disease, ectopic ACTH-producing tumors, female acne and hirsutism, oligomenorrhea in female athletes, polycystic ovarian syndrome, Stein-Levinthal syndrome, and virilizing congenital hyperplasia.

 

TESTES

From Leydig cells, the testis elaborates testosterone,

androstenedione, and dehydroepiandrosterone (also

from adrenal cortex). Luteinizing hormone from the

pituitary stimulates the formation of testosterone, which

is inactivated and conjugated in the liver and excreted as

glucuronide. Testosterone production rates in men are

2-8 mg/day; in women, 0.5-2.5 mg/day.

Actions

Testosterone maintains sex organs and controls

development of male sex characteristics, inhibits pituitary

LH, promotes long-bone growth without closure of

epiphyses, and has many anabolic effects (e.g. retention

of sodium, chloride, water, decrease in gluconeogenesis).

It is required for spermatogenesis. However, it cannot be

taken exogenously for this purpose since it would suppress

FSH and thus prevent this process.

Clinical Disorders

Deficiency

Before puberty, eunuchoidism or cryptorchism. After

puberty, asthenia, loss of beard and potency, atrophy

of sex organs, hot flushes, nervousness, depression and

osteoporosis. Partial deficiency syndromes may occur (e.g.

Klinefelter, Del Castillo).

Excess

Masculinization as with adrenocortical tumors, Leydig

cell tumors, testicular teratomas and seminomas.

Administered excess may depress spermatogenesis which

“rebounds” to supranormal level after withdrawal.

Methods of Evaluation

Physical Examination

Noting pubic and temporal hair, prostate, and testes.

The study of male hypogonadism or sperm deficiencies

involves testicular biopsy, examination of the semen

and spermatozoa count, and such urinary hormone

determinations as indication of androgen production (17-ketosteroid excretion) or inhibition or lack of

the pituitary gonadotropins (FSH determination). The

absence of hyaluronidase from semen may indicate an

obstructive lesion of the ducts leading from the testes,

where the enzyme is produced. Urinary testosterone and

plasma testosterone measurements are very helpful.

Gonadotropin Stimulation Test

Hypogonadism originating in the testis is accompanied by

high excretory and serum levels of LH and FSH, whereas

both are low when the defect is in the pituitary. Evidences

of hypogonadism will disappear and 17-ketosteroid

excretion will rise in a patient with hypopituitarism when

gonadotropins are administered. This treatment is ineffective when the defect originates in the gonad.

The patient should not be receiving endocrine therapy

at the time of testing.

Chorionic gonadotropin is given intramuscularly in a

daily dose of 2000 IU for 3 weeks. The patient is watched for

abatement of evidences of hypogonadism: in men, sperm

count, testicular biopsy, 17-ketosteroids, testosterone,

secondary sex characteristics, in women, vaginal smear for

estrogenic effects, secondary sex characteristics.

Disappearance of the evidences of hypogonadism

indicates hypogonadism secondary to pituitary failure.

780 Concise Book of Medical Laboratory Technology: Methods and Interpretations Testosterone, Free, Blood

Normal values

pg/mL SI Units

pmol/L

Percentage

of total

testosterone

Males values

Adults 50–210 174–729 1.0–2.7

Children

Cord blood 5–22 17.4–76.3 2.0–4.4

Newborn 1.5–31.0 5.2–107.5 0.9–1.7

4 weeks- 3.3–8.0 11.5–62.5 0.4–0.8

3 months

3–5 months 0.7–14.0 2.4–48.6 0.4–1.1

5–7 months 0.4–4.8 1.4–16.6 0.4–1.0

6–9 years 0.1–3.2 0.3–11.1 0.9–1.7

10–11 years 0.6–5.7 2.1–19.8 1.0–1.9

12–14 years 1.4–156 4.9–541 1.3–3.0

15–17 years 80–159 278–552 1.8–2.7

Female values

Adults 1.0–8.5 3.5–29.5 0.5–1.8

Children

Cord blood 4.0–16.0 13.9–55.5 2.0–3.9

Newborn 0.5–2.5 1.7–8.7 0.8–1.5

4 weeks-3 months 0.1–1.3 0.3–4.5 0.4–1.1

3–5 months 0.3–1.1 1.0–3.8 0.5–1.0

5–7 months 0.2–0.6 0.7–2.1 0.5–0.8

6–9 years 0.1–0.9 0.3–3.1 0.9–1.4

10–11 years 1.0–5.2 3.5–18.0 1.0–1.9

12–14 years 1.0–5.2 3.5–18.0 1.0–1.9

15–17 years 1.0–5.2 3.5–18.0 1.0–1.9

Increased

Androgen resistance, hirsutism, polycystic ovary

syndrome, tumor (virilizing) See also testosterone, total,

blood.

