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T P Foley

Publications and source records attributed to T P Foley.

At least 19 recordsLinked to original sources
PubMed2001

Menopause in type 1 diabetic women: is it premature?

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.

Adult↗
PubMed1998

Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus.

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<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. In conclusion, because of the strong association of IDDM with AITD, testing for multiple islet autoanti-bodies could be useful as a predictive marker for risk of progression to IDDM onset amongst patients with autoimmune thyroid disorders.

Adolescent↗
PubMed1998

The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1.

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 > or = 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.

Adolescent↗
PubMed1998

Hashimoto's thyroiditis and insulin-dependent diabetes mellitus: differences among individuals with and without abnormal thyroid function.

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.

Abortion, Spontaneous↗
PubMed1997

Radioiodine treatment of juvenile Graves disease.

Ablation of the thyroid gland with radioactive iodine-I131 is an effective and safe method of therapy for older children and adolescents, as with adults, to treat hyperthyroidism of Graves disease (Graves-Basedow disease). The use of radioiodine as initial therapy or, as more often, the second line of therapy following antithyroid drug treatment is highly efficacious and rarely associated with short-term or long-term side effects. The indications for radioiodine therapy are failure of antithyroid drug therapy, idiosyncratic hypersensitivity reactions to antithyroid drugs, contraindications for surgical therapy including patients who refuse surgery, and the desirability to permanently prevent the development of hyperthyroidism. The treatment will induce permanent primary hypothyroidism within months after the use of ablative doses of radioiodine. The safety and simplicity of clinical management with L-thyroxine therapy for hypothyroidism favor radioiodine therapy for Graves disease over the potential risks from treatment with antithyroid drugs or surgery, and from untreated or relapsing hyperthyroidism. Radioiodine therapy is associated with the lowest morbidity and mortality among the currently available methods of therapy for Graves disease.

Adolescent↗
PubMed1997

Thyroid function and perimenopausal lipid and weight changes: the Thyroid Study in Healthy Women (TSH-W).

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 pressure < 100 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.

Adult↗
PubMed1997

Molecular epidemiology of autoimmune thyroid disease.

This paper presents preliminary data regarding the prevalence and risk factors for autoimmune thyroid disease in IDDM probands ascertained from the Children's Hospital of Pittsburgh IDDM Registry for 1950-1965 (n = 669). Living IDDM probands who participated in the 1990 follow-up survey (n = 380) were recruited for the Familial Autoimmune and Diabetes Study. Siblings and parents were also invited to participate. To date, 255 IDDM probands and 597 parents and siblings have been evaluated. The diagnosis of autoimmune thyroid disease was based on a clinical evaluation, medical history, and laboratory determinations. Graves disease was rare in this cohort (n = 5). However, Hashimoto's thyroiditis was common among women. Prevalence rates ranged from 54% for IDDM women age < 40 years to 75% for those > 50 years. Corresponding age-specific estimates for female relatives were 22% and 44%, respectively. Approximately one-half of the Hashimoto's individuals were euthyroid; they were more likely to have other autoantibodies and a positive family history than those who were hypothyroid or had no thyroid disease. Genetic analyses revealed a 2-fold increase in DQA1*0501-DQB1*0201 among the Hashimoto's compared to the non-Hashimoto's haplotypes. These findings suggested that Hashimoto's thyroiditis was common in IDDM families, which may be due, in part, to common disease susceptibility genes.

Adolescent↗
PubMed1995

Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women.

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 < 0.001); this relationship was statistically significant even after excluding those with subclinical hypothyroidism (TSH > 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.

Adult↗
PubMed1995

Ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 in twins.

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 casual relationship between the chromosome 1 anomaly and hypopituitarism.

Choristoma↗
PubMed1993

Pituitary stalk and ectopic hyperintense T1 signal on magnetic resonance imaging. Implications for anterior pituitary dysfunction.

OBJECTIVE: To determine if improved delineation of hypothalamic-pituitary neuroanatomy by magnetic resonance imaging, especially the posterior pituitary hyperintense T1 signal, 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.

Adolescent↗
PubMed1993

Insulin therapy increases low plasma growth hormone binding protein in children with new-onset type 1 diabetes.

