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BMJ Case Rep. 2010; 2010: bcr08.2009.2218.
Published online 2010 February 19. doi:  10.1136/bcr.08.2009.2218
PMCID: PMC3028278
Rare disease

Primary hypothyroidism with infiltrative ophthalmopathy and dermopathy


Diffuse toxic goitre, infiltrative ophthalmopathy and dermopathy are well known associations of Graves’ disease. We report the case of a 31-year-old man who had a rare combination of infiltrative ophthalmopathy and infiltrative dermopathy with thyroprivic hypothyroidism due to Hashimoto’s thyroiditis.


Infiltrative ophthalmopathy, dermopathy and hyperthyroidism are the cardinal manifestations of Graves’ disease. Association of infiltrative ophthalmopathy with thyroprivic hypothyroidism is uncommon, while there are only anecdotal case reports describing occurrence of both ophthalmopathy and dermopathy with thyroprivic hypothyroidism.14

Case presentation

A 31-year-old man presented with a history of constipation, cold intolerance, easy fatigability and periorbital puffiness for 6 years. He also had complaints of proptosis of both eyes for the same duration, and thickening and roughness of skin with hyperpigmentation over both lower legs for the last 3 years. He had no family history of any autoimmune disease or autoimmune thyroid disorder. He was a non-smoker.

The patient was evaluated outside earlier and diagnosed as having thyroprivic hypothyroidism: serum total T3 (tri-iodothyronine) 1.45 nmol/l (normal range (NR) 1.2–3.0); total T4 (thyroxine) 47.62 nmol/ (NR 61.8–163.4); and thyroid stimulating hormone (TSH) 43.47 mU/l (NR 0.27 – 4.2). He was started on L-thyroxine 50 μg replacement and he felt some symptomatic improvement, but his proptosis and skin lesions persisted. He was referred to our institute for further management.

On examination, his height was 176 cm, weight 69 kg, pulse rate 80 beat/min, and blood pressure 130/80 mm Hg. He had diffuse firm grade I goitre and pandigital clubbing. He also had periorbital puffiness and bilateral severe proptosis (28 mm both eyes) with clinical activity score of 2/7 (fig 1A). His visual acuity was 6/6 in the right eye and 6/9 in the left eye. The skin over both the lower limbs was hyperpigmented and showed pronounced induration (fig 2A). His deep tendon reflexes were delayed.

Figure 1
(A) Clinical photograph at baseline showing bilateral proptosis; clinical activity score of 2/7. (B) Clinical photograph after 3 months showing decreased proptosis; clinical activity score of 0/7.
Figure 2
(A) Clinical photograph showing skin over both the lower limbs, being hyperpigmented with pronounced induration. (B) Clinical photograph showing improvement in demopathy over both the lower limbs.


On investigation, total T3 was 1.43 nmol/l; total T4 66.0 nmol/l; TSH 57.43 mU/l; anti-TPO (thyroid peroxisomal) antibodies 600 IU/ml (NR <34); and cortisol at 08.00 h was 392 nmol/l (NR 171–536). The patient’s renal function and lipid profile were within normal range. Ultrasonography confirmed an enlarged isthmus while both lobes were normal. Computed tomography (CT) of the orbit revealed an enlarged medial rectus muscle (fig 3). Biopsy from the shin skin lesion showed deposition of myxoedematous material in the upper dermis and atrophy of the appendages in the deeper dermis consistent with pretibial myxoedema.

Figure 3
Computed tomography of the orbit showing enlarged medial rectus muscle.


The patient was treated with L-thyroxine 125 μg once a day, methylcellulose eye drops and dark goggles for ophthalmopathy, and local steroid application over the skin lesion. He was advised to follow-up after 3 months.

Outcome and follow-up

On follow-up after 3 months the patient’s visual acuity had improved to 6/6 in both eyes, his clinical activity score decreased to 0/7 with a modest decrease in proptosis (27 mm right side and 26 mm left side, fig 1B). His skin lesions improved remarkably (fig 2B).


Graves’ disease is characterised by diffuse toxic goitre, infiltrative ophthalmopathy and dermopathy.4 All these cardinal features may exist at one time and may precede or follow or may not occur during the lifetime. Out of these three cardinal manifestations at least two should be there to substantiate the diagnosis of Graves’ disease on clinical grounds, unless it is corroborated with estimation of TSH receptor stimulating antibodies.4 Clinically, the prevalence of thyroid associated ophthalmopathy is around 40–50%, whereas dermopathy ranges from 3–5% in association with Graves’ disease.5 Uncommonly, Hashimoto’s thyroiditis can also be associated with infiltrative ophthalmopathy in 3–5% of cases and rarely with dermopathy as well.14

With the availability of better techniques, the TSH receptor stimulating as well as blocking immunoglobulins have been demonstrated in autoimmune thyroid disorders,6,7 and the clinical state depends upon the predominance of either of these. TSH receptors are distributed not only on thyroid follicular cells but also on orbital and dermal fibroblasts, therefore these thyroid stimulating immunoglobulins act on these extra-thyroidal receptors, and produce the manifestations—namely, infiltrative ophthalmopathy and dermopathy.6 In patients with Graves’ disease the above said three cardinal manifestations can easily be explained by the presence of TSH receptor stimulating antibodies. But all these manifestations are usually not present together, possibly because TSH receptor density may be variable at different sites or TSH receptor blocking antibodies might be interfering with its actions at those sites.

Hashimoto’s thyroiditis as corroborated by high TPO antibody titre in our patient suggests that ongoing autoimmune destruction was responsible for his hypothyroid state. Autoimmune thyroprivic hypothyroidism is usually not associated with thyroid associated ophthalmopathy or dermopathy, despite increased concentrations of TSH which may act on TSH receptors present on ocular or dermal fibroblasts similar to thyroid stimulating immunoglobulins (TSI). The probable reasons are that autoimmunity in Hashimoto’s thyroiditis is confined to thyroid gland only and/or thyroid stimulating immunoglobulins possibly act on some other orbital or dermal antigens other than TSH receptors. A limitation of our case study is the lack of measurement of TSH receptor antibodies, and therefore these remain as postulations.

Therefore, these two infiltrative complications occurring in the above case can possibly be explained by the complex interplay between TSH receptor stimulating and blocking immunoglobulins.

Learning points

  • Infiltrative ophthalmopathy and dermopathy with hyperthyroidism are the cardinal manifestations of Graves’ disease.
  • Rarely, infiltrative ophthalmopathy and dermopathy may occur with hypothyroidism due to Hashimoto’s thyroiditis.


Competing interests: None.

Patient consent: Patient/guardian consent was obtained for publication.


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