Iatrogenic Hypothyroidism Following Radioiodine Treatment

Betty, a 14-year-old, spayed domestic shorthair cat, was presented for a recheck examination, urinalysis, and evaluation of CBC, serum chemistry profile, and total thyroxine concentration 3 months after receiving radioiodine treatment for hyperthyroidism. The owner had noted weight gain and resolution of previous clinical signs related to hyperthyroidism (ie, polyphagia, vocalization). Previously, at the 1-month posttreatment evaluation, a low serum thyroxine (T4) concentration had been detected (Table 1), and CBC and serum chemistry profile results were normal. Given the low T4 concentration, Betty’s thyroid-stimulating hormone (TSH) concentration was also evaluated (using the canine TSH assay*) and found to be increased above the reference range (Table 1). Because iatrogenic hypothyroidism may be transient, no treatment was initiated at that time, and re-evaluation was postponed until the recheck examination scheduled for 3 months after radioiodine treatment.

At the 3-month recheck examination, Betty was bright, alert, and responsive, and vital signs were within normal limits. Betty had a BCS of 5/9 (3/9 prior to radioiodine treatment) and was noted to have gained 1.54 lb (0.7 kg) since beginning radioiodine treatment. The rest of the physical examination was unremarkable.

CBC was unremarkable. Serum chemistry profile results revealed azotemia, with a BUN of 64 mg/dL (22.8 mmol/L) (range, 18-32 mg/dL [6.4-11.4 mmol/L]) and creatinine of 2.6 mg/dL (230 μmol/L) (range, 1-1.8 mg/dL [88-159 μmol/L]; Table 1). The rest of the serum chemistry profile results were unremarkable, as were the urinalysis results, aside from a urine specific gravity of 1.014 (normal, >1.035). A thyroid profile showed a decreased serum T4 concentration and an increased serum TSH concentration (Table 1). The low serum T4 concentration was suggestive of hypothyroidism or a nonthyroidal illness related to azotemia. TSH was obtained to differentiate iatrogenic hypothyroidism from nonthyroidal illness secondary to azotemia. The combination of increased serum TSH concentration and decreased serum T4 concentration was suggestive of overt hypothyroidism.

Treatment with levothyroxine (0.1 mg PO q24h) was initiated, and serum T4 and TSH concentrations were rechecked one month after initiation of treatment. Serum T4 concentration had increased into the reference range, serum TSH concentration had decreased, and azotemia had improved. Peak T4 concentration was low-normal, and TSH concentration remained elevated; thus, the levothyroxine dose was increased to 0.15 mg PO q24h to obtain a peak T4 concentration in the middle to upper half of the reference range and a TSH concentration within the reference range. After 2 months of levothyroxine treatment at the increased dose, serum T4 and TSH concentrations were within reference range, and azotemia had resolved (Table 1; see Treatment at a Glance).

Isabella, a 14-year-old, spayed domestic shorthair cat, was presented for recheck examination and blood work 3 months after receiving radioiodine treatment for hyperthyroidism. On presentation, the owner noted that Isabella was polyuric and polydipsic. At the time radioiodine treatment was initiated, Isabella had a slightly increased BUN (37 mg/dL [13.2 mmol/L]) and normal creatinine concentrations (1.1 mg/dL [97 μmol/L]). Two months earlier at the 1-month posttreatment evaluation, serum T4 concentration was low and serum TSH concentration was normal, with azotemia present on serum chemistry profile results (Table 2).

Isabella was bright, alert, and responsive, and vital signs were within normal limits. Isabella had a BCS of 4/9 (3/9 prior to radioiodine treatment) and was noted to have gained 0.88 lb (0.4 kg) since receiving radioiodine treatment. The rest of the physical examination was unremarkable.

CBC was unremarkable. Serum chemistry profile results revealed progressive azotemia, with a BUN of 43 mg/dL (15.4 mmol/L) and creatinine of 3.5 mg/dL (309 μmol/L) (Table 2). The remainder of the serum chemistry profile and urinalysis results were unremarkable, except for a urine specific gravity of 1.012 (normal, >1.035). Thyroid profile demonstrated a low-normal serum T4 concentration and an increased serum TSH concentration. Azotemia had progressed over the 2-month period since first noted at the 1-month posttreatment recheck examination. Low-normal serum T4 and high serum TSH concentrations were consistent with subclinical hypothyroidism.

