Hormone Testing – Indications and Appropriate Use

Testosterone – Total^1–10  (T)

MSP cost: $15.81

Investigation of male hypogonadism.

Monitoring of males receiving androgen replacement.

Confirming adequacy of anti-androgen therapy in males with prostate carcinoma. 

Investigation of female androgen excess.

Screening for biochemical evidence of hypogonadism is not indicated in males without symptoms. Some symptoms of hypogonadism overlap with normal effects of aging.³

Not useful for investigation of decreased libido in females.⁷

Not useful for monitoring females receiving androgen therapy for low libido unless overuse is suspected or unexpected virilization has developed.

Notes: For the investigation of male hypogonadism. Diurnal variation of T requires that collection be performed within 3 hours of waking. Only tandem mass spectrometry is sufficiently sensitive to accurately measure the low total testosterone seen in normal females or males rendered
chemically castrate for prostate carcinoma.

In BC, free testosterone is calculated by measuring total testosterone, SHBG and albumin. Refer to Appendix A: Testosterone Testing and Measurements in BC (PDF, 92.5KB) for more information.

For information, refer to BCGuidelines.ca: Testosterone Testing Protocol.

Sex Hormone Binding Globulin (SHBG)

MSP cost: $13.56

Clarification of borderline low total testosterone.

Investigation of males with high testosterone of endogenous origin.

Clarification of borderline high total testosterone results.

Notes: In adult males (>18 yrs.), SHBG should only be performed on patients whose TT lies within the upper half of the subnormal range (approximately 3-8 nmol/L for modern assays). SHBG may be ordered for investigation of high total testosterone (approximately 30-35 nmol/L) in men who are not receiving androgen replacement therapy.

Total testosterone ordered for the purposes of monitoring androgen deprivation therapy for prostate cancer should be referred to a laboratory that performs tandem mass spectrometry with a total allowable error of less than 30% at a total testosterone concentration of 0.7 nmol/L. Alternatively, the laboratory could refer the sample to be measured by an alternate immunoassay methodology that meets this minimum standard. The total allowable error limit of 30% is in comparison to a reference method for testosterone.

Estradiol² (E2)

MSP cost: $22.43

Not indicated in routine clinical practice.

Investigation for estrogen producing neoplasms in males demonstrating spontaneous feminization including gynecomastia. 

Investigation of primary ovarian insufficiency or infertility.

For investigation of primary ovarian
insufficiency. Where possible, order
concurrently with FSH on day 3 of menstrual cycle (not day 21).

Monitoring of patients receiving aromatase inhibitor therapy.

Detection of estrogen-producing neoplasms.

For monitoring of females undergoing fertility treatment.

Not indicated in the investigation of male osteoporosis.¹¹

Not indicated for monitoring of men receiving testosterone therapy.¹²

Not indicated to determine if a woman is in menopause except in those with prior hysterectomy without bilateral salpingo-oophrectomy.

Not indicated for monitoring of patients receiving ERT.

Notes: E2 immunoassay performance is poor at low concentration^2,13 ranges making these assays inadequate for use in females receiving aromatase inhibitors¹⁴ and in most male patients. E2 analysis by tandem mass spectrometry can be arranged for females receiving aromatase inhibitors.

For the investigations of female osteoporosis, see BCGuidelines.ca: Osteoporosis: Diagnosis, Treatment and Fracture Prevention.

Progesterone 

MSP cost: $14.86

Not indicated.

Investigation of infertility.

Identification of prior ovulation.

Investigation of pregnancy viability.¹⁵

Not indicated to determine if a woman is in menopause except in those with prior hysterectomy without bilateral salpingo-oophrectomy.

Notes: Fertility measurement is made at day 21 or midluteal phase.

Luteinizing Hormone^{16, 17} (LH)

MSP cost: $12.41

Investigation of primary or secondary hypogonadism.

Investigation of primary or secondary hypogonadism.

Investigation of infertility.

Prediction of ovulation (by LH surge).

LH / FSH ratio is not  recommended to identify women with PCOS.¹⁸

Not indicated to determine if a woman is in menopause except in those with prior hysterectomy without bilateral salpingo-oophrectomy.

Notes: Usually performed in combination with measurement of appropriate sex steroids (T for males, E2 for females).

Follicle Stimulating Hormone^{16, 17} (FSH)

MSP cost: $36.09

Investigation of primary or secondary hypogonadism.

Investigation of oligospermia or azoospermia. 

Investigation of primary or secondary hypogonadism.

Investigation of infertility.

Investigation of primary ovarian insufficiency or infertility—where possible, order in conjunction with E2 on day 3 of menstrual cycle.

