Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.
Cesarean Section ; Craniosynostoses ; Emergencies ; Exons ; Female ; Germ-Line Mutation ; Humans ; Hydrocephalus ; Hyperthyroidism* ; Immunoglobulins, Thyroid-Stimulating ; Iodide Peroxidase ; Korea ; Male ; Mutation, Missense ; Parents ; Parturition ; Pregnancy ; Propranolol ; Propylthiouracil ; Receptors, Thyrotropin ; Tachycardia ; Thyroglobulin ; Thyroid Function Tests ; Ventriculoperitoneal Shunt

BACKGROUND: The incidence of thyroid nodules has increased worldwide in recent years. Thyroid dysfunction is a potential risk factor for hypercholesterolemia, cardiovascular disease, osteoporosis, arrhythmia, and neuropsychiatric disease. This study investigated the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism in Koreans. METHODS: In this nationwide population-based cohort study, 51,834,660 subjects were included using the National Health Information database from 2006 to 2015, after the exclusion of subjects with thyroid cancer. RESULTS: The prevalence in Korea in 2015 of thyroid nodules, hypothyroidism in patients taking thyroid hormone, and hyperthyroidism in patients undergoing treatment was 15.82/1,000 population, 15.94/1,000 population, and 2.76/1,000 population, respectively. All these diseases were more prevalent among women than among men. The number of incident cases of these three thyroid diseases steadily increased from 2006 to 2012, and then decreased through 2015. The incidence of thyroid nodules, hypothyroidism treated with thyroid hormone, and treated hyperthyroidism was 6.79/1,000 population, 1.76/1,000 population, and 0.55/1,000 population, respectively, in Korea in 2015. The use of methimazole continuously increased, from 33% of total antithyroid drug prescriptions in 2006 to 74.4% in 2015, and it became the most frequently prescribed antithyroid drug in Korea. In contrast, the use of propylthiouracil continuously decreased. CONCLUSION: This was the first nationwide study of the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism to take into account recent changes and to include the current status of patients receiving treatment.
Arrhythmias, Cardiac ; Cardiovascular Diseases ; Cohort Studies* ; Drug Prescriptions ; Female ; Humans ; Hypercholesterolemia ; Hyperthyroidism ; Hypothyroidism ; Incidence* ; Korea* ; Male ; Methimazole ; Osteoporosis ; Prevalence* ; Propylthiouracil ; Risk Factors ; Thyroid Diseases* ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule

Raynaud syndrome is a medical condition that causes pain, numbness, and changes in skin color at the distal extremities. Raynaud syndrome can be subdivided into primary Raynaud's and secondary Raynaud's. The former is diagnosed when the cause is unknown and the latter is caused by an underlying condition, such as connective tissue diseases, injury, smoking, or certain medications. Both cancer chemotherapy and β-blockers are relatively common causes of Raynaud syndrome but there are no reports of its association with methimazole administration. The authors encountered a 43-year old woman with hyperthyroidism who developed digital ulcers associated with Raynaud syndrome after a methimazole treatment. Her digital ulcers and Raynaud syndrome were improved after methimazole was replaced with propylthiouracil and conventional therapy. This paper reports this case along with a review of the relevant literature.
Connective Tissue Diseases ; Drug Therapy ; Extremities ; Female ; Humans ; Hyperthyroidism ; Hypesthesia ; Methimazole* ; Propylthiouracil ; Skin Pigmentation ; Smoke ; Smoking ; Ulcer

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been reported in Graves' disease patients treated with antithyroid drugs (ATDs), especially propylthiouracil. ATD-induced ANCA-associated vasculitis usually involved the kidneys followed by the respiratory organs and skin. The treatment of ANCA-associated vasculitis induced by ATDs is to stop ATD therapy immediately, which often leads to an overall good prognosis. We report a case of ANCA-associated vasculitis in the peripheral nerves of the lower extremities in a 66-year-old woman who was treated with methimazole (MMI) for Graves' disease. To our knowledge, this is the third case of peripheral nervous system (PNS) involvement of ATD-induced vasculitis and the first case of PNS vasculitis associated with MMI.
Aged ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Antibodies, Antineutrophil Cytoplasmic ; Antithyroid Agents ; Female ; Graves Disease ; Humans ; Kidney ; Lower Extremity ; Methimazole ; Peripheral Nerves ; Peripheral Nervous System ; Prognosis ; Propylthiouracil ; Skin ; Vasculitis