Decreased

Hypogonadism, P-450 enzyme deficiency. (See also

testosterone, total, blood.

Description

Free testosterone is that portion of circulating testosterone

that is not bound to the sex hormone-binding globulin

(SHBG) plasma protein. This test is used to differentiate

true abnormal testosterone levels from those caused by

abnormally low or high amounts of circulating SHBG. (See

also Testosterone, Total, Blood).

Increased

Adrenal hyperplasia, adrenal tumor, arrhenoblastoma,

central nervous system lesions, hirsutism (idiopathic),

hyperthyroidism, ovarian tumor (virilizing), testicular

feminization, testicular tumor, virilizing luteoma, and

virilization. In women, idiopathic hirsutism, cystic

acne, polycystic ovary syndrome, adrenogenic alopecia,

abnormal menstruation, anovulation, adrenogenital

syndrome with virilization, ovarian tumor, and SteinLeventhal syndrome with virilization. Drugs include

anticonvulsants, barbiturates, cimetidine, clomiphene,

estrogens, gonadotropin (males), and oral contraceptives.

Decreased

Anemia, cirrhosis, cryptoorchidism, Down syndrome,

gynecomastia, hypogonadism (male), hypopituitarism,

impotence, Klinefelter’s syndrome, male climacteric,

obesity, and orchidectomy. Drugs include androgens,

cyproterone, dexamethasone, diethylistilbestrol, digoxin

(males), digitalis, estrogens (males), ethanol, glucose,

glucocorticoids, gonadotropin-releasing hormone analogs,

halothane, ketoconazole, metoprolol, metyrapone, phenothiazines, spironolactone, and tetracyline.

Description

Testosterone is the dominant androgen found

in the adrenal glands, brain, ovary, pituitary, skin, kidney,

and testes. It circulates both freely, and bound to plasma

proteins (sex hormone-binding globulin [SHBG]).

Testosterone promotes the growth and development of

the male sexual organs, and increases body mass and hair

replacement. This test measures total testosterone levels in

clients with normal SHBG levels.

Interfering Factors

In adult males, an inverse correlation of free testosterone

with age occurs. The upper limit of normal range generally

decreases from the age of 20 to 60 years. The lower range of

free normal does not change significantly with age.

The Endocrine System 781

Testosterone, Total, Blood

Normal values

Male Female

ng/dL SI Units nmol/L ng/dL SI Units mmol/L

Adult 300–1200 10.4–41.6 30–95 1.0–3.3

Prepubertal values

Cord blood 13–55 0.45–1.91 5–45 0.17–1.56

Premature infant 37–198 1.28–6.87 5–22 0.17–0.76

Newborn 75–400 2.6–13.9 20–64 0.69–2.22

1–5 months 1–177 0.03–6.14 1–5 0.03–0.17

6–11 months 2–7 0.07–0.24 2–5 0.07–0.17

12 months-5 years 2–25 0.07–0.87 2–10 0.07–0.35

6–9 years 3–30 0.10–1.04 2–20 0.07–0.69

Pubertal values

Tanner stage

 1 2–23 0.07–0.80 2–10 0.07–0.35

 2 5–70 0.17–23 5–30 0.17–1.04

 3 15–280 0.52–9.72 10–30 0.35–1.04

 4 105–545 3.64–18.91 15–40 0.52–1.39

 5 265–800 9.19–27.76 10–40 0.35–1.39

STEROIDS

Estriol

Reference Values

Estriol Serum

Normal Values in ng/ml

Weeks of pregnancy

14 0.2–3.0

15 0.2–3.5

16 0.3–4.2

17 0.4–5.2

18 0.4–5.8

19 0.4–6.2

20 0.4–6.8

22 0.4–9.1

24 0.4–9.1

26 1.9–9.5

28 2.2–10.1

30 2.0–10.8

32 2.5–11.3

34 2.2–12.7

36 2.5–25.0

37 3.6–25.3

38 6.6–29.7

39 6.7–25.3

40 7.2–22.9

41 8.8–31.5

Estriol Values are Increased in

Feminizing tumors, true precocious puberty, liver cirrhosis

and multiple pregnancy. Drugs include oxytocin.

