Endocrinology Flashcards
Hormones released by anterior vs posterior pituitary gland and their function?
Anterior:
→ FSH/LH = gamete production
→ TSH = T3/T4 production
→ PRL = milk production, breast development
→ GH = IGF production
→ ACTH = glucocorticoid production
Posterior:
→ ADH = water balance
→ oxytocin = uterine contractions
Outline the thyroid hormonal axis?
- Hypothalamus secretes TRH
- Pituitary gland secretes TSH
- Thyroid gland secretes T3 and T4
- T4 -ve feedback on hypothalamus/pituitary
Ratio of T4:T3 production and clinical relevance?
20:1
T4 is a better indicator of thyroid function
Cause of primary vs secondary hyper/hypothyroidism?
Primary = thyroid abnormality
Secondary = hypothalamus or pituitary abnormality
Typical TFTs for primary and secondary hypothyroidism and hyperthyroidism?
Primary hypothyroidism = high TSH, low T3/T4
Primary hyperthyroidism = low TSH, high T3/T4
Secondary hypothyroidism = low TSH, low T3/T4
Secondary hyperthyroidism = high TSH, high T3/T4
Typical TFTs for subclinical hypothyroidism vs subclinical hyperthyroidism vs sick euthyroid?
Subclinical hypothyroidism = high TSH, normal T3/T4
Subclinical hyperthyroidism = low TSH, normal T3/T4
Sick euthyroid = low or normal TSH, low T3/T4
Investigation for thyroid nodule?
Thyroid US +/- biopsy
Features of hypothyroidism vs hyperthyroidism?
Hypothyroidism = cold, weight gain, fatigue, dry skin/hair, constipation, menorrhagia, carpal tunnel
Hyperthyroidism = warm, weight loss, restlessness, anxiety, tremor, palpitations, hyperhidrosis, diarrhoea, oligomenorrhoea, thyroid acropachy
Triad of thyroid acropachy?
Digital clubbing
Swelling of hands and feet
Periosteal new bone formation
Most common cause of hypothyroidism in the developed world vs developing world?
Developed world = hashimoto’s thyroiditis
Developing world = iodine deficiency
Features of Hashimoto’s thyroiditis and associated antibodies?
Hypothyroid symptoms
Firm, non-tender goitre
PMH autoimmune disease
Antibodies = anti-TPO and anti-Tg
Cancer linked to Hashimoto’s thyroiditis?
MALT lymphoma
Treatment for hypothyroidism and dosing guidance?
Levothyroxine:
→ elderly or CVD = 25mcg
→ everyone else = 50-100mcg
→ increase dose by 25-50mcg in pregnancy
Monitoring of levothyroxine?
TFTs monitored 8-12 weeks after dose change
Aim for TSH 0.5-2.5
Typical TFTs of patient with poor levothyroxine compliance and explain?
High TSH, normal T3/T4
→ patient takes medication just before blood test
→ thyroxine (T4) is normal
→ TSH lags reflecting chronic low levels
Drugs which reduce levothyroxine absorption and advice?
Iron, calcium
Take 4 hours apart
Management of subclinical hypothyroidism?
Offer levothyroxine if:
→ TSH > 10
→ TSH 5.5-10 and symptomatic
Management of myxoedema coma (hypothyroid crisis)?
IV fluids + IV levothyroxine + IV corticosteroid
Hypothyroidism after a post-partum haemorrhage?
Sheehan syndrome
Most common cause of hyperthyroidism?
Grave’s disease
Features of Grave’s disease and assocated antibodies?
Hyperthyroid symptoms
Eye disease e.g. exophthalmos
Pretibial myxoedema “orange peel skin”
Thyroid acropachy
Antibodies = anti-TSH receptor and anti-TPO
Investigation and feature of Grave’s disease?
Thyroid scinctigraphy
Globally increased iodine uptake
Key lifestyle risk factor for Grave’s disease?
Smoking
Treatment for hyperthyroidism?
1st line = carbimazole (1st choice) or propylthiouracil (2nd choice)
2nd line = radioiodine therapy
3rd line = surgery
N.B. propanolol is used to block adrenergic symptoms
Management of hyperthyroidism during pregnancy?
1st trimester = propylthiouracil
2nd trimester onwards = carbimazole
Major side effect of carbimazole and PPU?
Agranulocytosis
Phases and features of subacute (De Quervain’s) thyroiditis?
