by Gregory Nacarelli
~edited by Baljit Khamba, ND, MPH
Fourth-year interns at Bastyr University are actively developing their clinical skills through treating patients at the school’s clinic. They engage their didactic skills in rigorous case taking, examinations, evaluation, and a naturopathic-focused treatment plan under the supervision of their attending doctor. The interns are able to gain experience in areas such as mental health, mind-body medicine, oncology, hydrotherapy, physical medicine, out-reach community care, IV treatment, biofeedback, and so on. Each one of these opportunities presents a prime opportunity for the students to enrich their knowledge about conditions and approaches to care. In efforts to salient their understanding, the students write case reports under the supervision of Dr. Baljit Khamba in their course “Advanced Case Studies.” By completing these reports, future practitioners gain a valuable skill that they can then utilize once they graduate.
The first case report in this new column is by Gregory Nacarelli.
Iodine Administration Leading to Shortness of Breath
by Gregory Nacarelli
Introduction
Iodine is essential in the production of the thyroid hormones T3 and T4. Iodine is classified as a trace mineral, and the recommended daily allowance is set to 150 mcg daily for non-pregnant adults, 90 mcg per day for children ages 6-12, and 250 mcg per day during pregnancy and lactation.(1) Iodine-rich foods consist of seaweed, cranberries, fish, eggs, dairy, and sea salt. Iodine can also be administered in supplemental form. One popular form of supplemental iodine is known as Lugol’s iodine. Lugol’s iodine is two parts potassium iodine and one part elemental iodine. This form of iodine is typically used as a disinfectant but can be used to protect the thyroid gland from radiation.(2)
Iodized salt contains 77 micrograms of iodine per 1 gram of salt.1 This is the major form of salt consumed in the United States. This constitutes the major source of iodine consumption in developed countries; iodine-deficient-based thyroid disorders are more commonly seen in third world countries without iodized salt.
The idea behind excess iodine being detrimental to health has been well documented. The Wolf-Chaikoff effect alludes to the phenomenon in which excess iodine consumption will decrease normal thyroid function, making said person hypothyroid.(3) This effect will typically last three-to-four weeks.(3) Through lab testing, one can measure this effect by seeing an initial drop in circulating T3 and T4 levels and an increase in TSH levels. It is also well documented that iodine administration can also be detrimental if someone already has pre-existing hyper or hypothyroidism.(4) In regions of iodine deficiency, hyperthyroidism was seen in upwards of 20% of the population in which iodine was administered.(4) It is rare for iodine to cause hyperthyroidism in patient populations in which there was no underlying thyroid issues present previously.(5)
According to one study only 10% of iodine ingested via iodized salt is bioavailable.(2) Based upon this study and others like it, some members of the medical community suggest increasing iodine consumption beyond the RDA set by the FDA, as we are not absorbing enough iodine to meet our bodies’ needs when following the RDA’s requirements. Another reason for the suggestion for increasing iodine consumption is the increase in environmental toxins over the last several decades, mainly bromine, fluoride, and chloride derivatives, which will alter the metabolism of iodine in the body.(6)
Diagnosis of iodine-induced thyroid disease should include measurements of Free T3, Free T4, TSH, TSH receptor antibodies, radioactive iodine uptake assessment, and thyroid ultrasound. The presence of TSH receptor antibodies are indicative of Graves’ disease. The radioactive iodine assessment should help to distinguish Graves’ hyperthyroidism from iodine-induced hyperthyroidism. Iodine-induced hyperthyroidism can last from one month to 18 months and is treated by discontinuing iodine and, if indicated, administering a beta-adrenergic antagonist, such as atenolol.(4) Methimazole can also be utilized if symptoms are severe. Methimazole works by inhibiting thyroid peroxidase, which is responsible for facilitating the addition of iodine to thyroglobulin.(4)
Symptoms of iodine-induced hyperthyroidism may include resting tremor, enlarged thyroid, hair loss, arrhythmia, onycholysis, gynecomastia, proptosis, hyperreflexia, heat intolerance, irritability, insomnia, weight loss, increased appetite, diarrhea, amenorrhea, decreased libido, and photophobia.(4) Wolf-Chaikoff hypothyroid symptoms may include lethargy, memory loss, hearing loss, weight gain, insomnia, joint/muscle aches, hair loss, constipation, cold intolerance, parasthesias, thinning lateral eyebrows, periorbital edema, weak pulse, edema, and cold/dry skin.
