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Biochemical Assessment of Endocrine

Function

Hypopituitarism
Feedback Loops
•Multiple hormones involved in coordinating
homeostatic responses that keep their conc. at
optimal physiologic levels

•Feedback loops control the increase or decrease


in hormone production

•Lack of negative feedback would result in


hyperfunctioning of the gland
Primary, Secondary, Tertiary Disorders

•1° - Involve the organs that produce the


hormone

•2 ° - Related to pituitary that produces


trophic hormones

•3 ° - Hypothalamic problems
Biochemical Assessment of Endocrine
Function

•Make use of direct measurement of hormone


conc.

•Stimulation test

•Suppression test
Tests
•Competitive protein - binding assays -
sensitive to very low levels of a hormone (e.g.
nanomole conc.)

•Stimulation tests performed when a


hypofunction endocrine disorder is suspected.

•Suppression tests utilized with diagnosis of


hyperfunction.
Assessment of hypofunction of pituitary

Hypopituitarism
Hypopituitarism: gonadotropins
(FSH and LH)

GnRH stimulation test:


Procedure
•Determine the FSH and LH baseline
•GnRH 100 ug IV
•Sampling every 30 min for 1-2 hour

Interpretation
•Lack of an increase in LH (3 to 10
fold) and FSH (1.5-3 fold) over the
baseline indicates an anterior
pituitary disorder

•Increase of FSH and LH indicates a


hypothalamic disorder
Hypopituitarism: growth hormone (GH)
Stimulation with:
•L-dopa (250 mg orally, GH measured
after 60 min)
•L-arginine (arginine HCl, 0.5 g/kg BW,
IV over a 30 min period, GH measured
60-120 min)
•Insulin tolerance test (Regular insulin
0.1-0.15 U/kg), IV push, GH measured
30, 60 and 90 min.
•Exercise (20 min of vigorous exercise
and GH is measured immed. after
exercise
GH should rise by 10 ng/ml
Lack of an increase in GH suggest a
anterior pituitary or hypothalamic
disorder
Hypopituitarism:

Thyrotropin-releasing hormone
(TRH) stimulation test:

Procedure
Determine the baseline TSH
500 ug TRH IV
Determine TSH at 30 and 60 min
after injection

Interpretation:
A typical response is a 5-10 fold
increase of TSH
lack of an increase in TSH
indicates an anterior pituitary
disorder, while an eventual rise
indicates a hypothalamic problem.
Hypopituitarism: corticotrophin releasing
hormone (CRH)
Stimulation test:

Procedure
Determine serum cortisol at baseline
After 15 min inject CRH 1ug/kg BW
Determine serum ACTH and cortisol at 5,
15,30,60,120 and 180 min after CRH injection

Interpretation
Normal response ACTH con. peaks after 30 min
and cortisol peaks after 60 min
No response for patients with pituitary ACTH
deficiency
Patient with hypothalamic disease have a
prolonged ACTH response
Hypopituitarism: vasopressin or
ADH

Stimulation Test
(Water deprivation test):

Dehydration provides a strong


stimulus for ADH release that can
be assessed by measuring urine ,
osmolality or plasma ADH.
If urine remains hypo-osmolal
during water deprivation, ADH is
administered to differentiate the
hypothalamic diabetic insipidus
(HDI, failure of the pitu. to secrete
ADH ) or nephrogenic DI (NID,
failure of the kidney to respond to
ADH)
Interpretation (Water deprivation test)

•Normal response no rise in plasma sodium but a


concentrated urine is produced with no further increase
in urine osmolality after ADH Admin.

•Patients with HDI elevated plasma Na and urine


osmolality will be less concentrated than normal and
no change in plasma ADH levels but urine osmolality
will rise by 10% after ADH admin.

•Patient with NDI urine osmolality is similar to HID but a


rise plasma ADH and no further increase of urine
osmolality after ADH admin.

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