Phase I = hyperthyroidism, painful goitre, flu-like symptoms, raised inflammatory markers e.g. ESR, CRP
Phase II = euthyroid
Phase III = hypothyroidism
Phase IV = euthyroid
Investigation and feature of subacute (De Quervain’s) thyroiditis?
Thyroid scintigraphy
Globally reduced iodine uptake
Main drug associated with thyrotoxicosis?
Amiodarone
Features of thyrotoxicosis?
Fever
Tachycardia
Hypertension
Confusion, agitation
Heart failure (especially in elderly)
Management of thyrotoxicosis?
IV propanolol + IV hydrocortisone + propylthiouracil
N.B. IV digoxin if heart failure
Investigation, feature and management of toxic multinodular goitre?
Thyroid scintigraphy
Patchy increased iodine uptake
Management = radioiodine therapy
Types of thyroid cancer and most common?
Papillary (most common)
Follicular
Medullary
Anaplastic
Lymphoma
Thyroid cancer associated with young females, elderly females, MEN 2, lymph node invasion, vascular invasion, raised calcitonin?
Young females = papillary
Elderly females = anaplastic
MEN 2 = medullary
Lymph node invasion = papillary
Vascular invasion = follicular
Raised calcitonin = medullary
Management of papillary and follicular carcinoma?
Total thyroidectomy + radioiodine
Outline the parathyroid-thyroid hormone axis?
- Parathyroid gland senses low calcium
- Chief cells secrete PTH
- PTH increases calcium
- Thyroid gland senses high calcium
- C-cells secrete calcitonin
- Calcitonin decreases calcium and has negative feedback on parathyroid gland
How does PTH increase and calcitonin decrease calcium levels?
PTH = (1) activates osteoclasts, (2) increases calcium re-absorption in kidneys and (3) triggers calcitriol (active vitamin D) formation which increases gut calcium absorption
Calcitonin = inhibits osteoclasts
Features of hypercalcaemia?
Bone pain
Renal stones
Constipation
Pancreatitis
Polydipsia/polyuria
Depression
Cause of primary vs secondary vs tertiary hyperparathyroidism?
Primary = excess PTH secretion
Secondary = increased PTH secretion in response to low calcium
Tertiary = autonomous PTH secretion after prolonged secondary cause, usually CKD
Blood test features of primary vs secondary vs tertiary hyperparathyroidism?
Primary = normal/high PTH, high calcium, low phosphate
Secondary = high PTH, low calcium, high phosphate
Tertiary = high PTH, high calcium, low phopshate, high ALP
X-ray features of hyperparathyroidism?
“Pepperpot” skull
Osteopenia
Osteitis fibrosis cystica
Management of hyperparathyroidism?
1st line = total parathyroidectomy
2nd line = calcimemetic (e.g. cinacalcet)
Most common cause of hypoparathyroidsm?
Parathyroid injury during thyroid/neck surgery
Management of hypoparathyroidism?
Vitamin D analogue e.g. alfacalcidol
Features of hypocalcaemia?
Tetany e.g. cramps, parasthaesia
Trosseau’s sign (carpal spasm)
Chvostek’s sign (facial twitch)
Psychological disturbance e.g. depression
Which electrolyte is vital for maintaining calcium levels and clinical relevance?
Magnesium
→ patient not responding to calcium and vitamin D supplements should have magnesium checked
Features of MEN 1, MEN 2a and MEN 2b?
MEN 1 = (3 Ps) parathyroid tumour, pituitary tumour, pancreatic tumour
MEN 2a = (1 M, 2 Ps) medullary carcinoma, parathyroid tumour, phaeochromocytoma
MEN 2b = (2 Ms, 1 P) medullary carcinoma, marfanoid habitus, phaeochromocytoma
Features of a phaeochromocytoma?
Hypertension
Headaches
Flushing
Anxiety
Palpitations
Investigation and management of a phaeochromocytoma?
Investigation = 24hr urinary metanephrines
Management = alpha-blocker (e.g. phenoxybenzamine) BEFORE beta-blocker (e.g. propanolol) + surgery
Classification of pituitary adenomas?
Microadenoma (< 1cm) or macroadenoma (> 1cm)
Functioning (secretory) or non-functioning (no secretion)
Features of pituitary adenoma?
Hormonal excess
Hormonal deficit
Headaches
Bitemporal hemianopia
Most common cause of hypopituitarism vs hyperpituitarism?
