MLA Endocrinology Flashcards
OGTT threshold for diabetes diagnosis?
> 11.1
Which investigation as an alternative to HbA1c is recommended in patients with existing haemoglobinopathy?
Fructosamine test
What is the diagnostic threshold for type 2 diabetes mellitus on fasting blood glucose?
> 7.0
What is the HbA1c range associated with impaired glucose tolerance?
42-47
Which auto-antibody (3) is associated with type 1 diabetes mellitus?
Islet cell
Anti-GAD
ZnT8
Which blood test should be performed in patients with suspected type 1 diabetes?
C-peptide (low) indicates insulin deficiency (marker of beta-cell function)
Which type of T1DM presents in adulthood?
Latent autoimmune diabetes in adults (LADA)
What is the cause of type 3c diabetes mellitus?
Pancreatogenic e.g., chronic pancreatitis, pancreatic cancer, CF, haemochromatosis
What are the side effects associated with metformin?
Diarrhoea
Lactic acidosis
What are the common adverse effects associated with SGLT-2 inhibitors?
UTIs
Thrush
Fournier’s gangrene
Euglycaemic ketoacidosis
What should be done to sustained release metformin in patients presenting with diarrhoea?
Switch to a modified release
Which anti-hyperglycaemic drug is associated with weight gain?
Sulfonylureas / glitazones
Which cancer risk is increased in patients on glitazones?
Bladder cancer
What is the initial insulin regimen for diabetes?
Basal bolus regimen
What severe features are associated with non-proliferative diabetic retinopathy?
Cotton wool spots
On biopsy, what is the characteristic finding observed in patients with diabetic nephropathy?
Kimmelstein-Wilson nodules
Which neuropathic medication is indicated in the management of diabetic neuropathy?
Duloextine
Amitriptyline
Gabapentin
Pregablin
Which nerve in the thigh is affected in amyotrophy (diabetes)?
Femoral nerve
What rheumatological manifestations are associated with T2DM?
Charcot neuroarthropathy
Adhesive capsulitis
What is the glucose threshold for hypoglycaemia in patients with diabetes?
<4.0 mmol/L
Which drug class can cause impaired hypoglycaemia awareness?
Beta-blockers
What is the first-line management option in patients with hypoglycaemia (conscious)?
Oral glucogel
Sugary drink
Unconscious - hypoglycaemia management (1st line)
IM glucagon or IV glucose (10-20%)
pH diagnostic threshold for DKA?
<7.3
Bicarbonate threshold for DKA?
<15
1st line management for DKA?
1L stat 0.9% sodium chloride then 1 hour then 2 hours.
Following fluid resuscitation, what is the next most appropriate management for DKA?
Fixed-rate insulin 0.1 Units /kg
What is the glucose threshold to begin administering glucose?
CBG <14
What is the complication of rapid correction of glucose?
Central pontine myleinolysis
What is the fasting plasma glucose level for gestational diabetes?
5.6
What is the 2-hour OGTT threshold for gestational diabetes?
7.8
What are the foetal complications associated with gestational diabetes?
Macrosomia
Shoulder dystocia
Polyhydramnios
Hypoglycaemia (neonatal)
Stillbirth
When is a 75 g 2 hour OGTT test performed during pregnancy?
At 24-28 weeks
If the FPG is >7.0 during pregnancy, what medication is recommended?
Insulin
1st line management for gestational diabetes if fasting blood glucose is 6.0 - 6.9?
Metformin
When are diabetic drugs discontinued during gestational diabetes?
Immediately postpartum
Which criteria is used to diagnose FH?
Simon–Broome Criteria
What is the inheritance pattern for familial hypercholesterolaemia?
Autosomal dominant
What is the total cholesterol threshold for FH?
> 7.5 mmol/L
What is the first line management of cranial diabetes insipidus?
Desmopressin
What is a common cause of pseudohyponatraemia?
High glucose, lipids or paraproteins
What sodium level is associated with severe hyponatraemia?
<120 mmol/L (normal range 135-145)
What is the management of hyponatraemia in patients with SIADH?
Fluid restriction and vaptans
What is the most common cause of hypercalcaemia?
Primary hyperparathyroidism (parathyroid adenoma)
What ECG findings are consistent with hypercalcaemia?
