Transient Hypothyroidism After Delivery in Autoimmune Thyroiditis NOBUYUKI AMINO, KIYOSHI MIYAI, TOSHIO ONISHI, TAKUMA HASHIMOTO, KAYOKO ARAI, KAICHIRO ISHIBASHI, AND YUICHI KUMAHARA The Central Laboratory for Clinical Investigation, Osaka University Hospital, Osaka, Japan 60%. Then 6-9 months after delivery, the enlarged thyroid gland decreased in size, and the values in thyroid function tests returned to the normal range without any treatment. Anti-thyroglobulin antibodies were positive in 3 cases. Anti-thyroid microsomal antibodies were positive in all cases with titers of L10 4 -1:10 s , and titers were highest during the period of hypothyroidism and decreased thereafter. We suggest that these transient changes might be induced by pregnancy and delivery during the course of autoimmune thyroiditis. (J Clin Endocrinol Metab 42: 296, 1976)
ABSTRACT. The spontaneous occurrence of, and recovery from primary hypothyroidism were observed after delivery in 6 women with autoimmune thyroiditis. Diffuse goiter was noticed 1-3 months after delivery. The blood thyroid hormone level was found to be lowest at 3-6 months post-partum, with a thyroxine iodine value of 1.0 ± 0.6 figjdl (mean ± SD) (normal 3.0-7.2), triiodothyronine value of 77 ± 1 1 ng/dl (normal 90-190) and T3 resin sponge uptake of 21 ± 2.8% (normal 24-37). During this period the serum level of thyrotropin was increased to 307 ± 235 /i,U/ml (normal < 8) and 131I thyroid uptake in 24 hours was more than
I
DIOPATHIC primary hypothyroidism in adults is considered to be the end result of autoimmune thyroiditis (1,2,3). Therefore it is generally agreed that acquired spontaneous hypothyroidism should be treated with thyroid hormone throughout life, although it is a matter of controversy whether euthyroid patients with autoimmune thyroiditis should be treated or not. Spontaneous transient hypothyroidism has been observed in subacute thyroiditis (4), but no detailed report is available on transient hypothyroidism in autoimmune thyroiditis. Recently we observed unusual cases of transient hypothyroidism during the course of autoimmune thyroiditis. In these cases, this transient phenomenon was related to pregnancy and delivery. Postpartum hypo-
thyroidism has long been recognized as the result of hypopituitarism in Sheehan's syndrome (5). This paper describes six patients who showed transient primary hypothyroidism after delivery. Possible pathogenic factors related to this phenomenon are discussed. Materials and Methods
The six patients investigated were seen at the Endocrine Clinic of Osaka University Hospital. They all attended the clinic with the chief complaint of swelling of the front of the neck after delivery. Their clinical course was observed without any treatment. All the patients had delivered healthy infants after full term, uncomplicated pregnancy and none had any previous history of serious diseases. A preliminary report on the clinical course of case 1 has already appeared (6). Relatives of two of the cases had rheumatoid arthritis and Graves' Received July 8, 1975. disease. None of the cases had significant inSupported by a Research Grant for Specific Diseases gestion of iodide, or drugs or foods containing from the Ministry of Health and Welfare of Japan. Reprints: Nobuyuki Amino, M.D. The Central organic iodine. Protein-bound iodine (PBI) was measured by Laboratory for Clinical Investigation, Osaka University Hospital, 1-1-50 Fukushima, Fukushima-ku, the method of Crowly and Jensen (7). Thyroxine iodine (T4I) and triiodothyronine (T3) resin Osaka 553, Japan. 296
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 16:46 For personal use only. No other uses without permission. . All rights reserved.
