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In the last 70 years, atomic disasters have occurred several times. The nuclear power plant accident at Chernobyl in 1986 in North-Central Ukraine was a unique experience in population exposures to radiation by all ages, and ongoing studies have brought a large amount of information effects of radiation on human organism. Concerning the deteriorating global security situation and the strong rhetoric of some of the world leaders, the knowledge on the biological effects of ionizing radiation and the preventive measures designed to decrease the detrimental effects of radiation gains a new dimension, and involves all of us. This review focuses on the long-term effects of Chernobyl catastrophe especially on the endocrine system in children and in adults, and includes a summary of preventive measures in case of an atomic disaster.

HLA antigens A and B were determined in a group of 41 patients with congenital hypothyroidism and 36 of their mothers. Twenty-nine patients had thyroid dysgenesis of whom 23 were functionally athyreotic, four had ectopic and two had hypoplastic thyroid glands. Twelve patients had thyroid dyshormonogenesis, seven of whom had iodide organification defect. A total of 48 antigens were typed in the A and B loci. The results were analyzed in comparison to 388 normal adult subjects from the general population. The only statistically significant difference was an increase in the frequency of HLA-Bw44(12) (48.8% vs 19.3%, P less than 0.02). The incidence of HLA-Bw44(12) was 44.2% in the mothers. There was a decreased frequency of HLA-B7 in the patients which was not significant.

In the last 70 years, atomic disasters have occurred several times. The nuclear power plant accident at Chernobyl in 1986 in North-Central Ukraine was a unique experience in population exposures to radiation by all ages, and ongoing studies have brought a large amount of information on effects of radiation on human organism. Concerning the deteriorating global security situation and the strong rhetoric of some of the world leaders, the knowledge on the biological effects of ionizing radiation and the preventive measures designed to decrease the detrimental effects of radiation gains a new dimension, and involves all of us. This review focuses on the long-term effects of Chernobyl catastrophe especially on the endocrine system in children and in adults, and includes a summary of preventive measures in case of an atomic disaster.

OBJECTIVE—To evaluate menstrual cycle histories among women with type 1 diabetes, their sisters, and unrelated control subjects without diabetes across all reproductive ages. RESEARCH DESIGN AND METHODS—Menstrual and reproductive histories were obtained by questionnaire from 143 women with type 1 diabetes, 186 sisters without diabetes, and 158 unrelated control subjects without diabetes participating in the Familial Autoimmune and Diabetes study. RESULTS—Women with type 1 diabetes had more menstrual problems (long cycles, long menstruation, and heavy menstruation) before age 30 years than sisters and control subjects. These differences were all statistically significant, except for heavy menstruation at age CONCLUSIONS—The results suggest that type 1 diabetes is an independent risk factor for menstrual disturbances in young adults. Future studies may determine whether addressing menstrual disturbances improves quality of life and health for these women.

Background: The Chernobyl Childhood Illness Program (CCIP) was a humanitarian assistance effort funded by the United States Congress. Its purpose was to assist the Ukrainian Government to identify and treat adolescents who developed mental and physical problems following their exposure as young children to Chernobyl radiation. Thirteen years after the Chernobyl nuclear plant accident in 1986, the CCIP examined 116,655 Ukrainian adolescents for thyroid diseases. Of these, 115,191 were also screened for depression, suicide ideation, and psychological problems. The adolescents lived in five of Ukraine’s seven most Chernobyl radiation contaminated provinces. They were up to 6 years of age or in utero when exposed to nuclear fallout, or were born up to 45 months after Chernobyl. Methods: Ukrainian endocrinologist and ultrasonographers used physical examination and ultrasonography of the neck to evaluate the adolescents for thyroid tumors. The adolescents were then screened for depression by the Children’s Depression Inventory (CDI). After this, Ukrainian psychologists conducted individual psychological interviews to corroborate the adolescents’ CDI responses. Results: Papillary thyroid carcinoma was diagnosed in eight adolescents, a high prevalence rate similar to that reported by other studies from the Soviet Union. Screening identified thyroid nodules in 1,967 adolescents (1.7%). Depression was diagnosed in 15,399 adolescents (13.2%), suicide ideation in 813 (5.3%), and attempted suicide in 354 (2.3%). Underlying components of the participants’ depression were negative mood, interpersonal difficulties, negative self-esteem, ineffectiveness, and anhedonia. Depression was greater in females (77%). Those with thyroid and psychological problems were referred for treatment. Conclusions: The adolescents screened by CCIP represent the largest Ukrainian cohort exposed to Chernobyl radiation as children who were evaluated for both thyroid tumors and depression. The group had an increased prevalence of thyroid cancer, thyroid tumors, depression, and suicide ideation. CCIP demonstrated that psychological problems among Chernobyl exposed adolescents began earlier in life than previously reported. They also experienced socioeconomic problems from their relocation from radiation-affected areas and from the Soviet’s inadequate responses to their health needs. CCIP’s findings underscore the requirement that governments prepare plans to deal promptly with the diagnosis and treatment of nuclear accident victims’ medical and psychological problems. J Clin Med Res. 2015;7(5):332-338 doi: http://dx.doi.org/10.14740/jocmr2018w

