The Indian Journal of Pediatrics

https://doi.org/10.1007/s12098-018-2704-2

CLINICAL BRIEF

Van Wyk Grumbach Syndrome: A Rare Consequence of Hypothyroidism

Pavan Reddy 1 & Kritika Tiwari 1 & Abhishek Kulkarni 1 & Ketan Parikh 1 & Raju Khubchandani 1

Received: 28 April 2018 / Accepted: 4 May 2018

# Dr. K C Chaudhuri Foundation 2018

Abstract
Long standing hypothyroidism presenting as an ovarian mass has been well described in literature as the Van Wyk Grumbach
syndrome (hypothyroidism, isosexual precocious puberty and ovarian mass). Here, authors report this entity in a 11 y 7 mo old
girl child who was referred to a surgeon in view of intestinal obstruction along with a multiloculated ovarian cyst. On evaluation,
she was found to have raised serum creatinine, short stature, delayed bone age and pituitary enlargement. She was diagnosed with
autoimmune thyroiditis and was started on replacement therapy with thyroxine, after which the ovarian cysts regressed. This
entity should be kept in mind in cases of ovarian cysts, especially those with isosexual precocity, to prevent unnecessary
evaluation and surgical misadventures.

Keywords Hypothyroidism . Precocious puberty . Ovarian mass . Van Wyk Grumbach syndrome

Introduction to presentation. Examination revealed an adynamic ileus. A

The term ‘Van Wyk Grumbach Syndrome’ (VWGS) was
coined in 1960 to describe a constellation of hypothyroidism,
precocious puberty and ovarian mass [1]. Seen in cases of
longstanding, untreated hypothyroidism, this is a hormonal
overlap syndrome. Precocious puberty here is associated with
a delayed bone age and is isosexual and incomplete [2].
Complete resolution of all the features is seen after starting
thyroid hormone replacement therapy.
The authors describe a case who first presented to the pe-
diatric surgeon and a timely diagnosis saved unnecessary sur-
gical exploration.
Case Report
An 11 y 7 mo old female child was referred to a pediatric
surgeon (KP) with slowly progressive abdominal distension
over 2 years, aggravated over last 8 days, associated with
generalized continuous dull aching pain, decreased appetite
and lassitude. She also had bilious vomiting for 3 days prior
* Pavan Reddy
pavanry@gmail.com
1
Department of Pediatrics, Jaslok Hospital and Research Centre,
Mumbai, India
vertical X-ray abdomen showed multiple air fluid levels sug-
gesting intestinal obstruction and an ultrasonography of the
abdomen showed a large multiloculated cystic mass in the
pelvis measuring 11.7 × 9.9 × 7.6 cm. Both the ovaries were
not visualized separate from the lesion prompting the
sonologist to report it as an ovarian mass. Contemplating ex-
ploration, the surgeon performed preoperative investigations
which showed a hemoglobin of 8.1 g/dl and a creatinine of
2.3 mg/dl. Tumor markers were HCG-beta – < 5.0mIU/ml,
AFP – 5.55 ng/ml, CEA – <1 ng/ml, CA125 – 116 U/ml. In
view of raised serum creatinine, low hemoglobin and adynam-
ic ileus without signs of peritonitis, the case was referred to
medical services (RK).
The authors further elicited history of chronic constipation
with progressive abdominal distension and slowing of growth
since one and a half years. She also had irregular scanty vaginal
spotting since one year. On examination, her weight was 45.6 kg
(between 50-75thcentile), height was 127 cm (<3rdcentile, target
height –147 cm) and body mass index (BMI) was 28.6 (>95th
centile). As per Tanner’s staging, her sexual maturity rate was 4
for breast development and 1 for pubic hair. Hemodynamically,
she was stable. She had pallor and markedly dry, scaly skin with
acanthosis nigricans on the neck. Her abdomen was distended
(girth −90 cm), umbilicus everted, bowel sounds were absent,
liver and spleen were not palpable. There was evidence of asci-
tes. Other systems were normal. The constipation, dry skin,
arrested growth, generalized weakness and adynamic ileus led
authors to suspect hypothyroidism.