Estriol Values are Decreased in

Anencephaly, abortion, anemia, choriocarcinoma, diabetes

mellitus, erythroblastosis, fetalis, fetal adrenal aplasia,

fetal Down syndrome, fetal growth retardation, fetal

encephalopathy, gynecomastia, hepatic disease, hemoglobinopathy, hydatidiform mole, intrauterine death, menopause, postmaturity, preeclampsia, and Rh-immunization,

drugs include betamethasone, cascara, corticosteroids

(large doses), dexamethasone, diuretics, glutethimide,

estrogens, mandelamine, meprobamate, penicillins,

phenazopyridine, phenophthalein, probenecid and senna.

17-β-ESTRADIOL

Reference Values

The serum or plasma 17-β-estradiol values are comprised

in the following intervals:

Women Follicular phase 30–120 pg/mL

Ovulatory peak 150–400 pg/mL

Luteinic phase 70–200 pg/mL

Menopause < 60 pg/mL

Men < 40 pg/mL

Children < 60 pg/mL

782 Concise Book of Medical Laboratory Technology: Methods and Interpretations The measurement of estradiol is important for the

evaluation of normal sexual development (menarche),

causes of infertility (anovulation, amenorrhea, dysmenorrhea), and menopause, normal estradiol levels are

lowest at menses and into the early follicular phase and

then rise in the late follicular phase to a peak just before

the LH surge, initiating ovulation. If conception occurs,

estradiol levels continue to rise. At menopause, estradiol

levels remain low.

Estradiol is Increased in

Adrenal tumors, cirrhosis, gynecomastia in males,

hyperthyroidism, Klinefelter’s syndrome, liver tumors,

ovarian neoplasm, polycystic ovary syndrome.

Estradiol is Decreased in

Amenorrhea, anorexia nervosa, hypopituitarism, infertility,

menopause, osteoporosis, ovarian hypofunction, pituitary

disease, and polycystic ovary syndrome.

DHEAS (DEHYDROEPIANDROSTERONE

SULFATE)

Reference Values

The serum or plasma dehydroepiandrosterone sulfate

values are comprised in the following intervals:

Women (µg/mL) Men (µg/mL)

Newborns 0.9 – 1.8 0.9–1.8

Before puberty 0.25–1.0 0.25–1.0

Adults 0.9–3.6 0.9–3.6

After menopause < 0.25–1.0

Pregnancy 0.25–1.8

Values are Increased in

Adrenal cortex adenoma and carcinoma, Cushing’s

disease, ectopic ACTH-producing tumors, female acne

and hirsutism, oligomenorrhea in female athletes,

polycystic ovarian syndrome, Stein-Levinthal syndrome,

and virilizing congenital hyperplasia.

Values are Decreased in

Primary and secondary adrenal insufficiency. Low levels

in amniotic fluid indicate anencephaly in the fetus.

∆4-ANDROSTENEDIONE

Reference Values

The serum or plasma androstenedione values are

comprised in the following intervals:

seconds intervals. Maximum effect appears in 2 minutes and lasts for 3-5 minutes. If pheochromocytoma is strongly suspected, a dose of 1 mg should be administered to avoid

 Test Significance

This test is useful in detecting primary or secondary

aldosteronism. Patients with primary aldosteronism

characteristically have hypertension, muscular pains and

cramps, weakness, tetany, paralyses and polyuria.

Clinical Relevance

1. Elevated levels occur in primary aldosteronism as in:

a. Aldosterone producing adenoma

b. Adrenal cortical hyperplasia

c. Glucucorticoid remediable hyperaldosteronism.

2. Elevated levels also occur in secondary aldosteronism

when aldosterone output is elevated due to external

stimuli or because of greater activity in the reninangiotensin system as in:

a. Salt depletion

b. Potassium loading

c. Large doses of ACTH

d. Cardiac failure

e. Hepatic cirrhosis with ascites

f. Nephrotic syndrome

The Endocrine System 777

g. Bartter’s syndrome

h. Postsurgical syndrome

i. Hypovolemia and hemorrhage.

Interfering Factors

Values are increased in pregnancy and by posture.

Clinical Disorders of Mineralocorticoids

Primary Hyperaldosteronism

Primary hyperaldosteronism is usually due to

adrenocortical adenoma. The principal manifestations

of excess aldosterone secretion are hypertension and

hypokalemia. Urinary aldosterone levels are high and

plasma-renin activity is reduced or absent.