Women with type 1 diabetes have a delayed menarche and a greater prevalence of menstrual disorders than women without diabetes. However, little is known about the menopause transition among type 1 diabetic women. The Familial Autoimmune and Diabetes (FAD) Study recruited both adult individuals who were identified from the Children’s Hospital of Pittsburgh Type 1 Diabetes Registry for the years 1950–1964 and their family members. Unrelated nondiabetic control probands and their relatives were also evaluated. Women with type 1 diabetes (n = 143) compared with nondiabetic sisters (n = 186) or unrelated control subjects (n = 160) were more likely to have an older age at menarche (13.5, 12.5, and 12.6 years, respectively, P < 0.001), more menstrual irregularities before 30 years of age (45.7, 33.3, and 33.1%, respectively, P = 0.04), and a younger age at menopause (41.6, 49.9, and 48.0 years, respectively, P = 0.05). This resulted in a 6-year reduction in the number of reproductive years (30.0, 37.0, and 35.2 years, respectively, P = 0.05) for women with type 1 diabetes. Risk factors univariately associated with earlier menopause included type 1 diabetes (hazard ratio [HR] 1.99, P = 0.04), menstrual irregularities before 30 years of age (HR 1.87, P = 0.04), nulliparity (HR 2.14, P = 0.01), and unilateral oophorectomy (HR 6.51, P < 0.0001). Multivariate analysis confirmed that type 1 diabetes (HR 1.98, P = 0.056), menstrual irregularities by 30 years of age (HR 2.36, P = 0.01), and unilateral oophorectomy (HR 9.76, P < 0.0001) were independent determinants of earlier menopause in our cohort. We hypothesize that an earlier menopause, which resulted in a 17% decrease in reproductive years, is a major unstudied complication of type 1 diabetes.

The objective of the present study was to examine the prevalence of self-reported autoimmune diseases among offspring of type 1 fathers, type 1 diabetic mothers, and non-diabetic parents. Type 1 diabetic probands (n=265; mean age=42 yr), who were ascertained from the Children's Hospital of Pittsburgh Registry for 1950-1964, recently participated in the Familial Autoimmune and Diabetes Study. Non-diabetic probands (n=96), identified from voter registration lists and matched by age, race, median income, and duration of residence in the Pittsburgh area, were also enrolled. Offspring of type 1 diabetic probands were more likely to have a reported autoimmune disease (5.8% vs. 2.4%; p=0.067) than offspring of non-diabetic probands. Half the cases in the diabetic families were disorders other than type 1 diabetes, (e.g., rheumatoid arthritis, Crohn's disease, etc.). Stratification by parental gender revealed a marginally higher risk for type 1 diabetes among offspring of type 1 diabetic fathers compared to mothers (4.9% vs. 3.4%; p=0.38, respectively, through age 20 yr). However, the risk for other autoimmune disorders was statistically significantly increased among offspring of type 1 diabetic mothers (0% vs. 6.2%; p=0.02, respectively, through age 20 yr). These data suggest that offspring of type 1 diabetic parents may be at high risk of developing other autoimmune disorders during childhood, with pediatric diabetes representing the 'tip of an autoimmune iceberg'. The observed risk differences by parental gender, which have also been reported for other autoimmune disorders, warrant further investigation.

