Endocrine Flashcards
What are incretins?
Hormones produced by the GI tract which are secreted in response to a big meal and reduce blood glucose levels. They;
- Increase insulin secretion
- Inhibit glucagon production
- Slow glucose absorption by the GI tract
Main incretin = GLP-1
Which enzyme inhibits incretins?
DPP-4 (dipeptidyl peptidase - 4)
Metformin
MOA = increases insulin sensitivity + decreases hepatic gluconeogenesis
SE = GI upset / Lactic acidosis
Contraindications = eGFR < 30
Sitagliptin
Type = DPP-4 Inhibitor (Increases levels of GLP-1)
SE = GI upset / URTI symptoms / Headaches / Inc risk of pancreatitis
SLGT-2 Inhibitors
Dapagliflozin / empagliflozin
MOA = Inhibit SGT in the PCT which increases glucose excretion.
SE = Increased UTIs/Thrust / Fourniers gangrene / Can cause DKA!
Pros = causes weight loss
*NOTE - dapagliflozin is also licensed in the management of HF.
Liraglutide / Exanatide
GLP-1 Agonists
SC Injection + also licensed for weight loss
SE = Hypoglycemia!!! N&V / GI upset / Dizziness
May increase risk of pancreatitis
Piaglitazone
Thiazolidinedione
MOA = Activates PPAR-gamma receptors in adiopcytes which increases insulin sensitivity + decreases hepatic gluconeogenesis
SE = Fluid retention / HF / CKD / Anemia / Liver dysfunction / Inc risk of bone fractures / WEIGHT GAIN / can inc risk of bladder cancer
Sulfonylureas
Gliclazide
MOA = Inhibits K+ channels on beta cells leading to insulin secretion
SE = HYPOGLYCEMIA / weight gain / Hyponatremia / bone marrow toxicity
Contraindications: avoid post MI or Renal failure
Which diabetic agents cause weight gain
Pioglitazone + sulfonylureas (gliclazide)
Which diabetic agents can cause DKA
SGLT-2 inhibitors
Which diabetic agents are most likely to cause Hypoglycemia
GLP-1 Agonists
Sulfonylureas
Which diabetic agents can aid weight loss
GLP 1 agonists + SLGT-2 inhibitors
Central diabetes insipidus
Decreased secretion of ADH from posterior pituitary
Causes = Idiopathic or secondary to pituitary surgery, head injury, haemochromatosis, CNS infection, Craniopharyngiomas .
Nephrogenic diabetes insipidus
A failure of the Collecting ducts to respond to ADH
Causes = tubulo-interstitial nephritis / Lithium therapy / avpr2 mutation / hypercalcemia / hypokalemia / Sjogren’s syndrome
Which cancer is hashimoto’s thyroiditis associated with?
MALT lymphoma
Hashimoto’s thyroiditis autoantibodies
Anti-TPO + Anti-thyroglobulin (Anti-Tg)
Which drug most commonly exacerbates hyperthyroidism
Amiodarone
Functions of cortisol
Increases alertness
Increases blood glucose
Increases metabolism
Inhibits the immune system
Inhibits bone formation
ABG/VBG findings in Cushing’s disease
Hypokalemic metabolic alkalosis + Hypernatremia
Blood findings in Addison’s disease
Hyponatremia + Hyperkalemia
Management of acromegaly in a patient who cannot undergo surgery
GH antagonists (pegvisomant)
Somatostatin analogue (Ocreotide) - inhibit GH release
Dopamine agonists (Bromocriptine)
Advice for pregnant women with hypothyroidism
Increase levothyroxine dose by 50%
Digoxin causes gynaecomastia, true or false?
