Toxic Multinodular Goiter in a Patient with End-stage Renal Disease and Hemodialysis

Abstract

The management of symptomatic hyperthyroidism in patients with end stage renal disease (ESRD) is challenging because of altered clearance of medications and iodine with dialysis; moreover, many patients meeting these criteria are medically fragile. A 77-year-old man with type 2 diabetes and ESRD requiring hemodialysis, with dilated cardiomyopathy and paroxysmal atrial fibrillation, was found to have subclinical hyperthyroidism. Over a 2-year period he became clinically hyperthyroid with serum TSH level of <0.05 mIU/L and free T4 level of 4.3 ng/dL, attributed to toxic multinodular goiter. Despite antithyroid medication, he developed rapid ventricular rate from his atrial fibrillation that resulted in decompensated heart failure and multiple hospitalizations. His hyperthyroidism was successfully controlled with high dose methimazole and potassium iodide treatment, which were eventually discontinued after prolonged use. Nearly 6 months off medications, his hyperthyroidism recurred but was readily resolved when methimazole was restarted. Hyperthyroidism in the medically fragile ESRD patient may precipitate emergent conditions. Antithyroid medications are effective and should be considered as primary therapy for the treatment of hyperthyroidism in patients with hemodialysis. Moreover, clinical guidelines for the characterization and management of individuals with ESRD and subclinical hyperthyroidism should be developed.

Introduction

Thyroid hormone abnormalities in chronic renal failure (CRF) are usually characterized by low levels of serum levothyroxine (T4) and liothyronine (T3) attributed to decreased concentration of and impaired binding to thyroxine binding globulin (TBG), and decreased conversion of T4 to T3.¹ Hypothyroidism and goiter with nodularity appears prevalent in CRF.^2,3 The prevalence of subclinical hypothyroidism ranged from 7% in individuals with Chronic Kidney Disease (CKD) Stage 2 (≥ 90 ml/min) to 17.9% for CKD Stage 3 or worse (< 60 ml/min), and 2-fold excess of nodular goiter was observed in uremic patients (54.8%) than non-renal failure patients (21.5%).^4,5 However, thyrotropin or thyroid stimulating hormone (TSH) and FreeT4 levels are usually normal in these patients despite symptoms consistent with hypothyroidism such as fatigue, swelling, lethargy, constipation, dry skin, and hair loss.¹

The prevalence of hyperthyroidism in end-stage renal disease (ESRD) is similar to the non-CRF population.^1–3 However, symptomatic hyperthyroidism in CRF patients is uncommon with a few studies reporting the evaluation and treatment of thyrotoxicosis. ^6–10 The management of hyperthyroidism in patients with ESRD is difficult and challenging because of hemodialysis (HD) or peritoneal dialysis, altered renal clearance of medications and iodine, and the medical fragility of these patients that may impact evaluation and treatment. This is a report of a case of symptomatic hyperthyroidism attributed to toxic multinodular goiter in a patient with diabetes mellitus and ESRD requiring hemodialysis and a discussion of the clinical course and treatment.

Case Presentation

A 77-year-old Japanese man with ESRD secondary to diabetes mellitus type 2, developed paroxysmal atrial fibrillation and was found to have subclinical hyperthyroidism with serum TSH level of < 0.05 mIU/L (NL range 0.27 – 4.2 mIU/L) and free T4 level of 1.17 ng/dL (NL range 0.9 – 2.1 ng/dL) for the previous 2 years. His past medical history was significant for dilated cardiomyopathy with paroxysmal atrial fibrillation along with his diabetes mellitus that appeared well controlled on oral anti-hyperglycemic medications. He also had a history of idiopathic hypogonadotropic hypogonadism.

During an initial visit at an outpatient clinic, he was found to be overtly hyperthyroid with tremors, palpitations, and weight loss, and his free T4 level had increased to 4.3 ng/dL. His serum anti-thyroid peroxidase and anti-thyroglobulin antibody titers were < 10 IU/ml (Normal < 35) and < 20 IU/ml (Normal < 20), respectively. Physical exam revealed blood pressure of 110/50 mmHg and irregular heart rate of 80/minute. He was obese with a weight of 187 lbs and BMI of 34.2, which have been fairly stable since he was subclinically hyperthyroid. Pertinent findings included irregularly irregular rhythm without murmurs, a non-palpable thyroid, absence of proptosis, and dry skin. Despite treatment with beta-blocker and methimazole, the patient was hospitalized for decompensated heart failure and atrial fibrillation with a rapid ventricular response. His methimazole dose was increased gradually from 10mg daily to 60 mg daily prior to discharge after the 3-day hospitalization, however his symptoms persisted, as a result of which a second admission for congestive heart failure (CHF) was required.

During the second hospitalization, saturated solution of potassium iodide (SSKI) 1 gm/ml, 2 drops (approx. 600 mg) three times a day was added to his methimazole 60 mg daily treatment. His atrial fibrillation-induced rapid ventricular rate resolved and CHF markedly improved at discharge. On outpatient follow up 2 weeks after discharge, his free T4 level decreased to 2.5 ng/dL and he showed suppressed TSH level of <0.07 mIU/L. With continued methimazole and SSKI treatment, his TSH and free T4 levels normalized to 0.88 mIU/L and 0.8 ng/dL, respectively. An ultrasound of thyroid gland showed multiple nodules in both lobes consistent with multinodular goiter (multiple nodules of the thyroid gland; left lobe nodules measuring 3.3 x 2 x 2.2 cm and 2.1 x 2.6 x 2.7 cm; and right lobe with 8 nodules with largest measuring 1.7 x 1.2 x 1.2 cm; Figure 1).

