Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (224 page)

   Laboratory Findings

I.   ACTH and cortisol

  1.  Basal ACTH secretion. Serum cortisol should be measured between 8 and 9 AM. Serum cortisol value ≤3 μg/dL is strongly suggestive of cortisol deficiency and in a patient with pituitary or hypothalamic disease indicates ACTH deficiency. Cortisol values ≥18 μg/dL indicate sufficient basal ACTH secretion. Values between 3 and 18 μg/dL, which persist on repeat determination, are an indication for the evaluation of ACTH reserve.

  2.  ACTH reserve.

a.   Metyrapone test. Metyrapone blocks the conversion of 11-deoxycortisol to cortisol by CYP11B1 (11β-hydroxylase, P450c11), the last step in the synthesis of cortisol, and induces a rapid fall of cortisol and an increase of 11-deoxycortisol in serum. The metyrapone test can be performed as an overnight single-dose test or as a 2- or 3-day test. Cortisol and 11-deoxycortisol should be measured at 8 AM. A normal response is 8 AM serum 11-deoxycortisol concentration of 7–22 μg/dL. A serum cortisol concentration at 8 AM of <5 μg/dL confirms adequate metyrapone blockade and thereby documents compliance and normal metabolism of metyrapone. Serum 11-deoxycortisol concentrations <7 μg/dL with concomitantly suppressed cortisol values indicate adrenal insufficiency.

b.   Insulin tolerance test (insulin-induced hypoglycemia test). Patients should be administered regular insulin 0.1 U/kg intravenously, and glucose and cortisol should be measured at 15, 30, 60, 90, and 120 minutes after injection. If glucose level falls to 35–40 mg/dL, cortisol should increase to >18 μg/dL. Decreased cortisol levels indicate adrenocortical insufficiency secondary to hypopituitarism. The test requires close observation for hypoglycemia and is risky in patients with cardiac or neurologic dysfunction.

c.   ACTH stimulation test. Cosyntropin is synthetic ACTH, which has the full biologic potency of native ACTH. It is a rapid stimulator of cortisol and aldosterone secretion. The response to ACTH varies with the underlying disorder. If the patient has hypopituitarism with deficient ACTH secretion and secondary adrenal insufficiency, then the intrinsically normal adrenal gland should respond to maximally stimulating concentrations of exogenous ACTH if given for a sufficient length of time. The response may be less than in normal subjects and initially sluggish due to adrenal atrophy resulting from chronically low stimulation by endogenous ACTH. If, on the other hand, the patient has primary adrenal insufficiency, endogenous ACTH secretion is already elevated and there should be little or no adrenal response to exogenous ACTH.

II.  TSH

A.   Basal function. Low FTI or free T
₄
in the absence of appropriately elevated TSH is suggestive of secondary hypothyroidism. Medications that decrease thyroid hormone binding such as phenytoin, salsalate, or high-dose aspirin should be ruled out. Patient should also be taken off glucocorticoid treatment.

B.   TRH test. TRH is administrated intravenously (200–500 μg). Three blood specimens are collected for serum TSH testing, one immediately prior to TRH injection, and one 15 minutes and one 30 minutes after TRH injection. A significant rise in serum TSH from a basal level of 2–3 μU/mL is normal. Secondary (pituitary) hypothyroidism shows no rise in the decreased TSH level. A delayed peak is suggestive of hypothalamic rather than pituitary dysfunction, but is relatively nonspecific.

III.  Gonadotropins

A.   Low levels of FSH and LH in postmenopausal women or in men with low testosterone are suggestive of gonadotropin deficiency.

B.   Gonadotropin-releasing hormone (GnRH) test. Patients should be given GnRH (100 μg intravenously), and LH and FSH should be measured at 0, 30, and 60 minutes. LH should increase by 10 IU/L and FSH by 2 IU/L.

IV.  Growth hormone (GH)

A.   Basal GH and insulin-like growth factor-I (IGF-I) levels are nonspecific.

B.   Provocative tests with insulin, L-arginine, vasopressin, glucagon, or L-dopa should not be used. Peak GH should be >5–10 ng/mL.

V.  Vasopressin

A.   Basal serum sodium, osmolality, and urine osmolality. Hypotonic urine in the presence of increased serum sodium and serum osmolality is suggestive of diabetes insipidus. Twenty-four–hour urine should be collected for volume and specific gravity measurement.

B.   Water deprivation test. The inability to concentrate urine with a response to exogenous vasopressin is diagnostic of central diabetes insipidus.

   Imaging Studies

A.   An MRI scan (T1, T2 +/− gadolinium) is the first choice to evaluate the pituitary gland, hypothalamus, and pituitary stalk.

B.   A high-resolution CT with thin sections through the pituitary fossa is a reasonable alternative.

Suggested Readings

Khan F, Sachs H, Pechet L, et al.
Guide to Diagnostic Testing
. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.

Snyder PJ. Causes of hypopituitarism. In: Rose B, (ed).
UpToDate
, Waltham, MA: UpToDate, Inc.; 2009.

Snyder PJ. Clinical manifestations of hypopituitarism. In: Rose B, (ed).
UpToDate
, Waltham, MA: UpToDate, Inc.; 2009.

Snyder PJ. Diagnosis of hypopituitarism. In: Rose B, (ed).
UpToDate
, Waltham, MA: UpToDate, Inc.; 2009.

PITUITARY TUMORS

   Definition

Pituitary tumors are represented by any new growth of the pituitary gland, independent of size or symptoms.

   Overview

Pituitary adenomas are the most common cause of sellar masses. Most tumors are considered benign.

   Classification

  1.  Hormonally active tumors

A.   Growth hormone–secreting tumors

B.   Prolactin-secreting tumors

C.   ACTH-secreting tumors

  2.  Hormonally inactive tumors

A.   Nonsecreting pituitary adenoma

B.   Metastatic tumor (breast and lung are the most common primary sites)

C.   Other brain tumors such as craniopharyngioma, meningioma, and glioma

   Who Should Be Suspected?

Pituitary masses can present with neurologic symptoms, abnormalities related to undersecretion or oversecretion of pituitary hormones, or as an incidental finding on radiologic examination performed for some other reason.

I.   Symptoms

A.   Hormonally active tumors can be associated with symptoms of secretion or deficiency.

a.   Growth hormone–secreting tumors present with symptoms of acromegaly.

b.   Prolactin-secreting tumors present with symptoms of galactorrhea.

c.   ACTH-secreting tumors present with symptoms of Cushing syndrome.

B.   Nonsecreting tumors do not become symptomatic until their size becomes sufficient to cause with pituitary hormone insufficiency (e.g., gonadal dysfunction, secondary hypothyroidism, adrenal insufficiency, growth failure, delayed puberty in children).