LH / FSH ratio is not recommended to identify women with PCOS.¹⁸

Not indicated to determine if a woman is in menopause except in those with prior hysterectomy without bilateral salpingo-oophrectomy.

Notes: Usually performed in combination with measurement of appropriate sex steroids (T for males, E2 for females).

Androstenedione

MSP cost: $36.09

Not indicated in routine clinical practice.

May be useful in monitoring therapy in patients with established CAH.¹⁹

Not indicated in routine clinical practice.

Functions as a second–line tool in the investigation of PCOS often in specialty practice.

May be useful in monitoring therapy in patients with established CAH.¹⁹

Not indicated in the investigation of male hypogonadism as this is primarily an adrenal steroid.

Dehydroepiandrosterone (DHEA)

MSP cost: $18.55

Not indicated.

Not indicated in the investigation of male hypogonadism as this is an adrenal steroid. 

Dehydroepiandrosterone–sulphate²⁰ (DHEA-S)

MSP cost: $18.55

Not indicated in routine clinical practice.

Investigation of adrenal carcinoma. 

Investigation of PCOS.

Investigation of adrenal mass.

Not useful for the investigation of male hypogonadism as this is an adrenal steroid.

17-hydroxyprogesterone (17-OHP)                    

MSP cost: $41.71

Not indicated in routine clinical practice.

For the diagnosis of non-classic CAH as a cause of hirsutism and for monitoring of CAH therapy.

Prolactin

MSP cost: $13.49

Investigation of infertility / hypogonadism /amenorrhea.

Investigation of galactorrhea.

Investigation for prolactinoma and other pituitary tumours.

Monitoring of prolactinoma in patients treated medically or surgically.

Not useful for monitoring pregnant or lactating patients.

25-hydroxyvitamin D (25(OH)D)

MSP cost: $61.32

Investigation of vitamin D nutritional status only by specialists in clinical scenarios where biochemical identification of vitamin D deficiency is necessary.

Not useful in the investigation of hypercalcemia unless there is clinical suspicion of vitamin D supplement overdose.

Notes: Not intended for other metabolites of Vitamin D.

Payable only for beneficiaries under the age of 19 years or when requested by a specialist. Refer to BC Guidelines.ca: Vitamin D Testing Protocol for additional information.
There is some evidence Vitamin D may boost immune function.²² As it is unlikely a patient develop vitamin D toxicity at recommended dosing, it is advisable to encourage supplementation rather than testing. 

1,25 dihydroxyvitamin D (1,25(OH)2D)

MSP cost: $94.49

Investigation of hypercalemia with concomitantly low PTH.

Should not be used for the investigation of vitamin D nutritional status.

Should not be used to monitor levels of pharmaceutically administered calcitriol.

Notes: Not intended for other metabolites of Vitamin D.

Payable only for beneficiaries under the age of 19 years or when requested by a specialist. Refer to BC Guidelines.ca: Vitamin D Testing Protocol for additional information.
There is some evidence Vitamin D may boost immune function.²² As it is unlikely a patient develop vitamin D toxicity at recommended dosing, it is advisable to encourage supplementation rather than testing. 

Parathyroid Hormone (PTH)

MSP cost: $17.52

Investigation of hyper and hypocalcemia.

Monitoring and treatment of renal osteodystrophy.

Notes: In patients with previously identified hypo or hypercalcemia, measure concomitantly with a repeat total or ionized calcium.

Aldosterone, plasma and urine

MSP cost: $170.92

Investigation of secondary causes of hypertension: primary aldosteronism, renal artery stenosis.

Not indicated for the initial investigation of syncope or hypotension caused by possible adrenal insufficiency. For adrenal insufficiency, screen with am cortisol and proceed to 250 µg ACTH stimulation test as indicated.

Notes: For ambulatory patients meeting criteria for primary aldosteronism screening, order upright plasma aldosterone and plasma renin activity after 1-2 hours ambulation and before 10 AM.²¹

Numerous physiological states and medications interfere with sensitivity and specificity of screening.²¹

Renin

MSP cost: $63.87 – $98.11

Investigation of secondary causes of hypertension: primary aldosteronism and renal artery stenosis.

Monitoring of CAH and mineralocorticoid supplementation in Addison’s Disease.

Cortisol, 24-hour urine free                                                                                           MSP cost: $26.01

Used for targeted screening for Cushing Syndrome caused by endogenous cortisol excess only.

Not useful for the diagnosis of Addison's Disease.

Do not order in patients receiving exogenous glucocorticoids.

Notes: Numerous studies have found males to have higher excretion rates than females. Application of sex specific reference intervals advised in cases where elevation is equivocal.^{22, 23}  

Cortisol, serum/plasma

MSP cost: $13.28

Used in the targeted screening and diagnosis of both Addison's Disease (primary adrenal insufficiency) and Cushing Syndrome.