The most effective screening method is to determine

whether hypertension is due to hyperaldosteronism or not

is the serum potassium measurement. The disease must be

suspected if more than 50 mEq of potassium are excreted in

24 hours and the serum potassium level is below 3 mEq/L.

The patient should be on a high salt intake (2 g of salt with

each meal for 4 days before electrolyte measurements

and ECG are done). The electrocardiographic changes are

those of prolonged hypertension and hypokalemia.

The patient with hyperaldosteronism frequently

complains of severe headache. Potassium depletion

causes weakness, paresthesia, flaccid paralysis, polyuria,

and nocturia. Transient correction of hypokalemia by

administration of spironolactone, 400 mg daily in divided

doses for 3 days, is presumptive evidence of primary

hyperaldosteronism. A diabetic glucose tolerance curve is

present in about half of cases.

Isothenuria which does not respond to vasopressin is

also due to potassium depletion.

Sodium retention causes hypernatremia and dilutional

anemia due to increased plasma volume (low hematocrit).

Autonomic dysfunction is manifested by a postural fall in

blood pressure without changes in pulse rate.

Desoxycorticosterone acetate, 20 mg IM daily in

divided doses for 3 days, causes no change in aldosterone

production, if an aldosterone-producing tumor is present.

The measurement of plasma aldosterone can be used.

Care must be taken because of its increased response

to posture, activity, and salt restriction. The plasma

aldosterone does not normally increase 2-to 3-fold after

4 hours upright in patients with adenoma. While 83% of

patients with the syndrome of primary aldosteronism have

a solitary adenoma, the hypertension seen in patients

with hyperplasia in the remaining 17% usually does not

respond to subtotal or total adrenalectomy.

Secondary Hyperaldosteronism

Excessive secretion of aldosterone is seen in edematous

states, such as cirrhosis with ascites, nephrosis, congestive

heart failure, and toxemia of pregnancy; in non-edematous

states, such as malignant hypertension; in unilateral renal

arterial narrowing, and after diuretic therapy. Useful

differential diagnostic aids are: (i) low serum concentration,

(ii) blood volume, usually reduced in hypertensive patients,

and (iii) normal or elevated plasma-renin activity.

Isolated Hypoaldosteronism

Hyperkalemia unexplained by diminished renal function

can be the presenting finding in patients with reduced

aldosterone levels. All other adrenal steroids are normal,

and the defect resides in the defective release or production

of renin.

ADRENAL MEDULLA

The adrenal medullary hormones are catecholamines:

(i) epinephrine, and (ii) norepinephrine, the parent

compound from which epinephrine is formed by addition

of a methyl group.

Catecholamines, Plasma

Normal Values

Normal range SI units

Fractionation

Standing

Epinephrine 0–140 pg/mL 0–762 pmol/L

Norepinephrine 200–1700 pg/mL 1088–9256 pmol/L

Dopamine 0–30 pg/mL 0–163 pmol/L

Supine

Epinephrine 0–110 pg/mL 0–599 pmol/L

Norepinephrine 70–750 pg/mL 381–4083 pmol/L

Dopamine 0–30 pg/mL 0–163 pmol/L

Fractionation Free

Total 150–650 pg/mL 886–3843 pmol/L

Catecholamines, Urine

Normal Values

SI units

Random urine

Total catecholamines 0–18 µg/dL 0–103 nmol/dL

Daytime specimen

Total catecholamines

24 hours urine

1.4–7.3 µg/h 8–43 nmol/h

Contd...

778 Concise Book of Medical Laboratory Technology: Methods and Interpretations Actions

Epinephrine is sympathomimetic, increases cardiac output

and rate, systolic blood pressure, blood glucose, hepatic

glycogenolysis, basal metabolic rate, sweating, and causes

mydriasis and skin-vessel constriction. By contrast, norepinephrine causes bradycardia, peripheral vasoconstriction,

and rise in diastolic blood pressure, and has much less

prominent metabolic effects.

Clinical Disorders

Deficiency

Hypotension. Idiopathic spontaneous hypoglycemia

(failure of epinephrine response to hypoglycemia).

Excess

Paroxysmal or persistent hypertension, headaches,

sweating, tachycardia, elevated blood glucose.

Method of Evaluation

Chemical assay of epinephrine or norepinephrine

in blood or urine, provocative and blocking tests for

pheochromocytoma; glucose tolerance test; X-rays of

suprarenal area.

