Author Information
Ganapathi T *, Daigavane M **, Samant P ***
(* Third
Year Resident, ** Assistant Professor, *** Additional Professor, Department of
Obstetrics and Gynecology, Seth G.S. Medical
College and K.E.M.
Hospital , Mumbai , India.
Abstract
Prolactinoma is the most frequently occurring hormone- secreting pituitary tumor and account for approximately 25-30% of all
pituitary adenomas. Those with
diameter less than 10 mm are microprolactinomas and ones larger than 10 mm are
macroprolactinomas. They are detected earlier in women due to their effects on fertility and
menstrual cycles. Pituitary adenomas with asynchronous prolactin and growth
hormone secretion and acromegalic features are known. We present a case of
macroprolactinoma in pregnancy with acromegaloid features.
Introduction
Prolactinomas make up about 40% of pituitary tumors.[1] Prolactinoma results in
excess synthesis and secretion of prolactin. Pituitary
gland normally undergoes enlargement during pregnancy and regresses after
delivery up to six months postpartum.[2] Macroprolactinomas require
aggressive management to prevent pressure effects and complications. The
choice of treatment is difficult during pregnancy; medical
treatment is the first choice. With possibility of growth and pressure
symptoms, if adequate response is not achieved with dopamine agonists, surgery
is recommended prior to pregnancy.[3] Some adenomas are heterogeneous.
Researchers have hypothesized that patients with prolactinoma are likely to
have acromegaly as the disease progresses.[4]
Case Report
A 33 year old lady married for 5 years, with
1 abortion and with 36 weeks 3 days gestation, was referred from private hospital in
view of uncontrolled blood pressure (BP), on three antihypertensive medications. She was a known
case of hypothyroidism and hyperprolactinemia.
The patient had a spontaneous abortion 5 years
ago after which she did not conceive. Two years after abortion she noticed galactorrhea.
Also, she had rapid weight gain for a year and amenorrhea of 8 months, for
which she consulted a private practitioner. She had neither neurological nor visual
complaints.
Her blood chemistry showed hyperprolactinemia
with prolactin level of 121.2 ng/ ml. Computed Tomography (CT) scan revealed
pituitary gland enlargement of 9 mm. She was treated with cabergoline, 1 mg orally
twice a week. Cabergoline therapy was stopped after her prolactin levels fell
to normal (15.6 ng/ ml). She conceived one month after
stopping the drug.
In her present pregnancy she had uncontrolled BP,
and was on 3 antihypertensive medications, namely alfa methyl dopa
500 mg qid, nifidepine 10 mg qid and labetolol 100 mg bd. On
examination, she was obese with basal metabolic index of 40 kg/ m2.
She had acromegalic features in the form of frontal bossing, enlargement of nose and lips,
widening of distal fingers and toes, generalised hyperpigmentation, acanthosis nigricans and bilateral pedal edema. She was afebrile with pulse of 86/ min, BP of 170/110 mmHg. She had albuminuria but no premonitory symptoms. Antihypertensive
drugs were continued and labor was induced with dinoprostone gel in view of leaking per vaginum at term. The patient delivered uneventfully, a male baby
of 2.91 kg.
Figure 1. Enlargement
of forehead and jaw, enlargement of the nose and lips, oily skin.
Figure 2. Widening of distal fingers,
hands soft bread dough like.
Figure 3. Widening of distal toes and hyperpigmentation
of skin.
Her investigations were as follows: hemoglobin 13.1gm
%, fasting blood sugar of 97 mg %, postprandial sugar of 78 mg %, fasting
insulin level of 24.5 mIU/ L and thyroid stimulating hormone 5.790 U/ml. Her
postpartum abdominal and pelvic sonography was normal, and chest X-ray showed
no evidence of cardiomegaly. Magnetic resonance imaging (MRI) brain done
postpartum was suggestive of pituitary macroadenoma, 1.6 x 1.2 x 1.4 cm T2 hyperintense, T1 hypointense sellar lesion with homogenous post- contrast
enhancement. The lesion had a suprasellar extension reaching upto chiasma, left parasellar extension till the median carotid line without any right parasellar extension. The normal pituitary stalk was deviated to the right and
normal pituitary gland was compressed in the right.
Endocrinology evaluation was done and
investigations were as follows: serum prolactin of 204.6 ng/ml (in dilution of
1:5 indicating actual value of more than 1000 ng/ml), serum insulin like growth
factor (IGF-1) of 210ng/ml (normal) and glycosylated hemoglobin (HbA1 C) of 6.1%.
Endocrinologist advised that in the absence of any complaints, she should continue breastfeeding and follow up after 3 months. Further management would be decided according to hormone levels and lactating
pattern of the patient.
Discussion
Prolactinomas are seen commonly in women of
reproductive age and are seen 10 times more in women than in men. The exact
incidence of prolactinoma during pregnancy is not known. The
diagnosis of prolactinoma requires both radiographic and biochemical evidence.
Sustained hyperprolactinemia
should be documented. Normal prolactin levels in women and men are below 25
ng/ml. A
level above 250 ng/ml
is
more likely to be associated with prolactinoma and
level >500 ng/ml makes the diagnosis almost certain.[3,5] Most prolactinomas
are usually medically responsive to dopamine agonist (DA) therapy. Drugs
available for treatment are bromocriptine, cabergoline and quinagolide. Ovulation and fertility are rapidly
restored in these women and they should be informed of the same. Normalization
of prolactin levels and evidence of tumor reduction are to be ascertained in
these women to prevent effects of pressure.[6]
Managing prolactinoma during pregnancy is
challenging due to concerns about therapy with dopamine agonists. DA should be
immediately stopped once pregnancy is confirmed, except in women with invasive
macroprolactinomas.[5] Some patients with prolactinoma develop
acromegaly. They may have normal IGF-1 levels at the diagnosis of
hyperprolactinemia. In a study by Andersen et al, 3 out of 78 patients
developed acromegaly and had elevated IGF-1 levels within 2 to 5 years.[4] This
is a group with a pituitary adenoma who secrete prolactin and growth hormone
asynchronously. In such patients, annual IGF-1 screening may be recommended.[4]
Our patient had acromegaloid features but normal IGF-1 levels and is likely to
be from this category who may later develop high IGF-1 levels. Female patients
with possibly heterogeneous adenomas may primarily approach clinicians for
infertility, amenorrhea or galactorrhea. Periodic evaluation of pituitary
endocrine function is recommended in hyperprolactinemic patients.[4,7] Our
patient was evaluated for galactorrhea and amenorrhea primarily and developed
acromegaloid features in pregnancy. Visual problems or progressive headaches in
pregnancy warrant an MRI without contrast to assess tumor size, and a dopamine
agonist may be restarted. If it does not work, trans-sphenoidal surgery may be
an option.[8] Lactating Women should not be given dopamine agonists as it will
impair lactation. Lactation period
does not have any harmful influence on tumor growth in a case of prolactinoma.[8]
This is in agreement with the opinion of our endocrinologists.
Conclusion
Macroprolactinoma
in pregnancy is a rare occurrence, and its
treatment during pregnancy and lactation is challenging requiring
a combined approach by gynecologists, endocrinologists and neurosurgeons.
Patients with hyperprolactinemia may present with acromegaloid features, hence
it is essential to regularly screen these patients for overt acromegaly.
References
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Ganapathi T, Daigavane M, Samant P. Pituitary Macroprolactinoma with Acromegaly in Pregnancy: A Diagnostic Challenge. JPGO 2015. Volume 3 No. 4. Available from: http://www.jpgo.org/2016/04/pituitary-macroprolactinoma-with.html