Glucose Variability Before and After Treatment of a Patient with Graves’ Disease Complicated by Diabetes Mellitus: Assessment by Continuous Glucose Monitoring
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Endocrine Journal 2014, 61 (4), 321-328 ORIGINAL Glucose variability before and after treatment of a patient with Graves’ disease complicated by diabetes mellitus: Assessment by continuous glucose monitoring Keiichi Torimoto, Yosuke Okada, Tadashi Arao, Hiroko Mori, Sunao Yamamoto, Manabu Narisawa, Akira Kurozumi and Yoshiya Tanaka First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushyu 807-8555, Japan Abstract. 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. Key words: Graves’ disease (GD), Continuous glucose monitoring (CGM), Dawn phenomenon HYPERTHYROIDISM can interfere with glucose ability patterns that were otherwise not possible with metabolism through various mechanisms, and 50% of the self-monitoring of blood glucose (SMBG). To our patients with thyrotoxicosis are reported to have abnor- knowledge, however, no studies have assessed glucose mal glucose tolerance [1]. Known factors responsi- variability by CGM before and after treatment of hyper- ble for abnormal glucose tolerance include enhanced thyroidism. Here, we report a patient with Graves’ dis- glucose absorption via the digestive tract [2, 3] and ease complicated by diabetes mellitus, who presented increased endogenous gluconeogenesis [4]. However, with disturbance of endogenous insulin secretion. In as a compensatory mechanism, excessive insulin secre- this patient, hyperthyroidism resulted in not only post- tion [5, 6] is typically effective; hyperglycemia is often prandial hyperglycemia but also elevation of fasting absent even in patients with thyrotoxicosis. plasma glucose (FPG) level due to the dawn phenome- The prevalent use of continuous glucose monitor- non, and CGM was employed to confirm alleviation of ing (CGM) has provided details on blood glucose vari- the dawn phenomenon following improvement of thy- roid function. Submitted Oct. 2, 2013; Accepted Dec. 22, 2013 as EJ13-0410 Released online in J-STAGE as advance publication Jan. 11, 2014 Research Design and Methods Correspondence to: Yoshiya Tanaka, M.D., Ph.D., First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, The CGM device used to assess intraday glucose Yahatanishi-ku, Kitakyushu 807-8555, Japan. variability in the presence of hyperthyroidism (CGMS® E-mail: [email protected] System Gold™, Medtronic, Minneapolis, MN) can con- ©The Japan Endocrine Society 322 Torimoto et al. tinuously measure glucose level in the interstitial fluid system symptoms, and heart failure symptoms of the in the range of 40–400 mg/dL. The sensor is inserted Japan Thyroid Association diagnostic criteria of thy- into the subcutaneous tissue, and glucose levels in the roid storm [9]. Therefore, the diagnosis was confirmed interstitial fluid are converted to electrical signals, to be thyrotoxic crisis (a score of 60 according to the enabling measurement at 5-min intervals (288 mea- diagnostic criteria of Burch et al. [10] for thyrotoxic surement sessions per day at maximum). It has been crisis). Laboratory tests showed marked hyperglyce- reported that the interstitial glucose level measured by mia, with FPG level of 212 mg/dL and hemoglobin A1c CGM correlates well with the venous blood glucose concentration of 11.2%. She was thereafter started on level [7]. In this study, although the CGM measured intensive insulin therapy, as well as treatment for acute the interstitial glucose level, it was corrected by data heart failure, and also treated with propylthiouracil from SMBG; thus, the interstitial glucose level is here- (300 mg/day), potassium iodide (KI; 50 mg/day), and inafter referred to as “blood glucose level. For the val- prednisolone (PSL; 30 mg/day). The general condition ues measured by CGM devices, previous data indicate improved following the treatment, and she was referred ~15 to 20 mg/dL measurement error due to ~5-15 min- to our hospital after discontinuation of PSL and KI for ute time lag, compared with blood glucose level mea- further management. sured in venous blood, in addition to a lower accuracy On admission, she was 162.0 cm tall and weighed of measurement in hypoglycemia [8]. 