HYPOTHYROIDISM AND GOITER IN A YOUNG MALE WITH SUSPECTED DIETARY IODINE DEFICIENCY FOLLOWED BY THYROTOXICOSIS AFTER IODINE SUPPLEMENTATION

Objective:

Iodine deficiency disorders (IDDs) remain a major public health concern in most parts of the world but are extremely rare in North America. We describe a case of goiter in a young male with dietary history and findings suggestive of IDD.

Methods:

Laboratory and imaging procedures including thyroid function tests, autoantibodies, urine iodine, thyroid ultrasound, and radioactive iodine (RAI) uptake scan were performed.

Results:

On initial presentation, thyroid-stimulating hormone (TSH) was 24.4 mIU/L (normal range is 0.4 to 5.0 mIU/L), free thyroxine was <0.4 ng/dL (normal range is 0.8 to 1.8 ng/dL), and thyroid peroxidase antibody was positive at 43 IU/mL (normal range is <35 IU/mL). He reported consuming strawberries and peanut butter sandwiches with no intake of dairy or seafood due to gastrointestinal issues (abdominal pain, bloating, and nausea). Physical exam revealed a diffusely enlarged, palpable thyroid gland (grade II goiter). Ultrasound of the neck showed an enlarged thyroid gland with no nodules. RAI uptake scan showed diffuse increased uptake (91%). Given his poor diet, a 24-hour urinary iodine excretion test was ordered which was suggestive of very low iodine intake. He was started on multivitamins with 150 μg of iodine daily. On follow up, clinical exam showed grade I goiter and TSH had normalized to 0.7 mIU/L and free thyroxine was 1.2 ng/dL. He continued on iodine supplementation and tolerated iodine-rich foods. Six months later, thyroid function tests showed hyperthyroidism with TSH of <0.002 ng/dL and free thyroxine was elevated to 2.8 ng/dL. Iodine supplements were stopped.

Conclusion:

Hypothyroidism and goiter due to IDD should be suspected in the setting of poor dietary intake. IDDs can be rapidly diagnosed in a patient on a restricted diet with multiple urinary iodine determinations and RAI study. Regular thyroid labs should be done to monitor for hyperthyroidism that can develop after iodine supplementation.

INTRODUCTION

Iodine is an essential component of the diet and its deficiency leads to impairment of thyroid hormone synthesis. Iodine deficiency disorders (IDDs) are a gamut of disorders which include multiple adverse health effects due to iodine deficiency at various stages of life (1). The most serious and important preventable consequence is cognitive impairment due to its major role on fetal neurodevelopment.

IDDs are a major public health concern in certain parts of the world which are deficient in iodine because of a lack of a national program for iodine supplementation. Fortunately, with the introduction of iodized salt in the United States in the 1920s, these conditions were eradicated in North America to a great extent (2). However, certain populations like those with restricted diets, food allergies, or increased iodine requirement (such as pregnant and lactating women) might still be at increased risk of IDD. Only a few cases of iodine deficiency-induced hypothyroidism or goiter have been reported in the literature (3,4). Here, we describe a case of goiter in a young male with a dietary history and other findings suggestive of IDD.

CASE REPORT

A 27-year-old, Caucasian male was referred to the endocrinology clinic for abnormal thyroid function tests and enlarged thyroid gland. He reported chronic nausea, bloating, and abdominal pain. His dietary history was consistent with eating peanut butter sandwiches and strawberries for the past few years. He denied consuming dairy, seafood products, and multivitamins. He reported low energy levels with cold intolerance and denied dysphagia, odynophagia, or hoarseness. He denied history of upper respiratory tract infection, radiation exposure, neck pain, or tenderness. His physical exam revealed diffusely enlarged thyroid gland (grade II goiter) with rubbery consistency, but no nodules were palpated.

