British Journal of Radiology (2006) 79, 84-86
© 2006 British Institute of Radiology
doi: 10.1259/bjr/23776068
A deformed skull with enlarging hand and feet in a young female
B Guglani, MD1,
C J Das, MD, DNB1,
A Seith, MD1,
N Tandon, DM2 and
B A Loway, MD2
1 Radiodiagnosis and 2 Department of Endocrinology, All India Institute of Medical Sciences, New Dehli, India
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Introduction
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A 25-year-old woman presented with a 6 year history of gradually enlarging swelling at the back of her head. She had also noticed enlarging hands and feet with increased prominence of eyes for the last 3–4 years. She had been amenorrhoeic for the past 2 years. On physical examination, her height was 163 cm. There was facial deformity with a prominent right side of the face and bony swelling in the region of the external occipital protuberance. Her hands and feet were enlarged with a doughy consistency. In addition, mild scoliosis was found in the mid-thoracic region with convexity towards the right side. The left humerus was short and bowed and the left rib cage was deformed with multiple swellings. There was no evidence of abnormal skin pigmentation. Her thyroid was mildly enlarged. Galactorrhoea was also observed. Visual field examination revealed bitemporal hemianopsia on perimetry. Endocrine evaluation showed a non-suppressible growth hormone level (GH) of 60 ng ml–1 and an increased prolactin level of 43 µg l–1. Plain radiography of the skull was obtained (Figure 1
). Subsequently, contrast enhanced MRI (CEMRI) of the sella was performed (Figure 2). What is the diagnosis in this case?
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Discussion
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The diagnosis of acromegaly was clinically and biochemically unequivocal in this case. Subsequently, we performed contrast enhanced MRI (CEMRI) of the sella for evaluation of the patient's acromegaly. A T1 weighted image of the sella revealed a large sellar, suprasellar mass compressing the optic chiasm and causing expansion of the sella. The mass showed enhancement in post-contrast imaging suggestive of a pituitary macroadenoma, thus confirming the clinical diagnosis of acromegaly. Marked, diffuse expansion of the skull base was also noted enhancing on contrast administration (Figure 2
).
The patient sought medical advice primarily for her marked skull expansion seen in the occipital region, which had increased gradually over the last 6 years. Plain radiography of the skull showed gross expansion of the skull base and occiput with areas of sclerosis and ground glass density. Enlarged maxillary and frontal sinuses were also seen. A CT performed for detailing of the foraminal compression in the skull base showed the typical ground-glass appearance of fibrous dysplasia (Figure 3). Narrowing of the bilateral optic canal and orbital apices were also seen. A subsequent skeletal survey revealed that the involvement was indeed multifocal with expansile lesions seen in the ribs, left humerus and radius (Figure 4). All of these features pointed to a pathology in addition to acromegaly due to a GH secreting pituitary adenoma. Based on the radiological appearance of the ground glass density and their characteristic distribution, a differential diagnosis of coexisting fibrous dysplasia was made. As both of these conditions are associated in only one genetic abnormality, a final diagnosis of McCune-Albright syndrome – polyostotic fibrous dysplasia with acromegaly due to pituitary macroadenoma – was made.
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Figure 3. Axial CT image (bone-window) showing ground-glass expansion of skull base with narrowed basal foramina, bilateral optic canal and orbital apices.
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The McCune-Albright syndrome (MCAS) is a sporadic disorder characterized by polyostotic fibrous dysplasia, cutaneous pigmentation and endocrine hyperfunction. The presence of any two of the three lesions (skin, bone and endocrine glands) is sufficient for the diagnosis of MCAS [1]. The genetic basis of MCAS is now reasonably understood and is due to the post-zygotic activating mutations of arginine 201 in the guanine-nucleotide-binding protein (G protein) alpha-subunit (Gsalpha), leading to a mosaic distribution of cells bearing constitutively active adenylate cyclase [2]. The resultant disorder depends on when the mutation occurs; during embryonic development or post-natal life. The earlier it takes place, the more cells are affected. Somatic mutations in a small cell mass result in MCAS; whereas in a larger cell mass, mutation results in polyostotic fibrous dysplasia [3]. The distribution of affected cells follows embryological lines of ectodermal migration, which explains the unilateral and focal expression of MCAS in bones as well as in endocrine tissue.
Various endocrinopathies reported in MCAS include precocious puberty, thyrotoxicosis, Cushing's syndrome, acromegaly, hyperprolactinaemia and hypophosphataemic rickets [4, 5]. The association of polyostotic fibrous dysplasia and acromegaly, although rare, is a well described entity [5]. In MCAS, gigantism/acromegaly usually present at an earlier age (less than 30 years) than in classical acromegaly [6–8]. A pituitary adenoma may be found less often than in classical acromegaly [5, 8]. Moreover, the macroadenomas in MCAS are smaller than those in classical acromegaly [5, 8].
The association of acromegaly and fibrous dysplasia may pose a diagnostic challenge to the clinician and the radiologist. The majority of patients with MCAS are short in stature because of precocious puberty, recurrent fractures and hypophosphataemic rickets, whereas those with associated GH excess/acromegaly usually reach a normal height [5, 9]. Also, since fibrous dysplasia has a predilection for skull base involvement, the facial dysmorphism may mask the usual features of acromegaly causing delay in diagnosis.
CT and MRI play a pivotal role in the evaluation of these patients. MRI is better than CT in assessment of sella in the presence of bony skull base thickening due to fibrous dysplasia. The distinction between pituitary gland and abnormal fibrous bone tissue at skull base is better made on MRI. The combination of pre- and post-contrast images is useful in this regard. However, CT of skull base plays a useful role in some cases for detailing neural foraminal compression, especially if surgery is being contemplated [10].
Craniofacial fibrous dysplasia may mimic hyperostotic meningioma (meningioma en plaque) or even osteoma, especially in a monostotic lesion [9]. Association of acromegaly and meningioma has also been described [12, 13].
MCAS with acromegaly and skull base fibrous dysplasia is also a therapeutic challenge as transpituitary surgery is often not possible in the presence of fibrous dysplasia of skull base whereas radiation therapy can induce bone sarcomatous transformation [14]. Some authors have suggested a transfrontal route to approach the pituitary adenoma [15]. In a series by Akintoye et al, the authors described a distinct clinical phenotype of MCAS due to GH excess which is characterized by inappropriately normal stature, thyroid releasing hormone (TRH) responsiveness, prolactin cosecretion, small or absent pituitary tumours, a consistent but inadequate response to treatment with cabergoline and an intermediate response to long acting octreotide [5]. In our patient too, the medical treatment was chosen because surgery was not possible due to the fibrous dysplasia of the skull base and radiotherapy would increase the risk of sarcomatous transformation. The patient received octreotide LAR 40 mg (intramuscular) monthly. The plasma growth hormone levels (post-oral glucose) decreased from an initial 60 ng ml–1 to 23 ng ml–1 1 month after first injection.
In conclusion, the association of acromegaly with MCAS may pose a diagnostic and therapeutic challenge. MRI is vital in the evaluation of such patients for the delineation of the pituitary adenoma separate from the skull base abnormality. CT is a useful adjunct pre-operatively to delineate the foraminal compression.
Received for publication February 25, 2005.
Revision received April 22, 2005.
Accepted for publication May 31, 2005.
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References
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Introduction
Discussion
