Harr MLS Review Chemistry 5.8 Clinical Endocrinology

A serum thyroid panel reveals an increase in total T4, normal TSH, and normal free T4. What is the most likely cause of these results?

Euthyroid with increased thyroxine-binding protein Patients with a normal TSH are euthyroid, and most commonly an increase in total T4 in these patients is caused by an increase in TBG. An increase in TBG causes an increase in total T4 but not free T4. Subclinical hypothyroidism is usually associated with a high TSH, but normal free T3 and free T4. When TSH is indeterminate, the diagnosis is made by demonstrating an exaggerated response to the TRH stimulation test.

Which of the following is the mechanism causing Cushing's disease?

Excess secretion of pituitary ACTH Cushing's disease refers to adrenal hyperplasia resulting from misregulation of the hypothalamic-pituitary axis. It is usually caused by small pituitary adenomas. Cushing's syndrome may be caused by Cushing's disease, adrenal adenoma or carcinoma, ectopic ACTH-producing tumors, or excessive corticosteroid administration. The cause of Cushing's syndrome can be differentiated using the ACTH and dexamethasone suppression tests.

A patient has an elevated serum T3 and free T4 and undetectable TSH. What is the most likely cause of these results?

Primary hyperthyroidism An undetectable TSH with increased T3 is caused by primary hyperthyroidism (suppression via high free thyroid hormone). In secondary hyperthyroidism, the TSH will be elevated in addition to at least the T3. Patients with an increased thyroxine-binding protein level will have an increase in total T3 but not free T4 or TSH. Patients with euthyroid sick syndrome usually have a low total T3 due to deficient conversion of T4 to T3, normal free T4, and a normal or slightly elevated TSH.

Which of the following statements regarding thyroid hormones is true?

Total T3 and T4 are influenced by the level of thyroxine-binding globulin Total serum T4 and T3 are dependent upon both thyroid function and the amount of thyroxine-binding proteins such as thyroxine-binding globulin (TBG). Total T4 or T3 may be abnormal in a patient with normal thyroid function, if the TBG level is abnormal. For this reason, free T3 and T4 are more specific indicators of thyroid function than are measurements of total hormone. Only free hormone is physiologically active.

Which of the following conditions is characterized by primary hyperaldosteronism caused by adrenal adenoma, carcinoma, or hyperplasia?

Conn's syndrome Conn's syndrome is characterized by hypertension, hypokalemia, and hypernatremia with increased plasma and urine aldosterone and decreased renin. Cushing's syndrome results from excessive production of cortisol, and Addison's disease from deficient production of adrenal corticosteroids. Pheochromocytoma is a tumor of chromaffin cells (usually adrenal) that produces catecholamines.

Which metabolite is most often increased in carcinoid tumors of the intestine?

5-Hydroxyindolacetic acid (5-HIAA) 5-HIAA is a product of serotonin catabolism. Excess levels are found in urine of patients with carcinoid tumors composed of argentaffin cells. Carcinoid tumors are usually found in the intestine or lung, and produce serotonin and 5-hydroxytryptophan, a serotonin precursor. Serotonin is deaminated by monamine oxidase, forming 5-HIAA, and the 5-HIAA is excreted in the urine. Some carcinoid tumors produce mainly 5-hydroxytryptophan because they lack an enzyme needed to convert it to serotonin. The 5-hydroxytryptophan is converted by the kidneys to serotonin resulting in high urinary serotonin. Both 5-HIAA and serotonin are usually measured by HPLC with EDC.

In which case might a very low plasma TSH result not correlate with thyroid status?

After high-dose corticosteroid treatment In persons with severe chronic diseases or who have hCG-secreting tumors, TSH production may be suppressed. Some drugs, especially high doses of corticosteroids, will suppress TSH production. Low TSH levels not matching thyroid status can also be seen in patients who have recently been treated for hyperthyroidism because there is a delay in the pituitary response. High-sensitivity TSH assays that can measure as little as 0.01 mIU/L and free T4 and T3 can help differentiate these conditions from clinical hyperthyroidism. If the TSH is below .03 mIU/L and the free hormone levels are increased, this points to hyperthyroidism. Lab values in euthyroid sick syndrome may mimic mild hypothyroidism. In euthyroid sick syndrome, thyroid function will be normal, but TSH may be slightly increased owing to lower levels of free T3. In euthyroid sick syndrome, the rT3 will be increased.