Figure 1.

Ultrasound of thyroid gland. Neck was placed in hyperextended position and images obtained using a Philips HD 15 ultrasound machine. The right and left lobes of the thyroid gland were imaged in longitudinal and transverse planes. The location, size, number, and character of thyroid nodules were measured in three dimensions (Left lobe sagittal view-top; Right lobe sagittal view-bottom).

His SSKI was discontinued (side effect of constipation was noted) as he remained euthyroid (TSH and Free T4 levels of 2.18 mIU/L and 0.8 ng/dL, respectively). His methimazole was later tapered and also discontinued after nearly 9 months of prolonged treatment. About 6 months off medication, subclinical hyperthyroidism recurred as his TSH level was <0.01 mIU/L but his freeT4 level was 1.0 ng/dL. His radioactive iodine (RAI) uptake was 12% (10–30% normal uptake) at 6 hours with a heterogeneous distribution on thyroid scan (Figure 2). He was restarted on methimazole 10 mg daily, which normalized his thyroid functions.

Figure 2.

Thyroid scan. Five mCi of technetium(Tc)-99m pertechnetate was injected by vein after I-131 sodium iodide capsule was given orally. Fifteen minutes after intravenous injection of Tc-99m pertechnetate, pinhole views of thyroid gland were obtained in multiple projections.

Discussion

Symptomatic and clinically significant hyperthyroidism in chronic renal failure patients is uncommon and challenging; treatment options include RAI, anti-thyroid medications or subtotal thyroidectomy. In this case of thyrotoxicosis in ESRD with cardiac manifestations resolution of hyperthyroidism was critical in restoring HD and improving the patient's overall condition.¹¹ Antithyroid medications are propylthiouracil (PTU), methimazole, and carbimazole (not available in the United States).¹² Methimazole is dialyzable and used after dialysis, whereas PTU is protein bound and used independent of dialysis.^13,14 Propylthiouracil is administered at standard doses in patients with thyrotoxicosis and renal failure; a case of hyperthyroidism due to Graves' disease in a patient on regular hemodialysis was successfully treated with propylthiouracil.^7,9

RAI treatment provides permanent resolution of hyperthyroidism and appears safe with minimal exposure to staff and patients. A patient with Grave's disease on regular hemodialysis was successfully treated with I-131 after initial treatment with antithyroid drugs,⁷ and a case of toxic multinodular goiter in a hemodialysis patient was also successfully treated with I-131 ablation.⁸ The care needed to collect and dispose excess RAI during hemodialysis is challenging, requiring cautious effort, but RAI treatment has been performed safely and effectively in ESRD. ¹ Unfortunately, this patient had low to normal uptake (12%) of RAI even after 6 hours, which raised questions of the effectiveness of RAI treatment in our patient. Thyrogen (recombinant human Thyrotropin, rhTSH) could be used to increase radioactive iodide uptake in a low uptake condition such as this patient, but handling RAI excess remained a concern.^15,16 Moreover, the validity of RAI uptake in the setting of previous SSKI treatment in ESRD was uncertain. What is the expected uptake in patients with ESRD without thyroid disease; and what is the clearance of accumulated iodine with dialysis? Surgical intervention following normalization of thyroid functions with anti-thyroid medications was not an option in our patient with multiple medical problems. Other less common treatments such as cholestyramine were not considered but may have been an option for the treatment of this patient.¹⁷

This patient presented additional clinical dilemmas in the management and evaluation of hyperthyroidism in patients with ESRD. In retrospect, his subclinical hyperthyroidism should have been treated, especially with his pre-existing atrial arrhythmia. For nearly 2 years, the patient was observed as he was deemed clinically stable until he became overtly hyperthyroid which contributed to decompensated CHF and multiple hospitalizations. His recurrent subclinical hyperthyroidism was now addressed with low dose methimazole to normalize his thyroid status because of his past history.

Iodine excretion in ESRD is usually low and there is greater thyroid accumulation.^2,3 The use of SSKI during the patient's second hospitalization for the treatment of hyperthyroidism has not been previously reported. Indication and dosing of iodine in ESRD and hemodialysis is not clearly defined. The rapid reduction in thyroid levels with SSKI is noted in patients treated for thyroid crisis, but the effect in renal failure is unknown.¹² The patient responded to standard doses of SSKI added to high dose methimazole treatment.

The patient's hyperthyroidism recurred within 6 months after stopping prolonged methimazole treatment but was easily controlled with low dose therapy. The uncommon presentation of hyperthyroidism in ESRD and hemodialysis responded to antithyroid medications, which should be considered as primary and long-term therapy for these patients. Clinical guidelines for the characterization and management of individuals with ESRD and subclinical hyperthyroidism should be developed.

Conclusion

Hyperthyroidism in the medically fragile ESRD patient may precipitate emergent conditions. Antithyroid medications are effective and should be considered as primary therapy for the treatment of hyperthyroidism in patients with hemodialysis. Moreover, clinical guidelines for the characterization and management of individuals with ESRD and subclinical hyperthyroidism should be developed.

Conflict of Interest

None of the authors identify a conflict of interest.