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Trans Abstract

INTRODUCTION

Hypothyroidism develops when the thyroid gland fails to produce or secret as much thyroxine (T4) as the body needs. Because T4 regulates essential functions such as heart rate, digestion, physical growth, and mental development, a deficiency of this hormone might slow life-sustaining processes, damage tissues and organs in every part of the human body. Primary hypothyroidism is a relatively common endocrine disorder. Because awareness is now high and screening is easy, the condition is detected early in most patients, even when symptoms and signs are mild or sometimes non-specific. Patients with more severe hypothyroidism may present with clinical features such as slow speech, a hoarse voice, low basal body temperature, ascites, pericardial effusion, cerebellar ataxia, and even coma. These features mimic those of other conditions which can be overlooked.

We present a case in which the clinical presentation supported by a raised carbohydrate antigen 125 (CA 125) concentration with moderate pericardial and pleural effusion led us to make an incorrect presumptive diagnosis of disseminated intra-abdominal malignancy.

CASE REPORT

A 44-year-old woman was admitted for increasing abdominal circumferential diameter and progressive dyspnea over 3 months. She had suffered from general weakness, constipation, bilateral leg edema, cold intolerance, and dizziness over the preceding 3-4 months. In view of her age, she had a cachectic and old appearance. She denied history of alcohol use but smoked one pack per day. She had a very irregular menstruation period and had no pregnancy history. There was no history of diabetes, heart disease, liver or thyroid dysfunction but she had a right oophorectomy 20 years ago. She didn’t memorize well about the cause of right oophorectomy and just mentioned it seemed like an ovarian cyst. There was no information about her family history because she was an orphan. Her height was 159 cm, weight 44 kg, blood pressure 80/60 mmHg, pulse 35 beats/min, temperature 36 ℃. Her voice was hoarse and the abdomen was soft but distended. She had severe pitting edema on her both lower leg. The heart sounds were diminished without any murmur. The lung sound is clear and a chest radiograph (Fig. 1) revealed a remarkable cardiomegaly (73% of cardiothoracic ratio). There was no palpable mass or enlarged thyroid and lymph nodes on her body. The surface 12-leads electrocardiogram (EKG) (Fig. 2) demonstrated junctional escape rhythm with marked bradycardia and low voltage of QRS complex. The echocardiogram (Fig. 3) showed concentric left ventricular hypertrophy and large amount of pericardial effusion (separation between the posterior wall of left ventricle and pericardium 4.0 cm). We performed subxiphoid pericardiocentesis and decided to start temporary pacing through right ventricle (VVI mode, 60 pacing/min).

Figure 1.

Prominent cardiomegaly on the chest radiograph at admission.

Figure 2.

Junctional escape rhythm with marked bradycardia and low voltage in the QRS complex in all leads of a surface 12-lead electrocardiogram.

Figure 3.

A transthoracic echocardiogram revealed a large amount of pericardial effusion (open arrow) in the parasternal long-axis view (A) and short-axis view (B).

Serum thyroid-stimulating hormone (TSH) concentration was elevated at 93.27 μU/mL (normal range 0.38-4.7 μU/mL), free thyroxine was less than 0.40 ng/dL (normal range 0.71-1.85 ng/dL), Triiodothyronine was less than 25 ng/dL (normal range 45-137 ng/dL), Thyroid peroxidase antibody titer was 828.6 U/mL (normal range 0-34 U/mL), and thyroglobulin antibody titer was 1179 IU/mL (normal range 0-50 IU/mL). In complete blood cell count examination, WBC was 5.0 × 10³/mm (normal range 4-10 × 10³/mm), RBC 3.28 × 10⁶/mm³, Hemoglobin 11.5 g/dL (normal range 12-16 g/dL) and Platelet 187 × 10³/mm³ (normal range 140-440 × 10³/mm³). Serum lactate dehydrogenase level was 433 IU/L (normal range 0-400 IU/L), albumin 4.8 gm/dL (normal range 3.3-5 gm/dL), protein 7.8 g/dL (normal range 5.8-8 g/dL), and total cholesterol was high with level of 351 mg/dL (normal range 120-220 mg/dL). Other blood indicies including electrolyte, liver and kidney function were normal except aspartate aminotransferase level (64 IU/L, normal range 0-35 IU/L). Serum CA 125 concentration was 118 U/mL (normal range 0-37 U/mL) and carcinoembryonic antigen (CEA) was 10.7 ng/mL (normal range 0-5 ng/mL).

