Endocrinology Flashcards
How is a myxoedemic coma treated? How can this present?
Thyroxine and hydrocortisone
Eg presentation - confusion, bradycardia, hypotension
What happens to thyroxine dose in pregnancy?
Safe to take during pregnancy and breastfeeding
Increase by to 50% as early as 4-6 weeks
Diagnosis for insulinomas?
Supervised fasting with abnormally high insulin
CT pancreas
Treatment of thyrotoxicosis in pregnancy?
Propylthiouracil in 1st trimester
Carbimazole afterwards
When to avoid radioiodine in management of graves disease (hyperthyroidism) ?
When thyroid eye disease is present!
Investigation of acromegaly?
1st line - serum IGF1
Confirmed with OGTT and serial GH levels
Medical mx of phaeochromocytoma?
1st a-blocker eg PHenoxybenazmine (like PHaeo)
then B-blockers
When to add SGLT2 inhibitor to inital therapy in T2DM mx when on Metformin?
the patient has a high risk of developing cardiovascular disease (CVD, e.g. QRISK ≥ 10%)
the patient has established CVD
the patient has chronic heart failure
SGLT-2 inhibitors should also be started at any point if a patient develops CVD (e.g. is diagnosed with ischaemic heart disease), a QRISK ≥ 10% or chronic heart failure
Which supplement to be careful of when on levothyroxine?
Iron or Calcium carbonate tablets can reduce absorption of levothyroxine hence should be given 4 hours apart
Side effects of thyroxine therapy?
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
Management of thyrotoxic storm?
BB
Anti thyroid drugs - Propylthiouracil > Carbimazole due to effects on peripheral conversion
Steroids - prevent conversion of T4 -> T3
Blood gas findings in renal tubular acidosis?
Hyperchloraemic metabolic acidosis (normal anion gap)
What are the different types of RTA?
Type 1 RTA - Distal
Type 2 RTA - Proximal
Type 3 RTA - Mixed
Type 4 RTA - Hyperkalaemic
MEN 1, 2a and 2b?
MEN 1 (3Ps)
Parathyroid - hyper due to hyperplasia of gland
Pituitary
Pancreas
(Also adrenal and thyroid)
MEN 2a (2Ps)
Medullary thyroid cancer
Parathyroid
Phaeochromocytoma
MEN 2b (1P)
Medullary thyroid cancer
Phaeochromocytoma
Marfanoid appearance
Neuromas
Gene involved in MEN 1 v 2a v 2b
MEN 1 = MEN1 gene
MEN 2a + 2b = RET
Describe the hormonal responde to hypoglycaemia
1st - decreased insulin secretion
2nd - glucagon secretion
3rd - GH and Cortisol release
Describe the symathoadrenal responde to hypoglycaemia
Increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in PANS and CNS
Definitive mx of primary hyperparathyroidism?
Total parathyroidectomy
What cancer is associated with Hashimoto’s thyroiditis?
Thyroid lymphoma
Carbimazole v Propylthiouracil MoA?
Carbimazole + Propylthiouracil:
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
Propylthiouracil:
Also inhibits peripheral conversion of T4 to T3 via inibition of 5-deiodinase
Delayed puberty + hypogonadism + anosmia
LH & FSH low-normal and testosterone is low
Diagnosis?
Kallman’s syndrome
What to do in T2DM if HbA1c not controlled with triple therapy?
If triple therapy is not effective or tolerated consider switching one of the drugs for a GLP-1 mimetic:
BMI ≥ 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
Mx of infertility in PCOS?
Clomifene
Can also add metformin particularly if obese
Weight loss also important if appropriate
Drug causes of Gynaecomastia?
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin - used in prostate ca
oestrogens, anabolic steroids
Mx of stress incontinence?
Pelvic floor exercises - 8x3 daily - 3 months min
Surgical - retropubic midrethral tape procedures
Duloxetine - Offered if decline surgical procedures
Inheritance of Familial Hypercholesteraemia?
Autosomally dominant
Adverse effects of thiazolidinediones (-glitazones) used in T2DM?
Weight gain
Liver impairment - monitor LFTs
Fluid retention - CI in HF (increased risk if taking insulin)
Increased # risk
Increased risk of bladder ca
What to do to doses of long-term steroids in illness?
Double the dose of long-term steroids
MoA of Sulphonureas? Can these cause weight gain and hypoglycaemia?
Binding of ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta - CLOSES THE CHANNELS
Yes causes weight gain and hypoglycaemia
Glucocorticoid eg Pred effect on WBC?