Ultrasound (US) of the neck showed enlarged thyroid gland without nodules (Fig. 1). Laboratory workup revealed thyroid-stimulating hormone (TSH) was increased to 24.4 mIU/L (reference range is 0.4 to 5.0 mIU/L), free thyroxine level (FT4) was <0.4 ng/dL (reference range is 0.8 to 1.8 ng/dL), slightly increased thyroid peroxidase antibody of 43 IU/mL (reference range is <35 IU/mL), and negative thyroglobulin antibody. He was started on levothyroxine supplementation by his primary care physician but never took it. Three months later, his TSH was 6.1 mIU/L, thyroid peroxidase antibody was negative, and total triiodothyronine was within normal limits. FT4 test was not ordered at this time.

Fig. 1.

Ultrasound of the thyroid gland showing enlarged left lobe measuring about 7.4 cm at its widest.

The abnormal thyroid function tests suggested primary hypothyroidism likely as a sequela of Hashimoto thyroiditis as he had elevated antibodies at the initial workup. The TSH was improving, repeat thyroid peroxidase antibody was negative, and he was clinically euthyroid, hence no treatment was initiated at this time. A radioactive iodine (RAI) uptake scan was performed which surprisingly showed a 24-hour uptake of 91% with no hot or cold nodules (Fig. 2).

Fig. 2.

Radioactive iodine uptake scan of the thyroid gland showing diffusely increased uptake of iodine at 91% over 24 hours.

These findings were initially presumed to signify the patient was in the recovery phase of thyroiditis. A repeat US of the thyroid gland showed enlargement with a 1.5-cm nodule in the left posteroinferior region. However, given the patient's poor eating habits, urinary iodine levels were obtained. Urine testing showed a very low spot urine iodine level of 4 μg/L (reference range is 28 to 544 μg/L) along with low 24-hour urine iodine excretion of 10 μg/24 hours (performed by LabCorp, Burlington, NC; reference range is 100 to 460 μg/24 hours). The nontoxic goiter associated with primary hypothyroidism was thought to be secondary to severe iodine deficiency given the patient's low intake of dietary iodine for many years, however this was not firmly established as multiple 24-hour urine iodine or spot iodine levels were not measured.

The patient was started on a multivitamin supplement containing 150 μg of iodine daily and was advised to consume iodine-rich foods. On follow up in the clinic 3 months later, the spot urine iodine levels had improved to 91 μg/L (performed by LabCorp; reference range is 28 to 544 μg/L). Thyroid function tests had normalized with TSH within normal range (0.655 mIU/L) and FT4 normalized to 1.24 ng/dL. Physical exam showed grade I goiter, but repeat imaging with US or RAI scan was not performed.

The patient continued to be on daily iodine supplementation and was now able to tolerate a varied diet consisting of eggs, meat, seafood, vegetables and some breads. He was evaluated in the clinic 6 months later with repeat thyroid function tests and US of the thyroid gland. He complained of weight loss, palpitations, and pedal edema. Laboratory data suggested primary hyperthyroidism with TSH <0.002 mIU/L, FT4 elevated to 2.8 ng/dL (reference range is 0.7 to 1.9 ng/dL), and total triiodothyronine elevated to 326 ng/dL (reference range is 80 to 180 ng/dL). At this time, 24-hour urine iodine level was normal at 145 μg/24 hours (performed by Quest Diagnostics, Secaucus, NJ; reference range is 70 to 500 μg/24 hours). US showed enlargement of both thyroid lobes with increased blood flow and a 1.2-cm nodule in the posteroinferior aspect of the left lobe. Hyperthyroidism was likely secondary to increased uptake of iodine or an underlying autoimmune state leading to increased hormone production and secretion. Iodine supplementation was stopped as his diet had improved.

DISCUSSION

The daily iodine requirement according to the World Health Organization is in the range of 90 to 150 μg/day, with higher requirements during pregnancy (220 to 250 μg/day) and lactation (259 to 290 μg/day) (2,5). Median spot urine iodine concentration is used to define iodine status for a population. A median urinary iodine concentration of 100 to 199 μg/L is considered adequate iodine intake for a non-pregnant population, whereas levels below 100 μg/L indicate iodine deficiency (5).