Background: Some experts maintain that (1) >90% of patients with multiple endocrine neoplasia type 1 (MEN1) are first seen with hyperparathyroidism (HPTH) so that routine screening for other features is unnecessary and (2) MEN1 has ≥94% penetrance by age 50 years. Methods: We constructed a regional registry of patients with or at risk for MEN1 and examined phenotypic profiles in 34 patients. MEN1 was defined as (1) endocrinopathy of 2 of the 3 principal related tissues (parathyroid, gastrointestinal endocrine, pituitary) or (2) 1 such feature plus a first-degree relative with MEN1. Results: The initial feature of MEN1 was HPTH in 50%, pituitary tumor in 18%, and gastrointestinal endocrine tumor in 32% of patients, with overall incidences of 82%, 65%, and 74%, respectively. HPTH developed by age 50 years in 73% of patients and by age 70 years in 83%. Penetrance of MEN1 at age 50 years was 82%. Associated features included renal (1) and rectal (1) cancer, malignant thymic carcinoid (1), and malignant pheochromocytoma (1). Conclusions: Expression of MEN1 can vary considerably from established patterns. In our geographic region HPTH does not routinely precede other features of MEN1 and cannot be used to distinguish affected patients among those at risk. MEN1 can be inapparent until late in life and may be significantly underdiagnosed. (Surgery 1998;124:1106-14.)

Insulin-dependent diabetes mellitus probands from the Familial Autoimmune and Diabetes Study were evaluated for autoimmune thyroid disease (n = 265). The prevalence of Hashimoto's thyroiditis was 26.6%; 42.0% of these individuals were euthyroid, and 58.0% were hypothyroid. There was a female predominance among hypothyroid and euthyroid Hashimoto's cases compared to those with no thyroid disease (75% vs. 72.4% vs. 41.6%; P < 0.001). Insulin-dependent diabetes mellitus patients with hypothyroid Hashimoto's thyroiditis were more likely to report another autoimmune disease compared to euthyroid Hashimoto's patients or individuals with no thyroid disease (30.8% vs. 17.2% vs. 13.9%; P < 0.01). Sex-specific analysis revealed that this difference was significant for men but not for women. Both euthyroid and hypothyroid Hashimoto's cases were more likely to have a family history of the disease (66.7% vs. 69.2% vs. 47.7%; P < 0.05). No differences were observed in the prevalence of DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302 across the three groups. Body mass index, lipid levels, glycemic control, and diabetes complications were also similar. However, euthyroid Hashimoto's women were more likely to report spontaneous abortions than those with hypothyroid Hashimoto's thyroiditis or no thyroid disease (23.8% vs. 61.5% vs. 29.1%; P < 0.05). These data suggest that gender-specific risk factors may be primary determinants of Hashimoto's thyroiditis and other autoimmune diseases among women. However, disease-specific determinants may also increase susceptibility to other autoimmune diseases.

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.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.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 values2.5 mU/L. All subjects with TSH values4.0 mU/L tested positive for TAb. Eighteen women (3.6%) who tested normal during pregnancy tested abnormal in the postpartum.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.

Siegel SF, Ahdab-Barmada M, Arslanian S, Foley Jr TP. Ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 in twins. Eur J Endocrinol 1995;133:87–92. ISSN 0804–4643 Twin boys with hypopituitarism, hypoplasia of the anterior pituitary gland, ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 are described. The smooth appearance at the base of the median eminence and the absence of a pituitary stalk at autopsy in these boys implies that the hypopituitarism resulted from a developmental aberration. It remains to be determined if there is a causal relationship between the chromosome 1 anomaly and hypopituitarism. Selma F Siegel, Division of Endocrinology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA, 15213, USA

Autoimmune thyroiditis is the most common cause of subclinical hypothyroidism in North America, is more common in women than men, and is a risk factor for the development of coronary heart disease (CHD). We measured thyroid-stimulating hormone (TSH) and two thyroid antibodies, thyroid peroxidase and thyroglobulin, in stored sera of the participants (aged 44 to 54 years) of the Healthy Women Study. We selected 254 samples from the premenopausal baseline examination in 1983 to 1985 and from a follow-up examination that occurred an average of 5.7 years later (range, 3 to 7.7 years). At follow-up, 95 women remained premenopausal, 98 had ceased menstruating for at least 12 months, and 61 were taking postmenopausal hormone therapy. Overall, the prevalence of the thyroid antibodies in this healthy population was high at both time points (21 to 26%). Women with antibodies had higher TSH concentrations than did those with no antibodies (2.68 +/- 1.3 versus 1.51 +/- .73 mU/L, P 6.0 mU/L). TSH and antibody levels did not differ by menopausal status or hormone therapy use at follow-up. Given the high prevalence of thyroid antibodies among healthy middle-aged women, long-term follow-up is warranted to ascertain whether the presence of antibodies is associated with subsequent excess risk of disease, in particular, CHD.

