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Natural pregnancy in hypothyroid woman complicated by spontaneous ovarian hyperstimulation syndrome
Nappi et al.
March 1998 Am J Obstet Gynecol
Natural pregnancy in hypothyroid woman complicated by spontaneous ovarian hyperstimulation syndrome Raffaele G. Nappi, MD, Edoardo Di Naro, MD, Anna Pia D’Aries, MD, and Luigi Nappi, MD Bari, Italy A unique case of life-threatening spontaneous ovarian hyperstimulation syndrome, resulting from severe untreated hypothyroidism, was observed in a woman who conceived spontaneously and gave birth to a normal viable infant. (Am J Obstet Gynecol 1998;178:610-1.)
Key words: Hypothyroidism, pregnancy, spontaneous ovarian hyperstimulation syndrome
Spontaneous ovarian hyperstimulation syndrome in the absence of exogenous gonadotropins is an extremely rare occurrence and has been reported only in a woman From the Institute of Obstetrics and Gynecology II, University of Bari. Received for publication April 22, 1997; revised May 6, 1997; accepted August 13, 1997. Reprint requests: Luigi Nappi, MD, Institute of Obstetrics and Gynecology, University of Bari, Piazza Giulio Cesare, 70124 Bari, Italy. Copyright © 1998 by Mosby, Inc. 0002-9378/98 $5.00 + 0 6/1/85432
610
with polycystic ovary syndrome1 and in a hypothyroid patient with Down syndrome.2 This observation concerns the unique case of a normal child born physiologically to a hypothyroid mother who had a life-threatening ovarian hyperstimulation syndrome during a naturally occurring gestation. Case report A 34-year-old woman, gravida 2, was admitted because of abdominal pain, distention, and slight vaginal bleed-
Nappi et al. 611
Volume 178, Number 3 Am J Obstet Gynecol
ing at 12 weeks’ gestation. Hypothyroidism since birth and discontinuance of thyroid replacement therapy for several years were reported. The previous pregnancy ended with the birth of a normal child. The current gestation started spontaneously, and no medications had been taken by the patient during the preceding months. Pelvic examination revealed bilaterally enlarged cystic ovaries. Ultrasonography demonstrated a gestational sac with fetal pole and heartbeat corresponding to 12 weeks’ gestation and a hemorrhagic effusion of 8.5 × 5.0 cm within the amnion and chorion. Ovaries measured 13 cm in diameter (right) and 11 cm (left). A moderate amount of ascitic fluid was visualized in the pouch of Douglas. Table I summarizes the results of the hormonal tests performed. Nuclear magnetic resonance of the sella turcica showed diffuse pituitary hypertrophy and depression of the sellar floor. Thyroid ultrasonography showed no signs of glandular tissue in the thyroid area. The increasing ovarian size caused further abdominal distention that was made worse by the development of ascites. The formation of a pericardial effusion and onset of oliguria, nausea, and blurring of vision critically worsened the clinical picture. L-Thyroxine therapy 75 µg daily was instituted, which progressively reached the dose of 200 µg per day. Lowmolecular-weight dextran and electrolytic solutions were infused intravenously, with careful assessment of fluid intake and output. Within 2 weeks a remarkable improvement was observed, with gradual resolution of ascites and pericardial effusion, restoration of diuresis, reduction of ovarian size, and decrease in thyroid-stimulating hormone and β-human chorionic gonadotropin to levels close to normal. The scant show of blood observed on admission caused by decidual hemorrhage was no longer present. Fetal growth increased normally. By means of amniocentesis a normal fetal chromosome map (46,XX) could be evidenced. Thyroid therapy was never discontinued, and clinical and laboratory controls were periodically carried out up to 38 weeks’ gestation. At this time the woman went into spontaneous labor and gave birth to a viable child weighing 3250 gm. Comment Thyroid hormones play a direct role in ovarian physiologic features owing to two nuclear receptors, TRα and TRβ, that are present in human granulosa cells. High levels of thyroid-stimulating hormone stimulate follicular growth in young rats and can mediate ovarian hyperstimulation in hypothyroid women.2 In these patients a raised rate of 16α-hydroxylation of estradiol results in increased formation of estriol. This altered metabolism of estrogen
