Polyneuropathy after Radioactive Iodine Treatment of Hyperthyroidism and Beneficial Effect of Combined T4/T3 Therapy of Hypothyroidism

Abstract

Dear Sir, Five months after radioactive iodine treatment for Graves' hyperthyroidism, I developed severe hypothyroidism. Three months after treatment, TSH, FT4 and FT3 values were within reference range (0.44 mlU/l, 15.9 and 4.5 pmol/l, respectively), but 7 weeks later, FT4 level was 2.6 pmol/l, and the highest level of TSH was 75 mlU/l. The symptoms of sensitive polyneuropathy manifested soon after introducing levothyroxine therapy. Fatigue, lack of concentration, forgetfulness, depression, and widespread neuropathic pain persisted more than 2 years in spite of levothyroxine replacement therapy (125 μg levothyroxine daily) and TSH level of about 1 mlU/l. The levels of total and LDL cholesterol were increased. ENG showed sensitive, predominantly axonal polyneuropathy of the smaller nerves in the lower extremities and arms (table ​(table1).1). Extensive clinical investigation did not find any potential cause of polyneuropathy other than hypothyroidism. Table 1 Nerve conduction examination Then I introduced combined T4/T3 therapy on my own, i.e., 100 μg of T4 and 10 μg of T3 administered in 2 daily doses. Positive effects on cognition and mood appeared very fast and were very impressive. During levothyroxine treatment, my FT3/FT4 concentration ratio in serum was low (table ​(table2).2). During T4/T3 treatment, this ratio was physiological 2 h after taking the medicine (table ​(table3)3) [1]. During levothyroxine treatment 125 μg/day, the serum FT4 concentration was slightly above reference range, while TSH concentration was within limits 2 h after receiving the medicine – which was the proof of a reduced sensitivity of the thyroid-pituitary feedback mechanism, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion (table ​(table2)2) [1]. Total cholesterol serum concentration dropped significantly after the introduction of combined T4/T3 therapy. The same applied to LDL cholesterol (table ​(table33). Table 2 Serum free thyroid hormone and TSH, FT3/FT4 ratio, cholesterol, LDL, HDL, and triglycerides levels while being treated with LT4 therapy Table 3 Serum free thyroid hormone and TSH, FT3/FT4 ratio, cholesterol, LDL, HDL, and triglycerides levels while being treated with combined T4/T3 therapy (levothyroxine 100 µg, triiodothyronine 10 µg) administered in 2 daily doses TSH serum concentrations were approximately the same with LT4 and combined T4/T3 therapy, 0.57 and 0.70 mlU/l, respectively (table ​(table2,2, ​,33). During levothyroxine monotherapy, my hands were cold, especially in winter. It was unusual for me. This winter, being treated with T4/T3 therapy, my hands have become warm. This could be the consequence of a stronger effect of combined T4/T3 therapy on normalization of the peripheral vascular resistance [2.] Five months after starting the combined T4/T3 therapy, I still have the symptoms of sensitive polyneuropathy. Nevertheless, the symptoms are not so severe and do not interfere with my sleep. Endocrinologists whom I have visited are not familiar with the association between hypothyroidism and sensitive polyneuropathy. But, there is an extensive scientific literature addressing this topic. Sensitive polyneuropathy is common in untreated or treated clinical or even subclinical hypothyroidism, independently of the cause of the disease [3,4,6,7,8,9]. On the other hand, T3 is the most powerful neurotrophic substance in nature [5]. There is a huge difference among athyroid patients in T3 production capacity from orally administered levothyroxine [1]. Therefore, suboptimal intraneuronal T3 concentration in levothyroxine therapy due to polymorphic variation in thyroid pathway genes could be the reason for persisting peripheral nerve damage or development of polyneuropathy years after starting levothyroxine therapy in some patients [1,5,10,11,12,13,14]. Time and control ENG will tell if definite beneficial effects of combined T4/T3 therapy on peripheral nerves will be achieved in my case. I have not observed any undesirable effect of combined T4/T3 therapy during the first 5 months of treatment. I have to state that widely accepted levothyroxine monotherapy and its reputation of a simple and effective therapy for hypothyroidism neglects the fact that a significant number of patients treated with this therapy have lifelong hypothyroid symptoms which make them less productive or even unproductive members of society. A great ethical issue is the fact that some patients with hypothyroidism, resulting from the radioactive iodine or surgical treatment of hyperthyroidism, have symptoms of hypothyroidism in spite of levothyroxine therapy, but they have not been advised about it before treatment.