Cancer Therapy Vol 3, 397-400, 2005

Spontaneous ovarian hyperstimulation syndrome caused by hypothyroidism

Case Report

Azam Sadat Mousavi*, Nadereh Behtash, Malihe Hasanzadeh, Mitra Modares Gilani, Fatemeh Ghaemmaghami, Encie Shahroch, Tehrani Nejad

Department of Gynecology Oncology, Reproductive Health Research center, Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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*Correspondence: Azam Sadat Mousavi, Gynecology-Oncology Department, Vali-e-Asr Hospital, Imam Khomeini Hospital, Keshavarz Blvd., Tehran 14194, Iran.; Phone: # 98-21-723430, 773330, 6937766, 6930666; Fax: # 98-21-7880161, 8504404, 6937321, 6937766; E-mail: a3064@sina.tums.ac.ir, valrec2@yahoo.com

Key words:

Abbreviations: ovarian hyperstimulation syndrome, (OHSS); vascular endothelial growth factor, (VEGF)

Received: 16 May 2005; Revised: 10 June 2005

Accepted: 13 June 2005; electronically published: July 2005

Summary

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of assisted reproductive technology conception of unknown pathogenesis. Spontaneous ovarian hyperstimulation has been reported in women with hypothyroidism, polycystic ovary syndrome, pregnancy, gonadotroph pituitary adenoma. To our knowledge only four cases of spontaneous OHSS have been described in non pregnant women with primary hypothyroidism. A 26-year-old primiparous presented with abdominal pain, myxedematous facies and bilateral multiseptated ovarian cysts. Thyroid stimulating hormone was elevated and total thyroxin and T₃ and free thyroxin index and T₃ resin uptake were low. Hypothyroidism associated with spontaneous ovarian hyperstimulation was confirmed. She had sever abdominal pain. We performed aspiration of cysts. Abdominal pain disappeared. We also started levothyroxin. After six months, follow up serial sonography is normal. Hypothyroidism can be associated with ovarian hyperstimulation. We must treat these patients with conservative management.

I. Introduction

Ovarian hyperstimulation syndrome usually occurs in association with ovulation induction, but the physiopathologic mechanisms are understood poorly (Mcelhinney and Mcclure, 2000). Spontaneous ovarian hyperstimulation has been reported in women with hypothyroidism (Rotmonsch and Scommegna, 1989; Van Voorhis et al, 1994; Hansen et al, 1997; Nappi et al, 1998; Cardoso et al, 1999), polycystic ovary syndrome and pregnancy (Zalel et al, 1995), gonadotroph pituitary adenoma and pregnancy (Shimon et al, 2001). A med line search using the key words spontaneous ovarian stimulation, hypothyroidism revealed only four cases, one of whom had Down syndrome (Cardoso et al, 1999).

The causal relationship between hypothyroidism and ovarian hyperstimulation is suggested by the consistent regression of the ovarian cysts after the institution of thyroid hormone replacement therapy (Taher et al, 2004).

II. Case report

This paper presents one new cases of OHSS and primary hypothyroidism. In Feb 2004, a 26-year-old woman (primiparous) was referred to Gynecology oncology unit in Vali-e-Asr hospital, Tehran, Iran. Upon her visit in our clinic, she had abdominal pain in lower quadrant. In physical exam, there were ascitis and bilateral adenexal, tender masses. Pelvic and abdominal sonography (Figure 1) showed bilateral multiseptated ovarian masses: the left measuring 66x63x99mm and the right 69x63x96 mm. Liver, spleen, pancreas and both kidneys were normal. There was no para-aortic lymph node enlargement and a normal urinary bladder and uterus. Bilateral pleural effusion (Right more than left) were noted on chest x-ray, CA 125 was 81 Iu/ml (normal<35u/ml), another tumor markers were negative. Primary diagnosis was ovarian cancer. In past medical history, she had hypothyroidism, nine years ago. She interrupted her treatment six years ago. Hormonal studies

confirmed hypothyroidism with TSH>50 miu/lit (0.2-5.1 miu/lit), total T₄ 0.3 mcg/dl (4.5-12.5 mcg/dl), T₃ resin uptake 20% (25-35), free thyroxin index 0.1 (1.4-4.4), T₃ 0.4 ng/ml (0.7-2.1 ng/ml).

She was started on levothyroxin 100 mcg per day. Due to abdominal pain, aspiration of ovarian cysts was done under ultrasonographic guidance. Cytology of specimen was negative.

Six months after starting thyroxin replacement and aspiration, serial follow up sonography show normal size her ovaries.

III. Discussion

Our patient presented with acute severe abdominal pain and was found to have bilateral large complex ovarian masses, mimicking ovarian cancer. CA125 was elevated, she was also found to have pleural effusion. Early diagnosis was ovarian cancer. Due to past medical history of hypothyroidism, hormonal studies performed. Thyroid hormonal studies confirmed primary hypothyroidism.

The exact mechanism by which ovarian hyperstimulation might occur in hypothyroid patients is not understood clearly. A possible explanation was suggested by Rotmensch and Scommegna, on the basis of preferential formation of estriol in hypothyroid patients, Estriol is a weaker suppressor of gonadotropin release than estradiol and there is excessive gonadotropin release (Rotmonsch and Scommegna, 1989).

Grumbach explained another explanation, on the basis of low levels of thyroid hormone. It might activate the release of FSH and LH besides the targeted activation of TSH release (Grumbach and Styne, 1998). Another explanation of this rare association is that TSH has weak FSH activity on FSH receptors causing gonadal stimulation (Anasti et al, 1995).

It has been suggested that follicular aspiration offers partial protection against the hyperstimulation syndrome (Speroff et al, 1999).

Abu-louz reported one case of hyperstimulation syndrome was associated with pregnancy, aspiration of large superficial ovarian cyst was done under ultrasonographic guidance and laparatomy avoided (Abu-Louz et al, 1997).

Ovarian hyper stimulation can be life-threateniy. The ovaries are tremendously enlarged with multiple follicular cysts, stromal edema, and many corpora lutea. Because of this enlargement, torsion of the adnexa is a relatively Common complication of this Syndrome. It might be expected that the mild type would be relatively common.

The genesis of the ascites is unclear. The very high level of estrogen secretion by the ovaries may be the primary factor, inducing increased local capillary permeability and leakage of fluid from the peritoneal capillaries as well as the ovaries.

A growing body of evidence implicates vascular endothelial growth factor (VEGF) in the pathophysiology of the hyper stimulation syndrome. The origin of VEGF is presumed to be the ovarian follicle, and increased capillary permeability and the severity of the syndrome are correlated with circulatory levels of VEGF. Other cytokines, especially the interlukin family is also believed to be involved in the permeability changes, and it is the hypothesized that these agents effect the nitric oxide system.

Aspiration of ascites can also be accomplished transvaginally (with ultrasound guidance).

Transvaginal aspiration of follicular structures should be considered to interfere with the intra ovarian mechanism responsible for the clinical picture. laparatomy should be avoided in these precarious patients.

The key point is that the hyper stimulation syndrome will undergo gradual resolution within several months.

IV. Conclusion

This case suggests a possible relationship between spontaneous ovarian hyperstimulation and primary hypothyroidism. Thyroid hormone replacement seems to be the best therapeutic approach in such patients; thyroid function should be measured in women with spontaneous hyperstimulation ovaries. We must mention that t the hyperstimulation syndrome will undergo gradual resolution with times and laparatomy should be avoided in these patients. Follicular aspiration is one option of conservative management in acute condition.

The key point is that theovarian hyperstimulation syndrome in hypothyroid patients may mimic ovarian tumors.

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