Due to the development of subclinical hypothyroidism and progressive azotemia, treatment for hypothyroidism with levothyroxine (0.15 mg PO q24h⁴) was initiated. Isabella was also started on a renal diet. After 3 months of levothyroxine treatment, both serum T4 and TSH concentrations were within reference range, and azotemia had not progressed any further (Table 2). Because peak T4 concentration was within the upper half of the reference range and TSH concentration was within reference range, the levothyroxine dosage was maintained at 0.15 mg PO q24h (see Treatment at a Glance).

Both Betty and Isabella had developed azotemia and iatrogenic hypothyroidism (overt and subclinical, respectively) after radioiodine treatment. A low T4 concentration and high TSH concentration are indicative of overt hypothyroidism, whereas a low-normal T4 concentration and high TSH concentration are indicative of subclinical hypothyroidism. Cats that develop iatrogenic hypothyroidism are more likely to develop azotemia, as hypothyroidism leads to decreased glomerular filtration rate^1,2; this is of particular importance in cats with preexisting chronic kidney disease (CKD). In addition, azotemic hypothyroid cats have shorter survival times as compared with nonazotemic hypothyroid cats, and hypothyroid cats that are untreated have shorter survival times as compared with treated hypothyroid cats.^3,4 A study of cats with iatrogenic hypothyroidism that were treated with levothyroxine at 0.15 mg PO q24h showed improved-to-normalized serum creatinine concentrations.⁴ Both Betty and Isabella exhibited either stabilization or improvement of azotemia when treated with levothyroxine supplementation at 0.15 mg PO q24h, and this stabilization or improvement of azotemia should have a positive impact on their overall survival.

Iatrogenic hypothyroidism can occur in approximately 10% to 30% of hyperthyroid cats following radioactive iodine treatment, with studies showing considerable variations in prevalence (1%-78%; see Take-Home Messages).^5-10 Considering the impact iatrogenic hypothyroidism has on kidney function and overall survival, early diagnosis is ideal. Clinical signs (eg, weight gain, lethargy) alone may not raise suspicion of hypothyroidism, as clinical signs can overlap with resolution of hyperthyroidism.⁴ The screening test of choice for hypothyroidism in dogs is evaluation of total T4 concentration, which is also routinely monitored in cats following treatment for hyperthyroidism. However, a total T4 concentration below reference range does not confirm hypothyroidism, as the presence of nonthyroidal illness can confound the diagnosis. This is particularly true in cats with CKD, in which serum T4 concentration is low in approximately 50% of cases.^11-14 The combination of low T4 concentration and high TSH concentration is used to diagnose overt iatrogenic hypothyroidism, as seen in Betty.⁴ Conversely, some hypothyroid cats can have a low-normal T4 concentration; an increased TSH concentration in these cats is indicative of subclinical hypothyroidism, as seen in Isabella.⁴ Therefore, only monitoring T4 concentration in cats that have undergone treatment for hyperthyroidism can lead to overdiagnosis or can preclude the diagnosis of hypothyroidism. Periodic evaluations—including evaluation of T4 and TSH concentrations—at 1, 3, 6, and 12 months following radioiodine treatment are recommended. If persistent, overt iatrogenic hypothyroidism is detected, treatment with levothyroxine should be considered, particularly in cats that develop azotemia. Similarly, if hypothyroidism is detected in cats receiving methimazole therapy, the dose should be appropriately adjusted.

Pet owners should be informed of the risks and complications of iatrogenic hypothyroidism, the importance of posttreatment monitoring, and the necessity of levothyroxine supplementation in select cases following radioiodine therapy. Preventive strategies for iatrogenic hypothyroidism, particularly in cats with mild-to-moderate hyperthyroidism, can include treatment with lower doses of radioactive iodine, which has been shown to lower the prevalence of iatrogenic hypothyroidism without compromising treatment efficacy.⁹