Investigations
1st investigations to order
serum electrolytes
Test
Electrolyte abnormalities are helpful in directing suspicion towards hormonal disorders.
Result
low sodium (in adrenocorticotrophic hormone and thyroid-stimulating hormone deficiency); elevated sodium (in diabetes insipidus)
serum and urine osmolarity
Test
Necessary for diagnosis of central diabetes insipidus.[32]
A low urine osmolarity in conjunction with high serum osmolarity strongly suggests diabetes insipidus.
Result
with high serum osmolarity (>295 mOsm/L), normal response is a high urine osmolarity (>600 mOsm/L); in diabetes insipidus, urine osmolarity is low (<300 mOsm/L)
8 a.m. cortisol and adrenocorticotrophic hormone
Test
Normal reference ranges vary depending on lab, time of collection, and assay. Cortisol more than or equal to 414 nanomol/L (15 micrograms/dL) suggests that basal adrenocorticotrophic hormone (ACTH) secretion is sufficient. An 8 a.m. cortisol level between 83 nanomol/L (3 micrograms/dL) and 414 nanomol/L (15 micrograms/dL) necessitates an ACTH stimulation test.[32]
Result
cortisol ≤83 nanomol/L (3 micrograms/dL) and inappropriately low ACTH
thyroid function tests
Test
Secondary hypothyroidism is associated with thyroid-stimulating hormone (TSH) of low bioactivity (normal TSH levels but reduced activity in stimulating thyroid hormone release). Therefore, TSH alone should not be used in screening for hypothyroidism in patients who have hypothalamic or pituitary disease.
Result
low free thyroxine (T4) and free triiodothyronine (T3); normal or low TSH
8 a.m. testosterone, follicle-stimulating hormone, and luteinising hormone in men
Test
All are low in secondary hypogonadism.
Gonadotrophin-releasing hormone stimulation test (rarely used) may not provide any additional information in adults.[50]
Measurement of free or bioavailable testosterone levels is useful in patients with total testosterone levels near the lower limit of normal or if sex hormone-binding globulin abnormalities are suspected.[45]
A combination of symptoms and two low fasting morning testosterone levels is necessary to establish a diagnosis of late-onset hypogonadism.[45]
Testing should be performed in the absence of acute/subacute illness.[32]
Result
low
estradiol, follicle-stimulating hormone, and luteinising hormone in women
Test
Follicle-stimulating hormone and luteinising hormone may be low or inappropriately normal in secondary hypogonadism.
A normal menstrual cycle is a more sensitive indicator of an intact pituitary and normal gonadal function than any biochemical test.
Gonadotrophin-releasing hormone stimulation test (rarely used) does not provide any additional information in adults.[32][50]
In post-menopausal women not on hormone replacement therapy, the absence of high serum follicle-stimulating hormone and luteinising hormone is sufficient for a diagnosis of gonadotrophin deficiency.
Result
low
prolactin
Test
It is important to exclude high-dose hook effect (a laboratory test limitation that can result in an artificially low level of prolactin) in patients with macroadenomas with 1:10 dilution, or serial dilution of the prolactin specimen, as this assay limitation may lead to a falsely low level of prolactin.[51]
It is important to consider macroprolactinaemia caused by a circulating antibody producing an artificial elevation of prolactin that can be removed by polyethylene glycol precipitation prior to assay, as this may also cause a false elevation in prolactin levels.
Result
slightly elevated (due to stalk compression); higher if prolactinoma (macroadenoma) causing hypopituitarism
insulin-like growth factor-1
Test
Also known as somatomedin-C. Insulin-like growth factor-1 reflects growth hormone levels over time.
Reference ranges are age- and sex-specific.
May be low in malnutrition and chronic illness.
The Endocrine Society recommends against biochemical work-up for growth hormone deficiency in patients with obvious features of deficiency and three other documented pituitary hormone deficiencies.[32]
Result
low
cosyntropin/tetracosactide stimulation test
Test
250 micrograms of cosyntropin (synthetic ACTH 1-24) is administered intramuscularly or intravenously; serum cortisol levels are measured at 30 and 60 minutes.
Peak cortisol concentrations less than 500 nanomol/L (18.1 micrograms/dL) at 30 or 60 minutes indicate adrenal insufficiency.
Result
inadequate cortisol response
Investigations to consider
insulin tolerance test
Test
0.05 to 0.15 units of insulin/kg is administered intravenously and serum glucose, cortisol, and growth hormone (GH) are measured before and after 15, 30, 60, 90, and 120 minutes after injection.
In normal people, serum cortisol increases to ≥498 nanomol/L (18 micrograms/dL) if the serum glucose falls to <2.78 mmol/L (50 mg/dL).
A normal GH response is a peak of >5 micrograms/L in the setting of hypoglycaemia (glucose <2.78 mmol/L [50 mg/dL]). GH deficiency is present when the peak GH response is <3 micrograms/L.
Result
inadequate cortisol or GH response to the acute stress of hypoglycaemia
water deprivation and desmopressin response test
Test
Patients are deprived of fluids for 8 hours or until 5% loss of their body weight is reached.
Plasma osmolarity is measured every 4 hours and urine volume and osmolarity every 2 hours. Patients are then given desmopressin 2 micrograms intramuscularly, and serum osmolarity, as well as urine osmolarity and volume, are measured over the next 4 hours.
In patients with central diabetes insipidus, their kidneys respond to desmopressin and subsequently develop a concentrated urine.
False-negative results may be seen in patients with partial central diabetes insipidus who are hyper-responsive to the submaximal rise in antidiuretic hormone induced by water deprivation.
Alternatively, a saline infusion test may be performed.
Result
low paired urine and plasma osmolalities; low urinary sodium; low urine specific gravity (<1.005); large volumes of urine produced (>3 L/24 hours)
MRI pituitary
Test
Should only be performed after complete biochemical work-up, as there is a high prevalence of pituitary incidentalomas.[52]
Result
lesion in sellar or parasellar regions
CT pituitary
Test
Should only be performed after complete biochemical work-up and if a craniopharyngioma is suspected.
Result
calcification if craniopharyngioma present
metyrapone testing of the adrenal axis
Test
An alternative to the cosyntropin/tetracosactide stimulation test in the hospital setting. However, its use is limited by the difficulty in obtaining metyrapone.
Result
inadequate cortisol response
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