. 85% of
in plasma is protein bound, eg to thyroxine- binding globulin (
3
thus vital for growth and mental development. They also catecholamine eects.
Thyroid hormone abnormalities are usually due to problems in the thyroid gland
itself, and rarely caused by the hypothalamus or the anterior pituitary.
Fig 5.
12
Pathways involved in thyroid function.
Basic tests
See table
5.3
. Free
T
and
4
TBG
. Total
fected by
oestrogen therapy (
T
HRT
drome and malnutrition (both from protein loss), drugs (androgens, corticosteroids,
phenytoin), chronic liver disease, and acromegaly.
• Hyperthyroidism suspected Ask for
TSH
- secreting pituitary adenoma). Most have
rare
• Hypothyroidism suspected or monitoring replacement Ask for only
T
does not add any extra information.
3
30
% higher during darkness, so during monitoring, try to do at the same time.
Sick euthyroidism In any systemic illness,
pattern is for ‘everything to be low’. The test should be repeated after recovery.
Assay interference is caused by antibodies in the serum, interfering with the test.
Other tests
Thyroid autoantibodies
antibodies or antithyroglobulin antibodies may be increased in autoimmune thyroid disease: Hashimoto’s or Graves’ disease. If + ve in Graves’, there is an increased
risk of developing hypothyroidism at a later stage.
•
receptor antibody Useful to diagnose Graves’ disease.
• Serum thyroglobulin Useful in monitoring the treatment of carcinoma (p
in detection of factitious (self- medicated) hyperthyroidism, where it is low.
• Isotope scan (
for determining the cause of hyperthyroidism and to detect retrosternal goitre, ectopic thyroid tissue, or thyroid metastases (+ whole body
cious nodules, the question is: does the area have increased (hot), decreased (cold),
or the same (neutral) uptake of isotope as the remaining thyroid (
tral and almost no hot nodules are malignant.
123
Iodin e, 99technetium pertechnetate, etc.; see fig
Surgery is most likely to be needed if:
inant nodule on scintigraphy
• Ultrasound This di stinguishes cysti c (usua lly, but no t always, benign) fro m solid (pos -
sibly malignant) nodules. If a solitary (or dominant) large nodule, in a multinodular
goitre, do a fine- needle aspiration to look for thyroid cancer; see
S)
TSH
fig
T
and
4
, oral contraceptives), and hepatitis.
= thyrotropin), a glycoprotein, is produced from
5.12
). The thyroid produces mainly
is formed from peripheral conversion of
3
T
and
T
cell metabolism, via nuclear receptors, and are
3
4
T
are more useful than total
3
T
are when
3
TBG
is and vice versa.
T
,
T
3
4
TSH
TFT
Antithyroid peroxidase (
T
and
4
TSH
is very useful:
, and
TSH
. All will have
T
, but ~1% have only raised
4
varies through the day: trough at
S may become deranged. The typical
TPO
; formerly called microsomal)
20
% of ‘cold’ nodules are malignant.
• rapid growth • compression signs • dom-
• nodule 3cm • hypo- echogenicity. See also p
T
, which is 5- fold less
4
T
. Most
4
TBG
). The unbound
T
as the latter are af-
3
TBG
is in pregnancy,
TBG
is in nephrotic syn-
TSH
(except the
T
13.21
, p
593
CT
). If there are suspi-
fig
5.13
)? Few neu-
fig
13.22
, p
593
T
and
3
and
4
2PM
592
), and
.) Useful
722
.
.
TSH
T
.
3
.
;
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