Thyroid disease is the most common endocrine disorder during adolescence. Approximately one third of adolescents with insulin-dependent diabetes mellitus develop autoimmune thyroid disease. Goiter or thyromegaly are synonymous terms used to describe an enlargement of the thyroid gland. This article discusses many aspects of goiter in adolescents, indicating that prognosis of thyroid disease in adolescents is usually excellent.

Evidence supports the presence of a genetic predisposition to an abnormality in immune surveillance, with environmental factors precipitating the development of Graves' disease.

Background Thyroxin (T 4 ) plays an important role in the regulation of the rate of metabolism of proteins, fats, and carbohydrates. Congenital hypothyroidism, an inherited deficiency of thyroid hormones, is screened in newborns using a variety of methods that include total T 4 or thyroid stimulating hormone (TSH). Some laboratories measure either total T 4 or TSH as a means of detecting infants with hypothyroidism with a subset that analyzes both total T 4 and TSH as a primary screen or a combination of primary and secondary screens. Methods We have developed a new MS/MS method that measures T 4 from a filter paper blood spot following methanol extraction using the essentially the same method as MS/MS analysis of amino acids. Product ion spectra show a transition of 833.8 → 731.8 (102 Da). An SRM for T 4 and 13 C 6 –T 4 was added to the MS/MS analysis of acylcarnitines and amino acids. Results Analysis of T 4 by MS/MS compares well with the immunoassay. The mean of 10,225 newborn screening specimens was 14.4 μg/dl (range 2.4–33) for MS/MS and 16.9 μg/dl (range 1.4–71.8) for AutoDELFIA. The MS/MS assay was linear with a correlation coefficient of 0.998. Regression analysis of MS/MS with the AutoDELFIA had a slope of 0.7, a y -intercept of 3.25, and a correlation coefficient of 0.727. We determined a MS/MS detection limit of 0.97 μg/dl and a lower LoQ (limit of quantification) of 2 μg/dl. Conclusion This method may provide a cost effective means of analyzing both T 4 and TSH by consolidating a T 4 analysis into the MS/MS panel.

Aim/hypothesis: To assess the prevalence of autoimmune thyroid disease (ATD) in insulin-treated youth with clinical features of type 2 diabetes mellitus (T2DM). Methods: We evaluated prevalence of thyroid peroxidase (TPO) and thyroglobulin (TGA) antibodies at onset of insulin-treated diabetes and follow-up in 183 White and Black children. Of these, 136 had a body mass index (BMI)

Near-adult height (AH) was determined in 121 children (72 males and 49 females) with GH deficiency (GHD) who were prepubertal when they began treatment with recombinant DNA-derived preparations of human GH. AH as a SD score was -0.7 +/- 1.2 (mean +/- SD), significantly greater than the pretreatment height SD score (-3.1 +/- 1.2), the predicted AH SD score (-2.2 +/- 1.2; Bayley-Pinneau method), and the height SD score at the start of puberty (-1.9 +/- 1.3). In contrast to studies of GH treatment outcome, which used pituitary-derived GH (pit-GH) in lower doses, we found that males did not have a higher AH SD score than females, spontaneous puberty did not diminish AH, and AH was significantly greater than that predicted at the start of GH treatment. In a multiple regression equation, the statistically significant variables (all P < 0.0001) related to AH (r2 = 0.70) were the following: duration of treatment with GH, sex (males were taller than females, as expected for the normal population), age (younger children had a greater AH) and height at the start of GH, and growth rate during first year of GH. For the AH SD score (r2 = 0.47), pretreatment predicted AH, duration of GH, and bone age delay were significant (P < 0.0002) explanatory variables. Bone age delay (chronological age-bone age) had a negative impact on the AH SD score. Target height, etiology of GHD, previous treatment with pituitary GH, and the presence or absence of spontaneous puberty did not significantly improve the prediction of AH. Early diagnosis of GHD and continuous treatment with larger doses of GH to near AH should improve the outcome in children with short stature due to GHD.

