A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction.

Immune function in normal pregnancy and the postpartum period remains poorly defined. We hypothesized that a comparative study between pregnant women with normal and abnormal immune function would further our understanding of the immune mechanisms of pregnancy. We chose to study a cohort of pregnant women at risk for the development of postpartum thyroid dysfunction (PPTD) as well as a group of normal controls. We chose PPTD as the model for abnormal immune function because of the relative ease of monitoring disease development and the relatively high prevalence for PPTD reported in earlier studies. Five hundred and fifty-two women were screened for the presence of thyroid autoantibodies in the first trimester of pregnancy. Thirty-three thyroid autoantibody-positive women and 28 thyroid autoantibody-negative women were followed prospectively throughout pregnancy and 6 months into the postpartum period. Lymphocyte subset analyses, thyroid function tests, and thyroid autoantibodies (antihuman thyroglobulin and antithyroid peroxidase) were performed at defined intervals. All patients were HLA serotyped. Normal pregnancy was principally characterized by decreased CD4+ T-cells and increasing CD8+ T-cells, causing a significant fall in the CD4+/CD8+ ratio in late pregnancy and into the postpartum period. Women who developed PPTD had 1) a higher CD4+/CD8+ ratio (P = 0.04), 2) activation of T-cells in the postpartum period (P = 0.02), and 3) significantly higher thyroid autoantibody titers (antihuman thyroglobulin, P = 0.02; antithyroid peroxidase, P = 0.0018). We found an overall incidence for PPTD of 8.8%. These data demonstrated that women who were thyroid autoantibody positive in the first trimester of pregnancy had a one in three chance of developing PPTD. We observed a significant fall in the T-cell helper/suppressor ratio in normal pregnant women, which was associated with distinct T-cell subset changes. This pregnancy-initiated T-cell regulation reflected an overall suppression of immune function. The development of PPTD was a frequent postpartum event in our population and was associated with a triad of immune markers: a reduction in the normal immune suppression of pregnancy (as indicated by higher T-cell helper/suppressor ratios), enhanced postpartum T-cell activation, and elevated thyroid autoantibodies. The reduction in the degree of immune suppression was, therefore, a major factor in the development of PPTD. Our results define immunological changes that occur in normal pregnancy and distinct immunological abnormalities necessary for the development of PPTD.

Adrenocorticotropic hormone testing in idiopathic hirsutism and polycystic ovarian disease: a test of limited usefulness.

The plasma 17 alpha-hydroxyprogesterone (17-OHP) concentration was determined in the basal state and 60 minutes after cosyntropin, 0.25 mg, in 139 patients with idiopathic hirsutism (IH) and polycystic ovarian disease (PCOD). Although there was an increased response of 17-OHP in subjects with PCOD when compared with IH subjects, in no instance was stimulated 17-OHP abnormal in the presence of normal basal 17-OHP. Two subjects with 21-hydroxylase (21-OH) deficiency were discovered; both demonstrated elevated basal levels of 17-OHP. We therefore conclude that routine adrenocorticotropic hormone testing is not a useful tool in detecting 21-OH deficiency in hyperandrogenic women.

Hyperthyroidism in patients treated with lithium: report of nine cases.

Nine cases of hyperthyroidism which developed in patients on lithium therapy are presented and analyzed and the literature is briefly reviewed. The findings strongly suggest that lithium therapy does not cause hyperthyroidism.

Thyroid carcinoma and Graves' disease.

OBJECTIVE: To describe an unusual patient with thyroid carcinoma who had metastatic pulmonary nodules that regressed transiently during the active phase of Graves' disease. METHODS: The clinical, pathologic, and laboratory findings in a female patient with thyroid carcinoma, pulmonary lesions, and Graves' ophthalmopathy are presented. In addition, the patient's clinical course and results of serial studies are reviewed. RESULTS: A 62-year-old woman underwent excision of a follicular carcinoma of the thyroid and then total thyroidectomy in 1984. Two years later, chest radiography disclosed multiple pulmonary lesions; open-lung biopsy revealed follicular carcinoma. Thyroglobulin determinations continued to increase, and computed tomography of the chest showed an increase in the size and number of pulmonary nodules. Clinically, the patient remained unchanged until 4 years postoperatively, when she noted rapid onset of diplopia, proptosis, and diminished visual acuity. During this time, a thyroid-stimulating immunoglobulin assay was strongly positive, thyroglobulin levels were decreased, and computed tomography and radiography of the chest showed evidence of tumor regression. Orbital decompression partially restored vision, and the inflammatory signs decreased gradually. Concurrently, the thyroid-stimulating immunoglobulin level declined, the thyroglobulin level increased, and the pulmonary lesions increased in size and number. The patient ultimately died of metastatic disease. CONCLUSION: The reduction in size of the pulmonary nodules and decrease in thyroglobulin levels when the thyroid-stimulating immunoglobulin level was high and the regrowth of lesions when it declined suggest a causal relationship. The hypothesis of an operative autoimmune factor cannot be substantiated without serologic evidence in this case but should prompt physicians to search for other such occurrences.