Short QT interval
J waves
What is the most important blood test to perform in a patient with hypercalcaemia?
Serum parathyroid hormone
What is the first line management of hypercalcaemia?
Intravenous fluids 4-6 L in 24 hours
What is the second step in the management of hypercalcaemia?
IV bisphosphonates
What is the main cause of secondary hyperparathyroidism?
Vitamin D deficiency, Chronic kidney disease
What is the mechanism of action of Denusomab?
RANK-L inhibitor
What is a common complication of thyroidectomy?
Hypocalcaemia
What is the first line management of severe symptomatic hypocalcaemia?
IV calcium gluconate
What ECG findings are associated with hypokalaemia?
ST depression
T-wave flattening
PR prolongation
U waves
What is the standard rate of potassium replacement in hypokalaemia?
10 mmol/hour
What drug is indicated to stabilise the cardiac membrane in patients with hyperkalaemia and ECG changes?
Calcium gluconate
Where is aldosterone produced in the adrenal cortex?
Zona glomerulosa
Where are glucocorticoids produced in the adrenal cortex?
Zona fasciculata
Which drugs can induce adrenal insufficiency?
Long-term steroids
Ketoconazole
What is the first line test for diagnosing Addison’s disease?
9 am cortisol + ACTH (Synacthen test)
What is the first line management for an Addisonian crisis?
IV hydrocortisone
Sick day rules for Addison’s disease?
Double hydrocortisone dose and keep the fludrocortisone dose the same
What is the acid-base status for Addison’s?
Hyperkalaemic metabolic acidosis
What is the most common autoimmune cause of hypothyroidism?
Hashimoto’s thyroiditis, primary atrophic hypothyroidism
Which mineral deficiency is associated with hypothyroidism?
Iodine deficiency
What is a hallmark feature of severe hypothyroidism?
Myxoedema coma - marked by hypothermia, hypoventilation, hyponatraemia, heart failure and confusion
Which blood test is recommended as first line for suspected hypothyroidism?
Serum TSH
↓ T4/T3, ↑ TSH Diagnosis?
Primary hypothyroidism
↓ T4/T3 and TSH diagnosis?
Secondary hypothyroidism
Which autoantibody is associated with hypothyroidism?
Serum thyroid peroxidase antibodies
In patients with normal thyroid function, yet symptoms of hypothryoidism, what investigation is recommended?
Neck ultrasound
Elevated TSH levels, and normal free T4, suggests what?
Subclinical hypothyroidism
What is the long-term therapy for hypothyroidism?
Levothyroxine monotherapy
How is levothyroxine taken?
Oral on an empty stomach, in the morning before food
How frequently should TSH be monitored following levothyroxine therapy?
Every 3 months
How should the levothyroxine dose be adjusted during pregnancy?
Increase by 25-50 micrograms
What is the criteria for starting levothyroxine in subclinical hypothyroidism?
TSH is >10 mU/L and FT4 is within the reference range on 2 separate occasions 3 months apart.
or
- If <65 years, consider a 6-month trial of LT4 if:
- TSH is 5.5 – 10 mU/L on 2 separate occasions 3 months apart, and there are symptoms of hypothyroidism.
What is the management for asymptomatic subclinical hypothyroidism?
Watch and wait; repeat TFTs in 6 months
What is the first line management for myxoedema coma?
- Oxygen
- Rewarming (for hypothermia)
- Rehydration
- IV T4/T3
- IV hydrocortisone (in case hypothyroidism is secondary to hypopituitarism)
What autoantibody is associated with Graves’ disease?
Anti-TSH receptor antibody
What is the second most common cause of hyperthyroidism?
Toxic multinodular goitre
Which drug is associated with AIT Type 1 hyperthyroidism?
Amiodarone
Which ovarian tumour is associated with hyperthyroidism?
Struma ovarii
Which is a dose-dependent risk factor for Graves orbitopathy?
Smoking
What are the signs of Graves’ orbitopathy?
Periorbital oedema, proptosis, conjunctival oedema, increased tears, ophthalmoplegia, optic nerve atrophy
Goitre description in Graves’ disease?
Diffuse symmetrical
What is the goitre presentation in toxic adenoma?
Unilateral non-tender thyroid mass
Which imaging. modality is indicated in patients with a palpable thyroid goitre?
