Lateral cephalometric radiograph examination showed massive mandibular prognathism, prominent supraorbital ridges and an enlarged sella turcica (fig. (fig.4).4). Additionally, magnetic resonance imaging (MRI) scans confirmed the expansively growing tumour mass within and above the sella turcica (fig. (fig.5).5). Furthermore, the entire calvarian bone was thickened, thus confirming the provisional diagnosis of acromegaly. The patient had been referred for examination by an endocrinologist. Diagnosis of a pituitary GH producing macroadenoma was confirmed as well as reactive hyperprolactinaemia and deficiency of the gonadotropin axis. Diabetes mellitus was not found.

Endocrinological examination showed increased levels of the insulin-like growth factor-I (IGF-I) (627.0 ng/ml; norm: 117.0 to 329.2 ng/ml), increased prolactin (63.69 μg/l; norm: 2.10 to 17.7 μg/l) and depressed testosterone levels (0.84 μg/l; norm: 2.41 to 8.30 μg/l). Ultrasonography showed hepatosplenomegaly and an enlarged left kidney. In addition, colonoscopy showed dilatation of the colonic lumen. Ophthalomological screening showed a large bi-temporal visual field defect due to tumour compression of the optic chiasm. The patient underwent trans-sphenoidal surgery with complete tumour resection.

Histological examination showed a highly vascularised pituitary adenoma with a diffuse (solid) growth pattern. Higher magnification showed uniform cells with broad eosinophilic cytoplasm and round to oval nuclei (fig. (fig.6a).6a). The proliferation index was very low with approximately 3% of cells showing immunoreactivity against MiB-1 (fig. (fig.6b).6b). Parts of the tumour cells showed immunopositivity for prolactin in peripheral parts of cytoplasm (fig. (fig.6c).6c). However, no immunoreactivity was present that provided an antibody against the human growth hormone (fig. (fig.6d6d).

Acromegaly is a rare disease with a prevalence of 40 to 70 cases per million people in the population and an annual incidence of 3 to 4 new patients per million [4,5]. Owing to its insidious onset, acromegaly is often diagnosed late (4 to over 10 years after onset) at an average age of about 40 years. The disease affects men and women equally [6,7].

In our patient, the diagnosis of acromegaly was considered because of the patient's manifestations and symptoms at first presentation. Mandibular prognathism is amongst the most commonly found oral manifestations of acromegaly and it was the main reason for the patient to seek orthodontic treatment. Enlargement of the lips and the tongue, such as in our patient, may impair swallowing, chewing and speaking. Frontal bossing, prognathism, macroglossia and an increased size of hands and feet have often been described in the literature as cosmetic changes associated with GH adenomas [2,8-10]. All these changes were present in our patient. Lateral cephalometric radiograph examination of our patient showed massive mandibular prognathism, prominent supraorbital ridges and an enlarged sella turcica. Patients with acromegaly usually exhibit enlargement of all parts of the neurocranium and orofacial bones except the maxilla. The mandible usually shows the biggest enlargement, and the ramus is more affected than the body of the mandible [11,12]. The enlargement of the sella turcica caused by the tumour expansion of the pituitary gland is a striking manifestation that is detectable on lateral cephalometric radiographs in almost every patient with acromegaly [5,11,13]. Other symptoms reported by our patient included fatigue, daytime somnolence and joint pain.

Decreased energy, osteoarthritis and somnolence occur in about 50% of patients [2,9]. Patients also exhibit cardiovascular hypertension, congestive heart failure and impaired glucose metabolism, but these diseases were not present in our patient. Diabetes mellitus, sleep apnea (90%), lumbar stenosis and carpal tunnel syndrome (20%) are other possible manifestations of GH adenomas [1,7,14,15]. In adolescents, GH excess manifests clinically as acromegaly and gigantism if the onset of the disease occurs before the closure of the epiphyseal plates [8,10,16].

Adenomas that grow upwards or expand massively, such as in our patient, may compress the optic chiasm. Such a compression may lead to visual field defects, which begin in the superior temporal sectors and then progress to bitemporal hemianopsia. Persistent compression may lead to blindness. Routine assessment of visual fields and acuity is therefore essential.

Measurement of GH response to glucose load is the standard diagnostic test. An increase in the serum concentration of IGF-I, the main GH dependent growth factor, confirms this diagnosis [2,10]. MRI has emerged as the imaging modality of choice for evaluating pituitary glands [8]. Some adenomas are mixed; mixed GH- and prolactin (PRL)-secreting adenomas occur frequently (25%). Therefore, elevated prolactin levels, such as in our patient, are not unusual.

Available treatment options include surgery, medication and radiotherapy [16]. Trans-sphenoidal surgery is regarded as the first-line treatment of acromegaly [9]. Depending on the tumour size, long-term remission is achieved in 50% [9] to 67% [10,17] of patients, but safe removal of all tumour tissue can be difficult. Microadenomas (less than 10 mm in diameter) are more amenable to cure. Preoperative GH concentration seems to be the best indicator for successful treatment and a permanent reduction of GH and IGF-I [18]. If surgery fails to cure acromegaly, medical treatment with somatostatin analogues is recommended rather than radiotherapy [10]. Regardless of the initial choice of treatment, patients should be followed up indefinitely [2,10,16]. Our patient was treated with trans-sphenoidal surgery, which adequately reduced GH and IGF-I levels up to six months postoperatively.