Content Reviewers:Yifan Xiao, 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.
It is linked to the hypothalamus by the pituitary stalk, and it is divided into the anterior pituitary and the posterior pituitary.
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.
Fourth, thyrotrophs secrete thyroid stimulating hormone, or TSH. TSH makes the thyroid gland release thyroid hormones, T3 and T4.
Thyroid hormones speed up the basal metabolic rate in all cells, so it keeps cellular processes going at an optimal rate.
And finally, gonadotroph cells secrete luteinizing hormone, or LH, and follicle-stimulating hormone, or FSH, that stimulate ovarian or testicular production of sex cells and sex hormones.
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.
If the tumor grows superiorly, it can compress the nearby optic chiasm, which is where the optic nerves partially cross.
This leads to visual abnormalities like bitemporal hemianopia, or narrowing of the vision field, a very high yield fact to remember!
If it extends laterally, it can invade the cavernous sinus, a structure made of venous channels located on both sides of the sella turcica, and press on the nerves that pass through it.
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.
Symptoms are similar to those caused by compression like bitemporal hemianopia and severe headaches, but meningeal signs like neck stiffness can also be present.
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.
Now, another high-yield consequence is that excess prolactin suppresses hypothalamic production of gonadotropin-releasing hormone or GnRH, which leads to the pituitary secreting less LH and FSH.
And without gonadotropin stimulation, gonads can’t secrete sex hormones like estrogen and progesterone, causing hypogonadism.
Hypogonadism symptoms can include infertility, amenorrhea, which is absent menstruation, and vaginal dryness.
And as a result, these female individuals tend to suffer fragility fractures.
Males typically develop decreased libido, impotence, infertility, gynecomastia, and, rarely, galactorrhea.
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.
Excess growth hormone causes different symptoms in children versus adults.
In children, it causes gigantism, which is an increase in body size and height with disproportionately long arms and legs.
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.
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.
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