A Mercury Toxicity Case Complicated byMatthew HyponatremiaCarter, DO,a Abdul Abdi, MD,a Fareeha Naz, MD, anda Farouq Thabet, Abnormal MD,a Arpita Vyas, MDa,b Endocrinological Test Resultsabstract
Mercury (Hg) poisoning is considered a rare disease by the National Institutes of Health and the diagnosis can present great challenges to clinicians. Children who are exposed to Hg can present with a wide variety of symptoms, including acrodynia, tremor, excessive salivation, aDepartment of Pediatrics and Human Development, and psychiatric symptoms, including insomnia. However, endocrinologic College of Human Medicine, Michigan State University, East manifestations from Hg exposure are less well known. This is a case report Lansing, Michigan bDepartment of Pediatrics, Texas Tech University, Odessa, Texas of a 12-year-old boy who presented with body rash, irritability, insomnia, and profuse sweating after returning from a summer camp. The child was Dr Abdi was involved in the direct care of this patient and helped to draft the initial report, initially managed in the outpatient setting, and the investigation was mainly including literature reviews; Dr Carter was involved targeted toward infectious etiology, including Rocky Mountain spotted fever in the direct care of this patient, helped review and Lyme disease. He was eventually admitted to the hospital with altered and edit the manuscript to its final copy, and was mental status and was noted to have hyponatremia with serum sodium of involved in literature reviews and submission of the report; Dr Naz was an attending physician involved 121 mEq/L. Thyroid studies also revealed elevated free thyroxine levels in the patient’s care, and assisted with supervision in the presence of normal triiodothyronine and thyrotropin. The patient of the project and in review of the manuscript; developed hypertension and tachycardia, and was found to have elevated Dr Thabet was involved in the direct care of this patient and helped to draft the initial report; Dr 24-hour vanillylmandelic acid and metanephrines. Finally, heavy metal Vyas was the attending endocrinologist involved in measurements revealed a blood Hg level that was greater than the reference the patient’s care, coordinated and supervised the values of 0 to 9 ng/mL. Chelation treatment with 2,3-dimercaptopropane- project, and critically reviewed the report; and all authors approved the final manuscript as submitted 1-sulfonate was subsequently initiated and over a period of 8 months his and agree to be accountable for all aspects of the symptoms resolved and his thyroid function test returned to normal. This work. case highlights some of the challenges commonly encountered in identifying DOI: https://doi.org/10.1542/peds.2016-1402 Hg exposure. More importantly, it illustrates that exposure to Hg should Accepted for publication Jan 10, 2017 be considered in children who present with the symptoms and abnormal Address correspondence to Arpita Vyas, MD, endocrinologic test results described in this report. Department of Pediatrics, Texas Tech University, 701 W 5th St, Odessa, TX 79763. E-mail: arpita.vyas@ ttuhsc.edu Mercury (Hg) exposure can occur in occur in its vapor form, which, if PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). many ways, including contaminated inhaled, can result in toxic effects food, water, dental amalgams, disk on various tissues, as up to 80% Copyright © 2017 by the American Academy of Pediatrics batteries, inhalation of vapors from of metallic Hg vapor is absorbed 4 FINANCIAL DISCLOSURE: The authors have gold-mining activities, environmental from the lungs into the blood. indicated they have no financial relationships accidents, and historically in laxatives1,2 Clinical manifestations of metallic relevant to this article to disclose. and diaper and teething powders. Hg vapor exposure can be diverse, FUNDING: No external funding. Thus, a thorough review of exposure including intention tremors, excessive pathways is necessary when Hg salivation, insomnia, body rash, To cite: Carter M, Abdi A, Naz F, et al. A Mercury exposure is suspected. Metallic and mood and behavioral changes. Toxicity Case Complicated by Hyponatremia Hg is a silver-white liquid at room Several body systems can be affected, and Abnormal Endocrinological Test Results. Pediatrics. 2017;140(2):e20161402 temperature and is present in various3 including the central nervous system, commercially available products. cardiovascular system, kidneys,1,5, 6lungs, Human exposure to metallic Hg can and the gastrointestinal tract. The Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 140, number 2, August 2017:e20161402 CASE REPORT 125 156 100 toxicological effects of heavy metals, receiving 3% hypertonic saline. Pulse, 60 – 120 Beats per Min including Hg, are more devastating in Initial blood work was suggestive the pediatric population, with respect of hyponatremia, secondary to
to the developing central7 nervous the syndrome of inappropriate system in particular. Furthermore, antidiuretic hormone. Brain imaging Height 144/93 113/73 102/58 the endocrinologic manifestations studies, including MRI, were normal <123/<78 mm Hg for Sex/Age/ Blood Pressure, from Hg exposure are less known, with the exception of pars intermedia and abnormal laboratory test results cyst in the pituitary area. During may further distract the clinician his 2.5-week hospitalization, his e from making a prompt diagnosis. symptoms progressed to include 9.9 11 10.3 mg/g Cr
