Pituitary Gland

Normal pregnancy:
the pituitary gland enlarges by ~135%
changes in vision are minimal
Note: the incidence of pituitary prolactinomas
is not increased during pregnancy
When these tumors are large before pregnancy
(a macroadenoma is 10 mm or greater) then
enlargement during pregnancy is more likely
Pituitary Gland
The maternal pituitary gland is not essential for
maintenance of pregnancy
Many women have undergone hypophysectomy,
completed pregnancy successfully, and
undergone spontaneous labor while receiving
glucocorticoids along with thyroid hormone and
vasopressin
Pituitary Gland
Growth Hormone:
1st trimester growth hormone is secreted
predominantly from the maternal pituitary gland;
concentrations in serum and amnionic fluid are
within nonpregnant values (0.5 - 7.5 ng/mL)
8 weeks growth hormone secreted from the
placenta becomes detectable
Pituitary Gland
~17 weeks the placenta is the principal source
of growth hormone secretion
Maternal serum values increase slowly from ~3.5
ng/mL at 10 weeks to plateau after 28 weeks at
~14 ng/mL
Growth hormone in amnionic fluid peaks at 14 to
15 weeks and slowly declines thereafter to reach
baseline values after 36 weeks
Pituitary Gland
Although growth hormone is abundant in the fetal
circulation, at least in the second half of gestation,
it has not been considered to be a major
hormonal regulator of fetal growth
anencephalic fetuses cannot produce significant
amounts of pituitary growth hormone, yet they
usually have near normal weight and length
Pituitary Gland
Chellakooty and co-investigators the first
to demonstrate that the rate of fetal growth
significantly correlated with the increase in
placental growth hormone in the latter half of
pregnancy
they also found that the gestational age when peak
concentrations of placental growth hormone were
reached was associated with the onset of labor
After delivery growth hormone is elevated for
some time but at levels lower than during late
pregnancy
Pituitary Gland
Prolactin:
Plasma levels increase markedly during the course
of normal pregnancy
Serum concentration levels are usually 10-fold
greater at term (about 150 ng/mL)
After delivery the plasma prolactin
concentration decreases even in women who are
breast feeding
Early lactation pulsatile bursts of prolactin
secretion occur apparently in response to suckling
Pituitary Gland
Physiological cause: not entirely certain
It is known, however, that estrogen stimulation
increases the number of anterior pituitary
lactotrophs and may stimulate the release of
prolactin from these cells
Thyroid-releasing hormone cause an
increased prolactin level; the response decreases
as pregnancy advances
Serotonin also believed to increase prolactin
Prolactin-inhibiting factor (dopamine)
inhibits secretion of prolactin
Pituitary Gland
Principal function: to ensure lactation
Early in pregnancy it initiates DNA synthesis
and mitosis of glandular epithelial cells and the
presecretory alveolar cells of the breast
It also increases the number of estrogen and
prolactin receptors in these same cells
Prolactin also promotes mammary alveolar
cell RNA synthesis, galactopoiesis, and
production of casein and lactalbumin,
lactose and lipids
Thyroid Gland
Important changes in thyroidal economy:

Pregnancy induces a marked increase in circulating

levels of the major thyroxine transport protein
(thyroxine-binding globulin) in response to high
estrogen levels
Several thyroidal stimulatory factors of placental
origin are produced in excess
Pregnancy is accompanied by a decreased
availability of iodide for the maternal thyroid
Thyroid Gland
During pregnancy, the thyroid undergoes moderate
enlargement caused by glandular hyperplasia
and increased vascularity
Glinoer and colleagues (1990) found that mean
thyroid volume increased from 12.1 mL in the first
trimester to 15.0 mL at delivery
Total volume was found to be inversely proportional
to serum thyrotropin concentration
These enlargements are not pathological and normal
pregnancy does not typically cause significant
thyromegaly, thus, any goiter should be investigated
Thyroid Gland
Beginning early in the first trimester, thyroxine-
binding globulin increases, reaches its zenith at
about 20 weeks, and stabilizes at
approximately double baseline values for the
remainder of pregnancy
Total serum thyroxine (T4) increases sharply
beginning between 6 and 9 weeks, and reaches
a plateau at 18 weeks
Thyroid Gland
Free serum T4 levels rise slightly and peak along
with hCG levels, then they return to normal
The rise in total triiodothyronine (T3) is
more pronounced up to 18 weeks, and
thereafter, it plateaus
Thyroid-releasing hormone (TRH) levels
are not increased during normal pregnancy, but
this neurotransmitter does cross the placenta
and may stimulate the fetal pituitary to secrete
thyrotropin
Thyroid Gland
The secretion of T4 and T3 is not similar for all
pregnant women
Approximately 1/3 of women experience:
relative hypothyroxinemia
preferential T3 secretion
higher, albeit normal, serum thyrotropin levels
Thyroid Gland
hCG the -subunits of the two glycoproteins
are identical whereas the -subunits, although
similar, differ in their amino acid sequence
hCG has intrinsic thyrotropic activity, and
thus, high serum levels cause thyroid
stimulation
Thyrotropin levels decrease in more than 80%
of pregnant women, even though levels are in
the normal range for nonpregnant women
Thyroid Gland
These many complex alterations in thyroid
regulation during pregnancy do not appear to alter
maternal thyroid status as measured by metabolic
studies
Although BMR increases progressively during
normal pregnancy by as much as 25%, most of this
increase in oxygen consumption can be attributed to
fetal metabolic activity
If fetal body surface area is considered along with
that of the mother, the predicted and observed BMR
are quite similar to nonpregnant women
Parathyroid Glands
The regulation of calcium concentration is closely
interrelated to magnesium, phosphate,
parathyroid hormone, vitamin D, and calcitonin
physiology
Any alteration of one of these factors is likely to change
the others
In a longitudinal investigation of 20 women, More and
associates (2003) found that all markers of bone
turnover increased during normal pregnancy and failed
to reach baseline level by 12 months postpartum
They concluded that the calcium needed for fetal growth
and lactation may be drawn at least in part from the
maternal skeleton
Parathyroid Gland
Parathyroid Hormone and Calcium
Acute or chronic decreases in plasma calcium
or acute decreases in magnesium release
of parathyroid hormone
Increase in calcium and magnesium
suppression of parathyroid hormone levels
Parathyroid Gland
Parathyroid hormone plasma concentrations:
decrease during the first trimester
increase progressively throughout the remainder of
pregnancy
Increased levels likely result from the lower
calcium concentration in the pregnant woman
This is the result of:
increased plasma volume
increased glomerular filtration rate
maternalfetal transfer of calcium
Parathyroid Gland
Ionized calcium is decreased only slightly, and Reitz
and co-workers (1977) suggest that during
pregnancy a new "set point" is established for
ionized calcium and parathyroid hormone
Estrogens block the action of parathyroid
hormone on bone resorption, resulting in another
mechanism to increase parathyroid hormone during
pregnancy
Net result:
physiological hyperparathyroidism of
pregnancy
Parathyroid Gland
Calcitonin and Calcium
Calcitonin-secreting C cells derived
embryologically from the neural crest and are
located predominantly in the perifollicular areas
of the thyroid gland
Calcium and magnesium increase the
biosynthesis and secretion of calcitonin
Other factors that increase calcitonin levels:
Gastric hormones (gastrin, pentagastrin,
glucagon, and pancreoxymin)
Food ingestion
Parathyroid Gland
Action of calcitonin oppose those of
parathyroid hormone and vitamin D to protect
skeletal calcification during times of calcium
stress
Pregnancy and lactation cause profound
calcium stress calcitonin levels are appreciably
higher than in nonpregnant women
Parathyroid Gland
Vitamin D and Calcium

1,25-
dihydroxyvitamin D3
Vit. D (kidney, decidua and
(ingested/synthesized in the skin) placenta)