Neutrophillia
How to distinguish between renal artery stenosis v primary hyperaldosteronism?
Both has raised aldosterone
Renin = low in primary hyperaldosteronism as HTN -> excessive renal perfusion-> decreased renin production (negative feedback mechanism)
Renin = high in renal artery stenosis for opposing reasons
MODY mechanism of inheritance?
Autosomally dominant
Klinefelter karyotype?
47 XXY
Which drugs can cause hypercalcaemia?
Thiazides
Ca-containing antacids
Statins in established CVD (stroke, IHD or PVD)?S
High intensity (Atorvastatin 80mg)
Gliclazide type of drug? MoA description?
Sulfonyureas - increase stimulation of insulin secretion by pancreatic B-cells and decrease hepatic clearance of insulin
Blood gas findings in Cushings?
Hypokalaemic metabolic alkalosis
Which HPV increases risk of cervical cancer? what are some other RFs?
HPV 16, 18, 33
Smoking
HIV
Earky first intercourse / multiple partners
High parity
Lower socio-economic status
COCP
Which type of thyroid ca is associated with RET oncogene?
Medullary
Which diabetic medications cause weight gain?
Insulin
Sulfonylureas
Thiazolidiones
Which diabetic meds can cause hypoglycaemia?
Insulin
Sulfonylureas
SGLT2 inhibitors
Medical mx of urge incontinence?
Muscarinic antagonist eg tolterodine, oxybutinin or solifenacin
Target improvement when using statins?
NICE look for a 40% reduction in non-HDL cholesterol after 3 months
If not improving by this level to consider titrating to 80mg
High LH, Low Testosterone
Infertile
Dx?
Klinefelters
Effect of corticosteroids on WBC?
Neutrophilia
How should 9am cortisol levels be interpreted?
> 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
What is addisons disease?
Low cortisol and aldosterones
Blood sugar targets in gestational DM?
fasting: 5.3mmol/L
AND
1 hour postprandial: 7.8 mmol/L or
2 hours postprandial: 6.4 mmol/L
Causes of pseudohyponatraemia?
Hyperlipidaemia
Hyperproteinaemia
Blood taken from drip arm
Severe hyperglycaemia -> draws intracellular water into extracellular place
Cause of Bartters syndrome?
defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle
Note- loop diuretics work by inhibiting this so think of bartters as taking large doses of furosemide
What is Hashimotos thyroiditis associated with?
MALToma
Why should slow infusion given to younger patients with DKA?
cerebral oedema
DKA insulin dose?
Diabetic ketoacidosis: the IV insulin infusion should be started at 0.1 unit/kg/hour
Which antibodies in hashimotos thyroiditis
anti-TPO
Important adverse effects of SGLT2 inhibitors?
Normoglycaemic ketoacidosis
Increased risk of lower limb amputation
Urinaru + genital infection secondary to glycosuria
How is a thyrotoxic storm managed?
counteracting the peripheral effects of thyroid hormone (using propranolol)
preventing peripheral conversion of T4 to active T3 (using steroids),
inhibiting further thyroid hormone synthesis (using antithyroid drugs and Lugol’s iodine).
When to refer for parathyroid surgery in primary hyperparathyroidism?
Symptoms of hypercalcaemia (e.g. thirst, polyuria, constipation)
End-organ disease (renal calculi, fragility fractures or osteoporosis)
Corrected serum calcium of 2.85 mmol/L or above
Which type of thyroid ca is associated with Hashimotos thyroiditis? (AI thyroiditis)
Lymphoma
What is anti-SS-A also known as? Which rheumatological condition is this associated with?
Also known as anti-ro and is associated with Sjogrens
Blood gas findings in Cushings?
Hypokalaemic metabolic acidosis -> excess cortisol prodcution leading to Na / water retention
Which type of RTA can show nephrocalcinosis?
Type 1 RTA
Which type of RTN is associated with osteomalacia?
Type 2 RTN
What is type 3 RTN caused by?
Carbonic anhydrase II deficiency
What are causes of type 4 RTN?
Hypoaldosteronism and diabetes
What are the causes of hypokalaemia with HTN?
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
Liddle’s syndrome
11-beta hydroxylase deficiency*
What are the causes of hypokalaemia without HTN?
diuretics
GI loss (e.g. Diarrhoea, vomiting)
renal tubular acidosis (type 1 and 2**)
Bartter’s syndrome
Gitelman syndrome
What happens to GLP-1 levels in T2DM?
