Endocrine Testing




Endocrine-Related Autoantibody Tests


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Catecholamines

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Gastrointestinal Hormone–Related Tests

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Gonad Function Tests


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Growth and Growth Hormone Tests

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Hypothalamic-Pituitary Tests

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Parathyroid/Bone Tests


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Renal and Fluid-Balance Tests


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Thyroid Function Tests


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Genetic Tests

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Adrenal Dynamic Tests



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FIGURE 155-1. Relationship of serum osmolarity and plasma arginine vasopressin (AVP) levels in normal subjects and patients with central and nephrogenic diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The nephrogenic DI range and the normal range are similar (Ref. 1).


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FIGURE 155-2. Relationship of urine osmolarity and urine arginine vasopressin (AVP) levels in normal subjects and in patients with central and nephrogenic diabetes insipidus (DI) and antidiuretic hormone (ADH)-secreting tumors (Ref. 1). SIADH, Syndrome of inappropriate antidiuretic hormone secretion.


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FIGURE 155-3. Relationship of serum (total) calcium and intact parathyroid hormone (PTH) concentrations in patients with primary hyperparathyroidism, hypoparathyroidism, and hypercalcemia of malignancy (Ref. 1). Patients with hypercalcemia of malignancy usually also have elevated levels of parathyroid-related protein (PTHRP). ICMA, Immunochemiluminometric assay.


(Data from Clinical Correlations Department Quest Diagnostics Nichols Institute.)


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FIGURE 155-4. Relationship of serum free thyroxine (T4) (direct dialysis) and thyroid-stimulating hormone (TSH) concentrations in normal subjects and patients with thyroid disorders (Ref. 1). The log linear relationship is shown, whereby a linear change in serum free T4 produces a logarithmic change in serum TSH concentration. Normal values are shown for 589 normal subjects (289 children, 5 months to 20 years of age and 300 adults 21 to 54 years of age), 84 hypothyroid, and 116 hyperthyroid patients obtained through the Nichols Institute Clinical Correlations division. The samples from patients with thyroid hormone resistance were provided by Dr. Samuel Refetoff of The University of Chicago. Samples from patients with central hypothyroidism were provided by Dr. Peter Singer of the University of Southern California, Dr. Mary Samuels of Oregon Health Sciences University, Dr. Susan Clark of Loma Linda University, and Dr. Arlan Rosenbloom of the University of Florida. All patients were sampled prior to treatment, thus representing the native disease state.


Table 155-1. Adrenocorticotropic Hormone Stimulation Test, Standard56,57






Indication: Suspected adrenal insufficiency; suspected adrenal biosynthetic defect or ACTH unresponsiveness

Medication: 10 µg/kg, maximum 250 µg (0.25 mg), cosyntropin (Cortrosyn, synthetic 1–24 ACTH) by IV bolus; dilute in 2 to 5 mL physiologic saline. Intramuscular dosing is equally effective; dilute in 1 mL physiologic saline.

Sampling: Serum cortisol at 0 and 30 or 60 minutes

Interpretation: The usual normal response is an approximate doubling of the basal level, provided that the basal level does not exceed the normal range. Analysis of 8 reported studies including 122 patients indicated sensitivities of 97% and 57%, respectively, at 95% specificity for diagnosis of primary and secondary adrenal insufficiency using a serum cortisol cutoff of 15 µg/dL.

Comments: Normal response excludes primary adrenal insufficiency. Patients with secondary (ACTH) adrenal insufficiency usually show a blunted response but may have a normal result. Disparate levels of baseline precursor and product steroids (precursor > product) localize enzyme dysfunction in severe CAH cases. The ratio of precursor to product tends to be similar at baseline and peak sampling times. In children with milder defects, localization is defined by substantially disproportionate increases in precursor and product steroid levels after ACTH.

Table 155-2. Rapid Adrenocorticotropic Hormone Stimulation Results in Normal Adults: (250 µg Intravenous Bolus 1–24 ACTH) Glucocorticoid Pathway*

































Steroid Blood Level (ng/dL) Except Cortisol*
0 60 min
17-Hydroxypregnenolone 20–450 290–910
17-Hydroxyprogesterone 17–104 42–250
Dehydroepiandrosterone 230–955 545–1845
Androstenedione 56–135 72–290
11-Deoxycortisol 21–130 82–290
Cortisol (µg/dL) 6–19 14–41

* Quest Diagnostics Nichols Institute: 10 females, 10 males, healthy young adults; results are observed ranges (Ref. 1).


