A Rare Coexistence of Thyrotropin-Secreting Pituitary Adenoma and Graves Disease

Abstract

The coexistence of Graves disease (GD) and a thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is a rare and diagnostically challenging condition. In general, GD typically manifests with low TSH because of excess thyroid hormone production; contrastingly, a TSHoma causes secondary hyperthyroidism with normal or elevated TSH levels. This unusual overlap poses diagnostic and therapeutic challenges; therefore, a careful approach is required to distinguish and manage both conditions. We present the case of a 51-year-old woman with symptoms of hyperthyroidism, elevated thyroid hormones, low TSH, and positive anti-TSH receptor antibodies, which were suggestive of GD 10 years prior. After stopping thiamazole and levothyroxine because of the favorable control of thyroid function 6 months prior, the patient presented a syndrome of inappropriate secretion of TSH and magnetic resonance imaging revealed a pituitary macroadenoma; accordingly, she was diagnosed with concurrent GD and a TSHoma. Treatment involved transsphenoidal resection of the TSHoma and antithyroid medication to control GD. This case illustrates the rarity of coexisting GD and TSHoma and the diagnostic and therapeutic complexities of managing dual hyperthyroidism etiologies. Biochemical testing, antibody assessment, and imaging examination are essential for accurate and early diagnosis of the condition.

Keywords: Graves disease; diagnosis; hyperthyroidism; thyrotroph pituitary adenoma.

Figure 1.

Magnetic resonance imaging (MRI) of the pituitary tumor across different stages of treatment. (A, B) Initial MRI with gadolinium enhancement. (A) Sagittal T1-weighted image showing the tumor. (B) Coronal T1-weighted image revealing tumor size (diameter was 10 × 12 × 13 mm) and morphology before treatment. (C, D) MRI after somatostatin analog injection with gadolinium enhancement. (C) Sagittal T1-weighted image showing the tumor shrinkage responded to treatment. (D) Coronal T1-weighted image demonstrating tumor size reduction. (E, F) Postoperative MRI with gadolinium enhancement following endoscopic transsphenoidal surgery. (E) Sagittal T1-weighted image showing the resection cavity. (F) Coronal T1-weighted image illustrating the residual normal pituitary tissue.

Figure 2.

Surgical and pathological evaluation of the thyroid-stimulating hormone (TSH)-secreting pituitary adenoma. (A–C) Endoscopic surgical views. (A) Pre-resection view showing the tumor in situ. (B) Scene of tumor resection; the black arrow indicates the normal pituitary gland and the asterisk shows the tumor. (C) Postresection view showing the normal pituitary gland and arachnoid membrane after tumor removal; the black arrow indicates the normal pituitary gland and the star shows the arachnoid membrane. (D–F) Pathological evaluation of the resected tumor. (D) Hematoxylin and eosin (HE) staining demonstrating the cellular morphology of the tumor. (E) Immunohistochemical staining for TSH confirming the hormone production by the tumor. (F) Somatostatin receptor (SSTR)2 and (G) SSTR5 are expressed in the tumor cellular membrane.

Figure 3.

Changes in thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels during the treatment course. The graph illustrates the dynamic changes in TSH and FT4 levels over time in response to treatment. Initial medical therapy for Graves disease (GD) resulted in an increase in TSH levels and a decline in FT4 levels in 2014. Upon the cessation of oral medication in November 2023, FT4 levels rebounded with normal TSH levels, thus leading to a syndrome of inappropriate TSH secretion. After preoperative lanreotide injection in February 2024, the FT4 levels became normalized and inappropriate TSH secretion was resolved. However, the underlying GD state persisted in June 2024, 2 months later from endoscopic transsphenoidal gross total tumor resection, thus requiring ongoing management.