Pregnancy in Acromegaly: Successful Therapeutic Outcome1
Vivien Herman-Bonert,
Maria Seliverstov and
Shlomo Melmed
Division of Endocrinology and Metabolism, Department of Medicine,
Cedars-Sinai Medical Center, University of California School of
Medicine, Los Angeles, California 90048
Address all correspondence and requests for reprints to: Dr. Shlomo Melmed, Cedars-Sinai Medical Center, Division of Endocrinology and Metabolism, 8700 Beverly Boulevard, Becker B-131, Los Angeles, California 90048. E-mail: melmed{at}CSMC.edu
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Introduction
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Acromegaly usually results from GH hypersecretion
elaborated by a somatotroph adenoma. With the advent of advanced
surgical and medical management of these patients, increasing numbers
of women with the disorder are choosing to become pregnant. Several
factors may impact the course of pregnancy in acromegaly. As the
pituitary controls the gonadotropin axis, perturbed pituitary function
often leads to infertility or early pregnancy termination due to
failure to maintain intrauterine implantation. Furthermore, GH is a
potent insulin antagonist, and pregnant patients with GH hypersecretion
are therefore prone to added glucose intolerance (1).
In contrast, pregnancy itself may impact on the course of the pituitary
tumor. During pregnancy, the normal pituitary increases in size (2),
and therefore, tumors are at risk for hemorrhage due to enhanced
pituitary vascularity and edema in addition to estrogen-mediated
pituitary hyperplasia (3). We here report the course of successful
pregnancy in four patients with acromegaly.
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Case 1
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A 30-yr-old Caucasian female presented with a 12-yr history of
gradual change in appearance, headache, increase in shoe and ring size,
acne, hirsutism, and skin tags. She also experienced carpal tunnel
syndrome, overbite, and widening of incisor spaces. Nine months before
diagnosis, she developed galactorrhea and amenorrhea. After parlodel
administration, she underwent transsphenoidal removal of a GH-secreting
pituitary adenoma, with an excellent symptomatic response.
Postoperative magnetic resonance imaging (MRI) revealed minimal
residual enhancing tissue in the sella turcica and a partially empty
sella. Random GH and insulin-like growth factor I (IGF-I) levels were
10 (normal, <10 ng/mL) and 591 (normal, 123463 ng/mL)
respectively.
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Obstetric history
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In 1987, 6 yr before diagnosis, the patient discontinued oral
contraceptive pills, but was unable to become pregnant. After
transsphenoidal surgery, her periods became regular, and 6 months
later, she conceived. No symptom exacerbation occurred during
pregnancy, and IGF-I and PRL levels were both in the normal ranges for
pregnancy. Oral glucose tolerance tests performed during pregnancy at
3, 6, and 9 months yielded respective 2-h GH levels of 0.1, 0.8, and
1.5 ng/mL.
A normal full-term infant was delivered. Five months postpartum, the GH
level measured 2 h after oral glucose administration was 1.1
ng/mL, and the pituitary MRI scan showed no change. One year
postpartum, however, the postglucose GH level was 3.9 ng/mL despite an
IGF-I level of 364 ng/mL (normal, 114483 ng/mL). An octreoscan also
revealed enhanced pituitary uptake; consequently, therapy with
octreotide was initiated.
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Case 2
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A 31-yr-old Caucasian female was assessed for nausea, headache,
and vomiting. Two years previously, she had undergone transsphenoidal
resection of a GH-secreting pituitary macroadenoma with supraseller and
cavernous sinus extension. She had experienced secondary amenorrhea for
8 yr before surgery. Postoperative MRI revealed residual tumor in the
sphenoid sinus, and a random GH measurment was 17 ng/mL. Six months
postoperatively, postglucose GH was 34 ng/mL, with an elevated IGF-I
level (308 ng/mL). Octreotide treatment was initiated (50 µg, sc,
three times daily) and suppressed GH to 1.8 ng/mL 2 h after a
morning injection. However, the patient discontinued octreotide after 1
month due to nausea, vomiting, and diarrhea. Six months later, she
became pregnant and vaginally delivered a normal full-term infant.
The patient had also delivered three normal full-term infants by
cesarean section during the time when she had symptomatic evidence of
acromegaly (assessed in retrospect). She had, in fact, received
ovulation induction treatment for her second pregnancy because of the
amenorrhea. After pituitary surgery, her menstrual cycles returned to
normal.
