See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/6237470

Hyperthyroidism Due to Coexistence of Graves' Disease and Struma Ovarii

Article  in  Endocrine Practice · May 2007

DOI: 10.4158/EP.13.3.274 · Source: PubMed

CITATIONS READS
14 222

5 authors, including:

Maria Grazia Chiofalo Luigi Insabato

Istituto Nazionale per lo Studio e la Cura dei Tumori. Fondazione G. Pascale, Napoli I… University of Naples Federico II
90 PUBLICATIONS   1,200 CITATIONS    258 PUBLICATIONS   5,514 CITATIONS   

SEE PROFILE SEE PROFILE

Secondo Lastoria Luciano Pezzullo

Istituto Nazionale Tumori "Fondazione Pascale" Istituto Nazionale Tumori "Fondazione Pascale"
258 PUBLICATIONS   5,227 CITATIONS    179 PUBLICATIONS   2,730 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Antibiotic prophylaxis and risk of infections in thyroid surgery: Results from a national study View project

Cytopathology of the thyroid gland View project

All content following this page was uploaded by Luciano Pezzullo on 09 March 2016.

The user has requested enhancement of the downloaded file.

Case Report
HYPERTHYROIDISM DUE TO COEXISTENCE
OF GRAVES’ DISEASE AND STRUMA OVARII
Maria G. Chiofalo, MD,1 Claudia Misso, MD,1 Luigi Insabato, MD,3
Secondo Lastoria, MD,2 and Luciano Pezzullo, MD1
ABSTRACT
Objective: To report an unusual case of persistent thy-
rotoxicosis after treatment of Graves’ disease, because of
coexistence of struma ovarii.
Methods: We report the clinical history, imaging
studies, laboratory and pathologic data, and treatment in a
patient with persistent hyperthyroidism after surgical
treatment of Graves’ disease. In addition, we discuss some
aspects of the pathogenesis of hyperthyroidism due to
functioning struma ovarii.
Results: A 42-year-old woman underwent near-total
thyroidectomy for treatment of Graves’ disease. Post-
operatively, hyperthyroidism was still present.
Methimazole was administered again, and performance of
a 131I whole-body scan demonstrated a focus of intense
uptake in the pelvis. Pelvic ultrasonography revealed a
mass (11 by 8 by 7.1 cm) arising from the right ovary,
with both solid and cystic components. Abdominal surgi-
cal exploration was performed, and the final histologic
diagnosis was struma ovarii. The symptoms of hyperthy-
roidism diminished, and 3 weeks postoperatively, the thy-
roid hormone levels were in the hypothyroid range.
Conclusion: In patients with refractory hyperthy-
roidism after thyroid surgical treatment, radioiodine scan-
ning should be performed to diagnose or exclude the func-
tioning profile of ovarian masses. (Endocr Pract.
2007;13:274-276)
Abbreviation:
TSH = thyroid-stimulating hormone (thyrotropin)
Submitted for publication April 5, 2006
Accepted for publication July 11, 2006
From the 1Department of Surgical Oncology and 2Department of Nuclear
Medicine, National Cancer Institute, Naples, Italy, and 3Department of
Pathology, University Federico II, Naples, Italy.
Address correspondence and reprint requests to Dr. Luciano Pezzullo, Via
S. Caterina 78, Naples, Italy 80132.
© 2007 AACE.
274 ENDOCRINE PRACTICE Vol 13 No. 3 May/June 2007
INTRODUCTION
Struma ovarii is a rare ovarian teratoma composed
predominantly or entirely of thyroid tissue. It constitutes
2% to 4% of ovarian teratomas (1). This tumor is often
asymptomatic and discovered incidentally. Only 8% of
patients with struma ovarii present with clinical hyperthy-
roidism (2).
We report an unusual case of hyperthyroidism attrib-
utable to concurrent Graves’ disease and struma ovarii.
CASE REPORT
A 42-year-old woman was admitted to our hospital
for treatment of Graves’ disease; the patient had had anx-
iety, palpitations, and weight loss for several months.
Physical examination revealed a large bilateral goiter,
tachycardia (95 beats/min), and a slight tremor. Eye signs
were absent.
Laboratory evaluation (Table 1) showed elevated
serum free thyroxine levels (22.84 pg/mL; reference
range, 9.3 to 17) in conjunction with low thyrotropin (thy-
roid-stimulating hormone or TSH) levels (<0.001
μIU/mL; reference range, 0.4 to 4.5) and a high titer of
TSH receptor antibodies (77.9 U/L; reference range, 0 to
1.5). Technetium-99m pertechnetate scanning of the thy-
roid showed diffuse enlargement of the gland and diffuse
increased uptake.
After preparation with an antithyroid drug (methima-
zole, 30 mg/day) and a β-adrenergic blocking agent,
euthyroidism was achieved (Table 1), and the patient
underwent near-total thyroidectomy. Histopathologic
examination revealed typical Graves’ disease.
Six months postoperatively, only slight improvement
was noted. The thyroid hormone levels had not normal-
ized (Table 1), and the patient still had symptoms of
hyperthyroidism. Furthermore, she indicated that she had
abdominal discomfort. Methimazole was administered
again (10 mg/day), and a 131I whole-body scan was per-
formed immediately after the patient had voided the blad-
der. The scan showed small foci of low radioiodine uptake
(<2%) in the thyroid bed as well as intense uptake in the
pelvis (15%) (Fig. 1). Subsequent pelvic ultrasonography
 Graves’ Disease and Struma Ovarii, Endocr Pract. 2007;13(No. 3) 275

