THYROIDVolume 9, Number 5, 1999Mary Ann Liebert, Inc.

Struma Ovarii and HyperthyroidismTHOMAS DUNZENDORFER,1 ANTONIO deLAS MORENAS,2 TAMARA KALIR,3 and

ROBERT M. LEVIN4

ABSTRACT

Struma ovarii is a teratoma of the ovaries that contains a large amount of thyroid tissue. Like the cervical thy-roid gland, this ectopic thyroid tissue can become autonomous. We present a case of hyperthyroidism caused bythyroid tissue in a large ovarian cystic teratoma and provide detailed endocrinological, radiological, and patho-logical preoperative and postoperative data. This is also the first documented case of struma ovarii in associationwith a secreting pituitary tumor. In addition, we provide a retrospective pathological analysis of 1390 surgicallyremoved ovarian tumors at 2 major academic centers.

INTRODUCTION

Struma ovarii is a benign cystic teratoma of the ovariesin which thyroid tissue constitutes a major cellular por-

tion of the neoplasm (1). Clinically insignificant smallquantities of thyroid tissue are occasionally found in ovar-

ian teratomas, as was first described in 1889 (2). However,the diagnosis of struma ovarii requires either thyroid tis-sue as a major constituent, or sufficient thyroid hormoneproduction to cause hyperthyroidism (3). Thyrotoxicosisdue to hyperfunctional autonomous ovarian thyroid tissueis extremely rare (4). A major review in 1973 uncoveredonly 10 patients in whom symptoms compatible with thy-rotoxicosis resolved after an ovarian resection (5). The trueincidence of hyperthyroidism due to struma ovarii is un-

known, particularly as some of the reported cases date backto a time when precise thyroid function tests were un-

available.

CASE REPORT

A 40-year-old woman presented with galactorrhea,oligomenorrhea, and infertility. She had 4 healthy childrenand had regular menses until her current presentation. Herlast pregnancy occurred at age 30. Despite further effortsto conceive, she remained infertile. Laboratory evaluationat that time revealed an elevated prolactin (PRL) level of73 MIU/mL. Thyroid function tests and routine blood tests

were normal (Table 1 ). A head computed tomographic scan

(CT) showed a normal pituitary gland. The patient was

lost to follow-up.Three years later, at age 43, the patient saw an en-

docrinologist. She was still infertile and oligomenorrheicbut galactorrhea had resolved spontaneously. Physical ex-amination including visual field examination was againnormal, and endocrine tests (Table 1 ) were significant forsuppressed thyroid-stimulating hormone (TSH) and hy-perprolactinemia. A magnetic resonance imaging (MRI) re-

vealed a 5-mm pituitary adenoma. The diagnosis of a mi-croprolactinoma was made, and she was started on dailybromocriptine 2.5 mg, and levothyroxine 50 pg.

One year later, at age 44, and still on bromocriptine, re-sults from a pituitary MRI were normal. Repeated testsover the following 5 years revealed normal PRL levels,normal to high-normal triiodothyronine (T3) and thyrox-ine (T4) levels and suppressed, or very low TSH levels(Table 1).

Five years later, at age 49, the patient presented at ourcenter with persistent complaints of oligomenorrhea andinfertility, but was otherwise well. Physical examinationwas normal. There was no thyromegaly. Levothyroxinewas stopped, but 6 months later TSH remained suppressedand T3, T4, reverse T3, and T3-uptake were still in the highnormal range (Tables 1 and 2). Ectopic thyroid hormoneproduction was suspected after factitious thyrotoxicosiswas excluded by finding thyroglobulin to be markedly el-evated at 1690 ng/mL (normal: 2.3-52.5). A thyroid 123-

1 Berkshire Physicians and Surgeons, Pittsfield, Massachusetts.2Mallory Institute of Pathology, Boston Medical Center, Boston, Massachusetts.3Department of Pathology, The Mount Sinai Medical Center, New York, New York.4Section of Endocrinology, Boston Medical Center, Boston, Massachusetts.

499

500 DUNZENDORFER ET AL.

Table 1. Clinical and Hormonal Data

TSH LT4 Tg PRL Treatment

40 0.9 643 <0.05 6.444 <0.03 11.949, before oophorectomy <0.03 11.349, 2 weeks after oophorectomy <0.03 4.249, 8 weeks after oophorectomy 2.8 6.6

17163

169034

73929.42.63.13.3

levothyroxine, bromocriptinelevothyroxine, bromocriptine

BromocriptineBromocriptineBromocriptine

Thyroid function tests from 9 years before to 2 months after resection of struma ovarii.TSH, thyrotropin, normal: 0.35-5.5 MIU/L; LT4, levothyroxine; normal: 4.5-10.9 ng/dL; Tj, triiodothyronine; normal: 60-181 ng/dL;

Tg, thyroglobulin; normal: 2.3-52.5 ng/mL; PRL, prolactin; normal: 1.4-18.1 MIU/mL.