Hypopituitarism = compression of pituitary gland via non-secretory adenoma
Hyperpituitarism = secretory adenoma
Investigation for hypopituitarism and explain?
Insulin stress test
→ insulin given, GH and cortisol measured
→ normally GH and cortisol should rise
→ low response indicates hypopituitarism
Most common type of secretory adenoma?
Prolactinoma
What normally inhibits prolactin release?
Dopamine
Features of prolactinoma?
Pituitary adenoma symptoms
Amenorrhea
Galactorrhoea
Infertility
Erectile dysfunction
Investigation and management of a prolactinoma?
Investigation = MRI
1st line = dopamine agonist e.g. cabergoline, bromocriptine
2nd line = trans-sphenoidal surgery
Second most common cause of secretory adenoma?
GH adenoma
What normally inhibits GH release?
Somatostatin
Features of acromegaly?
Pituitary adenoma symptoms
Large “spade-like” hands/feet
Protruding jaw and brow
Interdental spaces
Hyperhidrosis
Investigations and management of acromegaly?
Investigation = serum IGF-1, OGTT if IGF-1 raised
1st line = trans-sphenoidal surgery
2nd line = somatostatin analogue (e.g. ocreotide)
3nd line = GH antagonist (e.g. pegvisomant), dopamine agonist (e.g. bromocriptine)
Types of corticosteroids hormone, where they are produced in the adrenal glands and example?
Glucocorticoids (zona fasciculata) = cortisol
Mineralocorticoids (zona glomerulosa) = aldosterone
List side effects of glucocorticoids?
Osteoporosis
Peptic ulcers
Steroid psychosis
Hyperglycaemia
Cushing’s syndrome
Proximal myopathy
Immunosuppression
Glaucoma, cataracts
Stunted growth in kids
List side effects of mineralocorticoids?
Fluid retention
Hypertension
Hypokalaemia
Effect of cortisol vs aldosterone vs ADH on the kidneys?
Cortisol and aldosterone = water and Na retention, K excretion
ADH = water retention, Na and K excretion
Cushing’s vs hyperaldosteronism vs Addison’s?
Cushing’s = excess CORTISOL
Hyperaldosteronism = excess ALDOSTERONE
Addison’s = lack of CORTISOL AND ALDOSTERONE
Classification of Cushing’s syndrome causes?
ACTH-dependent e.g. pituitary adenoma, ectopic ACTH
ACTH-independent e.g. adrenal adenoma
Features of Cushing’s syndrome?
Moon face
Hirsutism
Central obesity
Abdominal striae
Buffalo hump
Thin limbs
Hypertension
Osteoporosis
Investigations of Cushing’s syndrome?
Overnight low-dose DST
Low-dose 48 hour DST
High-dose 48 hour DST
High-dose DST results for Cushing’s causes?
ACTH suppressed, cortisol not = adrenal adenoma
ACTH and cortisol suppressed = pituitary adenoma
ACTH and cortisol not suppressed = ectopic ACTH
Management of Cushing’s syndrome?
Steroid blocker (e.g. metyrapone) + surgery
Replacement steroids post-surgery
Most common causes of primary aldosteronism?
Bilateral adrenal hyperplasia
Adrenal adenoma (Conn’s syndrome)
Features of hyperaldosteronism?
Polydipsia/polyuria
Headaches
Hypertension
Hypokalaemia
Investigations for primary hyperaldosteronism?
Plasma aldosterone:renin ratio
Imaging e.g. CT abdomen
Adrenal vein sampling (to differentiate between unilateral or bilateral pathology)
Aldosterone:renin ratio results in primary vs secondary hyperaldosteronism?
Primary = high aldosterone, low renin
Secondary = high aldosterone, high renin
Management of primary hyperaldosteronism?
Adrenal adenoma = surgery
Bilateral adrenal hyperplasia = aldosterone antagonist e.g. spironolcatone
Most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency
Most common cause of primary hypoadrenalism?
Addison’s disease
Features of Addison’s disease?
Weight loss
Fatigue
Salt craving
Hyperpigmentation
Hypotension
Hypoglycaemia
Hyponatraemia/hyperkalaemia
Why can Addison’s present with hypoglycaemia?
Cortisol normally increases blood sugar
Investigations and management for Addison’s disease?
Investigations = short Synacthen test
Management = hydrocortisone + fludricortisone
Guidance for unwell patients on steroids?
