Pituitary incidentalomas ( PI) are clinically unsuspected pituitary lesions typically discovered on radiological imaging for unrelated medical problems, such as headaches, neurological injuries, or trauma.
They are a common finding in neuroimaging tests. Many will be non-functional benign adenomas and most patients will be asymptomatic at the time of diagnosis. However, all cases require a complete endocrine evaluation.
The literature on the definition of IH varies. In this article, in the definition of IH the authors included the definition of lesions radiologically compatible with an adenoma and cystic lesions of the pituitary gland and surrounding structures. Pituitary adenomas, commonly called pituitary tumors, are classified according to their size and hormone production status (functioning and non-functioning tumors). Historically, lesion size was used to classify adenomas, such as microadenomas (<10 mm) and macroadenomas (≥10 mm).
Pituitary incidentalomas are relatively common, with a prevalence of 10% observed on imaging studies, in contrast to 1.8% and 39.5% depending on the size of the adenoma and the hormone it secretes.
| Assessment |
All patients with IH should have an evaluation with detailed history, physical examination, relevant hormonal measurements, and radiological imaging.
In the presence of symptoms such as visual alterations and others that suggest hypersecretion of pituitary hormone, it is necessary to actively search for hypopituitarism.
Clinical signs suggestive of hormonal hypersecretion , such as cushingoid or acromegalic features, can be detected on physical examination . Regardless of the presence of symptoms and signs of hypopituitarism or hormonal hypersecretion, a basic laboratory evaluation should be performed to investigate pituitary function. This evaluation should include the measurement of cortisol at 9:00 a.m., thyroid-stimulating hormone (TSH), free thyroxine (T4), prolactin, morning testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol. , growth hormone (GH) and insulin-like growth factor1 (IGF1).
Hypopituitarism refers to the complete deficiency of pituitary hormones . The size of the IH is important in the evaluation of hypopituitarism because it is more likely to enlarge with larger tumors.
Microadenomas may be hormonally active, with hypersecretion, but this does not necessarily indicate the existence of hypopituitarism, particularly when they are <5 mm .
After non-functioning adenomas, the second most common IH are prolactinomas . In macroprolactinomas (>10 mm) prolactin is usually >5000 Mil/l and lower in microprolactinomas. In patients with large adenomas, prolactin levels should be measured in diluted serum to ensure that levels are not falsely reduced by a hook effect.
Symptoms of hyperprolactinemia are more evident in women, who generally present secondary amenorrhea or galactorrhea. In men, symptoms of sexual dysfunction may not be very evident unless hypogonadism is severe, and therefore large prolactinomas in men may be found incidentally on brain scans performed for other causes. When hypersecretion of other hormones is suspected in the presence of an IH, additional diagnostic evaluation by a specialist, particularly an endocrinologist, is required.
Some pituitary lesions are the result of inflammation and infiltration of the pituitary gland and/or pituitary stalk, called hypophysitis. Patients with this condition may have deficiencies in anterior and posterior pituitary hormones. Arginine vasopressin, also known as antidiuretic hormone, is produced in the hypothalamus, crosses the pituitary stalk, and is released from the posterior pituitary.
People with antidiuretic hormone deficiency have severe polyuria and polydipsia (also known as diabetes insipidus). In addition to laboratory hormonal evaluation, all individuals with visual symptoms or radiographic evidence of IH abutting or compressing the optic chiasm should undergo formal evaluation of visual fields. The visual symptoms and extent of visual field defects caused by the pituitary tumor determine the urgency of pituitary surgery to decompress the optic chiasm.
MRI provides more detailed information about pituitary lesions. When lesions are detected incidentally on brain computed tomography (CT) images, in addition to evaluation using pituitary-specific MRI protocols, gadolinium contrast should be performed unless contraindicated. Finally, in patients who present with acute-onset severe headache and/or neuro-ophthalmologic deficits, newly diagnosed or pre-existing pituitary tumor on brain imaging, clinicians should consider pituitary apoplexy as a differential diagnosis.
