Dr. S. Krishnakumar is the chief consultant at JK Women Hospital in Mumbai suburban area. He is the secretary general of Indian Association of Gynaecological Endoscopists (IAGE) and Indian Society for Assisted Reproduction (ISAR). He is also an honorary consultant at Fortis Hospital. He is an excellent teacher and has trained may postgraduate candidates in the field of endoscopy and reproductive medicine via ICOG courses. He has an ESHRE certification for reproductive endoscopic surgery. He is a dynamic orator and a diligent clinician. He has revolutionized the outlook on hysteroscopic surgery around the world and conducts numerous training programs for budding gynecologists.
Ovarian hyperstimulation syndrome (OHSS) is a devastating complication seen in patients undergoing ovulation induction, usually with gonadotropins. Rarely, young patients may present with a spontaneous OHSS. This has been reported in cases of gonadotropin-secreting pituitary adenoma, primary hypothyroidism and at times even in normal pregnancy [1, 2]. Here, we report a case of a young adolescent presenting with bilateral large ovarian masses with multiple differential diagnosis but eventually detected as a case of spontaneous OHSS secondary to hypothyroidism.
Case Report
An adolescent who was 10 years and 8 months old presented
to us with chief complaints of severe pain in abdomen since
1 week and amenorrhea since 6 months. There was no history
of headache, vomiting, visual disturbances or seizures.
She attained her menarche at the age of 10 years and had two
cycles of bleeding at an interval of 15 days. On examination,
she was well built with a height of 137 cm, weight of
47.2 kg, pulse rate of 96/min, BP of 100/70 mmHg, cushingoid
face with thick skin and pallor was present; however,
there was no edema. As per Tanner’s staging, her sexual maturation score was B3 and P3 for breast and pubic hair,
respectively, and sparse axillary hair were present. On per
abdominal examination, abdomen appeared distended below
umbilicus and a 24-week irregular mass was felt arising
from the pelvis.
Investigations revealed hemoglobin of 11.5 g/dl, total
leukocyte count of 9500 and ESR of 53. Hormonal investigations
were performed with LH < 0.09 IU/L, FSH
9.46 mIU/L, prolactin 55.42 ng/ml, ACTH 13.2 pg/ml,
DHEAS 17.1 mcg/dl and GH 0.27 ng/ml. Her thyroid function
test showed FT3-135 ng/dl, FT4-8.4 ng/dl and TSH-
1.82 μIU/ml. Elevated prolactin levels prompted an MRI
brain which revealed a diffusely enlarged homogenously
enhancing pituitary with a convexity along superior margin
suggestive of a possibility of pituitary macro-adenoma or
pituitary hyperplasia. As the gonadotropin values being in
the normal range and lack of associated symptoms, the possibility
of pituitary adenoma was ruled out.
Ultrasound revealed markedly enlarged ovaries
with multiple cystic spaces with right ovary measuring
14.6 × 10.7 × 9.1 cm and left ovary 10.4 × 7.3 × 5.8 cm.
However, on Doppler, fairly high-resistance flow was noted.
MRI pelvis was suggestive of bilateral multiloculated cystic
adnexal lesions with differential diagnosis of mucinous cystadenoma,
endometriosis or hyperstimulated ovaries. Serum
tumor markers done to rule out malignancy were CA-125
72.3 U/ml, alpha-fetoprotein 5.47 ng/ml and LDH 885 IU/L
(Fig. 1).
Despite high LDH and CA-125 levels, the radiological
findings were not coherent with malignancy. Also the characteristic
soap bubble appearance noted on ultrasound was
suggestive of the probability of ovarian hyperstimulation.
Hence, due to high clinical suspicion, a repeat thyroid profile
was done and values noted were as follows: FT3 50.08 pg/
ml, FT4 1.97 ng/ml and TSH > 500 μIU/ml. TPO antibody
level was 897 IU/ml, and thyroglobulin antibody 11.9 IU/ml.
A diagnosis of spontaneous OHSS secondary to hypothyroidism
was made, and she was started on levothyroxine
75 μg. Subsequent ultrasonography done after 3 months
revealed a significant decrease in the ovarian size and volume, right ovary measuring 3.6 × 3.3 × 3.1 cm (vol.
18.4 cc) and left ovary measuring 3.5 × 3.3 × 3 cm (vol.
17.3 cc). There was also a complete resolution of her symptoms.
Repeat thyroid profile done after 3 months showed
values in the normal range (FT3-5.97 pg/ml, FT4-1.41 ng/
dl and TSH-2.20 μIU/ml) (Fig. 2).
Spontaneous OHSS is an uncommon clinical entity occurring
due to non-iatrogenic aetiologies. De Leener et al.
described a classification system of spontaneous OHSS
which divides it into three types:
Type I Related to mutations in the FSH receptor.
Type II Secondary to elevated levels of human chorionic
gonadotropin (HCG) hormone seen in hydatidiform
mole, multiple pregnancies and polycystic
ovarian patients who are pregnant.
Type III Due to primary hypothyroidism.
The exact pathogenesis of this entity is complex. In type
III patients, long-standing deficiency of thyroid hormone
induces hyperplasia of the lactotropic as well as thyrotropic
cells in the pituitary gland leading to elevated levels of
prolactin and thyroid-secreting hormone (TSH). The beta
subunit of TSH has identical configuration with that of
FSH; hence, it stimulates the FSH receptor. In addition, it
leads to pituitary hyperplasia which may mimic a pituitary
adenoma. Also, there is a preferential formation of estriol
which is a weak form of estrogen leading to over-production of gonadotropins. All these can contribute to the hyperstimulation
of ovaries.
The clinical symptomatology can vary depending upon
the severity of OHSS and occurs primarily due to extravascular
accumulation of fluid. Hormonal evaluation in these
patients reveals a markedly elevated TSH and raised anti-
TPO-antibodies suggestive of autoimmune involvement. The
treatment is often simple and involves a dramatic response
to thyroid supplementation [3].
The suspicion of malignancy is high in a young adolescent
presenting with large bilateral ovarian masses. Germ
cell tumors are more common in this age group. Serum
tumor markers and specific radiological findings like the
presence of solid areas and ascites can aid in the diagnosis.
Van Wyk-Grumbach syndrome is also an important differential
diagnosis in these cases and is characterized by isosexual
precocious puberty, juvenile hypothyroidism, a delayed
bone age and the presence of ovarian cysts [4]. Pituitary
adenoma can also present with similar complaints; however,
characteristic features like visual field defects, headache,
galactorrhea and unexpected bone growth help to reach the
diagnosis.
A wide array of investigations need to be performed to
identify the aetiology of spontaneous OHSS. Ultrasonography
in these cases reveals a classical soap bubble or spokes
in wheel appearance of the ovarian masses. These represent
enlarged multiple follicles arranged peripherally. The final
treatment in these cases depends on the underlying pathology.
Knowledge of such uncommon conditions among
gynecologists, radiologists and primary care physicians is
essential to avoid misdiagnosis, unnecessary surgery and
loss of ovarian reserve.
Conflict of interest The authors declare that they have no conflicts of interest.
