Noon Report by Dr. Yoo.
In noon report today, we discussed a 67-year-old male who had multiple admissions for fatigue, lightheadedness, and malaise. In workup, he was found to be hyponatremic to 122.
Further labs were done as follows:
ACTH < 5 (L)
Aldosterone < 4 (L)
Random cortisol 0.9
FSH 1.3 (L)
LH 0.9 (L)
Testosterone 15.3 (L)
Prolactin 8.5
TSH 0.024 (L)
Free T4 0.75
Free T3 0.8
MRI of his head revealed a "2.1 cm circumscribed heterogenous mixed solid and cystic sellar mass most compatible with pituitary microadenoma".
A Review of the Pituitary
The anterior pituitary is the glandular portion.
Blood supply comes from the hypothalamus through the hypothalamic-pituitary portal plexus.
It is regulated by the hypothalamus.
It secretes and releases 6 hormones
ACTH- released in response to corticotrophin-releasing hormone (CRH). ACTH acts on the adrenal glands to promote the synthesis and secretion of cortisol.
TSH- released in response to thyrotropin-releasing hormone (TRH). TSH acts on the thyroid.
LH- Released in response to pulses of gonadotropin-releasing hormone (GnRH). Regulates reproductive function.
FSH-Released in response to pulses of gonadotropin-releasing hormone (GnRH). Regulates reproductive function.
Growth Hormone (GH)-regulated by somatostatin. Regulates growth.
Prolactin-inhibited by dopamine. Regulates lactation
The posterior pituitary is the neural portion.
This is a direct extension of neurons from the hypothalamus.
Hormones are synthesized in the hypothalamus, transmitted via hypothalamic neurons to be secreted by the posterior pituitary gland.
The hormones secreted by the posterior pituitary are:
Oxytocin- Needed for childbirth.
Antidiuretic hormone (ADH, vasopressin)- Regulates water balance.
The anterior and posterior portions of the pituitary are connected by the Rathke Pouch.
Pituitary Adenomas
Pituitary adenomas are benign tumors and the most common tumor of the pituitary gland.
< 1 cm = Microadenoma
> 1 cm = Macroadenoma
When a pituitary adenoma is identified, the following needs to be deteremined:
Is it causing mass effect?
Is it secreting excess hormone?
Is it going to grow and cause future problems?
1. Is it causing mass effect?
Even non-functioning adenomas can result in compressive symptoms. Remember that both pregnancy and untreated primary hypoparathyroidism result in an increase in pituitary size. Ultimately, compresison can result in:
Impaired pituitary gland function, which can manifest as partial hormone deficiencies or panhypopituitarism.
Visual Changes-classically bitemporal hemianopsia from compression of the optic chiasm, but complete blindness can result. Additionally, extrapituitary invasion can occur resulting in diplopia and & ocular muscle palsies.
Headaches- Size of the tumor does NOT correlate with presence and/or severity of headache.
Seizures- Extrapituitary invasion can result in seizures.
Elevated Prolactin Levels- It is critical to note that a nonfunctioning pituitary tumor can cause hyperprolactinemia by compressing the pituitary stalk and prohibiting the inhibition of dopamine. This is different than a prolactinoma (discussed below) and a critical distinction because the treatments differ. (Surgery versus medication!). In general, a non-functioning macroadenoma will cause a mild elevation of prolactin (<100) although very large macroprolactinomas can raise prolactin levels even higher than 10,000!
Non-functioning pituitary adenomas with mass effect or evidence of growth should still be surgically removed.
2. Is it secreting excess hormone?
Pituitary tumors are called "functional tumors" when they secrete excessive amounts of hormone. Adenomas secreting excess hormone are generally referred to by the type of hormone they are secreting. We will focus on two important functional tumors below.