Adrenal medullary hyperactivity, as in pheochromocytoma, produces symptoms and signs, including

hypertension, through the release of large amounts of

epinephrine and norepinephrine into the bloodstream.

The most satisfactory single diagnostic procedure is

the discovery of plasma levels of norepinephrine in

excess of 0.5 µg/L. Jaundice, azotemia, and tetracycline

administration also cause high levels.

When pheochromocytoma is suspected and hypertension is intermittent, or the basal blood pressure is less

than 170/110, a provocative test with histamine may cause

a characteristic rise in the blood pressure and in the urine

and plasma catecholamines. Higher levels of basal blood

pressure are best investigated by the phentolamine test.

The levels of urinary catecholamines and their

metabolites (such as Vanillylmandelic acid—VMA

normetanephrine and metanephrine) are greatly increased

(10-100 times) in the presence of pheochromocytoma. The

usual 24 hours excretion of epinephrine is up to 50 mg, of

the metabolite, VMA, 2.5 µg/mg creatinine and less than

1.3 mg/24 hours for 1 ml metanephrine. The ingestion of

tea, coffee, bananas, vanilla, salicylates, phenobarbital,

fruit, morphine, iproniazid, and methocarbamol will

invalidate the VMA measurement. Tetracyclines,

vasopressors, and methyldopa can influence catecholamine determination. Monoamine oxidase inhibitors may

cause a rise in metanephrine and a low VMA. The pressor

amine output at rest is about half that during normal

daily activity. If the urine contains increased amounts of

epinephrine (40% of cases), the tumor is almost always

in one of the adrenal areas or the organ of Zuckerkandl. If

urine contains increased amounts of norepinephrine (60%

of cases), the tumor may still be expected to be in or near

one of the adrenal areas in two-third of cases; and in the

remaining one-third, all possible sites must be considered.

In both, provocative and blocking tests, control blood

pressure must be taken and the pressure must restabilize

after venipuncture before the drug is given. Hypotensive

drugs, e.g. rauwolfia, chlorothiazide, or sedatives, will

confuse the results if given within 24 hours before testing.

No diagnosis of pheochromocytoma should be based on

these tests alone.

Histamine Provocative Test

Keep phentolamine ready for a case where there is a severe

blood pressure rise in a hypertensive patient.

Method: A cold pressure test is first performed by placing

the patient’s forearm in a water-ice bath for 1 minute after

basal blood pressure reading has been taken, and then

recording postimmersion blood pressure readings at 30

seconds intervals for 3 minutes or until the basal state

Total catecholamines 0–135 µg/M2

/D2 0–796 nmol/m2

/D2

Panic level >200 µg/M2

/D2 >1180 nmol/m2

/D2

Epinephrine

Adult 0–15 µg 0–82 nmol/D

Children

Age 1–4 0–6 µg/D 0–33 nmol/D

Age 4–10 0–10 µg/D 0–55 nmol/D

Age 10–15 0.5–20 µg/D 2.7–110 nmol/D

Epinephrine > 50 µg/D > 295 nmol/D panic level

Norepinephrine

Adult 0–100 µg/D 0–590 nmol/D

Children

Age 1–4 0–29 µg/D 0–170 nmol/D

Age 4–10 8–65 µg/D 47–380 nmol/D

Age 10–15 15–80 µg/D 89–470 nmol/D

Dopamine

Age 4 years to adult 65–400 µg/D 384–2364 nmol/D

Age 4 years or less 40–260 µg/D 236–1535 nmol/D

Contd...

The Endocrine System 779

is reachieved. At this time, 0.01-0.05 mg of histamine

phosphate in 0.5 mL of isotonic saline is injected rapidly

IV, and the readings are again followed to a basal level at

30-seconds intervals.

Interpretation: Normal subjects experience flushing,

headache, and slight blood pressure fall. An elevation in

blood pressure significantly greater than the cold pressure

response within 2 minutes of the injection, or an increase

in the basal levels of plasma catecholamines following

histamine stimulation, may indicate pheochromocytoma.

Phentolamine Blocking Test

This test is used for diagnosis of pheochromocytoma in the

hypertensive phase. Barbiturates interfere with the test.

Method: When the resting patient has achieved a basal

blood pressure level, 5 mg of phentolamine are given

rapidly IV and the blood pressure is determined at 30

seconds intervals. Maximum effect appears in 2 minutes

and lasts for 3-5 minutes. If pheochromocytoma is strongly

suspected, a dose of 1 mg should be administered to avoid

profound and prolonged hypotension.