This case report discusses a patient who is displaying signs and symptoms concordant with thyroid dysfunction after ingesting 15 mg of iodine per day for 10-12 days. The question to be had from this research report is if the patient is indeed experiencing thyroid dysfunction from the iodine supplementation or if there is some other underlying issue present. Laboratory findings suggestive of hypoinsulinemia are discussed as well as the correlation to the patient’s current disposition.
Case Description
The patient described in this case is a 35-year-old Caucasian male. His first visit to the Bastyr University Clinic was in January 2016. He came to the clinic with reports of malaise and fatigue. His review of systems was positive for diarrhea, thinning eyebrows, cold intolerance, dry skin, numbness in hands, dizziness, and anxiety. Other health history includes a paleolithic-based diet in which he avoids grains, dairy, and nightshades. He does not consume caffeine and has one glass of wine per night. A working diagnosis of hypothyroidism was made, and labs were ordered.
Results of significance were as follows: High: ALT (49 IU/L), AST(32 IU/L), Bilirubin (1.5 mg/dL), A/G (2.9), and borderline low glucose (66 mg/dL). His thyroid levels were as follows: TSH: 1.27 uIU/mL (0.45-4.5); free T3: 2.5 ng/dL (2-4.4); free T4: 1.58ng/dL (0.82-1.77).
His anti-TPO antibodies were a 7 IU/mL with a range of 0-34 IU/mL. His CBC and other CMP parameters were all within range. His anti-TG antibodies were negligible. The patient did not return for a follow-up for discussion of his lab results.
The patient then returned to the Bastyr University clinic on July 6, 2017, complaining of shortness of breath and chest palpitations. He said that four weeks prior he took 15 milligrams of Lugol’s iodine per day for 10-12 days. He did this because he felt like he met the criteria for hypothyroidism and thought that iodine administration would help his symptoms. The bulk of the patient’s information regarding what form of iodine to take and the dosage came from Dr. David Brownstein’s website. After the 10-12 days of iodine administration, the next day he began to experience chest palpitations, anxiety, shortness of breath, and night sweats. These symptoms lasted for three days. At one point he noticed chest palpitations and took his blood pressure, which was “really low.” When he began to experience dizziness, he went to the ER. At the ER, they found that he had high neutrophils (71.7%), low lymphocytes (21.6%), and a borderline depressed TSH (0.596 uIU/mL). After the ER visit his symptoms lessened but never fully went away. He would still notice the shortness of breath, night sweats, and chest palpitations at night, especially after falling asleep. Two weeks later he returned to the ER complaining of dizziness and shortness of breath. An x-ray was run on him, which was normal. To rule out cardiac myocyte injury, they measured the cardiac marker troponin I, which was not elevated. An EKG was run which displayed possible atrial enlargement. His TSH was measured at this second ER visit and was 0.493 uIU/mL. The patient’s last ER visit was two days prior to the Bastyr University clinic visit.
Other medical history included gastrointestinal issues after a trip to Nepal 10 years before. The patient believed the onset of his hypothyroid-like symptoms started then. While the patient has complained about hypothyroid-like symptoms in the past, he states he never experienced any cardiac/respiratory issues prior to taking the iodine supplementation. The patient experienced prostatitis-like symptoms six months ago that resolved with the use of antibiotics. The patient is still consuming the same paleolithic, grain-free, dairy-free diet that he was consuming last visit. He occasionally takes magnesium supplements but is not currently taking any other supplements daily. His profession involves work around Chinese medicine. He tried Mai Men Dong botanical Chinese formula around the onset of his symptoms, but he said this made his symptoms worse. The patient has been getting between four to eight hours of sleep per night, depending on the severity of his chest palpitations. He rates his current stress level at a 4/10, though in previous weeks he rated it 7/10 due to the stress his health issues are causing.
His review of systems was positive for the following: insomnia, stress, lateral eyebrow thinning, syncope, chest palpitations, shortness of breath, cold sweats at night, muscle weakness, muscle cramps, concentration impairment, and depression. On physical examination, his height was 5 ft. 8.6 in., blood pressure was 96/70, pulse was 65 beats per minute, his temperature was 98.3 Fahrenheit, respirations per minute were 12, and oxygen saturation was 98%. His weight was 128.6 lb., which was a 20-pound drop from his weight in January 2016. The patient attributes his weight loss to decreased physical activity and weight lifting. Cardiac auscultation revealed regular heart rate and rhythm, no murmurs or gallops. Lungs were clear to auscultation, though the patient had to pause between breaths due to feeling shortness of breath. No clubbing or cyanosis was present in digits. Deep tendon reflexes were +2 and muscle strength was +5. It should be noted the patient was comfortably wearing three layers of clothing in an 80 °F clinic room.
