Biochemistry of endocrinology

Question 1

problems to be aware of with endocrine tests

Answer 1

critically ill/stressed patients may have hyperglycaemia, high serum cortisol, or abnormal thyroid hormone results which could be misinterpreted

Question 2

pituitary system biochemistry

Answer 2

combined anterior pituitary function test: give TRH, GnRH, insulin
assess TSH, LH/FSH, ACTH/GH at 0, 30, 60 mins and GH also at 90 and 120 (no insulin admin if established coronary disease or epilepsy, iv dextrose and hydrocortisone must be readily available in case of hypoglycaemia too); admin of GHRH and CRH is replacing admin of insulin

Question 3

thyroid function tests

Answer 3

TSH assay, a v sensitive marker of thryoid function due to log-linear relationship with TRH but TSH cant be used to diagnose hypopituitarism
must monitor free T4 during antithyroid treatment or when giving thyroxine
useful to measure free T3 for hyperthyroidism
anti-TPO antibodies may be useful in hypothyroidism and stimulating thyroid receptor antibodies in thyrotoxicosis
if find an autoimmune thyroid condition, be aware that there may be other autoimmune conditions which have been overlooked

Question 4

hypothyroidism biochem

Answer 4

if suspect then measure TSH and free T4
TSH elevated, T4 normal: it is hypothyroidism, give replacement T4
TSH elevated, T4 not quite normal but within reference limits: hypothyroidism may be developing, measure autoantibodies and repeat analysis after 2-3 months
TSH within reference, T4 low: non thyroid illness likely, investigate T3 levels and repeat analyses once non-thyroid condition cleared up
TSH low, T4 low: central problem so check cortisol/FSH/LH/prolactin
sick patients have low serum levels of T4/3 as transport proteins (eg albumin) down and FFAs up which compete for binding spots, so postpone treatment until illness resolved unless suspect the hypothyroidism is contributing to the illness
always start with small doses of thyroxine and increase gradually

Question 5

hyperthyroidism

Answer 5

TSH low, T4 raised confirms diagnosis
in pregnancy, oestrogen stimulates thyroid binding globulin synthesis in liver so total T4 raised, although free T4 will be normal
binding proteins also altered in eg women on the pill, patients with nephrotic syndrome
some patients will have normal T4 but elevated T3
if suspect, measure TSH and T4
TSH undetectable, T4 raised: thyrotoxicosis
TSH detectable, T4 raised: repeat the analysis or immunoassay interference
TSH undetectable, T4 normal: likely find T3 elevated
elderly thyrotoxic patients often dont show the usual sign of hyperthyroidism, some will only present with atrial fibrilliation, or else weight loss leading to anxiety and a futile search for malignant disease

Question 6

HPA axis biochemistry

Answer 6

cortisol fluctuates widely so little use measuring it
dynamic tests of cortisol response can be useful
stress and sleep-wake cycle both affect so must try to ensure both are normal (esp in terms of eg illness of patient)

Question 7

adrenal insufficiency

Answer 7

hyponatraemia, hyperkalaemia, elevated serum urea
short synacthen test: iv 250microg of synthetic ACTH analogue, measure cortisol at 0, 30, poss 60 mins
if results inadequate then long synacthen test where given im 1mg for 3 days then on 4th repeat SST
addisons disease must always be considered in patients with hyperkalaemia, esp if no renal failure

Question 8

cortisol excess

Answer 8

urinary free cortisol assessed over 24 hours or by ratio of cort:creatinine in early morning urine, if repeatdly high then do further tests but if neg on 3 occasions can exclude Cushings from the differential diagnosis
may struggle to induce hypoglycaemia with normal level of insulin due to resistance; also will not see much of a rise in cortisol when hypoglycaemia induced so if you do find this can exclude Cushings
excessive alcohol intake can manifest as pseudocushings syndrome which will resolve after 2-3 weeks abstinence
cortisol diurnal rhythm is absent in cushings

Question 9

androgen and aldosterone excess

Answer 9

may find either
primary hypraldosteronism/Conns disease is rare, usually due to adrenocortical adenoma
must determine serum and urine electrolytes over several days, and assay for aldosterone, renin, or plasma renin activity
in hypokalaemic patient, can diagnose if aldosterone raised above interval
secondary hyperaldosteronism common and associated with renal/heart/liver disease

Question 10

androgen screen in women

Answer 10

to find cause of elevated testosterone
elevated DHA sulphate suggests adrenal gland or tumour overproducing androgens
if ovary is source then only androstenedione will be raised

Question 11

investigating subfertility in the man - biochem

Answer 11

if normal sperm analysis then no endocrine tests needed
if abnormal sperm count then measure testosterone, gonadotrophins, prolactin
test down, gonad up: primary testicular failure
test down, gonad down: hypogonadtrophic hypogonadism
test down, prolact up: hyperprolactinaemia
FSH and LH up when interstitial and tubular cells damaged, only FSH up when only tubular damage and in this second case may also find androgens normal

Question 12

investigating subfertility in the woman - biochem

Answer 12

normal menses, measure progesterone: >30nmol/L ovulating, <10nmol/L not ovulating so measure FSH/LH/prolactin
oligo/amenorrhoea: pregnancy test, if pos no more tests needed, if neg then measure FSH/LH/prolactin
after measuring the three hormones for either reason: high FSH (+LH) suggests ovarian failure, high LH and low FSH polycystic ovary syndrome, high prolactin then further investigate for hyperprolactinaemia
all normal: further tests indicated