When should progesterone be measured when evaluating an adult female for an ovulation?

At the mid cycle just after LH peaks Progesterone is often measured along with LH, FSH, estrogen, and prolactin to evaluate female infertility and dysmenorrhea. Progesterone is produced by the corpus luteum and levels are very low during the early follicular phase of the cycle. Progesterone is released by the corpus luteum following the LH surge that occurs 1-2 days prior to ovulation and is an indication that ovulation occurred. Low progesterone at midcycle indicates that ovulation did not occur. This is often the case in polyovarian cyst syndrome.

Which of the following statements applies to both measurement of VMA and metanephrines in urine?

Both can be measured by specific HPLC and MS assays VMA and metanephrines can both be measured as vanillin after oxidation with periodate. However, these methods are affected by dietary sources of vanillin; coffee, chocolate, bananas, and vanilla must be excluded from the diet. Metanephrines, VMA, and HVA are most often measured by HPLC-EDC.

Which statement best describes the relationship between luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in cases of dysmenorrhea?

Both hormones normally peak 1-2 days before ovulation In women, serum or urine LH and FSH are measured along with estrogen and progesterone to evaluate the cause of menstrual cycle abnormalities and anovulation. Both hormones show a pronounced serum peak 1-2 days prior to ovulation and urine peak 20-44 hours before ovulation. Normally, the LH peak is sharper and greater than the FSH peak; however, in menopause, the FSH usually becomes higher than LH. In patients with primary ovarian failure, the LH and FSH are elevated because low estrogen levels stimulate release of luteinizing hormone-releasing hormone (LHRH) from the hypothalamus. Conversely, in pituitary failure, levels of FSH and LH are reduced, and this reduction causes a deficiency of estrogen production by the ovaries.

Urinary HVA is most often assayed to detect

neuroblastoma HVA is the major metabolite of dopa, and urinary HVA is elevated in more than 75% of neuroblastoma patients. Neuroblastomas also usually produce VMA from norepinephrine. Thus, HVA and VMA are assayed together and this increases the sensitivity of detection to around 90%.

Which is normally the most abundant corticosteroid hormone secreted by the adrenal cortex?

Cortisol Cortisol is the most abundant adrenal hormone, and abnormal levels have pronounced effects on carbohydrate and lipid metabolism. Cortisol is a 21-carbon steroid with a dihydroxyacetone group at C17 and hydroxyl group at C11 that account for its glucocorticoid potency. Plasma and urinary cortisol measurements are used to diagnose most types of adrenocortical dysfunction. Dehydroepiandrosterone (DHEA), an adrenal androgen, is the next most abundant adrenal hormone. Aldosterone is the principal mineral corticoid made by the adrenals, and corticosterone is the immediate precursor to aldosterone. Both regulate salt balance.

Which of the following statements regarding adrenal cortical dysfunction is true?

Cushing's syndrome is associated with glucose intolerance Patients with Cushing's syndrome have elevated levels of cortisol and other adrenal corticosteroids. This causes the characteristic cushingoid appearance that includes obesity, acne, and humpback posture. Osteoporosis, hypertension, hypokalemia, and glycosuria are characteristics. Addison's disease results from adrenal hypoplasia and produces the opposite symptoms including hypotension, hyperkalemia, and hypoglycemia.

Which set of results is most likely in a female with hypogonadotropic ovarian failure?

Decreased LH, FSH, and estrogen Hypogonadotropic ovarian failure is the result of pituitary dysfunction. It may be caused by low levels of both LH and FSH, or it may be caused by high levels of prolactin as in prolactinoma, since prolactin will inhibit LHRH and result in low LH and FSH.

The onset of menopause is usually associated with what hormone changes?

Decreased estrogen and progesterone, and increased LH and FSH In menopause, estrogen production decreases to where the menstrual cycle and ovarian follicle maturation stop. The decreased estrogen causes the pituitary release of LH and FSH. In menopause, the FSH at midcycle is higher than LH. The increased LH causes the ovaries to secrete testosterone and androgens.

Select the main estrogen produced by the ovaries and used to evaluate ovarian function.

Estradiol (E2) E2 is the major estrogen produced by the ovaries and 2 gives rise to both estrone (E1) and E3. E2 is used to evaluate both ovarian function and menstrual cycle dysfunction.

