PEDIATRIC PUZZLER

GEORGE K. SIBERRY, MD, MPH, SECTION EDITOR

Lower body weakness in an ADHD teen:
Is he "hyper" after all?

By Sam Adler, MD, and Kimberly Hightower, MD

The end of another long week of inpatient hospital rounds! But before you can leave the pediatric floor, you're called to examine an adolescent boy who has just been admitted to the teaching service for evaluation. The residents fill you in: This 15-year-old was seen in the emergency department (ED) of another hospital before referral to your institution for a third episode of bilateral lower extremity and truncal weakness. At the referring hospital, intravenous fluids were administered and he was transported here for workup. By the time he arrived at your hospital, his symptoms had resolved, and now he's walking about the room easily, enthusiastically awaiting discharge.

From the history in the chart, you learn that his first episode of lower-extremity weakness occurred three weeks earlier. He was treated then as he was earlier today—with IV fluids—for what was recorded as "dehydration," with subsequent resolution of symptoms. Two weeks later, a second episode of similar symptoms prompted a visit to yet another ED; there, he was discharged shortly after receiving IV fluids.

Now, speaking with you, the patient denies headache or muscle ache. He has seen no changes in the pattern of bowel movements or in urinary habits. He also denies heat or cold intolerance, but does acknowledge an occasional sensation of palpitations. He has not lost or gained weight recently, and his mother, accompanying him, describes him as always being one of the taller children in his class. He admits to having been "fidgety" as a child; he had been treated for attention deficit hyperactivity disorder (ADHD) with stimulant medication for two years before this problem developed, but he confesses noncompliance.

This young man is the product of a full-term pregnancy, during which his mother denies having used alcohol, tobacco, or illicit drugs. He achieved normal milestones in infancy and childhood and reports being an "average" student in school. Academic performance declined about two years ago, and he was given a diagnosis of ADHD after evaluation by a neurologist. There is no history of medical or psychosocial illness in other family members. He denies using alcohol, tobacco, and illicit drugs. He has, he acknowledges, a very large appetite—especially for pasta meals.

On physical exam, you find a well-nourished, Caucasian male at the 50th percentile for height and above the 90th percentile for weight. He appears pleasant but restless. He is mildly tachycardic without murmur (heart rate, 92/min); respirations are 18/min and blood pressure is 130/76 mm Hg. You see no signs of head trauma and no focal neurologic signs. He walks well, easily. Reflexes are present but sluggish in the upper and lower extremities. There is a mild intention tremor bilaterally upon extension of the upper extremities. The eyes demonstrate mild lid lag bilaterally.

The thyroid is smooth and palpable at 7 cm x 3.5 cm x 7 cm; no bruit can be heard over the gland. Pulses are present, equal, and normal in the upper and lower extremities. The abdomen is obese, soft, and without organomegaly. Genitalia are Tanner stage IV.

A low point in your evaluation

You next repeat the blood chemistry tests that have already been run at his previous visits to the referring ED. Findings today include a sodium level of 144 mEq/L; potassium, 4.3 mEq/L; chloride, 105 mEq/L; CO₂, 24 mEq/L; calcium, 9.7 mg/dL; glucose, 118 mg/dL; blood urea nitrogen, 14 mg/dL; and creatinine, 0.4 mg/dL. The components of the complete blood count, the erythrocyte sedimentation rate, and liver function tests—all are normal.

You pore over data from the referring ED, making special note of the lab results. Everything has appeared normal each time—except the serum potassium level, which, you realize, has been low at all ED visits! You review the electrocardiogram tracings made each time lab tests were ordered: All reveal findings characteristic of hypokalemia: a prolonged QT interval and flattened T waves.

His vigor at the moment notwithstanding, you decide that it's best to observe the boy and order more lab tests. You're worried about that enlarged thyroid, but even more worrisome is the finding on neurologic exam of some diminution of strength and reflex in the lower extremities. Your plan? Have the patient evaluated by the neurologist in the morning.