Table 2. Biochemical Tests

Reverse T3; normal; 90-350 pg/mL

T3 uptake; normal: 22%-37%

before oophorectomy 311after oophorectomy 89before oophorectomy 33after oophorectomy 28

Luteinizing hormone (nl: follicular phase: 1.9-12.5 MIU/mL) 10.6Follicle stimulating hormone (nl: follicular phase: 2.5-10.2 MIU/mL) 9.8Progesterone (nl: follicular phase: 0.15-1.4 ng/mL) 1.7Estradiol (nl: 23-443 pg/mL) 78.2Human chorionic gonadotropin b-HCG (nl: <2 MIU/mL) <2

T3, triiodothyronine.

iodine uptake and scan was performed. It revealed low cer-

vical thyroid uptake (<5%), and showed no radioactivityover the pelvis. The whole-body scan was then repeatedusing 131-iodine and intense uptake in the pelvis was ob-served (Fig. 1). Abdominal ultrasound showed a 5 X 5 X6 cm left ovarian mass. Color flow and Doppler imagingrevealed prominent vascular flow within the echogenic por-tion of the mass.

The patient underwent salpingo-oophorectomy. The re-

sected ovarian cyst consisted of a mature teratoma con-

taining predominantly thyroid tissue (Fig. 2).Two weeks postoperatively, thyroid hormone levels fell

into the hypothyroid range and thyroglobulin had de-creased to normal (Tables 1 and 2). TSH was still sup-pressed due to prolonged feedback inhibition by the strumaovarii. Eight weeks postoperatively, her thyroid functiontests had completely normalized.

FIG. 1. 131I scanning shows the cervical thyroid on top andan area of intense uptake in the pelvis.

FIG. 2. Photomicrograph of resected struma ovarii (X50).Thyroid kolloid is apparent on the right bottom, and ovariantissue on top left.

STRUMA OVARII AND HYPERTYHROIDISM 501

Table 3. Pathology of Ovarian Tumors

TeratomaOvarian tumor Teratoma with thyroid foci Struma ovarii

Mount Sinai Hospital 1276 123 (9.6%) 5 (0.4%) 2 (0.2%)Boston Medical Center 114 44(38.6%) 3(2.6%) 3(2.6%)Total 1390 167 (12%) 8 (0.6%) 5 (0.4%)

Review of all surgically removed ovarian tumors over the past 2 years at The Mount Sinai Medical Center, New York City and Boston MedicalCenter, Massachusetts.

REVIEW OF OOPHORECTOMY SPECIMENS

All surgically removed ovarian tumors over the past 2years at Mount Sinai Medical Center, New York City andBoston Medical Center, Massachusetts, were reviewed. Atotal of 1390 cases were identified (Table 3). At BostonMedical Center, which covers mostly unselected patientsincluding a pédiatrie population, 38% of all ovarian tu-mors represented teratomas, while at Mount Sinai Med-ical Center, teratomas represented only 9.6% of all ovar-ian neoplasms.Teratomas with foci of thyroid tissue were seen in 8

cases (0.6%) of all specimens. Struma ovarii was diag-nosed in 2 cases at Mount Sinai Medical Center and 3cases at Boston Medical Center for a total of 0.4% ofovarian tumors.

DISCUSSION

The thyroid tissue in struma ovarii is biologically andmicroscopically identical to cervical thyroid tissue. Conse-quently, struma ovarii may demonstrate all pathologicalfeatures seen in the normal thyroid gland (6). It can pre-sent in 5 forms: (1) Asymptomatic ovarian tumor is themost common type. (2) Hyperthyroidism: this is due to au-

tonomous production of thyroid hormones by strumaovarii causing suppression of the cervical thyroid gland.After surgical resection and a period of hypothyroidism,the cervical gland resumes normal function. This situationis exceedingly rare and has been documented with thyroidhormone assays and/or uptake and scans in only a few case

reports (3-5). The other reported cases date back to a timewhen the diagnosis of hyperthyroidism was made on clin-ical grounds, and some patients were also noted to havecervical goiters. Without radioactive iodine uptake andscans one cannot be sure which patients had hyperthy-roidism on the basis of hyperfunctioning struma ovarii ordue to a cervical goiter with the incidental presence ofstruma ovarii. A recent review of 1501 ovarian neoplasmsdid not reveal a single case of hyperthyroidism due tostruma ovarii (7), and our own review of 1390 ovarian tu-mors identified 5 cases of struma ovarii but only 1 (thecurrent report) with hyperthyroidism. (3) Coexistence ofstruma ovarii and cervical goiter. This is presumably dueto coincidence of a common (cervical goiter) and a rare