There is decreased levels of GLP1
- released by small intestine in response to oral glucose load
Inheritance pattern of familial hypercholesteraemia?
Autosomally dominant
What is distal RTA (type 1) caused by?
Inability to secrete H+ in distal tubule
causes hypokalaemia
Can lead to nephrocalcinosis and renal stones (calcium phosphate)
What is distal (type 1) RTA linked to?
Idiopathic, rheumatoid arthritis, SLE, Sjogren’s, amphotericin B toxicity, analgesic nephropathy
What is proximal (type 2) RTA caused by?
decreased HCO3- reabsorption in proximal tubule
causes hypokalaemia also
Can lead to osteomalacia
What are the causes of proximal (type 2) RTA?
Idiopathic, as part of Fanconi syndrome, Wilson’s disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors (acetazolamide, topiramate)
What is mixed RTA (type 3) caused by?
extremely rare
caused by carbonic anhydrase II deficiency
results in hypokalaemia
What are the features and causes of hyperkalaemic RTA (type 4)?
reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium excretion
causes hyperkalaemia
causes include hypoaldosteronism, diabetes
Describe the different BMI classes?
Underweight < 18.49
Normal 18.5 - 25
Overweight 25 - 30
Obese class 1 30 - 35
Obese class 2 35 - 40
Obese class 3 > 40
What are the management options for obesity?
conservative: diet, exercise
medical
> orlistat - pancreatic lipase inhibitor -> faecal urgency / incontinence + flatulence + oily / fatty stools
> liraglutide - GLP1 mimetic
surgical
What are the tx options for urge incontinence?
Bladder retraining min 6 weeks - increasing intervals between voiding
Bladder stabilising meds:
1st line = antimuscarinics (oxybutinin, tolterodine or darifenacin) - avoid IR oxybutinin in frail older women risk of confusion + delirium
2nd line (if worried in older women) = Mirabegron (b3 agonist)
When can SGLT2 inhibitors be added in T2DM mx with context of CVD?
SGLT-2 should be introduced at any point they develop CVD, a high risk of CVD or chronic heart failure
What is the most common cause of thyroiditis?
Graves
In the primary prevention of CVD using statins aim for a reduction of what?
In the primary prevention of CVD using statins aim for a reduction in non-HDL cholesterol of > 40%
If not consider titrating up to 80mg
What are the adverse effects associated with fibrate use?
GI side effects
Increased risk of VTE
What antibodies are seen in Graves?
TSH receptor stimulating antibodies - seen in 90%
anti-thyroid peroxidase antibodies (75%)
Features of Bartters syndrome?
usually presents in childhood, e.g. Failure to thrive
polyuria, polydipsia
hypokalaemia
normotension
weakness
Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide
Which hormone is under constant inhibition?
Prolactin
What to do to Metformin dose during Ramadan?
for patients taking metformin the expert consensus is that the dose should be split one-third before sunrise (Suhoor) and two-thirds after sunset (Iftar)
What to do to sulphonylureas during Ramadan?
expert consensus also recommends switching once-daily sulfonylureas to after sunset.
For patients taking twice-daily preparations such as gliclazide it is recommended that a larger proportion of the dose is taken after after sunset
What to do to Pioglitazone during Ramadan?
no adjustment is needed for patients taking pioglitazone
Complications associated with Acromegaly?
hypertension
diabetes (>10%)
cardiomyopathy
colorectal cancer
What drugs can lead to SiADH?
sulfonylureas*
SSRIs, tricyclics
carbamazepine
vincristine
cyclophosphamide
What is hungry bone syndrome and what causes it?
Post-parathyroidectomy -> rapid drop in PTH levels which previously provided stimulation to osteoclasts when this drops rapid remineralisation occurs leading to
This leads to low Ca and to XR changes similar to metastatic lytic leisons if untreated
What is Pendred syndrome?
AR genetic disorder characterised by:
- Sensorineural deafness
- Mild hypothyroidism
- Goitre
Often head trauma worsens sensorineural hearing loss
What do bloods show in pseudohypoparathyroidism?
↑ PTH
↓ calcium
↑ phosphate
> short fourth and fifth metacarpals, short stature
learning difficulties, obesity, round face
What are meglitinides and who are they used for? what are possible adverse effects? suffix?
Meglitinides - increase pancreatic insulin secretion
Like sulphonylureas bind to ATP-dependent K+ channel on panc beta cells
Used in patients with erratic lifestyles
Adverse effects - weight gain + hypoglycaemia
Suffix = -glinide
Which antithyroid tx can exacerbate Graves eye disease sx? how can you reduce this risk?
radioiodine treatment may increase the inflammatory symptoms seen in thyroid eye disease.