VMA, <7.0 This case report highlights the effects episodes of syncope, tachycardia, of Hg exposure on systemic hormonal hypertension, disinhibited behavior, milieu, including perturbation of and muscle fasciculation. Thyroid
e thyroid hormone and catecholamine blood test results showed elevated 212 244 177 levels, together with sodium free thyroxine (T4) and intermittently imbalance. high total T4, with normal free 69 – 221 μ g/24 h Metanephrines, triiodothyronine (T3) and thyrotropin Patient Presentation levels. Thyroid-binding globulin, thyroid-stimulating immunoglobulin, 6 — 112
Range thyroid anti-microsomal antibody, and Reference Established Urine Hg, No anti-thyroglobulin antibody studies A 12-year-old boy with no significant – past medical history presented were normal. Elevated norep inephrine
in the late summer to an urgent 991 pg/mL8 (reference range 70 750
<1 care clinic after developing an pg/mL) and dopamine 39 pg/mL8 ng/mL erythematous macular rash involving (reference range <30 pg/mL)
Serum Hg, 0 – 9 ’ the palms and scalp hairline, muscle were noted. These laboratories twitching, irritability, insomnia, and and the patient s tachycardia,
— profuse sweating. He had recently hypertension, profuse sweating, and ng/dL 87 – 178 Total T3, returned from a summer camp in anxiety prompted investigation for the midwestern United States where possible pheochromocytoma and d 1.37 his symptoms had begun. Over the paraneoplastic syndrome. Full-body ng/dL Free T4, 0.61 – course of a month, he clinically imaging was essentially normal, with decompensated with increasing the exception of a fine nodular pattern fatigue, headaches, poor sleep, in the left middle lung. These findings 1.29 0.90 μ IU/mL
0.35 – 4.01 muscle twitching, and more frequent resolved on follow-up computed Thyrotropin, syncopal episodes, in addition to other tomography. A fungal serology panel symptoms. There were no known was normal. The patient also had — 161774 1.03 1.16 2.24 1.68 140 102 13 17 elevated 24-hour vanillylmandelic Urine sick contacts or fever, and history ∼ 9.5 months after symptom onset. ∼ 1 month after symptom onset. 250 – 1200 mOsm/kg Osmolality, reated for Suspected Hg Poisoning did not reveal any known exposures, acid and metanephrines; serum ingestions, or intoxications. The norepinephrine and dopamine levels patient was initially managed as an remained elevated. His hyponatremia outpatient, with the investigation resolved with daily fluid restriction — Serum 280 – 295
mOsm/kg focused on ruling out infectious of 1500 mL/d. Inductively coupled Osmolality, etiologies, including Rocky Mountain plasma-optical emission spectroscopy spotted fever and Lyme disease. He revealed an elevated blood Hg level of
K, was treated with a 10-day course of 13 ng/mL, greater than the reference
mEq/L 8 3.5 – 4.5 doxycycline, but continued to worsen values of 0 to 9 ng/mL. This level was clinically. Without improvement, inaccurately deemed insignificant by Na, 121140141 3.4 3.5 3.7 250 286 the patient presented to a local toxicology during his admission due to mEq/L 135 – 145 emergency department and was found minimal elevation. Laboratory and Vital Sign Values of a Child T to have serum sodium level of 121 c a b 3 1 2 mEq/L, potassium of 3.4 mEq/L, serum After discharge of the patient, 2.5 months after symptom onset. DMPS used for chelation therapy, 5 mg/kg 3 times a day for 2 weeks. Before chelation therapy, ∼ 2.5 months after symptom onset. DMPS used for Free T4 level was obtained 3 months after the treatment started. Initial laboratory samples were collected over a 2-week course, Checked 10 days after starting DMPS. Laboratory samples collected 7 months after chelation therapy, osmolality of 250 mOsm/kg, and urine further toxicological consultation TABLE 1 Laboratory, Reference Range VMA, vanillylmandelic acid. — , no value. a b c d e osmolality of 161 mOsm/kg (Table 1). resulted in a full investigation. As He was transferred to our PICU after the local health department and Downloaded from www.aappublications.org/news by guest on September 24, 2021 e2 Carter et al environmental health protective thyrotropin with elevated free diuretic before15 the advent of modern- agencies intervened, it was revealed T4 and to rule out a thyrotropin- day diuretics. A study published that the patient was exposed to producing adenoma. Analyzed blood in the early 1950s suggests that – elemental Hg starting just before and urine samples from the US mercurial diuretics depress the renal16 summer camp when he accidentally NHANES, 2007 2008 cohort, found tubular reabsorption of sodium. ’ broke an old bottle of Hg that an inverse relationship between Subsequent to receiving 3% saline, belonged to his grandfather. He had thyroid levels and blood Hg levels. the patient s natriuria appeared to attempted to clean it up by scooping The survey also showed thyrotropin increase, with a urine sodium level the Hg into a bag, which was then levels were10 not altered by Hg of 218 mEq/L, which then decreased put in his room and also brought to exposure. Additionally, in a study to 51 mEq/L within 48 hours. summer camp. High levels of Hg were of 47 chloralkali workers exposed to Furthermore, an exaggerated process 3 found in his room, 12890 ng/m ; Hg vapor, the ratio of T4 to T3 was of pressure natriuresis may have 3 his duffle bag, 26000 ng/m3 ; and on higher than nonexposed