AssessmentsPituitary tumors: Pathology review
USMLE® Step 1 style questions USMLE
A 48-year-old man comes to his outpatient provider because of headaches and changes in vision, which started two-months ago. The headaches are worse in the morning. Past medical history is notable for Cushing syndrome refractory to medical treatment, for which the patient underwent a bilateral adrenalectomy seven-months ago. He was prescribed hydrocortisone supplements after the surgery but has been inconsistent in taking them. In the office, his temperature is 37.2°C (99.0°F), pulse is 75/min, respirations are 20/min, and blood pressure is 115/77 mmHg. Physical exam shows hyperpigmentation of the skin. Visual field testing reveals bitemporal hemianopsia. Which of the following is the next best step in the diagnosis of this patient?
Content Reviewers:Yifan Xiao, MD
Contributors:Elizabeth Nixon-Shapiro, MSMI, CMI, Salma Ladhani, MD, Kaylee Neff, Daniel Afloarei, MD
While doing your rounds, you see a 6 year-old named Alex who presents with severe headaches and vision impairment which began six months ago.
More specifically, he has some difficulty seeing things on the periphery, what he describes as tunnel vision.
Examination reveals bitemporal hemianopia and a much taller stature than expected for his age, with disproportionately long arms and legs.
Soon after, you see Maria, who says she has been unsuccessfully trying to have a baby for the last two years.
She also mentions that she hasn’t had her menstruation in 3 months, but had milky nipple discharge.
Hormone serum measurements were performed in both, showing an increase in insulin-like growth factor-1 levels in Alex and an increase in prolactin levels in Maria.
Now, both seem to have a disease affecting the pituitary.
But first, a bit of physiology.
The pituitary is a small gland situated in a tiny bony space called the sella turcica.
The posterior pituitary is not glandular; thus it doesn’t make its own hormones.
By contrast, the anterior pituitary has five types of hormone producing cells.
Thyroid hormones speed up the basal metabolic rate in all cells, so it keeps cellular processes going at an optimal rate.
Now, most pituitary tumors are adenomas, which are benign tumors.
These tumors could arise spontaneously, but may also be associated with certain disorders like multiple endocrine neoplasia type 1, or MEN1 where tumors also develop in the parathyroid glands and the pancreas.
Okay, so when a pituitary adenoma is under one centimeter across, it is called a microadenoma. Because these tumors are small, they rarely cause any symptoms and are usually incidental findings on brain imaging.
If the tumor is larger than one centimeter across, it’s called a macroadenoma.
As they grow, macroadenomas can press on the normal parts of the pituitary and cause severe headaches and hypopituitarism, which is when one or all of the anterior pituitary hormones are decreased.
This leads to visual abnormalities like bitemporal hemianopia, or narrowing of the vision field, a very high yield fact to remember!
This causes cavernous sinus syndrome.
The syndrome consists of ophthalmoplegia, which is weakness or paralysis of the muscles involved in eye movement due to compression of CN III, IV, and VI; decreased corneal and maxillary sensations due to compression of CN V; and Horner syndrome due to compression of the sympathetic plexus within the sinus.
Remember that Horner syndrome is a combination of miosis, decreased pupil size; ptosis, a drooping eyelid; and anhidrosis or decreased sweating.
Both micro and macroadenomas can be non-functional or functional.
Now, most non-functional adenomas grow for a really long time without causing any trouble, until reaching the size of a macroadenoma.
Macroadenomas present with compression symptoms, especially headache, bitemporal hemianopia, and double vision.
Sometimes, hypopituitarism features, like impaired growth, sexual dysfunction, and intolerance to cold might also develop.
Another possible consequence is pituitary apoplexy, occurring when the blood vessels of the adenoma rupture and cause a hemorrhage that compresses the blood vessels of the pituitary itself.
Because blood supply to the pituitary is obstructed, this leads to pituitary ischemia, necrosis, and loss of pituitary function.
Non-functional adenomas are usually diagnosed by brain MRI, while pituitary hormone screening might also show a decrease in hormone levels in those with hypopituitarism. Treatment of symptomatic individuals consists of transsphenoidal surgery.
Asymptomatic adenomas smaller than 2 centimeters, however, can be monitored with an MRI, visual field testing, and screening for hormone hypo- or hypersecretion.
Functional adenomas, on the other hand, often lead to an excess of hormones.
First, lactotroph adenomas, or prolactinomas, are the most common type.
Now, what you need to know is that, normally, prolactin secretion is controlled by the hypothalamus, which inhibits its production by releasing dopamine via the tuberoinfundibular pathway, and stimulates its production via TSH.
Prolactin also causes negative feedback by inhibiting its own secretion since it causes dopamine release from the hypothalamus.
However, when there’s too much prolactin, dopamine inhibition is lost, and the hypothalamus can’t regulate prolactin production anymore.
Now, a macroadenoma can also obstruct the flow of dopamine from the hypothalamus, but compared to prolactinomas, the elevation in prolactin is usually mild and under 100 ng/ml.
And without gonadotropin stimulation, gonads can’t secrete sex hormones like estrogen and progesterone, causing hypogonadism.
And as a result, these female individuals tend to suffer fragility fractures.
Most individuals can also present with compression symptoms like bitemporal hemianopia and headaches as well.
A brain MRI scan showing the tumor's size and extent and a blood test showing high serum prolactin levels confirm the diagnosis.
Somatotroph adenomas make growth hormone and are the second most common type of pituitary adenoma.
Excess growth hormone causes different symptoms in children versus adults.
Something to remember is that these kids can get really tall because, because unlike other causes of gigantism, GH doesn’t accelerate epiphyseal closure of the bone, which is responsible for linear growth.
In adults, it causes acromegaly, where there’s enlargement of the bones of the skull, hands, and feet.
Other possible features of acromegaly include a large tongue with deep furrows, deep voice, diaphoresis, which is excessive sweating, impaired glucose tolerance, and increased risk of colorectal polyps and cancer.
In both gigantism and acromegaly, there can also be enlargement of visceral organs, like the heart.
Screening for a somatotroph adenoma is actually a high-yield topic.
It’s done by measuring insulin-like growth factor 1, or IGF-1 levels, which is a liver-produced hormone through which GH stimulates long bone growth.
- "Robbins Basic Pathology" Elsevier (2017)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
- "Greenspan's Basic and Clinical Endocrinology, Tenth Edition" McGraw-Hill Education / Medical (2017)
- "The prevalence of pituitary adenomas" Cancer (2004)
- "Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline" The Journal of Clinical Endocrinology & Metabolism (2006)
- "Nelson's syndrome" European Journal of Endocrinology (2010)