44.7 kg (body mass index, 16.7 kg/m2); blood pres- During hospitalization, the patient received a diabetic sure was 133/78 mmHg, heart rate was 80 bpm, and diet with a daily calorie intake of 1400 kcal (25 kcal/ consciousness was clear. Diffuse goiter was noted but kg ideal body weight; 60% carbohydrate, 20-25% lipid, no exophthalmos, ocular retraction, or lid lag were 15-20% protein), which was continued, without any evident on clinical examination. The respiratory and modification, following admission to another hospital. heart sounds were normal, and neurological examina- tion was normal. Case Report Laboratory tests on admission (Table 1) showed normal hepatic and renal functions, as well as normal Clinical summary serum electrolytes. Glucose metabolism-related tests The patient was a 48-year-old woman who was showed reduced endogenous insulin secretion [FPG, diagnosed in 1999 with Graves’ disease and treated 122 mg/dL; blood C-peptide reactivity (CPR), 0.8 ng/ with thiamazole. She discontinued the treatment at her mL; urinary CPR, 1.8 μg/day] associated with inten- own discretion 6 months later following alleviation of sive insulin therapy. Although the disease duration was symptoms. Around 2009, she began to lose weight and considered long based on the presence of preprolifera- eat greater amounts of food and snacks than before. tive diabetic retinopathy, the patient had no history of Around August 2010, she developed marked thirst, ketosis. However, the family history was positive for polydipsia, and polyuria. Early in January 2011, she diabetes and the patient was anti-GAD antibody-nega- began to experience palpitations at rest, accompanied tive. Thus, the patient was diagnosed with type 2 dia- by edema and dyspnea on effort. The dyspnea gradu- betes mellitus. ally worsened. Later, she developed dyspnea at rest On the day of admission to our hospital (hospital day and was transferred to a local hospital by ambulance, 1), thyroid function tests showed free T3 level of 4.0 where physical examination showed wheezing, pitting pg/mL and free T4 level of 2.6 ng/dL. Based on these edema of the upper and lower extremities, tachycar- findings, propylthiouracil treatment (300 mg/day) was dia, and hypoxemia, together with pulmonary conges- continued (Fig. 1). With regard to treatment of dia- tion on radiography. She was diagnosed with conges- betes mellitus, intensive insulin therapy with insulin tive heart failure (New York Heart Association class aspart (9 U in the morning, 7 U at noon, 6 U in the 4). Signs of hyperthyroidism were noted (TSH level evening) and insulin glargine (6 U in the evening) was <0.001 μIU/mL, 2.18 ng/dL free T4), accompanied continued without modification. However, glycemic by New York Heart Association class 4 heart failure control gradually worsened following the recurrence of and reduced consciousness (somnolence or Glasgow signs of thyrotoxicosis (e.g., tachycardia, palpitation, Coma Scale score 12 and Japan Coma Scale score and tremor). On hospital day 6, the FPG level was 173 II–10), meeting the essential items, central nervous mg/dL. From the fifth hospital day onward, CGM was CGM of glucose variability in GD 323 Table 1 Results of laboratory tests on admission Peripheral blood Brain natriuretic peptide 133 pg/mL White blood cells 4000/μL Fasting plasma glucose 131 mg/dL Red blood cells 415×104/μL HbA1c (NGSP) 11.0% Hemoglobin 11.2 g/dL C-peptide immunoreactivity 0.8 ng/mL Platelets 26.7×104/L Anti-GAD antibody < 1.3 U/mL Blood biochemistry TSH 0.01 µIU/mL Total protein 6.0 g/dL fT3 4.00 pg/mL Albumin 3.1 g/dL fT4 2.66 ng/dL Aspartate aminotransferase 12 U/L TRAb 10.9 U/mL Alanine aminotransferase 10 U/L Tg-Ab 578 U/mL γ-glutamyltranspeptidase 23 U/L TPO-Ab 141.7 U/mL Blood urea nitrogen 15 mg/dL TSAb 188% Creatinine 0.30 mg/dL Uric acid 4.7 mg/dL Urinalysis Sodium 138 mEq/L C-peptide immunoreactivity 1.8 µg/day Chloride 97 mEq/L ACR 364.5 mg/g ● Cre Potassium 3.9 mEq/L HbA1c was estimated as the National Glycohemoglobin Standardization Program (NGSP) equivalent value, which was calculated as HbA1c (NGSP) (%) = HbA1c (Japan Diabetes Society [JDS]) (%) + 0.4%. fT3, free T3; fT4, free T4; TRAb, TSH receptor antibody; Tg-Ab, anti-thyroglobulin antibody; TPO-Ab, anti thyroperoxidase antibody; TSAb, thyroid stimulating antibody; ACR, albumin-creatinine ratio Fig.