We present 2 patients with pituitary metastases from thyroid carcinoma—the first from anaplastic thyroid carcinoma and the second from follicular thyroid carcinoma. The first patient, a 50-year-old lady, presented with 2-week history of hoarseness of voice, dysphagia, dyspnoea, and neck swelling. Imaging revealed metastatic thyroid cancer to lymph nodes and bone. Histology from surgery confirmed anaplastic thyroid cancer. She was found to have pituitary metastases postoperatively when she presented with nonvertiginous dizziness. She subsequently underwent radiotherapy and radioiodine treatment but passed away from complications. The second patient, a 65-year-old lady, presented with loss of appetite and weight with increased goitre size and dyspnoea. Surgery was performed in view of compressive symptoms and histology confirmed follicular thyroid carcinoma. Imaging revealed metastases to bone, lung, and pituitary. She also had panhypopituitarism with hyperprolactinemia and diabetes insipidus. She received radioiodine therapy but eventually passed away from complications.
Pituitary metastases are rare. They are found in only 1% of all pituitary resections and only 2% of these are from thyroid carcinoma [
A 50-year-old woman presented with a 2-week history of progressive neck swelling, hoarseness of voice, dyspnoea, and dysphagia. Systemic review was otherwise unremarkable. Physical examination revealed a hard thyroid mass extending from the thyroid cartilage to just above the supraclavicular notch. Initial fine needle aspiration cytology (FNAC) of the thyroid, done at another institution, was suspicious for Hurtle cell carcinoma.
Three months later, she sought a second opinion at our institution. Computed tomography (CT) and F-18-FDG-positron emission tomography (PET) whole body scans (from skull vertex to upper thighs) were done to evaluate the extent of disease and revealed aggressive thyroid carcinoma with metastases to the manubrium and left cervical levels II–IV and supraclavicular lymph nodes (Figures
PET-CT scan showing (a) hypermetabolic enlarged thyroid gland, (b) hypermetabolic left cervical lymph node, and (c) hypermetabolic focus in right side of manubrium (indicated by arrows).
She was discharged but readmitted 26 days after surgery with nonvertiginous dizziness. Magnetic resonance imaging (MRI) of the brain showed enhancing tissue in the left cavernous sinus, left V3 branch of trigeminal nerve, and left sphenoid sinus. There was also involvement of the pituitary gland and erosion of the left lateral aspect of sellar floor. Hormonal profile showed normal pituitary function and no evidence of diabetes insipidus. She was scheduled for 10 fractions of 30 Gy palliative radiotherapy to the base of skull and cavernous sinus metastasis. Her postoperative thyroglobulin level was 704 UG/L (2–70 UG/L), with negative thyroglobulin antibodies.
However, she developed left ptosis and diplopia while undergoing radiotherapy. Physical examination revealed left complete ptosis and incomplete left eye adduction. Repeat MRI imaging of the pituitary gland showed enlargement of the pituitary gland with mildly thickened infundibular stalk and a stable left cavernous sinus mass measuring
MRI brain (T2-weighted, contrast, and coronal) showing (a) pituitary involvement and (b) invasion into left cavernous sinus (indicated by arrows).
She completed the full course of radiotherapy and was also given a single ablative dose of radioactive iodine at 200 mci. The pituitary metastasis was non-iodine-avid. Unfortunately, she showed no improvement in her clinical condition and passed away a few months later.
A 65-year-old woman presented with loss of appetite and weight, increased goitre size, and increased dyspnoea. Systemic review was unremarkable. Physical examination revealed a nodular goitre with retrosternal extension with no associated cervical lymphadenopathy.
CT scan revealed a large L4 vertebral body lytic lesion and an 8 mm pulmonary nodule in the left lung base, suspicious for metastases. She underwent a CT-guided biopsy of the L4 vertebral body lytic lesion which revealed the presence of tumour cells which stained positive for CK7, TTF-1, and thyroglobulin. These findings suggested possible primary pulmonary or thyroid malignancy. FNAC of the thyroid, however, revealed benign follicular cells with focal Hurtle cell changes.
CT scan of the neck was performed to evaluate the degree of airway obstruction and, limited views of the brain, incidentally revealed a pituitary mass. There was asymmetric enlargement of the thyroid with heterogeneous enhancement and areas of calcifications. The left thyroid lobe measures
The pituitary mass was further evaluated by MRI imaging. It measured
Baseline laboratory results showing presence of panhypopituitarism, hyperprolactinemia, and diabetes insipidus.