Interpretation: In normal individuals, phentolamine

causes a slight transient fall in blood pressure. In the

presence of pheochromocytoma with hypertension, a fall

in systolic blood pressure of more than 35 mm Hg and a

fall in diastolic blood pressure of more than 25 mm Hg

appearing in 2 minutes and lasting for at least 2½ minutes

is characteristic.

2. Urine should ideally be refrigerated during collection. 3. Venous blood specimen is added to a heparinized or EDTA vial. Separate the cells from plasma immediately.

 

Normal Ranges

LH:mIU/mL FSH: mIU/mL PRL:(ng/mL)

Women: 1.2 – 15.5

Follicular phase 0.8 – 10.5 3.0 – 12.0

Midcycle 18.4 – 61.2 8.0 – 22.0

Luteal phase 0.8 – 10.5 2.0 – 12.0

Postmenopausal 8.2 – 40.8 35.0 – 151.0 1.5 – 18.5

Men 0.7 - 7.4 1.0 – 14.0 1.8 – 17

Sample Collection and Storage

LH and FSH

Plasma, serum or urine can be used for LH and FSH

measurements. Both hormones are stable for 8 days

at room temperature and for 2 weeks at 4°C; for longer

periods, the specimen should be stored frozen at or below

–20°C. Because of episodic, circadian and cyclic variations

in the secretion of gonadotrophins, a meaningful clinical

evaluation of these hormones may require determinations

in pooled blood specimens, multiple serial blood

specimens, or timed urine specimens (Fig. 24.22).

Prolactin

Serum is the specimen of choice for PRL assays and can

be stored at 4°C for 24 hours. Freezing is preferred for

maintaining long-term stability. Specimens should be

collected 3 to 4 hours after the patient has awakened,

since PRL levels rise rapidly during sleep and peak in early

morning hours. Emotional stress, exercise, ambulation,

and protein ingestion also elevate PRL levels. As PRL is

secreted episodically, multiple sampling techniques may

be advantageous (e.g. pooling equal volumes of sera from

specimens drawn at 6 to 18 min intervals).

The ranges will differ from laboratory to laboratory and

depend on the reference preparation used for the standards.

The range of values is plotted on a logarithmic scale.

Measured values differ significantly, depending on the

laboratory and immunoassay system employed (Fig. 24.23).

FIG. 24.21: Epitype characterization

FIG. 24.22: The ranges will differ from laboratory to laboratory and depends on the reference preparation used for the standards.

The dotted line represents the clinically important lower range

Schematic representation of the range of basal serum gonadotropin concentrations observed in various clinical states

774 Concise Book of Medical Laboratory Technology: Methods and Interpretations The dotted line signifies the upper limit of the normal

range in many laboratories.

Hyperprolactinemia

Hyperprolactinemia is defined as consistently elevated

Prolactin levels in the absence of pregnancy or postpartum

lactation and is considered as pituitary disorder.

Prolactin is a pituitary hormone that plays a role in a

variety of reproductive functions. It is essential for normal

production of breast milk following childbirth. Also, it

negatively modulates the secretion of pituitary hormones

responsible for gonadal function.

Causes for Hyperprolactinemia

Common causes: Pituitary tumors, usually prolactinomas,

which are under 10 mm in diameter.

Primary hypothyroidism, due to increased TRH

resulting in increased TSH and Prolactin.

Ingestion of certain drugs, including phenothiazine,

certain high blood pressure medicines (a-methyldopa),

tranquilizers and opioids, anti nausea drugs, oral

contraceptives.

Chronic kidney failure and other medical conditions.

Unexplained in about 30%.

Also associated with hypogonadotropinism and

hypogonadism.

Symptoms of Hyperprolactinemia

¾ Amenorrhea

¾ Oligomenorrhea

¾ Corpus luteum dysfunction

¾ Headaches and visual difficulties

¾ Loss of libido and sexual profency in men

¾ Lowered levels of LH and FSH

¾ Symptoms of estrogen deficiency (such as those of

menopause—hot flashes, dyspareunia), even in case of

normal estrogen production

¾ Signs of increased levels of androgens in women.

Diagnosis

Basal Prolactin level can adequately be used to gauge

pituitary tumor size and be followed over time.

Serum FSH, LH and estradiol—usually low to normal in

hyperprolactinemia.

