Maternal Autoimmunization to Thyroid as a Probable Cause of Athyrotic Cretinism

Blizzard, Robert M.; Chandler, Robert W.; Landing, Benjamin H.; Pettit, Mary DeWitt; West, Clark D.

doi:10.1056/nejm196008182630702

Cited by 113 publications

(21 citation statements)

References 16 publications

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“…For these reasons, it has been necessary to consider other explanations for the sporadic congenitally hypothyroid infant. Current theory proposes that genetic factors may predominate, although it is likely that the transplacental transfer of circulating autoantibodies or other unidentified intrauterine thyrocytoxic factors might cause damage to the fetal thyroid (9,18). I n one series (22), 9 of 20 instances of congenital hypothyroidism due to dyshormonogenesis had evidence for an autosomal recessive inheritance.…”

Section: Speculationmentioning

confidence: 99%

“…~n a t o m i c and ,,lated growth hormone and glucagon secretion. ~~~h subject had, histologic studies demonstrate sympathetic nerve endings directly on three separate occasions, infusion of arginine alone or in on the pancreatic islet (9,18), and stimulation of the splanchnic conjunction with LY (phentolamine) or P (propranolol) adrenergic sympathetic nerve in dogs (25), cats (8), and calves (4), causes a blockade. ~l i~i~~l l~, there was evidence of adequate blockade rise in glucagon secretion.…”

Section: Effect Of Adrenergic Blockade On Glucagon and Growth Hormonementioning

confidence: 99%

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Endocrine Studies of the Untreated Progeny of Thyroidectomized Rats

et al. 1975

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ExtractExperiments were conducted to assess late and persistent endocrine changes in the progeny of rats born of and/or nursed by thyroidectomized ( T x ) dams. Forty-five female rats were radiothyroidectomized several weeks before mating with normal males, and compared with the progeny of 26 control females. In all, 248 progeny were studied when adult.T x dams had significantly reduced fertility (87% of controls), increased pup (11% versus 0) and maternal mortality (27% versus 0), and smaller litters (6.5 versus 11.8 pups/litter). It was shown that the offspring of thyroidectomized female rats had delayed eye opening (15.3 versus 14.3 days), smaller weaning (40.4 versus 54.4 g ) and adult body weights (230 versus 260 g), smaller pituitary glands (12.2 versus 14.0 mg), and enlarged thyroid glands (14.2 versus 12.4 mg). Ovarian and testicular weights were decreased (73.9 versus 83.7 mg and 3.2 versus 3.6 g, respectively). The serum thyroid stimulating hormone ( T S H ) concentrations were increased from 53.8 to 84.4 wU/ml in the males. The pituitary T S H contents were not significantly altered, and the serum T S H response to thyrotropin releasing hormone ( T R H ) was normal. These persistent effects differed from the late effects of both fetal and neonatal hypothyroidism and neonatal underfeeding. Cross-fostering experiments showed that the diminished weaning weights were the result of the pups being nursed by the hypothyroid dams. The increased nursing mortality and the pituitary and thyroidal changes were the result of prenatal influences produced by the hypothyroid dams, since being nursed by a normal foster dam did not prevent them. The persistently enlarged thyroid glands and the elevated serum T S H in the male offspring of thyroidectomized dams suggested a permanent alteration in the set point of pituitary-thyroid regulation as the consequence of maternal hypothyroidism. SpeculationIt is speculated that the intrauterine environment provided by the pregnant hypothyroid mother produces permanent alterations in endocrine regulatory mechanisms in the offspring. It is suggested that the transplacental transfer of fetal thyroxine (T,) to the hypothyroid mother places a burden on the fetal pituitary-thyroid axis that permanently alters its function in these progeny. W e have shown previously that during a critical perinatal period, T , excess or deficiency can permanently alter hypothalamo-pituitary regulatory function in the offspring.Whether or not maternal hypothyroidism can cause fetal or congenital hypothyroidism has been an enigma for many years. It has been stated that if a woman has given birth to two cretins she has an increased chance of producing a cretin in the next pregnancy (10). However, even severely hypothyroid mothers usually deliver normal infants (21), and most mothers of cretins are euthyroid throughout their pregnancy. For these reasons, it has been necessary to consider other explanations for the sporadic congenitally hypothyroid infant. Current theory proposes that genetic factors may p...

