CASE OF THE WEEK – "Unilateral Graves' disease (GD) is a rare disease variant (case reports)" by Dr. Shekhar Shikare, Consultant, Nuclear Medicine at NMC Royal Hospital Sharjah

CASE OF THE WEEK – "Unilateral Graves' disease (GD) is a rare disease variant (case reports)" by Dr. Shekhar Shikare, Consultant, Nuclear Medicine at NMC Royal Hospital Sharjah

Introduction

Graves’ disease (GD) is an autoimmune disorder involving thyroid gland. It is believed that Graves’ disease occurs due to circulating autoantibodies directed against thyroid‑stimulating hormone (TSH) receptors on the thyroid gland, thus producing the stimulatory effects of TSH. The thyroid gland is generally enlarged or sometimes of the same size in Graves’ disease. Patients usually present with symptoms of hyperthyroidism such as weight loss, palpitations, sweating, and hyper defecation. On a 99mTc pertechnetate thyroid scan, the thyroid gland generally appears diffusely enlarged with homogenously increased radiotracer concentration. A symptomatic patient with elevated thyroid profile and increased uptake on 99mTc pertechnetate thyroid scan is usually considered diagnostic for Graves’ disease. Unilateral increased tracer uptakes on a Thyroid scan in a patient with Graves’ disease is a rare entity with less documented cases. It is a condition wherein the patient presents with typical Graves’ symptoms, sometimes with features of Graves’ ophthalmopathy and elevated thyroid hormones but radiotracer concentration being observed only in one lobe of the thyroid gland

Differential diagnosis of unilateral GD includes other disease states presenting with unilateral involvement on thyroid scan like thyroid hemi agenesis, Hashimoto disease, toxic adenoma, toxic multinodular goiter and subacute thyroiditis. Thyroid hemi agenesis can be ruled out with high resolution ultrasonography. Thyrotoxicosis of Hashimoto disease depends on destruction of thyroid tissue which causes decreased uptake on thyroid scan. Toxic adenoma was ruled out since ultrasonography which is the gold standard technique for detection of thyroid nodules & reveals no nodules. Unilateral subacute thyroiditis of the thyroid gland has a clinical presentation with fever, generally tender thyroid gland on examination and elevated acute phase reactants on laboratory examination and the affected lobe is found to be suppressed on thyroid scan.

Case 1

36 years old lady with history of myalgia, fatigue and tirdness of short duration.

Biochemcial parameters

FT3 8.63 ( 2.63-5.70), FT4 17.92 ( 9.0-19.0), TSH <0.0300 ( .3500-4.94). TSH receptors antibody 1.14 IU/L ( <1.75), Anti thyroglubulin and anti thyroid peroxidae antibodies- Not elevated.

ALT 14 (0-55), Sr Creatinine 53.4 ( 50.4-981), FBS 5.45( 3.89-5.60), Full blood count-wnl, USG thyroid. The right lobe of the thyroid measure 4.2 cc and left lobe 2.9 cc in volume. The right lobe shows a central ill defind hypoechoic area inkeeping with low level of thyroiditis. No true nodule is seen. On the left side, there is colloid cyst in the upper pole measuring 9*13 mm.

Impression- Thyroid gland shows features of low level of thyroiditis with a hypoechoic area on the right side and a simple colloid cyst on the left side.

99mTechnetium Pertechnetate Thyroid Scan Right lobe shows uniformly increased tracer uptakes, while left lobe uptakes are decreased.

Tc-uptakes (0.4% to 3.0%)
5.2% (right lobe 4.4% and left lobe 0.9% uptakes).

IN VIEW OF LOW TSH VALUES & THE SCAN FINDINGS, IT FAVORS RIGHT LOBE hyperthyroidism WITH PARTIAL SUPPRESSION OF THE UPTAKES IN the left lobe of thyroid gland.


Figure 1,2,3 Right lobe shows uniformly increased tracer uptakes, while left lobe uptakes are decreased.

Case 2

62 years old lady with history of papitations since last 2-3 months.