Given the history, positive review of symptoms (ROS), and physical exam (PE) findings, the patient was diagnosed with cold intolerance, weight loss, and shortness of breath. We suspect these symptoms are due to thyroid dysfunction, possibly due to excess iodine administration. We decided to run the following labs: CMP, TSH, FT4, FT3, TSI, anti-TG, and anti-TPO antibodies. We recommended the patient use a stool parasite testing kit from Doctor’s Data to see if there were any lingering parasite issues since the trip to Nepal. We recommended that he follow-up in three weeks after his test results came in.
The following lab results came back abnormal: glucose was 55 mg/dL and alkaline phosphatase was 37 mg/dL (39-117). His thyroid levels were as follows: TSH: 0.6 uIU/mL (0.45-4.5); FT3: 3 ng/dL (2-4.4); FT4: 1.5 ng/dL (0.82-1.77). His anti-TPO antibodies and anti-TG antibodies were within range. We are still waiting on his TSI and parasitology results.
The patient followed-up for review of his lab results on August 17, 2017. His vitals were all within normal limits. His weight was 131.6 lbs., a three-pound increase from his last visit. The patient mentioned that his chest palpations have decreased significantly but his shortness of breath has gotten worse, while also experiencing occasional dizziness. On physical exam, lungs were clear to auscultation. The patient had to pause between breaths. The patient mentioned that if he doesn’t eat every couple hours his shortness of breath and dizziness get worse. Testing for ketone production via urinalysis was negative.
Based upon his ROS, PE, and previous lab results, we decided to test the patient’s fasting serum insulin, serum c-peptide, GAD-65, insulin antibodies, and glucose. These were ordered to get a better idea of his pancreatic function. His fasting insulin was low at 1.7 uIU/mL (range: 2.6-24.9 uIU/mL); his c-peptide was low at 1 ng/mL (range: 1.1-4.4 ng/mL); and his glucose was borderline low at 65 mg/dL. His GAD-65 and insulin antibody levels were normal at <5 U/mL. We called the patient to let him know his lab results were suggestive of hypoinsulinemia and referred him to an endocrinologist.
Discussion
From the information gathered from the history, ROS, PE, we suspect the iodine administration is implicated with the hypoinsulinemia. We are also considering further testing for kryptopyrroluria. Kryptopyrroluria involves the overproduction of hydroxyhempyrolin, a protein in the heme biosynthetic pathway.(7) Stress is one of the main triggers for this, but the cause can be genetic.(7) Loss of function of the enzyme aminolevulinate synthase is linked with excessive production of pyrroles and, also, x-linked sideroblastic anemia.7 Some of the symptoms of pyrrole disorder include hypoglycemia, low alkaline phosphastase, fatigue, dizziness, and memory impairment. The patient has all these symptoms. The test for pyrrole disorder involves testing for kryptopyrroles via a urine test. Testing for this involves an at-home urine test; information for the patient to purchase this testing kit has been provided. The link between increased hydroxyhempyrolin production and thyroid dysfunction requires further investigation.
Sufficient thyroid production requires the following compounds: B6, selenium, zinc, vitamin C, B2, magnesium, iodine, among other compounds.(9,11) If the patient does indeed have kryptopyrroluria, it would be sequestering his body of B6 and zinc.(8) This would make him nutrient deficient in the co-factors necessary for thyroid hormone production. Future plans involve checking his body for current levels of vitamins and minerals. Depending on the patient’s vitamin and mineral levels, we will recommend supplementation and/or IV vitamin and mineral therapy to make sure the patient is getting adequate nutrition.
Environmental toxicity is also a concern for exacerbating or causing thyroid dysfunction.(10) In order to assess the patient’s toxin load, a future plan will involve running an environmental toxicity panel. If there is a toxin burden, we will suggest a detoxification protocol which consists of sauna, detoxification nutritional support and, if necessary, heavy metal chelation. More research is needed to elucidate the effect of heavy metal chelation on circulating iodine levels. There exists a link between excess iron burden and kryptopyrroluria.(13) This is due to iron’s ability to displace zinc from its binding sites.(13)
We are limited because iodine testing in humans is unreliable at this time. The current literature mentions that Wolf-Chaikoff-induced hypothyroidism lasts roughly 3-4 weeks,(3) and iodine-induced hyperthyroidism can last between 1-18 months.(4) The standard for patients in iodine excess is to treat the symptomology. The patient’s severity of symptoms will be assessed next visit. Beta-adrenergic antagonists, such as atenolol, will be considered if he is still experiencing the heart palpitations. A link between excess iodine consumption and low insulin status remains to be elucidated. The finding of hypoinsulinemia seems to be an incidental finding.