¾ TSH to rule out hypothyroidism.

¾ CT or MRI to identify microadenomas.

¾ Visual-field examination—in case of macroadenomas

(>10 mm diameter) or any patient electing medical

therapy or surveillance only.

FIG. 24.23: The range of values is plotted on a logarthmic scale. Measured values differ significantly, depending on the laboratory and

immunoassay system employed. The dotted line signifies the upper limit of the normal range in many laboratories. The arrow signifies the

clinically important lower range

Schematic representation of the range of basal serum prolacting levels (ng/ml)

observed in various pathologic and pharmacologic states

The Endocrine System 775

Treatment

For patients >100 ng/mL of prolactin and normal CT/MRI

or patients with only microadenomas—Bromocriptine or

unmedicated surveillance.

Exogenous estrogen, in some cases, to combat low

estrogen levels.

ADRENAL CORTEX

The adrenal cortex produces four major groups of

hormones: (i) glucocorticoids (cortisol, cortisone), (ii)

androgens (androstenedione, dehydroepiandrosterone),

(iii) Mineralocorticoids (aldosterone, deoxycorticosterone,

corticosterone), and (iv) estrogens and progesterone.

Adrenal corticosteroid production is controlled by

a number of factors originating in the hypothalamicpituitary system. The ACTH is the major tropic substance

of the system. Aldosterone is under minimal control of

ACTH, and its secretion is mainly influenced by volume

receptors, angiotensin II and potassium concentration.

The plasma cortisol, in turn, regulates ACTH secretion.

The direct feedback mechanism does not seem operative

for aldosterone secretion.

Cortisol-binding globulin (CBG) avidly binds cortisol

and corticosterone and is the main carrier protein at

normal concentrations. Estrogens increase CBG are

inactive but are in equilibrium with free unbound steroid.

Actions

The mineralocorticoids increase reabsorption of sodium

and chloride, increased excretion of potassium, and

allow an exchange of intracellular potassium with

extracellular sodium. Aldosterone is most effective in this

regard. The glucocorticoids affect protein, carbohydrate,

and fat metabolism, raising blood glucose, increasing

gluconeogenesis and protein catabolism (with resulting

osteoporosis), metabolising hepatic fat depots, decreasing

tubular reabsorption of urates, increasing uropepsin

secretion, and lyzing eosinophils and lymphocytes.

Clinical Disorders of Adrenal Steroids

a. Deficiency

1. Acute: Addisonian crisis, Waterhouse-Friderichsen syndrome

2. Chronic: Addison’s disease.

b. Excess

1. Principal glucocorticoids: Cushing’s syndrome.

2. Principal androgen excess: Adrenogenital syndrome in females, macrogenitosomia in males.

3. Aldosterone excess: Primary hyperaldosteronism.

Methods of Evaluation of Glucocorticoids and

Androgens

Evaluation of adrenocortical function may depend upon:

(i) physical examination, noting particularly pigmentation

of the skin and mucous membranes, pubic and axillary

hair growth, blood pressure and the presence of edema,

(ii) determination of serum sodium, potassium, chloride,

CO2, urea and protein, (iii) X-ray studies of the bones for

osteoporosis and of the adrenal region, with or without

retroperitoneal pneumography and tomography, (iv)

determination of blood and urine levels of 17-ketosteroids,

17-hydroxycorticosteroids, aldosterone and specific excretory products such as androsterone and etiocholanolone,

pregnanetriol, and pregnenetriolone, (v) specific function

tests such as the water loading test and the response of

hormone excretion levels to stimulation by exogenous

ACTH, inhibition of ACTH production by corticosteroids,

or inhibition of 11-β hydroxylation by metyrapone; and

(vi) in the absence of interfering factors, the number of

circulating eosinophils, normally between 100 and 300/ml,

varying inversely with adrenocortical activity.

Urinary 17-Hydroxycorticosteroids, 17-Ketosteroid

Excretion, Ketogenic Steroids, or Free Cortisol

The basal 24 hours urine excretion of 17-hydroxycorticosteroids is the most frequently used test in assessing

adrenocortical activity. Paraldehyde, quinine, colchicine,

iodides, sulfamerazine, and chlorpromazine interfere with

the Porter-Silber steroid determination. The 17-hydroxycorticosteroids are metabolites of cortisol and cortisone.