Which of the following hormones is often decreased by approximately 25% in the serum of pregnant women who have a fetus with Down syndrome?

Estriol (E3) E3 is produced in the placenta and fetal liver from dehydroepiandrosterone derived from the mother and fetal liver. E3 is the major estrogen produced during pregnancy, and levels rise throughout gestation. Serum free E3 is often lower than expected for the gestational age in a pregnancy associated with Down syndrome. The combination of low serum free estriol, low-α fetoprotein, high hCG, and high- inhibin A is used as a screening test to detect Down syndrome. When one of the four markers is abnormal, amniocentesis should be performed for the diagnosis of Down syndrome by karyotyping or FISH. The four markers have a combined sensitivity (detection rate) of approximately 75%.

Which of the following statements is true regarding reverse T3 (rT3)?

Formed in the blood by degradation of T4 Reverse T3 is formed from the deiodination of T4 in the blood. It is an inactive isomer of T3, (3,3 ́,5 ́-triiodothyronine). Reverse T3 is increased in acute and chronic illness and is used to identify patients with euthyroid sick syndrome.

Hyperparathyroidism is most consistently associated with:

Hypophosphatemia Hyperparathyroidism causes increased resorption of calcium and decreased renal retention of phosphate. Increased serum calcium leads to increased urinary excretion. The distal collecting tubule of the nephron reabsorbs less bicarbonate as well as phosphate, resulting in acidosis.

In which situation is the plasma or 24-hour urinary cortisol not consistent with the clinical picture?

In congenital adrenal hyperplasia Congenital adrenal hyperplasia (adrenogenital syndrome) results from a deficiency of an enzyme required for synthesis of cortisol. Approximately 90% of cases are caused by a deficiency of 21-hydroxylase blocking conversion of 17-α hydroxyprogesterone to 11-deoxycortisol. Most other cases are caused by 11-hydroxylase deficiency, which blocks conversion of 11-deoxycortisol to cortisol. Precursors of cortisol, usually either 17-α hydroxyprogesterone or 11-deoxycortisol are increased. This results in low serum cortisol levels, but high levels of these intermediates (mainly 17-ketogenic steroids). The two most common features of CAH are salt wasting caused by increased mineral corticoid activity and virilization due to increased androgens.

Which set of results is most likely in an adult male with primary testicular failure?

Increased LH, FSH, and decreased testosterone Primary testicular failure produces a picture that is hypergonadotropic. The LH and FSH are increased because the pituitary gland is normal and responds to decreased free testosterone. Androstenedione is an adrenal androgen and is unaffected. In testicular failure secondary to pituitary deficiency (hypogonadotropic testicular failure), the LH, FSH, and testosterone are low.

Which statement about multiple endocrine neoplasia (MEN) is true?

It is associated with hyperplasia or neoplasia of at least two endocrine organs Multiple-endocrine neoplasia syndrome is inherited as an autosomal dominant disease involving excess production of hormones from several endocrine glands. MEN I results from adenomas (usually benign) of at least two glands, including the pituitary, adrenal cortex, parathyroid, and pancreas. The parathyroid gland is the organ most commonly involved, and in those patients an elevated Cai is an early sign. The pancreas is the next most frequently involved organ, but the hormone most commonly oversecreted is gastrin (not insulin). MEN II is characterized by pheochromocytoma and thyroid carcinoma. MEN II-B is a variant of MEN II showing the addition of neurofibroma.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) causes:

Low serum electrolytes SIADH results in excessive secretion of vasopressin (ADH) from the posterior pituitary, causing fluid retention and low plasma osmolality, sodium, potassium, and other electrolytes by hemodilution. It is suspected when urine osmolality is higher than plasma, but urine sodium concentration is normal or increased. Patients with sodium depletion have a urine osmolality higher than plasma, but low urine sodium.

Which method is most often used to measure fractionated catecholamines (epinephrine, norepinephrine, and dopamine)?

