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Dear Editor,

Pituitary masses in children are concerning, and it is important to identify causes that could obviate invasive surgical investigation. Reactive pituitary hyperplasia secondary to primary hypothyroidism is a benign cause of pituitary enlargement warranting description.

We present a 9-year-old girl, on no medications, who was investigated for new onset afebrile seizures. Her family history detailed a brain tumour of unknown subtype in the maternal grandmother, thyroid nodules in the paternal grandmother, and a grand aunt with hypothyroidism. Magnetic resonance imaging (MRI) discovered a pituitary mass of uniform signal extending into the suprasellar region, measuring 14 mm in diameter (Fig. 1).

figure

Figure 1. Sagittal T1-weighted view showing pituitary hypertrophy.

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Upon urgent endocrinology review, the only clinical manifestations of pituitary hormone imbalance were cool feet and sluggish reflexes. There were no visual field defects. Serum investigation revealed markedly elevated thyroid-stimulating hormone (TSH) 739.7 mU/L (0.5–4.5), low free T4 2 pmol/L (10–25) and low T3 1.8 pmol/L (4.4–7.1), along with an elevated prolactin 1471 mU/L (102–496). IGF1, IGFBP3 and mane cortisol were normal in the prepubertal child. Elevated antibodies to thyroglobulin 1529 IU/mL (<150) and thyroid peroxidise 1125 IU/mL (<150) and an enlarged, hypervascular, multinodular thyroid gland on ultrasound resulted in the diagnosis of autoimmune primary hypothyroidism. A delayed bone age of 7 years and 2 months suggested the hypothyroidism was long-standing. The child was 128.7 cm tall (10–25th centile) with weight 32.2 kg (50–75th centile).

Following 9 months of thyroxine treatment, repeat MRI showed significant reduction in pituitary gland size to 6.7 mm. The serum prolactin normalised. Unfortunately, seizures continued and epilepsy was treated with anticonvulsants.

In the setting of primary hypothyroidism, loss of thyroxine feedback causes hypothalamic production of thyrotropin-releasing hormone (TRH), which stimulates thyrotroph cells of the pituitary to produce TSH.[1] Histological analysis of TRH-stimulated pituitary glands reveal large oval thyrotrophs with increased cytoplasm (‘thyroidectomy cells’).[2] Elevation in prolactin may reflect both pituitary stalk compression and concomitant lactotroph hyperplasia.[2] In a review of 53 cases of adult primary hypothyroidism, 69.8% patients had pituitary enlargement on imaging at presentation.[3]

The differential diagnosis for pituitary enlargement in children includes cerebral tumours such as craniopharyngioma, germinoma, adenoma (including prolactinoma), glioma and astrocytoma, along with arachnoid cysts, Rathke cleft cysts, vascular malformations, abscess, granulomatous disease, lymphocytic hypophysitis, Langerhans cell histiocytosis and genetic transcription factor mutations (e.g. PROP1).[4] Although the serum prolactin level was elevated in this child at presentation, in prolactinoma a much higher level would be expected and there would be absence of the significantly elevated TSH.

Reactive pituitary hypertrophy secondary to primary hypothyroidism can mimic intracranial tumour, and accurate diagnosis permits avoidance of surgical intervention.

Acknowledgements

Authors from the Murdoch Children's Research Institute are supported by The Victorian Government Operational Infrastructure Support Program. MA Sabin is supported through a National Health and Medical Research Council Health Professional Training Fellowship (APP1012201). JK Hewitt is supported through a National Health and Medical Research Council Postgraduate Scholarship (APP607439).

References

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  2. References
  • 1
    Joshi AS, Woolf PD. Pituitary hyperplasia secondary to primary hypothyroidism: a case report and review of the literature. Pituitary 2005; 8: 99103.
  • 2
    Eiland L, Oyesiku NM, Ritchie JC, Isaacs S, Ioachimescu AG. Pathogenesis of marked pituitary enlargement and increased serum thyroid-stimulating hormone in primary hypothyroidism. Thyroid 2012; 22: 101102.
  • 3
    Khawaja NM, Taher BM, Barham ME et al. Pituitary enlargement in patients with primary hypothyroidism. Endocr. Pract. 2006; 12: 2934.
  • 4
    Low MJ. Neuroendocrinology. In: Kronenberg HM , Melmed S , Polonsky K et al., eds. Williams Textbook of Endocrinology, 11th edn. Philadelphia: Elsevier, 2008; 85154.