Your wake-up call

Before you can get to the hospital the next morning, however, you are paged by the nurse on the floor, who is alarmed: The morning lab results for your patient show a potassium level of 1.4 mEq/L, and he is now experiencing the same lower extremity weakness he reported on earlier occasions! A check with the lab confirms that, no, that level is not in error. Now, suspecting a periodic paralysis caused by hypokalemia, you opt for oral potassium supplementation. Within an hour, his weakness is resolving and the retested potassium level is normal! But then a call from the laboratory brings another turn of the screw: The boy's thyroid function test results are back, and thyroid-stimulating hormone is almost undetectable at 0.03 mIU/mL (normal for age, 0.3–5 mIU/mL); free T₄ is 3.8 ng/dL (normal, 0.7-1.6 ng/dL) and total T₃ is 538 ng/dL (normal, 72–176 ng/dL). With those findings in hand, the diagnosis reveals itself: Your patient experiences hypokalemic periodic paralysis as a consequence of hyperthyroidism.

Periodic paralyses are autosomal dominant disorders linked by their distinct clinical feature of weakness. Once, they were classified on the basis of the serum potassium level; now, they are differentiated by the particular skeletal muscle ion channel in which an abnormality is found: Disorders of the sodium channel cause hyperkalemic periodic paralysis and paramyotonia congenita; disorders of the calcium channels lead to hypokalemic periodic paralysis (hypoPP); and disorders of chloride channels are linked with Thomsen's (autosomal dominant) and Becker's (autosomal recessive) myopathies.^1,2 Hypokalemic periodic paralysis can be either primary (familial) or secondary to an underlying disease state. Familial hypoPP (FPP), the most common periodic paralysis, is linked to chromosome 1q31-32 and has reduced penetrance in women. It usually presents after puberty, with acute onset of muscle weakness occurring during rest after strenuous exercise, a carbohydrate-rich meal, or increased sodium load. The hypokalemia may be accompanied by characteristic EKG changes.¹

Secondary hypoPP usually results from intracellular potassium depletion from a renal, gastrointestinal, endocrine, or drug-induced mechanism.¹ Late onset of hypoPP (during late adolescence and adulthood) and an extremely low level of potassium should raise strong suspicion of a secondary disorder rather than a primary one.¹ Gastrointestinal causes of hypoPP, such as villous adenoma, non-insulin-secreting pancreatic tumor, gastrointestinal fistula, laxative abuse, and nontropical sprue,¹ are usually associated with diarrhea, weight loss, and volume depletion. Urinary chloride loss is usually less than 20 mEq/day. Renal loss of potassium is attributable to abnormalities of the potassium secretory mechanism of the distal nephron.³ Bartter syndrome, Fanconi syndrome, and renal tubular acidosis (RTA) typically present in infancy as failure to thrive, vomiting, constipation, polyuria, and polydyspia.⁴ Urinary chloride loss is typically increased (>20 mEq/day ) in the presence of renal potassium loss.

Primary hyperaldosteronism and thyrotoxicosis are endocrinopathies associated with hypoPP. Primary aldosteronism, also known as Conn syndrome, is usually the result of adrenal hyperplasia or an adenoma. The two cardinal findings are hypertension and suppressed renin activity.³ Diagnosis usually rests on an elevated 24-hour urinary aldosterone level and suppressed renin activity.³

Thyrotoxic periodic paralysis (TPP) is a well-established entity first described in 1902 in Germany.^5,6 Except for the findings caused by hyperthyroidism, which are often subtle in patients with TPP, the clinical and biochemical features of TPP are identical to those of FPP.⁶ TPP tends to be seen later in life (third and fourth decades) and in Asian males; FPP tends to present earlier—in the first and second decades and is more common in Caucasians.⁶ Earlier reports from Asia noted symptoms and signs of hyperthyroidism before the onset of TPP, and some experts in the US have observed the simultaneous occurrence of hyperthyroidism and TPP. In rare cases, TPP presents before evidence of hyperthyroidism.⁶

The precise pathophysiology of TPP has not been elucidated. Thyroid hormone increases sodium-potassium (Na-K) ATPase activity in skeletal muscle, liver and kidney, resulting in increased intracellular transport of potassium in the setting of hyperthyroidism.⁶ Hyperthyroidism also increases tissue responsiveness to b-adrengergic stimulation, which may explain, first, the role of epinephrine in precipitating exacerbations of TPP and, second, why symptoms resolve with b-adrenergic blockade.⁷ Na-K ATPase is also activated by insulin, a likely explanation for the relationship between paralytic attacks and insulin challenges.⁶