Thyroid dysfunction during pregnancy can result in serious complications for both the mother and infant. However, these complications can be prevented by the optimal treatment of overt maternal thyroid dysfunction. The serum thyroid-stimulating hormone (TSH) concentration is the most reliable measure of thyroid function during pregnancy. Due to the physiologic changes in TSH levels during pregnancy, the correct interpretation of thyroid function requires knowledge of the gestational week and the appropriate population-based reference interval. In addition to a TSH test, the measurement of thyroid peroxidase antibody helps determine whether to treat subclinical hypothyroidism during pregnancy. Since the use of antithyroid drugs during pregnancy is associated with birth defects, it is recommended to discontinue the medication and to perform repeated thyroid function testing during the first trimester. If therapy is needed during the first trimester, propylthiouracil is preferred over methimazole.
Antithyroid Agents ; Congenital Abnormalities ; Female ; Humans ; Hyperthyroidism ; Hypothyroidism ; Infant ; Iodide Peroxidase ; Methimazole ; Mothers ; Pregnancy Trimester, First ; Pregnancy ; Propylthiouracil ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin

Sweet's syndrome, or acute febrile neutrophilic dermatosis, occurs in association with autoimmune diseases such as Hashimoto's thyroiditis but is rare in Graves' disease, in which all cases are induced by propylthiouracil (PTU). We report a case of Sweet's syndrome in a patient with Graves' disease treated with methimazole (MMI) during three weeks. A 34-year-old man presented with the acute onset of high fever, skin rashes on the whole body, arthralgia, and acroparesthesia. Laboratory results showed leukocytosis and elevated C-reactive protein. MMI first stopped and antibiotics and antihistamine therapy started, but his symptoms dramatically improved after oral prednisolone. Graves' disease has again been treated by MMI because of his aggravated ophthalmopathy. After one year of retreatment with MMI, there has been no recurrence of Sweet's syndrome, supporting that Sweet's syndrome in this case was not related to MMI exposure. To our knowledge, this is the first report of Sweet's syndrome associated with Graves' disease per se but not PTU or MMI use.
Adult ; Anti-Bacterial Agents ; Arthralgia ; Autoimmune Diseases ; C-Reactive Protein ; Exanthema ; Fever ; Graves Disease* ; Humans ; Leukocytosis ; Methimazole ; Prednisolone ; Propylthiouracil ; Recurrence ; Retreatment ; Sweet Syndrome* ; Thyroid Gland ; Thyroiditis

BACKGROUND: Increased oxidative stress has been suggested as one of the underlying mechanisms in iodide excess-induced thyroid disease. Metallothioneins (MTs) are regarded as scavengers of reactive oxygen species (ROS) in oxidative stress. Our aim is to investigate the effects of propylthiouracil (PTU), a thyroid peroxidase inhibitor, perchlorate (KClO4), a competitive inhibitor of iodide transport, and thyroid stimulating hormone (TSH) on mitochondrial superoxide production instigated by high concentrations of iodide in the thyroids of MT-I/II knockout (MT-I/II KO) mice. METHODS: Eight-week-old 129S7/SvEvBrd-Mt1(tm1Bri) Mt2(tm1Bri)/J (MT-I/II KO) mice and background-matched wild type (WT) mice were used. RESULTS: By using a mitochondrial superoxide indicator (MitoSOX Red), lactate dehydrogenase (LDH) release, and methyl thiazolyl tetrazolium (MTT) assay, we demonstrated that the decreased relative viability and increased LDH release and mitochondrial superoxide production induced by potassium iodide (100 µM) can be relieved by 300 µM PTU, 30 µM KClO4, or 10 U/L TSH in the thyroid cell suspensions of both MT-I/II KO and WT mice (P<0.05). Compared to the WT mice, a significant decrease in the relative viability along with a significant increase in LDH release and mitochondrial superoxide production were detected in MT-I/II KO mice(P<0.05). CONCLUSION: We concluded that PTU, KClO4, or TSH relieved the mitochondrial oxidative stress induced by high concentrations of iodide in the thyroids of both MT-I/II KO and WT mice. MT-I/II showed antioxidant effects against high concentrations of iodide-induced mitochondrial superoxide production in the thyroid.
Animals ; Antioxidants ; Iodide Peroxidase ; Iodides ; L-Lactate Dehydrogenase ; Metallothionein* ; Mice ; Mice, Knockout* ; Oxidative Stress ; Potassium Iodide ; Propylthiouracil* ; Reactive Oxygen Species ; Superoxides* ; Suspensions ; Thyroid Diseases ; Thyroid Gland* ; Thyrotropin*