Pericardial fluid was 770 mL, straw colored, exudates (PH 7.5, specific gravity 1.035, glucose 88 mg/dL, RBC 180/mm, WBC 25/mm, neutrophil 38%, lymphocyte 62%, protein 5.3 g/dL, lactate dehydrogenase level 272 IU/L), no malignant cells, and no bacterial growth.

The ascitic fluid was found to be an exudate (protein 3.2 g/dL, PH 7.5, glucose 126 mg/dL, RBC 84/mm, WBC 15/mm, neutrophil 0%, lymphocyte 100%, albumin 2.1 gm/dL, lactate dehydrogenase 155 IU/L) with high CA 125 concentration of 108.7 U/mL but no malignant cells neither bacterial growth. Adenosine deaminase of ascites was normal. Computed tomo-graphy (Fig. 4) of the abdomen showed large amount of ascites with enlarged left ovary (34 mm in diameter) with nodular enhancements, and omental and mesenteric infiltration. Thyroid ultrasonography revealed diffuse thyroiditis.

Figure 4.

Abdominal computed tomography scans showing the large volume of ascites (A) and enlarged left ovary (34 mm in diameter, open arrow) with nodular enhancement (13 mm in diameter, arrow head) (B).

We suspected ovarian carcinoma or unknown primary tumor concomitant with disseminated peritoneal, pericardial metastasis in a patient with hypothyroidism. However, gastroscopy, colonoscopy, transvaginal ultrasonography gave normal results, and there was no evidence of malignancy through PET-CT(positron emission tomography–computed tomography). To confirm the diagnosis, she had a diagnostic abdominal laparoscopic biopsy on omentum and left ovary. The gynecologist sent some tissues to pathologist during the operation. The result of frozen biopsy was benign. But we could not exclude the possibility of malignancdy because the inner surface of tumor is partially covered with hemorrhagic materials and severe inflammation was observed around ovary and omentum. The left salpingo-oophorectomy was done.

The result of biopsy showed no evidence of malignancy. Supplement treatment with oral levothyroxine was started at 100 μg per day since she was diagnosed as hypothyroidism. We removed pericardiocentesis catheter, temporary pacemaker after 10 days later. The follow-up echocardiogram after 2 weeks showed that there was little pericardial effusion and sinus bradycardia (Fig. 5) was noted on EKG. Her TSH level was decreased to 22.09 μU/mL (normal range 0.38-4.7 μU/mL), free thyroxine was increased to 1.33 ng/dL (normal range 0.71-1.85 ng/dL) after 3 weeks of thyroxine supplementary therapy. CA 125 also decreased to 94 U/mL. She described a considerable improvement in her general state and an increased tolerance for exercise. After 17 weeks of therapy, TSH level was 0.3 μU/mL, free thyroxine level was 1.29 ng/dL, CA 125 level was 21 U/mL.

Figure 5.

Sinus rhythm was restored after 2 weeks of levothyroxine treatment.

The patient was maintained on 75 μg per day of thyroxine and she remained well, with no recurrent evidence of pericardial effusion, ascites, leg swelling, and junctional bradycardia.

DISCUSSION

Hypothyroidsm has many effects on the cardiovascular system which some of them are pericardial effusion, hypertension and pleural effusion. However, hypothyroidism is the cause of ascites in less than 5% [1], and less than 4% of hypothyroidism cases are complicated by ascites [2]. The pathogenesis of hypothyroidism associated ascites is unclear, so often confused with other diseases. The serum-to ascites albumin gradient (SAAG) may be more useful than exudate-transudate concept in the differential diagnosis of acites [3]. A high SAAG is seen in cases of cirrhosis, alcoholic hepatitis, congestive heart failure, constrictive pericarditis, hepatic metastases, and Budd Chiari syndrome, whereas a low SAAG is associated with peritoneal carcinomatosis, tuberculosis, nephritic syndrome, and pancreatitis.