Thyroid-antibody screening is recommended for several adult populations, including the elderly and pregnant and postpartum women, and analysis of filter paper-dried blood spots (DBSs) has been a cost-effective means of screening newborns for hypothyroidism for more than 30 years. The aim of this study was to show that DBS specimens can be used to test adults for thyroid-stimulating hormone (TSH) antibodies and thyroid antibodies during screening for thyroid disease in a community setting. Thyroid peroxidase antibody and thyroglobilin antibody enzyme-linked immunosorbent assay kits for serum have been adapted for use with DBSs. A TSH assay for newborn DBSs was adapted for the screening of adults. Parallel specimens, serum and DBSs, were collected during routine care of patients attending a thyroid clinic. In addition, 962 DBS specimens were collected from volunteers at community centers and nursing homes. Twelve months later, a second specimen was collected from each of 411 original volunteers. Antibody results are reported as normal and positive. Ninety-seven percent of the serum/DBS results correlated exactly. Of 962 volunteers from nursing homes and community centers, testing for antibodies was positive or indeterminate (borderline) in 266 (27%). Eighty percent of the patients with an initially normal TSH reading who were positive on the 12-month collection were positive for at least one antibody in the first collection. The use of DBSs is a convenient and efficient way to screen for thyroid antibody as a means of detecting occult thyroid disease in adults.

Thyroid hormones play major roles in the regulation of a wide range of metabolic and physiologic processes, but the genes and environmental factors that affect normal, quantitative variation in thyroid hormone concentrations are largely unknown. Using quantitative genetic methods, we evaluated the effects of genes and environmental factors on thyroid hormone variation in 586 women and 425 men from 27 randomly ascertained Mexican-American families from the San Antonio Family Heart Study. Data were available on free and total T(4), free and total T(3), TSH, thyroglobulin, and T(4)-binding globulin, as well as on covariates, including sex, age, weight, lifestyle habits, physical activity, and others. These covariates accounted for 2-18% of total phenotypic variation, whereas genes accounted for 26-64% of the variation. Overall, free T(3) had the highest heritability, which is noteworthy because it is the most biologically active thyroid hormone and accounts for the vast majority of metabolic and physiologic effects of thyroid hormones. Our results indicate that genes account for a substantial portion of variation in human thyroid hormone levels, and suggest that further studies to identify the genes involved in this variation could reveal important insights into the processes that govern thyroid-mediated metabolism.

Objective: Symptoms of hypothyroidism in adults can be mistaken for medical and psychiatric diseases, as well as for general signs of ageing such as weakness, lethargy and fatigue. The incidence of hypothyroidism is many-fold higher in adults than in newborn children. The latter have been routinely screened for the condition using filter paper dried blood spots (DBS) for nearly three decades but this cost-effective screening technique has only recently been applied to adults. This study was undertaken to show that DBS testing in adults and older children is an accurate way to screen for hypothyroidism. Methods: Serum and DBS specimens were collected from adults and children. Assays were run on both specimens and the results correlated. In addition 972 specimens were collected from adults at community centres and nursing homes. Follow-up studies were performed on patients with positive results. Results: The correlation coefficient for 118 matched serum and DBS specimens was 0.99. Thyroid-stimulating hormone (TSH) values were elevated in 50 of the 972 adults from nursing homes and community centres. Thirteen of these individuals were on thyroid medication and 28 had either high serum TSH or high thyroglobulin (TgAb) or thyroid peroxidase (TPOAb) antibody levels. Conclusions: Individuals can be screened for hypothyroidism by collecting finger stick DBS specimens at community centres, nursing homes and other locations which can be mailed by regular postal service to a central laboratory for accurate and inexpensive testing.

Hypothyroidism in neonates and very young infants is usually caused by thyroid dysgenesis associated with an absent, ectopic, or hypoplastic gland1. It can be detected by neonatal screening, even if it is not clinically evident at that time. Although this condition is usually permanent, it can be transient, as it is, for example, in infants of mothers with chronic autoimmune thyroiditis2,3. In these infants transplacental passage of maternal thyrotropin-receptor antibodies inhibits the action of thyrotropin on the infant's thyroid gland until the antibodies are metabolized by the infant during the first several weeks of life2–4. . . .

There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. We determined the frequency of these autoantibodies by radioimmunoassay in 199 sera from patients with autoimmune thyroid diseases (AITD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC), and compared the results with those from 507 newly diagnosed patients with IDDM and 280 healthy controls. ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.

