Long-term follow-up of seven patients with ophthalmopathy not associated with thyroid autoimmunity: heterogeneity of autoimmune ophthalmopathy

Figures & data

Table 1 Demographics, thyroid function, and thyroid ultrasound findings at the first visit in seven patients with euthyroid Graves’ disease

Patient number	Age/sex	Ethnicity	Thyroid function		Thyroid ultrasound	Histologya
			f T4	TSH
1	63/F	Caucasian	12.6	1.1	Normal
2	53/F	Malay	16	1.91	One large nodule, one small nodule, else normal	Follicular cell adenoma, no lymphocytes on FNA, or at thyroidectomy
3	50/F	Asian	9.9	0.84	Not performed	Nil
4	60/F	Asian	14	0.69	One small nodule, else normal	Nil
5	55/F	Caucasian	12.3	0.74	Normal	Nil
6	49/F	Caucasian	13	0.97	Several big nodules and overall colloid features	Colloid goiter, no lymphocytes at thyroidectomy
7	30/M	Lebanese	13.8	0.87	Enlarged, but normal texture	Nil

Notes:

a assessed from fine needle aspiration (FNA) biopsy (patients 2, 6) or thyroidectomy (patient 2).

Abbreviations: fT₄, free T4; TSH, thyroid-stimulating hormone.

Table 2 Thyroid antibodies, other autoantibodies, personal and family history of thyroid, and other autoimmune disorders in seven patients with euthyroid Graves’ disease

Patient number	Thyroid antibodiesa				Other autoantibodies		Personal history of thyroid or other autoimmunity	Known family history of thyroid or other autoimmunity
	TPO	Tg	TRAb	TSI	ANA	Other
1	<20	<20	<0.1	8.45	Neg	Fp	Nil	Hashimoto’s thyroiditis
	<20	<20	NT	19.38
	<20	<20	NT	NT
	<20	<20	NT	6.89
2	<20	<20	<0.1	17.64	Neg	Fp	Nil	Nil known
	<20	<20	NT	20.79
	<20	<20	NT	6.05
3	<20	<20	<0.1	13.71	Neg	NT	Nil	Rheumatoid arthritis
4	<20	<20	NT	NT	Neg	GPC	Vitiligo	Nil known
			NT	16.22
			NT	25.07
			NT	16.53
5	<20	<20	<0.1	13.16	Neg	NT	Nil	Nil known
6	<20	<20	<0.1	10.43	NT	NT	Nil	Nil known
7	<20	<20	NT	NT	NT	NT	Nil	Nil known

Notes:

a Thyroid antibodies were measured in a commercial ELISA; TSH-receptor antibodies were measured as TSH-r-binding antibody (TRAb) (ref range < 2 IU/L) and as thyroid-stimulating immunoglobulin (TSI), (ref range 0%–19% B/B0). Results are shown for the first and subsequent clinic visits.

Abbreviations: ANA, antinuclear antibody; Fp, flavoprotein (the 64-kDa protein); GPC, gastric parietal cell; NT, not tested; Tg, thyroglobulin (cut off titer 20); TPO, thyroid peroxidase (cut off titer 20).

Table 3 Eye findings, smoking status, and treatment in seven patients with euthyroid Graves’ disease

Patient number	Duration of follow up (years)	Smokes	Eye signs				Orbital CT findings	Treatment
			NOSPECS classa	CAS	Nunery typeb	UER^d
1	8	No	4	4	2	Yes	Enlarged EOM	Nil
2	10	No	4	4	2	No	Enlarged EOM	Prednisolone 25 mg
3	6	No	3	5	1	Yes	Normal EOM	Nil
4	8	No	2	3	1	No	Normal on two occasions 1 year apart	Prednisolone (50 mg/day) + steroid eye drops
5	7	No	4	1	2	No	EOM volumes increased	Prednisolone 7.5 mg
6	6	No	3	4	1	No	Minimal EOM swelling	Nil
7	3	No	3	2	1	Yes	Normal EOM, dilated ophthalmic vein	Nil

Notes:

a NOSPECS classes of Werner¹⁸;

b Nunery types 1 (ophthalmopathy without ocular myopathy) and 2 (with ocular myopathy)¹⁶;

Abbreviations: CAS, clinical activity score of Mourits et al¹⁷; EOM, extraocular muscles; UER, upper eyelid retraction.

Table 5 Eye findings, smoking status, and treatment at the time of the first clinic visit in 13 patients with Graves’ ophthalmopathy matched for age, sex, and ophthalmopathy severity, and activity with the patients with EGD