(struma ovarii) disorder. (4) The association with ascitesis surprisingly common and can occur in up to 10% of allcases of struma ovarii (6,8,9). The character of the fluid isvariable and it can be associated with pleural effusion. The

latter has been designated as modified Meigs' syndrome,because the original description required the presence ofan ovarian fibroma with ascites and hydrothorax (9). (5)Malignant transformation of ovarian thyroid tissue is ex-

ceedingly rare and has only been described in individualcase reports (10).

Treatment of choice for struma ovarii is bilateraloophorectomy followed by estrogen replacement therapy(6). The contralateral ovary is removed because of a 10%chance of a contralateral teratoma (4). Alternatively, par-ticularly in women wishing to preserve fertility, if thefrozen section examination indicates absence of malig-nancy, the contralateral ovary can be preserved. Severelyhyperthyroid patients should probably be pretreated withantithyroid drugs in order to render the patient euthyroidpreoperatively. In malignant struma ovarii, body scanningafter administration of 131-iodine is as helpful in locatingmetastatic sites as it is in the discovery of struma ovarii it-self. Therapeutic doses of 131-iodine have been used totreat typical differentiated metastatic thyroid carcinoma as

well as struma ovarii (10). Obviously, after this treatment,adequate replacement of thyroid hormone has to be con-

tinued indefinitely.The review of pathological diagnoses of ovarian resec-

tion specimens at our institutions over the past two yearsuncovered a total of 1390 ovarian tumors (Table 3).Twelve percent of these were mature cystic teratomas. Thismean value falls within the range given in the literature, of5%-25%. (11) We found only 5 cases, or 0.4%, of struma

ovarii, which is similar to the reported incidence of1%. (7)

REFERENCES

1. Greer MA 1991 Thyrotoxicosis of extrathyroid origin. In:Braverman LE, Utiger RD (eds) Werner and Ingbar's: the Thy-roid. 6th ed. Philadelphia: J.B. Lippincott, p 730.

2. Boettlin R 1889 Ueber Zahnentwicklung in Dermoidzystendes Ovariums. Virchows Arch Path Anat. 115:493-504.

3. March DE, Desai AG, Park CH, Hendricks PJ, Davis PS 1988Struma ovarii: Hyperthyroidism in a postmenopausal woman.

J Nucl Med 29:263-265.4. Hamel P, Crouet H, Balouet P, Herlicoviez M 1996 Goitre

ovarien avec hyperthyroidie. J Gynecol Obstet Biol Reprod25:797-798.

5. Brown WW, Shetty KR, Rosenfeld PS 1973 Hyperthyroidismdue to struma ovarii. Acta Endocrinol 73:266-272.

6. Kempers RD, Dockerty MB, Hoffman DL, Bartholomew LG1970 Struma ovarii—Ascitic, hyperthyroid, and asympto-matic syndromes. Ann Intern Med 72:883-898.

502 DUNZENDORFER ET AL.

7. Ayhan A, Yanik F, Tuncer R, Tuncer ZS, Ruacan S 1993Struma ovarii. Int J Gynaecol Obstet 42:143-146.

8. Szyfelbein YM, Young RH, Scully RE 1995 Sttuma ovariisimulating ovarian tumors of other types. A report of 30 cases.

Am J Surg Pathol 19:21-29.9. Bethune M, Quinn M, Rome R 1996 Struma ovarii present-

ing as acute pseudo-Meigs syndrome with an elevated CA 125level. Aust N Z J Obstet Gynecol 36:372-373.

10. Mango L 1997 Radiotherapy with iodine-131 in recurrent

malignant struma ovarii. Eur J Nucl Med 24:233.11. Talerman A 1994 Germ cell tumors of the ovary. In: Kur-

man RJ (ed) Blaustein's Pathology of the Female GenitalTract. 4th ed. Springer Verlag, New York, p. 880.

Address reprint requests to:Thomas Dunzendorfer, M.D.

Berkshire Physicians and Surgeons777 North Street

Pittsfield, MA 01201

E-mail: lisatom@bcn.net