• Objective. —To determine if improved delineation of hypothalamic-pituitary neuroanatomy by magnetic resonance imaging, especially the posterior pituitary hyperintense T1signal, can be correlated with anterior and posterior pituitary endocrine function. Design. —Children with ectopic posterior pituitary tissue were identified at the Endocrine Clinic of the Children's Hospital of Pittsburgh (Pa) and their records were reviewed. Participants.—Ten children with ectopic posterior pituitary tissue. Measurements. —Anterior pituitary hormone status, determined by standard testing, was correlated with the morphologic anomalies of the hypothalamic-pituitary region on magnetic resonance imaging. Results. —Patients were categorized by the appearance of the pituitary stalk based on the magnetic resonance image: attenuation of the stalk (group 1) or nonvisualization of the stalk (group 2). Patients in group 1 retained partial anterior pituitary function. Patients in group 2 had panhypopituitarism. Conclusion. —Prospective evaluation of affected individuals may provide insight into the pathophysiologic mechanisms of idiopathic hypopituitarism. (AJDC. 1993;147:647-652)

Throughout pregnancy the fetus is dependent upon the placental transport of nutrients from the mother to support growth and differentiation. By this same mechanism the fetus is exposed to a variety of maternal factors that may adversely affect thyroid embryogenesis and function during pregnancy and postnatal life. The maternal factors include altered concentrations of iodide, immunoglobulins primarily in the G class (IgG), drugs, environmental goitrogens and other substances that are poorly understood or defined.

We evaluated the longitudinal response in 43 infants with congenital primary hypothyroidism during the first year of L-thyroxine therapy. Diagnosis was confirmed by serum thyroid hormone measurements by 4 weeks of age in 38 infants and between 40 and 80 days of age in the remainder. This group of infants was divided by radionuclide thyroid imaging into 34 infants with thyroid dysgenesis and nine with dyshormonogenesis. The group with thyroid dysgenesis was subdivided into 21 infants with athyreosis and 13 with residual thyroid tissue (11 ectopic and 2 hypoplastic glands). L-Thyroxine therapy, at an average dose of 10 to 14 micrograms/kg/day, was begun immediately after diagnosis, and serum concentration of total thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyroid-stimulating hormone were determined serially. Serum concentration of total and of free thyroxine became normal within 1 week of the start of therapy in all groups. Despite a similarly mild degree of hypothyroidism at diagnosis observed in infants with dyshormonogenesis or with ectopia or hypoplasia, those with dyshormonogenesis had a more sensitive response to initial thyroid hormone replacement than did patients with thyroid dysgenesis, as judged by L-thyroxine does and thyroid-stimulating hormone suppression. We conclude that the prompt restoration of clinical and biochemical euthyroidism during early infancy with doses of L-thyroxine between 10 and 14 micrograms/kg/day is a safe and effective method of therapy for children with congenital hypothyroidism.

Disorders of the thyroid gland have been recognized for more than 2,000 years. Endemic goiter and cretinism were evident during the fourth century B.C. by Andean sculptures of goitrous dwarfs and descriptions recorded in Europe during the first century B.C. (Gaitan, 1975; Cranefield, 1962). Thyromegaly associated with the symptoms and signs of hyperthyroidism was first recognized by Parry in 1786 although not published until 1825 (Parry, 1825). The most common cause of hyperthyroidism is named after Robert Graves who reported the disease in 1835 and associated the enlargement of the thyroid with the cause of the clinical disease (Graves, 1835). Not until the second half of the nineteenth century was an absence of the thyroid gland associated with clinical features of cretinism (Curling, 1850) and myxedema (Ord, 1878). Medical therapy for hypothyroidism was discovered approximately 100 years ago, and antithyroid drugs and radioiodine were introduced as treatment for hyperthyroidism approximately 50 years ago.

Thyrotropin receptor antibodies (TRAb) were measured in serum from 49 patients with active and inactive juvenile Graves disease, and the results were compared with values from control subjects and patients with Hashimoto disease. With a thyrotropin binding inhibition immunoglobulin (TBII) assay, TRAb were found in serum from 25 (93%) of 27 patients with untreated, active Graves disease. The TRAb values remained positive in 20 (72%) of 29 patients during the first 6 months of antithyroid therapy and in 13 (54%) of 24 patients during the second 6 months. After discontinuation of antithyroid therapy, 15 patients experienced 18 episodes of relapse of thyrotoxicosis; during relapse TRAb values were positive in all but one patient. Among 19 patients who remained clinically and biochemically euthyroid after cessation of antithyroid therapy, TRAb were not detected in 28 (78%) of 36 serum specimens. Of the eight positive values from six patients, no antiidiotypic antibodies were found, and thyroid stimulating immunoglobulins (TSI) were not detected in four specimens. The TRAb determination correctly predicted the subsequent clinical course in 26 (72%) of 36 patients. Furthermore, TRAb values and results of triiodothyronine suppression tests were in agreement in 27 of 36 patients, or 75% of the time. TSI were present in serum from only 19 (73%) of 26 patients with active disease; however, TSI were negative in all patients with inactive Graves disease. During the management of Graves disease, TRAb measurements by TBII determinations are valuable in the diagnosis of active disease, assist in the decision to discontinue antithyroid drug therapy, and are useful as the T3 suppression test to predict the clinical course of the disease. The TSI measurement is most useful to determine the activity of the disease when TRAb values are positive in a euthyroid patient.