Table 1
Thyroid Hormone Profile at Baseline and During Follow-Up

Before 6 mo Before
Study thyroid after first abdominal Reference
Variable entry operation* operation operation* range

Thyroid-stimulating hormone (μIU/mL) <0.001 <0.001 0.008 0.008 0.4-4.5

Free triiodothyronine (pg/mL) 16.4 4.9 13.4 1.8 1.8-4.6
Free thyroxine (pg/mL) 22.84 10.4 22.9 8.4 9.3-17
Human thyroglobulin antibodies (U/mL) 254 … … … 0-100
Thyroid peroxidase antibodies (U/mL) 1,607 … … … 0-20
Thyrotropin receptor antibodies (U/L) 77.9 … 72.4 … 0-1.5

*During therapy with an antithyroid drug.

revealed a mass (11 by 8 by 7.1 cm) arising from the right Malignant struma ovarii is very rare and has an incidence
ovary, with both solid and cystic components; ascites was of 0.1% to 0.3%. Only 8% of patients with struma ovarii
present. A computed tomographic scan of the abdomen have clinical hyperthyroidism (1,2).
and pelvis confirmed these findings. Tumor markers, Although goiter is rather common in patients with
including carcinoembryonic antigen and CA 125, were struma ovarii, being reported in 16% to 41% of cases (1),
normal. TSH receptor antibodies were still present. the coexistence of hyperfunctioning struma ovarii and
The presence of a functioning struma ovarii with Graves’ disease has rarely been described. Only 7 cases
ectopic thyroid hormone production was clearly consid- have been reported in the medical literature since 1970.
ered the primary cause of the clinical symptoms. These cases included 6 patients with benign struma ovarii
The patient underwent an exploratory laparotomy, and Graves’ disease and 1 patient with a combination of
and a salpingo-oophorectomy was performed. At malignant struma ovarii and Graves’ disease. One more
histopathologic examination, the ovarian mass was 12 by case of malignant struma ovarii coexisting with Graves’
8.5 by 4 cm, and the capsule was intact; mild irregularities
were present on the outer surface. The cut surface was
composed of both a solid part and multilocular cysts. An
immunohistochemical stain for thyroglobulin was positive
within the epithelium of the follicle as well as in the lumi-
nal contents; this result confirmed the thyroid epithelial
nature of the lesion. The histologic diagnosis was struma
ovarii, with absence of malignant involvement (Fig. 2).
The patient’s postoperative course was uneventful.
The symptoms of hyperthyroidism were alleviated, and 3
weeks postoperatively, the thyroid hormone levels were in
the hypothyroid range.
Replacement therapy with levothyroxine was initiat-
ed, and euthyroidism was achieved. Currently, the patient
is well, without evidence of hyperthyroidism.

