Thyroid Scan Conundrum in a Rare Case of McCune–Albright Syndrome

Introduction

McCune–Albright syndrome (MAS) is a rare disorder that presents with polyostotic fibrous dysplasia and multiple hyperfunctioning endocrinopathies. It is caused by an activating postzygotic somatic mutation of the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) gene* (Gsaplha).[1] (*GNAS-gene is located on chromosome 20 [20q13.30]).

Patients need to undergo thorough screening and imaging for diagnosis of all involved organs. ^99mTc bone scintigraphy with complementary anatomical imaging is required for the exact delineation of all involved bones in polyostotic fibrous dysplasia. The association of both hyperthyroidism and thyroid adenoma is well known with this entity, ^99mTcO^4-thyroid scintigraphy can help in differentiating diffuse toxic goiter from an autonomously functioning thyroid nodule (AFTN).

Case Report

A 15-year-old female presented with complaints of irregular cycles for 1 year with first episode of vaginal bleeding at 5 years of age. The uterus and ovaries were found to be normal on ultrasonography (USG). On further evaluation, she was diagnosed with hyperthyroidism, FT3 - 9.51 pg/mL (N: 2.30–4.20), FT4 - 2.38 ng/dL (N: 0.89–1.76), thyroid-stimulating hormone (TSH) - <0.01 uIU/mL (N: 0.35–5.5) and was started on oral carbimazole 5 mg which was subsequently increased to 15 mg. After taking medication for 18 months, her cycles were still irregular. She was further evaluated for serum prolactin which was markedly elevated (1800 ng/mL). She underwent magnetic resonance imaging brain which was suggestive of prolactinoma [Figure 1]. She was started on oral cabergoline 0.25 mg weekly after which her cycles became regular. After 2 years, she noticed swelling in her right cheek and right eye region which was progressive in size. Due to underlying precocious puberty, hyperthyroidism, and prolactinoma, clinical suspicion of MAS was raised with the possibility of fibrous dysplasia. CT scan head and neck showed a ground-glass matrix with loss of normal trabecular pattern predominantly in the skull and maxillo-facial bones on the right side, typical of fibrous dysplasia [Figure 2]. Bone scan (^99mTc-MDP) revealed increased tracer activity in skull, facial bones (predominantly on right), mandible, few bilateral ribs, and visualized appendicular skeleton consistent with polyostotic fibrous dysplasia with classical pirate sign [Figure 3]. She was started on parenteral zoledronic acid.

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Figure 1 Magnetic resonance imaging brain showing macroadenoma likely consistent with fibrous dysplasia

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Figure 2 (a) Patient showing right cheek swelling. (b-d) Computed tomography head and neck showing ground-glassing and few lytic lesions in right maxilla-facial bones and right hemimandible

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Figure 3 ^99mTc-MDP scintigraphy revealed increased tracer activity in skull, facial bones (predominantly on right), mandible, few bilateral ribs, and visualized appendicular skeleton consistent with classical pirate sign consistent with polyostotic fibrous dysplasia

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With a clinical diagnosis of MAS, she underwent a complete hormonal profile to rule out other endocrinopathies. Her hormonal profile revealed normal prolactin (10 ng/mL) and was subclinical hyperthyroid, TSH - 0.03 uIU/mL (N: 0.27–4.20), FT3 - 3.6 pg/mL (N: 2.0–4.4), and FT4 - 176 ng/dL (N: 80–200) on tablet carbimazole 5 mg OD. She was referred to the nuclear medicine department for radioiodine ablation since she was taking carbimazole for 5 years. On examination, a nodule was palpable on the right lobe of the thyroid. USG neck revealed a iso to hyperechoic solid nodule measuring ~1.2 cm × 1.8 cm in the upper pole of right lobe of thyroid with smooth margins and no abnormal echogenic focus-TIRADS – 3 lesion with an atrophic left lobe [Figure 4]. The patient underwent a ^99mTc-pertechnetate thyroid scan [Figure 5] which showed increased tracer uptake in the right lobe of the thyroid with absent uptake in left lobe region and suppressed uptake in salivary glands. This left us with possible differentials of Lobar Graves’ versus Marine-Lenhart syndrome versus AFTN. Thus, the patient underwent additional single-photon emission computed tomography/computed tomography (SPECT/CT) to localize the uptake. On SPECT/CT increased, tracer avidity was noted in the upper pole of right lobe corresponding to the nodule with decreased uptake in the rest of the right lobe and background suggesting an AFTN. She was treated with 15 mCi of oral ¹³¹I.

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Figure 4 Ultrasonography neck reveals TIRADS-3 nodule in right lobe of thyroid with atrophic left lobe

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Figure 5 (a and b) ^99mTc-pertechnetate thyroid scan (planar imaging) revealed increased tracer uptake in right lobe of thyroid. (c and d) On fused SPECT/CT and CT images show increased tracer uptake in nodule in right lobe of thyroid with suppressed uptake in rest of right lobe

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Discussion

MAS is a rare noninherited disorder that requires a thorough clinical, endocrinological, and radiological evaluation. It causes a variety of manifestations at different time points, hence, long-term follow-up is essential.[2] Our patient had history of vaginal bleeding with first episode at 5 years of age consistent with precocious puberty, which was not evaluated further. Hence, vaginal bleeding in prepubertal girl should always prompt evaluation with endocrinologist.[3]

Fibrous dysplasia has been reported to be found in the majority of patients with MAS with the majority involving multiple bones. It is mostly diagnosed on X-ray and can result in bone deformity and bone fracture. Hence, it is essential to know all sites of involvement in which bone scan plays an important role.[4] The case presented here shows deformity in the right cheek region, with a bone scan showing involvement of multiple bones consistent with polyostotic fibrous dysplasia. The craniofacial region is the most commonly involved region, can result in facial asymmetry of deformity.[5] Fibrous dysplasia involving the sphenoid bone has been described as the pirate sign which is also present in our case.[67]

Studies have shown an association of hyperthyroidism with MAS with incidence of nearly 40%.[8] There is activation of the TSH/G-protein/cAMP pathway due to presence of Gsaplha mutation, resulting in hyperfunction. On USG, usually a mixture of cystic and some solid lesions are present.[9] In our case, on thyroid USG patient had TIRADS 3 nodule with low suspicion of malignancy and an atrophic left lobe. On thyroid scintigraphy, there was a challenge whether it was a diffuse toxic goiter of right lobe in the background of absent left lobe or autonomous functioning nodule which was unclear in planar imaging. Hence, the patient underwent additional SPECT/CT which showed tracer avidity in nodule with absence of uptake in rest of the right lobe making conclusive diagnosis of AFTN. Hence, although routinely SPECT/CT is not used in thyroid scintigraphy, it should be utilized in challenging cases. Hyperthyroidism responds well to antithyroidal drugs but spontaneous resolution is unlikely to occur. Since thyroid hormone excess can cause deleterious effect on fibrous dysplasia including higher risk of long-bone fractures, these patients need to undergo definite treatment. Therefore, surgical or medical ablation is usually required.[10111213]

Conclusion

MAS has a wide spectrum of manifestations with imaging playing an important role in diagnosis. Although routine planar ^99mTc-pertechnate imaging is sufficient for diagnosing diffuse toxic goiter or AFTN, in our case, the incremental role of SPECT/CT is noted.