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Pituitary adenomas and pituitary hyperfunction: Clinical practice

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Pituitary adenomas and pituitary hyperfunction: Clinical practice

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A 25-year-old woman comes to her primary care physician because of a six-month history of amenorrhea. The patient previously had regular menstrual cycles at 30-day-intervals. In addition, she has noticed scant white discharge from the breasts bilaterally. Past medical history is notable for asthma, for which she takes albuterol occasionally. Temperature is 37.3°C (99.1°F), pulse is 80/min, respirations are 20/min, and blood pressure is 118/77 mmHg. BMI is 20 kg/m2. Physical examination is unremarkable. Radiographic imaging reveals the following findings:

 
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Laboratory testing reveals serum prolactin of 320 ng/mL (normal <25 ng/ml in non-pregnant females). Which of the following is the next best step in the management of this patient?  

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Content Reviewers:

Rishi Desai, MD, MPH

Pituitary adenomas are benign tumors of the anterior pituitary that derive from one of the five types of pituitary hormone producing cells.

One group of cells are the somatotrophs which secrete growth hormone, or GH.

Then, there are the corticotrophs, and they secrete adrenocorticotropic hormone, or ACTH for short.

ACTH makes the adrenal glands secrete cortisol.

Another cell group are the lactotrophs which secrete prolactin, which stimulates breast milk production, and inhibits ovulation and spermatogenesis.

There are also thyrotrophs which secrete thyroid stimulating hormone, or TSH.

Last but not least, there are gonadotroph cells, which secrete luteinizing hormone, or LH, and follicle-stimulating hormone, or FSH, both of which stimulate the ovaries or testes.

Sometimes, pituitary adenomas can be entirely asymptomatic, and they’re discovered incidentally on a head MRI performed for another reason, like a head trauma.

On an unenhanced MRI, meaning, without contrast, normal pituitary tissue has a greater signal intensity than brain tissue - so it looks whiter.

A pituitary adenoma, on the other hand, has a signal that is similar to surrounding brain tissue - so it’s “just as grey” instead.

Following administration of Gadolinium as contrast, normal pituitary tissue lights up like a christmas tree.

An adenoma typically takes in more contrast than the central nervous system, but less than the healthy part of the pituitary - so grey-wise, it’s somewhere in between the two.

The MRI helps ascertain the size of the tumor - pituitary adenomas smaller than 1 centimeter are called microadenomas, whereas those larger than 1 centimeter are called macroadenomas.

Both micro and macroadenomas can be functional, meaning that they secrete hormones, or non-functional, meaning they don’t - so any individual with a confirmed pituitary adenoma should be screened for hormone hypersecretion.

Functional adenomas typically secrete prolactin, growth hormone, or ACTH, and the excess hormones typically cause symptoms.

With excess prolactin, females have symptoms of hypogonadism, like infertility, oligomenorrhea or amenorrhea, as well as galactorrhea - which is a milky nipple discharge outside of pregnancy or breastfeeding.

Males present with decreased libido, impotence, infertility and, rarely, gynecomastia.

Serum prolactin levels higher than 200 nanograms per milliliter confirm the diagnosis, and treatment relies on dopamine agonists like cabergoline, that inhibit prolactin secretion just like dopamine would.

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 limbs.

In adults, it causes acromegaly, which is where there’s enlargement of the bones of the skull, hands and feet.

In both gigantism and acromegaly, excess growth hormone causes enlargement of visceral organs, like the heart.

Screening for a growth-hormone secreting adenoma is done by measuring… no, not growth hormone levels, but insulin-like growth factor 1, or IGF-1 levels.

See, daily growth hormone secretion is pulsatile, sometimes more and sometimes less. However, the mean concentrations of growth hormone are sufficient to make the liver release a constant amount of IGF-1 throughout the day, so IGF-1 levels are a better estimate of growth hormone secretion - with high levels suggesting growth hormone hypersecretion.

If there are high IGF-1 levels, serum growth hormone is measured to confirm the diagnosis.

Specifically, serum growth hormone is measured before and two hours after giving an individual 75 grams of glucose dissolved in a bit of water. Normally, serum growth hormone two hours after ingesting glucose is less than 1 nanogram per milliliter, but if there’s growth hormone hypersecretion, the level is higher than 1 nanogram per milliliter.

Treatment is usually surgical, through transsphenoidal resection.