Table I. Results of hormonal tests β-Human chorionic gonadotropin 17β-Estradiol Follicle-stimulating hormone Thyroid-stimulating hormone Triiodothyronine Thyroxine Free triiodothyronine Free thyroxine Luteinizing hormone Progesterone Prolactin Human growth hormone Somatomedin
12,8461 mIU/ml 9150 pg/ml 0.6 mIU/ml >350 µU/ml 0.31 ng/ml 0.8 µg/dl Undetectable Undetectable 0.5 mIU/ml 89.4 ng/ml 50.7 ng/ml >0.5 ng/ml 40.5 ng/ml
may cause an inadequate feedback at the pituitary level, with unrestrained release of gonadotropins. The excessive levels of this hormone on ovarian tissue may induce a severe cystic reaction of the ovaries and a fluid shift into the third space responsible for ascites, hydrothorax, hydropericardium, hypovolemia, oliguria, electrolyte imbalance, and hemoconcentration, thus producing the ovarian hyperstimulation syndrome. In animal models the often massive collection of fluid found in ovarian hyperstimulation syndrome has been related to increased capillary permeability, particularly of the ovarian vessels. However, elevated levels of vascular endothelial growth factor in the follicular fluid, cytokines, angiotensin II, interleukin-2, interleukin-6, and a variety of other substances (prostaglandins, histamine, serotonin, prolactin) have also been postulated as possible mediators of the capillary permeability increase. Actually, the real cause of the third-space fluid shift is still not clearly understood, and no specific treatment is known. In this patient thyroid replacement therapy and fluid administration produced a prompt improvement of the ovarian hyperstimulation syndrome, favoring the continuation of pregnancy to term. Occult hypothyroidism should always be suspected in spontaneous ovarian hyperstimulation syndrome.
REFERENCES
1. Zalel Y, Orvieto R, Ben-Rafael Z, Homburg R, Fischer O, Insler V. Recurrent spontaneous ovarian hyperstimulation syndrome associated with polycystic ovary syndrome. Gynecol Endocrinol 1995;9:313-5. 2. Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. Am J Obstet Gynecol 1989;160:1220-2.
March 1998 Am J Obstet Gynecol
Natural pregnancy in hypothyroid woman complicated by spontaneous ovarian hyperstimulation syndrome Raffaele G. Nappi, MD, Edoardo Di Naro, MD, Anna Pia D’Aries, MD, and Luigi Nappi, MD Bari, Italy A unique case of life-threatening spontaneous ovarian hyperstimulation syndrome, resulting from severe untreated hypothyroidism, was observed in a woman who conceived spontaneously and gave birth to a normal viable infant. (Am J Obstet Gynecol 1998;178:610-1.)
Key words: Hypothyroidism, pregnancy, spontaneous ovarian hyperstimulation syndrome
Spontaneous ovarian hyperstimulation syndrome in the absence of exogenous gonadotropins is an extremely rare occurrence and has been reported only in a woman From the Institute of Obstetrics and Gynecology II, University of Bari. Received for publication April 22, 1997; revised May 6, 1997; accepted August 13, 1997. Reprint requests: Luigi Nappi, MD, Institute of Obstetrics and Gynecology, University of Bari, Piazza Giulio Cesare, 70124 Bari, Italy. Copyright © 1998 by Mosby, Inc. 0002-9378/98 $5.00 + 0 6/1/85432
610
with polycystic ovary syndrome1 and in a hypothyroid patient with Down syndrome.2 This observation concerns the unique case of a normal child born physiologically to a hypothyroid mother who had a life-threatening ovarian hyperstimulation syndrome during a naturally occurring gestation. Case report A 34-year-old woman, gravida 2, was admitted because of abdominal pain, distention, and slight vaginal bleed-
Nappi et al. 611
Volume 178, Number 3 Am J Obstet Gynecol
