Download Elevated prolactin levels

Dr. Abdul Hussein A. Al-Agenabi
Assistant Professor
Clinical Chemistry
Objectives of 2nd lecture
 To shed light on the normal function of ADH as
example of hypothalamic hormones.
 Draw attention to the clinical disorders that results
from abnormal ADH levels.
 The pituitary composed of 2 lobes:
 anterior lobe “ adenohypophysis”
 posterior lobe “neurohypophysis”
Posterior Pituitary:
 Hormones synthesized in the hypothalamus are
transported down the axons to the endings in the
posterior pituitary
 Hormones are stored in vesicles in the posterior
pituitary until release into the circulation
 Principal Hormones: Vasopressin & Oxytocin
Arginine-vasopressin (ADH)
ADH is a polypeptide hormone has a short half life (15-20 min) and
metabolised in kidneys and liver
In hyperosmolality e.g. during dehydration, this hormone is
released from posterior pituitary and acts on renal tubule
through special receptors enhancing water reabsorption
from tubules to the blood (without salts).
it will dilute the blood and therefore corrects osmolality, but
concentrated urine is produced.
The reverse is true:
when the subject drinks a lot of water/fluid, this will decrease
blood osmolality and inhibits ADH secretion, with more loss
of water in urine (dilute urine is produced),
Posterior Pituitary: Regulation of
Osmolality
Plasma Osmolality is monitored by osmoreceptor
in the hypothalamus
Increases in plasma Osmolality stimulates
secretion of vasopressin (ADH)
Small changes above the normal plasma osmotic
pressure (285 mosm/kg) stimulate release of
vasopressin
Disorders of ADH:
Is of 2 types:
1)
Def. of ADH
2)
Excess ADH
Disease or trauma that causes damage of hypothalamus or
posterior pituitary causes deficiency of ADH resulting in a
syndrome called Central diabetes insipidus (CDI).
Also, congenital absence of tubular receptors of ADH (renal
cause), results in a similar syndrome called nephrogenic
diabetes insipidus.
Q: Are there hormones involved in control of body
water?
Yes, Atrial natriuretric peptide (ANP), aldosterone,
prostoglandins and angiotensin II but ADH is the
most imp one
Causes of central DI
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Secretion of vasopressin is regulated at the
paraventricular & supraoptic nuclei, which sense changes
in osmolarity
Destruction of the paraventricular or supraoptic nuclei
or of the posterior pituitary results in decreased
vasopressin secretion
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Brain tumor
pituitary / cranial surgery
closed head trauma
granulomatous disease
Histiocytosis X
CNS infections
DI may be idiopathic or inherited either as an autosomal
dominant or as an autosomal recessive trait (locus
20p13)
Nephrogenic DI (NDI)
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Nephrogenic DI either acquired or hereditary.
The acquired is due to certain drugs and
chronic diseases and can occur at any time during
life.
The hereditary form is caused by genetic
mutations, and its signs and symptoms usually
become apparent within the first few months of life.
NDI arises from defective or absent receptor sites
at the cortical collecting duct segment of the
nephron or defective or absent aquaporin, the
protein that transports water at the collecting duct
Aquaporin enhances water entry into the cell from
the lumen
Absence of the vasopressin receptor does
not allow this process to take place, causing
inhibition of water uptake and polyuria
 Alternatively, defective or absent aquaporin
impairs the process in the presence of normal
V2 receptors
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Signs and symptoms
 The most common symptom of diabetes
insipidus are:
◦ Polydepsia
◦ Polyuria
◦ Nocturia & bed-wetting
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Diabetes insipidus can cause dehydration
which can cause:
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Dry mouth
Muscle weakness
Hypotension (low blood pressure)
Sunken appearance of the eyes
Weight loss
 Diabetes insipidus can also cause an electrolyte
imbalance (Hypernatremia & hyperchloremia)
 Electrolyte imbalance can cause symptoms such as
headache, fatigue, irritability and muscle pains
 Seizure secondary to Hypernatremia can happen
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Diagnostic Studies
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Diagnosis should be suspected in any patient with
sudden increased thirst & urination
Laboratory examination will reveal very diluted urine,
made up mostly of water with no solute
Examination of the blood will reveal very concentrated
blood, high in solute and low in fluid volume
◦ The serum sodium may be as high as 170
mEq/L
◦ Specific gravity of < 1.005 (low)
◦ Urine osmolality of < 100 mOsm/kg (low)
◦ Serum osmolality > 290 mOsm/kg (High)
Diagnostic Tests
 The water deprivation test is useful in patients with
polyuria.
