Endocrinology

Question 1

what does the adrenal cortex produce, and what do they do?

Answer 1

steroids.
Salt - Sugar - Sex (it gets sweeter as you go deeper)
mineralocorticoids (e.g. aldosterone) - control sodium and potassium balance.
glucocorticoids (e.g. cortisol) - affect carbohydrate, lipid and protein metabolism.
androgens - sex hormones.

Question 2

how is the adrenal cortex stimulated to produce cortisol/androgens?

Answer 2

corticotrophin-releasing factor (CRF) from hypothalamus stimulates ACTH secretion from pituitary - stimulates cortisol and androgen production.

Question 3

what is the main cause of acromegaly?

Answer 3

pituitary adenoma - secretes excess GH

Question 4

give 4 symptoms of acromegaly

Answer 4

persistent numbness and tingling in hands and feet
headache
amenorrhoea
sweating
arthralgia
increase in weight
low libido, backache
“my rings and shoes don’t fit anymore”

Question 5

give 4 signs of acromegaly

Answer 5

growth of hands, feet and jaw
coarsening face, wide nose
macroglossia
darkened skin
obstructive sleep apnoea
goitre
carpal tunnel syndrome
puffy lips
laryngeal dyspnoea

Question 6

what cardiac disease can acromegaly cause?

Answer 6

hypertrophic cardiomyopathy

Question 7

what would you find on blood tests in acromegaly?

Answer 7

raised IGF-1, GH and prolactin - secreted by adenoma

Question 8

what specific test would you do to confirm a diagnosis of acromegaly? what else can be helpful when trying to diagnose acromegaly?

Answer 8

oral glucose tolerance test - diagnostic if GH is not suppressed by the glucose.

old photos of the patient.

Question 9

what is the 1st line treatment of acromegaly?
if that is CI, what would you try?

Answer 9

transphenoidal surgery.

if CI - somatostatin analogues (GH is inhibited by somatostatin) - lanreotide, ocreotide.
GH antagonist - pegvisomant.

Question 10

what are the metabolic actions of GH?

Answer 10

stimulates IGF-1 to be produced and secreted by the liver.
increases collagen and protein synthesis, opposing the action of insulin (same as glucagon).
promotes retention of calcium and nitrogen.
mainly secreted nocturnally.

Question 11

explain the renin-angiotensin-aldosterone system

Answer 11

renin is secreted by the kidneys in response to hypoperfusion of the kidneys, which then cleaves angiotensinogen into angiotensin I, which is an inactive form.
angiotensinogen is made in the liver, and circulates in the plasma.
angiotensin I is converted by ACE (produced in lungs) into angiotensin II in the lung and vascular endothelium.
angiotensin II causes vasoconstriction and stimulates the zona glomerulosa to increase its production of aldosterone - raises blood pressure and sodium retention - increasing blood volume.

Question 12

what is diabetes insipidus?

Answer 12

passage of large volumes (>3L/day) of dilute urine due to impaired water resorption by kidney

Question 13

what is the difference between cranial and nephrogenic DI?

Answer 13

cranial is due to reduced ADH secretion from posterior pituitary.
nephrogenic is due to impaired response of the kidney to ADH.

Question 14

give 3 causes of cranial DI

Answer 14

idiopathic, congenital, tumour (craniopharyngioma, metastases, pituitary tumour), trauma, hypophysectomy, autoimmune hypophysitis, infiltration (histiocytosis, sarcoidosis), haemorrhage, infection (meningoencephalitis).

Question 15

give 3 causes of nephrogenic DI

Answer 15

inherited.
metabolic - low potassium, high calcium.
drugs - lithium, demeclocycline.
chronic renal disease.
post-obstructive uropathy.

Question 16

give 3 symptoms of diabetes insipidus

Answer 16

polyuria, nocturia, polydipsia, hypernatraemia

Question 17

give 3 signs of diabetes insipidus

Answer 17

dehydration, enlarged and palpable bladder, no weight loss

Question 18

what specific test can you do to confirm a diagnosis of diabetes insipidus, and what result would you expect?

