Chapter 24 Evaluation Of Endocrine Function

Front 1

Clinical Consultation: A 30-year-old male has been showing the physical manifestations of acromegaly over a 2-year period. A random insulin-like growth
factor-1 (IGF-1) is elevated at 1650ng/mL (four times the upper reference limit).
What test do you recommend to confirm the clinician's suspicion, in addition to an MRI of the brain?
After a surgical resection of a pituitary adenoma, what two tests may be used to
monitor this patient?

Back 1

The oral glucose tolerance test ( OG1T) should be performed. An acromegalic patient will fail to suppress GH to less than 1 ng/mL and may show a
paradoxical rise in GH with the glucose load. These patients are usually monitored with insulin-like growth hormone (IGF-1) after surgical removal of
their pituitary tumor, although the OGGT may also be used.

Front 2

What is the most common hormone secreted by a pituitary adenoma?

Back 2

Prolactin-secreting adenomas are the most common adenoma of the pituitary.

Front 3

Clinical Consultation: A 67-year-old female with small cell carcinoma of the lung is suspected of having syndrome of inappropriate antidiuretic hormone (SIADH) . Her serum sodium today is 132 mmolf L, Cr is 1.0 mgfdL. She weighs 60 kg. Assist the
clinician in performing a water load test.

The clinician says that the patient completed chemotherapy 3 months ago. What other medications do you want to know about, as they can cause SIADH?
She takes no medications at this time. Her water load should be _____mL, to be consumed within____ minutes. The clinician should collect
urine every____ for the next ______hours .
The woman does as you instruct, and passes a total of 610 mL of urine over 5 hours.
Your diagnosis: ??

Back 3

A person with such a devastating malignancy may be on antidepressants; both tricyclics and monoamine oxidase inhibitors, as well as nicotine can cause
SIADH. At 60 kg, this woman should drink 20 x 60 = 1200 mL of water over 30 minutes. Urine is collected hourly for 5 hours, and volume and osmolality
are tested on each sample. She passed less than 80% of the water load in 5 hours, excreting only 51%. This, in the absence of other causative factors, is sufficient for the diagnosis of SIADH.

Front 4

What is the first test to perform in determining thyroid dysfunction, because of its high sensitivity?

Back 4

This is thyroid-stimulating hormone (TSH).

Front 5

T3 thyrotoxicosis, due to elevated serum triiodothyronine, has what laboratoty values (high, normal, or low)?
T4:
Free T4:
T3:
TSH:

Back 5

In T3 thyrotoxicosis, T4 and free T4 are normal, while T3 is elevated. TSH is suppressed and low.

Front 6

Clinical Consultation: A 28-year-old female is found to have lost 15 lb on a routine physical examination and has a mild tremor. The clinician suspects Graves' disease and finds that her TSH is very low and T4 is elevated. Upon further questioning, he finds that she seems unconcerned with her abnormal results and reluctant to pursue any more studies. He then wonders if she is taking thyroxine surreptitiously.
What two tests can you recommend to distinguish these two disorders?

Back 6

Thyroglobulin is a key test here. It will be undetectable in thyrotoxicosis factitia, but will be elevated in Graves' disease. Another option is the TSH receptor antibodies, which are present in Graves', but would be absent in a factitious disorder.

Front 7

If plasma free metanephrine and normetanephrine are not available, then what methodology of what test is the most sensitive urine screening test for pheochromocytoma?

Back 7

A 24-hour urinary total metanephrine assay, measured by high-performance liquid chromatography (HPLC), would be best. A 24-hour sample will pick
up the intermittent release of metanephrines, and a total metanephrines is preferred over individual metanephrines in a screening test. Additionally,
urinary catecholamines are a sensitive test. VMA lacks sensitivity, with 10-30% false negatives .

Front 8

Which test has the greatest sensitivity (90% of patients positive) in children with suspected neuroblastoma?

Back 8

This is urinary homovanillic acid (I·IVA). Additionally, urinary vanillymandelic acid is present in 75% of cases of neuroblastoma.

Front 9

Most inborn errors of adrenal cortical steroid metabolism involve what type of enzyme?

Back 9

This is a hydroxylase enzyme in the steroid biosynthesis pathway.

Front 10

What is the most common congenital enzyme deficiency of the adrenal cortex?

Back 10

21-hydroxylase deficiency is by far the most common, accounting for 95% of cases.

Front 11

What are the genes responsible for 21-hydro:xylase and 11beta-hydroxylase deficiencies?

Back 11

21-0H is CYP21; 11beta-0H is CYP11B 1 and 2.

Front 12

What is the substrate for 21-hydroxylase, which is present in excess in the plasma of persons with the enzyme deficiency?

Back 12

This is l7a-hydroxyprogesterone.

Front 13

Why do persons with 11beta-hydroxylase deficiency have hypertension when the pathway to aldosterone is blocked?

Back 13

Deoxycorticosterone (DOC) has mineralocorticoid activity. This is one of the steroids in excess in these patients.

Front 14

In 17-hydroxylase deficiency, testosterone levels are low, because progesterone cannot be converted to the precursor of the sex steroids, which is:

Back 14

This is l7a-hydroxyprogesterone.

Front 15

ACTH levels can discriminate between primary and secondary adrenal insufficiency, without the need for a stimulation test. What levels of ACTH are useful cutoffs?

Back 15

In primary adrenal insufficiency, levels are elevated, usually above 50-100 pg/mL, as the pituitary tries to whip the adrenal into action. In secondary adrenal insufficiency, levels are decreased, often to less than
10pg/mL.

Front 16

Which methodology offers high specificity for both serum cortisol and urinary free cortisol measurements?

Back 16

This is HPLC.

Front 17

What is the most common endogenous disorder of glucocorticoid excess?

Back 17

This is Cushing's disease, due to an ACTH-producing tumor of the pituitary.

Front 18

What will be the effect of the high-dose dexamethasone suppression test on a patient with adrenal adenoma or adrenal carcinoma?

Back 18

Patients with adrenal adenomas or carcinomas usually do not suppress with high-dose dexamethasone.

Front 19

How specific is the overnight dexamethasone suppression test in hospitalized patients?

Back 19

Not very specific. There is a 30% false-positive rate. Patients in hospital frequently have excess cortisol. because they are stressed.

Front 20

Outline the principle of the metyrapone test to assess for pituitary insufficiency.
What is the major risk in performing this test?

Back 20

Metyrapone is taken orally at midnight. It is an inhibitor of 11-hydroxylase and thus blocks cortisol production. This should stimulate the pituitary to release ACTH to increase cortisol levels. Plasma 11 -deoxycortisol and cortisol are measured the following morning at 8 a.m. to assess the response. The major
drawback is that patients with inadequate pituitary fundion may suffer acute adrenal insufficiency during the test when you shut off what little cortisol they
have.

Front 21

What are the typical changes in these laboratory parameters in primary hyperaldosteronism?
serum K:
urine K:
plasma renin:
urine aldosterone:

Back 21

Serum K is low, as it is lost in the urine, so urine K is high. Plasma renin is low, as it is suppressed by the high levels of aldosterone. Urine aldosterone is high
as the person excretes the excess.