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Case 3
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A 28-yr-old Caucasian female was diagnosed with acromegaly when
she presented with failure to lactate postpartum. Twenty-five percent
of her macroadenoma mass was removed by transsphenoidal resection, and
she received subsequent postoperative pituitary radiation. She was
treated with parlodel for 2 yr until octreotide was started, which
suppressed IGF-I levels from 5.4 to 1.8 U/mL and GH to 1.6 ng/mL 2
h after injection. Soft tissue swelling and acne improved, energy level
increased, and menses returned to normal. She continued octreotide (100
µg, sc, three times daily) for 3 yr until becoming pregnant for the
second time. Octreotide was then discontinued, and visual field
examinations and postglucose GH levels were assessed every 46 weeks.
At 3 months, the postglucose GH level was 11.5 ng/mL, and IGF-I was 356
(normal, 114492); at 6 months, GH was 2.9 ng/mL, and IGF-I was 427;
and at 7 months, GH was 22 ng/mL, and IGF-I was 564 ng/mL. She
delivered a normal, full-term infant.
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Case 4
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A 30-yr-old Caucasian female presented with a 1-yr history of
amenorrhea. Examination revealed clinical features suggestive of
acromegaly, including large hands, broad feet, and prominent nose. The
IGF-I level was 1719 ng/mL (upper normal limit, 492 ng/mL), a random GH
measurment was 260 ng/mL, and PRL was normal. MRI revealed a pituitary
macroadenoma with suprasellar extension and extension into the right
cavernous sinus. The patient had transsphenoidal removal of the
pituitary adenoma 1 month after diagnosis.
Postoperatively, amenorrhea persisted with increases in shoe and ring
size. Three months postoperatively, the IGF-I level was 1016 ng/mL, and
an oral glucose tolerance test revealed a basal GH level of 37 ng/mL,
which suppressed to 14 ng/mL 2 h after oral glucose. She was
started on octreotide and despite increasing doses demonstrated
persistently elevated IGF-I and nonsuppressible GH levels. While
receiving 1200 µg octreotide/day, the IGF-I level was 1106 ng/mL, and
GH assayed 2 h after injection was 8.6 ng/mL. Postoperative MRI
revealed persistent tumor in the sella with some normal gland as well
as residual tumor in the cavernous sinus. Because of persistent GH
hypersecretion, despite maximal doses of octreotide, the patient
underwent repeat transphenoidal surgery 2 yr after initial surgery.
Tumor encased in the scar as well as in the cavernous sinus could not
be removed, and the patient was treated with
-knife irradiation 1 yr
after the second transsphenoidal surgery. Six months later, GH
concentrations 2 h after oral glucose were 4.2 ng/mL, and the
IGF-I level was 663 ng/mL. Octreotide treatment was reinitiated (100
µg three times daily). GH levels fell to 2.2 ng/mL 2 h after
octreotide injection, and the IGF-I level was 662 ng/mL. Two months
after
-knife irradiation, the patient began menstruating
regularly.
Six months after GH and IGF-I normalization, the patient became
pregnant, and octreotide was discontinued. Currently, she is 7 months
pregnant and is being evaluated for signs of tumor enlargement monthly
and for visual field assessment every 46 weeks.
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Discussion
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We report here a spectrum of four different cases of pregnancy
occurring in patients harboring GH-secreting pituitary tumors. The
first patient became pregnant 7 months after successful surgical
removal of a GH-secreting macroadenoma. Four months after delivery of a
normal full-term infant, she developed recurrent GH hypersecretion.
The second patient has been pregnant seven times while experiencing
active clinical and biochemical acromegaly. She had five pregnancies,
resulting in three normal full-term births and two miscarriages before
the diagnosis of acromegaly, and required fertility treatment for the
fourth pregnancy. Incomplete resection of a GH-secreting macroadenoma
resulted in persistent postoperative biochemical GH hypersecretion. The
patient was noncompliant with octreotide treatment and became pregnant
14 months postoperatively even though her GH levels were elevated. The
fetus died in utero at 5 months gestation, associated with
the development of anticardiolipin antibodies in the patient. One month
after dilation and curettage, the patient again became pregnant.
