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Review
. 2023 Jul 28;12(4):e220223.
doi: 10.1530/ETJ-22-0223.

Central hyperthyroidism combined with Graves' disease: case series and review of the literature

Caiyan Mo  1 , Han Chen  1 , Qi Zhang  1 , Ying Guo  1 , Liyong Zhong  1
Affiliations
Review

Central hyperthyroidism combined with Graves' disease: case series and review of the literature

Caiyan Mo et al. Eur Thyroid J. .

Abstract

Background: Central hyperthyroidism is characterized by elevated free thyroid hormone and unsuppressed thyroid-stimulating hormone (TSH), and this laboratory feature includes TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone β (RTHβ). Central hyperthyroidism combined with Graves' disease (GD) has been rarely reported.

Case report: We describe three patients with TSHoma combined with GD and one patient with GD combined with RTHβ and pituitary adenoma. These three patients with TSHoma combined with GD showed elevated thyroid hormone, while TSH level was normal or elevated, and TSH receptor antibodies were positive. After thyrotoxicosis was controlled, they all underwent transsphenoidal surgery. We also describe a patient with an initial presentation of GD who developed hypothyroidism after anti-hyperthyroidism treatment and TSH was inappropriately significantly increased. His head magnetic resonance imaging revealed a pituitary adenoma. Genetic testing confirmed a heterozygous mutation in the thyroid hormone receptor β gene c.1148G>A (p.R383H). After levothyroxine and desiccated thyroid tablet treatment, the TSH level decreased to normal.

Conclusion: These four cases highlight the need to consider the diagnosis of GD combined with central hyperthyroidism when faced with inconsistent thyroid function test results, illuminating the specific diagnostic and therapeutic challenges of coexisting primary and central hyperthyroidism. Finally, we propose clinical management for central hyperthyroidism combined with GD.

Keywords: Graves’ disease; central hyperthyroidism; resistance to thyroid hormone β; thyroid-stimulating hormone-secreting pituitary adenoma.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

Figures

Figure 1
Figure 1
Pituitary enhanced MRI, thyroid function change, and treatment of case 1. ATD, antithyroid drugs; FT3, free tri-iodothyronine; FT4, free thyroxine; SSA, somatostatin analog; TRAb, thyroid-stimulating hormone receptor antibodies; TSH, thyroid-stimulating hormone; TSS, transsphenoidal surgery. Normal ranges: FT4 7.64–16.03 pmol/L, FT3 3.28–6.47 pmol/L, TSH 0.49–4.91 μIU/mL, TRAb 0–1.7 IU/L.
Figure 2
Figure 2
Pituitary enhanced MRI, thyroid function change, and treatment of case 2. FT3, free tri-iodothyronine; FT4, free thyroxine; SSA, somatostatin analog; TRAb, thyroid-stimulating hormone receptor antibodies; TSH, thyroid-stimulating hormone; TSS, transsphenoidal surgery. Normal ranges: FT4 7.64–16.03 pmol/L, FT3 3.28–6.47 pmol/L, TSH 0.49–4.91 μIU/mL, TRAb 0–1.7 IU/L.
Figure 3
Figure 3
Pituitary-enhanced MRI, thyroid function change, and treatment of case 3. DA, dopamine receptor agonist; FT3, free tri-iodothyronine; FT4, free thyroxine; SSA, somatostatin analog; TRAb, thyroid-stimulating hormone receptor antibodies; TSH, thyroid-stimulating hormone; TSS, transsphenoidal surgery. Normal ranges: FT4 7.64–16.03 pmol/L, FT3 3.28–6.47 pmol/L, TSH 0.49–4.91 μIU/mL, TRAb 0–1.7 IU/L.
Figure 4
Figure 4
Pituitary-enhanced MRI, thyroid function change, and treatment of case 4. DA, dopamine receptor agonist; FT3, free tri-iodothyronine; FT4, free thyroxine; L-T4, levothyroxine; SSA, somatostatin analog; TRAb, thyroid-stimulating hormone receptor antibodies; TSH, thyroid-stimulating hormone; TSS, transsphenoidal surgery. Normal ranges: FT4 7.64–16.03 pmol/L, FT3 3.28–6.47 pmol/L, TSH 0.49–4.91 μIU/mL, TRAb 0–1.7 IU/L.
Figure 5
Figure 5
Clinical management plan for GD combined with central hyperthyroidism. ATD, antithyroid drugs; FT3, free tri-iodothyronine; FT4, free thyroxine; GD, Graves' disease; LLN, low limit of the normal range; L-T4, levothyroxine; RTHβ, resistance to thyroid hormone β; SSA, somatostatin analog; T3, tri-iodothyronine; THRB, thyroid hormone receptor β; TRAb, thyroid-stimulating hormone receptor antibodies; TRH, thyroid-stimulating hormone releasing hormone; TSH, thyroid-stimulating hormone; TSHoma, pituitary TSH adenoma; TSS, transsphenoidal surgery; ULN, upper limit of normal range.
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