In a recent study of patients with Graves’ disease around 15% developed, or had worsening of, eye disease.
Prednisolone may help reduce the risk
Why does metformin help boost fertility in those with PCOS?
Increases peripheral insulin sensitivity -> lead to complicated changes in the hypothalamic-pituitary-ovarian axis.
Which thyroid ca is likely to cause pressure symptoms?
Anaplastic thyroid cancer - aggressive, difficult to treat and often causes pressure symptoms
Stress incontinence mx?
pelvic floor muscle training- NICE recommend at least 8 contractions performed 3 times per day for a minimum of 3 months
surgical procedures: e.g. retropubic mid-urethral tape procedures
duloxetine may be offered to women if they decline surgical procedures
What causes Gitelmans syndrome? What are the features?
Gitelman’s syndrome is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the DCT
Features:
> normotension
> hypokalaemia
> hypocalciuria
> hypomagnesaemia
> metabolic alkalosis
What electrolyte abnormalities are seen in Addisons disease?
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
What is definitive ix for Addisons?
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.
Describe how 9am serum cortisol can be interpreted in Addisions
> 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
What is the limitation of the ACTH stimulation test (short synacthen)
Excludes only primary adrenal failure and does not exclude cortisol deficiency secondary to failure of the pituitary to produce ACTH
When can you add metformin in T1DM?
NICE recommend considering adding metformin if the BMI >= 25 kg/m²
Nuclear scintigraphy in toxic multinodular goitre?
Nuclear scintigraphy reveals patchy uptake
tender goitre, hyperthyroidism and raised ESR is suggestive of ?
Subacute thyroiditis (De Quervains)
What can cause pseudohyponatraemia?
pseudohyponatraemia include hyperlipidaemia (increase in serum volume) or a taking blood from a drip arm
What are some causes hyponatraemia with urinary sodium <20mmol/L?
Sodium depletion, extra-renal loss
> diarrhoea, vomiting, sweating
> burns, adenoma of rectum
Water excess (patient often hypervolaemic and oedematous)
secondary hyperaldosteronism
> heart failure, liver cirrhosis
> nephrotic syndrome
> IV dextrose
> psychogenic polydipsia
What are some causes hyponatraemia with urinary sodium >20mmol/L?
Sodium depletion, renal loss (patient often hypovolaemic)
diuretics: thiazides, loop diuretics
> Addison’s disease
> diuretic stage of renal failure
Patient often euvolaemic
> SIADH (urine osmolality > 500 mmol/kg)
> hypothyroidism
What is diagnosis of gestational diabetes based on?
these have recently been updated by NICE, gestational diabetes is diagnosed if either:
fasting glucose is >= 5.6 mmol/L
2-hour glucose is >= 7.8 mmol/L
Mx of GDM?
if the fasting plasma glucose level is < 7 mmol/l a trial of diet and exercise should be offered
if glucose targets are not met within 1-2 weeks of altering diet/exercise metformin should be started
if glucose targets are still not met insulin should be added to diet/exercise/metformin
gestational diabetes is treated with short-acting, not long-acting, insulin
if at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be started
if the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of complications such as macrosomia or hydramnios, insulin should be offered
glibenclamide should only be offered for women who cannot tolerate metformin or those who fail to meet the glucose targets with metformin but decline insulin treatment
Hyperthyroidism -> hypothyroidism +- viral infection preceeding is suggesive of?
De quervains thyroiditis (subacute)
Main issue with oestrogen only HRT v combined oestrogen+progesterone?
Raised risk of endometrial ca
What does FSH + LH do in menstrual cycle and which phase mainly?
A rise in FSH results in the development of follicles which in turn secrete oestradiol
When the egg has matured, it secretes enough oestradiol to trigger the acute release of LH. This in turn leads to ovulation
This both occurs in Follicular phase (proliferative)
how to assess diabetic neuropathy in feet?
A 10 g monofilament
Rules re HGV licence for those DM with insulin (+ other hypoglycaemic agents)?
there has not been any severe hypoglycaemic event in the previous 12 months
the driver has full hypoglycaemic awareness
the driver must show adequate control of the condition by regular blood glucose monitoring*, at least twice daily and at times relevant to driving
the driver must demonstrate an understanding of the risks of hypoglycaemia
here are no other debarring complications of diabetes
Recent transsphenoidal pituitary surgery can lead to what endo issue?
