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Diagnosis About Hyperemesis | Mothers | Family & Friends | Health Professionals | About H.E.R
Treatments
Risks & Outcomes
Complications
About Hyperemesis Gravidarum
Impact of HG
Hyperemesis gravidarum (HG) is similar to a severe form of morning sickness. HG is
generally described as unrelenting, excessive pregnancy-related nausea and/or vomiting that
prevents adequate intake of food and fluids. If severe and/or inadequately treated, it is
typically associated with:

loss of greater than 5% of pre-pregnancy body weight (usually over 10%)

dehydration and production of ketones

nutritional deficiencies

metabolic imbalances

difficulty with daily activities

HG usually extends beyond the first trimester and may resolve by 21 weeks; however, it can
last the entire pregnancy in less than half of these women. Complications of vomiting (e.g.
gastric ulcers, esophageal bleeding, malnutrition, etc.) may also contribute to and worsen
ongoing nausea.

There are numerous theories regarding the etiology of hyperemesis gravidarum.

Unfortunately, HG is not fully understood and conclusive research on its potential cause is
rare. New theories and findings emerge every year, substantiating that it is a complex
physiological disease likely caused by multiple factors.

Diagnosis is usually made by measuring weight loss, checking for ketones, and assessing
the overall condition of the mother. If she meets the standard criteria and is having difficulty
performing her daily activities, medications and/or other treatments are typically offered.

Treating HG is very challenging and early intervention is critical. HG is a multifaceted

disease that should be approached with a broad view of possible etiologies and complications.
When treating mothers with HG, preventing and correcting nutritional deficiencies is a high
priority to promote a healthy outcome for mother and child.

Most studies examining the risks and outcomes for a pregnant woman with nausea and
 vomiting in pregnancy find no detrimental effects long-term for milder cases. Those with
more severe symptoms that lead to complications, severe weight loss, and/or prolonged
nausea and vomiting are at greatest risk of adverse outcomes for both mother and child. The
risk increases if medical intervention is inadequate or delayed.

The list of potential complications due to repeated vomiting or severe nausea is extensive,
all of which may worsen symptoms. Common complications from nausea and vomiting include
debilitating fatigue, gastric irritation, ketosis, and malnutrition. Aggressive care early in
pregnancy is very important to prevent these and more life-threatening complications such as
central pontine myolinolysis or Wernicke's encephalopathy. After pregnancy and in
preparation of future ones, it is important to address any resulting physical and psychological
complications.

Hyperemesis Gravidarum impacts societies, families and individuals. Recent,

conservative estimations suggest HG costs nearly $200 million annually just for inpatient
hospitalization. Considering many women are treated outside the hospital to save costs, the
actual cost is likely many times greater. Beyond financial impact, many family relationships
dissolve and future family plans are almost always limited. Women often lose their
employment because of HG, and women are frequently undertreated and left feeling
stigmatized by a disease erroneously presumed to be psychological.

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About Hyperemesis

HCG & Estrogen

Hormones
About Hyperemesis | Mothers | Family & Friends | Health Professionals | About H.E.R
Psychological Causes
Thyroxine Levels
Gastric Neuromuscular Theories & Research
Dysfunctions
Deficiences of Nutrients
There are numerous theories regarding the etiology of HG, however, none are as of yet,
Other Theories & Links
conclusive. Determining a cause is very difficult and most likely not due to only one factor. It
may vary between women depending on her biological make-up (genetics), body chemistry,
and her overall health. However, as is common in poorly understood disorders, a
psychological cause is named when a physiological one is not known. This is especially true
when so many of the symptoms like nausea are not subjectively measurable. It is thus easy
to dismiss a woman's symptoms as being psychological, exaggerated, or imaginary, when in
fact they are very real and may in fact be very severe. However, accurately determining
severity is difficult, especially if there is not obvious "proof" of how sick a woman is. Proof,
such as severe weight loss or dehydration, often comes after she is very sick for some time,
and it is then more difficult to manage her symptoms.