Blood investigations | Result | Normal reference |
---|---|---|
Random cortisol (10 am) |
|
— |
Free thyroxine |
|
8.8–14.4 |
Thyroid stimulating hormone | 0.846 |
0.65–3.70 |
Follicle stimulating hormone | 1.7 |
1.0–14.0 |
Luteinizing hormone |
|
1.0–24.0 |
Estradiol | 38.4 |
37.0–1284 |
Prolactin |
|
5.0–27.7 |
Growth hormone | 0.3 |
0–28.5 |
Insulin-like growth factor-1 | 84.0 |
80–197 |
Sodium | 147 |
135–145 |
Osmolality | 308 |
275–301 |
Urine osmolality | 112 |
50–1200 |
Given the clinical context of an enlarging goitre with relative rapidity, the likelihood of a thyroid malignancy was deemed more probable than pulmonary malignancy. In view of significant obstructive symptoms, she underwent a total thyroidectomy without bilateral neck dissection and histology revealed a diagnosis of follicular thyroid carcinoma with capsular and vascular invasion of T4N0M1 staging. Test for BRAF mutation was not performed. Her postsurgical thyroglobulin was 11710 UG/L (2–70 UG/L) with a corresponding thyroglobulin antibody of 835 U/mL (0–60 U/mL).
She had progressive blurring of vision and a repeat MRI pituitary scan showed a further enlargement of the pituitary mass, with dimensions of
(a) MRI pituitary (T1-weighted, contrast, and coronal) showing pituitary mass (long arrow) with mass effect on the optic chiasm (short arrow). (b) MRI pituitary (T1-weighted, contrast, and sagittal) showing presence of increased signal intensity in the pituitary mass, representing presence of blood products (long arrow).
She underwent a transsphenoidal resection of the pituitary mass which confirmed the presence of pituitary metastases from the thyroid follicular carcinoma. She subsequently suffered a left femur shaft fracture after a fall requiring internal fixation. Tissue histology from the fracture site revealed thyroid follicular carcinoma. She received 2 doses of radioactive iodine (250 mci each approximately 5 months apart) but unfortunately passed away from intraventricular haemorrhage after the second RAI treatment. The pituitary metastases were iodine-avid and after first RAI thyroglobulin was 27490 UG/L.
Metastatic tumours can involve the pituitary by means of haematogenous spread, direct invasion from skull base metastasis, or meningeal spread through the suprasellar cistern [
Summary of reported cases (including our 2 cases).
Authors | Year | Cell type* | Pituitary complications | Known thyroid primary | Timing from thyroid primary | RAI if known thyroid primary | Other Rx | Other sites of metastases | Age | Sex | Rx | Outcomes |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Johnson and Atkins [ |
1965 | P | Visual field defect |
Yes | 14 years | No | External beam RT | Local recurrence | 56 | F | Roentgen therapy |
Follow-up |
|
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Pelosi et al. [ |
1977 | P | Hypopituitarism |
No | NA | NA | No | No | 32 | M | Transcranial surgery | Death 1 month after presentation |
|
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Sziklas et al. [ |
1985 | P | Hypopituitarism |
Yes | 25 years | No | No | Bone |
44 | M | Transsphenoidal resection |
Death 13 months after due to massive intrathoracic haemorrhage |
|
||||||||||||
Masiukiewicz et al. |
1999 | P | Central hypothyroidism Hypogonadism |
Yes | 5 years | Yes, at diagnosis and repeated doses for recurrence | Repeated surgical clearance | Repeated local recurrence |
56 | M | No surgery |
Progressive lung and bone metastases |
|
||||||||||||
Masiukiewicz et al. (Case 2) [ |
1999 | P | CN III deficit |
Yes | 20 years | Yes, several years after diagnosis without clinical response | Radiosurgery | Local recurrence Bone |
55 | F | Stereotactic radiosurgery |
Death after 7 months |
|
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Bell et al. [ |
2001 | P | Visual field defect |
Yes | 25 years | For pulmonary metastases 8 years after thyroidectomy | Neck RT at diagnosis of thyroid cancer | Lung | 35 | F | Transsphenoidal resection | Follow-up |
|
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Barbaro et al. (Case 2) [ |
2013 (2011) | P | Ophthalmoplegia | Yes | 2 months | Yes | No | No | 65 | F | Surgical intervention |
Follow-up for 2 months |
|
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Trunnell and Marinelli [ |
1949 | F | Visual field defect | Yes | 1 year | No | No | Bone | 42 | F | 2 RAI | Follow-up |
|
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Kistler and Pribram [ |
1975 | F | Visual field defect |
Yes | 9 years | Yes | No | No | 69 | F | Craniotomy but unresectable |
Death |
|
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Ochiai et al. [ |