Cranial DI
How to distinguish between Gitelmans and Barters syndrome?
Levels of calcuria - high in Barters, low in Gitelmans
Low Ca + Mg in addition to low Na, K and Cl - Gitelmans
Metabolic alkalosis - both
What are some signs of GI autonomic neuropathy that can occur in DM?
Gastroparesis - erratic BMs, bloating + voming
Chronic diarrhoea - often at night
GORD - decreased lower oesophageal sphincter pressure
Mx of gastroparesis due to DM?
Prokinetic agents - metoclopramide, domperidone, erythromycin
evolocumab moa and what is us used for?
Evolocumab prevents PCSK9-mediated LDL receptor degradation
used for hypercholesteramia in rare cases
What can cause euglycaemic DKA? when to consider?
Can be seen with use of novel oral hypoglucaemic agents eg SGLT2 inhibitors
Consider if people with unexplained raised anion gap acidosis and normal blood sugar level who is on one of these medications
What is a rare haematological complication of uterine fibroids and why?
Polycythaemia due to autonomous production of EPO
Describe the hormonal and sympathoadrenal responses to hypoglycaemia?
hormonal response: the first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released but later
sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system
Often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels but low testosterone
Dx?
Klinefelters
Triple therapy and adding a GLP 1 mimetic ?
You should switch a drug for the GLP 1 mimetic not add on a 4th
What are the fasting glucose and 2 hours post glucose ingestion targets in GDM?
fasting blood glucose in gestational diabetes is <5.3 mmol/L. T
he target for blood glucose two hours after an oral glucose tolerance test is <6.4
What hyperthyroidism features are unique to Graves disease?
1)Ex“opathalmo”s+“ Opthalmo”plegia [ NOT lid lag]
2) Pretibial myxedema
3) Thyroid acropachy (clubbing)
Mx of subacute thyroiditis?
usually self-limiting - most patients do not require treatment
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops
Main adverse effects of GLP 1 mimetics
N+V
Also risk of pancreatitis
Radioiodine most common side effect + most problematic
Most common = hypothyroidism
Most problematic = exacerbation of thyroid eye disease
Typical presentation of insulinoma?
of hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness, sweating etc
rapid weight gain may be seen
high insulin, raised proinsulin:insulin ratio
high C-peptide
Advantage of Block+replace v block therapy in Graves mx?
Block and replace regimens are shorter duration than carbimazole titration
Starting dose of carbimazole in Graves? main complication?
40mg and reduce gradually continued for 12-18m
Agranulocytosis = major complication
What does clitoromegaly suggest?
High androgen levels -> if suspecting PCOS investigate further to exclude ovarian / adrenal androgen secreting tumour
Most common causes of ACTH dependent and independent Cushings?
ACTH dependent causes
>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
ACTH independent causes
> iatrogenic: steroids
> adrenal adenoma (5-10%)
> adrenal carcinoma (rare)
> Carney complex: syndrome including cardiac myxoma
> micronodular adrenal dysplasia (very rare)
What is pseudo-cushings? causes? and what are the investigations
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
Causes of raised ALP?
liver: cholestasis, hepatitis, fatty liver, neoplasia
Paget’s
osteomalacia
bone metastases
hyperparathyroidism
renal failure
physiological: pregnancy, growing children, healing fractures
Riedel’s thyroiditis - what is it? how does it present? what is it associated with?
Rare cause of hypothyroidism characterised by dense fibrous tissue replacing normal thyroid parenchyma
O/E - diffuse neck goitre that is hard on palpation, non-tender and fixed in position.
Associated with retroperitoneal fibrosis
Hyperlipidaemia describe cases which are predominantly hypertriglycerides v hypercholesteraemia?
TRIGLYCERIDES
diabetes mellitus (types 1 and 2)
obesity
alcohol
chronic renal failure
drugs: thiazides, non-selective beta-blockers, unopposed oestrogen
liver disease
CHOLESTEROL
nephrotic syndrome
cholestasis
hypothyroidism
Kallmans v Klinefelters?
Kallmans- hyPOgonadotropic hyPOgonadism
Kallman’s = 1 ball and tall, can’t smell at all, no hormones, balls may be undescended
Klinefelters- HyPERgonado. hyPOgonad.
Klinefelters = Tall, titties, tiny testes, high gonad hormones
Which patients may not respond to glucagon in hypoglycaemia?
Those with alcoholic liver disease - give IV glucose 20% / oral if conscious
Sick euthyroid syndrome bloods?