workers. contributed to his hyponatremia. the floor, 11881 ng/m , exceeding Furthermore, the concentration of This process is a component of a normal3 9 reference range of 5 to 10 reverse triiodothyronine (rT3) was the feedback system for long- ng/m . A 24-hour urine Hg level significantly11,12 higher in the exposed term control of arterial pressure, was high, 112 ng/mL, just before group. Similar to those reports, whereby increases in renal perfusion chelation therapy. Progressions our patient had an intermittently pressure lead to decreases in sodium of his laboratory test values are increased total T4, as well as an reabsorption17 and increases in sodium outlined in Table 1. Treatment increase in the T4 to T3 ratio excretion. This is enhanced because – with 2,3-dimercaptopropane-1- and an elevated rT3 (44 ng/dL; of excess dopamine,– which acts on sulfonate (DMPS) was initiated by reference range 8 25 ng/dL). These renal receptors18 20 leading to excretion the toxicologist shortly after the findings indicate that exposure to of sodium. Additionally, because exposure at home was mitigated, Hg may affect the function of type I the degree of nephrotoxicity may 1 month after hospital discharge iodothyronine deiodinase, which is vary depending on the form of Hg, and 2.5 months after presentation essential in the conversion of T4 to multiple routes of exposure were of his symptoms. By 8 months the active hormone T3. A diagnosis considered in our patient, including after his initial presentation, his of euthyroid sick syndrome with inhalation and ingestion. symptomatology, blood pressure, abnormal findings on thyroid thyroid function tests, and function tests was considered, catecholamines returned to normal. given an elevated rT3 and normal Although rare, there are other cases thyrotropin, but the usual pattern Discussion in the literature that presented would give low T3 and normal T4, 13 similar to our patient, with elevated which was not seen in our patient. catecholamines. For example, Additionally, medications, such a 4-year-old boy was exposed As evidenced by this case, the as amiodarone, dexamethasone, to metallic Hg, and developed diagnosis of Hg intoxication can propranolol, and anesthetic agents,14 both hyponatremia and elevated be challenging. Unfortunately, the can cause an increase in rT3 levels. catecholamines, suggestive20 of longer the exposure,1,6 the greater the To our knowledge, our patient had pheochromocytoma. Other cases intoxication. Factors that delayed not been exposed to any of these with similar findings were described4,20 diagnosis for this patient were a low medications. in the same report and elsewhere. index of suspicion, initial lack of an The increase in catecholamines exposure history, and nonspecific Our patient also presented with relates to interference with the clinical manifestations, along with euvolemic hyponatremia with normal catabolic processing of multiple irregularities in laboratory decreased serum osmolality and catecholamines via the cytosolic data. Our patient had elevated free T4 inappropriately increased urine enzyme catechol-amine-O-21,22 levels with intermittently high total osmolality, suggestive of syndrome methyltransferase. This enzyme T4, but normal free T3, thyrotropin, of inappropriate antidiuretic requires the use of the methyl and thyroid antibodies, as stated hormone. The association between group provided by coenzyme previously. This was not suggestive Hg exposure and hyponatremia S-adenosylmethionine (SAM). SAM of autoimmune disease but can is not well documented in the is essential in the conversion of be consistent with Hg exposure. medical literature. However, the norepinephrine to epinephrine. Hg Found normal in this case, brain effect of Hg on serum sodium level inactivates SAM; as a consequence, MRI with pituitary protocol was is not surprising, considering that norepinephrine, dopamine, and justified in view of a nonsuppressed inorganic Hg had been used as a epinephrine accumulate in increased Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 140, number 2, August 2017 e3 Acknowledgment amounts in the urine20 where they before making the appropriate can be detected. Additional diagnosis. This renders a timely The authors thank Dr Susan studies done on bovine chromaffin diagnosis difficult, as seen in Smolinske, attending toxicologist and cells support the hypothesis that the present case and previously director of the Michigan Regional high levels of Hg also could affect referred cases. Poison Control Center. the calcium channel currents Abbreviations Conclusions and consequently the release of 23 ’ catecholamines, resulting in an increase in the patient s levels even DMPS: 2, Hg exposure should be considered further. 3-dimercaptopro- in children who present with pane-1-sulfonate Hg intoxication is relatively hypertension, acrodynia, ’ Hg: mercury uncommon in the clinical setting. insomnia, mood changes, and rT3: reverse triiodothyronine A patient s physical examination associated endocrinologic SAM: coenzyme and laboratory studies can sway abnormalities, including S-adenosylmethionine the examining physician to hyponatremia, elevated T3: triiodothyronine investigate other causes, including catecholamines, and abnormal T4: thyroxine catecholamine-secreting tumors, thyroid hormone studies.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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