Case Study: Non-Endoscopic Gastroenterology
The following case study was used by James P. Keating, MD, MSc, medical director, St. Louis Children’s Hospital Diagnostic Center, and his co-editor, Andrews J. White, MD, division director of pediatric rheumatology/immunology, as part of the “Patient of the Week” (POW) series. Many of the POW case studies cover uncommon illnesses, or common illnesses with unusual symptoms that can be overlooked. If you would like to be added to the POW e-mail distribution list, send an e-mail to jkeating@wustl.edu or white_a@wustl.edu.
Pediatrician: Hood
GI: Heuckeroth
Endo: Thomas/Hruz
16-year-old Caucasian youth came to the GI office with CC: emesis after exercise.
HPI: For the past year, he has had NBNB emesis and palpitations with intensive exercise. The symptoms progressed to emesis with less strenuous activity—golf, umpiring, etc. He reduced his activity level. Nine months ago, he started experiencing restlessness and tremors. Over the past two months, he vomits at least three times a week. Over the past month, he has had difficulty swallowing solids. Lost 10 lbs over the past four months despite a voracious appetite.
ROS: He has some dizziness, lightheadedness, headaches, but no abdominal pain, fevers, diarrhea or mood swings.
PMH: Hospitalized in summer of 2010 for 48 hrs of IVF diagnosed with stomach flu.
Meds: Omeprazole for three weeks in July—unclear if it helped alleviate his symptoms.
FH: Mother and maternal grandmother had a thyroidectomy for a goiter and now are hypothyroid (treated with oral thyroid).
SH: Lives with parents and sister in Illinois. In 10th grade, good student.
PE: BP 110/58. Height 180.5cm (75th %). Weight 55kg (25th %). BMI 17.0 (3rd %). General: thin, fidgety. Skin: Moist and warm. 3cm hyperpigmented macule on abdomen. HEENT: PERRLA. Disc margin blurred on left. No proptosis or exophthalmos. Neck: palpable nontender thyroid - 5x4cm without nodules. Lungs: No crackles, wheezes or stridor. CV: Tachycardic. Normal S1, S2. Bounding pulses. No m/r/g. Abd: No HSM. GU: Tanner 5. Ext: No edema. Neuro: Unsteady tandem gait. Clonus at the ankles. 2+ DTR - patellar. Strength 5/5. Subtle resting tremor in both hands.
Studies: CBC - normal CMP - normal tTG Ab - 2.9 (0-19.9) IgA - 50.5 (70-370) L TSH - 0.01 (0.35-5.5) L Free T4 - 4.12 (0.8-1.8) H Radioactive Iodine Uptake - 65.6% (10-30%) H Diagnosis: Hyperthyroidism (Grave’s Disease)
Plan:
1) Was started on atenolol (beta blocker) 25mg PO qDay for symptomatic relief.
2) One week later underwent radioactive iodine ablation treatment. Vomiting is not a commonly described symptom of Grave’s, but it rapidly improved with treatment and will be further investigated if the symptom returns.
Discussion: Grave’s disease, or diffuse toxic goiter, accounts of up to 90% of hyperthyroidism in pediatric patients. Of the general population, 0.5% is affected by Grave’s disease. Pathogenesis is due to circulating IgG antibodies that bind to and activate the G-protein-coupled thyrotropin receptor. The activation stimulates follicular hypertrophy and hyperplasia of the thyroid gland, which increases thyroid hormone production. Female-to-male ratio is 5-10:1. Peak incidence is between 40-60 years old, although it can occur at any age. A family history of thyroid disease, especially in maternal relatives, is associated with increased incidence of Grave’s disease and at a younger age of onset.
Children often suffer from hyperactivity, poor sleep, emotional lability, decreased school performance, palpitations, tremors, diaphoresis, frequent bowel movements (not necessarily diarrhea), ophthalmopathy (30-50% of patients), proximal muscle weakness, menstrual irregularity and goiters. Unlike in adults, weight loss and gain are found in children. A paradoxical weight gain is possible secondary to an increased appetite and food intake.
The patients are generally tachycardic upon presentation and have a widened pulse pressure (as our patient did). The degree of tachycardia parallels the severity of the hyperthyroidism. The thyroid is smooth, symmetrically enlarged and may have a palpable thrill or audible bruit. The disease can progress to thyroid storm—with a change in mentation, hypertension and cardiovascular instability. Mortality of untreated hyperthyroidism is 20-50%, due to the development of atrial fibrillation, cardiomyopathy and congestive heart failure. Laboratory evaluation demonstrates a suppressed TSH secondary to stimulation of the gland by TSI and an elevated free T4 and total T3. In Grave’s disease, the patient may have TPO or TG antibodies present. Radioactive uptake scan reveals a diffusely high uptake of iodine in the thyroid gland.
The three options for treatment are as follows:
1) Medication—Antithyroid drugs are known as thioamides and consist of propylthiouracil (PTU) or methimazole. Both block synthesis of thyroid hormone by interfering with thyroid peroxidase-mediated iodination of tyrosine residues in thyroglobulin, but PTU can also prevent conversion of T4 to T3 in the thyroid and peripheral tissues. Methimazole is currently the preferred treatment based on a black box warning on PTU causing severe liver failure, due to an allergic hepatitis, requiring transplantation. Side effects occur in 5-14% of patients ranging from rash, arthralgia, lupus-like reaction, thrombocytopenia and agranulocytosis. Beta blockers (i.e., atenolol) are used if the patient has cardiac symptoms.
2) Radioactive iodine ablation—Destroys the thyroid over 2-4 months and requires either lifetime monitoring of thyroid levels or treatment with Synthyroid for hypothyroidism. If sufficient radioiodine is administered, hypothyroidism develops in 80-90% of patients.
3) Surgery—Rarely used in children. Complications include hypothyroidism, hypoparathyroidism and damage to laryngeal nerves. An RCT comparing the treatment options showed that all were similarly effective, although the relapse rate was highest among patients who received antithyroid drugs (~40%) vs. radioactive ablation (21%) vs. surgery (5%).
References:
1. American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002; 8:457-469.
2. Brent, GA. Grave’s Disease. NEJM 2008; 358:2594-2605.
3. Cooper, DS. Antithyroid Drugs. NEJM 2005; 352:905-917.
4. Ross, DS. Radioiodine Therapy for Hyperthyroidism. NEJM 2011; 364:542-550.
Torring O, Tallstedt L, Wallin G, et al. Grave’s hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine—a prospective, randomized study. J Clin Endocrinol Metab 1996; 81:2986-2993.