DISCUSSION

Struma ovarii is a rare ovarian teratoma that accounts

for approximately 0.3% to 1% of all ovarian tumors. It is
biochemically and histologically identical to the cervical
thyroid tissue and can demonstrate all the pathologic pat-
terns that may be found in the thyroid gland. It occurs
most commonly in patients in the 4th to 6th decades of life Fig. 1. Whole-body 131I scan of study patient, showing intense
and is unilateral and asymptomatic in most cases. uptake in pelvic area and uptake in residual thyroid bed.
 276 Graves’ Disease and Struma Ovarii, Endocr Pract. 2007;13(No. 3)
A B
Fig. 2. Histologic appearance of ovarian mass, demonstrating struma ovarii. A, Macrofollicular and microfollicular areas are evident.
(Hematoxylin-eosin; original magnification ×100.) B, Thyroglobulin reactivity of the tumor cells. (Immunohistochemical stain; origi-
nal magnification ×200.)
disease has been reported, but in that instance, hyperthy-
roidism was related to the Graves’ disease alone (1,3-9).
In patients with struma ovarii, hyperthyroidism could
depend on 2 possible conditions: (1) the ovarian tumor can
autonomously produce hyperfunction and (2) hyperthy-
roidism can be caused by coexisting Graves’ disease. In
this situation, the hyperfunction could be correlated with
the presence of circulating TSH receptor antibodies. In
fact, TSH receptor antibodies can stimulate the thyroid tis-
sue of the struma ovarii in the same manner as in the cer-
vical thyroid gland (3).
Hyperthyroidism due to the coexistent presence of
Graves’ disease and struma ovarii is an extremely rare
condition. The peculiarity of the current case was the
unexpected persistence of thyrotoxicosis after the treat-
ment of Graves’ disease. The symptoms of hyperthy-
roidism, initially attributed to Graves’ disease, persisted
after a thyroid surgical procedure. Serum TSH and free
thyroxine levels failed to normalize, and high titers of cir-
culating TSH receptor antibodies were still present (Table
1). The ectopic thyroid hormone production was detected
by a whole-body scan with 131I. On the basis of the clini-
cal history and the positive TSH receptor antibodies, we
postulated that Graves’ disease preceded the struma ovarii
and that the ovarian tumor was stimulated by circulating
TSH receptor antibodies.
In most cases of struma ovarii previously reported in
the literature, radioiodine scanning was not performed;
however, in 4 cases of struma ovarii coexisting with
Graves’ disease, the diagnosis of struma ovarii was sug-
gested preoperatively by radioiodine uptake or 99mTc
pertechnetate scanning (1,3,5,7). The evidence of radioio-
dine uptake in the lower abdominal area, where an ovari-
an tumor was present, strongly suggested the presence of
struma ovarii. Alternatively, the differential diagnosis of
increased radioiodine uptake in the abdomen also includes
metastatic lesions of thyroid cancer and the very rare so-
called pseudo-struma ovarii (1).
View publication stats
CONCLUSION
In patients with refractory hyperthyroidism after thy-
roid surgical treatment, radioiodine scanning should be
performed to diagnose or rule out the functioning profile
of ovarian masses.
DISCLOSURE
The authors have no conflicts of interest to disclose.
REFERENCES
1. Bayot MR, Chopra IJ. Coexistence of struma ovarii and
Graves’ disease. Thyroid. 1995;5:469-471.
2. Kouraklis G, Safioleas M, Glinavou A, Xipolitas N,
Papachristodoulou A, Karatzas G. Struma ovarii: report
of two cases and clinical review. Eur J Surg. 2001;167:470-
471.
3. Mimura Y, Kishida M, Masuyama H, et al. Coexistence
of Graves’ disease and struma ovarii: case report and litera-
ture review. Endocr J. 2001;48:255-260.
4. Kempers RD, Dockerty MB, Hoffman DL,
Bartholomew LG. Struma ovarii—ascitic, hyperthyroid,
and asymptomatic syndromes. Ann Intern Med. 1970;72:
883-893.
5. Lazarus JH, Richards AR, MacPherson MJ, et al.
Struma ovarii: a case report. Clin Endocrinol (Oxf). 1987;
27:715-720.
6. Kung AW, Ma JT, Wang C, Young RT. Hyperthyroidism
during pregnancy due to coexistence of struma ovarii and
Graves’ disease. Postgrad Med J. 1990;66:132-133.
7. Bartel TB, Juweid ME, O’Dorisio T, Sivitz W, Kirby P.
Scintigraphic detection of benign struma ovarii in a hyper-
thyroid patient. J Clin Endocrinol Metab. 2005;90:3771-
3772.
8. Sussman SK, Kho SA, Cersosimo E, Heimann A.
Coexistence of malignant struma ovarii and Graves’ dis-
ease. Endocr Pract. 2002;8:378-380.
9. Kano H, Inoue M, Nishino T, Yoshimoto Y, Arima R.
Malignant struma ovarii with Graves’ disease. Gynecol
Oncol. 2000;79:508-510.