What is the recommended workup for a 13-year-old patient with a month of weight loss, exophthalmos, and a recent history of fever?

Workup for 13-Year-Old with Weight Loss, Exophthalmos, and Fever

This patient requires urgent evaluation for Graves' disease/hyperthyroidism and malignancy (particularly lymphoma or leukemia), with thyroid function tests and complete blood count with differential as the highest priority initial laboratory studies.

Immediate Laboratory Evaluation

Essential First-Line Tests

• Thyroid function tests (TSH, free T4, free T3) to evaluate for hyperthyroidism, which commonly presents with weight loss and exophthalmos in adolescents 1
• Complete blood count with differential to assess for cytopenias, thrombocytopenia, or abnormal cells suggesting leukemia or lymphoma 2, 1
• Peripheral blood smear if CBC shows any abnormalities, as lymph nodes >2 cm with cytopenias warrant immediate evaluation for acute lymphoblastic leukemia 1
• Inflammatory markers (ESR, CRP, procalcitonin) to distinguish infectious from non-infectious causes and assess disease severity 1, 3
• Comprehensive metabolic panel including liver function tests, as hepatosplenomegaly may accompany systemic disease 1, 3
• Blood cultures (multiple sets before any antibiotics) if infectious etiology is suspected 1

Additional Laboratory Studies

• Urinalysis and urine culture (catheterized specimen) as UTIs account for >90% of serious bacterial infections in febrile children, though less likely in this age group 1, 3
• Thyroid antibodies (TSI, anti-TPO, anti-thyroglobulin) if thyroid function tests suggest Graves' disease 4

Imaging Studies

Priority Imaging

• Chest radiograph (PA and lateral) to evaluate for mediastinal lymphadenopathy or mass, which could indicate lymphoma or thymic pathology 2, 1
• Orbital imaging (CT or MRI of orbits) to characterize the exophthalmos and evaluate for retro-orbital masses, thyroid eye disease, or other orbital pathology 5

Secondary Imaging (Based on Initial Findings)

• PET/CT scan (skull base to mid-thigh) if lymphoma is suspected based on lymphadenopathy or constitutional symptoms, as this is essential for staging 2
• Neck ultrasound or CT to evaluate thyroid gland size, nodules, and vascularity if hyperthyroidism is confirmed 1
• Abdominal/pelvic CT or ultrasound if hepatosplenomegaly is detected on examination 1, 5

Physical Examination Priorities

Critical Examination Components

• Comprehensive lymph node examination of all lymphoid regions (cervical, axillary, inguinal), noting size (>2 cm is concerning), consistency (hard/matted nodes suggest malignancy), and mobility 2, 1
• Thyroid examination for enlargement, nodules, bruit, or tenderness 1
• Ophthalmologic assessment to quantify exophthalmos (Hertel exophthalmometry if available), assess extraocular movements, visual acuity, and funduscopic examination 2, 5
• Hepatosplenomegaly assessment by palpation and percussion 1, 3
• Cardiovascular examination for tachycardia, flow murmurs, or signs of high-output state (hyperthyroidism) 1

Specific Historical Details to Elicit

• B symptoms: Document exact fever pattern, night sweats (drenching vs. mild), and quantify weight loss percentage 2
• Thyroid symptoms: Heat intolerance, palpitations, tremor, increased appetite, diarrhea, anxiety 1
• Visual symptoms: Diplopia, eye pain, photophobia, vision changes 2, 5
• Infectious exposures: Travel history, animal contacts, tick exposures, sick contacts 1
• Medication history: Any new medications in past 3 weeks (drug fever has mean lag time of 21 days) 1

Diagnostic Algorithm

If Thyroid Function Tests Are Abnormal (Hyperthyroidism)

1. Confirm Graves' disease with thyroid antibodies (TSI) 4
2. Obtain thyroid ultrasound to assess gland characteristics 1
3. Refer to endocrinology for management and ophthalmology for thyroid eye disease evaluation 2
4. Critical pitfall: Exophthalmos in Graves' disease may be an autoimmune disorder requiring separate management from hyperthyroidism 4

If CBC Shows Cytopenias or Abnormal Cells

1. Immediate bone marrow examination is mandatory if blasts are present or unexplained cytopenias persist with lymphadenopathy >2 cm 1
2. Obtain chest imaging before bone marrow biopsy to evaluate for mediastinal mass (risk of airway compromise with sedation) 2, 1
3. Do not delay bone marrow examination for viral testing, as viral infections do not preclude coexisting malignancy 1

If Initial Workup Is Unrevealing

1. Consider excisional lymph node biopsy (not fine-needle aspiration) if lymphadenopathy persists, with immunostaining for CD3, CD15, CD20, CD30, CD45, CD79a, and PAX5 to evaluate for lymphoma 2
2. Evaluate for infectious causes: Consider Q fever serologies if epidemiologic risk factors present (phase I and II IgG/IgM) 2, 1
3. PET/CT may be valuable for fever of unknown origin in this age group to identify occult infection or malignancy 6

Critical Pitfalls to Avoid

• Do not assume that one month of symptoms rules out acute leukemia; lymphoblastic leukemia can present subacutely 1
• Do not rely on clinical appearance alone; serious conditions may present with relatively preserved general condition initially 3
• Do not delay ophthalmology referral; exophthalmos requires baseline examination and may indicate sight-threatening disease 2, 5
• Do not attribute all findings to a single diagnosis without excluding malignancy; weight loss and fever with exophthalmos could represent concurrent Graves' disease and lymphoma 1, 7
• Do not perform echocardiography unless Kawasaki disease criteria are met (fever ≥5 days plus 4 of 5 criteria), which is unlikely with low-grade fever and 2-month symptom duration 1

Urgent Referrals

• Endocrinology if hyperthyroidism confirmed 1
• Hematology/oncology if CBC abnormalities or lymphadenopathy concerning for malignancy 2, 1
• Ophthalmology for all patients with exophthalmos to assess vision threat and quantify severity 2, 5