Currently, many theories are tested and new ones emerge every year. Most center around
known pregnancy-related factors like hormonal changes (e.g. estrogen increase) and physical
changes (e.g. relaxed esophageal sphincter), since the onset is related to pregnancy and
ends before or at delivery. The research is limited and minimal funding is allotted for
hyperemesis research, so high-quality studies with decisive results are uncommon.

Human Chorionic Gonadotropin (hCG) & Estrogen Hormones

Most theories center around the increase in hCG & estrogen hormones like progesterone in early
pregancy.

Psychological Causes
Some mistakenly state pyschological causes, but most if not all women experience pyschological
effects (e.g.: frustration, feelings of helplessness, isolation, depression, etc.) secondary to HG.

Thyroxine Levels
Increase in serum thyroxine levels have been documented in 70% of pregancies complictaed by
HG.

Gastric Neuromuscular Dysfunctions

A recent theory cites a dysfunction that results in regurgitation of duodenal content back into the
stomach and subsequent naseau and vomiting.

Deficiencies of Nutrients
Another theory attributes HG to deficiencies of pyridoxine and zinc, though results are not
conclusive.

Other Theories & Resource Links

Links & abstracts to various other physiological and immunological theories.

Home About Hyperemesis Theories & Research

Copyright 2000-2003 H.E.R. Foundation

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Updated on: Sep. 05, 2003

 Site Search

Site Map | Contact Us

Theories & Research

HCG & Estrogen

Hormones
About Hyperemesis | Mothers | Family & Friends | Health Professionals | About H.E.R
Psychological Causes
Thyroxine Levels
Gastric Neuromuscular Human Chorionic Gonadotropin (hCG) & Estrogen
Dysfunctions
Deficiences of Nutrients
Hormones
Other Theories & Links
Hormonal changes are the most studied theory but fail to show consistency among all women
with HG. Most studies focus on the changes in hCG and steroid hormones like cortisol,
estrogen, and progesterone in early pregnancy because onset and peak of symptoms
correlate with elevations in these hormones.

Psychological Causes

Offsite Research:

Human Chorionic Gonadotropin and Hyperemesis Gravidarum

T. Murphy Goodwin, MD

There are a number of reasons for considering the association of human chorionic gonadotropin (hCG)
with hyperemesis gravidarum. The temporal relationship between peak hCG levels and the most
common time of nausea and vomiting has long been noted. More recently, the relationship of hCG to
transient hyperthyroidism of hyperemesis gravidarum (THHG) has been described. Several experiments
of nature have suggested that hCG plays a role. We will consider these interrelated lines of evidence.

Pathophysiology of the gastrointestinal tract during pregnancy

Singer AJ, Brandt LJ.
Department of Medicine, Montefiore Hospital and Medical Center, Albert Einstein College of
Medicine, Bronx, New York.
Am J Gastroenterol 1991 Dec;86(12):1695-712

Pregnancy is associated with a wide variety of physiologic changes in virtually all the organ systems of
the body. Some of these changes, such as the hyperventilation of pregnancy with its resulting
respiratory alkalosis, are clinically silent, whereas others, such as heart-burn and hemorrhoids, cause
significant distress. The effects of pregnancy on the hepatobiliary system have been the subject of much
scrutiny and many publications, whereas disturbances of the hollow viscera have been infrequently
reviewed. In this report, we will discuss the major pathophysiologic changes that occur along the length
of the hollow viscera of the gastrointestinal tract during pregnancy.
 Serum chorionic gonadotrophin (hCG), schwangerschaftsprotein 1 (SP1),
progesterone and oestradiol levels in patients with nausea and vomiting in early
pregnancy.
Masson GM, Anthony F, Chau E.
British Journal of Obstetrics Gynaecology. 1985 Mar;92(3):211-5