Measurement by HPLC with electrochemical detection HPLC-ECD separates catecholamines by reverse- phase chromatography, then detects them by oxidizing the aromatic ring at +0.8 V to a quinone ring. Current is proportional to epinephrine and norepinephrine concentration. Fluorescent methods employing ferricyanide (trihydroxyindole method) or ethylenediamine (EDA method) show interference by Aldomet and several other drugs and are obsolete. The radioenzymatic assay of catecholamines is a specific alternative to HPLC but requires a liquid scintillation counter. The method uses the enzyme COMT to transfer a tritiated methyl group from S-adenosyl methionine to the catecholamines. This results in formation of radiolabeled metanephrines that are measured. HPLC with fluorescence detection is not as sensitive as HPLC-ECD. Electrospray ionization tandem-mass spectroscopy is an alternative to HPLC-EDC for measurement of fractionated catecholamines and metanephrines.

Which assay using 24-hour urine is considered the best single screening test for pheochromocytoma?

Metanephrines Catecholamines are metabolized to metanephrines and VMA. Urinary catecholamines are increased by exercise and dietary ingestion. Measurement of 24-hour urinary metanephrine is about 95% sensitive for pheochromocytoma, and is the best single test. Specificity and sensitivity for detecting pheochromocytoma approach 100% when both VMA and metanephrines are measured.

Which is the most widely used screening test for Cushing's syndrome?

Overnight low-dose dexamethasone suppression test Dexamethasone is a synthetic corticosteroid that exhibits 30-fold greater negative feedback on the hypothalamus than cortisol. When an oral dose of 1 mg of the drug is given to a patient at 11 p.m., the 8 a.m. serum total cortisol level should be below 5.0 μg/dL. Patients with Cushing's syndrome almost always exceed this cutoff. Therefore, a normal response to dexamethasone excludes Cushing's syndrome with a sensitivity of about 98%. CRH stimulation and petrosal sinus sampling are confirmatory tests for Cushing's disease, and are used when the high-dose dexamethasone suppression test is inconclusive. The metyrapone stimulation test measures the patient's ACTH reserve. Metyrapone blocks cortisol formation by inhibiting 11-β hydroxylase. This causes an increase in ACTH output in normals. A subnormal ACTH response is seen in persons with Addison's disease caused by pituitary failure.

Which of the following is the most common cause of Cushing's syndrome?

Overuse of corticosteroids The most common cause of Cushing's syndrome is the administration of medications with cortisol or glucocorticoid activity. Excluding iatrogenic causes, approximately 60%-70% of Cushing's syndrome results from hypothalamic-pituitary misregulation and is called Cushing's disease. Adrenal adenoma or carcinoma (non-ACTH-mediated Cushing's syndrome) comprise about 20% of cases, and ectopic ACTH production accounts for 10%-20%.

Which statement regarding the use of PTH is true?

PTH levels differentiate primary and secondary causes of hypocalcemia Serum Cai is the best screening test to determine if a disorder of calcium metabolism is present, and will distinguish primary hyperparathyroidism (high Cai) and secondary hyperparathyroidism (low Cai). PTH levels are used to distinguish primary and secondary causes of hypocalcemia. Serum PTH is low in primary hypocalcemia (which results from parathyroid gland disease), but is high in secondary hypocalcemia (e.g., renal failure). Serum PTH is also used for the early diagnosis of secondary hypocalcemia because PTH levels rise prior to a decrease in the serum Cai. Serum PTH is used to help distinguish primary hyperparathyroidism (high PTH) and hypercalcemia of malignancy (usually low PTH), and pseudohypoparathyroidism from primary hypoparathyroidism. Pseudohypoparathyroidism results from a deficient response to PTH and is associated with normal or elevated serum PTH.

Which of the following is most often elevated in hypercalcemia associated with malignancy?

Parathyroid hormone-related protein (PTHRP) PTHRP is a peptide produced by many tissues and normally present in the blood at a very low level. The peptide has an N-terminal sequence of eight amino acids that are the same as found in PTH and that will stimulate the PTH receptors of bone. Some malignancies (e.g., squamous, renal, bladder, and ovarian cancers) secrete PTHRP, causing hypercalcemia-associated malignancy. Because the region shared with PTH is small and poorly immunoreactive, the peptide does not cross-react in most assays for PTH. For this reason, and because tumors producing ectopic PTH are rare, almost all patients who have an elevated Cai and elevated PTH have primary hyperparathyroidism. The immunoassay for PTHRP will frequently be elevated in patients who have not yet been diagnosed with malignancy but have an elevated Cai, without an elevated serum PTH. Calcitonin is a hormone produced in the medulla of the thyroid that opposes the action of PTH. However, calcitonin levels do not greatly influence the serum calcium. Assay of calcitonin is used exclusively to diagnose medullary thyroid cancer, which produces very high serum levels.

