Med. J. Cairo Univ., Vol. 84, No. 1, March: 143-148, 2016 www.medicaljournalofcairouniversity.net

Abnormalities in Thyroid Function and Morphology in Chronic Hemodialysis Patients IHAB A. IBRAHIM, M.D. 1 ; YOMNA K. RAMADAN, M.D. 2 ; EHAB A. HASSAN, M.D. 3 and AMAL H. EISSA, M.D. 4 The Departments of Internal Medicine, Division of Nephrology 1 , Division of Endocrinology 2, Faculty of Medicine, Cairo University, the Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, Fayoum University 3 and The Department of Clinical Pathology, Faculty of Medicine, Cairo University 4

Abstract

metabolism, decreased binding to carrier proteins, possible reduction in tissue hormone content, and increased iodine storage in the thyroid gland [2] . Advanced renal failure is associated with decreased iodide excretion, subsequent elevations of plasma iodide, and initially an increment in thyroidal iodide uptake [3] . Elevated total body inorganic iodide can potentially block thyroid hormone synthesis (the Wolff-Chaikoff effect), which may explain the higher frequency of goiter and hypothyroidism in patients with renal failure [2] . The exact reasons for an increased thyroid gland volume are not known. Potential pathogenic factors include enhanced iodide trapping by the thyroid gland and the possibility of accumulation of an unidentified goitergen or strumigenic substance in uremic plasma [2] .

Background: The kidney has an important role in the metabolism of thyroid hormones. Impaired renal function and the resulting accumulation of uremic toxins may disturb thyroid physiology at various levels. The prevalence of goiter and thyroid nodules is significantly increased in patients with ESRD compared with other hospitalized patients admitted for treatment of non-renal disease. The purpose of this study was to assess thyroid dysfunction and thyroid morphology in patients with ESRD on regular maintenance hemodialysis. Methods: Thyroid function tests (TSH, free T 3 and free T 4 ) and thyroid gland ultrasound imaging were assessed before hemodialysis in 40 ESRD patients treated with regular maintenance hemodialysis compared to 20 healthy matched controls for age and gender. Results: Plasma levels of free T 3 and free T 4 were significantly lower and TSH levels were insignificantly higher in hemodialysis patients compared to controls. Thyroid gland volume and thyroid lesions (nodules and cysts) are clearly increased in hemodialysis patients. Logistic regression analysis revealed no relationship between thyroid abnormalities and age, gender, BMI or duration of dialysis.

Chronic renal failure is a widely recognized cause of non-thyroidal illness [2] . Low levels of the active form of the thyroid hormone, free triiodothyronine (FT 3 ), are the hallmark of this disturbance. Approximately one fourth of patients with ESRD display low FT 3 , thyroid dysfunction being an emerging problem also in patients with moderate to severe chronic renal disease [4,5] . Moreover, low T 3 levels have been considered as an independent predictor for all-cause mortality in patients on hemodialysis [6] .

Conclusion: Our results revealed that ESRD patients on regular maintenance hemodialysis have a higher prevalence of alteration of thyroid function (low free T 3 and free T 4 ). Also, thyroid lesions (cysts and nodules) and thyroid gland volume were clearly increased compared to healthy controls. Key Words: Thyroid function – Thyroid morphology – Endstage renal disease (ESRD) – Hemodialysis.

Introduction THE kidney plays an important role in the metabolism, degradation and excretion of several thyroid hormones [1] . Patients with End-Stage Renal Disease (ESRD) have multiple disorders in the thyroid function and morphology, including low circulating thyroid hormone levels, altered peripheral hormone

The purpose of our study was to assess thyroid dysfunction and thyroid morphology in regular maintenance hemodialysis patients. Material and Methods The study was conducted on 60 subjects. Forty clinically stable maintenance hemodialysis patients with no previous history of thyroid dysfunction

Correspondence to: Dr. Yomna K. Ramadan, E-Mail: [email protected]