The third patient was diagnosed with acromegaly after her first
delivery. Incomplete transsphenoidal resection of a GH-secreting
macroadenoma followed by pituitary radiation necessitated octreotide
treatment, with an excellent biochemical response. After 3 yr, the
patient again became pregnant. At this time, octreotide was
discontinued, and she delivered a normal full-time infant.
The fourth patient had an initial incomplete transsphenoidal resection
of a GH-secreting pituitary tumor, followed by a second pituitary
resection and
-knife irradiation. Persistently elevated GH levels
postoperatively were normalized with octreotide treatment. The patient
became pregnant, octreotide was discontinued, and the patient is
currently being followed for signs of tumor enlargement during the
pregnancy.
Acromegaly and fertility
Reports of pregnancy occurring in acromegalic patients are
uncommon. Menstrual irregularities are an early and frequent finding in
acromegaly (4). Several mechanisms may contribute to amenorrhea and
infertility in acromegaly. Hypopituitarism and decreased gonadotropin
reserve may be caused by the expanding tumor mass. Hyperprolactinemia
occurs in 3040% of acromegalic patients (5) and results in
hypothalamic-pituitary-ovarian axis dysfunction at several levels,
including reduction in pulsatile GnRH secretion (6, 7) as well as
hypoestrogenism (8). Normalization of hyper-prolactinemia
frequently restores menstruation and fertility. GH and IGF-I also
regulate ovarian function. GH increases ovarian responsiveness to
gonadotropins (9), thereby sensitizing the ovary to the stimulatory
effects of gonadotropins. GH also stimulates local IGF-I production in
the ovarian follicle (10). Whether GH acts directly on the ovary or
whether its sensitizing effect is mediated by IGF-I is as yet
unclear.
A review of the current literature revealed 24 cases of pregnancy and
acromegaly subsequent to the 34 cases initially reported in the 1950s
(11). Reported pregnancies occurred in the context of a wide spectrum
of clinical scenarios of acromegaly, ranging from undiagnosed,
untreated acromegaly (11, 12, 13) to patients treated with bromocriptine
(14, 15, 16), octreotide (17, 18), and transsphenoidal surgery without (19, 20) or with (21) fertility treatment. The majority of reported cases
were treated with bromocriptine only (14, 15, 16) or in conjunction with
radiation (22, 23) or surgery (24). Bromocriptine was not
associated with teratogenicity or fetoplacental insufficiency in
three cases (14, 15, 16); however, prematurity was reported in one patient
(16), and intra-uterine growth delay (13, 23) has been reported in
two cases. There are four cases (including our two cases) of pregnancy
ensuing after successful treatment of acromegaly with octreotide (17, 18). In all cases, octreotide was discontinued when pregnancy was
diagnosed. Intrauterine fetal exposure to octreotide for the first
month did not cause notable fetal malformations. Pregnancy has occurred
after surgical intervention alone (19, 25) despite the persistence
of GH hypersecretion (25). Selective transsphenoidal removal of
GH-secreting microadenomas (19) with return of regular menses in half
of the patients (12 of 23) resulted in three pregnancies.
GH physiology during normal pregnancy and acromegaly
Maternal circulating GH levels are derived from different sources
depending on the trimester. In normal women during the first trimester
(26, 27), GH is pituitary in origin and is secreted in a pulsatile
pattern. Thereafter, placental GH, contributes the major component of
circulating GH (26). This variant form of GH is secreted continuously
rather than in a pulsatile pattern and is not detected by routine
clinical RIA or immunoradiometric assay. RIAs using antibodies that
recognize specific epitopes on the placental GH variant (26)
distinguish pituitary from placental GH. These assays use two
monoclonal antibodies, one of which recognizes pituitary and placental
GH, the other of which recognizes only pituitary GH (Fig. 1
). Thus, to diagnose acromegaly during
pregnancy, specific RIAs for the placental variant are required to
differentiate elevated GH levels from pituitary vs.
placental sources.

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Figure 1. GH profile throughout pregnancy (mean
± SEM). Graph A represents circulating levels of pituitary
GH only, whereas B represents circulating levels of placental as well
as pituitary GH variants. As pituitary GH secretion is suppressed
during pregnancy, graph B values truly reflect placental GH secretion
during the last trimester of pregnancy. (From Caufriez A, Frankenne F,
Hennen G, Copinschi G. 1993 Regulation of maternal IGF-I by placental
GH in normal and abnormal human pregnancies. Am J Physiol.