Somatostatin is a known inhibitor of hormone secretion and of nutrient transport. Because somatostatin-like immunoreactivity has been detected in amniotic fluid and the placenta has both hormone secretory and nutrient transport functions, we investigated the possible existence of somatostatin receptors on placenta cell membranes. Binding of 125I-Tyr1- and 125I-Tyr11-somatostatin (5-21%) to solubilized placenta cell membranes was observed. Binding was time-, temperature-, and pH-dependent and occurred maximally with incubation at concentrations of 25 micrograms of membrane protein. Displacement of binding of 125I-Tyr1 and Tyr11 somatostatin by cold cyclic and linear somatostatin and somatostatin analogs Ala-5, Ala-8, and Ala-11 was observed. Scatchard analysis of data revealed high capacity of (Ro 0.44 mol/micrograms X 10(-12) but low affinity (Kd 1.8 M X 10(-7) binding sites similar to that reported in other tissues. Binding was not reversible under our experimental conditions. The significance of this low affinity binding of somatostatin to placenta cell membranes remains to be determined.

The diagnostic evaluation of the patient with thyromegaly will be determined by the clinical history and an examination of the thyroid gland (Table 9). In most instances the diagnosis will not be in doubt, and only a few tests will be necessary. For example, the euthyroid adolescent female with an asymmetrically or symmetrically enlarged, firm thyroid gland has a presumptive diagnosis of CLT, and only tests of thyroid function (T4 and TSH) and thyroid antibodies may be needed for confirmation. Similarly, the patient with clinical symptoms and signs of hyperthyroidism, exophthalmus, and a diffusely enlarged, soft thyroid gland has a presumptive diagnosis of Graves disease. The necessary tests include only a measurement of T4, an estimate of free T4, and WBC and differential counts prior to the initiation of antithyroid drug therapy. [See table in the PDF file] In the absence of an obvious diagnosis, the clinician will select the specific diagnostic tests depending upon the examination of the thyroid gland. The cause of smooth, symmetrical, diffuse enlargement of the thyroid gland can be suspected with careful history for familial disease, history of exposure to goitrogens and goitrogenic drugs, and the determination of thyroid antibodies in serum. If the clinical history is suggestive of hyperthyroidism, the tests of thyroid function tests should include determination of serum T3 concentration; if the history is compatible with euthyroidism or hypothyroidism, thyroid function tests should include determination of serum TSH concentration for the presence of compensated primary hypothyroidism. If results of these tests are normal, no additional tests are necessary, and the patient should be reassured and seen again in six months. If the patient has a test that is negative for thyroid antibodies and an elevation of serum TSH concentration, a radioactive [123I]iodide uptake and perchlorate discharge test will be helpful in the diagnosis of familial dyshormonogenesis. The patient with constitutional symptoms of inflammatory disease, history of a recent upper tract respiratory infection, and a tender or nontender enlarged thyroid gland may have subacute thyroiditis; a low or absent uptake of radioiodine with high-normal or elevated T4 and T3 concentrations will be suggestive of that diagnosis. In patients with thyromegaly and mild symptoms of hyperthyroidism, a TRH test will help to discriminate hyperthyroxinemia secondary to increased or abnormal serum thyroxine binding proteins from early Graves disease, factitious hyperthyroidism, toxic thyroiditis, and TSH-mediated hyperthyroidism. The T3 suppression test is a definitive diagnostic test for early, mild Graves disease. The euthyroid patient with mild-to-moderate thyromegaly and tests that are negative for thyroid antibodies usually deserves no further diagnostic evaluation, but should be followed with a presumptive diagnosis of idiopathic goiter or mild CLT. On follow-up evaluation, initially at six-month intervals and subsequently at yearly intervals, the patient should have a clinical and biochemical assessment until thyromegaly regresses and the gland is normal in size and consistency. The patient with a nontender, firm, irregular enlargement of the thyroid gland usually has CLT. If results of thyroid function tests are normal and tests for thyroid antibodies are negative, the patient should be seen again in four to six months and serum thyroid antibody determinations again performed. Another test that may give abnormal results in patients with CLT is the perchlorate discharge test. The approach to the patient with the solitary thyroid nodule differs from that of the previously described clinical presentations. The most important studies for the patient with a thyroid nodule are those designed to determine the structure and consistency of the thyroid gland, namely, ultrasonography to distinguish between solid and cystic lesions, and the radionuclide scan to determine whether the nodule is functioning (hot) or nonfunctioning (cold). To assure that the thyroid nodule is not associated with a nonsurgical lesion such as Hashimoto thyroiditis, serum thyroid antibody determinations are important. As malignancy of the thyroid gland is usually not associated with abnormalities of thyroid function, it is important to perform laboratory tests to exclude hyperthyroidism (a serum T3 determination) and hypothyroidism (a serum TSH determination) at the time of initial evaluation. Additional tests are usually not necessary unless the patient had mild hyperthyroidism with an autonomously functioning nodule, in which case the T3 suppression test and TRH test are often useful; rarely, the TSH stimulation test is helpful in determing whether thyroid tissue throughout the remainder of the gland is suppressed. A solitary, solid, nonfunctioning (cold) nodule requires excisional biopsy.