TSH is inappropriately normal / raised
Low T4 and T3
Usually reversible following recovery from systemic illness hence no tx needed
Possible causes of sick euthyroid?
myocardial infarctions, starvation, burns, trauma, surgery, malignancy, diabetic ketoacidosis, any organ failure and inflammatory conditions.
Causes of raised prolactin??
oestrogens
acromegaly: 1/3 of patients
Ps
pregnancy
prolactinoma
physiological - stress, exercise, sleep
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
phenothiazines, metoclopramide, domperidone
Drug causes of raised prolactin?
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
NB bromocriptine is used to counteract this
Remnant hyperlipidaemia, also known as dysbetalipoproteinaemia or type III hyperlipoproteinaemia, is characterised by increased levels of remnant lipoproteins (chylomicron and VLDL remnants)
Mx?
Fibrates
work by activating peroxisome proliferator-activated receptors (PPARs), particularly PPAR-alpha, which leads to increased lipolysis and elimination of triglyceride-rich particles from plasma
Complete androgen insensitivity syndrome (CAIS)
features? mx?
‘primary amenorrhoea’
little or no axillary and pubic hair
undescended testes causing groin swellings
breast development may occur as a result of the conversion of testosterone to oestradiol
MX:
counselling - raise the child as female
bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
oestrogen therapy
Two types of IGR (impaired glucose regulation) + causes and differentiation?
impaired fasting glucose (IFG) - due to hepatic insulin resistance
impaired glucose tolerance (IGT) - due to muscle insulin resistance
a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
impaired glucose tolerance (IGT) is defined as 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
You can buy lots of unhealthy snacks at a 7/11, which might give you diabetes.
7 = cutoff for fasting flucose
11 = cutoff for random or after glucose load
Steroids mineralcorticoid v glucorticoid activity?
Mnemonic - From mineralcorticoid activity»_space;> glucocorticoid activity: Free Hotels Provide Delicious Breakfasts
Fludrocortisone > Hydrocortisone > Prednisolone > Dexamethasone & Betmethasone
T1DM when to provide 20mg atorvastatin?
older than 40 years, or
have had diabetes for more than 10 years or
have established nephropathy or
have other CVD risk factors
NB see point 3 - also offer in CKD
Describe tertiary hyperparathyroidism
autonomous hypersecretion of PTH due to hypertrophied parathyroid glands
occurs after a period of long standing secondary hyperparathyroidism
treatment involves parathyroidectomy
Causes of pseudohyperkalaemia?
haemolysis during venipuncture (excessive vacuum of blood drawing, prolonged tourniquet use or too fine a needle gauge)
delay in the processing of the blood specimen
abnormally high numbers of platelets, leukocytes, or erythrocytes (such as myeloproliferative disorders)
familial causes
Causes of hypokalaemia with acidosis v alkalosis?
Hypokalaemia with alkalosis
1. vomiting
2. thiazide and loop diuretics
3. Cushing’s syndrome
4. Conn’s syndrome (primary hyperaldosteronism)
Hypokalaemia with acidosis
1. diarrhoea
2. renal tubular acidosis
3. acetazolamide
4. partially treated diabetic ketoacidosis
NB mg deficiency can also cause hypokalaemia
Insulin stress test, when to use and findings?
When is it CI?
used in investigation of hypopituitarism
IV insulin given, GH and cortisol levels measured
with normal pituitary function GH and cortisol should rise
CI - Epilepsy, IHD and adrenal insufficiency
Describe what happens in dynamic pituitary tests and what is measured with this?
Insulin, TRH and LHRH are given to the patient following which the serum glucose, cortisol, growth hormone, TSH, LH and FSH levels are recorded at regular intervals.
Prolactin levels are also sometimes measured*
Normal changes:
GH level rises > 20mu/l
cortisol level rises > 550 mmol/l
TSH level rises by > 2 mu/l from baseline level
LH and FSH should double
Why should subclinical hyperthyroidism be managed?
Potential risk on cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis)
Impact on QoL + dementia risk
Nesidioblastosis features?
diffuse proliferation of pancreatic β-cells, would show elevated C-peptide levels alongside the high insulin levels, as the insulin is being produced endogenously
Seen in neonates or post-bariatric surgery
Features of sulphonylurea abuse?
Raised c peptide - stimulates endogenous insulin
Glitazones cellular moa?
agonists of PPAR-gamma receptors, reducing peripheral insulin resistance
Acute phase proteins? negative acute phase - increased liver degreation?