265:E572E577, with permission.)
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IGF-I values are less useful in the diagnosis of acromegaly in
pregnancy, as they are elevated during normal pregnancy. Circulating
placental GH induces maternal hepatic IGF-I production, which, in turn,
inhibits pituitary GH secretion (25). The placenta also secretes GHRH,
whose physiological role is unknown (28). In acromegalic patients,
pituitary GH secretion persists during the entire pregnancy, and
circulating pituitary GH levels are not significantly different during
pregnancy. Thus, the autonomous adenomatous somatotrophs are resistant
to factors that usually inhibit pituitary GH secretion during the
second trimester of normal pregnancy (Fig. 2
). Serum IGF-I increases in the second
half of pregnancy in normal as well as acromegalic pregnancies (29).
This increase in IGF-I secretion occurs despite stable pituitary GH
secretion, suggesting that the increased IGF-I levels are not pituitary
GH dependent during late pregnancy. Paradoxical GH release after TRH
occurs in pregnant acromegalic patients, but is not observed in normal
pregnant control subjects (25).

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Figure 2. Proposed model for regulation of pituitary
and placental GH secretion in normal and acromegalic women. (Adapted
with permission from Melmed S. 1990 Acromegaly. N Engl J Med.
322:966977; and Beckers A, Stevenaert A, Foidart J, Hennen G,
Frankenne F. 1990 Placental and pituitary growth hormone secretion
during pregnancy in acromegalic women. J Clin Endocrinol Metab.
71:725731.)
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Does pregnancy aggravate acromegaly?
The pituitary gland enlarges during normal pregnancy, and
pituitary volume may increase by 45% during the first trimester (30).
Pituitary enlargement is due to hyperplasia of mature lactotrophs with
concomitant reduction in gonadotroph numbers (31). Large amounts of PRL
are produced primarily by the increased lactotroph mass as well as by
suppressed (as evidenced by low GH messenger ribonucleic acid content)
pluripotent somatrotrophs that can engage in PRL production and can
also transform to lactotrophs under specific conditions (32).
Theoretically, the stimulatory effect of peripheral hormone surges
during pregnancy could cause adenoma enlargement due to tumor growth or
hemorrhage, or tumor infarction in patients with GH adenomas. The
normal increase in pituitary gland size during pregnancy also
contributes to the mass pressure effect on the optic nerve. However,
earlier reports did not confirm that macroadenomas posed a greater risk
for visual loss during pregnancy than microadenomas (33, 34). A recent
study showed that the risk of visual loss is small in pregnant patients
harboring functioning and nonfunctioning pituitary microadenomas (35).
However, patients with adenomas greater than 1.2 cm are at greater risk
of developing visual loss during pregnancy. Imaging techniques employed
in this latter study were more sensitive and precise than those used in
previous studies.
In reviewing all cases reported in the literature, pregnancy
exacerbated acromegaly in 4 of 24 (17%) patients, necessitating
therapeutic abortion in one patient at 10 weeks because of active
disease. Recurrence of GH hypersecretion and return of clinical signs
of acromegaly (including headache, increase in glove and shoe size, and
coarsening of facial features) was reported (23) in a patient in whom
bromocriptine treatment was discontinued at the start of pregnancy.
Another reported patient (18) developed signs of increased intracranial
pressure at 39 weeks gestation. Cesarean section was performed for
fetal distress, and the patient underwent transsphenoidal resection for
reexpansion of the adenoma.
How does acromegaly influence pregnancy?
Metabolic and cardiovascular complications of acromegaly can
potentially cause medical complications to the mother and fetus during
pregnancy. GH antagonizes insulin action, resulting in carbohydrate
intolerance in 60% and diabetes mellitus in 1332% of patients (36).
As pregnancy itself is an insulin-resistant state, the pregnant
acromegalic patient is at greater risk for hyperglycemia. There is also
an increased incidence of hypertension and coronary artery disease in
acromegalic patients, which poses potential risks to the fetus.
However, none of these potential complications of elevated GH have been
shown to have a deleterious effect in pregnant acromegalic
patients.