Table 155-3. Mineralocorticoid Pathway*

























Steroid Blood Level (ng/dL)
0 60 min
Progesterone 5–50 21–44
Deoxycorticosterone 3–10 14–33
18-Hydroxycorticosterone 11–46 54–161
Aldosterone 2–9 5–20

* Quest Diagnostics Nichols Institute: 10 females, 10 males, healthy young adults; results are observed ranges (Ref. 1).



Table 155-4. Rapid Adrenocorticotropic Hormone Stimulation Results in Normal Children and Adolescents (250 µg Intravenous Bolus 1–24 ACTH) Glucocorticoid Pathway*

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Table 155-5. Mineralocorticoid Pathway*

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Table 155-6. Adrenocorticotropic Hormone Stimulation Test, Prolonged56






Indication: Suspected secondary adrenal insufficiency; differentiates primary from secondary adrenal insufficiency

Medication: 0.5 IU/m2 corticotropin (Acthar gel) intramuscularly every 12 hours for 3 days or 10 µg/kg cosyntropin (Cortrosyn) intravenously in 100 to 250 mL of physiologic saline over 8 to 12 hours for 1 to 2 days; maximum, 250 µg.

Sampling: Serum cortisol before and 2 hours after each injection or infusion for 3 days and/or 24-hour urine samples for 4 days (baseline + 3 stimulation days)

Interpretation: Serum cortisol to exceed 25 µg/dL. Urine 17-hydroxycorticosteroids or free cortisol values usually increase twofold.

Comments: May give dexamethasone (20 µg/kg/d) to prevent adrenal crisis—will not interfere with test. Normal subjects and patients with secondary adrenal insufficiency will respond to prolonged stimulation.

Table 155-7. Adrenocorticotropic Hormone Stimulation Test, Low-Dose56,57






Indication: Suspected adrenal insufficiency, biosynthetic enzyme defect, or ACTH unresponsiveness

Medication: 1.0 µg/1.73 m2 cosyntropin (Cortrosyn, 1–24 synthetic ACTH) by IV bolus in 1.0 mL saline

Sampling: Blood for measurements of cortisol at 0, 30, and 40 minutes

Interpretation: Serum cortisol should be ≥15 µg/dL.

Comments: The low-dose test is useful in infants, avoiding underdiagnosis of hypothalamic-pituitary-adrenal axis impairment. It is particularly useful in assessing adrenal responsiveness before discontinuation of dexamethasone treatment. Glucocorticoid should be withheld for 12 hours prior to testing. In older patients, the low-dose test has equal sensitivity to the standard ACTH test.

Table 155-8. Low-Dose Short Synacthen Testing (LDSST)11



















Indications:

Suspected hypothalamic-pituitary-adrenal (HPA) axis impairment

Suspected cortisol deficiency

Alternative to insulin tolerance testing (ITT)
Testing:

Baseline blood sample for plasma cortisol measurement

1.0 µg (microgram) tetracosactrin (ACTH 1–24) IV

Blood samples for plasma cortisol at 0, 20, 30 minutes
Expected Results:

A peak plasma cortisol level of 2.17 µg/dL (600 nmol/L) indicates an intact HPA axis
Comment:

There is a high correlation between the ITT and LDSST peak cortisol responses (r = 0.89; p < 0.0001)

Sensitivity of the LDSST approximates 100%

Table 155-9. Aldosterone Suppression Test56,58






Indication: Suspected primary hyperaldosteronism

Medication: IV saline loading (2 L of 0.9% NaCl infused over 4 hours) or oral sodium loading for 3 to 4 days (urine sodium excretion >200 mEq/24-h) or administration of 0.1 mg fludrocortisone acetate every 6 hours plus NaCl × 4 days

Sampling: Aldosterone and direct renin or plasma renin activity (PRA) are measured before and after suppression.

Interpretation: In normal subjects, the serum aldosterone is <5 ng/dL after suppression. PRA is suppressed to the lower limit of detection.