In the typical case of TPP, normalization of thyroid function with avoidance of precipitating factors at the initiation of treatment leads to complete cessation of paralytic attacks.³ Oral potassium chloride supplements may be sufficient to treat the hypokalemia associated with TPP, although it may be necessary to use agents such as propanolol or spironolactone and to treat the underlying hyperthyroidism.³

Recurrent hypokalemic paralysis with subtle physical findings of intention tremor, lid lag, and thyromegaly made hyperthyroidism the likely cause of this patient's problem. Antithyroid globulin antibodies as well as antimicrosomal antibodies were later determined to be present (in titers of 1:80 and 1:1,600, respectively). The patient was started on propanolol and an oral potassium chloride supplement before discharge; propylthiouracil was added later. At follow-up, six months after discharge, the boy reported no recurrence of paralysis and thyroid studies had normalized.

A lesson for clinicians

A behavioral disturbance may herald the onset of organic disease in a child (and in an adult). ADHD can be confused with various organic processes, including those listed in the "ADHD masqueraders" table,⁷ and your patient's diagnosis of ADHD at 13 years of age—which led to an individualized education plan at school and a course of methylphenidate—may in fact have marked the onset of hyperthyroidism and not ADHD in the textbook sense. Children who display disruptive behavior in adolescence deserve careful attention and evaluation to rule out an underlying organic problem.

REFERENCES

1. Rose M, Griggs R: Muscle disorders: Channelopathies, in Goetz CG: Textbook of Clinical Neurology, ed 1. Philadelphia, Pa., WB Saunders, 1999, pp 719–723

2. Gutmann L: Metabolic myopathies: Periodic paralysis. Neuro Clinics 2000;18:195

3. Andreoli TE: Renal disease, in Evanoff GV, Ketel BL, Shah SV, et al (eds): Cecil's Essentials of Medicine. Philadelphia, Pa., WB Saunders, 1993, pp 204–205

4. DiGeorge AM, LeFranchi S: Hyperthyroidism, in Berhmann PE, Kliegman RM, Jenson HB: Nelson Textbook of Pediatrics, ed 16. Philadelphia, Pa., 2000, pp 1709–1712

5. Stedwell RE, Allen KM, Binder LS: Hypokalemic paralyses: A review of etiologies, pathophysiology, presentation and therapy. Am J Emerg Med 1992;10:143

6. Ober KP: Thyrotoxic periodic paralysis in the United States. Report of 7 cases and review of literature. Medicine (Baltimore) 1992;71:109

7. Pearl PL, Weiss RE, Stein MA: Medical mimics: Medical and neurological conditions simulating ADHD. Ann NY Acad Sci 2001;931:97

DR. ADLER is an assistant professor of pediatrics at Drexel University College of Medicine, Philadelphia, and is on the faculty in the section of general pediatrics at Monmouth Medical Center, Long Branch, N.J., where DR. HIGHTOWER is a third-year pediatric resident.

DR. SIBERRY is an assistant professor of pediatrics in the divisions of general pediatric and adolescent medicine and pediatric infectious diseases at The Johns Hopkins Hospital.

ADHD masqueraders

Anemia

Bipolar disorder

Congenital brain anomalies

Depression

Enterobius vermicularis (pinworm) infestation

Epilepsy

Fetal alcohol syndrome/effects

Fragile X syndrome

Hearing loss

Lead poisoning

Learning disabilities

Medication effects

Mental retardation

Metabolic disorders (e.g., adrenoleukodystrophy)

Narcolepsy

Neurofibromatosis I

PANDAS*

Pervasive developmental disorder

Posttraumatic stress disorder

Sex chromosome abnormalities

Sleep apnea

Sleep deprivation

Static encephalopathy

Sydenham chorea

Thyroid disorders

Tourette syndrome

Vision loss

*Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

 

Sam Adler, Kim Hightower. Pediatric Puzzler: Lower body weakness in an ADHD teen. Contemporary Pediatrics October 2003;20:24.