297
POSTPARTUM TRANSIENT HYPOTHYROIDISM sponge uptake (RT3U) were measured using commercially available kits (Tetrasorb and Trios orb, respectively, Dainabot Radioisotope Laboratories, Tokyo). Serum thyrotropin (TSH) was measured by double-antibody radioimmunoassay (8). Serum T 3 was measured by radioimmunoassay (9) using antibody prepared in our laboratory. Thyroid auto-antibodies to thyroglobulin and microsomes were measured by the tanned sheep red cell hemagglutination technique, using commercially available kits, (Thyroid test and Microsome test, respectively, from Fujizoki Pharmaceutical Co., Ltd., Tokyo) (10). The size of the goiter was expressed as the transverse width of the thyroid gland, and it was measured by one of the authors (N.A.) on each examination of the cases. Serial serum samples obtained from each patient were first stored at - 2 0 C, and then all were assayed at the same time for T3 and thyroid auto-antibodies.
Results Clinical data on the six patients with postpartum transient hypothyroidism are summarized in Table 1. Three had a small goiter before pregnancy. They all noticed remarkable enlargement of the thyroid gland (to 3-5 times the normal size) at 1-3 months postpartum and were observed without having had any treatment for 6 months-6 years. The goiters were all diffuse and soft. None of the patients had either neck pain or fever. Patients 1 and 2 complained of mild constipation and easy fatiguability. Case 3 had cold intolerance. Four cases had edematous eyelids. Delayed
relaxation of Achilles tendon reflexes was observed in three cases. In three cases the body weight was highest during the period of hypothyroidism and decreased thereafter. Figure 1 shows the clinical course of case 2. She delivered a baby in August, 1973, and first noticed thyroid enlargement in October. Her indices in thyroid function tests were all in the hypothyroid range, and her basal metabolic rate (BMR) was -20% in November, 1973. However, she recovered spontaneously and was euthyroid in March, 1974. The laboratory data on the six cases are summarized in Table 2. All were hypothyroid 3-6 months after delivery. Their blood thyroid hormone levels were lowest at 3-4 months postpartum and their serum TSH levels were all more than 100 /xlJ/ml. The BMR was less than -10% in the four cases examined. In the two patients observed, the 24 Hour thyroid 131I uptakes were 80% (case 1) and 66% (case 3). Thyroid function tests all returned to the normal range concomitantly with decrease in goiter size at 6-9 months after delivery. The red blood cell sedimentation rate and serum y-globulin were normal in five patients. Anti-thyroglobulin hemagglutination antibodies (TGHA) were positive in 3 cases, while anti-thyroid microsomal hemagglutination antibodies (MCHA) were positive with high titers in all cases. Moreover, the MCHA titers were highest during the period
TABLE 1. Summary of clinical data on six patients with postpartum transient hypothyroidism
Case no. 1 2 3 4 5 6
Chief complaint Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid
enlargement enlargement enlargement enlargement enlargement enlargement
Age at last delivery (years)
Gravida
25 28 24 23 22 35
3 2 1 2 2 3
Time of changes after delivery (months)
Para
Age at time when goiter first noticed (years)
Thyroid gland enlargement
Remission of* hypothyroidism
Period of observation after delivery
2 2 1 1 1 3
23 28 18 23 21 35
3 2ft 2y2 3 1 1
7 7 9 6 6 6
6 yr. 14 mo. 2 yr. 7 mo. IMJ yr. 6Vi mo.
• Time when T4I and RT3U became normal.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 16:46 For personal use only. No other uses without permission. . All rights reserved.
AMINO ET AL.
298
JCE & M • 1976 Vol 42 • No 2
lOr
11 1973
12 1974
FIG. 1. Changes of body weight, goiter size, thyroid function, and thyroid antibodies in the clinical course of a patient with postpartum transient hypothyroidism (case 2).
of hypothyroidism and decreased after 4 months postpartum (Fig. 1 and Table 2). Although the enlarged thyroid gland decreased in size in all cases, the goiters did
not completely disappear during observation periods of 6 months-6 years but the consistency tended to change from a soft to an elastic, firm type.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 16:46 For personal use only. No other uses without permission. . All rights reserved.