Glucocorticoid dose should be doubled
Mineralocorticoid dose should stay the same
Management of Addisonian crisis?
IM or IV hydrocortisone
IV saline 0.9% (dextrose if hypoglycaemic)
What is pre-diabetes (“impaired glucose tolerance”) and clinical values?
Impaired fasting glucose (6.1-6.9) or
Impaired glucose tolerance (7.8-11.0)
Cause of T1DM vs T2DM?
Type 1 = absolute insulin deficiency caused by autoimmune destruction of pancreatic beta cells
Type 2 = relative insulin deficiency caused by insulin resistance
Main features of diabetes?
Polydipsia/polyuria
Weight loss (type 1)
Obesity (type 2)
Investigations and clinical values for T2DM?
If patient is symptomatic:
→ random glucose or OGTT ≥ 11.1
→ fasting glucose ≥ 7.0
→ HbA1c ≥ 48.0
If patient is asymptomatic:
→ above must be demonstrated on 2 occasions
HbA1c monitoring guidance and targets?
Monitor every 6 months once stable
Lifestyle changes +/- metformin = 48.0
Other anti-diabetic drugs = 53.0
What can interfere with HbA1c interpretation and examples?
Conditions which shorten RBC lifespan e.g. sickle-cell disease
Conditions which prolong RBC lifespan e.g. IDA, splenectomy
Drug options for T2DM?
1st line = metformin (+ SGLT-2 inhibitor if known CVD or QRISK > 10%)
2nd line = add DPP-4 inhibitor or pioglitazone or sulfonylurea or SGLT-2 inhibitor
3rd line = metformin + dual therapy of above or insulin
4th line = switch a medication for a GLP-1 mimetic
HbA1c level which would prompt addition of 2nd line therapy?
≥ 58.0
NICE guidance for insulin in T2DM?
Start with isophane insulin (intermediate-acting)
Antidiabetic medications associated with hypoglycaemia?
Sulphonyureas
DPP-4 inhibitors
GLP-1 mimetics
Insulin
Metformin mechanism of action and side effects?
Mechanism of action = increases insulin sensitivity, decreases hepatic gluconeogenesis
Side effects = GI upset, lactic acidosis
Metformin prescribing guidance?
Should be titrated up slowly (to reduce GI upset)
If not tolerated, offer modified-release metformin
SGLT-2 inhibitor examples, mechanism of action and side effects?
Examples = dapagliflozin, empagliflozin
Mechanism of action = inhibits glucose reabsorption in the kidneys
Side effects = weight loss, GU infection
Sulfonylurea examples, mechanism of action and side effects?
Examples = gliclazide, glipizide
Mechanism of action = increases insulin production
Side effects = weight gain, hypoglycaemia
Pioglitazone mechanism of action and side effects?
Mechanism of action = reduces peripheral insulin resistance
Side effects = weight gain, hepatotoxic, heart failure, increased risk of bladder cancer
DPP-4 inhibitor examples, mechanism of action and side effects?
Examples = sitagliptin, alogliptin
Mechanism of action = prevents incretin breakdown
Side effects = GI upset, hypoglycaemia
GLP-1 mimetic examples, mechanism of action and side effects?
Examples = liraglutide, exenatide
Mechanism of action = increases insulin secretion, inhibits glucagon secretion
Side effects = weight loss, N&V, hypoglycaemia, pancreatitis
Outline sick day rules for diabetes mellitus?
- Check blood sugar 4 hourly (or more)
- Keep well hydrated (aim for 3L/day)
- Take ALL diabetic medications
→ hold metformin if dehydrated
Main factors leading to diabetic foot disease?
Diabetic neuropathy
Peripheral arterial disease
Drug options for diabetic neuropathy?
1st line = amitriptyline, duloxetine, pregabalin, gabapentin
2nd line = another of the above options
N.B. tramadol can be used for exacerbations
Drug options for gastroparesis?
Metaclopramide
Domperidone
Erythromycin
Diabetic nephropathy screening and management?
Yearly albumin:creatinine ration (ACR)
ACR > 3 = ACEi/ARB
Osmolality calcuation?
2(Na) + glucose + urea
Outline the pathophysiology of Hyperosmolar Hyperglycaemic State (HHS)?
- Hyperglycaemia increases serum osmolality
- Body compensates by increased glycosuria
- Water follows into urine down osmotic gradient
- Polyuria leading to volume depletion
Features of HHS?