Neck ultrasound
What are the TFT results for amiodarone-induced hyperthyroidism?
Low TSH and raised FT4
What is the definitive imaging investigation for Graves’ disease?
Radioisotope uptake scan (Tc99) - diffuse uptake
Multiple hot nodules with suppression of the rest of the thyroid gland is consistent with what diagnosis?
- Toxic multinodular goitre
Thyrotoxicosis following a flu-like illness?
- De Quervains thyroiditis
Which investigation is indicated for Graves’ orbitopathy?
CT/MRI of orbits
What is the first line management for symptomatic hyperthyroidism?
Beta-blockade e.g., atenolol, propanolol
What is the mechanism of action of carbimazole?
Competitive inhibitor of thyroid peroxidase - blocks thyroid hormone synthesis
Which anti-thyroid drug inhibits peripheral conversion of T4 to active T3?
o Propylthiouracil
Which anti-thyroid drug is preferred during the first trimester of pregnancy/pre-pregnancy?
o Propylthiouracil
What are the contraindications of carbimazole?
Severe blood disorders, acute pancreatitis, women of childbearing potential (Risk of congenital malformations during the 1st trimester).
Which drugs are interacted with carbimazole?
Azathioprine (Increased myelosuppression); warfarin (enhances anticoagulant effect – INR monitoring); methotrexate, digoxin.
What is the most concerning adverse effect associated with carbimazole?
Agranulocytosis
What is the major adverse effect associated with propylthiouracil?
Liver disease
Normal duration of carbimazole for Grave’s disease?
18 months
What is the definitive management for Grave’s disease?
Radioactive iodine (1-131)
How does radioactive iodine therapy work in the management of hyperthyroidism?
Destroys thyroid follicular cells
What are the contraindications of radioactive iodine thearpy?
Pregnancy
Breastfeeding
Active/severe orbitopathy
How long should pregnancy be avoided following radioactive iodine therapy?
4-6 months
What is the indication for a thyroidectomy in hyperthyroidism?
Local compression secondary to thyroid goitre e.g., upper airway obstruction/dysphagia
What is the pre-operative management for hyperthyroidism?
Euthyroid state and control hypertension
Prescribe oral potassium iodide and propranolol
What is first line management for Grave’s orbitopathy?
Smoking cessation, and consider steroids
What is the main cardiac complication associated with hyperthyroidism?
Atrial fibrillation (3-fold increase)
What rheum complication is associated with hyperthyroidism?
Osteoporosis
What are the complications of surgery associated with hyperthyroidism?
Recurrent laryngeal nerve palsy
Hypothyroidism
Hypoparathyroidism (more common)
What is the long-term complication associated with subclinical hyperthyroidism?
Osteoporosis and atrial fibrillation
What is the tumour marker for papillary thyroid cancer?
Thyroglobulin
What are the histological findings associated with papillary thyroid carcinoma?
Orphan Annie eyes, and Psammoma bodies
Which thyroid cancer is associated with a very good prognosis?
Papillary thyroid carcinoma
Which thyroid cancer is very aggressive, and common in the elderly?
Anaplastic thyroid cancer
What is the tumour marker associated with medullary thyroid cancer?
Calcitonin
Which familial disorder is associated with medullary thyroid cancer?
Men2a/2b
What is the diagnostic investigation for thyroid cancer?
Fine needle aspiration cytology (FNAC)
What is the most common cause of primary adrenal insufficiency?
Autoimmune mediated
Why is there hyperpigmentation in Addison’s disease?
increased MSH levels (POMC precursor)
What electrolyte imbalance is associated with Addison’s disease?
Hyponatraemia
Hyperkalaemia
What is the acid-base imbalance associated with Addison’s disease?
Metabolic acidosis
What is the first-line investigation for Addison’s disease?
9 am cortisol (<100 - diagnostic - admit)
100 -500 refer to endocrinology
What is the diagnostic investigation to confirm adrenal insufficiency?
Short SynACTHen test
Administer 250ug Synacthen intramuscularly and measure the subsequent cortisol response (within 30 minutes) . In patients with adrenal hypofunction, there is reduced cortisol secretion unresponsive to ACTH stimulation, thus the cortisol response is absent – minimal change.