299
POSTPARTUM TRANSIENT HYPOTHYROIDISM TABLE 2. Summary of laboratory data on six patients with postpartum transient hypothyroidism Time at which tests were done after delivery
Case no. 1
2
3
Hypothyroid Stage Euthyroid Stage Hypothyroid Stage Euthyroid Stage Hypothyroid Stage Euthyroid Stage
4 mo. 7 mo. 6 yr.
BMR % + 18
T3 ng/dl 74
TSH jtU/ml
TGHA
MCHA
5
1 x 10 l x 10" 3 x 102
lxlO9 1 x 107 l x 103
20 20 negative
5 x 105 6 x 1O4 6x10"
ABSTRACT. The spontaneous occurrence of, and recovery from primary hypothyroidism were observed after delivery in 6 women with autoimmune thyroiditis. Diffuse goiter was noticed 1-3 months after delivery. The blood thyroid hormone level was found to be lowest at 3-6 months post-partum, with a thyroxine iodine value of 1.0 ± 0.6 figjdl (mean ± SD) (normal 3.0-7.2), triiodothyronine value of 77 ± 1 1 ng/dl (normal 90-190) and T3 resin sponge uptake of 21 ± 2.8% (normal 24-37). During this period the serum level of thyrotropin was increased to 307 ± 235 /i,U/ml (normal < 8) and 131I thyroid uptake in 24 hours was more than
I
DIOPATHIC primary hypothyroidism in adults is considered to be the end result of autoimmune thyroiditis (1,2,3). Therefore it is generally agreed that acquired spontaneous hypothyroidism should be treated with thyroid hormone throughout life, although it is a matter of controversy whether euthyroid patients with autoimmune thyroiditis should be treated or not. Spontaneous transient hypothyroidism has been observed in subacute thyroiditis (4), but no detailed report is available on transient hypothyroidism in autoimmune thyroiditis. Recently we observed unusual cases of transient hypothyroidism during the course of autoimmune thyroiditis. In these cases, this transient phenomenon was related to pregnancy and delivery. Postpartum hypo-
thyroidism has long been recognized as the result of hypopituitarism in Sheehan's syndrome (5). This paper describes six patients who showed transient primary hypothyroidism after delivery. Possible pathogenic factors related to this phenomenon are discussed. Materials and Methods
The six patients investigated were seen at the Endocrine Clinic of Osaka University Hospital. They all attended the clinic with the chief complaint of swelling of the front of the neck after delivery. Their clinical course was observed without any treatment. All the patients had delivered healthy infants after full term, uncomplicated pregnancy and none had any previous history of serious diseases. A preliminary report on the clinical course of case 1 has already appeared (6). Relatives of two of the cases had rheumatoid arthritis and Graves' Received July 8, 1975. disease. None of the cases had significant inSupported by a Research Grant for Specific Diseases gestion of iodide, or drugs or foods containing from the Ministry of Health and Welfare of Japan. Reprints: Nobuyuki Amino, M.D. The Central organic iodine. Protein-bound iodine (PBI) was measured by Laboratory for Clinical Investigation, Osaka University Hospital, 1-1-50 Fukushima, Fukushima-ku, the method of Crowly and Jensen (7). Thyroxine iodine (T4I) and triiodothyronine (T3) resin Osaka 553, Japan. 296
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 16:46 For personal use only. No other uses without permission. . All rights reserved.
297
POSTPARTUM TRANSIENT HYPOTHYROIDISM sponge uptake (RT3U) were measured using commercially available kits (Tetrasorb and Trios orb, respectively, Dainabot Radioisotope Laboratories, Tokyo). Serum thyrotropin (TSH) was measured by double-antibody radioimmunoassay (8). Serum T 3 was measured by radioimmunoassay (9) using antibody prepared in our laboratory. Thyroid auto-antibodies to thyroglobulin and microsomes were measured by the tanned sheep red cell hemagglutination technique, using commercially available kits, (Thyroid test and Microsome test, respectively, from Fujizoki Pharmaceutical Co., Ltd., Tokyo) (10). The size of the goiter was expressed as the transverse width of the thyroid gland, and it was measured by one of the authors (N.A.) on each examination of the cases. Serial serum samples obtained from each patient were first stored at - 2 0 C, and then all were assayed at the same time for T3 and thyroid auto-antibodies.
