These hormones control the release of anterior pituitary hormones. The release of these factors is controlled by feedback from the target organ hormone to maintain the

 

ADH

It is also known as vasopressin. In the presence of ADH,

the kidneys reabsorb more water from the forming urine

within renal tubules. Without ADH the kidney tubules

are almost completely impermeable to water such that a

very dilute urine is excreted (diabetes insipidus). The ADH

has a direct effect on vascular smooth muscle causing

vasoconstriction and an increase in blood pressure when

present in large doses. They are stimulated by a high blood

osmolarity (increased concentration) causing the release

of ADH. The hormone then causes the kidney tubules

to reabsorb more water to return osmolarity to normal.

Volume receptors also play a role when they sense a low

blood pressure. Alcohol inhibits ADH secretion.

Normal Values

Serum osmolarity ADH level SI units

270–280 mOsm/kg <1.5 pg/mL <1.4 pmol/L

280–285 mOsm/kg <2.5 pg/mL <2.3 pmol/L

285–290 mOsm/kg 1–5 pg/mL 0.9–4.6 pmol/L

290–295 mOsm/kg 2–7 pg/mL 1.9–6.5 pmol/L

295–300 mOsm/kg 4–12 pg/mL 3.7–11.1 pmol/L

The ADH elaboration is initiated by increase in the

extracellular fluid osmotic pressure, by direct nervous

system stimulation of the hypothalamus; and to a minor

degree, by extracellular fluid volume. It is formed by the

neurosecretory cells in the supraoptic and paraventricular

nuclei of the hypothalamus, and travels along axons to the

posterior lobe, where it is stored. Lesions at any of these

sites interfere with ADH release to the body.

Clinical Disorders

A. Deficiency of ADH: ADH deficiency produces diabetes

insipidus if the anterior pituitary is still functioning.

B. Excess ADH: Inappropriate ADH secretion syndrome.

Methods of Evaluation

Deficiency

Study for intracranial lesion (lumbar puncture, skull

film, EEG), STS, chest X-ray (metastasis), bone marrow

examination (multiple myeloma, eosinophilic granuloma).

However, 45% are classified as idiopathic. Differentiate

diabetes insipidus (10 to 15% cases) by administration of

vasopressin. The simple measurement of a urine volume

of more than 5 liters/day is strong presumptive evidence

of deficiency.

1. Water restriction

Though quite simple, careful supervision is necessary

so that losses of 3 to 5% of body weight are avoided.

Greater care has to be exercised in children. Volume

and concentration (specific gravity or mOsm/kg) are

The Endocrine System 737

determined at each voiding. Urine flow should reach less

than 0.5 mL/minute, and urine concentration should be

greater than 800 mOsm/kg (specific gravity 1.020).

2. Hypertonic saline test

(Carter-Robbins test, Hickey-Hare test)

This test is used to differentiate psychogenic polydipsia

from diabetes insipidus. Here again caution is needed, since

dehydration may cause vasomotor collapse in patients with

diabetes insipidus. Administration of hypertonic saline

solution may be hazardous in cardiac or renal disease.

Antidiuretic therapy is stopped until urine output reaches

its original level. The patient may be cautiously dehydrated

for 8-12 hours or this step may be omitted. Just before the

test, the patient drinks 20 mL of water per kg of body weight

in 1 hour. Urine is collected at 15 minutes intervals.

When the urine flow exceeds 5 mL/min, 2.5% saline

solution is given IV at a rate of 0.25 mL/kg body weight/

min for 45 minutes.

In normal subjects and in psychogenic polydipsia, a

marked reduction in urinary flow will occur during the

saline infusion or during the two 15 minutes intervals

immediately following it.

In 85 to 95% of patients with true diabetes insipidus,

the urine flow does not decrease with the saline infusion,

but administration of 0.1 unit of vasopressin will inhibit

diuresis in the absence of renal disease.

3. Response to vasopressin

This test also differentiates diabetes insipidus from

vasopressin-resistant polyuria due to other causes, e.g.

a. Potassium depletion

b. Hypercalcemia

c. Chronic renal disease

d. Congenital nephrogenic diabetes insipidus

e. After renal transplantation

f. Sjögren’s syndrome

g. Obstructive uropathy.

Urine volume and specific gravity, and symptoms of

polyuria and polydipsia are observed before and after

repeated subcutaneous injections of 0.2 mL (4 units)

vasopressin every 3 or 4 hours day and night for 24 hours,

or before and after a 1 hour of infusion of aqueous vasopression (5 µm/minute).

Patients with chronic nephritis or vasopressin-resistant

diabetes insipidus experience no relief of symptoms during

test period. In diabetes insipidus or psychogenic polydipsia,

symptoms may improve, urine volume may decrease, urine

specific gravity may increase to 1.015 or more, and urine

osmolality may rise above serum osmolality.