| Clinical factors and precipitating factors of pituitary apoplexy |
| Clinical features |
| Sudden onset headache Vomiting Meningismus Reduced visual acuity Ophthalmoplegia Reduced consciousness |
| Precipitating factors |
| Hypertension Major surgery Coronary artery bypass surgery Dynamic pituitary testing Anticoagulant treatment Pregnancy Head trauma Initiation of estrogen therapy |
In most patients, radiological images. show signs of intratumoral hemorrhage. There are several factors that precipitate pituitary apoplexy, causing infarction or hemorrhage of the pituitary gland and resulting in sudden failure of the pituitary gland. Pituitary stroke is a medical emergency because patients can have a severe cortisol deficiency. Immediate intravenous replacement of hydrocortisone can be life-saving and urgent endocrine opinion and neurosurgical evaluation should be sought.
| Driving |
Treatment of IH depends on the presence of hormonal hypersecretion (functional adenomas), the size of the adenoma, and the presence of visual field deficits resulting from tumor compression in the optic chiasm or optic nerves. The authors provide a simple flowchart describing the initial evaluation and management of IH based on endocrinological guidelines.
| Medical treatment |
Non-functioning pituitary adenomas do not respond to medical treatment. Prolactin-secreting pituitary adenomas (prolactinomas) respond to dopamine agonists (eg, cabergoline or bromocriptine) as preferential first-line therapy, regardless of the size of the prolactinoma. Dopamine agonists reduce prolactin levels and can also cause tumor shrinkage. These medications can be used effectively even in tumors that slightly compress the optic chiasm, due to the expected reduction in its volume. In most patients, this can happen within a few weeks of treatment. In patients with large prolactinomas resistant to treatment with dopamine agonists.
Hypopituitarism may be seen in patients with larger pituitary adenomas and is less likely to be present in patients with microadenomas. If present, hormone replacement therapy should be guided by the endocrine team as appropriate. The most important hormone is cortisol since if it is not replaced, its deficiency can be life-threatening.
Hydrocortisone is the most common way to replace glucocorticoids. The usual dose is 15-20 mg/day, in 2-3 divided doses. Patients should be informed to double doses during periods of illness. They should also receive education about the use of emergency hydrocortisone injections and steroid alert cards, to support early recognition and treatment of adrenal crisis in adults. Emergency hydrocortisone injections are particularly important if there is an acute state of malabsorption (e.g., vomiting or diarrhea).
Levothyroxine is used to replace thyroid hormone deficiency , although care must be taken not to replace glucocorticoids because it can precipitate an adrenal crisis. To adjust hormone replacement in central hypothyroidism resulting from pituitary tumors, serum T4 should be used instead of TSH because TSH no longer responds with normal feedback values to thyroid hormone levels.
Testosterone, GH, and AVP replacement should be initiated according to local endocrine team guidelines.
| Surgical indications |
Surgical resection is the preferred first-line treatment for all functioning pituitary adenomas except prolactinoma.
The objective is the remission of hormonal hypersecretion and the reduction of tumor burden in patients in whom the tumor is not completely resectable.
For non-functioning pituitary adenomas in patients with visual field deficits due to compression of the optic nerves by the pituitary adenoma, emergency pituitary surgery is indicated.
In patients with pituitary apoplexy and persistent visual disturbance, urgent neurosurgical evaluation is recommended. Neurosurgical referral is also appropriate when significant growth of the IH is observed on serial images, and in those with adenomas close to the optic chiasm.
| Radiological monitoring |
Macroincidentalomas require prolonged radiological surveillance due to their greater tendency to grow than microincidentalomas. Growth is usually slow, increasing a few millimeters per year, except for a few aggressive tumors. There is no clear evidence of the frequency with which radiological surveillance should be carried out. This depends on the size of the lesion, its proximity to the optic chiasm and surrounding brain structures, the age of the patient, and any tumor size that may have occurred in the previous years.
Guidelines recommend repeating the MRI scan for macroadenomas months after the initial diagnosis, repeating the scan every year for the next 3 years. If there is no change in the size of the adenoma on serial images, the interval between scans may be prolonged in the later stages. In patients who have undergone surgery and histological subtyping, markers of tumor proliferation (eg, Ki-67 index) can be used as prognostic markers for regrowth, to help determine the frequency of imaging.
Non-functioning microincidentalomas are less likely to grow. A follow-up MRI is recommended 1 year after diagnosis. Subsequent imaging should be less frequent in lesions that have not changed. In asymptomatic patients with unchanged lesions <5 mm, additional images would not be necessary.