Consequences of treatment on pregnancy
Bromocriptine. This dopamine agonist has not been associated
with increased complication risk during pregnancy or with congenital
malformations when given through the first few weeks of gestation in
hyperprolactinemic patients (5, 37). Nine years of follow-up of
children born to mothers treated with bromocriptine in the first few
weeks of pregnancy revealed no differences in teratogenicity compared
to expected rates (38). Several amenorrheic acromegalic patients
conceived after normalization of hyperprolactinemia with bromocriptine
(14, 15, 16, 22). Uncomplicated delivery of normal infants occurs even when
bromocriptine treatment is continued throughout the pregnancy (14, 16).
Octreotide. There are only two previously reported cases of
pregnant acromegalic patients treated with octreotide during early
pregnancy (17, 18). The pregnancies and deliveries were uneventful, and
the infants were normal. However, octreotide should be discontinued
during pregnancy until more safety data are obtained.
Surgery. There are no data pertaining specifically to the
impact of transsphenoidal surgery during pregnancy. Although there is
no reported increased incidence of congenital abnormalities, surgery
during early pregnancy may be associated with an increased incidence of
spontaneous abortion, probably due to anesthesia effects (39). However,
other investigators report no significant difference in abortion and
perinatal mortality rates but found a significant difference in
prematurity (8% vs. 37%) in pregnant patients treated
surgically for pituitary tumors (33).
Management of acromegaly in women of childbearing age
The aims of therapy in female acromegalic patients wishing to
conceive are normalization of PRL and GH levels to promote fertility
and conception, prevention of tumor expansion during pregnancy, and
delivery of a normal full-term infant. Surgery and medical therapy have
distinct advantages and disadvantages in the pregnant acromegalic
patient.
Patients with microadenomas who are biochemically responsive and
tolerant to medical management (bromocriptine or octreotide) can
continue medical management and should be advised to discontinue
treatment when pregnancy is confirmed. This approach has been shown to
be safe for the fetus, and the risk of tumor enlargement for the mother
is small. Alternatively, transsphenoidal resection of microadenomas
before conception does not impair fertility. Pregnant patients with
microadenomas should be assessed clinically during each trimester for
symptoms of tumor enlargement (Fig. 3
).
GH-secreting macroadenomas subjected to transsphenoidal resection
before conception pose a greater risk of postoperative hypopituitarism,
with concomitant compromise of fertility. On the other hand, if
macroadenomas are not removed before pregnancy, the risk of pituitary
enlargement with possible visual loss is greater. In addition, the
safety of continuous bromocriptine and octreotide treatment during
pregnancy has not been established, and it is recommended that these
drugs be discontinued very early in pregnancy despite the concomitant
rare risk of tumor reexpansion. Patients with macroadenomas should have
visual fields evaluated when pregnancy is diagnosed and every 6 weeks
thereafter. Pituitary MRI for patients harboring micro- and
macroadenomas is indicated before conception and should be repeated
during pregnancy only if there is evidence of headache or visual field
loss. However, MRI is only recommended after 4 months gestation (40).
In the absence of clinical evidence of tumor expansion, MRI for micro-
as well as macroadenomas can be repeated postpartum. When there is
evidence of pregnancy-associated tumor enlargement with visual loss,
emergency transsphenoidal resection should be recommended.
Pituitary MRI should be repeated postpartum in patients with micro- and
macroadenomas to assess tumor size. If the tumor has, in fact,
enlarged, patients should be followed by repeat imaging at 6-month
intervals.
Women with microadenomas can breastfeed their infants, as there are no
data to suggest that PRL elevation caused by breastfeeding causes tumor
expansion.
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Footnotes
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1 This work was supported by the Steinberg Foundation and Grant
DK-50238. 
Received August 6, 1997.
Revised November 6, 1997.
Accepted November 13, 1997.
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References
|
---|
-
Davidson, MB. 1987 Effect of growth hormone on
carbohydrate and lipid metabolism. Endocr Rev. 8:115131.[Medline]
-
Erdheim J, Stumme E. 1909 Uber die
schwangerschaftsveranderung der hypophyse. Beitr Z Pathol Anat. 46:1132.
