Prediction for recurrence following antithyroid drug therapy for Graves’ hyperthyroidism

Weng, Huan; Tian, Wen Bo; Xiao, Zi Dong; Xu, Lin

doi:10.20945/2359-3997000000609

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Archives of Endocrinology and Metabolism

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Original Article • Arch. Endocrinol. Metab. 67 (4) • 2023 • https://doi.org/10.20945/2359-3997000000609 copy

Prediction for recurrence following antithyroid drug therapy for Graves’ hyperthyroidism

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

A common problem with antithyroid drugs (ATD) treatment in patients with Graves’ disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China.

Subjects and methods:

Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant.

Results:

A total of 127 Graves’ hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00).

Conclusions:

Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Keywords
Antithyroid agents; recurrence; Graves’ disease; risk factors; sleep initiation; maintenance disorders

		Nonrecurrence	Recurrence	P-value
Number		72	55	-
Male sex, N (%)		20 (27.78)	12 (21.82)	0.44
Age, y, mean (SD)		39.6 (13.3)	35.2 (13.3)	0.07
Family history, yes, N (%)		27 (37.50)	17 (30.91)	0.44
Non-iodized salt, yes, N (%)		62 (86.11)	39 (70.91)	0.04
Current smoking, yes, N (%)		16 (22.22)	8 (14.55)	0.27
Insomnia, yes, N (%)		7 (9.72)	18 (32.73)	0.001
Goiter size, N (%)				<0.001
	0-I	26 (36.11)	4 (7.27)
	II-III	46 (63.89)	51 (92.73)
Thyroid volume, N (%)
	Grade III	26 (36.11)	34 (61.82)	0.004
FT3/FT4 ratio, mean (SD)		0.5 (0.1)	0.6 (0.4)	0.15
TSH, uIU/mL, N (%)				0.55
	≤0.003	21 (29.17)	21 (38.18)
	0.004-0.014	24 (33.33)	17 (30.91)
	0.015-0.216	27 (37.50)	17 (30.91)
TRAb, N (%)				<0.001
	1.82-12.00	31 (43.06)	11 (20.00)
	12.01-24.99	27 (37.50)	15 (27.27)
	≥25.00	14 (19.44)	29 (52.73)
Thyroid inferno, yes, N (%)		43 (59,72)	52 (94.55)	<0.001
Graves’ ophthalmopathy, yes, N (%)		4 (5.56)	15 (27.27)	0.001
Maintenance dose of MMI, mg/d, N (%)				<0.001
	≤5	64 (88.89)	28 (50.91)
	>5	8 (11.11)	27 (49.09)
L-T4 therapy, yes, N (%)		12 (16.67)	12 (21.82)	0.46

		Crude HR (95% CI)	Adjusted HR (95% CI)
Male sex		0.83 (0.44-1.57)	0.70 (0.30-1.66)
Age		0.98 (0.96-1.00)	0.99 (0.97-1.01)
Family history, yes		0.83 (0.47-1.46)	0.98 (0.53-1.82)
Non-iodized salt, yes		0.57 (0.32-1.03)	0.83 (0.42-1.62)
Current smoking, yes		0.69 (0.33-1.46)	0.68 (0.24-1.92)
Insomnia, yes		2.52 (1.43-4.45) ^* ***** P < 0.001.	2.94 (1.47-5.88) ^ P < 0.01
Goiter size
	0-I	1.00	1.00
	II-III	4.85 (1.75-13.43) ^ P < 0.01	3.34 (1.11-10.07) ^* * P < 0.05
Thyroid volume
	Grade I & II	1.00	1.00
	Grade III	2.06 (1.19-3.55) ^* * P < 0.05	1.31 (0.69-2.5)
FT3/FT4 ratio		1.52 (0.81-2.86)	0.80 (0.32-1.96)
TSH, uIU/mL
	≤0.003	1.00	1.00
	0.004-0.014	1.35 (0.71-2.56)	0.82 (0.41-1.66)
	0.015-0.216	1.06 (0.54-2.08)	1.00 (0.48-2.10)
TRAb
	1.82-12.00	1.00	1.00
	12.01-24.99	1.48 (0.68-3.22)	1.24 (0.50-3.06)
	≥25.00	3.40 (1.69-6.85) ^ P < 0.01	2.66 (1.12-6.31) ^* * P < 0.05
Thyroid inferno		7.37 (2.30-23.64) ^ P < 0.01	3.04 (0.84-10.97)
Graves’ ophthalmopathy		2.85 (1.56-5.19) ^* ***** P < 0.001.	1.85 (0.93-3.67)
Maintenance dose of MMI, mg/d
	≤5	1.00	1.00
	>5	3.38 (1.98-5.78) ^* ***** P < 0.001.	2.14 (1.14-4.00) ^* * P < 0.05
L-T4 therapy		1.19 (0.63-2.26)	1.01 (0.48-2.12)

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[1] Correspondence to: Lin Xu, School of Public Health, Sun Yat-sen University 74 Zhongshan 2nd Road, Guangzhou 510080 , Guangdong Province, China xulin27@mail.sysu.edu.cn