Glucose variability before and after treatment of a patient with Graves' disease complicated by diabetes mellitus: assessment by continuous glucose monitoring.

A 48-year-old woman was diagnosed and treated for Graves' disease (GD) in 1999 but she discontinued treatment at her own discretion. In 2011, she was admitted to a local hospital for management of thyrotoxic crisis. Treatment with propylthiouracil, iodide potassium (KI), and prednisolone (PSL) was started, which resulted in improvement of the general condition. PSL and KI were discontinued before she was transferred to our hospital. At the local hospital, fasting plasma glucose (FPG) was 212 mg/dL and hemoglobin A1c concentration was 11.2%; intensive insulin therapy had been instituted. Upon admission to our hospital, FPG level was 122 mg/dL, but insulin secretion was compromised, suggesting aggravation of thyroid function and deterioration of glycemic control. The FPG level increased to 173 mg/dL; continuous glucose monitoring (CGM) identified dawn phenomenon at approximately 0400 h. Resumption of KI resulted in improvement of FPG and disappearance of the dawn phenomenon, as assessed by CGM. These results indicate that in patients with compromised insulin secretion, hyperthyroidism can induce elevation of not only postprandial blood glucose, but also FPG level due to the dawn phenomenon and that the dawn phenomenon can be alleviated with improvement in thyroid function. To our knowledge, no studies have assessed glucose variability by CGM before and after treatment of Graves' disease. The observations made in this case shed light on the understanding of abnormal glucose metabolism associated with Graves' disease.

Prevalence of thyrotoxicosis, antithyroid medication use, and complications among pregnant women in the United States.

BACKGROUND: Population-based estimates of the prevalence of thyrotoxicosis (TTX), the frequency of antithyroid drug (ATD) use, and risk of adverse events in pregnant women and their infants are lacking. Therefore, our objective was to obtain epidemiologic estimates of these parameters within a large population-based sample of pregnant women with TTX. METHODS: A retrospective claims analysis was performed from the MarketScan Commercial Claims and Encounters health insurance database for the period 2005-2009. Women aged 15-44 years, enrolled for at least 2 years, and who had a pregnancy during the study period were included. Diagnosis of TTX was based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes using narrow (TTX-1=ICD 242.0) and broad (TTX-2=ICD 242.0 or 242.9) definitions. ATD use was based on prescriptions filled for propylthiouracil (PTU) or methimazole (MMI). Adverse events in mothers and infants were determined from the ICD-9-CM diagnosis codes recorded on submitted claims. RESULTS: The database contained 904,497 eligible women. The average yearly prevalence per 1000 pregnant women was 2.46 for TTX-1 and 5.88 for TTX-2. Thirty-nine percent used ATD at any time during the study period. Compared to women without a TTX diagnosis, there was more than a twofold increase for liver disease among women with TTX (odds ratio [OR]=2.08, p<0.001) and a 13% increased risk for congenital anomalies (OR=1.13, p=0.014), but no association was observed with ATD use. The rates of congenital defects (per 1000 infants) associated with ATD use were 55.6 for MMI, 72.1 for PTU, and 65.8 for untreated women with TTX, compared to 58.8 among women without TTX. CONCLUSIONS: There was some indication of an elevated risk of liver disease and congenital anomalies in women with TTX, but the risk did not appear to be related to the ATD use. There seems to be a higher pregnancy termination rate for women with TTX on MMI, which likely reflects elective pregnancy terminations.

Assessment of fetal thyroid function by colored Doppler echography.

BACKGROUND: The association of hyperthyroidism and pregnancy is a rare but serious condition which can jeopardize fetal outcome. Classical follow-up relies on: serial clinical and echographic assessment; serial funipuncture to determine fetal thyroid status, and maternal propylthiouracil (PTU) treatment to treat fetal and/or maternal hyperthyroidism. CASE: We report the case of a euthyroid patient with Graves' disease who had already been delivered of two hyperthyroid fetuses; the present pregnancy revealed a hyperthyroid fetus diagnosed by funipuncture. Echography showed a fetal goiter at 28 weeks of gestation (WG) with important signal on colored Doppler echography. We observed an extinction of this signal as maternal PTU treatment was intensified. The patient was delivered of a mildly hyperthyroid newborn at 37 WG. Both newborn and patient are doing well. CONCLUSION: Fetal thyroid assessment by colored Doppler echography could help in the management of fetal thyroid dysfunction.

Soluble CD antigen (cytokine) expression in various hyperthyroid states and use in the assessment of propylthiouracil treatment.

