endocrine Flashcards
GLP-1 stimulated by
oral glucose load
GLP-1 secreted by
small intestine L cells
What is the Incretin Effect?
a higher insulin spike is seen with oral glucose than IV glucose
Mediated by GLP-1, decreased in T2DM
example of a GLP-1 mimetic
exenetide
s/c injection 60mins before morning and evening meals
can be combined with metformin/sulphonylurea
When should exenatide be started?
when insulin would be started
obesity a problem (BMI >35)
continue if beneficial (decrease HbA1c and weight loss)
Risks of exenatide
SE nausea and vomiting
risk of pancreatitis and renal impairment
example of Dipeptidyl peptidase-4 (DPP-4) inhibitors
sitagliptin,
Vildagliptin
act of DPP-4i
DPP-4 inactivates GLP-1, therefore potentiating the effect of GLP-1 (increase insulin release, inhibit glucagon)
do DPP-4’s cause weight gain?
no
no evidence of increased hypoglycaemias
another name for subacute thyroiditis
De Quervain’s
cause of subacute thyroiditis
ususally following a viral infection
Mx of subacute thyroiditis
usually self limiting
NSAIDs
may need steroids, particularly if hypothyroidism develops.
Organs affected in Multiple endocrine neoplasia type 1
Parathyroid (95%) - hypercalcaemia
Pituitary (70%) - most commonly prolactinoma
Pancreas (50%) - most commonly insulinoma
From the MEN1 gene
how is an insulinoma diagnosed
what is the management
supervised prolonged fasting +/- CT
Mx: surgery or diazoxide/somatostatin if unfit for surg.
Mx of diabetic neuropathy
1st: duloxetine (SNRI),
2nd: amitriptyline
3rd: + pregabalin
4th: + tramadol
Haemochromatosis:
inheritance
pathology
features
auto rec
iron accumulation
bronzing of skin, ED, tired, arthralgia (esp hands)
chronic liver disease (and cirrhosis)
DM
cardiac failure (2ndary to dilated cardiomyopathy)
hypogonadism (2ndary to cirrhosis and pituitary dysfunction)
action of pioglitazone
PPAR gamma receptor agonist
SEs of pioglitazone
weight gain fluid retention - C/I in HF liver impairment - monitor LFTs increased risk of bladder ca increased risk of fractures
causes of low potassium with a raised BP
things affecting RAS system: Cushing's (and metabolic alkalosis) Conn's (primary hyperaldosteronism) Liddle's (increased renin) 11 beta hydroxylase deficiency liquorice
causes of low potassium with normal BP
diuretics
RTA (type 1 (distal) and 2 (proximal))
GI loss (d&v)
Bartter’s (genetic defect in loop of henle - like diuretics)
Gitelman’s (same as above but less severe)
Causes of hirsutism
PCOS (most common) cushing's syn obesity (peripheral conversion of oestrogen to androgens) androgen secreting tumour adrenal tumour CAH drugs: phenytoin
Mx of hirsutism
weight loss if obese
COCP
Ix for acromegaly
oral glucose tolerance test with GH measurements
normally GH is suppressed by hyperglycaemia
screening for gestational diabetes
previous gestational DM: OGTT 16-18w, and at 28w if 1st was normal
other RFs: test at 24-28w
Mx of pre-existing diabetes in pregnancy
lose weight if BMI >27
stop oral hypoglycaemics apart from metformin and start insulin
folic acid 5mg OD until 12/40
Mx of gestational DM
responds to diet and exercise in 80% of women
if poor glucose control or complications (macrosomia) ; metformin or glibenclamide (sulfonylurea) or insulin
stop hypoglycaemics post delivery, OGTT 6weeks postpartum
C/I for radioiodine in Graves
pregnancy (and should be avoided 4-6/12 post Rx)
<16 yrs
thyroid eye disease (relative C/I)
conditions that can give higher than expected HbA1c levels
increased RBC lifespan:
B12/folate deficiency
iron deficiency
splenectomy
most common cause of primary hyperparathyroidism
solitary adenoma (80%)
classical features of primary hyperparathyroidism
elderly female with unquenchable thirst and inappropriately normal/raised PTH
raised calcium, low phosphate
indications for orlistat
what is the target weight loss
BMI >28 with RFs
BMI >30 with no RFs
aiming for >5% weight loss at 3 months.