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Section: Speculationmentioning

confidence: 99%

Section: Effect Of Adrenergic Blockade On Glucagon and Growth Hormonementioning

confidence: 99%

Endocrine Studies of the Untreated Progeny of Thyroidectomized Rats

et al. 1975

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“…The morphological substrate, though, is little known. Hypothyrosis in utero or postnatally is mainly seen in the following situations: The most com mon situation is that of a congenital athyrosis, due to disturbances of the thyroid anlage, sometimes caused by a maternal antithyroid autoimmuni zation; less often there is a congenital disturbance of hormonal synthesis in the newborn thyroid gland, a defect that may be inherited; iodine de ficiency-induced endemic cretinism and hypothyrosis due to antithyroid treatment of the mother are today rare or are not germane to the pre sent discussion; lastly, the least common cause of neonatal hypothyrosis is maternal hypothyrosis [5,21].…”

Section: Maternal Endocrinopathiesmentioning

confidence: 99%

Perinatal Encephalopathies Caused by Maternal Diseases during Pregnancy

Brun¹

1972

Eur Neurol

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The most important perinatal encephalopathies, which are caused by diseases of the mother during pregnancy, comprise brain damage due to malnourishment and some inherited metabolic diseases, dysthyroidism and diabetes, infectious diseases, hypoxic circulatory disturbances and kernicterus. Besides the brain alterations directly caused by these conditions, changes of a secondary nature are discussed. These are mainly due to curtailed or perverted maturational and late developmental processes. The end-result thus will be a complex of primary and secondary changes and the type and distribution of alterations are dependent not only upon the nature of the harmful factor but also on the time of its operation.

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“…46 Severe maternal hypothyroidism clearly is associated with devastating neurodevelopmental outcomes and death. 15,17 Another study found higher maternal TSH levels at delivery to be associated with significantly lower scores on the general cognitive index at age 5.5 years among infants born at £ 34 weeks to mothers with mild maternal thyroid dysfunction. 44 Currently, a multicenter randomized placebo-controlled clinical trial organized by the Maternal Fetal Medicine Unit at the National Institutes of Health is in progress to determine the IQ outcome of the child at age 5 years.…”

Section: Discussionmentioning

confidence: 99%

“…13,[15][16][17] Most cases are caused by TSH-receptor blocking antibodies that adversely affect the fetus by transplacental transport. 13 As a result of serum screening studies, a scientific panel 14 recommended TSH measurements in women who are pregnant or wish to become pregnant and who have these risk factors: (1) family or personal history of thyroid disease, (2) physical findings or symptoms suggestive of goiter or hypothyroidism, (3) diabetes mellitus type 1, or (4) a personal history of specific autoimmune disorders.…”

Section: Introductionmentioning

confidence: 99%

Maternal Screening for Hypothyroidism and Thyroiditis Using Filter Paper Specimens

Foley

Henry

Hofman

et al. 2013

Journal of Women's Health

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Background and Objective: Hypothyroidism and autoimmune thyroiditis are more prevalent than previously considered in women during pregnancy and the postpartum, and are associated with adverse effects on the mother and her fetus. We determined the efficacy and accuracy of screening women for primary hypothyroidism and autoimmune thyroiditis by testing TSH and two thyroid antibodies (TAb): thyroperoxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), in eluates of filter paper specimens collected during early pregnancy and the postpartum. Methods: We enrolled 494 first-trimester pregnant women with no exclusion criteria into a prospective study to detect primary hypothyroidism and autoimmune thyroiditis. Finger stick blood was applied to filter paper, dried in room air, eluted, and promptly tested for TSH and TAb. A total of 178 of the pregnant women (36%) were tested in the early postpartum. Women with abnormal results had confirmatory serum tests. Results: It was found that 91 pregnant women (18.4%) and 43 postpartum women (24.2%) had abnormal TSH values ( > 4.0 mU/L) and/or positive TAb; 140 pregnant women (28.3%) had TSH values > 2.5 mU/L. All subjects with TSH values > 4.0 mU/L tested positive for TAb. Eighteen women (3.6%) who tested normal during pregnancy tested abnormal in the postpartum. Conclusions: This study confirms that TSH and TPOAb measured in eluates of blood-spotted filter paper specimens are excellent screening tests to detect primary hypothyroidism and autoimmune thyroiditis in pregnant and postpartum women. Results are very comparable to serum data in this population published in the literature.

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Maternal Autoimmunization to Thyroid as a Probable Cause of Athyrotic Cretinism

Cited by 113 publications

References 16 publications

Endocrine Studies of the Untreated Progeny of Thyroidectomized Rats

Endocrine Studies of the Untreated Progeny of Thyroidectomized Rats

Perinatal Encephalopathies Caused by Maternal Diseases during Pregnancy

Maternal Screening for Hypothyroidism and Thyroiditis Using Filter Paper Specimens

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