Serum concentrations of human chorionic gonadotrophin (hCG), schwangerschaftsprotein 1(SP1),

progesterone and oestradiol were measured in 116 pregnant women experiencing varying degrees of
nausea and vomiting or no nausea at all at between 9 and 16 weeks gestation. The patients were
categorized into four groups, namely asymptomatic, nausea alone, nausea and vomiting and
hyperemesis gravidarum. The distribution of levels for each group were examined in relation to the
calculated normal ranges. Statistically higher hCG levels were found in out-patients with nausea alone or
nausea and vomiting than in the asymptomatic women. No significant differences were found between
the groups for any of the other measured variables, including the progesterone/oestradiol concentration
ratio.

Home About Hyperemesis Theories & Research Human Chorionic Gonadotropin (hCG) & Estro
Hormones

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Updated on: Sep. 05, 2003

HUMAN CHORIONIC GONADOTROPIN AND

HYPEREMESIS GRAVIDARUM
T. Murphy Goodwin, MD
Co-Director of Maternal and Foetal Medicine, LAC-USC Women's and Children's
Hospital, Director of Maternal Foetal Medicine at Good Samaritan Hospital, Medical
Director, Pregnancy Help Center of San Gabriel Valley, Associate Professor, Division of
Maternal Foetal Medicine, Department of Obstetrics and Gynaecology, University of
Southern California, U.S.A.

There are a number of reasons for considering the association of human chorionic gonadotropin
(hCG) with hyperemesis gravidarum. The temporal relationship between peak hCG levels and the
most common time of nausea and vomiting has long been noted. More recently, the relationship of
hCG to transient hyperthyroidism of hyperemesis gravidarum (THHG) has been described. Several
experiments of nature have suggested that hCG plays a role. Let us consider these interrelated lines
of evidence, beginning with the latter.

EXPERIMENTS OF NATURE

Nausea and vomiting of pregnancy (NVP) is more common in women with molar gestation, in which
hCG is quite often markedly elevated. The consistent finding that NVP is more common with multiple
gestation in which hCG is significantly elevated compared to singletons supports this observation as
well. More recently, it has been noted that mothers carrying foetuses with Down's syndrome, a
condition associated with elevated hCG, are more likely to have NVP. By way of contrast, in my
experience, women with trisomy 18, in which hCG is very low, report much less nausea in
pregnancy.

PEAK LEVELS OF HCG CORRESPOND TO TIME OF MAXIMAL NVP

It has long been noted that peak concentrations of hCG and the most rapid rate of rise correspond
to the time of maximal NVP (8-12 weeks' gestation). Several investigators have studied hCG
concentrations in women with hyperemesis but the results are not consistent. Our group found that
hCG was elevated in women with vomiting compared to gestational age-matched controls, but there
was significant overlap (Figure 1). If hCG is the cause of hyperemesis, why do many women with
high levels have little vomiting and vice versa?

FIGURE 1 - RELATIONSHIP BETWEEN THE SEVERITY OF VOMITING AND HCG

CONCENTRATION

Two other related observations suggest an answer to this. The rise in hCG corresponds temporally to
a consistent thyroid stimulation in the mother (Figure 2). Since hCG closely resembles its sister
glycoprotein hormone, thyroid stimulating hormone (TSH), it has been conjectured that hCG is the
thyroid stimulator of pregnancy. Of greater interest to the question of the cause of NVP, however, is
the observation that the severity of NVP correlates closely with the degree of biochemical
hyperthyroidism.

FIGURE 2 - RELATIONSHIP OF HCG AND THYROID FUNCTION IN

HYPEREMESIS AND CONTROL SUBJECTS
During an 11-month period we studied 57 controls (30 with no vomiting and 27 with mild nausea
and occasional vomiting) and 57 patients with hyperemesis gravidarum (38 with hyperemesis and
19 with severe hyperemesis).1 Hyperemesis gravidarum was defined as persistent vomiting that
resulted in greater than 5% weight loss and large ketonuria on dip urine examination. All patients
were seen at less than 16 weeks' gestation and had onset of vomiting in the first trimester.
Exclusions were history of thyroid disease, goiter or presence of thyroid antibodies, fever or
evidence of other conditions responsible for vomiting, and multiple gestation. Study and control
subjects were enrolled contemporaneously and did not differ with respect to age, parity, or
gestational age.