Answer 18

fluid deprivation test - failure of urine concentration despite fluid restriction.

can give desmopressin - cranial DI will show an increase in urine osmolality.

Question 19

how would you treat cranial diabetes insipidus?

Answer 19

desmopressin - synthetic ADH analogue.
MRI head to find cause.

Question 20

why would treatment for cranial DI not work for nephrogenic and what would you use instead?

Answer 20

nephrogenic DI is a defect in channels rendering the kidneys insensitive to vasopressin - so desmopressin will have no effect.

treat cause.
if persists - bendroflumethiazide, and NSAIDs to lower the urine volume and plasma sodium.

Question 21

explain the effect of vasopressin on the body

Answer 21

vasopressin is synthesised in the hypothalamus and migrates to the posterior pituitary where it is released into the circulation.
stimulates V2 receptors in kidney, making the collecting ducts more permeable to water via aquaporin 2 channels - decreasing diuresis and promoting water retention.

Question 22

what types of malignancy can cause the syndrome of inappropriate ADH secretion?

Answer 22

small cell lung cancer, pancreas, prostate, thymus, lymphoma

Question 23

list some causes of the syndrome of inappropriate ADH secretion

Answer 23

malignancies.
neuro - stroke, SAH, Guillain-Barre, SLE, vasculitis, meningoencephalitis.
resp - TB, pneumonia, abscess.
endocrine - hypothyroidism.
drugs - opiates, psychotropics, SSRIs, cytotoxics.

Question 24

what is the main metabolic abnormality in the syndrome of inappropriate ADH secretion?

Answer 24

hyponatraemia

Question 25

despite water retention, what is NOT a feature of the syndrome of inappropriate ADH secretion?

Answer 25

oedema

Question 26

describe the urine of a patient with the syndrome of inappropriate ADH secretion

Answer 26

concentrated urine with hyponatraemia and a low plasma osmolality

Question 27

what clinical features might you see in the syndrome of inappropriate ADH secretion?

Answer 27

hyponatraemia features - anorexia, nausea and malaise.
then headache, irritability, confusion, weakness, decreased GCS and seizures.

Question 28

how would you treat the syndrome of inappropriate ADH secretion?

Answer 28

restrict fluid intake + treat cause.
give salt ± a loop diuretic if severe.

Question 29

somatostatin analogues are used in which pituitary disease and how do they work?

Answer 29

acromegaly, they inhibit the release of growth hormone from the anterior pituitary

Question 30

what renal drug can you use to treat Conn’s?

Answer 30

spironolactone - it is an aldosterone antagonist, so increases potassium reabsorption.

Question 31

name 2 calcitonin drugs, and what they treat

Answer 31

miacalcin, fortical.
postmenopausal osteoporosis, hypercalcaemia

Question 32

how do calcitonin drugs work?

Answer 32

calcitonin is produced in thyroid gland by C cells and increases deposition of calcium and phosphate in bone, lowering circulating levels.
calcitonin drugs inhibit calcium resorption by intestine, inhibit osteoclast activity in bones, stimulate osteoblast activity and inhibit renal reabsorption of calcium.

Question 33

what class of drug is pegvisomant and what is it used to treat?

Answer 33

growth hormone receptor antagonist.
acromegaly, if pituitary tumour can’t be controlled with surgery/irradiation

Question 34

how does pegvisomant work?

Answer 34

blocks action of GH at the GH receptor to reduce production of insulin-like growth factor-1 (responsible for most of the symptoms of acromegaly).

Question 35

what generally causes a patient to go into hyperosmolar, hyperglycaemic state?

Answer 35

very high glucose levels develop due to combination of:
illness e.g. infection (pneumonia!)
dehydration
inability to take normal diabetes meds due to illness (so poor control).

Question 36

how does sitagliptin, a DPP-1 inhibitor, work?

Answer 36

inhibits DPP-1, which results in increased insulin secretion in response to meals, and decreased glucagon secretion by alpha cells of pancreas.
brings glucose levels nearer to normal, without any risk of hypos.