Which test is the most specific for establishing a diagnosis of Cushing's disease (pituitary Cushing's)?

Petrosal sinus sampling following corticotropin-releasing hormone stimulation Although dexamethasone suppression tests have a high sensitivity, some patients without Cushing's syndrome have indeterminate results (e.g., values between 5 and 10 μg/dL) or abnormal results owing to medications or other conditions. When corticotropin-releasing hormone is given intravenously, patients with Cushing's disease have an exaggerated ACTH response. Samples are drawn from the sinuses draining the pituitary gland and from the peripheral blood. In patients with pituitary tumors, the ACTH will be several times higher in the sinus samples than in the peripheral blood samples.

Which of the following statements is correct in assessing GH deficiency?

Pituitary failure may involve one, several, or all adenohypophyseal hormones; but GH deficiency is usually found Because GH is the most abundant pituitary hormone, it may be used as a screening test for pituitary failure in adults. Pituitary hormone deficiencies are rare and are evaluated by measuring those hormones associated with the specific type of target organ dysfunction. GH secretion peaks during sleep, and pulsed increases are seen following exercise and meals. In adults, a deficiency of GH can be ruled out by demonstrating normal or high levels on two successive tests. In children, there is extensive overlap between normal and low GH levels, and a stimulation (provocative) test is usually needed to establish a diagnosis of deficiency. Exercise is often used to stimulate GH release. If GH levels are greater than 6 μg/L after vigorous exercise, then deficiency is ruled out. In addition to exercise, drugs such as arginine, insulin, propranolol, and glucagon can be used to stimulate GH release. Deficiency is documented by registering a subnormal response to two stimulating agents.

Which of the following statements regarding the catecholamines is true?

Plasma levels show both diurnal and pulsed variation Catecholamines—epinephrine, norepinephrine, and dopamine—are produced from the amino acid tyrosine by the chromaffin cells of the adrenal medulla. Plasma and urinary catecholamines are measured in order to diagnose pheochromocytoma. Symptoms include hypertension, headache, sweating, and other endocrine involvement. Plasma catecholamines are oxidized rapidly to metanephrines and VMA; only about 2% is excreted as free catecholamines. The zona glomerulosa is the outermost portion of the adrenal cortex, where aldosterone is mainly produced.

Which of the following conditions will increase total T4 by increasing TBG?

Pregnancy or estrogens Pregnancy and estrogens are the most common cause of increased TBG. Other causes include hepatitis, morphine, and clofibrate therapy. Acute illness, anabolic steroids, and nephrotic syndrome decrease the level of TBG. Normal pregnancy causes an elevated serum total T4. Suitable assays are available that estimate free T4 and T3 and these should be used instead of total hormone assays.

Which of the following statements about the diagnosis of Addison's disease is true?

Primary and secondary Addison's disease can often be differentiated by plasma ACTH ACTH (Cortrosyn) stimulation is used as a screening test for Addison's disease. A 250-μg dose of Cortrosyn is given intravenously. Normal patients show a 2-5 times increase in serum cortisol. A subnormal response occurs in both primary and secondary Addison's disease. Plasma ACTH is high in primary but is low in secondary Addison's disease. Patients with secondary Addison's disease (pituitary failure) do not respond to metyrapone because their ACTH reserve is diminished.

When pituitary adenoma is the cause of decreased estrogen production, an increase of which hormone is most frequently responsible?

Prolactin Prolactinoma can result in anovulation because high levels of prolactin suppress release of LHRH (gonadotropin-releasing hormone), causing suppression of growth hormone (GH), FSH, and estrogen. Prolactinoma is the most commonly occurring pituitary tumor accounting for 40%-60%. Adenomas producing FSH have a frequency of about 20%, while those pituitary tumors secreting LH and TSH are rare.

Select the hormone which when elevated is associated with galactorrhea, pituitary adenoma, and amenorrhea.

Prolactin Serum prolactin may be increased from hypothalamic dysfunction or pituitary adenoma. When levels are greater than five times the URL, a pituitary tumor is suspected. Prolactin is measured by enzyme immunoassay (EIA).

Which test is used to distinguish Cushing's disease (pituitary Cushing's) from Cushing's syndrome caused by adrenal tumors?