CRP*
procalcitonin
ferritin
fibrinogen
alpha-1 antitrypsin
caeruloplasmin
serum amyloid A
serum amyloid P component**
haptoglobin
complement
-ve acute phase:
albumin
transthyretin (formerly known as prealbumin)
transferrin
retinol binding protein
cortisol binding protein
Features of metabolic syndrome?
WTH BestFriend?!!!
Waist Circumference - inc
Triglycerides - inc
HDL - low
BP - high
Fasting glucose - high
NB - LDLs are not involved
Other associated features include:
raised uric acid levels
non-alcoholic fatty liver disease
polycystic ovarian syndrome
circumstances under which parathyroidectomy should be considered in primary hyperparathyroidism?
Age under 50 years.
Adjusted serum calcium concentration that is 0.25 mmol/L or more above the upper end of the reference range.
Estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 although this threshold depends on other factors, such as age.
Renal stones or presence of nephrocalcinosis on ultrasound or CT.
Presence of osteoporosis or osteoporotic fracture.
Symptomatic disease
Autoimmune polyendocrinopathy syndrome aka APS type 1 and type 2 features?
APS type 2 has a polygenic inheritance and is linked to HLA DR3/DR4. Patients have Addison’s disease plus either:
- type 1 diabetes mellitus
- autoimmune thyroid disease
NB type 2 is way more common
Features of APS type 1 (2 out of 3 needed)
- chronic mucocutaneous candidiasis (typically first feature as young child)
- Addison’s disease
- primary hypoparathyroidism
Can get vitiligo in both types
What food are high in K and avoided in CKD?
salt substitutes (i.e. Contain potassium rather than sodium)
bananas, oranges, kiwi fruit, avocado, spinach, tomatoes
What is the majority of hypercalcaemia of malignancy caused by?
PTHrp - even in non scc lung ca
What increases risk of breast ca in HRT?
Progesterone
Chovstek v Trousseau which is more sensitive / specific for hypocalcaemia?
Trousseau’s sign is more sensitive and specific than Chvostek’s sign
NB Chvostek’s sign, which involves twitching of the facial muscles in response to tapping over the area of the facial nerve, is less sensitive and specific for hypocalcaemia than Trousseau’s sign. Trousseau’s sign involves carpal spasm induced by inflating a blood pressure cuff above systolic pressure for 2-3 minutes; it has greater sensitivity and specificity for hypocalcaemia.
Addison’s disease what may be seen in women?
Loss of pubic hair + axillary hair due reduced production of testosterones from the adrenal gland
Describe results of high dose dex and interpretation
Cortisol suppressed, ACTH supressed - Cushings disease (Pituitary adenoma -> ACTH)
Cortisol not suppressed, ACTH supressed - Cushing’s syndrome due to other causes (e.g. adrenal adenomas)
Cortisol and ACTH not supressed - Ectopic ACTH
Petrosal sinus sampling interpretation?
A central-to-peripheral gradient of ACTH (higher levels in the petrosal sinus compared to peripheral blood) indicates pituitary adenoma.
Conversely, similar ACTH levels in both sites suggest ectopic ACTH production
Do when Cushings syndrome picture but no clear adenoma on MRI H
CRH stimulation interpretation?
if pituitary source then cortisol rises
if ectopic/adrenal then no change in cortisol
Tests to confirm Cushing’s syndrome?
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
Bloods in hypothalamic amenorrhoea?
Gonadotrophins: Low levels of LH and FSH indicate a hypothalamic cause.
Oestradiol: Levels are usually low due to decreased gonadotrophin release.
Causes of hypocalcaemia with different phosphate levels?
- Low Phosphate (Hypophosphataemia):
- Vitamin D deficiency: Osteomalacia or rickets.
- Chronic kidney disease: Early stages may present with low phosphate.
- Malnutrition: Inadequate dietary intake of calcium and phosphate. - Normal Phosphate:
- Hypoparathyroidism: Post-surgical or autoimmune causes.
- Pseudohypoparathyroidism: Genetic condition causing resistance to PTH.
- Acute pancreatitis: Can lead to transient hypocalcaemia without significant phosphate changes. - High Phosphate (Hyperphosphataemia):
- Chronic kidney disease: Impaired renal excretion of phosphate.
- Rhabdomyolysis: Release of intracellular phosphate during muscle breakdown.
- Massive blood transfusion: Citrate anticoagulant can bind calcium and release phosphate.
Causes of hyperuricaemia - increased synthesis?