-
Soluboff LG, Ezrin C. 1969 Effect of pregnancy on
the somatotroph and prolactin cell of the human adenohypophis. J
Clin Endocrinol Metab. 29:15331538.[Medline]
-
Davidoff LM. 1940 Hyperpituitarism and
hypopituitarism. Bull NY Acad Med. 16:227.
-
Molitch ME. 1985 Pregnancy and hyperprolactinemic
women. N Engl J Med. 312:13641370.[Medline]
-
Winters JJ, Troen P. 1984 Altered pulsatile
secretion of lutenizing hormone in hypogonadal men with
hyperprolactinemia. Clin Endocrinol (Oxf). 21:257163.[Medline]
-
Sauder SE, Frager M, Case GD, Kelch RP, Marshall
JC. 1984 Abnormal patterns of pulsatile luteinizing hormone
secretion in women with hyper-prolactinemia and amenorrhea:
resonses to bromocriptine. J Clin Endocrinol Metab. 59:941948.[Abstract]
-
Demura R. Ono M, Demura H, Schizume DK, Oouchi H. 1982 Prolactin directly inhibits basal as well as
gonadotropin-stimulated secretion of progesterone and 17ß-estradiol
in the human ovary. J Clin Endocrinol Metab. 54:12461250.[Abstract]
-
Advis JP, White SS, Ojeda SR. 1981 Activation of
growth hormone short loop negative feedbak delays puberty in the female
rat. Endocrinology. 108:13431352.[Abstract]
-
Hsu CJ, Hammond JM. 1987 Concomitant effects of
growth hormone on secretion of insulin-like growth factor I and
progesterone by cultured porcine gramulosa cells. Endocrinology. 121:13431348.[Abstract]
-
Abelove WA, Rupp JJ, Paschkis KE. 1954 Acromegaly
and pregnancy. J Clin Endocrinol Metab. 14:32.[Medline]
-
Yap AS, Clouston WM, Mortimer RH, Drake RF. 1990 Acromegaly first diagnosed in pregnancy: the role of bromocriptine
therapy. Am J Obstet Gynecol. 163:477478.[Medline]
-
Cundy T, Grundy EN, Melville H, Sheldon J. 1984 Bromocriptine treatment of acromegaly following spontaneous conception.
Fertil. Steril. 42:134136.
-
Bigazzi M, Ronga R, Lacranjan I, et al. 1979 A
pregnancy in an acromegalic woman during bromocriptine treatment:
effects on growth hormone and prolactin in the maternal, fetal and
amniotic compartments. J Clin Endocrinol Metab. 48:9.[Abstract]
-
Aono T, Shioji T, Kohno M, Ueda G, Kurachi K. 1976 Pregnancy following 2-bromo-alpha-ergocryptine (CB-154)-induced
ovulation in an acromegalic patient with galactorrhea and amenorrhea. Fertil Steril. 27:341344.[Medline]
-
Espersen T, Ditzel J. 1977 Pregnancy and delivery
under bromocriptine therapy. Lancet. 2:985.
-
Landolt AM, Schmid J, Wimpfheimer C, Karlsson Er,
Boerlin V. 1989 Successful pregnancy in a previously infertile
woman treated with SMS201995 for acromegaly [Letter]. N Engl
J Med. 320:671672.[Medline]
-
Montini M, Pagani G, Gianola D, Pagani MD, Piolini R,
Camboni MG. 1990 Acromegaly and primary amenorrhea: Ovaluation and
pregnancy induced by SMS 201995 and bromocriptine [Letter]. J
Endocrinol Invest. 13:193.[Medline]
-
Wislawski J, Hartwig W, Kasperlik-Zaluska A, Ostrowski
K. 1982 Treatment of acromegaly by the surgical approach through
the sphenoid bone. Clinical results. Neurol Neurochir Polska16
:281286.
-
Landolt AM, Froesch ER, Konig MP. 1988 Spontaneous
postoperative normalization of growth hormone levels in two patients
with acromegaly not cured by transsphenoidal surgery. Neurosurgery. 23:634637.[Medline]
-
Aso T, Goto K, Takeuchi J, Kotsuji F, Tominaga T. 1987 A triplet pregnancy after gonadotropin-releasing hormone pulsatile
infusion therapy in a postoperative case of growth hormone-producing
pituitary macroadenoma. Endocrinol Jpn. 34:395405.[Medline]
-
Luboshitzky R, Dickstein G, Barzilai D. 1980 Bromocriptine induced pregnancy in an acromegalic patient. JAMA.