4. Nicotine stimulation

Various side effects (nausea, vomiting and sweating) limit

the usefulness of this test. Give 0.5–1 mg IV of nicotine base

to non-smokers and doses as high as 3 mg IV to habitual

smokers undergoing water diuresis. The normal response

to intravenous nicotine is secretion of vasopressin,

80% reduction in urine flow, and rise in osmolality.

Responsiveness to nicotine but not to hypertonic

saline stimulus suggests that osmoreceptor centers are

functionally separate from vasopressin sensory centers.

Syndrome of Inappropriate ADH Secretion (SIADH)

Hyponatremia is a frequently observed laboratory finding

in severely ill patients. The recognition of SIADH is critical

to their management. Findings consist of hyponatremia,

normal BUN, urinary sodium loss, competent circulatory

system, and increased urinary osmolality. These findings

are similar to the observations made after exogenous

administration of ADH to man. This syndrome is seen

most frequently in pulmonary neoplasms, but it is

reported in CNS disorders, tuberculous meningitis, head

trauma, pneumonia, intrathoracic tumors, myxedema,

acute intermittent porphyria, sickle cell anemia, cerebral

thrombosis and postoperative ADH release after morphine

or barbiturates. Neoplastic tissue in some cases has been

shown to possess ADH activity.

Oxytocin

A major role of this hormone is the stimulation of smooth

muscle cells in the pregnant uterus. When labor begins,

stretching of the cervix and vagina stimulates a reflex

production and release of oxytocin. Oxytocin then travels

in the blood to the uterus where it causes more forceful

contraction of the smooth muscle. This hormone is also

involved in lactation. It causes milk ejection by acting on

the smooth muscle surrounding the milk producing cells.

Again, its production and release is mediated by a neural

reflex, the suckling reflex. Emotion, anxiety and pain can

inhibit oxytocin release.

Feedback Mechanism

738 Concise Book of Medical Laboratory Technology: Methods and Interpretations DISORDERS OF THE PITUITARY SYSTEM

It is of two types:

Underproduction of hormones—hypopituitarism.

Overproduction of hormones—pituitary adenoma

(micro and macroadenoma)

The effects of these disorders vary with the hormone

and the target organ of action.

1. TSH Disorders

Hypothyroidism: Secondary or subclinical hypothyroidism.

Hyperthyroidism: TSH-secreting tumor leading to hyperthyroidism.

2. Prolactin Disorders

Hyperprolactinemia: Consistently elevated serum prolactin

(PRL>20 ng/mL) in the absence of pregnancy or postpartum

lactation.

Etiology: Prolactinoma, acromegaly, Cushing’s disease,

lactotroph hyperplasia, empty sella syndrome, other

pituitary tumors, hypothalamic disease, pharmacologic

agents, macroprolactinemia.

3. Gonadotropin Disorders

Excess and reduced production of gonadotrophs manifests

as fertility disorders. The hormones control gametogenesis

in males and females at different levels together with

negative feedback mechanism of the hypothalamus.

4. Growth Hormone Disorders

The symptoms of GH deficiency in adults are subtle,

consisting of decreased muscle strength and exercise

tolerance and a reduced sense of well-being (e.g. diminished

libido, social isolation). Patients with GH deficiency have

increased body fat, particularly intra-abdominally, and

decreased lean body mass compared with normal adults.

Some patients have decreased bone mineral density, which

may improve with GH replacement.

HYPOTHALAMUS

Anterior pituitary functions are controlled by the region

of the brain called the hypothalamus via the secretion

of releasing and inhibiting factors. Specialized neurons

in the hypothalamus, controlled by feedback and other

communication methods release factors that cause the

release of hormones from the anterior pituitary. The

pituitary trophic hormones then control the release of

other hormones from a target gland. With the exception of

prolactin, release promoting factors are more important to

the release of pituitary hormones.

¾ Somatostatin (inhibits GH release)

¾ Prolactin-inhibiting factor (PIF, dopamine)

¾ LH-releasing factor (LHRF)

¾ FSH-releasing factor (FSHRF)

¾ Prolactin-releasing factor (PRF)

¾ Corticotropin-releasing factor (CRF)

¾ Thyrotropin-releasing hormone (TRH).

These hormones control the release of anterior pituitary

hormones. The release of these factors is controlled by

feedback from the target organ hormone to maintain the

proper hormonal balance.

ADRENAL (SUPRARENAL) GLAND

The suprarenal glands are located on top of each of the

kidneys. The adrenal cortex (outer portions) produces four

major groups of hormones:

¾ Glucocorticoids: Cortisol, cortisone.

¾ Androgens: Androstenedione, dihydroepiandrostenedione (DHEA)

¾ Mineralocorticoids: Aldosterone, deoxycorticosterone,

corticosterone

¾ Estrogens and progesterones.