The differential diagnosis of polyuria are:
 Diabetes insipidus (either central or nephrogenic),
 psychogenic polydipsia, or
 an osmotic diuresis (e.g., hyperglycemia ) .
 Patients who undergo the water deprivation test
should have:
 The urine volume and urine osmolality every hour
and
 Plasma sodium concentration every two hours once
water deprivation begins.
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The test is stopped when:
◦ patient has lost > 5% of original body weight
◦ patient has reached certain limits of low blood pressure &
increased heart rate
◦ urine is no longer changing significantly from one sample to
the next in terms of solute concentration
The next step of the test involves injecting a
synthetic form of ADH, with one last urine sample
examined 60 minutes later
◦ Comparing plasma and urine osmolarity allows to diagnose
either
◦ central DI,
◦ Nephrogenic DI,
◦ partial DI, or
◦ psychogenic polydepsia
These two conditions (DI or polydipsia) are
characterized by polyuria with a dilute urine
osmolarity,
 So how to distinguish between them?
If the serum sodium is high (D.I.) but if it is low
(polydipsia)
 The problem is when serum sodium is within the
normal range!!!
 This can be solved by the next step (i.e. response to
Exogenous ADH) of WDT as follow:
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In central D.I., exogenous ADH leads to a
rapid rise in urine osmolality:
 In complete D.I., the urine osm will more
than double,
 while in partial central D.I. (which is more
common) there will be an increase of at
least 15% in the urine osm.
 Generally individuals with central D.I. are
able to concentrate their urine osm >
300 mosm/kg.
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How we can differentiate between DM & DI?
 Low urine specific gravity of DI distinguish it
from DM (High urine Specific Gravity) due to
presence of urine glucose in the latter case.
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Syndrome of Inappropriate
antidiuretic Hormone (SIADH)
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The syndrome of inappropriate secretion of ADH (SIADH) is
characterized by the non-physiologic release of ADH,
resulting in impaired water excretion with normal
sodium excretion
SIADH is characterized by:
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fluid retention
serum hypo- osmolarity
dilutional hyponatraemia
hypochloremia
concentrated urine in the presence of normal or
increased intravascular volume
◦ normal renal function
Diagnosis of SIADH
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is by measurement of urine & serum
osmolarity on the same time
◦ A serum osmolarity lower than the urine
osmolarity indicates the inappropriate excretion of
concentrated urine in the presence of very dilute
serum
◦ Dilutional hyponatraemia is indicated by serum
sodium < 134mEq/l, serum osmolarity less than
280mOsm/kg & urine specific gravity > 1.005
◦ other Labs include decreased BUN, creatinine
Treatment
 If symptoms are mild & serum sodium >125
meq:
◦ treatment may be fluid restriction of 8001000ml/day
This restriction should result in
◦ a gradual daily reduction in weight,
◦ progressive rise in serum sodium concentration
and osmolality, and
◦ symptomatic improvement
GH & Prolactin
Human Growth Hormone
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Is a glycoprotein H
The half life of HGH is only 20 hours.
The level of HGH in the body
decreases with age.
It is thought that the features of aging
such as smaller muscle mass and
wrinkles is due to the small amount of
HGH.
This hormone regulates growth and
development of the body.
It is also called somatotropin
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Human Growth Hormone:The highest blood level of this hormone occurs after
Severe exercise,
Deep sleep,
Some drugs
Insulin
These Four Hypoglycemic factors have been used in
Clinical Laboratory to estimate growth hormone
level after stimulation, to diagnose HGH deficiency.
GH has 2 important functions
Growth function through somatomedins
{ IGF I and IGF II} from liver cells in response to GH.
 promote their growth effect on target tissues
(bone and cartilage) through cell membrane
receptors.
 In addition, normal growth required also good
nutrition, emotional stability, and normal thyroid
function (T3 stimulates GH gene expression &
general metabolic function).