Lesch-Nyhan disease
myeloproliferative disorders
diet rich in purines
exercise
psoriasis
cytotoxics
Causes of hyperuricaemia - decreased excretion?
drugs: low-dose aspirin, diuretics, pyrazinamide
pre-eclampsia
alcohol
renal failure
lead
Patchy uptake in nuclear scintigraphy is what condition? mx>
Toxic multinodular goitre
mx = radioiodine
Concordance between identical twins is higher in type 2 diabetes mellitus than type 1 - true or false?
TRUE!
Hyper or hypothyroidism which leads to gynaecomastia?
Hyper more often!!
Different mutations in MODY?
The most common types are MODY2 (GCK mutation) - mild often asymptomatic / mildy not associated with T2DM
and MODY3 (HNF1A mutation), - more commonly causes T2DM
but others include MODY1 (HNF4A),
MODY4 (PDX1),
MODY5 (HNF1B), and so on. renal cysts + genital issues
Liddle’s syndrome? mx?
Liddle’s syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis.
Due to Na in DCT issues
mx - amiloride / triamterene
Dx of T2DM?
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.
7/11 snacks !!
What does drug induced acne look like?
Seen with glucocorticoids
This is characterised as monomorphic papular rash without comedones or cysts.
This does not respond to acne treatment but improves on drug discontinuation
Excessive flatulence is an extremely common side effect of what diabetic drug?
Acarbose - not used anymore
Addisons what adrenal steroid may be reduced?
Dehydroepiandrosterone DHEA
Hypothyroidism under medication - raised tsh but normal t4 interpretation?
Poor compliance - likely took doses prior to test
Bendroflumethiazide - effect on ca?
Hypercalcaemia due to renal ca reabsorption increased
When to screeen for GDM?
the oral glucose tolerance test (OGTT) is the test of choice
women who’ve previously had gestational diabetes: OGTT should be performed as soon as possible after booking and at 24-28 weeks if the first test is normal. NICE also recommend that early self-monitoring of blood glucose is an alternative to the OGTTs
women with any of the other risk factors should be offered an OGTT at 24-28 weeks
Skin manifestations of hypothyroidism?
dry (anhydrosis), cold, yellowish skin
non-pitting oedema (e.g. hands, face)
dry, coarse scalp hair, loss of lateral aspect of eyebrows
eczema
xanthomata
pruritis
Skin manifestations of hyperthyroidism?
pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli
thyroid acropachy: clubbing
scalp hair thinning
increased sweating
T2DM what type of insulin to offer?
Neutral Protamine Hagedorn (NPH) insulin [also known as isophane insulin] - OD / BD
Can add short acting esp if HbA1c >75
Insulin detemir or insulin glargine considered instead of NPH insulin if - needs assistance from carer for this, would reduce from BD to OD, lifestyle restriction due to symptomatic hypos
BPH why avoid amitriptyline?
Risk of urinary retention
pegvisomant when is this used and moa?
Used in acromegaly
GH receptor antagonist - doesnt reduce tumour volume but decreases IGF1 in 90% of cases to normal
DKA - on fixed rate insulin but not given long acting what to do?
Give long acting and when appropriate stop infusion with next meal?
How to calculate average plasma glucose based on HbA1c?
average plasma glucose = (2 * HbA1c) - 4.5
Mx of HHS?
IVF +- K (.5 - 1l / hr )
VTE prophylaxis due to hyperviscosity -> main cause of complications
No insulin unless BMs stop dropping with IVF
Features of HHS?
hypovolaemia
marked hyperglycaemia (>30 mmol/L)
significantly raised serum osmolarity (> 320 mosmol/kg) - can be calculated by: 2 * Na+ + glucose + urea
no significant hyperketonaemia (<3 mmol/L)
no significant acidosis (bicarbonate > 15 mmol/l or pH > 7.3 - acidosis can occur due to lactic acidosis or renal impairment)
The hyponatraemia and potassium towards the upper end of the normal range, coupled with hypoglycaemia
Suggest what disorder?
Addisons disease
Acute hyponatreamia with severe symptoms mx?
Patients with acute, severe (<120 mmol/L) or symptomatic hyponatraemia require close monitoring, preferably in an HDU or above setting.
Hypertonic saline (typically 3% NaCl) is used to correct the sodium level more quickly than would be done in patients with chronic hyponatraemia.
Pathophys of osmotic demyelination syndrome?
Astrocyte apoptosis
Primary polydipsia is aka?
Psychogenic polydipsia