Comments: None

Table 155-10. Corticotropin-Releasing Hormone Stimulation Test56






Indication: Suspected pituitary adrenocorticotropic hormone (ACTH) deficiency; suspected pituitary Cushing’s; rule out ectopic disease

Medication: 1.0 µg/kg (100 µg/1.73 m2; maximum dose 100 µg) synthetic sheep or human CRH administered as IV bolus over 30 seconds. Patient fasting 4 hours.

Sampling: Blood measurements of cortisol and ACTH at −5 and −1 minutes before CRH and at 15, 30, 45, and 60 minutes after CRH

Interpretation: Baseline ACTH increases 20% to 40% in 95% of normal subjects. Peak values (usually in the 20 to 100 pg/mL range) are observed at 30 to 60 minutes. Serum cortisol peaks at 30 to 60 minutes in the 20 to 25 µg/dL range.

Comments: The test can be conducted in the am or pm, but in normal subjects the responses vary with time of day. The ACTH increment is similar morning and evening, but peak values vary with baseline (higher in am). Cortisol levels peak at similar values morning and evening. Patients with pituitary ACTH deficiency have subnormal responses; those with hypothalamic disease tend to have augmented and prolonged ACTH responses with reduced cortisol response. Patients with primary adrenal insufficiency have high baseline ACTH, an augmented response to CRH, and low cortisol levels before and after CRH. Patients with Cushing’s disease (pituitary Cushing’s) usually show a >20% rise in cortisol and a >50% increase in ACTH. Patients with adrenal causes of Cushing’s syndrome or ectopic ACTH syndrome do not respond. Rarely, bronchial carcinoids producing ACTH may respond to CRH.

Table 155-11. Corticotropin-Releasing Hormone Stimulation Test, Adrenal Venous Sampling59






Indication: Distinguish between an adenoma or unilateral and bilateral hyperplasia in patients with primary aldosteronism. The test also is helpful when imaging studies fail to unequivocally identify an adenoma or when the identified adenoma is <1 cm in size.

Medication: 50 µg per hour of cosyntropin (Cortrosyn) is infused intravenously 30 minutes prior and continuously throughout the procedure.

Sampling: In this standard protocol, measurements for both cortisol (µg/dL) and aldosterone (ng/dL) are performed in serum samples obtained from the inferior vena cava (IVC) and each of the adrenal veins.

Interpretation: A catheterization is considered successful if the adrenal vein cortisol level is fivefold higher than the level in IVC. A lateralizing response is defined as a serum aldosterone/cortisol ratio fourfold higher in the adrenal vein draining the secreting side. A ratio of <3 is consistent with bilateral aldosterone hypersecretion; a ratio between 3 and 4 is an area of overlap.

Comments: Determination of aldosterone/cortisol ratio in samples of adrenal venous blood, obtained by an experienced radiologist, is the “gold standard” test. Unilateral disease is associated with a marked increase in the aldosterone/cortisol ratio on the side of the tumor, whereas there is little difference between the two sides in patients with bilateral hyperplasia. In a study of 163 men and 40 women with hyperaldosteronism, 56.7% of patients had a unilateral source of aldosterone secretion. The cutoff described above was able to lateralize the secreting site with 95% sensitivity and 100% specificity.

Table 155-12. CRH Stimulation Test, Petrosal Venous Sinus Sampling56,60






Indication: Differentiation between ectopic and pituitary causes of Cushing’s disease. This procedure can better distinguish between ectopic and pituitary ACTH hypersecretion than dexamethasone suppression, but it is invasive, may be associated with serious complications, and therefore should be performed by an experienced radiologist. This procedure appears to be less useful for lateralization of the tumor in cases in which the ACTH secretion appears to be of pituitary origin.

Medication: Ovine CRH (1 µg/kg body weight) administered as IV bolus

Sampling: Catheters are inserted via the jugular or femoral veins into both inferior petrosal veins. Blood is obtained from a peripheral vein via a third catheter or from a port in the iliac vein. Blood samples are drawn simultaneously from both inferior petrosal sinuses and the peripheral vein for plasma ACTH. At least 4 sets of 3 samples each are obtained: 2 sets are drawn immediately before injection of CRH as a baseline and 2 more are drawn between 2 and 3 and between 5 and 6 minutes after peripheral intravenous injection of CRH.

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Jan 16, 2017 | Posted by in ENDOCRINOLOGY | Comments Off on Endocrine Testing

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