What is the dose administration for hydrocortisone replacement in Addison’s disease?
3 divided doses (10 mg on waking, 5 mg at noon and 5 mg in the early evening).
What happens to the hydrocortisone in patients with intercurrent illness?
Double dose
What is the mineralocorticoid replacement of choice for Addison’s disease?
Fludrocortisone
What is the first line drug for the management of an Addisonian crisis?
IV hydrocortisone and rapid IV fluid rehydration
What is the most common cause of hyperaldosteronism?
Bilateral adrenal hyperplasia
What electrolyte imbalance is associated with primary hyperaldosteronism?
Hypokalaemia, Hypernatraemia
What is the first line of investigation for hyperaldosteronism?
Plasma aldosterone: renin ratio
(Raised - renin is suppressed)
What is the diagnostic investigation to confirm primary hyperaldosteronism?
CT adrenals
Which investigation is indicated to differentiate between unilateral and bilateral hyperaldosteronism?
Adrenal venous sampling
What is the medical management for hyperaldosteronism?
spironolactone, eplerenone
What is the management for a unilateral adrenal adenoma?
Unilateral laparoscopic adrenalectomy
For bilateral adrenal disease (hyperaldosteronism), what is the preferred management?
Spironolactone
Which cells produce catecholamines?
Chromaffin cells of the adrenal medulla
Which three familial syndromes are associated with phaeochromocytoma?
- Von-Hippel Lindau
MEN2
NF1
What is associated with Von-Hippel Lindau syndrome?
Phaeo, renal cell carcinoma, renal cysts, hemangioblastoma
What is MEN Type2a syndrome?
Phaeochromocytoma
Parathyroid adenoma
Medullary thyroid cancer
What is the first line investigation for suspected phaeochromocytoma?
24h urinary metadrenaline/metanephrines
What precursor test is involved for screening for phaeos?
Meta-lodobenzylguanidine scan
What is the first line management for phaeo?
- Alpha blockade (first) – phenoxybenzamine for 7-14 days preoperatively.
- An alpha blockade is first to prevent the precipitating of a hypertensive crisis.
What are the two drugs indicated for the management of Phaeochromocytoma?
Alpha-blockade and beta-blockade
What is the definitive management for phaeochromocytoma?
Adrenalectomy
What is the normal range of calcium?
2.2 to 2.6 mmol/L
What is the main cause of secondary hyperparathyroidism?
Chronic kidney disease
Which type of hyperparathyroidism can be associated with normal serum levels of PTH?
Primary hyperparathyroidism
Raised Calcium
Low phosphate
Normal/raised PTH
Raised ALP
Most likely diagnosis?
Primary hyperparathyroidism
Low calcium
Raised phosphate
Raised PTH/ALP
Most likely diagnosis?
Secondary hyperparathyroidism
Raised PTH, ALP, and low Vitamin D, low calcium and low phosphate
Most likely diagnosis?
Osteomalacia
Which marker is raised in Paget’s disease?
Serum ALP
Serum PTH level in hypercalcaemia of malignancy?
Low
What is pseudohypoparathyriodism?
PTH resistance (Type 1a = Albright’s Hereditary Osteodystrophy phenotype).
Which sign denotes tapping over the facial nerve eliciting twitching of the upper lip?
- Chvostek’s sign
Which sign is associated with a carpal spasm following inflation of a BP cuff?
- Trousseau’s sign
What is Albright Hereditary Osteodystrophy?
- Short stature
- Round face
- Shortened fourth/fifth metacarpal bones.
- Lab: Hypocalcaemia and hyperphosphatemia + raised PTH.
What is pseudopseudohypoparathyriodism?
phenotypic expression of ABO without PTH resistance
What ECG changes are associated with hypercalcaemia?
Short QT interval
Prolonged PR interval
Widened QRS complex and bradycardia
What is the first line management of hypercalcaemia?
0.9% saline fluid resuscitation
Following fluid resuscitation what is the next line in management?
- Bisphosphonates (IV)
Which adrenal zone secretes cortisol?
Zona fasciculata
Which lung cancer is associated with ectopic secretion of ACTH?
Small cell lung carcinoma
What is the first line investigation for suspected Cushing’s syndrome?