This study was undertaken (1) to evaluate growth hormone binding protein (GHBP) levels in newly diagnosed patients with Type 1 diabetes before and after insulin therapy and (2) to determine the relationship of GHBP to glycaemic control, C-peptide level and blood pH. GHBP, expressed as a percentage of (125I)GH bound, was determined in 33 patients with Type 1 diabetes (M/F = 19/14, 12.3 +/- 0.4 years) before (day 0), after 5 days (day 5) and after 3 months (month 3) of insulin therapy. At day 0, GHBP was lower in Type 1 diabetes compared with 38 matched healthy control subjects (3.9 +/- 0.4 vs 8.2 +/- 0.4%, p < 0.001). There was no significant improvement in GHBP at day 5 (4.4 +/- 0.3%). At month 3, GHBP increased to (6.0 +/- 0.4%, p < 0.001 vs day 0), but was still lower than controls, p < 0.001. At day 0 GHBP correlated with BMI (r = 0.50, p = 0.001), blood glucose (r = -0.43 p = 0.006) and pH (r = 0.48, p = 0.004), but not HbA1. GHBP at month 3 correlated with day 0 C-peptide (r = 0.41, p = 0.02). Thus, (1) circulating GHBP is low in newly diagnosed patients with Type 1 diabetes, and increases after 3 months of insulin therapy but does not normalize and (2) the severity of biochemical derangement and residual beta-cell function at diagnosis may determine GHBP status and its recovery. We conclude that insulin is an important modulator of GH binding protein in newly diagnosed children with Type 1 diabetes.

Adolescent↗
PubMed1993

Goiter in adolescents.

Enlargement of the thyroid gland during adolescence should be considered a pathologic rather than physiologic process. With diffuse enlargement in an asymptomatic patient, thyroid function tests and thyroid antibodies usually are the only tests needed to define the diagnosis of euthyroid autoimmune thyroiditis. Patients with lobular or nodular thyroid enlargement may require additional tests if the diagnosis of Hashimoto's thyroiditis cannot be established by the presence of thyroid antibodies in serum. The tests to define the anatomic and functional status of nodular thyroid disease include ultrasonography and radionuclide scintigraphy of the thyroid, but rarely fine needle biopsy. The only indications for surgical therapy of the thyroid are hyperfunctioning thyroid adenomas, the suspicion of thyroid carcinoma and Graves' disease in patients who are not responsive to antithyroid drug therapy and who are poor candidates for radioiodine ablative therapy. The prognosis of thyroid disease during c adolescence is usually excellent.

Adolescent↗
PubMed1992

Thyrotoxicosis in childhood.

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

Child↗
PubMed1992

The relationship between autoimmune thyroid disease and iodine intake: a review.

There is evidence to suggest that elevated levels of iodide in the diet are associated with autoimmune thyroid disease (ATD) in susceptible individuals, and that autoimmune thyroiditis (Hashimoto's disease) is less common in susceptible individuals who live in regions with dietary iodine deficiency. There are epidemiologic studies in endemic goiter areas that report an increase in ATD, particularly thyroiditis, after the therapeutic administration of iodized salt, bread and oil. Lymphocytic infiltration of the thyroid is rarely found in patients from severe endemic goiter regions, yet there is a reversal of this observation after dietary iodine supplementation. Thyroid antibodies, both thyroglobulin (TgAb) and peroxidase (TpAb) or microsomal, were not detected in serum from patients with endemic goiter, but became positive in 43% of subjects three and six months after therapy with iodized oil, and there developed transient hyperthyroidism. Similarly, the addition of iodine to the diet or the administration of iodine-containing medications increases the frequency of ATD and the severity of existing autoimmune thyroiditis. Furthermore, autoimmune thyroiditis has been induced by the administration of excess iodide to strains of chickens and rats that are genetically predetermined to develop the disease. We are beginning to understand the pathogenesis of ATD. In hyperthyroidism the evidence clearly supports the hypothesis that TSH receptor antibodies (TRAb) stimulate the TSH receptor to induce excessive and sustained secretion of thyroid hormones. Cellmediated immune mechanisms, such as antibody dependent cellmediated cytotoxicity (ADCC), initiate the lymphocytic infiltration and thyrocytotoxicity in autoimmune thyroiditis. The mechanisms that initiate the development of the abnormal immune response and the relationship of ATD with excess iodide are poorly understood. There is evidence that an increase in the iodination of thyroglobulin (Tg) enhances its immunogenicity. The results of clinical and experimental studies support the requirement of a genetic predisposition to the development of ATD that may be precipitated by exposure to certain environmental factors. Another mechanism supported by experimental data is the direct toxic effect of excess iodide on iodide-deficient thyroid glands. High concentrations of iodide after oxidation to iodine causes epithelial necrosis and inflammation associated with lipofuscin accumulation suggestive of toxicity mediated by lipid peroxidation from excessive amounts of free radicals. The epithelial damage would initiate inflammatory and immune responses. Although these mechanisms would relate to the onset of autoimmune thyroiditis on exposure to excessive amounts of iodide, the relationship of iodide intake and autoimmune hyperthyroidism is less clear.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