Frank iodine deficiency is mostly seen in underdeveloped and developing countries, and although iodine intake has been considered to be adequate in North America, this assumption is changing (6). The National Health and Nutrition Examination Survey (called NHANES) reported that iodine intake dropped by 50% from the 1970s to the 1990s in the U.S.A. (7). The median urinary iodine concentration reported in the 2009 to 2010 survey was 144 μg/L indicating that the overall U.S.A. population is iodine sufficient, but iodine intake varies a lot across the population (8).

Goiter is the enlargement of the thyroid gland as an adaptation to chronic iodine deficiency. Iodine deficiency leads to decreased thyroid hormone production resulting in increased TSH production by the pituitary gland. The increased TSH stimulates thyroid growth and leads to goiter formation. Our patient had elevated TSH on presentation along with enlarged thyroid seen on the US of the neck. In the initial stages of iodine deficiency, goiter is diffusely enlarged but over time it may become nodular by progressive accumulation of new follicles. Chronic TSH stimulation may also lead to “gain-of-function” mutations of thyroid follicles, seen more commonly in areas of endemic iodine deficiency (9,10). This can lead to toxic multinodular goiter and hyperthyroidism if iodine deficiency is not very severe.

Cretinism and mental retardation are the most profound manifestations seen in infants as a result of severe IDD in pregnancy. Children in areas with IDD can have enlarged thyroid glands. Goiter, hypothyroidism, and toxic multinodular goiter are commonly seen in the adults of these areas. In the industrialized world, primary hypothyroidism is mostly attributed to autoimmune disorders like Hashimoto disease and IDD is an exceedingly rare phenomenon. Since IDDs are rare in North America with only a few cases reported (3,11), IDD is not usually considered as an etiology of hypothyroidism. However, people with restricted diets (such as vegans and those with lactose intolerance), pregnant women, and lactating women are at increased risk (2). Given these concerns, physicians need to be aware of the risk factors for IDDs. Our patient ate an extremely restricted diet which was low in iodine that put him at increased risk for an IDD. Iodine deficiency should be considered as a cause of primary hypothyroidism in such patients.

RAI uptake scan performed in patients with IDD will show paradoxical finding of diffusely increased uptake. Furthermore, RAI uptake scans are not routinely performed as a part of workup for hypothyroidism. This often leads to underdiagnoses of iodine deficiency-induced hypothyroidism. This paradoxical finding on the RAI uptake scan in a euthyroid or a hypothyroid patient in the setting of iodine deficiency provides a strong clue to the diagnosis of IDD.

Our patient had signs and symptoms of hypothyroidism on presentation but RAI uptake scan paradoxically showed increased uptake of 91%. This, in addition to his history of restricted diet, prompted us to obtain a 24-hour urinary iodine level to screen for an underlying IDD. Since there is considerable variation in individual daily iodine intake, it has been suggested that 10 samples be collected to determine iodine status (12). Therefore, a single 24-hour urine iodine concentration cannot be used to diagnose IDD. In our patient, since more than one 24-hour urine iodine level was not measured on his usual diet, the diagnosis of IDD was only suggestive based on his dietary history, clinical features of hypothyroidism, and very low urine iodine levels.

When diagnosed with IDDs, patients should be started on daily iodine supplementation as recommended by the World Health Organization with careful monitoring of thyroid function at regular intervals. Patients should be counselled on the signs and symptoms of hyperthyroidism that can often develop after iodine supplementation (13). A cross-sectional study had shown that a Danish population with deficient iodine intake had a higher lifetime risk for hyperthyroidism, the most common cause of which was multinodular goiter (14,15).

As discussed earlier, iodine deficiency increases the risk of toxic multinodular goiter by development of autonomous thyroid cells. Iodine-induced hyperthyroidism can develop in such patients if they are exposed to excess iodine during fortification and if preexisting iodine deficiency was severe. This effect is seen more commonly in adults over 60 years of age with nodular thyroid (16) and can be reduced by gradual introduction of iodized salt to the diet.

CONCLUSION

Timely diagnosis of IDDs is important in patients who are on restricted diets. This should be performed by obtaining 24-hour urinary iodine levels and RAI uptake scan. A detailed dietary history should also be obtained in patients presenting with goiter or hypothyroidism, irrespective of the patient's geographical residence. IDD is a reversible condition when treated at early onset with dietary iodine supplementation.