Human chorionic gonadotropin was higher among hyperemesis subjects compared to controls (97
8 IU/mL, 29 2 IU/mL, p < 0.001), but there was a weak correlation between hCG and Free T4
and TSH. Most interestingly, there was a strong association between the severity of NVP and the
degree of hyperthyroidism (Figure 3). This finding has been shown by others as well. 2 This strongly
suggests that whatever the cause of the thyroid stimulation in pregnancy, it is very closely linked to
the cause of hyperemesis. It would not appear to be the hyperthyroidism per se however, since
hyperthyroidism itself rarely causes nausea and vomiting.

FIGURE 3 - RELATIONSHIP BETWEEN SEVERITY OF VOMITING AND SERUM

TSH
If hCG is the thyroid stimulator of pregnancy, how can there be such a weak association between
hCG and the degree of hyperthyroidism? The answer to this question may lie in the action of
variants of hCG of differing thyrotropic potential. The principle difference between hCG and other
glycoprotein hormones (luteinizing hormone [LH], follicle stimulating hormone [FSH], TSH) is the
large 31 amino acid tail, the -carboxyterminal portion (-CTP) (Figure 4). The -CTP has four sites
for glycosylation. Variants of hCG that lack the -CTP do not bind sialic acid moieties as readily as
intact hCG. Whereas LH is ten times more potent than intact hCG at stimulating the TSH receptor,
mutant hCG lacking the -CTP is as potent as LH. This variant form of hCG, having greater
thyrotropic potential, may also be found in otherwise normal pregnancies characterized by
hyperemesis.3

FIGURE 4 - STRUCTURE OF HCG AND OTHER GLYCOPROTEIN HORMONES

What is commonly referred to as immuno-reactive hCG is a mixture of free -hCG, free -hCG,
deglycosylated hCG, asialo-hCG, and hCG completely lacking the CTP. Molar tissue, in which only
3% of the measured hCG is fully glycosylated and a majority of the hCG is not intact, is an ideal
source for studying variants of hCG. We collaborated with Dr. Jerome Hershman who extracted large
amounts of hCG from these tissues and separated them by pH. Basic fractions of hCG were much
more potent than intact hCG in stimulating the release of cyclic adenosine monophosphate (cAMP)
when they combined with human TSH and LH receptors. These basic fractions correspond to the
deglycosylated hCG lacking the -CTP.4

Other mutations of hCG cause it to be unable to dimerize, i.e., for and subunits to join, which
they must for normal activity. Such mutations may manifest as elevated free -hCG. This is seen in
molar gestations. We found that, compared to 23 gestational age-matched controls, 39 patients
with hyperemesis had elevated free -hCG (101 70 ng/mL, 31 31 ng/mL, p < 0.001) (Figure
5).5 There was also a significant difference between groups for total hCG (9,237 3,613 ng/mL,
5,543 2,290 ng/mL, p < 0.01), but not for free -hCG (399 231 ng/mL, 377 214 ng/mL).
Thus, part of the puzzle of the relationship between hCG and NVP may lie in the fact that
measurements of intact hCG do not reflect various fractions of differing potency.