Results Clinical data on the six patients with postpartum transient hypothyroidism are summarized in Table 1. Three had a small goiter before pregnancy. They all noticed remarkable enlargement of the thyroid gland (to 3-5 times the normal size) at 1-3 months postpartum and were observed without having had any treatment for 6 months-6 years. The goiters were all diffuse and soft. None of the patients had either neck pain or fever. Patients 1 and 2 complained of mild constipation and easy fatiguability. Case 3 had cold intolerance. Four cases had edematous eyelids. Delayed
relaxation of Achilles tendon reflexes was observed in three cases. In three cases the body weight was highest during the period of hypothyroidism and decreased thereafter. Figure 1 shows the clinical course of case 2. She delivered a baby in August, 1973, and first noticed thyroid enlargement in October. Her indices in thyroid function tests were all in the hypothyroid range, and her basal metabolic rate (BMR) was -20% in November, 1973. However, she recovered spontaneously and was euthyroid in March, 1974. The laboratory data on the six cases are summarized in Table 2. All were hypothyroid 3-6 months after delivery. Their blood thyroid hormone levels were lowest at 3-4 months postpartum and their serum TSH levels were all more than 100 /xlJ/ml. The BMR was less than -10% in the four cases examined. In the two patients observed, the 24 Hour thyroid 131I uptakes were 80% (case 1) and 66% (case 3). Thyroid function tests all returned to the normal range concomitantly with decrease in goiter size at 6-9 months after delivery. The red blood cell sedimentation rate and serum y-globulin were normal in five patients. Anti-thyroglobulin hemagglutination antibodies (TGHA) were positive in 3 cases, while anti-thyroid microsomal hemagglutination antibodies (MCHA) were positive with high titers in all cases. Moreover, the MCHA titers were highest during the period
TABLE 1. Summary of clinical data on six patients with postpartum transient hypothyroidism
Case no. 1 2 3 4 5 6
Chief complaint Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid
enlargement enlargement enlargement enlargement enlargement enlargement
Age at last delivery (years)
Gravida
25 28 24 23 22 35
3 2 1 2 2 3
Time of changes after delivery (months)
Para
Age at time when goiter first noticed (years)
Thyroid gland enlargement
Remission of* hypothyroidism
Period of observation after delivery
2 2 1 1 1 3
23 28 18 23 21 35
3 2ft 2y2 3 1 1
7 7 9 6 6 6
6 yr. 14 mo. 2 yr. 7 mo. IMJ yr. 6Vi mo.
• Time when T4I and RT3U became normal.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 16:46 For personal use only. No other uses without permission. . All rights reserved.
AMINO ET AL.
298
JCE & M • 1976 Vol 42 • No 2
lOr
11 1973
12 1974
FIG. 1. Changes of body weight, goiter size, thyroid function, and thyroid antibodies in the clinical course of a patient with postpartum transient hypothyroidism (case 2).
of hypothyroidism and decreased after 4 months postpartum (Fig. 1 and Table 2). Although the enlarged thyroid gland decreased in size in all cases, the goiters did
not completely disappear during observation periods of 6 months-6 years but the consistency tended to change from a soft to an elastic, firm type.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 16:46 For personal use only. No other uses without permission. . All rights reserved.
299
POSTPARTUM TRANSIENT HYPOTHYROIDISM TABLE 2. Summary of laboratory data on six patients with postpartum transient hypothyroidism Time at which tests were done after delivery
Case no. 1
2
3
Hypothyroid Stage Euthyroid Stage Hypothyroid Stage Euthyroid Stage Hypothyroid Stage Euthyroid Stage
4 mo. 7 mo. 6 yr.
BMR % + 18
T3 ng/dl 74
TSH jtU/ml
TGHA
MCHA
5
1 x 10 l x 10" 3 x 102
lxlO9 1 x 107 l x 103
20 20 negative
5 x 105 6 x 1O4 6x10"