Causes of hypercholesterolaemia rather than hypertriglyceridaemia
nephrotic syn
cholestasis
hypothyroidism
Diagnostic features of metabolic syndrome
>3 of: increased waist circumference (central obesity) increased TG reduced HDL HTN raised fasting glucose/T2DM
associated features of metabolic syndrome
PCOS
non-alcoholic fatty liver disease
raised uric acid levels.
What is the risk of thyroid eye disease in Graves’ disease?
25-50%
Increased risk in smokers
Radio iodine may worsen eye disease
What are the criteria for familial hypercholesterolaemia Dx?
LDL >4.9
TC > 7.5
+/-Tendon xanthoma, FHx
Heterozygous disease, if homozygous most die before 10 of MI
What is the inheritance of familial hypercholesterolaemia?
Auto dom
Mx of hyperthyroid pt during pregnancy
Propylthiouracil - safe in pregnancy
Aim to keep free T4 levels in upper 2/3rds of normal to avoid foetal hypothyroidism
Diagnostic criteria for DKA
BM >11
Ketonaemia >3mmol/l
pH <7.3
Mx of DKA
ABCDE
IV fluids - usually need 5-8 litres
Insulin infusion - initially 0.1U/kg/hr
Replace potassium in second bag
features of autoimmune polyendocrinopathy type 1?
type 1:
rare auto rec AIRE1 gene defect
oral candidiasis, Addisons, hypoparathyroidism
features of autoimmune polyendocrinopathy type 2?
other name?
Schmidt’s syndrome
Addison’s disease plus T1DM or autoimmune thyroid
more common than type 1
10% of Addison’s disease patients have other endocrinopathies
mechanism of action of pegvisomant?
uses
GHr antagonist, once daily SC injection
used in acromegaly if not surgically fit. decreases IGF-1 to normal in 90% of patients
doesn’t reduce tumour size
Multiple endocrine neoplasia type 2 features
gene
2a: medullary cancer, parathyroid, phaeochromocytoma
2b: medullary cancer, phaeochromocytoma. Marfanoid body
RET oncogene
Repaglinide/nateglinide
mechanism of action
uses
SEs
ATP dependent K channel activators on pancreatic beta cells -> increase insulin release
used for patients not controlled on metformin with eratic lifestyles
hypoglycaemias (not as bad as sulphonylurea (gliclazide)), weight gain
Ix for MTC
pentagastrin stimulation test
gastrin normally leads to calcitonin release, in MTC there is a marked elevation in calcitonin
Features of carcinoid syndrome
which hormones released?
carcinoid tumours release serotonin and kallikrein
Flushing
diarrhoea
n&v
bronchoconstriction - histamine induced
2ndary restrictive cardiomyopathy - serotonin induced valvular fibrosis (mainly R heart)
Ix and Mx of carcinoid syndrome
24 urine 5-HIAA (breakdown product of serotonin)
octreotide scan may clarify distribution of the disease.
Mx: somatostatin analogues (octreotide) for symptomatic control +/- surgery
Biochemical changes in congenital adrenal hyperplasia
Low-normal cortisol
Markedly raised 17-hydroxyprogesterone
Due to 21-hydroxylase deficiency in steroid synthesis pathway -> decreased cortisol produced -> increased ACTH as decreased NF
Features of a glucagonoma
diabetes mellitus
weight loss
diarrhoea
necrolytic migratory erythema (red blistering rash of the groin buttocks and perineum)