25-hydroxyvitamin
D3
(converted in the liver)
Parathyroid Gland
Most likely this form is the biologically active
compound, and it stimulates resorption of calcium
from bone and absorption from the intestines
Conversion of 25-hydroxyvitamin D3 to 1,25-
dihydroxyvitamin D3
facilitated by parathyroid hormone and by low
calcium and phosphate plasma levels
opposed by calcitonin
Adrenal Glands
Cortisol
The serum concentration of circulating cortisol is
increased
Much of it is bound by cortisol-binding globulin or
transcortin
Rate of adrenal cortisol secretion: not increased;
probably it is decreased
Metabolic clearance rate of cortisol: lower
during pregnancy because its half-life is nearly
doubled over that for nonpregnant women
Administration of estrogen (oral contraceptives)
causes changes in serum cortisol levels and
transcortin similar to those of pregnancy
Adrenal Glands
Early pregnancy the levels of circulating
corticotropin (ACTH) are reduced strikingly
As pregnancy progresses, the levels of ACTH and
free cortisol rise
Nolten and Rueckert (1981) have presented
evidence that the higher free cortisol levels
observed in pregnancy are the result of a
"resetting" of the maternal feedback mechanism to
higher levels
They further propose that this might result from
tissue refractoriness to cortisol
Adrenal Glands
Keller-Wood and Wood (2001) later suggested
that these may result from an antagonistic
action of progesterone on
mineralocorticoids
Thus, in response to elevated progesterone levels
during pregnancy, an elevated free cortisol is
needed to maintain homeostasis
Adrenal Glands
Aldosterone
15 weeks the maternal adrenal glands secrete
considerably increased amounts of aldosterone
3rd trimester about 1 mg/day is secreted
Sodium intake restriction aldosterone secretion
is elevated
Levels of renin and angiotensin II substrate
normally are increased, especially during the
latter half of pregnancy
Adrenal Glands
This scenario gives rise to increased plasma levels
of angiotensin II, which by acting on the zona
glomerulosa of the maternal adrenal glands,
accounts for the markedly elevated aldosterone
secretion
Increased aldosterone secretion affords
protection against the natriuretic effect of
progesterone and atrial natriuretic peptide
Adrenal Glands
Deoxycortisone
It is progressively increases during pregnancy
Plasma levels of deoxycorticosterone rise to near 1500
pg/mL by term, a more than 15-fold increase
The marked elevation is not derived from adrenal
secretion; it represents increased kidney production
resulting from estrogen stimulation
The levels of deoxycorticosterone and its sulfate in fetal
blood are appreciably higher than those in maternal
blood, which suggests transfer of fetal
deoxycorticosterone into the maternal compartment
Adrenal Glands
Dehydroepiandrosterone Sulfate
The levels of dehydroepiandrosterone sulfate
circulating in maternal blood and excreted in the
urine are decreased during normal pregnancy
It is a consequence of increased metabolic
clearance through extensive 16-hydroxylation
in the maternal liver and conversion to
estrogen by the placenta
Adrenal Glands
Androstenedione and Testosterone
Androgens increased during pregnancy
This finding is not totally explained by alterations
in their metabolic clearance
Maternal plasma androstenedione and
testosterone are converted to estradiol in
the placenta, which increases their clearance
rates
Conversely, the increased sex hormone
binding globulin in plasma of pregnant women
retards testosterone clearance
Adrenal Glands
Thus, the plasma production rate of maternal
testosterone and androstenedione during
human pregnancy are increased
The source of this increased C19-steroid
production is unknown, but it likely originates in
the ovary
Little or no testosterone in maternal plasma
enters the fetal circulation as testosterone
Adrenal Glands
Even when massive testosterone levels are found
in the circulation of pregnant women, as with
androgen-secreting tumors, the testosterone levels
in umbilical cord venous plasma are likely to be
undetectable
This finding is the result of the near complete
conversion of testosterone to 17-estradiol by the
trophoblast
Musculoskeletal System
Progressive lordosis is a characteristic feature
of normal pregnancy
Compensating for the anterior position of the
enlarging uterus, the lordosis shifts the center of
gravity back over the lower extremities
Sacroiliac, sacrococcygeal, and pubic joints
have increased mobility during pregnancy
Marnach and co-workers (2003) found that
although joint laxity increased during pregnancy, it
did not correlate with maternal estradiol,
progesterone, or relaxin levels
Musculoskeletal System
Joint mobility may contribute to the alteration of
maternal posture, and in turn cause discomfort in
the lower back
This is especially bothersome late in pregnancy,
during which time aching, numbness, and
weakness also occasionally are experienced in the
upper extremities
This may occur as a result of the marked lordosis
with anterior neck flexion and slumping of the
shoulder girdle, which in turn produce traction on
the ulnar and median nerves
Musculoskeletal System
The bones and ligaments of the pelvis undergo
remarkable adaptation during pregnancy
In 1934, Abramson and colleagues described the
normal relaxation of the pelvic joints, and
particularly the symphysis pubis, that occurs during
pregnancy
They reported that most relaxation takes place in
the first half of pregnancy
Retrogression begins immediately following
delivery, and it is usually complete within 3 to 5
months
Eyes
Intraocular pressure decreases during
pregnancy
attributed in part to increased vitreous outflow
Corneal sensitivity decreased; the greatest
changes late in gestation
Most pregnant women demonstrate a
measurable but slight increase in corneal
thickness that is thought to be due to edema
Pregnant women may have difficulty with
previously comfortable contact lenses
Eyes
Brownish-red opacities on the posterior
surface of the cornea (Krukenberg spindles)
have also been observed with a higher than
expected frequency during pregnancy
Hormonal effects are postulated as the cause of
this increased pigmentation
Other than transient loss of
accommodation reported with both
pregnancy and lactation, visual function is
unaffected by pregnancy
Central Nervous System
Women often report problems with:
attention
concentration
memory
Pregnancy-related memory decline limited
to the third trimester
This decline was not attributable to depression,
anxiety, sleep deprivation, or other physical changes
associated with pregnancy
It was transient and quickly resolved following
delivery
Central Nervous System
Zeeman and co-workers (2003) used MRI to
measure cerebral blood flow across pregnancy in 10
healthy women
They found that mean blood flow bilaterally in the
middle and posterior cerebral arteries decreased
progressively from 147 and 56 mL/min when
nonpregnant to 118 and 44 mL/min late in the
third trimester, respectively
The mechanism and clinical significance of this
decrease is unknown
Central Nervous System
About 12 weeks to the first 2 months
postpartum women have difficulty going to sleep,
frequent awakenings, fewer hours of night sleep and
reduced sleep efficiency
Trakada and co-workers (2003) found that during
normal pregnancy, the frequency and duration of
sleep apnea episodes were decreased
significantly compared with those postpartum
In the supine position, however, average PaO2 levels
were lower
The greatest disruption of sleep is encountered
postpartum and may contribute to postpartum blues,
or even frank depression