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

HypopituitarismHypopituitarism

Hypopituitarism: gonadotropins Hypopituitarism: gonadotropins (FSH and LH) (FSH and LH)

GnRH stimulation test: GnRH stimulation test: ProcedureProcedure•Determine the FSH and LH baselineDetermine the FSH and LH baseline•GnRH 100 ug IVGnRH 100 ug IV•Sampling every 30 min for 1-2 hourSampling every 30 min for 1-2 hour

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

•Increase of FSH and LHIncrease of FSH and LH indicates a indicates a hypothalamic disorderhypothalamic disorder

Hypopituitarism: growth hormone (GH)Hypopituitarism: growth hormone (GH)

Stimulation with: Stimulation with: •L-dopa (250 mg orally, GH measured L-dopa (250 mg orally, GH measured after 60 min)after 60 min)

•L-arginine (arginine HCl, 0.5 g/kg BW, L-arginine (arginine HCl, 0.5 g/kg BW, IV over a 30 min period, GH measured IV over a 30 min period, GH measured 60-120 min)60-120 min)

•Insulin tolerance test (Regular insulin Insulin tolerance test (Regular insulin 0.1-0.15 U/kg), IV push, GH measured 0.1-0.15 U/kg), IV push, GH measured 30, 60 and 90 min.30, 60 and 90 min.

•Exercise (20 min of vigorous exercise Exercise (20 min of vigorous exercise and GH is measured immed. after and GH is measured immed. after exerciseexercise

GH should rise by 10 ng/mlGH should rise by 10 ng/ml

Lack of an increase in GH suggest a Lack of an increase in GH suggest a anterior pituitary or hypothalamic anterior pituitary or hypothalamic disorderdisorder

Hypopituitarism:Hypopituitarism:

Thyrotropin-releasing hormone Thyrotropin-releasing hormone (TRH) stimulation test: (TRH) stimulation test:

ProcedureProcedureDetermine the baseline TSHDetermine the baseline TSH500 ug TRH IV500 ug TRH IVDetermine TSH at 30 and 60 min Determine TSH at 30 and 60 min after injectionafter injection

Interpretation:Interpretation:A typical response is A typical response is a 5-10 fold a 5-10 fold increase of TSHincrease of TSHlack of an increase in TSH lack of an increase in TSH indicates an anterior pituitary indicates an anterior pituitary disorder, while an eventual rise disorder, while an eventual rise indicates a hypothalamic problem.indicates a hypothalamic problem.

Hypopituitarism: corticotrophin releasing Hypopituitarism: corticotrophin releasing hormone (CRH)hormone (CRH)Stimulation test: Stimulation test:

ProcedureDetermine 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

InterpretationNormal 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 Hypopituitarism: vasopressin or ADH ADH

Stimulation Test Stimulation Test (Water deprivation 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)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.