Prolactinoma-This is the most common functional pituitary tumor. Remember that prolactinomas are not the only cause of hyperprolactinemia! (Antipsychotics, pregnancy, primary hypothyroidism, etc. can result in elevated prolactin levels). Prolactinomas can present with galactorrhea (more common in women than men) and hypogonadotropic hypogonadism. Remember: Women of reproductive age are going to present MUCH earlier than others because they will develop amenorrhea. Men and post-menopausal women can go unrecognized for years. Treatment in prolactinomas focuses first on medical therapy with dopamine agonists (i.e. bromocriptine & cabergoline).Generally, pick cabergoline. It is better tolerated, more effective, and dosed only 1-2 times a week. The problem is it is also much more expensive, so bromocriptine may need to be used. Hormone replacement therapy may also be needed, but surgery is usually not necessary as medications will often shrink tumor size and activity.
ACTH-secreting Adenoma-ACTH-secreting pituitary adenomas result in Cushing Disease (in comparison to Cushing syndrome which is hypercortisolism from any source). This is an important disease to identify because it results in significant long-term morbidity, from diabetes, obesity, hypertension, and osteoporosis. When you suspect Cushing Disease, first prove that the patient has hypercortisolism. Once you've confirmed the presence of ACTH-dependent Cushing syndrome, next obtain a pituitary MRI. If negative (no tumor or a 6 mm or smaller tumor present), do an 8-mg dexamethasone suppression test with is confirmed biochemically, a pituitary MRI should be obtained. If no pituitary tumor or a tumor less than 6 mm is visualized on MRI, a high-dose (8-mg) dexamethasone suppression test is used to differentiate Cushing disease from an ectopic source of ACTH. Because this test has low-sensitivity and specificity, intrapetrosal sinus sampling (IPSS) is recommended before exploratory pituitary surgery.
3. Is it going to grow?
This piece is only important if the tumor is not causing mass effect and there is no evidence of hormone excess. If either of those two are present, you are going to intervene on the tumor anyways.
If not, a pituitary MRI should be repeated in 6 months for a macroadenoma and 12 months for a microadenoma to assess for growth. If no growth occurs in this time, you can repeat the MRI every 1 to 2 years for the next three years.
Hypopituitarism
Hypopituitarism is caused by one or more pituitary hormone deficiencies.
Secondary Cortisol Deficiency- These patients only have glucocortioid deficiency, as the remainder of the adrenal gland is functioning appropriately. This can present with nausea, vomiting, weight loss, lightheadedness, hypoglycemia, hypotension (less common), and/or hyponatremia (less common as mineralcorticoids are still present). Secondary cortisol deficiency is also diagnosed using an ACTH stimulation test. These patients require glucocorticoid replacement. Typically hydrocortisone (15-30 mg/day) is used in 2 to 3 doses a day. A typical regimen is 10 to 20 mg in the morning and 5 to 10 mg in the early afternoon. Stress dose steroids are needed with illness.
Secondary Hypothyroidism- This clinically presents similarly to primary hyperthyroidism but patients will have an inappropriately normal to low TSH (as in our patient) with a low free and/or total T4. Patients should still be treated with Synthroid but this is titrated to the free T4, not TSH.
GnRH deficiency- This results in low levels of LH and FSH, creating a hypogonadotropic hypogonadism. These patients require hormone replacement therapy.
Growth Hormone deficiency- This is often the first hormone deficiency to occur when a patient is developing pituitary insufficiency. However, it is rare in adults and as growth hormone's major effect is on linear growth, its clinical significance in adults is debated.
Central Diabetes Insipidus- Central DI occurs when the posterior pituitary gland does not produce enough ADH. Inadequate amounts of aquaporins are inserted in the collecting tubules resulting in excessive water excretion. Patients generally present with polyuria (>3L of urine per day) and excessive thirst. These patients rarely present with hypernatremia because they develop polydypsia and extreme thirst: if they have free access to water, they can maintain a serum sodium in the high normal range. Highly symptomatic patients (i.e hypernatremic, bad nocturia and polyuria) can be treated with desmopressin.
Thanks to Dr. Charles Yoo for a wonderful noon report!
References
MKSAP 17: Disorders of the Pituitary Gland.
Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011 Apr;96(4):894-904.
Klibanski A. Clinical Practice. Prolactinomas. N Engl J Med. 2010 Apr 1;362(13):1219-26.
Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273-88.
Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008 May;93(5):1526-40.
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