Patient number	Age/sex	Ethnicity	Duration of follow-up (years)	Personal history of thyroid or other autoimmunity	Known family history of thyroid or other autoimmunity	Smokes (Y/N)	TRAb^a	Eye signs				Orbital imaging findings	Thyroid antibodiesb	Treatment		Orbital antibodiesc
								NOSPECSd Class	CAS^e	Nunery typef	UER^g		TPO/Tg	Eyes	Thyroid	CASQ1	CollXIII
1	38/F	Caucasian	6	Nil	Scleroderma	Y	NT	2	2	1	Yes	Not performed	Neg/neg	Nil	LT4	350	126
2	58	Caucasian	4	Nil	Premature grey hair	Y	>40	4	5	2	Yes	Not performed	100/neg	Nil	Carb	48	130
3	41	Filipino	5	Nil	Nil	N	NT	2	2	1	Yes	Not performed	Neg/neg	Nil	LT4	194	109
4	47/F	Caucasian	11/2	Nil	Nil	Y	9.2 (+)	4	4	2	Yes	Increased EOM volumes	1600/100	Prednisolone 10 mg	LT4	147	233
5	63/F	Caucasian	6	Nil	Nil	N	>40	4	4	2	Yes	Normal	400/400	Nil	Nil	261	204
6	76/F	Asian	2	Nil	Nil	N	2.9 (pos)	5	3	2	Yes	Increased EOM volumes	Neg/neg	Prednisolone 10 mg/day/Imuran	LT4	NT	NT
7	51/F	Caucasian	3	Celiac disease	Strong history of thyroid autoimmunity in many members of family	Y	?	4	4	2	Yes	Increased EOM volumes	Neg/neg	Prednisolone 5 mg/day/Imuran	LT4	39	1891
8	58/F	Caucasian	3	Sjögren’s disease	Graves’ disease, Graves’ ophthalmopathy	Y	NT	4	3	2	No	Not performed	400/neg	Nil	LT4	15	15
9	64/F	Caucasian	8	Nil	Nil	Y	6.4 (pos)	4	5	2	Yes	Increased EOM volumes	>1600/>1600	Nil at first visit, later selenium 100 μg bds	LT4	90	106
10	50/F	Caucasian	2	Nil	Nil	Y	5.3 (+)	3	2	1	No	Not performed	>25600, 1600	Nil	LT4	496	241
11	30/F	Caucasian	3	Nil	Nil	N	NT	2	2	1	No	Not performed		Nil	LT4	344	175
12	64/F	Caucasian	6	Psoriasis	Graves’ disease	Y	4.3 (pos)	4	5	2	Yes	Not performed	>1000, 91	Nil	LT5	11	110
13	44/M	Caucasian	2	Nil	Nil	N	>40	4	4	2	Yes	Not performed	Neg/neg	Nil	Carb	20	0

Notes:

b thyroid antibodies were measured in a commercial ELISA; CAS, clinical activity score of Mourits et al¹⁷;

c orbital antibodies were measured in a standard ELISA (see methods); positive tests are indicated in bold. A positive test was taken as an OD > the upper limit of normal for 30 healthy males aged <30; namely, 194 for CASQ₁ and 174 for collagen XII;

d NOSPECS classes of Werner¹⁸;;

f nunery types 1 (ophthalmopathy without ocular myopathy) and 2 (with ocular myopathy)¹⁶.

Abbreviations: CAS, clinical activity score of Mourits et al¹⁷; CASQ₁, skeletal muscle calsequestrin; CollXIII, collagen type XIII; EGD, enthyroid graves’ disease; NT, net tested; Tg, thyroglobulin (cut off titer 20); TRAB, TSH-r-binding antibody; TRAb, TSHr antibodies; TPO, thyroid peroxidase (cut off titer 20); UER, upper eyelid retraction.

Table 4 Correlations between parameters of the ophthalmopathy and serum levels of thyroid and orbital antibodies in seven patients with euthyroid Graves’ disease studied prospectively

		Ophthalmopathy			Orbital antibodiesa
		CAS	NOSPECS	Nunery^b	UER	CASQ^Citation1	CollXIII
1	9/05	4	4	2	No	32	36
	11/05	3	4	2	No	127	108
	7/07	3	2	2	Yes	92	97
	3/09	4	1	1	No	276	168
2	2/06	3	4	2	No	186	83
	5/06	4	3	1	No	160	50
	1/07	1	2	1	Yes	74	275
	1/08	1	2	1	Yes	372	1043
	7/08	2	3	1	No	897	1228
3	2/09	4	3	1	No	40	467
4	4/06	3	2	1	No	161	699
	12/06	3	2	1	No	105	203
	9/07	4	2	1	No	38	280
	10/07	3	2	1	No	55	106
	8/08	4	2	1	No	121	200
	10/08	4	2	1	No	153	207
5	6/07	1	4	2	No	32	98
	10/07	1	4	2	No	235	424
	9/10	1	4	2	No	172	942
6	6/09	4	4	2	No	0	163
	9/09	2	3	2	Yes	150	44
7	12/10	2	3	1	Yes	NTf	573

Notes:

a Orbital antibodies were measured in a standard ELISA (see methods); positive tests are indicated in bold. A positive test was taken as an OD > the upper limit of normal for 30 healthy males aged <30; namely, 194 for CASQ₁ and 174 for collagen XII;

c NOSPECS classes of Werner¹⁸;

d nunery types 1 (ophthalmopathy without ocular myopathy) and 2 (with ocular myopathy).¹⁶

Abbreviations: CAS, clinical activity score of Mourits et al¹⁷; CASQ₁, skeletal muscle calsequestrin; CollXII, collagen type XII; UER, upper eyelid retraction; NT, not tested.

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