Biochemcial parameters

FT3 2.13 pg/ml ( 1.88-3.18), FT4 0.89 ( 0.7-1.48), TSH <0.08 miU/L (35-4.94). TSH receptors antibody <0.80 IU/L (<1.75), Anti thyroglubulin 5.61 IU/ml (<4.11), CRP <1.0mg/L ( 0-5), ESR 14 mm/Hr ( 0-20), Sr Uric acid 7.7 mg/dL (2.4-5.7), Total cholestrol 231 mg/dL (0-200) Vid D ( 25-OH0 43.6 ng/ml ( 30-100)

USG thyroid

Both the lobes and isthmus are decreased in size with overall coarse and heterogeneous echotexture showing numerous bilateral pseudonodular areas with moderate diffsue hypervascularity.

Impression- Picture of autoimmune thyroiditis.

99mTechnetium Pertechnetate Thyroid Scan

Right lobe shows increased tracer uptakes, while left lobe uptakes are decreased.

Tc-uptakes (0.4% to 3.0%)
0.7% (right lobe 0.5% and left lobe 0.2% uptakes).

IN VIEW OF LOW TSH VALUES & THE SCAN FINDINGS, IT FAVORS RIGHT LOBE hyperthyroidism WITH PARTIAL SUPPRESSION OF THE UPTAKES IN the left lobe of thyroid gland.


Figure 1,2,3 Right lobe shows mildly patchy but relatively increased tracer uptakes, while left lobe uptakes are decreased.

Discussion

One of the most common causes of hyperthyroidism is Graves’ disease, an autoimmune process in which the patient’s immune cells make antibodies against the thyroid stimulating hormone (TSH) receptor on the thyroid gland cells. These autoantibodies stimulate the thyroid to grow, resulting in a diffuse enlargement (goiter), and to produce excessive amounts of thyroid hormone, resulting in hyperthyroidism.

Although TSH receptor antibodies (TRAb) are detected in most patients with Graves’ disease. Some authors have described milder disease phenotypes in TRAb-negative patients including milder degrees of hyperthyroidism, smaller goiters, and varying levels of tracer uptakes than the patients with classic disease. The cause of TRAb negativity in such individuals is unclear, but it has been suggested that antibody-negative individuals may harbor intrathyroidal TRAbs, which do not spill into the circulation initially.

A small number of the patients may have a mutation of the TSH receptor resulting in the receptor being chronically turned on causing diffuse enlargement of the thyroid and clinical or subclinical hyperthyroidism. This would resemble the clinical and biochemical findings with Graves’ disease but without the antibodies. Screening of family members of these patients can identify additional patients with the mutations and will have subclinical or overt hyperthyroidism, while the other family members without the mutation had normal thyroid function.

Patients with the mutations did not have a spontaneous remission of the hyperthyroidism with or without antithyroid drugs, unlike some patients with Graves’ disease who may go into remission either spontaneously or after a course of antithyroid drug treatment. Nevertheless, the standard therapies of antithyroid drugs, radioactive iodine, or surgery can be used in these patients irrespective of the cause.

The involvement of only one lobe of the thyroid gland could not be explained by the diffuse autoimmune pathology of Graves’ disease.

The possible explanations for unilateral Graves’ disease could be as follows: Thyroid lobe is derived from different lobes of precursor cells. Each lobe appears to have differential sensitivity to TSH stimulation, as evident from the development of multinodular goiter in longstanding cases of nontoxic goiter. It seems that the clonal heterogeneity exists a priori, i.e., even before any pathology exists in the thyroid gland. This clonal heterogeneity possibly extends to involve three aspects. a. Differential expression of antigens triggers T‑cell responses. In Graves’ disease, most of the autoimmune response is due to locally infiltrating B‑lymphocytes, accumulating in the adjacent interstitium, as evident by the massive decline in anti‑TSH antibody levels after surgery. The local infiltration of B‑cells is stimulated by a prior T‑cell‑mediated mechanism that is based on recognition of T‑cell antigen by the CD4 T‑helper cells. Interestingly, the T‑cell recognizes a primary sequence of 10–14 amino acid sequences on the antigen as a stimulating. Differential expression and function of iodine uptake mechanism like Na/I symporter c. Differences in growth and activity in response to TSH receptor stimulation as seen in different parts of a well‑established multinodular goiter.

Conclusion

The incidence of unilateral Graves’ disease among all the patients with Graves’ disease may be minimal and most of the times may not alter the management of the patients. However, the reason for such condition to occur has to be evaluated, and it questions the established autoimmune pathology of the disease.

References

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