Differentials
Prolactin-secreting adenoma (prolactinoma)
SIGNS / SYMPTOMS
The presence of galactorrhoea suggests prolactinoma.
While macroprolactinomas may present with similar clinical pictures to non-functional pituitary macro-adenomas, microprolactinomas in pre-menopausal women may present with amenorrhoea and galactorrhoea, and with impotence and lack of libido in men. Hypogonadism in non-functional pituitary micro-adenomas is rare.
INVESTIGATIONS
Need to consider serial dilution in those with large pituitary macro-adenomas (>3 cm) to rule out hook effect secondary to very high prolactin levels, which results in only mild to moderate elevation of assay reported prolactin level (not necessary in labs using 2-step assay for prolactin measurement).[50]
Growth hormone-secreting adenoma (acromegaly)
SIGNS / SYMPTOMS
These are macro-adenomas in about 75% of cases. Patients typically have coarsening of facial features and acral enlargement.
Other signs and symptoms may include skin tags, macroglossia, hypertension, arthropathy, hyperhidrosis, symptoms associated with sleep apnoea, and glucose intolerance/diabetes.
INVESTIGATIONS
An age- and sex-matched insulin-like growth factor 1 is typically elevated, and patients fail to suppress growth hormone (GH) to less than 1 microgram/L (1 nanogram/mL), or <0.4 micrograms/L (<0.4 nanograms/mL) using ultrasensitive assays, during oral glucose tolerance test.
The immunostaining of the tumour will show diffuse staining for GH and may also be positive for prolactin.
Adrenocorticotrophic hormone-secreting adenoma (Cushing syndrome)
SIGNS / SYMPTOMS
These tumours are typically micro-adenomas and cause classic symptoms of Cushing syndrome, including skin atrophy, easy bruising, facial plethora, central adiposity, muscle wasting, and wide (>1 cm) purplish striae.
INVESTIGATIONS
Hypercortisolaemia is documented with an elevated 24-hour urinary free cortisol, elevated midnight salivary cortisol, or lack of cortisol suppression (<50 nanomol/L [<1.8 micrograms/dL]) following an overnight or 2 day low-dose dexamethasone suppression test.
The immunostaining of the tumour will show diffuse staining for adrenocorticotrophic hormone (ACTH), and patients would develop adrenal insufficiency after successful resection of an ACTH-producing pituitary adenoma.
Thyroid-stimulating hormone-secreting adenoma
SIGNS / SYMPTOMS
Patients present with typical features of hyperthyroidism such as palpitation, tremor, weight loss, and diaphoresis.
The pituitary tumour is usually a macro-adenoma.
INVESTIGATIONS
The free T4 and free T3 levels will be elevated in the setting of a normal or elevated thyroid-stimulating hormone (TSH). The alpha subunit is usually elevated.
The immunostaining of the tumour will show diffuse staining for TSH.
Rathke's cleft cyst
SIGNS / SYMPTOMS
Rathke's pouch remnants may develop to cysts of different sizes and be localised in the sellar and suprasellar region.
Rathke's cleft cysts are usually discovered incidentally but rarely may present as space-occupying lesions and be associated with mass effect such as hypopituitarism.
INVESTIGATIONS
The CT feature of Rathke's cleft cyst consists of a low-density, well-circumscribed, non-enhancing sellar mass that may be associated with suprasellar extension. On MR images, Rathke's cleft cysts may show various signal intensities but frequently are hyper-intense on T2-weighted image.
Craniopharyngioma
SIGNS / SYMPTOMS
Commonly seen in children but also has a second peak in adults in their sixth decade.
Patients may present with symptoms related to diabetes insipidus, such as polyuria, polydipsia, and nocturia.
INVESTIGATIONS
A cystic suprasellar lesion would suggest craniopharyngioma. Presence of calcification, which is best seen on CT scan, in up to 70% of patients would further support the diagnosis.
Meningioma
SIGNS / SYMPTOMS
Meningiomas occur more frequently in women, with a peak age between 40 and 50 years.
INVESTIGATIONS
A dense homogeneous enhancement on MRI and the presence of calcification on CT scan supports the diagnosis. The presence of a dural tail sign would suggest the diagnosis.
Hypophysitis
SIGNS / SYMPTOMS
Nine times more common in females and commonly affecting young women during late pregnancy or in the postnatal period.
There is increased association with other autoimmune disorders such as Hashimoto's thyroiditis.
INVESTIGATIONS
The chronological association with pregnancy or postnatal and isolated adrenocorticotrophic hormone deficiency may be clues to its diagnosis.
Sarcoidosis
SIGNS / SYMPTOMS
Neurosarcoidosis is seen in about 5% to 10% of individuals with sarcoidosis. It is more common in African Americans and frequently occurs in adults aged 25 to 50 years.
It can be associated with various degrees of hypopituitarism and diabetes insipidus.
INVESTIGATIONS
Among suggestive MRI findings include thickened pituitary stalk and leptomeningeal enhancement. Patients should have chest radiograph to look for systemic disease. The definitive diagnosis requires biopsy.
Infections
SIGNS / SYMPTOMS
Most patients with pituitary abscess present with symptoms related to mass effect (including headache), which at times can be very debilitating.
Pituitary tuberculoma presenting as an isolated central nervous system lesion, without systemic involvement, is very rare.
INVESTIGATIONS
The differentiation of pituitary abscess from non-functioning adenomas is difficult both clinically and radiologically. Pituitary abscess may be seen as a non-enhancing sellar mass with thick wall on MRI imaging.
Germinoma
SIGNS / SYMPTOMS
Germinomas may arise in the suprasellar region and are more common in children. They most commonly present with hypothalamic/pituitary dysfunction, including diabetes insipidus, delayed pubertal development, or precocious puberty (in children).
INVESTIGATIONS
On MRI, germinomas usually appear isointense on T1 sequences and typically show homogeneous enhancement with gadolinium or heterogeneous enhancement if cysts are present. Measurement of cerebrospinal fluid and serum alpha-feto protein, and beta-hCG may be helpful in some cases. MRI of the entire spine is imperative for adequate staging of paediatric germinomas, because 10% to 15% of patients will have leptomeningeal spread.
Pituitary hyperplasia
SIGNS / SYMPTOMS
Enlarged pituitary gland secondary to pituitary hyperplasia can be seen in pregnant women, patients with primary hypothyroidism, primary hypogonadism, and post-menopausal women.
Proper identification is important to prevent unnecessary surgery.
INVESTIGATIONS
The MRI usually shows an enlarged hill-shaped sellar mass that enhances homogeneously following contrast.
Cerebral aneurysm
SIGNS / SYMPTOMS
Suprasellar or intrasellar aneurysms of the carotid arteries or suprasellar aneurysms of the anterior and posterior communicating arteries can clinically resemble expanding pituitary tumours.
Based on their location, they may present with mass effect (e.g., visual field deficit and hypopituitarism).
INVESTIGATIONS
Aneurysms of sellar region may present with various signal intensities on MRI if partially thrombosed. MR angiography is used to confirm the diagnosis.
Metastatic lesions
SIGNS / SYMPTOMS
There is usually a known history of malignancy, typically from breast, lung, and kidney cancers.
INVESTIGATIONS
CT and MRI findings may suggest the diagnosis with extensive bony erosion, pituitary stalk thickening, and heterogeneous sellar mass. Diabetes insipidus is a common clinical finding in up to 70% of patients.[51] Rapid tumour growth on follow-up MRI supports the diagnosis.
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