The soluble CD antigens sCD8, sCD23, and sCD25 are increased in untreated Graves' hyperthyroidism. These levels remain elevated when euthyroidism is established in response to propylthiouracil (PTU) therapy but decrease to control values after PTU treatment is discontinued, when euthyroidism has been established and maintained. Neither sCD8 nor sCD23 are elevated in patients with euthyroid Graves' ophthalmopathy nor in the hyperthyroid phase of subacute thyroiditis. sCD25 is increased to an intermediate degree in these disorders. Soluble CD8 > or = 450 U/ml is sensitive, specific, and predictive of PTU success as sole therapy or need for definitive therapy in untreated and PTU-treated Graves' hyperthyroidism, exceeding the predictive values of thyroid-stimulating hormone receptor antibody, thyroid peroxidase antibody, and T3 radioimmunoassay.

Medicolegal analysis of errors in diagnosis and treatment of surgical endocrine disease.

BACKGROUND: The medicolegal impact of adverse events in surgical endocrine disease has not been described previously. This study was undertaken to determine the causes, costs, and outcomes of endocrine malpractice litigation. METHODS: Jury verdict reports from the U.S. civil court system from 1985 through 1991 were reviewed. Sixty-two malpractice cases were identified from 21 states. RESULTS: The 62 cases were classified into three categories, totaling 63 adverse events: (1) complications (n = 34, 54%) from thyroid (n = 32, 51%) or parathyroid (n = 2, 3%) surgery; (2) delayed diagnosis (n = 22, 35%) of thyroid cancer (n = 11, 18%), adrenal tumors (n = 9, 14%), and hyperparathyroidism (n = 2, 3%); and (3) medical morbidity (n = 7, 11%) from radioactive iodine (n = 5, 8%) or from propylthiouracil (n = 2, 3%). Surgical injuries, mostly recurrent nerve injuries by general surgeons, accounted for the greatest number of cases and the highest cost of litigation. CONCLUSIONS: Medical malpractice involving endocrine disease results in expensive litigation, a result of serious harm. Technical misadventures account for most cases, followed closely by delays in diagnosis. These data may aid design of risk prevention strategies in endocrine disease.

Amiodarone-induced hyperthyroidism: assessment of the predictive value of biochemical testing and response to combined therapy using propylthiouracil and potassium perchlorate.

In order to assess the value of thyroid function testing during amiodarone therapy, we reviewed all available tests in 128 patients treated with this drug. Nine patients (7.0%) developed biochemical hyperthyroidism with elevation of both free thyroxine index (FT4I) and free triiodothyronine index (FT3I) and marked suppression of serum thyroid stimulating hormone (TSH) after 1-46 months of therapy; six of these nine patients had clear clinical evidence of thyroid overactivity. Where serial tests were available before development of hyperthyroidism, this complication developed suddenly, despite previously stable normal indices of thyroid function, and could not be predicted by currently-available biochemical tests such as T4, T3, sensitive TSH, thyroglobulin or sex hormone binding globulin (SHBG) assays. Clinical features such as unexplained weight loss, proximal myopathy, exacerbation of arrhythmia, or heat intolerance appear to be the key to prompt diagnosis of this complication. Hyperthyroxinemia without T3 excess was found in 32.8% of patients without progression to true hyperthyroidism. Serum TSH remained detectable by sensitive assay in 17 out of 18 patients with amiodarone-induced euthyroid hyperthyroxinemia and was significantly higher than in patients with equivalent hyperthyroxinemia due to thyroxine therapy. Serial levels of SHBG were higher in patients with true hyperthyroidism than in those with euthyroid hyperthyroxinemia. The effect of combined treatment with propylthiouracil (800 mg/day) and potassium perchlorate (800 mg/day) was evaluated in five of the six clinically hyperthyroid patients. Biochemical euthyroidism was achieved after 7-19 weeks, a response slower than previously reported, indicating that this drug combination does not result uniformly in prompt resolution of amiodarone-induced hyperthyroidism.

Symptom rating scale for assessing hyperthyroidism.

A hyperthyroid symptom scale (HSS) was designed and administered to ten subjects with untreated Graves' disease. All subjects had clinical and chemical evidence of hyperthyroidism and reproducible HSS scores of 20 or more points. During sequential treatments with propranolol hydrochloride (phase 2) followed by propylthiouracil (phase 3) there was a significant decline in the HSS scores at each phase. Accompanying the decrease in HSS scores was a decrease in heart rate, but there was no change in thyroid function test results at phase 2 and a decrease in heart rate, thyroid function test results, and goiter size at phase 3. This new scale includes ten categories of symptoms, it is sensitive to changes in both the adrenergic and metabolic components of hyperthyroidism, and it is useful in the clinical assessment and management of patients with thyrotoxicosis.