244584.
-
OHerlihy C. Pregnancy in an acromegalic after
bromocriptine therapy. Ir J Med Sci. 149:281282.
-
Miyakava I, Taniyama K, Koike H, Mori N, Nagamine M,
Kuribayashi T. 1982 Successful pregnancy in an acromegalic patient
during 2-Br-
-ergocryptine (CB-154) therapy. Acta Endocrinol
(Copenh). 101:333338.[Medline]
-
Beckers A, Stevenaert A, Foidart J-M, et al. 1990 Placental and pituitary growth hormone secretion during pregnancy in
acromegalic women. J Clin Endocrinol Metab. 71:725.[Abstract]
-
Frankenne F, Closset J, Gomez F, et al. 1988 The
physiology of growth hormones (GHs) in pregnancy women and partial
characterization of the placental GH variant. J Clin Endocrinol
Metab. 66:11711180.[Abstract]
-
Eriksson L, Frankenne F, Eden S, Hennen G, von Schoultz
B. 1989 Growth hormone 24 hour serum profiles during
pregnancylack of pulsatility for the secretion of the placental
variant. Br J Obstet Gynecol. 96:949953.[Medline]
-
Margioris AN, Brockman G, Bohler HCL, Grino M,
Vanvakopulous N, Chroussos G. 1990 Expression and localization of
growth hormone-releasing hormone messenger RNA in rat placenta:
in vitro secretion and regulation of its peptide product. Endocrinology. 126:151158.[Abstract]
-
Wilson DM, Bennett A, Adamson GD, et al. 1982 Somatomedins in pregnancy: a cross-sectional study of insulin-like
growth factors I and II and somatomedin peptide content in normal human
pregnancies. J Clin Endocrinol Metab. 55:858869.[Abstract]
-
Gonzalez J, Elizondo G, Saldivar D, Nanez H, Todd L,
Villareal J. 1988 Pituitary gland growth during normal pregnancy:
an in vivo study using magnetic resonance imaging. Am J
Med. 85:217220.[Medline]
-
Scheithauer BW, Sano T, Kovacs KT, et al. 1990 The
pituitary gland in pregnancy: a clinicopathopathologic and
immunohistochemical study of 69 cases. Mayo Clin Proc. 65:461.[Medline]
-
Stefaneau L, Kovacs K, Lloyd RV, et al. 1992 Pituitary lactotrophs and somatotrophs in pregnancy: a correlative
in situ hybridization and immunohistochemical study. Virch
Arch Cell Pathol. 62:291296.
-
Magyar DM, Marshall JR. 1978 Pituitary tumors and
pregnancy. Am J Obstet Gynecol. 132:739751.[Medline]
-
Gemzell C, Wang CF. 1979 Outcome of pregnancy in
women with pituitary adenoma. Fertil Steril. 31:363372.[Medline]
-
Kupersmith MJ, Rosenburg C, Kleinberg D. 1994 Visual loss in pregnant women with pituitary adenomas. Ann Intern Med. 121:473477.[Abstract/Free Full Text]
-
Berelowitz M, and HowGo E. 1996 Non-insulin
diabetes mellitus secondary to other endocrine disorders. In: LeRoith
D, Taylor SI, Olefsky JM eds. Diabetes mellitus. A fundamental and
clinical text. New York: Lippincott-Raven; 496502.
-
Krupp P, Monka C, Richter K. The safety aspects of
infertility treatments. Proc of the 2nd World Congr of Gynecol and
Obstet. 1988; 9.
-
Raymond JP, Goldstein E. Konopka P, Leleu MF, Merceron
RE, Loria Y. 1985 Follow-up of children born of
bromocriptine-treated mothers. Horm Res. 22:239246.[Medline]
-
Brodsky JB, Cohen EN, Brown Jr BW, et al. 1980 Surgery during pregnancy and fetal outcome. Am J Obstet Gynecol.
138;1165.
-
Yamashita Y, Namimoto T, Abe Y, et al. 1997 MR
imaging of the fetus by a HASTE sequence. Am J Roentgenol. 168:513519.[Abstract]