Thyroid profile confirmed severe hypothyroidism due
to autoimmune thyroiditis [thyroid stimulating hormone
(TSH) 489.1 μIU/ml, T3 0.8 pg/ml (2.7–5.2), T4 0.07 ng/
ml (0.90–1.67), TPO 284 IU/ml, antithyroglobulin anti-
bodies −244.1 IU/ml]. The combination of autoimmune
hypothyroidism and an ovarian mass led to the diagnosis
of VWGS. Further investigations were done for pubertal
status which showed prepubertal levels of follicle stim-
ulating hormone (FSH), luteinizing hormone (LH) but
pubertal levels of estradiol (FSH-11.7 mIU/ml, LH <1m
IU/ml, estradiol-32.2 pg/ml). Bone age was delayed, i.e.,
8 years 9 months. MRI brain revealed a ‘mass’ in the
pituitary fossa of size 1.4 × 1.2 × 1.0 cm with suprasellar
extensions, reported as a pituitary adenoma (Fig. 1).
Thyroid gland was atrophic on sonography. The combi-
nation of hypothyroidism, isosexual precocious puberty,
ovarian mass and Bpituitary adenoma^ confirmed the di-
agnosis of VWGS.
The child was started on Thyroxine (75mcg and
100mcg on alternate days) and Metformin (500 mg).
The dose of thyroxine was titrated according to the
levels of TSH which was regularly monitored. She
showed excellent improvement and her ovarian cyst
regressed to 2.8 × 2.3 × 1.7 cm after one year of treat-
ment, height increased by 9 cm, irregular bleeding
stopped and creatinine levels normalized.
Discussion
In 1905, Kendle first described this entity in a 9 y old girl with
menarche at age of 5 y, fully developed breasts and clinical
symptoms of female cretinism [3]. Since then, more than 100
sporadic cases have been reported worldwide.
VWGS is most commonly seen in prepubertal girls
with breast development, vaginal bleeding, cystic ova-
ries, growth retardation, pituitary hyperplasia and
Fig. 1 MRI brain showing a ‘mass’ in the pituitary fossa
Indian J Pediatr
ovarian mass due to myxedematous infiltration of the
ovaries. It has rarely been reported in boys who present
with macroorchidism without virilization [4].
Several theories have been postulated to explain the mech-
anism that occurs in VWGS. Van Wyk and Grumbach origi-
nally attributed it to a hormonal overlap in pituitary feedback
mechanism. TSH, FSH, LH and human chorionic gonadotro-
pin (hCG) are glycoprotein hormones which share a common
alpha subunit but different beta subunits. Thus, TSH, in high
concentrations, stimulates the FSH receptor leading to an in-
crease in gonadal size and steroidogenesis [5]. In girls, ovarian
cysts form due to increased estrogen synthesis, which also
leads to breast development and uterine bleeding in the ab-
sence of pubic and axillary hair development. Another theory
states that elevated thyrotropin releasing hormone (TRH)
stimulates FSH secretion and causes thyrotroph hyperplasia
resulting in pituitary enlargement and expansion of the sella
turcica, often reported as a pituitary adenoma [6].
Mild elevation of CA125, which was seen in index case,
and alpha fetoprotein, is a known occurrence in these cases
and maybe due to increased secretion by ovarian cyst, perito-
neal inflammation, long standing hypothyroidism or delayed
clearance [7]. Elevated levels of serum creatinine are known
with hypothyroidism as it leads to a decrease in glomerular
filtration rate [8].
The present case is unique as the child presented with acute
intestinal obstruction and was referred to the surgeon. Lack of
knowledge of this entity may lead to unnecessary surgical
exploration, or even oophorectomy, a surgical misadventure
which has been described in literature [9].
Hypothyroidism is usually associated with delayed puberty
but in VWGS, it is associated with precocity. Secondly, bone
age, which is normally accelerated in precocious puberty, is
delayed in VWGS. The third paradox is that hypothyroidism
is known to be the cause of sparse hair growth but
hypertrichosis is seen in this syndrome. Hence, VWGS may
also be called the ‘syndrome of paradoxes’.
Conclusions
VWGS is an atypical presentation of a common endocrinal
disorder. Hypothyroidism presents with many subtle signs.
Knowledge of the varied presentations and its association
helps in early recognition of this condition and prevents un-
necessary investigations and surgical exploration.
Author Contributions PR: Work up of the case, followed up the case,
reviewed the literature and drafted the manuscript; KT: Reviewed the
literature and drafted the manuscript; AK: Work up and management of
the case; KP: Diagnosis and management of the case; RK: Work up and
management of the case, evaluation of manuscript and gave final approv-
al; RK will act as guarantor for the paper.
Indian J Pediatr

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Conflict of Interest None.
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