FIGURE 5 - PERCENT FREE SS-HCG IN HYPEREMESIS AND CONTROL

PATIENTS COMPARED TO GESTATIONAL AGE

Another important clue to the hormonal etiology of NVP may lie in variation within the hCG receptor.
Mutations have been described in the glycoprotein hormone receptors just as for the hormones
themselves. Some of these mutations, so-called gain of function mutations, offer another
explanation for the variation between hCG and thyroid stimulation, and hCG and hyperemesis itself.
A recently published case establishes just such an association. 6 A 27-year-old woman experienced
hyperemesis throughout pregnancy associated with hyperthyroidism. Both resolved after delivery.
This patient was found to have a familial gain-of-function mutation in the TSH receptor making her
extremely sensitive to the circulating hCG in pregnancy. This case may be related to those
previously described in which there is an association of hyperemesis, hyperthyroidism and
virilization. Such cases could be explained by a mutation in the glycoprotein hormone receptor in an
area common to the TSH and LH/hCG receptor or by variants of hCG that have greater potency in
stimulating not only the TSH receptor but also the LH/hCG receptor. They may also provide a further
clue to the puzzle that still remains. How does hCG cause hyperemesis? Despite the evidence that
hCG is very closely related to the cause of hyperemesis, there still lacks a good explanation for how
hCG can cause hyperemesis. The effect of hCG on steroid hormone synthesis is well-known, as is
the fact that steroid hormones modulate the response to nausea. It is likely that the
hyperthyroidism seen with hyperemesis is only a marker for increased hCG interaction with related
glycoprotein hormone receptors with the most significant interaction occurring within the ovary and
affecting steroid metabolism.

Along these lines, increased levels of oestradiol have been found by some investigators including
our own group, but not by all. It is possible that oestradiol or testosterone, or the rate of change in
these two hormones, is responsible for the nausea and vomiting of pregnancy and some of the
related mood changes that have been described. More work is needed in this area.

REFERENCES:

1. Goodwin TM, Montoro M, Mestman JH, Perkary AE, Hershman JM. The role of chorionic
gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin
Endocrinol Metab 1992;75:1333-7.
2. Mori M, Amino N, Tamaki H, Miyai K, Tanizaw A. Morning sickness and thyroid function
in normal pregnancy. Obstet Gynecol 1988;72:355-9.
3. Tsuruta E, Tada H, Tamaki H, Kashiwai T, Asahi K, Takeoka K, Mitsuda N, Amino N.
Pathogenic role of asialo human chorionic gonadotropin in gestational thyrotoxicosis. J
Clin Endocrinol Metab 1995;80:350-5.
4. Yoshimura M, Pekary AE, Pang XP, Berg L, Goodwin TM, Hershman JM. Thyrotropic
activity of basic isoelectric forms of human chorionic gonadotropin extracted from
hydatidiform mole tissues. J Clin Endocrinol Metab 1994;78:862-6.
5. Goodwin TM, Hershman JM, Cole L. Increased concentration of the free beta-subunit of
human chorionic gonadotropin in hyperemesis gravidarum. Acta Obstet Gynecol Scand
1994;73:770-2.
6. Rodien P, Bremont C, Sanson ML, Parma J, Van Sande J, Costagliola S, Luton JP,
Vassart G, Duprez L. Familial gestational hyperthyroidism caused by a mutant
thyrotropin receptor hypersensitive to human chorionic gonadotropin. N Engl J Med
1998;339:1823-6.

RELATED PUBLICATIONS BY THE SPEAKER:

Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol 1998;41:597-605.

Goodwin TM, Hershman JM. Hyperthyroidism due to inappropriate production of human chorionic
gonadotropin. Clin Obstet Gynecol 1997;40:32-44.

Pekary AE, Jackson IM, Goodwin TM, Pang XP, Hein MD, Hershman JM. Increased in vitro thyrotropic
activity of partially sialated human chorionic gonadotropin extracted from hydatidiform moles of
patients with hyperthyroidism. J Clin Endocrinol Metab 1993;76:70-4.

