Hypopituitarism as the presenting feature of bronchogenic carcinoma with metastases to the pituitary gland.

Tumours metastasizing to the pituitary gland are uncommon. Symptomatic patients with pituitary metastases can present with diabetes insipidus, headache, visual field defects and/or anterior pituitary hormonal dysfunction. Treatment options for pituitary metastases include, surgical resection, cranial or parasellar irradiation and/or chemotherapy, and hormonal replacement if indicated. The overall prognosis of pituitary metastases is poor. We present a case of hypopituitarism as the presenting feature of bronchogenic carcinoma with metastases to the pituitary gland.

INTRODUCTION

Tumours metastasizing to the pituitary gland are uncommon and are a rare cause of hypopituitarism. We present a case of an unusual extra-pulmonary manifestation of pituitary metastases from a bronchogenic carcinoma causing hypopituitarism.

CASE REPORT

A 78-year-old male presented with a four month history of general lethargy and one stone weight loss. He had a history of well controlled type 2 diabetes mellitus, hypertension and Barrett's oesophagus. He was an ex-smoker of 50 pack years. On clinical examination he had a blunted affect, grade 2 finger clubbing, a palpable liver edge and appeared unsteady on his feet; visual fields were normal and visual acuity was N5 bilaterally. Initial biochemical investigations, revealed normal renal function and central hypothyroidism fT4 8.3 pmol/L (NR: 9.4-18.6), TSH 0.21 mu/L (NR: 0.3- 4.4). Five months prior to admission, he was biochemically euthyroid fT4 14.0 pmol/L, TSH 1.16 mu/L, on routine testing at his general practitioner. On further questioning, he had no headache, visual disturbance, galactorrhoea or polyuria. The presence of a rapid progression of central hypothyroidism, as well as a sub-optimal short synacthen response [Table 1], prompted gadolinium-enhanced brain and pituitary magnetic resonance imaging (MRI). This revealed cerebral and cerebellar metastases and a sellar mass measuring 9.5 mm in AP dimension [Figures 1a and b], with invasion into the floor of the sella consistent with a pituitary metastatic deposit. Hypopituitarism (secondary hypothyroidism, hypoadrenalism and hypogonadism was confirmed biochemically [Table 1]. The rise in prolactin was attributable to pituitary stalk compression.

Table 1

Anterior pituitary hormonal investigations at presentation

Figure 1

(a) Gadolinium-enhanced brain magnetic resonance imaging (MRI) showing multiple enhancing lesions (white arrows). (b) Gadolinium-enhanced pituitary MRI revealing a mass lesion without evidence of haemorrhage or cystic change, occupying almost all of the pituitary gland (blue arrow), with invasion to the floor of the sella

He was commenced on hydrocortisone 30 mg at 8 am and 10 mg at 5 pm initially, and subsequently levothyroxine 100 mcg was cautiously introduced. As there were no clinical symptoms of hypogonadism, testosterone replacement was not commenced in the initial treatment phase. A computed tomography (CT) scan of chest [Figure 2] revealed a 4.3 Χ 3.3 cm right hilar mass consistent with bronchogenic carcinoma. In addition, features of liver and bilateral adrenal metastases were also present. There was no evidence of diabetes insipidus present possibly attributed to by the low serum cortisol levels, which can mask this condition. His admission was complicated by a brief episode of psychosis attributed to high dose dexamethasone (8 mg bd) for treatment of brain metastases, which resolved upon dose reduction. After discussion with the multidisciplinary team and given the extent of his disseminated disease he was treated with palliative measures. He subsequently died shortly after his admission.

Figure 2

Computed tomography scan of thorax demonstrating a right hilar mass (red arrow)

DISCUSSION

Tumours metastasizing to the pituitary gland are uncommon, accounting for 1-5% of all malignant tumours.[1-3] The majority of pituitary metastases are asymptomatic, as they mostly represent end stage disease and thus before the tumour effects are clinically or biochemically apparent, the patient succumbs to the original cancer. In an autopsy series by Teers et al., only 7% of pituitary metastases were reported to be symptomatic.[4] Most symptomatic patients with pituitary metastases present with diabetes insipidus, headache, visual field defects and/or anterior pituitary hormonal dysfunction.[5-7] Around 70% of pituitary gland metastases originate from breast and lung malignancy.[2] less common sites of origin, include gastrointestinal tract, prostate and kidney.[8-10] In a review by Komninos et al., of 380 patients with pituitary metastases on primary tumour origin, 90 (23.7%) originated from lung cancer,[1112] due to lymphatic or haematogenous spread. In another review of 201 cases of pituitary metastases, Chiang et al., showed that the posterior lobe either alone or combined with the anterior lobe accounted for 84.6% of cases, the anterior lobe alone was involved only in 15.4%.[2] The presence of biochemical anterior pituitary dysfunction as in this case, as a result of destruction of the anterior lobe due to pituitary metastases is relatively uncommon,[13] the presence of biochemical central hypothyroidism as the initial presenting feature of lung cancer from pituitary metastases, is even rarer. Treatment options for pituitary metastases include, surgical resection, cranial or parasellar irradiation and/or chemotherapy, the overall aim of treatment is to focus on the relief of symptoms, and offer hormonal replacement if indicated.[14] In the current case, surgical intervention was not undertaken, as there was no evidence of visual field defect or headache, a further reason for this, is that evidence suggests surgical intervention does not reverse established anterior pituitary dysfunction in pituitary metastases,[15] or improve survival time in comparison to non-surgically treated patients, however in some cases quality of life has been improved after surgery.[7] There is insufficient evidence to demonstrate whether localised sellar or whole cranial radiation confers any additional benefit. The choice to initiate chemotherapy depends on the pre-morbid status of the patient and the extent of the aggressive nature of the primary cancer, however, there is limited data on the use of chemotherapy on the effect of pituitary metastases. Due to the aggressive nature of the advanced cancer, the overall prognosis of pituitary metastases is poor with a mean survival time of 6-7 months.[16]

The rapid onset of central hypothyroidism, and subsequent hypopituitarism, the coexistence of extensive cerebral and cerebellar metastases, as well as radiological inferior extension to the floor of the sella, would indicate in this case, that the sellar mass was attributed to pituitary metastases and not from a pituitary adenoma. In this case, the extra-pulmonary manifestation of central hypothyroidism from pituitary metastases was the initial clue as to the underlying diagnosis of lung cancer in the absence of respiratory symptoms. While pituitary metastases are a rare cause of hypopituitarism the differential diagnosis should be always considered, particularly in patients within the setting of rapid onset of pituitary dysfunction, which should prompt evaluation for pituitary metastases and thus any underlying malignancy.