OBJECTIVES: This study aims to determine if there is a significant difference in the recovery time and duration of hospital stay of patients with anti-thyroid drug-(ATD) induced agranulocytosis with and without granulocyte colony-stimulating factor (GCSF) therapy. It also aims to describe the clinical characteristics of patients who had anti-thyroid drug-induced agranulocytosis.
METHODOLOGY: This is a retrospective study of hyperthyroid patients on anti-thyroid drugs (ATD) who had an absolute neutrophil count (ANC) of less than 500/?L. Their charts were reviewed for collection of data on age, gender, body mass index (BMI), type and duration of ATD and use of antibiotic and steroid. Recovery time and length of hospital stay were compared between those who received and did not receive GCSF.
RESULTS: With similar clinical features between the GCSF and non-GCSF groups, the recovery time from agranulocytosis and duration of hospitalization were significantly shorter in the GCSF group, despite lower ANC.
CONCLUSION: GCSF significantly decreased recovery time (4 versus 7 days, p=0.005) and duration of hospital stay (5 versus 7 days, p=0.009) of hyperthyroid patients with anti-thyroid drug-induced agranulocytosis compared to patients not given GCSF.

Human ; Male ; Female ; Middle Aged ; Adult ; Young Adult ; Adolescent ; Granulocytes ; Neutrophils ; Neutropenia ; Hyperthyroidism ; Granulocyte Colony-stimulating Factor ; Anti-bacterial Agents ; Antithyroid Agents ; Agranulocytosis ; Methimazole ; Propylthiouracil

BACKGROUND: Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients. METHODS: We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm3. RESULTS: The mean age of the patients (11 males, 43 females) was 38.2+/-14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (> or =6 days) and short recovery time (< or =5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization. CONCLUSION: The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.
Agranulocytosis* ; Antithyroid Agents ; Fever ; Granulocyte-Macrophage Colony-Stimulating Factor ; Graves Disease ; Hospitalization ; Humans ; Korea* ; Male ; Methimazole ; Neutrophils ; Pharyngitis ; Propylthiouracil ; Retrospective Studies ; Sepsis ; Tertiary Care Centers

Pyoderma gangrenosum (PG) is a rare disease that causes chronic skin ulcers, and it has recently been known to be related to changes in the immune system such as dysfunction of neutrophils. Over 50% of patients with PG have an underlying systemic disease, and rarely are there various medicines causing the disease, including iodide, bromide, and isotretinoin. A 49-year-old man had recurrent skin ulcers in his lower extremities. He had a history of taking propylthiouracil (PTU) for 10 years as a treatment for Graves' disease. Here, we describe a case of PTU-induced ANCA positive PG in a patient with hyperthyroidism, who has been improved after the cessation of PTU.
Antibodies, Antineutrophil Cytoplasmic* ; Graves Disease ; Humans ; Hyperthyroidism ; Immune System ; Isotretinoin ; Lower Extremity ; Middle Aged ; Neutrophils ; Propylthiouracil* ; Pyoderma Gangrenosum* ; Rare Diseases ; Skin Ulcer