Serum ACTH Serum ACTH assays are very helpful in distinguishing the cause of Cushing's syndrome. Patients with adrenal tumors have values approaching zero. Patients with ectopic ACTH tumors have values greater than 200 pg/dL. Fifty percent of patients with Cushing's disease have high 8 a.m. ACTH levels (between 100-200 pg/dL). The high-dose dexamethasone suppression test is also used. Patients with Cushing's disease show more than 50% suppression of cortisol release after receiving an 8-mg dose of dexamethasone, but patients with adrenal tumors or ACTH producing tumors do not. Inferior petrosal sinus sampling (the petrosal sinuses drain the pituitary) is used to determine if a high ACTH is from the pituitary glands, or from an ectopic source.

Which statement best describes the level of GH in patients with pituitary adenoma associated with acromegaly?

Some patients will require a glucose suppression test to establish a diagnosis Approximately 90% of patients with acromegaly will have an elevated fasting GH level, but 10% will not. In addition, a single measurement is not sufficient to establish a diagnosis of acromegaly because various metabolic and nutritional factors can cause an elevated serum GH in the absence of pituitary disease. The glucose suppression test is used to diagnose acromegaly. An oral dose of 100 g of glucose will suppress the serum GH level at 1 hour (postadministration) to below 1 μg/L in normal patients, but not in patients with acromegaly. Patients with acromegaly also have high levels of IGF-1, also called somatomedin C, which is overproduced by the liver in response to excess release of GH.

Which statement regarding thyroid hormones is true?

T3 is about 10-fold more active than T4 The rate of DIT synthesis is twice that of MIT and the rate of coupling favors formation of T4. Levels of T4 are about 50 times those of T3, but T3 is approximately 10 times more active physiologically. Eighty percent of circulating T3 is derived from enzymatic conversion of T4 by T4 5 ́-deiodinase.

Select the most appropriate single screening test for thyroid disease.

TSH assay TSH is produced by the anterior pituitary in response to low levels of free T4 or T3. A normal TSH rules out thyroid disease. TSH is low in primary hyperthyroidism and high in primary hypothyroidism.

Which statement about TSH and T4 in early pregnancy is correct?

TSH falls and thyroid hormones rise Estrogens released in pregnancy cause an increase in TBG, which causes an increase in total T4 and T3. In early pregnancy, the hCG produced by the placenta stimulates the thyroid, causing an increase in free thyroid hormones. This suppresses TSH production. In the second trimester, as hCG diminishes, free T4 levels fall, and may be lower than 0.8 ng/dL, the lower limit of the adult reference range due to expansion of the blood volume. Therefore, both TSH and free T4 should be evaluated during pregnancy using trimester-specific reference ranges. In early pregnancy, a TSH above the first- trimester reference range should be followed up with free T4 and thyroid peroxidase antibody levels to assess the need for thyroid treatment.

A female with severe excessive pubic and facial hair growth (hirsutism) should be tested for which of the following hormones?

Testosterone and dehydroepiandrosterone sulfate Excessive hair grown in females results from excessive androgen production, and is most commonly seen in polycystic ovarian syndrome, which produces high levels of ovarian-derived testosterone. It will also occur as a consequence of Cushing's syndrome and mild congenital adrenal hyperplasia. Therefore, cortisol and 17 α-hydroxyprogesterone can help identify those causes. Rapid onset of hirsutism can result from an ovarian or adrenal tumor. Dehydroepiandrosterone sulfate is produced only by the adrenals and would be useful in identifying those rare cases where the cause is an androgen-secreting adrenal tumor.

Which assay is used to confirm difficult cases of hypothyroidism?

Thyrotropin-releasing hormone (TRH) stimulation test The TRH stimulation test is used to confirm borderline cases of abnormal thyroid function. In normal patients, intravenous injection of 500 μg of TRH causes a peak TSH response within 30 minutes. In patients with primary hypothyroidism, there is an exaggerated response (>30 mU/L). Patients with hyperthyroidism do not show the expected rise in TSH after TRH stimulation.

Which statement regarding the measurement of urinary catecholamines is true?