MEN type 1
Parathyroid
Pituitary
Pancreas
+ Adrenal + Thyroid
Often presents as hypercalcemia (hyperparathyroidism) or recurrent hypoglycemia (insulinoma) or recurrent gastric ulcers (gastrinoma)
Mutation = MEN1 gene
MEN type 2
Parathyroid
Phaeochromocytoma
Medullary thyroid cancer
RET oncogene mutation
MEN type 3
Medullary thyroid cancer
Pheochromocytoma
Marfinoid
Neuromas
Main side effects of carbimazole
Agranulocytosis (infections)
Acute pancreatitis
Visual field defects seen in prolactinoma’s
Bitemporal hemianopia
Bitemporal superior quandrantopia
Hashimoto’s thyroiditis antibodies
Anti-TPO
Grave’s disease antibodies
TSH antibodies
First line treatment for cerebral mets
Dexamethasone
Hyperthyroidism management in pregnant ladies
First trimester = propylthiouracil
2nd + 3rd trimester = carbimazole
Diagnostic glucose measurements for diabetes
Fasting glucose >7mmol/L
Random glucose >11.1 (or after OGTT)
Pre-diabetes glucose measurements
Fasting glucose 6.1 - 6.9
Glucose tolerance / random plasm glucose 7.8 - 11.1
Features unique to T1DM (not seen in T2DM)
Low C peptide
Weight loss
Autoantibodies
Ketonuria
Primary Hypothyroisim
Low T4/T3
High TSH
Causes;
- Hashimoto’s
- Iodine deficiency
- Lithium
- Amiodarone
- Overtreatment of hyperthyroidism
Secondary hypothyroidism
Low T4/T4
Low TSH
Causes;
- Pituitary adenoma
- Pituitary surgery / trauma / radiotherapy
- Sheehan’s syndrome
Myxoedema coma
Severe hypothyroidism leading to decreased conciousness + coma
Management of myxoedema coma
IV fluids
IV levothyroixine
IV hydrocortisone
Sick Euthyroidism
T3/T4 low
TSH = innapropriately low / normal
Pt will typically have pneumonia / other illness at the same time
Grave’s disease Features
Autoimmune hyperthyroidism
- Bilateral expothalmus
- Opthalmoplegia
- Pretibial myxoedema
- Acropacy (clubbing)
May have a gotire
Scintigraphy shows increased uptake
Gotire with firm nodules and scintigraphy reveals patchy uptake
Multinodular goitre
Painful gotire with reduced, patch iodine uptake on scintigraphy
De quervain’s thyroiditis
De quervain’s thyroiditis
Initially causes a transient hyperthyroidism and then hypothyroidism.
Usually caused by a viral infection.
Medical management of hyperthyroidism
1st line = Carbimazole
2nd line = Propylthiouracil
Symptomatic relief with beta-blockers
Radioactive iodine if multinodular goitre
Thyrotoxic storm
Acute severe form of hyperthyroidism
Sx = hyperpyrexia + tachycardia + agitation
Tx = propylthiouracil + hydrocortisone + propanolol
ECG may show lateral T wave inversion
Most common type of thyroid cancer
Papillary
Management of papillary / Follicular thyroid cancers
Total thyroidectomy + radioiodine
Yearly TFTs/Calcitonin levels (as thats how a medullary one would present)
Causes of Hypoparathyroidism
Primary = usually due to thyroidectomy (Hypocalcemia + Low PTH + high phosphate)
Pseudo-hypoparathyroidism = resistance to PTH (would cause a hypocalcemia + raised PTH)
Symptoms of hypocalcemia
Tetany
Peri-oral parasthesia
Trousseau’s sign - BP cuff
Chvostek’s sign - parotid gland
Causes of cushing’s syndrome
- Exogenous steroid use (primary adrenal excess)
- Cushing’s disease (pituitary adenoma - secondary adrenal excess)
- Adrenal adenoma (primary)
- Paraneoplastic syndrome (ectopic ACTH release)
Clinical Features of cushings
Round moon face
Central obesity
Proximal limb muscle wasting
Buffalo hump
Abdominal striae
HTN + Cardiac hypertrophy + Hyperglycemia can all occur from high cortisol
Investigations & Findings in Cushing’s.
1st line = dexamethasone suppression test.