Conclusion
While an argument can be made regarding whether or not the RDA for iodine is sufficient for the average, healthy, adult human being, supplemental iodine administration should be used with caution as it can exacerbate pre-existing health conditions. Iodine dosing should be recommended under the guidance of a physician trained to rule out previously existing thyroid-related pathologies.
Testing for the etiology of thyroid pathologies is a complex process that involves ruling out food allergies, toxic exposures, nutritional deficiencies, as well as other pre-existing medical conditions, such as autoimmune diseases. This case report discusses a patient who is displaying symptoms of having thyroid dysfunction after iodine administration. Thorough investigation revealed he was affected by hypoinsulinemia. Treatment of a patient in this situation requires an endocrinologist as well as nutritional counseling for optimal thyroid functioning.
Gregory Nacarelli is a fourth-year naturopathic medical student at Bastyr University California. Before attending Bastyr University, he was a research scientist at Merck & Co. He possesses a master’s degree in molecular biology from Lehigh University and a bachelor’s degree in biology from Cabrini University. His interests include genetics, nutrition, and botanical medicine.
Baljit Khamba, ND, MPH, is a clinic supervisor at Bastyr University Clinic and a core faculty member at Bastyr University, California. She treats a variety of conditions but has special interest in nutritional approaches to mental health, particularly anxiety, stress, depression, ADHD, memory, and cognition. 
Dr. Khamba completed her honor’s Bachelor of Science at York University, Toronto, Canada, specializing in psychology, as well as her Master in Public Health from Lakehead University. Her interest in mental health guided her graduate thesis on nutritional influences of mood disorders. She received her naturopathic doctoral degree from the Canadian College of Naturopathic Medicine (CCNM).
Upon graduating, Dr. Khamba worked in integrative psychiatric clinics and was actively involved with research projects at the University of Alberta reporting on adverse effects from natural health products used alongside psychiatric medication.
Dr. Khamba is a licensed naturopathic doctor in California and accepts patients at Bastyr University Clinic alongside student interns.
References
1. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanandium, and zinc. Washington, D.C.: National Academy Press; 2001:258-289.
2. Keeling DH, Williams ES. Changes in the normal range of thyroidal radioiodine uptake, J Clin Pathol. 1972 Oct; 25(10): 863–866.
3. Chaikoff WJ. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem. 1948; 174:555.
4. Roti E, Uberti ED. Iodine excess and hyperthyroidism. Thyroid. 2001; 11:493.
5. Skare S, Frey HM. Iodine induced thyrotoxicosis in apparently normal thyroid glands. Acta Endocrinol (Copenh) 1980; 94:332.
6. Pavelka S. Metabolism of bromide and its interference with the metabolism of iodine. Physiol Res. 2004;53 Suppl 1:S81-90.
7. Hawkins D, Pauling L. Orthomolecular Psychiatry: Treatment of Schizophrenia. San Francisco: WH Freeman and Company; 1973:146-178.
8. Pfeiffer CC. Nutrition and Mental Illness: An Orthomolecular Approach to Balancing Body Chemistry. Rochester, VT: Healing Arts Press;1987.
9. Kawicka A, et al. Metabolic disorders and nutritional status in autoimmune thyroid diseases . , Ostepy Hig Med Dosw (Online). 2015 Jan 2;69:80-90.
10. Eisenbrand G, Gelbke HP. Assessing the potential impact on the thyroid axis of environmentally relevant food constituents/contaminants in humans . Arch Toxicol. 2016 Aug;90)8:(184157 .
11. Kieliszek M, Błażejak S. Current Knowledge on the Importance of Selenium in Food for Living Organisms: A Review. Molecules. 2016 May 10;21(5).
12. Diamanti A, et al. Autoimmune diseases and celiac disease which came first: genotype or gluten? Expert Rev Clin Immunol. 2016;12(1):67-77.
13. Bergdahl IA, et al. Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes. Pharmacol Toxicol. 1997;81(4):153.
14. Christianson A, Murray M. Textbook of Natural Medicine, 4th edition, Chapter 177, 1473-1480.
