What is the most important initial investigation to assess short stature in a child with skull changes, maxillary enlargement, and hepatosplenomegaly?

Hemoglobin is the Most Important Investigation

In a child presenting with short stature, skull bossing, maxillary enlargement, and hepatosplenomegaly, hemoglobin measurement is the most critical initial investigation because this clinical constellation is pathognomonic for thalassemia major (Cooley's anemia), where chronic severe anemia drives the short stature through multiple mechanisms including bone marrow expansion, chronic hypoxia, and iron overload.

Clinical Recognition of the Underlying Diagnosis

The triad of findings you describe points directly to a specific diagnosis:

• Skull bossing (frontal bossing) results from massive expansion of the bone marrow attempting to compensate for chronic severe anemia 1
• Maxillary enlargement (chipmunk facies) occurs from the same marrow hyperplasia mechanism 1
• Hepatosplenomegaly develops from extramedullary hematopoiesis and iron overload 1

This is not a case of isolated short stature requiring endocrine evaluation 1.

Why Hemoglobin Takes Priority

Direct Pathophysiologic Link

• Chronic severe anemia in thalassemia major causes growth failure through multiple pathways: chronic tissue hypoxia, endocrine dysfunction from iron overload (affecting pituitary, thyroid, and gonads), nutritional deficiencies, and the metabolic burden of ineffective erythropoiesis 1
• The skeletal changes themselves (bossing, maxillary enlargement) are consequences of the severe anemia driving marrow expansion 1

Diagnostic Certainty

• A severely low hemoglobin (typically <7 g/dL in untreated thalassemia major) immediately confirms the suspected diagnosis and explains all the clinical findings simultaneously 1
• This single test provides the answer to the short stature etiology, whereas pituitary hormones would be investigating a secondary consequence rather than the primary pathology 1

Why Not the Other Options

Pituitary Hormones (Option B)

• While growth hormone deficiency can occur secondary to iron overload in thalassemia, testing pituitary function before confirming the underlying hematologic disorder puts the cart before the horse 1
• The ACMG guidelines emphasize that when physical examination reveals associated abnormalities with short stature, the evaluation must focus on identifying the underlying syndrome first 1

Liver Function Tests (Option C)

• LFTs would show abnormalities from iron overload and extramedullary hematopoiesis, but they don't establish the primary diagnosis 1
• Hepatomegaly here is a consequence of the hematologic disorder, not a primary hepatic process causing growth failure 1

Clinical Approach Algorithm

When short stature presents with dysmorphic features and organomegaly:

1. Recognize the pattern - skull/facial bone changes + hepatosplenomegaly = chronic severe anemia 1
2. Confirm with hemoglobin - establishes severity and urgency 1
3. Follow with hemoglobin electrophoresis - confirms thalassemia type 1
4. Then assess complications - including secondary endocrinopathies, cardiac function, and iron overload 1

Critical Pitfall to Avoid

Do not pursue isolated short stature workup (bone age, IGF-1, growth hormone stimulation) when obvious syndromic features are present. The ACMG guidelines explicitly state that the diagnostic approach must first differentiate isolated short stature from short stature with associated physical abnormalities, and when the latter is present, identifying the underlying condition takes absolute priority 1.