propylthiouracil and Diabetes-Mellitus--Type-1

Topics: Abortion, Spontaneous; Adult; Antithyroid Agents; Autoantibodies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fertilization in Vitro; Gestational Age; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Infertility, Female; Iodine; Male; Menstrual Cycle; Menstruation Disturbances; Pregnancy; Pregnancy Complications; Prevalence; Propylthiouracil; Puerperal Disorders; Risk Factors; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyroiditis; Thyrotropin; Thyroxine; Ultrasonography

Pancreatic progenitors derived from human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating diabetes and are currently being tested in clinical trials. Yet, how the milieu of pancreatic progenitor cells, including exposure to different factors after transplant, may influence their maturation remains unclear. Here, we examined the effect of thyroid dysregulation on the development of hESC-derived progenitor cells in vivo. Hypothyroidism was generated in SCID-beige mice using an iodine-deficient diet containing 0.15% propyl-2-thiouracil, and hyperthyroidism was generated by addition of L-thyroxine (T4) to drinking water. All mice received macroencapsulated hESC-derived progenitor cells, and thyroid dysfunction was maintained for the duration of the study ("chronic") or for 4 weeks posttransplant ("acute"). Acute hyperthyroidism did not affect graft function, but acute hypothyroidism transiently impaired human C-peptide secretion at 16 weeks posttransplant. Chronic hypothyroidism resulted in severely blunted basal human C-peptide secretion, impaired glucose-stimulated insulin secretion, and elevated plasma glucagon levels. Grafts from chronic hypothyroid mice contained fewer β-cells, heterogenous MAFA expression, and increased glucagon(+) and ghrelin(+) cells compared to grafts from euthyroid mice. Taken together, these data suggest that long-term thyroid hormone deficiency may drive the differentiation of human pancreatic progenitor cells toward α- and ε-cell lineages at the expense of β-cell formation.

Topics: Animals; Antithyroid Agents; Biomarkers; Cell Differentiation; Cell Line; Cells, Immobilized; Diabetes Mellitus, Type 1; Disease Models, Animal; Heterografts; Human Embryonic Stem Cells; Humans; Hyperthyroidism; Hypothyroidism; Insulin-Secreting Cells; Iodine; Male; Mice, SCID; Propylthiouracil; Random Allocation; Thyroxine; Transplantation, Heterologous; Transplantation, Heterotopic

We report a case of 26-year-old woman with Graves' disease and idiopathic hypoparathyroidism diagnosed at 11 years of age, who subsequently developed insulin-dependent diabetes mellitus (IDDM) at 17 years of age. Treatment with antithyroid agents had failed to control her Graves' disease and her IDDM was unmanageable despite insulin therapy. Surgical intervention was carried out, resulting in an improvement of both her hyperthyroidism and IDDM. This case is the first report of polyglandular autoimmune (PGA) syndrome, presenting the association of IDDM, Graves' disease and idiopathic hypoparathyroidism.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycosuria; Graves Disease; Humans; Hypoparathyroidism; Insulin; Propylthiouracil; Thyroid Hormones

We report here six pregnancies in 5 women with juvenile diabetes and Graves disease. The diabetes was managed in a standard fashion. The Graves disease was managed with propylthiouracil when required. The course of neither the diabetes nor Graves disease was different than expected. When established guidelines for therapy are followed the two have no interaction with one another. One infant was mildly hypothyroid. None developed neonatal Graves disease. Four of the infants had hyperbilirubinemia.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Infant, Newborn; Insulin; Jaundice, Neonatal; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Propylthiouracil