Urinary 17-ketosteroids are metabolites of: (i) adrenocortical steroids such as cortisol, (ii) adrenal androgens,

and (iii) gonadal androgens.

The test, hence, reflects the activity of the adrenal

cortex and the gonads in the male and the adrenal cortex

in the female. There is a diurnal variation in excretion of

17-hydroxycorticosteroids and 17-ketosteroids of adrenal

origin. The contribution of testosterone metabolites to the

ketosteroids in the urine is minimal.

The 17-ketosteroid levels determined by the Zimmermann reaction are greatly reduced by probenecid and

meprobamate administration. These drugs should be

stopped for several days before urine collection.

The patient should not be receiving androgens or cortisol

when specimens are collected. Testosterone propionate is

excreted in the urine and is measured as 17-ketosteroids,

methyltestosterone does not appear in the urine.

776 Concise Book of Medical Laboratory Technology: Methods and Interpretations Method

A 24 hours urine specimen is collected in a jug containing

5 mL of 2% thymol glacial acetic acid.

Interpretation

High levels of excretion of both 17-hydroxycorticosteroids,

17-ketosteroids, ketogenic steroids, and urinary-free

cortisol are found in adrenocortical carcinoma and

adrenocortical hyperplasia, and of 17-ketosteroids and

pregnanetriol in the adrenogenital syndrome. Low levels

of excretion are found in hypopituitarism. Addison’s

disease, myxedema, and occasionally in anorexia nervosa.

Aldosterone

Aldosterone, Serum and Urine

Normal values

Average-Sodium diet Serum SI units

Peripheral blood

 Supine 3–10 ng/dL 0.14–1.9 nmol/L

 Upright

 Adult female

 pregnant 18–100 ng/dL 0.5–2.8 nmol/L

 Nonpregnant 5–30 ng/dL 0.14–0.8 nmol/L

 Adult male 6–22 ng/dL 0.17–0.61 nmol/L

Adrenal vein

Child

 1 week–12 months 1–60 ng/dL 0.03–4.43 nmol/L

 Age 1–3 years 5–60 ng/dL 0.14–1.7 nmol/L

 Age 3–11 years 5–70 ng/dL 0.14–1.9 nmol/L

 Age 11–15 years <5–50 ng/dL <0.14–1.4 nmol/L

Urinary aldosterone

Norm urine 2–26 mg/24 h 5.6–73 nmol/day

Urinary sodium Plasma renin µg/day nmol/day

<30 nmol/day 5–24 Al/mL/h 35–80 97–220

20–50 nmol/day 2–7 Al/mL/h 13–33 36–91

50–100 nmol/day 1–5 Al/mL/h 5–24 14–66

100–150 nmol/day 0.5–4 Al/mL/h 3–19 8–53

150–200 nmol/day 1–16 3–44

200–250 nmol/day 1–13 3–36

This cholesterol-derived hormone is the most potent

of the mineralocorticoids. Its foremost physiologic

effect is that of regulating the transport of ions across

cell membranes, especially those of renal tubules. This

hormone causes the retention of sodium and chloride and

the elimination of potassium and hydrogen. The second

is the maintenance of blood pressure. Minute quantities

will depress the urinary and salivary sodium to potassium

ratio primarily because of diminished sodium excretion.

The three main factors that apparently affect aldosterone

levels include the renin-angiotensin system, the plasmapotassium concentration and ACTH. The renin-angiotensin

system appears to be the major mechanism that controls

extracellular fluid by regulation of aldosterone secretion.

Potassium loading results in increased aldosterone levels,

whereas a potassium-deficient diet in the presence of

aldosterone excess will result in a lowered aldosterone level.

Increased concentrations of potassium in the blood plasma

directly stimulate adrenal production of the hormone. The

ACTH may affect aldosterone production in conditions

of acute stress, burns, hemorrhage, and other pathologic

conditions. Under physiologic conditions, ACTH seems to

have little effect on aldosterone production.

Method

1. A 24 hours urine specimen is obtained.

2. Urine should ideally be refrigerated during collection.

3. Venous blood specimen is added to a heparinized or

EDTA vial. Separate the cells from plasma immediately.

Specimen should be obtained in the morning after the

patient has been upright for at least 2 hours.

4. Specify and record the source of the specimen (e.g.

peripheral venous, etc.).

Diuretic agents, progestational agents, estrogens, and

liquorice should be discontinued 2 weeks prior to test. The

patient’s diet for 2 weeks before the test should be normal

and include 3 gm of sodium per day.