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Abnormalities in Thyroid Function & Morphology in Chronic Hemodialysis Patients

selected from dialysis unit, Nephrology Department, Cairo University between June 2011 and June 2014. These patients were on regular hemodialysis (four hours three times weekly) and 20 healthy age and sex matched control subjects. Consent has been taken from all study participants. Inclusion criteria for the studied patients were chronic renal failure from any cause, age was > 18 and less than 70 years, both sexes were involved, dialysis duration was >6 months and all were treated by standard bicarbonate dialysis for 4 hours, 3 times a week. Exclusion criteria were as follows: Patients with previous history of thyroid disease or thyroid surgery before commencing hemodialysis, those with biochemical evidence of hyper or hypothyroidism, patients with evidence of amyloidosis, active neoplasm, acute infections or chronic inflammatory disease, patients with clinical signs of severe liver or cardiopulmonary disease, those on current treatment with drugs known to interfere with thyroid function (amiodarone, propranolol, glucocorticoids, phenytoin, lithium) and all patients unable or unwilling to participate were excluded from the study. All patients and control were subjected to full medical history and clinical examination. Complete blood count, serum creatinine, blood urea, serum electrolytes (Na and K), liver function tests, total cholesterol and triglycerides level, serum measurement of thyroid profile (TSH, free T 3 , free T 4 ) were done for all patients and control. The Blood samples were taken just before starting dialysis. Serum levels of thyrotropin (TSH), free thyrotropin (T 3 ) and free thyroxin (T 4 ) levels were measured by Electrochemiluminescence Immunoassay (ECLIA). FT 4 was measured by Elecsys free-T 4 kit (Roche Diagnostic GmbH, D-68298 Mannheim, Germany); FT 3 was detected by Elecsys free-T 3 kit (Roche Diagnostic GmbH, D-68298 Mannheim, Germany) and TSH by Elecsys TSH kit (Roche Diagnostic GmbH, D-68298 Mannheim, Germany). Ultrasonography of the thyroid gland was performed for all patients and matched controls to measure the thyroid gland volume and to detect any thyroid lesions using a real time sonography device (HDI 5000 ultrasound system, Bothel, WA 98021, U.S.A.) with linear array transducer. All subjects were examined in a supine position with a pillow below their shoulders to hyperextend the neck to enable ultrasonographic examination of the inferior poles of both lobes of the thyroid gland. Scans of the two lobes were obtained in standard

transverse and longitudinal positions. Thyroid volume was calculated as length X width X depth X 0.479 (mL) for each lobe [7] . Enlargement of the thyroid gland was defined as a thyroid volume exceeding 18mL or 25mL for female and male patients, respectively [8] . All subjects with thyroid nodules larger than 1.0cm or less than 1.0cm with suspicious ultrasonic findings were referred for a fine needle aspiration biopsy [9] . Statistical analysis: Data were statistically described in terms of mean Standard Deviation (SD), or frequencies (number of cases) and percentages when appropriate. Comparisons between the maintenance haemodialysis patients and controls were assessed with student’s unpaired t-test, Mann-Whitney U test, Wilcoxon’s signed-rank test or the χ 2 test, as appropriate. Odds ratio and 95% confidence interval (and p-value) to measure the strength of the association between kidney disease and thyroid abnormalities. p-values less than 0.05 was considered statistically significant. Table (1): Comparison between hemodialysis patients and controls. Hemodialysis Control ppatients subjects value Mean ± SD Mean ± SD Age (years) Gender (M/F) (% males) BMI (kg/m2) Duration of hemodialysis (years) TSH (mU/L) Free T 4 (ng/dl) Free T 3 (pg/ml)

50.33 ±9.24 50% 22.6±4.1 6.38±3.14 2.56± 1.47 0.81 ±0.22 2.80± 1.17

47.65±8.93 50% 23.5±4.5 NA 1.92±0.78 1.12±0.18 3.37±0.56

0.290 0.89 0.63 NA 0.096 0.000* 0.013*

Table (2): Prevalence of thyroid function abnormalities in hemodialysis patients and controls. Study groups

Odds ratio (OR) Hemodialysis Controls 95% confidence interval (CI) patients (n) (n) Thyroid function abnormality

19

1

pvalue

17.19