The seasonal and chronological distributions of birth dates of 820 patients with congenital hypothyroidism due to thyroid dysgenesis were analysed in eight areas in the world. The incidence had some seasonal variations in certain areas. These observations suggest that some environmental factors cause this disease.

Thirty-six children with growth hormone deficiency were treated for up to 48 months with methionyl human growth hormone (hGH) synthesised by DNA recombinant methods. The growth rate for these children increased from 3.2 +/- 1.1 cm/yr to 10.5 +/- 2.2 cm/yr (mean +/- SD). This was similar to the effect of pituitary hGH in ten GH deficient children, 3.8 +/- 1.0 to 10.1 +/- 1.1 cm/yr. Serum somatomedin C rose from 0.26 +/- 0.23 U/ml to 0.79 +/- 0.53 U/ml after 6 months of methionyl-hGH therapy, similar to the effect of pituitary hGH. The incidence of antibody formation to methionyl-hGH was higher than that observed with pituitary hGH (Kabi) but poor growth was observed only in the one patient on methionyl-hGH who acquired high-titre high-binding-capacity antibodies to hGH. No consistent changes in levels of antibodies to Escherichia coli proteins were detected. No other allergic manifestations or systemic side-effects were demonstrable.

Twelve patients with low birth weights and/or birth lengths for gestational age were treated with one or more daily doses of human growth hormone (hGH) ranging from 1.0 to 10.2 mg. per square meter of body surface area per day for five to 18 months. Significant delay in skeletal maturation was found in all but one patient. Of the eight patients aged seven years or younger at the time of treatment, the growth rates of five (62.5 per cent) during treatment with hGH were at least twice their pretreatment growth rate; in six (75 per cent) the pretreatment growth rates were exceeded by 3.5 cm. or more per year. Among those patients who received their initial course of hGH therapy in a dose of 2 mg. or more per square meter of body surface area per day, five of eight patients (62.5 per cent) more than doubled their pretreatment growth rates during hGH therapy; seven of eight (88 per cent) increased their pretreatment growth rates by more than 3.5 cm. per year during hGH therapy. In sufficient dose hGH is an effective therapeutic agent in some young patients who have had intrauterine growth retardation.

The clinical, neuroradiologic, and endocrine features in 16 patients with septo-optic dysplasia are reviewed. All of the patients had clinical optic nerve hypoplasia with varying degrees of nystagmus and visual impairment. Only one-half of the patients had absence of the septum pellucidum. Fourteen children were growth hormone deficient, 9 were adrenocorticotrophic hormone deficient, 3 were thyroid-stimulating hormone deficient, and 4 had diabetes insipidus. In most instances, the diagnosis of septo-optic dysplasia can be established by physical examination and neuroradiologic findings, at which point a thorough evaluation of the hypothalamicpituitary endocrine function is indicated because of the high incidence of hypopituitarism with this syndrome.