Goodwin TM, Montoro M, Mestman JH. Transient hyperthyroidism and hyperemesis gravidarum:
clinical aspects. Am J Obstet Gynecol 1992;167:648-52.
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Site Map | Contact Us

Theories & Research

HCG & Estrogen

Hormones About Hyperemesis | Mothers | Family & Friends | Health Professionals | About
Psychological Causes H.E.R.
Thyroxine Levels
Gastric Neuromuscular
Dysfunctions
Thyroxine Levels
Deficiences of Nutrients
Increase in serum thyroxine levels have been documented in 70% of pregnancies
Other Theories & Links
complicated by HG. Thyroid hormones are stimulated by the increase in hCG and may
result in transient hyperthyroidism. Severity of HG is sometimes linked to the degree of
hyperthyroidism. Mutations of hCG or TSH receptors have also been found to be
elevated in women with HG.

Gastric Neuromuscular Dysfunctions

Offsite Research:

Human chorionic gonadotropin and hyperemesis gravidarum

Goodwin, TM
Associate Professor, Division of Maternal Foetal Medicine, Department of Obstetrics and
Gynaecology, University of Southern California, U.S.A.
Nausea and Vomiting of Pregnancy: State of the Art 2000 Conference

There are a number of reasons for considering the association of human chorionic gonadotropin
(hCG) with hyperemesis gravidarum. The temporal relationship between peak hCG levels and the
most common time of nausea and vomiting has long been noted. More recently, the relationship of
hCG to transient hyperthyroidism of hyperemesis gravidarum (THHG) has been described. Several
experiments of nature have suggested that hCG plays a role.

Thyroid function in patients with hyperemesis gravidarum

Bouillon R, Naesens M, Van Assche FA, De Keyser L, De Moor P, Renaer M, De Vos P,
De Roo M.
Am J Obstet Gynecol 1982 Aug 15;143(8):922-6

An increased free thyroxine (T4) index was observed in 73% of 33 consecutive pregnancies
complicated by severe hyperemesis gravidarum. The free triiodothyronine (T3) index was
increased in only four of 11 hyperthyroxinemic patients. In five hyperthyroxinemic patients tested,
no increase in serum thyrotropin was observed after the injection of thyrotropin-releasing
hormone (THR). Goiter, exophthalmos, or previous history of hyperthyroidism was absent in all
patients. The thyroxinemia returned to normal in one to several weeks, whether or not it was
treated with antithyroid drugs. The thyroid function during the period of hyperemesis had no
influence on the subsequent rate of abortion or duration of pregnancy. A lower birth weight,
however, was observed in children born to hyperthyroxinemic mothers. Hyperemesis gravidarum
should be included in the differential diagnosis of elevations in free T4 index during pregnancy and
included in the differential diagnosis of hyperthyroidism.

The role of chorionic gonadotropin in transient hyperthyroidism of

hyperemesis gravidarum.
Goodwin TM, Montoro M, Mestman JH, Perkary AE, Hershman JM.
The Journal of Clinical Endocrinology and Metabolism 1992;75:1333-7.

Biochemical evidence of hyperthyroidism is frequently encountered in hyperemesis gravidarum,

but its relationship to the cause of hyperemesis is unknown. TSH was suppressed in 60% of
hyperemesis patients and 9% of controls. hCG correlated directly with free T4(r = 0.45, P <
0.001) and inversely with TSH (r = -0.48, P < 0.001). Hyperemesis patients had significantly
greater mean serum hCG, free T4, total T3, and estradiol, and lesser serum TSH compared to
controls. Hyperemesis patients with suppressed TSH had significantly greater free T4 and hCG
compared to those with TSH in the normal range. The degree of biochemical hyperthyroidism and
hCG concentration varied directly with the severity of vomiting. These data show that biochemical
hyperthyroidism is a common finding in patients with hyperemesis gravidarum and suggest that
hCG is the thyroid stimulator in this state. The increased estradiol concentration in patients with
hyperemesis gravidarum may be attributed to the effects of hCG on steroidogenesis.

Morning sickness and thyroid function in normal pregnancy.