Twenty-four-hour urinary catecholamine assay avoids pulse variations associated with measurement of plasma catecholamines Measurement of total urinary catecholamines is not a specific test for pheochromocytoma. Urine levels may be increased by exercise and in muscular diseases. Catecholamines in urine may also be derived from dietary sources rather than endogenous production. Most catecholamines are excreted as the glucuronide, and the urinary free catecholamines increase only when there is increased secretion. Measurement of free hormone in urine is equal in clinical sensitivity and specificity to measurement of metanephrines. Twenty-four-hour urine is the sample of choice because plasma levels are subject to pulse variation and affected by the patient's psychological and metabolic condition at the time of sampling.

Which of the following statements about cortisol in Cushing's syndrome is true?

Twenty-four-hour urinary free cortisol is a more sensitive test than plasma total cortisol Serum cortisol can be increased by factors such as stress, medications, and cortisol-binding protein, and the cortisol level of normal patients will overlap those seen in Cushing's syndrome because of pulse variation. When cortisol levels become elevated, cortisol-binding protein becomes saturated, and free (unbound) cortisol is filtered by the glomeruli. Most is reabsorbed, but a significant amount reaches the urine as free cortisol. Twenty-four-hour urinary free cortisol avoids the diurnal variation that may affect plasma free cortisol levels and is a more sensitive test than serum total or free cortisol.

Which statement about sample collection for catecholamines and metabolites is true?

Twenty-four-hour urine creatinine should be measured with vanillylmandelic acid, homovanillic acid, or metanephrines Stress, exercise, and an upright position induce catecholamine elevation, and therefore, patients must be resting supine for at least 30 minutes prior to blood collection. The preferred method of collection is catheterization, so that the anxiety of venipuncture is not a factor. A 4-hour fast is also recommended. Many drugs contain epinephrine, which may falsely elevate catecholamine measurements. In addition, many drugs inhibit monoamine oxidase, which is needed to convert metanephrines to VMA. Therefore, medications should be removed prior to testing whenever possible. Twenty-four-hour urine samples for catecholamines are usually preserved with 10 mL of 6N HCl because some degradation occurs during storage when pH is greater than 3. Renal clearance affects excretion of catecholamine metabolites; it is preferable to report VMA, HVA, and metanephrines, in μg/mg creatinine. The urinary creatinine measurement should be at least 0.8 g/day, to validate the completeness of the 24-hour urine sample.

The best method of analysis for serum PTH involves using antibodies that detect

both the amino-terminal fragment and intact PTH PTH is a polypeptide comprised of 84 amino acids. The biological activity of the hormone resides in the N-terminal portion of the polypeptide, but the hormone is rapidly degraded and produces N-terminal, middle, and C-terminal fragments. Fragments lacking the N-terminal portion are inactive. Immunoassays for PTH using antibodies to different portions of the polypeptide will give different results. The assay of choice is a two-site double-antibody sandwich method that measures only intact PTH and active fragments. Methods that use single antibodies may detect inactive as well as active PTH fragments and are not as specific for parathyroid disease.

Zollinger-Ellison (Z-E) syndrome is characterized by great (e.g., 20-fold) elevation of:

gastrin Z-E syndrome is caused by a pancreatic or intestinal tumor secreting gastrin (gastrinoma), and results in greatly increased gastric acid production. A serum gastrin level 10-fold greater than the URL in a person with hyperacidity and stomach or duodenal ulcers is diagnostic. Confirmation of gastric hyperacidity is demonstrated using the basal acid output (BAO) test.

The serum TSH level is almost absent in:

primary hyperthyroidism Low TSH and a high T3 (and usually T4) occur in primary hyperthyroidism, but may also occur in systemic nonthyroid illnesses where T4 has been converted to T3. A 2-fold increase in free hormone can produce a 100-fold decrease in TSH. In primary hyperthyroidism, the TSH will be within a range of 0-0.02 mU/mL, while in nonthyroid illnesses it will be 0.03 mU/mL or higher. A high TSH and low T4 occur in primary hypothyroidism but can also occur in an acutely ill patient without thyroid disease, the euthyroid sick syndrome. Secondary hyperthyroidism is caused by pituitary hyperfunction, resulting in increased serum TSH.

Thyroid hormones are derived from the amino acid:

tyrosine Thyroid hormones are derived from the enzymatic modification of tyrosine residues on thyroglobulin. Tyrosine is halogenated enzymatically with iodine, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Enzymatic coupling of these residues form T3 (3,5,3 ́-triiodothyronine) and T4 (3,5,3 ́,5 ́-tetraiodothyronine). These are hydrolyzed from thyroglobulin, forming active hormones.