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Metabolic function
 it stimulates protein synthesis and lipolysis
(results in increased FFA in blood which is a
preferable source of energy during growth
phase).
 but it inhibits glucose uptake by peripheral
cells causing hyperglycemia, (i.e. it is one of
insulin antagonist hormone)
Gigantism
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If too much HGH is produced during
childhood than a condition called
gigantism occurs.
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Individuals with this disorder have
abnormally long skeleton bones.
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Treatment for this disorder include;
- Surgical removal of a tumor from the
pituitary gland
- Irradiation of the gland tissue.
Acromegaly
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Acromegaly is a condition caused when an adult body produces too
much HGH.The cause of the increased production of HGH is a tumor in
the pituitary gland. Symptoms of this condition may include;
-thickening of bone tissue.
-abnormal growth of the head, hands and feet.
-spinal deformities
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Treatment of acromegaly includes:
- surgical removal of the tumor
- radiation therapy
- injection of a growth hormone blocking drugs
Q: Why we measured serum GH in laboratory?
for two abnormalities.
1) Increased GH due to pituitary tumors, childhood,
(gigantism), adulthood (acromegaly).
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Biochemical Dx:
Basal S. GH level is higher than normal but it could
be within normal level so we should do:
 1) Glucose suppression test. Acromegaly diagnose if
there is NO fall of s. hGH.
 2) Plasma IGF-1 has long half life and it increased
with severity of disease.
 GH & IGF can be used in monitoring of Rx of
acromegaly.
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2. GH dysfunctions: results in short- stature [dwarfism]
Is of 2 types;
 GH-deficiency dwarfs w is due to true deficiency of
GH (because of pituitary damage or hypothalamic
disease)
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So both GH & IGF-1 levels are low
They respond well to GH therapy.
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GH insensitivity dwarfs caused by deficiency of
liver GH receptors [Laron dwarfs] or loss of IGF-1
response to GH i.e. loss of post-receptor response
[Pygmies dwarfs ]
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These patients have low IGF-1 but normal or high serum
GH level.
They not respond to GH therapy.
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Decreased GH (short stature), is due to
pituitary deficiency of GH
Lab Diagnostic Tests
Basal serum GH level…..if within high normal
range exclude hGH def.
 But low levels not confirm hGH def
 So we sd do GH provocation
(Stimulation)Test after exercise or
administration of drugs ex: clondine, arginine,
glucagon or insulin
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Prolactin
 polypeptide
hormone, also produced by the anterior
pituitary, stimulates the development of mammary
gland tissue and milk production (lactogenesis).
 The
hypothalamus secretes a hormone called
dopamine which inhibits the production of prolactin.
 In late pregnancy, an increase in estrogen will
stimulate prolactin production.
 Also, after a child is born breast feeding stimulates
nerve endings in the nipples which stimulates the
hypothalamus to release prolactin secreting
hormones.
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Prolactin :
It stimulates milk production from the breasts.
Q: Why we measured serum prolactin in
laboratory?
To investigate patients with
Galactorrhea (abnormal breast milk production),
Headaches,
Visual problems,
Irregular bleeding (menses) and
Infertility.
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Q: Is any elevation in serum prolactin level is
pathological?
No/ sometimes it is temporarily elevated after:
Eating,
Stress,
Sexual excitement and
Certain drugs.
If an elevation of prolactin is discovered, it should
be repeated to confirm or exclude the diagnosis.
Elevated prolactin levels cause: irregular periods,
and infertility. How?
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Elevated prolactin causes anovulation by interfering
with the normal release of FSH and LH from the
pituitary.
i.e. high levels of prolactin suppress GnRH of
hypothalamus and so associated with low LH and
FSH levels in blood.
Increased prolactin levels (through its effect on FSH) can
interfere with clomiphene’s effectiveness so it can
decreases the chance of pregnancy in treatment of
infertile that is, if it is elevated it should be treated.
Elevated prolactin not only has risk of
infertility, but it leads to:
1. Thickening of the endometrium
(endometrial hyperplasia or carcinoma)
because of unopposed estrogen effects.
2. Osteoporosis and heart diseases because
of the generally lower estrogen levels.
Q: Does PRL level affected by menstrual
cycle? And does it affect menstruation?
Yes; it causes irregular cycle and
amenorrhea. How?????
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