Not useful in the investigation of non-specific fatigue and lethargy unless accompanied by clinical syndromes of Addison's Disease or Cushing Syndrome.

Measurement of morning and afternoon cortisol (for diurnal variation) is not useful.

Notes: A morning cortisol measurement can be used to exclude adrenal insufficiency. Collect sample within 3 hours of waking. Do not order random cortisol levels for this purpose.

A morning serum/plasma cortisol is not useful as a screen for Cushing Syndrome. Use 1 mg overnight dexamethasone suppression, 24-hour urinary free cortisol or late-night salivary cortisol.^{25, 26} Please note on the requisition that patient has been given 1 mg dexamethasone and provide the time of administration. The dose should be given as close to midnight as possible.

For cortisol analysis after ACTH stimulation, see adrenocorticotropic hormone simulation test.

Measurement of cortisol in patients being treated with exogenous glucocorticoids presents numerous bioanalytical and interpretive challenges and is not advised without consultation with an endocrinologist’s and/or laboratory physician/scientist.

Cortisol, late night salivary

MSP cost: $77.25

Used to screen for Cushing Syndrome caused by endogenous cortisol excess only.

Notes: Restricted to Vancouver General Hospital.

Payable only when requested by General Internists, Endocrinologists, Pediatricians and General Surgeons.

The daily maximum is one per patient.

Adrenocorticotropic hormone stimulation test (ACTH stimulation test)

MSP cost: $45.24

Used in the diagnosis of Addison's Disease (primary adrenal insufficiency) and secondary adrenal insufficiency.

Used in the diagnosis of non-classic CAH.

Notes: Patients with Addison's Disease have marked elevations of plasma ACTH at initial presentation provided that they are not exposed to exogenous glucocorticoid.

17-OHP is also ordered if non-classic CAH is a diagnostic consideration.

Measurement of cortisol in patients being treated with exogenous glucocorticoids presents numerous bioanalytical and interpretive challenges and is not advised without consultation with an endocrinologists and/or laboratory physician/scientist.

Adrenocorticotropic (ACTH)

MSP cost: $36.57

Used in the diagnosis Addison's Disease (primary adrenal insufficiency) and secondary adrenal insufficiency.

Used to distinguish between Cushing Syndrome caused by adrenal adenoma and Cushing Syndrome caused by inappropriate ACTH production from pituitary adenoma or ectopic source.

Used in the diagnosis of non-classic CAH.

24-hour urinary excretion of catecholamines and metanephrines

MSP cost: $46.45 catecholamines
$155.77 metanephrines

Used in the diagnosis of pheochromocytoma and functional paraganglioma. 

Urinary vanillylmandelic acid, although the end metabolite of both epinephrine and norepinephrine, has test characteristics inferior to urinary catecholamines and metanephrines and is not required for the investigation of pheochromocytoma.²⁶

Urinary dopamine and homovanillic acid are not required for the initial investigation of pheochromocytoma.

This test is not to be used as a tool for psychiatric assessment.

Notes: This test is subject to false positives from physiological stressors, certain foods, and numerous medications. Appropriate patient preparation is required to yield meaningful results.^{27, 28} 

For more information, please see Catecholamines in Urine.

Plasma Catecholamines

This test is no longer offered in BC. Please see plasma free metanephrines.

Plasma Free Metanephrines

Used in the diagnosis of pheochromocytoma and functional paraganglioma. 

This test is not to be used as a tool for psychiatric assessment.

Notes: Not currently offered in BC. Can be arranged as an out of province send–out where required (e.g. for diagnostic clarity in ambiguous cases or for the oliguric patient). This test is sensitive to patient posture and supine collections are recommended.²⁸

Thyroid Stimulating Hormone (TSH)

MSP cost: $9.90

Used to screen for all causes of primary hypothyroidism and hyperthyrodism.

Monitoring of patients treated with thyroid hormone.

In isolation, TSH is not useful with the investigation of secondary (also known as central or pituitary) hypothyroidism. If secondary hypothyroidism is suspected, measure fT4.

Notes: TSH is the preferred test for the initial investigation of thyroid disease and for monitoring thyroid hormone replacement therapy.

For the initial diagnosis of thyroid disease, confirmation of an abnormal TSH with a free T4 is indicated.

Refer to BC Guidelines: Thyroid Function Testing in the Diagnosis and Monitoring of Thyroid Function Disorder for other situations and additional information.

Free Thyroxine (fT4)

MSP cost: $12.12

Used for diagnostic confirmation of hyper/hypothyroidism when TSH is abnormal.

Used to assess the severity of hyperthyroidism and ongoing management of Graves’ Disease and other forms of hyperthyroidism.

