Prolactin-Producing Pituitary Carcinoma, Hypopituitarism, and Graves' Disease-Report of a Challenging Case and Literature Review

Abstract

Introduction: The diagnosis of pituitary carcinoma is very rare, requires the evidence of metastatic disease, and has a poor overall survival. Malignant prolactinoma frequently requires dopamine agonist therapy, pituitary surgery, radiotherapy, and even chemotherapy.

Case description: A 19-year-old female presented with galactorrhea, primary amenorrhea, and left hemianopsia. Complementary study detected hyperprolactinemia and a pituitary macroadenoma with cavernous sinus invasion and suprasellar growth. She was treated with cabergoline and bromocriptine without clinical or analytical improvement. Resection of the pituitary lesion was programmed and a non-contiguous lesion of the nasal mucosa was detected during the approach. This metastasis led to the diagnosis of prolactin-producing pituitary carcinoma. After partial resection, the patient was submitted to radiotherapy for residual disease with persistent symptoms. She developed growth hormone deficiency, central hypothyroidism, hypogonadism, and permanent diabetes insipidus. Six years later she was admitted for the suspicion of secondary adrenal insufficiency and thyrotoxicosis. Physical findings, laboratory data, thyroid ultrasound, and scintigraphy achieved the diagnosis of Graves' disease and hypocortisolism. She was treated with hydrocortisone and methimazole, but central hypothyroidism recurred after antithyroid drug withdrawal. Nine years after the diagnosis of a pituitary carcinoma, she maintains treatment with bromocriptine, has a locally stable disease, with no metastases.

Conclusion: This report highlights an unusual presentation of a prolactin-producing pituitary carcinoma in a young female. The patient had multiple hormone deficiencies due to a pituitary lesion and treatments. The posterior development of hyperthyroidism and adrenal insufficiency brought an additional difficulty to the approach.

Keywords: Graves’ disease; adrenal insufficiency; hypopituitarism; pituitary carcinoma; pituitary surgery; prolactinoma.

Figure 1

Sagittal (A) and coronal (B) plane of the first pituitary magnetic resonance imaging (MRI) with an invasive macroadenoma with gadolinium enhancement. The pituitary tumor measured 32 mm × 30 mm × 25.5 mm in anteroposterior, craniocaudal, and transverse dimensions, respectively. The lesion had invasion of the right cavernous sinus, superior deviation of the left internal carotid artery, sphenoid sinus invasion, and compression and stretching of the optical chiasm. The tumor was isossignal area in T1 and T2 with small cysts and had marked contrast enhancement. The possible nasal metastasis was localized near the sphenoid rostrum in the left nasal fossa (arrows). The postoperative MRI (C,D) revealed a persistent expansive pituitary lesion with right cavernous sinus invasion. The last pituitary MRI (E,F) performed in October 2017 showed a pituitary tumor with markedly reduced dimensions.

Figure 2

Histology of a prolactin-producing pituitary tumor. Tumor with diffuse growth pattern of cells with elongated nuclei and inconspicuous nucleoli and moderate amount of slightly acidophilic cytoplasm [(A)—HE 400×]. Prolactin expression in neoplastic cells [(B)—400×].

Figure 3

Thyroid ultrasonography (A) showed a normal size gland, with heterogeneous texture and pseudonodular areas, without nodular lesions, suggesting thyroiditis. The color flow Doppler signal showed significantly increased vascularity with diffuse homogeneous distribution (thyroid inferno). There was a markedly hyperfunctioning thyroid in scintigraphy (B), with homogeneous activity distribution and no focal areas suggestive of hyper- or hypoactive nodular formations. The radioactive iodine uptake was 70.2% at the end of 24 h, markedly elevated compared to normal range (10–30%). Panel (C) shows the evolution of thyroid function. After pituitary surgery in 2009 the patient developed secondary hypothyroidism and initiated LT4. She was admitted with primary hyperthyroidism in April 2015 and initiated MMI. During antithyroid drug withdrawal before scintigraphy, FT4 and FT3 re-increased above the reference range. MMI was progressively reduced after 6 months of treatment, but after withdrawal in October 2015, central hypothyroidism recurred and she resumed LT4 since March 2016. Abbreviations: LT4, levothyroxine; MMI, methimazole; FT4, free thyroxine; FT3, free triiodothyronine.

Figure 4

Evolution of serum prolactin levels over time and its relation with medical, surgical, and radiation therapy. *Samples not diluted.