Prominent features of ascites with hypothyroidism include slight female predominance, a high cholesterol, and high protein content of the ascitic fluid (>2.5 g/dL), a high serum-ascites albumin gradient, a long duration of the ascites, and its resolution with thyroid replacement therapy [4]. This case was also compatible with these conditions-high cholesterol (351 mg/dL, normal range 120-220 mg/dL), high protein content of the ascitic fluid (3.2 g/dL) and high serum-ascites albumin gradient (2.7 SAAG). Typical presentation is that of long-standing, untreated, or unrecognized hypothyroidism resulting in mild to moderate ascites. Many of these patients have associated pleural effusions and generalized edema [1].

The unusual presentation of hypothyroid ascites includes significant elevation of serum CA 125 concentration [5]. CA 125 is an antigenic determinant recognized by murine monoclonal antibody OC125 and is usually used to monitor the clinical course of patients with ovarian cancer. However, this elevation is observed in many pathologic and physiologic conditions; this includes certain conditions such as abdominal surgery, bacterial peritonitis, pelvic inflammatory disease, endometriosis, and pericardial effusion [6]. The underlying mechanism for the synthesis of CA 125 and its secretion is not clear. There are reports in the literature that neoplastic cells do not in fact produce CA 125, and thus the idea has been put forward that the elevated CA 125 levels represent a reaction of pleuropericardial or peritoneal mesothelial cells to the tumor [7]. In non-malignant disease it may be that serosal irritation due to inflammation or trauma promotes the release of CA 125. Cytokines have also been implicated in the production of CA 125, and with respect to cardiac dysfunction, interleukin-6 may have an important role [8]. There are only a few published reports of transient elevation of serum tumor markers in hypothyroidism. Hashimoto and Matsubara [5] showed that the mean concentration of CEA, CA 125, CA 15-3 and fetoprotein in hypothyroid women was significantly higher than in euthyroid and hyperthyroid women. The mechanism of the elevation of CA 125 with hypothyroidism is not clear. But we can assume some hypotheses. At first, it may be because hypothyroidism might delay metabolism of CA 125 [9]. Second, Pericardial effusion, the complication of severe hypothyroidism, might affect CA 125 elevation. The severity of pericardial effusion and the presence is related to CA 125 level was reported by Seo et al. [10]. Last, High CA 125 level in myxoedema ascites might be due to peritoneal irritation. In other case of old woman with profound hypothyroidism, severe ascites, and CA 125 concentration of 684 U/mL, the patient’s ascites resolved and CA 125 concentrations fell towards the reference range as the patient became euthyroid [11]. This case showed that TSH level was returned to normal range after 17 weeks thyroxine supplement, as well.

This case also showed a junctional bradycardia with sick sinus syndrome. Sick sinus syndrome describes abnormalities caused by the malfunction of the heart’s natural pacemaker (sinoatrial node) when symptoms, such as dizziness, fainting, or syncope, are present [12]. Hypothyroidism causes slowing of the metabolic rate and affects almost all bodily functions, including heart rate and contractility. It causes similar slowing of electrical conduction throughout the heart. The most common electrocardiographic changes associated with hypothyroidism are sinus bradycardia, a prolonged QT interval, and inverted or flat T waves [13]. Most hypothyroid patients may have a low to normal heart rate (about 50-70 beats/min). Patients with severe hypothyroidism and those with pre-existing heart disease may also develop increasing degrees of heart block or bundle branch block (especially right bundle branch block) [14]. The first EKG of the patient showed junctional escape rhythm with narrow QRS complexes, no P waves and a heart rate of about 35 beats/minute (Fig. 2). As expected, our patient responded well to treatment with levothyroxine and P waves appear and junctional bradycardia abolished after 2 weeks of therapy (Fig. 5).

The CA 125 tumor marker is generally elevated in patients with malignant ovarian tumor. It can, however, be elevated in benign disorders, such as pelvic inflammatory disease, endometriosis and can also increase in pericardial, pleural and peritoneal irritation or inflammation. Several radiological and histopathological examination are required for the correct diagnosis since elevated serum CA 125 levels can be falsely positive for ovarian malignancy. This case shows very rare clinical features of hypothyroidism including ascites with an elevated CA 125, pericardial effusion, pleural effusion, and junctional bradycardia. After supplement treatment with oral levothyroxine, the clinical course of patient was improved. Thyroids function should be checked in all patients with ascites and raised CA 125 concentrations as part of there initial investigations.

Conflict of Interest

No potential conflict of interest relevant to this case presentation was reported.

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