Papillary Thyroid Cancer With Pituitary Gland Metastasis: A Unique Encounter

The pituitary gland is a rare metastatic site, and thyroid cancer (TC) metastasis to the pituitary gland is immensely uncommon. We report the case of a 45-year-old male in whom pituitary metastasis (PM) discovery during the immediate postoperative period complicated the management of papillary thyroid cancer (PTC). His postoperative magnetic resonance imaging (MRI) of the pituitary lesion showed a progression in size with persistent optic nerve compression. The critical location of the pituitary lesion and the rapid progression dictated the treatment course. The pituitary lesion was non-iodine avid, and thus we opted for external beam radiation therapy (EBRT). He received 1,200 centigray (cGy) with Gamma knife radiosurgery with steroid cover. In our case, the aggressive histological and clinical variant of PTC consisted of multiple metastatic sites involving large volume pulmonary, skeletal, and chest wall lesions coupled with crucial macro metastatic pituitary mass. The patient was offered radioactive iodine to treat other iodine avid metastases in the lungs and bones and was also offered EBRT to target skeletal lesions. Systemic treatment with tyrosine kinase inhibitor was also discussed with the patient. Our case encourages clinicians to exercise vigilance and a high index of suspicion for PM when a patient with any pre-existing cancer presents with visual disturbance, cranial nerve deficit, or symptoms suggestive of hormonal deficiency. It also highlights the importance of involving endocrinologists before performing any surgery on the endocrine organs to ascertain the integrity of the endocrine function of the glands.


Introduction
The pituitary gland is a rare metastatic site, representing only 1% of all patients operated on sellar or parasellar lesions [1]. The posterior lobe of the pituitary gland is involved in approximately 85% of the cases, making central diabetes insipidus (DI) the most common presentation. The anterior lobe alone is involved in a minority of the cases affecting nearly 15 % of the patients [1,2]. This predilection for the metastasis into the posterior pituitary could be related to the direct blood supply it receives from the hypophyseal arteries and its large contact area with the adjacent dura [3].
Pituitary metastasis (PM) often originates from primary lung and breast cancers. Thyroid cancer (TC) accounts for 2% of all PMs [1]. However, metastasis to the pituitary gland is immensely uncommon. TC complicated by PM carries a poor prognosis and constitutes a diagnostic and therapeutic challenge.
We report the case of a 45-year-old male in whom the discovery of PM during the immediate postoperative period complicated the management of papillary thyroid cancer (PTC).

Case Presentation
A 45-year-old male presented to the surgical clinic with a one-month history of neck swelling, weight loss, palpitations, and loss of appetite. He was healthy before this presentation and had no head and neck radiation exposure history. He did not suffer from COVID-19 infection. There was no history of TC within the family. A physical examination of the neck revealed a hugely enlarged right lobe of the thyroid gland.
Biochemical workup showed a low free thyroxine (FT4) level of 10.4 pmol/L with an inappropriately low thyroid-stimulating hormone (TSH) level of 0.008 mU/L. The neck ultrasound (US) scan confirmed a suspicious nodule measuring 6 x 4 cm on the right lobe of the thyroid gland, along with multiple enlarged lymph nodes in the neck. The nodule's fine needle aspiration cytology was suspicious of malignancy.
He underwent total thyroidectomy and bilateral neck dissection. Histopathology showed a 5-cm solid pattern PTC in the right lobe of the thyroid gland with focal columnar cell features, extensive lymphovascular invasion including venous invasion, involvement of margins, and multiple lymph nodes with metastasis. The most significant focus of the tumor in the lymph node was 3.7 cm without extranodal 1, 2 1 1 extension. Based on the histopathology and the subsequent radiological evidence, his disease was classed as stage II and T3a(s)N1bM1 (tumor, node, metastasis) according to the 8th edition of the American Joint Committee on Cancer classification ( Figure 1) [4].

