Severe Acquired Hypothyroidism and Van Wyk–Grumbach Syndrome

A 10-year-old boy was referred to the endocrinology department due to minimal linear growth between ages 7 and 10. His parents noted growth arrest over the past two years, worsening lethargy, constipation, difficulty at school, declining school performance, and extreme fatigue. No neurological or visual symptoms were reported.

The child’s growth velocity was 0 cm/24 months; his medical and family histories were unremarkable.

On examination, he weighed 31 kg (25th percentile) and was 126 cm tall (<3rd percentile) with normal vital signs except for a heart rate of 66 beats/min. He was cooperative but lethargic with slowed mentation, pale skin, periorbital puffiness, brittle hair, and dry skin. He had delayed intestinal transit and no goiter. His genitalia showed atypical pubertal development, with bilaterally enlarged testes (8 mL), a stretched penile length of 3.8 cm, and no pubic hair. Neurological and visual field exams were normal.

Laboratory tests were normal, including complete blood count, electrolyte, glucose, liver, and renal function. His total cholesterol and triglyceride levels were elevated. Primary hypothyroidism was diagnosed based on a TSH concentration of 2,400 mIU/L, fT4 concentration of 1 pmol/L, and thyroglobulin level of 21 μg/L. Elevated thyroid antibody levels confirmed autoimmune thyroiditis (AIT). Additional hormonal abnormalities included elevated prolactin and FSH levels and low LH levels (elevated FSH/LH ratio). Adrenal and somatotroph functions were normal.

Thyroid ultrasonography showed a normal thyroid gland with homogenous mild hypoechoic changes and diffuse hypervascularity. The bone age was determined to be 6 years. MRI of the hypothalamus and pituitary gland revealed an enlarged pituitary gland with a craniocaudal diameter of 18 mm and a convex superior margin. The posterior pituitary showed high signal intensity, and the optic chiasm was unaffected.

The boy was diagnosed with atrophic AIT and Van Wyk-Grumbach Syndrome (VWGS). 

Hormone replacement therapy with levothyroxine (5 μg/kg/day) was initiated. After six months, he showed symptom resolution, catch-up growth of 5 cm, a weight loss of 3 kg, and unchanged testicular enlargement. Thyroid function normalized, and pituitary dimensions regressed with a homogenous appearance on follow-up MRI.

VWGS should be considered in children with severe hypothyroidism presenting with growth arrest, incomplete precocious puberty, delayed bone age, and pituitary hyperplasia. Elevated TSH levels mediate its pathophysiology. Levothyroxine treatment restores a euthyroid state, avoiding unnecessary surgical interventions despite potential clinical emergencies related to VWGS. A multidisciplinary approach is crucial, especially regarding growth patterns and thyroid function.

Source: Nicolescu CR, Bazus L, Stephan JL. Case Reports in Pediatrics. 2024;2024(1):8919177.