Effects of treatment with methimazole on circulating CD4+ and CD8+ T cells positive for programed cell death protein-1 and on subsets of CD4+ T cells in untreated hyperthyroid patients with Graves' disease.

OBJECTIVE: We investigated longitudinal changes in circulating CD4+ and CD8+ T cells positive for programed cell death protein-1 (PD-1) and in other subsets of CD4+ T cells in untreated hyperthyroid patients with Graves' disease after treatment with methimazole (MMI). DESIGN AND PATIENTS: The study included 18 untreated hyperthyroid patients with Graves' disease and 18 age-matched controls. Before and after 12-week treatment with MMI, we used flow cytometry to measure circulating PD-1+  D4+ and PD-1+ CD8+ T cells and subsets of CD4+ T cells in peripheral blood, as well as serum levels of chemokines related to T-helper type 1 (Th-1) and Th-2 cells. RESULTS: At baseline, the percentage of CD4+ and CD8+ T cells expressing PD-1 was significantly higher in patients than in age-matched controls. Serum levels of chemokines related to Th-1 and Th-2 also were higher in patients. Twelve weeks after initiation of MMI, the percentage of CD4+ T cells expressing PD-1 was significantly lower than at baseline, but no such change was seen in CD8+ T cells. Furthermore, the percentage of Th-1 cells among CD4+ T cells and the serum levels of soluble CD26/dipeptidyl peptidase-4, a surface marker of Th-1 cells, also were significantly lower than at baseline. CONCLUSIONS: The expression of PD-1 on circulating CD4+ and CD8+ T cells is increased in hyperthyroid patients with active Graves' disease. MMI significantly decreases levels of circulating PD-1+  CD4+ T cells, suggesting that PD-1+ T lymphocytes may be associated with the pathogenesis of Graves' disease.

Switching from the tablet to the powder formulation of levothyroxine corrects severe hypothyroidism in a patient with lactose intolerance.

We describe a case of a 38-year-old woman who, after radioactive iodine therapy for Graves' disease, developed severe hypothyroidism despite receiving a high dose of levothyroxine (L-T4) tablet as replacement therapy. Her thyroid stimulating hormone (TSH) remained to be high despite the dose of L-T4 tablets to 400 µg/day after treatment for hypothyroidism, and the patient complained of general malaise and edema of the legs. Reduced intestinal absorption of L-T4 is the most common cause of failure to achieve the therapeutic target in hypothyroid patients receiving replacement therapy. She was admitted to our hospital for severe hypothyroidism due to resistance to treatment with L-T4 tablet. Our patient was found to have lactose intolerance (LI) by a detailed examination during hospitalization. Therefore, we assumed that LI was impairing intestinal absorption of L-T4 tablet in our patient, leading to severe hypothyroidism. The patient was switched to the powder formulation of L-T4 at the same daily dose, and serum levels of thyroid-stimulating hormone and thyroid hormones normalized. This is the case in which hypothyroidism due to reduced absorption of L-T4 tablet in a patient with LI was resolved by switching to L-T4 powder formulation.

A case of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome with a novel frameshift variant in GATA3, p.W10Cfs40, lacks kidney malformation.

Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis.

Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitor showing unfavorable outcomes despite immediate discontinuation of medication.

We experienced two cases of dipeptidyl peptidase-4 (DPP-4) inhibitor-associated bullous pemphigoid (BP) showing an unfavorable course despite its discontinuation. Clinicians should carefully monitor the course of DPP-4 inhibitor-associated BP even after withdrawal of DPP-4 inhibitor therapy, especially in very elderly patients.