PTC, papillary thyroid carcinoma
Postoperatively, he developed euvolemic hyponatremia. At this stage, the surgical team involved endocrinologists. Upon further questioning, he gave a history suggestive of hypogonadism, headaches, and blurred vision. Biochemical evaluation, including a short Synacthen test, suggested panhypopituitarism and mild hyperprolactinemia ( Table 1).  Visual field assessment confirmed bitemporal hemianopia ( Figure 2).    We initiated hormonal replacement, including glucocorticoids, followed by levothyroxine. After starting steroid replacement, the patient developed clinically and biochemically proven central DI treated with desmopressin ( Table 1). The differential diagnosis at that stage included an atypical pituitary macro adenoma versus a metastatic lesion in the pituitary gland, given the aggressive disease behavior and the atypical presentation.  The critical location of the pituitary lesion and the rapid progression dictated the treatment course. The patient had been deemed a case of high surgical risk due to a highly vascular and friable tumor. The pituitary lesion was non-iodine avid (Figure 4), and thus we opted for external beam radiation therapy (EBRT), a more favorable option over radioactive iodine (RAI). He received 1,200 centigray (cGy) with Gamma knife radiosurgery with steroid cover.

Labs
In our case, the aggressive histological and clinical variant of PTC consisted of multiple metastatic sites involving large volume pulmonary, skeletal, and chest wall lesions coupled with crucial macro metastatic pituitary mass that had threatened vision with the possibility of life-threatening pituitary apoplexy. We offered him RAI to treat other iodine avid metastases in the lungs and bones and also offered EBRT to target skeletal lesions. We discussed using systemic treatment with tyrosine kinase inhibitor. Despite multiple meetings with the patient and counseling him about the disease course and the treatment options, he refused further treatment and did not return for further care.

Discussion
PM occurs through the hematogenous spread, direct invasion from skull base metastasis, or meningeal spread through the suprasellar cistern [5]. The hematogenous route is not a typical route for dissemination of PTC, and tumors with a marked tendency toward hematogenous metastasis, such as follicular TC and PTC with extensive vascular invasion, have been reported to cause PM [6]. The lack of bony skull involvement, extensive vascular invasion, and diffuse systemic metastasis suggest that the hematogenous route was our case's predominant course of spread.
PM from TC can present in a very variable period. The presentation of PM can pre-date the diagnosis of TC. Barbaro et al. described one of their patients who presented with neurological manifestations from a sellar tumor [6]. The patient underwent surgical resection, and the pathology showed metastasis from the previously undiagnosed TC. The PM can present from a few months [6] to decades [7] after the diagnosis of TC and total thyroidectomy. In some cases, the diagnosis of TC and PM can present simultaneously, like in our case.
The manifestation of PM can be variable. Some patients present only with pressure symptoms such as optic nerve compression and cranial nerve deficit without the hormonal disorder [6], while some present just with hormonal insufficiency [8]. Our patient experienced both the pressure symptoms, such as bitemporal hemianopia and panhypopituitarism. Pituitary involvement was suspected early on in our case, given the inappropriately low TSH in the face of low FT4 levels, hyponatremia, and other symptoms of pituitary hormonal deficiency.
Radiological features are neither sensitive nor specific to differentiate an incidental pituitary adenoma from the PM. A dumbbell-shaped intrasellar and suprasellar tumor, like the one seen in our case, with a clear indentation at the level of the diaphragma sellae indicates the rapid growth of the lesion and, if present, is indicative of early stages of PM. This feature, in addition to the iso-intensity of the lesion on the T1weighted image, thickened pituitary stalk, and homogenous enhancement after gadolinium contrast, supported PM diagnosis [1].
Our patient had central hypothyroidism due to PM. Therefore, we did not use the traditional method of levothyroxine withdrawal to achieve the required elevated TSH levels before performing the diagnostic I-123 whole-body scan. We used rTSH, which is not licensed for use in patients with metastatic PTC. However, the American Thyroid Association has endorsed its use in patients with pituitary disease (recommendation 75) [9].
In line with the ATA recommendations, we prioritized the treatment of central nervous system metastasis with surgery and radiotherapy before considering the usual therapeutic approach, which involves radioiodine ablation of the systemic metastasis [9].

Conclusions
The pituitary gland is a rare site for metastasis in PTC that can present before, after, or simultaneously with the presentation of PTC. Symptoms of pituitary hormonal deficiency can easily be overlooked as these are nonspecific. Clinicians should exercise vigilance and a high index of suspicion for PM when a patient with any pre-existing cancer presents with visual disturbance, cranial nerve deficit, or symptoms suggestive of hormonal deficiency. We advocate that surgeons should always involve endocrinologists before performing any surgery on the endocrine organs to ascertain the integrity of the endocrine function of the glands.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.