Progresses over days/weeks
Type 2 diabetics (mostly)
Polyruria/polydipsia
Confusion, fatigue, N&V
Biochemical features of HHS?
Hyperglycaemia
Raised serum osmolality
What inhibits lipolysis and clinical relevance?
Insulin
→ T2DM patients still have some insulin so HHS does not present with ketoacidosis
Management of HHS?
IV fluid replacement
Do not give insulin unless blood glucose stops falling whilst giving IV fluids
Complication of giving insulin in HHS?
Cerebral pontine myelinolysis
Investigations and clinical values for T1DM?
If patient is symptomatic:
→ random glucose or OGTT ≥ 11.1
→ fasting glucose ≥ 7.0
If patient is asymptomatic:
→ above must be demonstrated on 2 occasions
Why is HbA1c not recommended for diagnosing T1DM?
May not reflect a rapid blood glucose increase
Additional blood test features of T1DM?
Low C-peptide
Anti-GAD, anti-islet cell, insulin antibody
T1DM autoantibodies?
Anti-GAD
Anti-islet cell
Insulin antibody
Management of T1DM?
MDI basal-bolus regime (rapid/short mealtime bolus + intermediate/long basal)
Give examples of rapid, short, intermediate and long acting insulin?
Rapid = aspart (NovoRapid), lispro (Humalog)
Short = Actrapid, Humulin S
Intermediate = isophane
Long = determir (Levemir), glargine (Lantus)
Insulin side effects?
Weight gain
Hypoglycaemia
Lipodystrophy
Management of hypoglycaemia?
Mild = 10-20g oral glucose or other fast-acting carbohydrate
Severe = IV dextrose + SC or IM glucagon
DVLA diabetes guidance?
- Must inform DVLA if taking insulin
- Check blood sugars within 2 hours of driving and every 2 hours during long journeys
- Surrender licence if 1 (group 2) or > 1 (group 1) hypoglycaemic episode requiring medical assistance in the past 12 months
Outline the pathophysiology of DKA?
- Lack of insulin leads to uncontrolled lipolysis
- Adipose tissue breaks down into fatty acids
- Fatty acids hydrolysed in the liver to ketones
- Ketones consume HCO3 leading to acidosis
Features of DKA?
Polydipsia/polyuria
Abdominal pain
Kussmaul’s breathing
Acetone-smelling breath
Drowsiness, coma
Biochemical features of DKA?
Severe hyperglycaemia
Raised serum osmolality
Hyperketonaemia
Metabolic acidosis
Hypokalaemia
Management of DKA?
IV 0.9% saline
IV insulin 0.1 unit/kg/hour
→ once glucose < 14.0 add IV 10% dextrose
Correct serum potassium
Continue normal long-acting insulin
Complication of fluid replacement in DKA?
Cerebral oedema
What is maturity-onset diabetes of the young, inheritance and most common form?
T2DM in patients < 25
Autosomal dominant
MODY 3
Types of diabetes inspidus and cause?
Cranial = lack of ADH secretion
Nephrogenic = insensitivity to ADH
Water deprivation and DDAVP test results for cranial vs nephrogenic DI?
Cranial = low urine osmolality after water deprivation, high urine osmolality after DDAVP
Nephrogenic = low urine osmolality after water deprivation, low urine osmolality after DDAVP
Management of DI?
Cranial = DDAVP (desmopressin)
Nephrogenic = low salt diet, thiazide diuretics
Normal urine osmolality before and after DDAVP in patient with polydipsia/polyuria?
Primary polydipsia e.g. excessive drinking
General guidance for diabetic management pre- and post-op?
- Variable rate insulin if poor glycaemic control or long surgery meaning more than one missed meal
- Otherwise, patients should just require their dosage (insulin and/or oral agents) adjusted
Only antidiabetic drug which should be omitted on the day of surgery?
SGLT-2 inhibitor
How to manage once daily vs twice daily insulin pre- and post-op?
OD = reduce by 20% (day before + day of)
BD = no change (day before), half morning dose and normal evening dose (day of)
Sex hormone levels in Klinefelter’s vs Kallman’s vs androgen insensitivity?
Klinefelter’s = high LH, low testosterone
Kallman’s (primary amenorrhoea) = low LH, low testosterone
Androgen insensitivity = high LH, normal/high testosterone