ing at 12 weeks’ gestation. Hypothyroidism since birth and discontinuance of thyroid replacement therapy for several years were reported. The previous pregnancy ended with the birth of a normal child. The current gestation started spontaneously, and no medications had been taken by the patient during the preceding months. Pelvic examination revealed bilaterally enlarged cystic ovaries. Ultrasonography demonstrated a gestational sac with fetal pole and heartbeat corresponding to 12 weeks’ gestation and a hemorrhagic effusion of 8.5 × 5.0 cm within the amnion and chorion. Ovaries measured 13 cm in diameter (right) and 11 cm (left). A moderate amount of ascitic fluid was visualized in the pouch of Douglas. Table I summarizes the results of the hormonal tests performed. Nuclear magnetic resonance of the sella turcica showed diffuse pituitary hypertrophy and depression of the sellar floor. Thyroid ultrasonography showed no signs of glandular tissue in the thyroid area. The increasing ovarian size caused further abdominal distention that was made worse by the development of ascites. The formation of a pericardial effusion and onset of oliguria, nausea, and blurring of vision critically worsened the clinical picture. L-Thyroxine therapy 75 µg daily was instituted, which progressively reached the dose of 200 µg per day. Lowmolecular-weight dextran and electrolytic solutions were infused intravenously, with careful assessment of fluid intake and output. Within 2 weeks a remarkable improvement was observed, with gradual resolution of ascites and pericardial effusion, restoration of diuresis, reduction of ovarian size, and decrease in thyroid-stimulating hormone and β-human chorionic gonadotropin to levels close to normal. The scant show of blood observed on admission caused by decidual hemorrhage was no longer present. Fetal growth increased normally. By means of amniocentesis a normal fetal chromosome map (46,XX) could be evidenced. Thyroid therapy was never discontinued, and clinical and laboratory controls were periodically carried out up to 38 weeks’ gestation. At this time the woman went into spontaneous labor and gave birth to a viable child weighing 3250 gm. Comment Thyroid hormones play a direct role in ovarian physiologic features owing to two nuclear receptors, TRα and TRβ, that are present in human granulosa cells. High levels of thyroid-stimulating hormone stimulate follicular growth in young rats and can mediate ovarian hyperstimulation in hypothyroid women.2 In these patients a raised rate of 16α-hydroxylation of estradiol results in increased formation of estriol. This altered metabolism of estrogen
Table I. Results of hormonal tests β-Human chorionic gonadotropin 17β-Estradiol Follicle-stimulating hormone Thyroid-stimulating hormone Triiodothyronine Thyroxine Free triiodothyronine Free thyroxine Luteinizing hormone Progesterone Prolactin Human growth hormone Somatomedin
12,8461 mIU/ml 9150 pg/ml 0.6 mIU/ml >350 µU/ml 0.31 ng/ml 0.8 µg/dl Undetectable Undetectable 0.5 mIU/ml 89.4 ng/ml 50.7 ng/ml >0.5 ng/ml 40.5 ng/ml
may cause an inadequate feedback at the pituitary level, with unrestrained release of gonadotropins. The excessive levels of this hormone on ovarian tissue may induce a severe cystic reaction of the ovaries and a fluid shift into the third space responsible for ascites, hydrothorax, hydropericardium, hypovolemia, oliguria, electrolyte imbalance, and hemoconcentration, thus producing the ovarian hyperstimulation syndrome. In animal models the often massive collection of fluid found in ovarian hyperstimulation syndrome has been related to increased capillary permeability, particularly of the ovarian vessels. However, elevated levels of vascular endothelial growth factor in the follicular fluid, cytokines, angiotensin II, interleukin-2, interleukin-6, and a variety of other substances (prostaglandins, histamine, serotonin, prolactin) have also been postulated as possible mediators of the capillary permeability increase. Actually, the real cause of the third-space fluid shift is still not clearly understood, and no specific treatment is known. In this patient thyroid replacement therapy and fluid administration produced a prompt improvement of the ovarian hyperstimulation syndrome, favoring the continuation of pregnancy to term. Occult hypothyroidism should always be suspected in spontaneous ovarian hyperstimulation syndrome.
REFERENCES
1. Zalel Y, Orvieto R, Ben-Rafael Z, Homburg R, Fischer O, Insler V. Recurrent spontaneous ovarian hyperstimulation syndrome associated with polycystic ovary syndrome. Gynecol Endocrinol 1995;9:313-5. 2. Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. Am J Obstet Gynecol 1989;160:1220-2.