1992 | F | CN III, CN IV | No | NA | NA | NA | No | 62 | F | Transsphenoidal resection |
Follow-up |
|
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Chrisoulidou et al. [ |
2004 (case 1996) | F | CN III | Yes | 4 years | Yes | External beam RT |
No | 60 | M | Transsphenoidal resection | Follow-up |
|
||||||||||||
Simon et al. [ |
2004 | F | CN III, CN IV |
No | NA | NA | NA | No | 23 | F | Transsphenoidal surgery abandoned RAI | Follow-up |
|
||||||||||||
Yilmazlar et al. [ |
2004 | F | Visual field defect |
Yes | 22 months | Yes | No | No | 43 | F | Transsphenoidal resection |
Follow-up |
|
||||||||||||
Prodam et al. [ |
2010 | F | Visual disturbance |
No | NA | RAI after thyroidectomy after pituitary lesion was found | No | Local lymph nodes |
45 | F | Transsphenoidal surgery |
Follow-up |
|
||||||||||||
Vianello et al. [ |
2011 (case 2001) | F | Visual field deficits |
No | NA | RAI after thyroidectomy after pituitary lesion was found | External beam RT | Lung |
61 | F | Transnasopharyngeal biopsy |
Follow-up for 10 years |
|
||||||||||||
Bhatoe et al. [ |
2008 (case 2001) | M | Visual field defect |
No | NA | NA | NA | No | 36 | M | Craniotomy and subfrontal resection |
Follow-up for 9 months |
|
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Santarpia et al. [ |
2009 (2005) | M | Raised intracranial pressure |
Yes | 15 years | No | No | Local lymph nodes |
23 | F | Transsphenoidal resection | Death 2 months after surgery due to intercurrent infection |
|
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Williams et al. [ |
2008 | M | DI |
Yes | 15 years | No | No | Lung |
23 | F | Transsphenoidal resection | Follow-up |
|
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Bobinski et al. [ |
2009 | M | Apoplexy |
No | NA | NA | NA | No | 46 | F | Craniotomy and tumour debulking | Death |
|
||||||||||||
Conway et al. [ |
2012 | M | DI |
No | NA | NA | NA | Parotid |
61 | M | Craniotomy |
Follow-up for 13 months |
|
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Case 1 | 2011 | A | CN III | Yes | 26 days | Yes | RT | Lymph node |
50 | F | RT |
Death |
|
||||||||||||
Case 2 | 2010 | F | Panhypopituitarism |
No | NA | Yes | NA | Bone |
65 | F | Transsphenoidal surgery |
Death |
From the reported cases, direct invasions from skull base metastasis tend to be associated with large metastasis and are mostly from follicular thyroid carcinoma. In our first case, there was erosion of the sellar floor but it is difficult to ascertain the mode of spread in view of the rapid and aggressive growth of the carcinoma. In our second case, there was selective involvement of the pituitary gland with no evidence of bony involvement or meningeal enhancement; hence haematogenous spread is most likely.
Patients can present with symptoms related to mass effect from parasellar mass enlargement, such as ptosis, blurring of vision, and oculomotor and abducens nerve palsies. Rarer symptoms include diabetes insipidus and hypopituitarism. Our first case presented with oculomotor nerve palsy and preserved pituitary gland function. Our second case presented with panhypopituitarism, diabetes insipidus, and optic neuropathy. In the first case, the initial F-18-FDG-PET/CT scan did not reveal the pituitary metastasis. We postulate two reasons: (i) aggressive cancer (the pituitary metastasis was not present initially but developed quickly over the course of 3 months); (ii) F-18-FDG-PET scan does not pick up pituitary metastasis well [
One other observation is that, in both our cases, the initial thyroid FNAC returned to be falsely reassuring, likely to be due to “sampling error” from the large thyroid mass [
The presence of pituitary metastases could be challenging to manage. If the metastases are large and locally invasive, surgical clearance may be difficult. In view of close proximity to the optic chiasm as well as cranial nerves like oculomotor nerve, trochlear nerve, and abducens nerve, external beam radiotherapy and radiosurgery could be difficult to plan. In patients with poorly differentiated thyroid carcinomas, there is typically poor radioiodine uptake which would reduce the efficacy of radioactive iodine therapy. In patients in whom there is radioactive iodine uptake by the thyroid carcinoma cells, there is also a potential risk of pituitary apoplexy or haemorrhage in view of the acute increase in pituitary volume from acute swelling induced by radioactive iodine [
Despite aggressive therapy, prognosis for patients who have pituitary metastases from thyroid carcinoma is poor. All the patients reported in the literature passed away except one [
The authors declare that there is no conflict of interests regarding the publication of this paper.