Used to monitor T4 supplementation in patients with secondary hypothyroidism (pituitary cause).

Not for use in an initial screen for thyroid dysfunction except in the unusual circumstance that there is specific reason to suspect pituitary disease. 

Free Triiodothyronine (fT3)

MSP cost: $9.35

Rarely indicated. Reserved for situations where hyperthyroidism is suspected clinically and TSH is suppressed, but fT4 is not elevated.

Not for use in an initial screen for thyroid dysfunction.

Total thyroxine/ triiodothyronine (Total T4/T3)

Not currently offered by any lab in BC.

Replaced by free hormone determination.

Thyroperoxidase antibodies

MSP cost: $20.22

Used for the diagnosis of Hashimoto’s thyroiditis in the investigation of primary hypothyroidism.

Serial measurements are not indicated.

Thyroglobulin/Antithyroglobulin 
(Tg/Anti Tg)

MSP cost: $27.90/$20.40

Serves as a tumor marker for patients who have undergone previous treatment for papillary or follicular thyroid carcinoma.

Anti-Tg measurements are not indicated for the investigation for general thyroid autoimmunity.

Tg measurement is not indicated in patients with an intact thyroid except in rare circumstances.

Notes: Anti-Tg must be measured concomitantly with Tg as the presence of Anti-Tg makes Tg results unreliable.

Antibodies to the thyroid stimulating hormone receptor (TRAb)

MSP cost: $22.48

Used for the diagnosis of Graves’ Disease.

In certain clinical scenarios TRAb testing may be used as a first-line tool to distinguish Graves’ Disease from other forms of hyperthyroidism. See notes.

Not indicated for the investigation for general thyroid autoimmunity.

Notes: Although radioactive iodine uptake remains the gold standard for the identification of hyperthyroidism caused Graves’ Disease, TRAb offers advantages in specific clinical scenarios: investigation of unilateral exophthalmos, euthyroid Graves opthalmopathy, diagnosis of Graves’ Disease where exposure to radioactive iodine is contraindicated (pregnancy) or where the patient is apprehensive about exposure to radiotracers. TRAb also serves as a prognostic tool in a number of clinical scenarios.^{30, 31} TRAb testing is more easily arranged and results are typically available sooner than radioactive iodine uptake and scan.

Growth Hormone (GH)

MSP cost: $30.38

Used to confirm diagnosis and to assess response to treatment in acromegaly by use of dynamic function tests.

Used to assess pituitary ability to generate GH in dynamic function tests for hypopituitarism or pituitary growth hormone deficiency.

A random GH should not be ordered to screen for the investigation of either acromegaly or GH deficiency.

Insulin-like Growth Factor 1 (IGF1)

MSP cost: $55.08

Used to screen for acromegaly and growth hormone deficiency in symptomatic patients.

Used for the monitoring response to treatment (surgical or medical) for acromegaly.

Used to monitor response to therapy in patients receiving recombinant GH.

Should not be ordered unless there are specific symptoms of acromegaly or evidence/risk factors for hypopitutarism.³²

Notes: Reference intervals are highly dependent on age. Please use age-specific reference interval provided on the lab report. A complete chart of reference intervals by age is available from St. Paul’s Hospital Department of Pathology and Laboratory Medicine, at providencelaboratory.com.

Insulin

MSP cost: $27.55

Investigation of hypoglycemia.

Note that the specimen collected at the time of hypoglycemia must be analyzed.

Fasting insulin may be useful in the investigation of PCOS in females.³³

Not indicated for patients receiving insulin therapy.

Not for the investigation of impaired fasting glucose or the establishment of insulin resistance.

Lack of standardization in insulin assays and lack of data for normative responses mean that glucose-stimulated insulin measurements are not recommended in clinical practice.^{34, 35}

Notes: Reference intervals are BMI-dependent and require fasting state.

May be helpful in distinguishing type I from type II diabetics in equivocal cases, prior to commencement of therapy.

For investigation of hypoglycemia, the specimen demonstrating hypoglycemia is required and must be frozen at the earliest possible opportunity.

Occasionally confirmation of surreptitious or accidental insulin administration is clinically indicated in cases of hypoglycemia. However, many insulin assays do not detect synthetic analog insulins well. Specialized analysis is required to detect synthetic analogues. Consult with laboratory physician or scientist for advice.

C-peptide

MSP cost: $47.42

Investigation of hypoglycemia.

Notes: Reference intervals are BMI-dependent and require fasting state.

May be helpful in distinguishing type 1 from type 2 diabetics in equivocal cases, prior to commencement of therapy.

C-peptide clearance is poor in patients with CKD, where large elevations above the reference interval are common.