Low dose = no supression of cortisol
High dose = allows you to determine the cause of the cushing’s
- Cortisol + ACTH are suppressed = Cushing’s disease
- Just ACTH suppressed = Adrenal adenoma
- Neither suppressed = Ectopic cause (SCLC)
Causes of Adrenal Insufficiency
Primary = Addison’s disease
Secondary = Pituitary surgery/inf/radiation/sheehan’s
Tertiary = Long term steroid use (can suppress the hypothalamus)
Presence of what clinical feature indicates a primary adrenal insufficiency rather than secondary/tertiary
Hyperpigmentation - as this suggests raised ACTH
1st line investigation for adrenal insufficiency
Short syncathen test (ACTH stimulation test)
= Failure for cortisol to rise
Which antibodies are seen in Addison’s disease
Adrenal cortex antibodies + 21-hydrozylase antibodies
Management of addison’s disease
Hydrocortisone
Fludrocortisone
Addisonian crisis presentation + management
Reduced consciousness
severe hypotension
Hyponatremia + Hyperkalemia
Hypoglycemia
Management = IV hydrocortisone + IV fluids + IV dextrose - monitor + treat hyperkalemia as required
Medical Management of acromegaly
Pegvisomant (GH antagonist)
Octreotide (Somatostatin analogue)
Causes of Hyperaldosteronism
Primary;
- Bilateral adrenal hyperplasia
- Conn’s syndrome (adrenal adenoma)
- Familial hyperaldosteronism
Secondary;
- Renal artery stenosis /obstruction
- HF
How to differentiate between causes of hyperaldosteronism
Renin:Aldosterone ratio
in primary there is a Low renin + high aldosterone
In secondary there is a high renin + high aldosterone
Blood/ABG/VBG findings in Hyperaldosteronism
pH = Alkalosis
Hypokalemia
Symptomatic relief of hyperaldosteronism
Spirinolactone
Causes of SIADH
Ectopic production - paraneoplastic syndrome (SCLC, Pancreatic + prostate cancer)
Meds - thiazides, NSAIDs etc
Neurological - stroke, head injury etc
Infection
Post op
Diagnostic findings of SIADH
High urine sodium + High urine osmolality + Hyponatremia + Euvolemia
Tolvaptan
ADH receptor blocker
Histology of papillary thyroid cancer
Cells with empty nuclei
Orphan annie eyes
Psammoma bodies (ca deposits in papillary cells)
Waterhouse Friedreichsen syndrome
Severe adrenal failure due to severe infection (often neisseria meningitis)
Essentially causes severe addisonian crisis + DIC + Shock
Increased uptake on scintigraphy in a well defined sphere shape
Most likely a thyroid adenoma - grave would cause a more diffuse increased uptake and a multinodule goitre causes patchy uptake
Which insulin is used in an insulin pump
Insulin lispro
What would an ECG of hypocalcemia show
Isolated QTc elongation
*can occasionaly cause torsades de pointes but not as common as QT elongation.
Causes of hypophosphatemia
DKA
Alcohol excess
Acute liver failure
Refeeding syndrome
Primary hyperparathyroidism
Osteomalacia
Consequences = Haemolysis + WBC dysfunction + Muscle weakness + Rhabdomylosis + CNS dysfunction.
Management of hypophosphatemia in DKA
Hypophosphatemia is a common complication of insulin therapy in DKA (as it causes an intracellular shift of phosphate).
You should never stop the insulin infusion because of this, just transfuse some phosphate if its severe (i.e levels < 0.3)
What type of malignancy is associated with Hashmimoto’s thyroiditis
MALT lymphoma
Treatment of acute severe symptomatic hyponatemia
Hypertonic saline solution (e.g 3% Sodium chloride)
Treatment of acute severe symptomatic hyponatemia
Hypertonic saline solution (e.g 3% Sodium chloride)
Central pontine myelinolysis
Occurs from rapid correction of hyponatemia (too fast) leading to brainstem damage.
Features = spastic quadriparesis, Pseudobulbar palsy and emotional lability.
If severe can lead to confusion, coma and even locked in syndrome.