Thyroid hormone excess and bone--a clinical review.

During the past several years, studies have suggested that exogenous thyroid hormone may adversely affect bone. In order to address this contention and to put the issue in perspective for clinicians who treat patients with thyroid hormone replacement, the available literature was reviewed, and the various study populations were characterized. Age, gender, and menopausal status of the patient are important factors, as are the indication for thyroid hormone replacement and the extent, duration, and severity of prior hyperthyroidism. Reliable measures of bone mineral density, particularly dual-energy x-ray, absorptiometry have become available, providing a more accurate reflection of this parameter in patients receiving thyroxine therapy in comparison with control subjects. The bulk of evidence indicates that long-term thyroxine therapy is safe if the dose is carefully monitored. Treatment with thyroxine does not produce clinically significant bone disease.

Paragangliomatosis associated with multiple endocrine adenomas.

A 19-year-old woman had multiple functioning extra-adrenal paragangliomas, a pituitary adenoma associated with acromegaly, parathyroid hyperplasia, and pigmentary abnormalities. This case differs from previously described instances of multiple endocrine adenomatosis (MEA) and has features that bridge the classic MEA type 1 and 2 syndromes and possibly Von Recklinghausen disease. The coexistence of pheochromocytoma with acromegaly is extremely rare, and the association with extra-adrenal paragangiliomas appears to be unique. Thyroid parafollicular cell proliferation could not be proved by immunohistochemical or electron microscopical studies. The large number and extensive distribution of paragangliomas, ranging from neck to pelvis, is another unique feature of this case. The concept of neurocrestopathy or of an endocrine polypeptide (APUD) cell system may offer an explanation for the interrelation of these diverse growths.

Hypothalamic-pituitary axis dysfunction in critically ill patients with a low free thyroxine index.

The purpose of this study is to investigate the association of hypothalamic-pituitary axis abnormalities with the free thyroxine index (FTI) in critically ill patients. Fourteen critically ill patients and twenty healthy volunteers were studied using combined anterior pituitary gland testing with CRF, GHRH, TRH, and GnRH. The subjects were grouped as follows: I-healthy volunteers; II-sick/normal FTI; and III-sick/low FTI. Serial measurements of hormones were performed over a two-hour interval and the following parameters were measured: baseline level, response amplitude and time to maximal response. Response velocities and area-under-the-curves (integrated responses) were also computed. Group III had a longer mean ICU duration prior to testing than group II. Urinary cortisol, serum cortisol and serum PRL levels were elevated in groups II and III. However, group III had lower baseline ACTH levels, slower ACTH and TSH response velocities and decreased PRL integrated responses. Cortisol response parameters were similar between groups II and III. There were no differences in LH, FSH or GH response velocities or integrated responses among the 3 groups. These data confirm that critically ill patients develop hyperprolactinemia and hypothalamic-pituitary-adrenal axis activation but when a low FTI exists, a plurality of changes occur reflected by attenuated PRL, TSH and ACTH responses despite unaffected adrenal cortisol output.

Thyroid nodules in the irradiated patient--an indication for total thyroidectomy.

Eight patients who received radiation therapy to the head, neck, or chest during infancy, childhood, or adolescence are reported. In these individuals, the presenting abnormality was a nodule of the thyroid gland, which was found to be benign at surgery. All patients were subsequently found to harbor a malignant lesion of the contralateral lobe. On the basis of this study and the discussion presented, we feel that a total thyroidectomy is the indicated therapeutic procedure in previously radiated patients presenting with a cold nodule.

Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies.

We screened 552 women who presented to their obstetrician in the first trimester of pregnancy using highly sensitive enzyme-linked immunosorbent assays for the presence of thyroglobulin and thyroid peroxidase autoantibodies and found an incidence of positivity of 19.6%. The tendency to secrete detectable levels of thyroid autoantibodies was significantly correlated with an increased rate of miscarriage. Thyroid autoantibody-positive women miscarried at a rate of 17%, compared with 8.4% for the autoantibody-negative women. Individual levels of thyroglobulin and thyroid peroxidase autoantibodies were similarly related to this increased miscarriage rate, with no evidence of autoantibody specificity in the relationship. Furthermore, the increase in miscarriages could not be explained by differences in thyroid hormone levels, the presence of cardiolipin autoantibodies, maternal age, gestational age at the time of maternal entry into the study, or previous obstetric history. We conclude that thyroid autoantibodies are an independent marker of "at-risk" pregnancy.