- Urine-free cortisol (at least two measurements)
- Late-night salivary cortisol (at least two measurements)
- 1-mg overnight dexamethasone suppression test (DST)
What is the second line investigation to differentiate between ACTH-dependent and ACTH-independent aetiologies of Cushing’s syndrome?
Serum ACTH
For ACTH-independent causes of Cushing’s syndrome, what is the next line of investigation?
CT adrenals
For ACTH-dependent causes of Cushing’s syndrome, what is the next line of investigation?
Bilateral inferior petrosal sinus sampling
Raised cortisol and raised ACTH following a high dose dexamethasone test, indicates what?
Ectopic ACTH aetiology
Serum cortisol result following high dose dexamethasone suppression test, in Cushing’s disease?
Suppressed
What is the medical management for Cushing’s?
metyrapone
What is the definitive management for an adrenal cause of Cushing’s?
Adrenalectomy and steroid replacement
What is the preferred definitive management for Cushing’s disease?
Surgical transsphenoidal resection
Which skin condition is suggestive of insulin resistance?
Acanthosis nigricans
What is the diagnostic cut-off for HbA1c for diabetes?
> 48 mmol/mol (>6.5%)
What factors can affect HbA1c results?
Haemoglobinopathies, severe anaemia, post-splenectomy, recent blood transfusion
Fasting plasma glucose cut-off for diabetes diagnosis?
> 7.0 mmol/L
OGTT cut-off for diabetes diagnosis?
> 11.1 mmol/L
What is the first line medical management for T2DM?
Metformin
What is a common side effect of metformin?
Diarrhoea
Metformin management in patients presenting with diarrhoea (side effect)?
Switch to modified-release
Which drug should be co-prescribed with Metformin in diabetic patients with chronic heart failure or established CVD?
SGLT-2 inhibitor
When should an SGLT-2 inhibitor be prescribed in the medical management plan for diabetic patients with underlying heart disease?
Once the metformin dose is optimised
What is the second line medical management for T2DM?
If monotherapy is ineffective consider adding one of the following:
* A DPP-4 inhibitor (e.g., Sitagliptin)
* Pioglitazone
* Sulfonylurea
* SGLT-2 inhibitor
What is the preferred triple therapy for T2DM?
- Triple therapy: DPP-4 inhibitor, pioglitazone, a sulfonylurea or an SGLT-2 inhibitor (canagliflozin or empagliflozin)
- Note: Dapagliflozin is recommended only in combination with metformin and sulfonylurea, not pioglitazone.
What is the BMI cut off for starting a GLP-1 receptor agonist?
- BMI >35 kg/m2
When should a GLP-1 agonist be discontinued?
If there is not demonstrated weight loss within 6 months (<3%)
How frequently should HbA1c be measured?
Every 3-6 months
What is performed during an annual diabetes check-up?
Diabetic foot check
Annual retinopathy, neuropathy and nephropathy screening
What is the HbA1c target for lifestyle and diet management in T2DM?
48 mmol/mol
What is the HbA1c target for lifestyle and single drug medical management in T2DM?
48
What is the HbA1c target for lifestyle and medical management (drug associated with hypoglycaemia e.g., sulfonylurea) in T2DM?
53
At what HbA1c should an additional diabetic drug be commenced?
> 58
What is an absolute contraindication for metformin?
Severe renal insufficiency - eGFR <30 mL/min
What is the risk of metformin in patients with renal impairment?
Lactic acidosis
What class of diabetic drug is glimepiride?
Sulphonylureas
Which drug is associated with interacting with ATP-sensitive potassium channels to promote insulin pancreatic secretion?
Sulphonylureas
What is the main adverse effect associated with Sulphonylureas?
Weight gain
Which two diabetic drugs are associated with weight gain?
Sulphonylureas and glitazones
What is the mechanism of action of gliptins?
DPP-4 inhibitors
What are the adverse effects associated with SGLT-2 inhibitor use?
Genital mycotic (fungal) infections – candida albicans (vaginal thrush and balanitis); normoglycemic ketoacidosis, increased risk of Fournier’s gangrene.
What type of calcium channel blocker is Verapamil?
non-dihydropyridine calcium channel blocker
Which calcium channel blocker is contraindicated in HFrEF?
non-dihydropyridine calcium channel blocker E.G., Verapamil