Mori M, Amino N, Tamaki H, Miyai K, Tanizaw A.
Obstetrics and Gynecology 1988;72:355-9.

The increased free T4 and hCG and decreased TSH correlated with the severity of morning
sickness, and these changes were especially marked in subjects with nausea and vomiting. The
individual serum levels of hCG in the pregnant group correlated significantly, directly with the
levels of free T4 and inversely with those of TSH. The increased free T4 and decreased TSH in
subjects with emesis returned to the normal ranges of non-pregnant controls after improvement
of emesis. These data indicate that the thyroid gland is physiologically activated in early
pregnancy, possibly by hCG or a related substance, which may induce gestational emesis.

Pathogenic role of asialo human chorionic gonadotropin in gestational

thyrotoxicosis.
Tsuruta E, Tada H, Tamaki H, Kashiwai T, Asahi K, Takeoka K, Mitsuda N, Amino N.
The Journal of Clinical Endocrinology and Metabolism 1995;80:350-5.

We reported that gestational thyrotoxicosis is induced by thyroid-stimulating activity (TSA) of

circulating hCG. Serum free T4 (FT4) and free T3 (FT3) levels were significantly higher and TSH
was lower in the hyperemesis (FT4, 23.42 +/- 5.02 pmol/L; FT3, 6.26 +/- 1.80 pmol/L; TSH, 0.30
+/- 0.44 mU/L) and in gestational thyrotoxicosis (FT4, 48.65 +/- 14.80 pmol/L; FT3, 14.71 +/-
3.47 pmol/L; TSH, < 0.04 mU/L) groups than in the no emesis group (FT4, 16.99 +/- 2.48
pmol/L; FT3, 5.51 +/- 0.75 pmol/L; TSH, 1.37 +/- 1.23 mU/L; P < 0.0005). TSA was also
significantly higher in the hyperemesis (566 +/- 187%) and gestational thyrotoxicosis (832 +/-
168%) groups than in the no emesis group (321 +/- 135%). We conclude that thyrotoxicosis with
hyperemesis may be caused by circulating asialo-hCG with higher thyrotropic bioactivity.

Thyrotropic activity of basic isoelectric forms of human chorionic

gonadotropin extracted from hydatidiform mole tissues.
Yoshimura M, Pekary AE, Pang XP, Berg L, Goodwin TM, Hershman JM.
The Journal of Clinical Endocrinology and Metabolism 1994;78:862-6.

These results indicate that isoforms of hCG with more thyrotropic activity were produced by
trophoblastic tissues in patients with hydatidiform mole. We speculate that these isoforms of hCG
may be responsible for the hyperthyroidism in some patients with hydatidiform moles.

Increased concentration of the free beta-subunit of human chorionic

gonadotropin in hyperemesis gravidarum.
Goodwin TM, Hershman JM, Cole L.
Acta Obstetricia et Gynecologica Scandinavica 1994;73:770-2.

The amount of free beta subunit hCG (free beta) has been reported to be increased in trophoblast
disease and Down's syndrome, conditions also associated with high total hCG. The concentration
of hCG was greater in hyperemesis patients (9237 +/- 3613 ng/ml, mean +/- s.d.) compared to
controls (5543 +/- 2290, p < 0.005) as was the concentration of free beta hCG (101 +/- 70 ng/ml
vs. 31 + 31, p < 0.001). A percent free beta greater than 0.6 was found in 33/39 hyperemesis
patients (85%) compared to 5/23 controls (22%), p < 0.001. Increased free beta hCG is found in
hyperemesis gravidarum. This finding strengthens the association of hyperemesis with abnormal
metabolism of hCG.

Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor

hypersensitive to human chorionic gonadotropin.
Rodien P, Bremont C, Sanson ML, Parma J, Van Sande J, Costagliola S, Luton JP,
Vassart G, Duprez L.
New England Journal of Medicine 1998;339:1823-6.

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