at: inbox

Endocrinology - Pituitary Disorders - Fast Facts | NEJM Resident 360

The pituitary gland weighs approximately 600 mg and consists of anatomically and functionally distinct anterior and posterior lobes. Hypothalamic neural cells produce hormones that are secreted into the portal vessels of the pituitary stalk to either stimulate or inhibit release of pituitary hormones.

Pituitary adenomas are benign neoplasms and are the most common cause of hypersecretion of pituitary hormones. Approximately 10% of pituitary glands at autopsy contain adenomas. A similar prevalence of pituitary adenomas has been reported in healthy volunteers on MRI imaging. Classification of pituitary adenomas is based on whether they secrete hormones and by size (microadenomas, <10 mm or macroadenomas, ≥10 mm). In this section, we will review the following:

• Pituitary Adenomas

• Nonfunctioning Pituitary Adenomas

• Hypopituitarism

• Posterior Pituitary

The Pituitary Gland

Figure 5: Coronal T-weighted gadolinium-enhanced MRI image of the pituitary region of the brain. Green - optic chiasm. Red - pituitary gland (I=infundibulum / pituitary stalk). Yellow - Cavernous sinus. Orange - internal carotid arteries.
(Case courtesy of Prof Frank Gaillard, Radiopaedia.org, rID: 17529.)

Pituitary Adenomas

Pituitary adenomas can arise from one of the five anterior pituitary-cell types defined by the hormones they secrete: lactotroph (prolactin), somatotroph (growth hormone), corticotroph (adrenocorticotropic hormone, ACTH), thyrotroph (thyroid-stimulating hormone, TSH), or gonadotroph (luteinizing hormone, LH; follicle-stimulating hormone, FSH). These tumors are characterized by hormone secretion that is autonomous with diminished responsiveness to physiologic inhibitory pathways. The most commonly secreted hormones from pituitary adenomas include prolactin (prolactinoma), growth hormone (acromegaly), and ACTH (Cushing disease).

Pituitary Adenoma

Magnetic resonance imaging of the brain revealing a giant pituitary adenoma measuring 48 mm in diameter (arrow)
(Source: Seesaw Nystagmus. N Engl J Med 2017.)

*Figure 25: Coronal T1-weighted gadolinium-enhanced MRI images of the pituitary region in two patients with pituitary adenomas. The patient in panel A has a small pituitary microadenoma that does not enhance with contrast (unlike the normal pituitary gland). This was an incidental finding on a brain MRI performed for other reasons. The patient in panel B has a macroadenoma (the patient presented with headaches and visual changes). The tumor is not only extending superiorly out of the enlarged fossa and compressing the optic chiasm, but also extending anteriorly into the sphenoid sinus. : Tumor. Arrows: Optic chiasm.
(Case courtesy of Prof Frank Gaillard, Radiopaedia.org, rID: 2648 and 16787.)

Prolactinoma

This prolactin-secreting tumor is the most common cause of secretory pituitary adenoma. Prolactin levels correspond to the size of the tumor mass.

Causes of elevated prolactin that require investigation include:

• medications (first- and second-generation antipsychotics)

• pregnancy

• empty sella syndrome

• primary hypothyroidism

• adrenal insufficiency

• pituitary stalk compression (lesions in the pituitary stalk inhibit the normal flow of dopamine to the anterior pituitary, which releases lactotrophs from tonic inhibition of prolactin release and leads to mild hyperprolactinemia)

• cirrhosis

• chest wall trauma or stimulation

In cases of large pituitary masses with only mild hyperprolactinemia, consider inaccurate assay results (“hook effect”) due to interference with the assay from extremely high prolactin levels. In cases of elevated prolactin levels without any obvious clinical sequelae, consider macroprolactinemia (multimers of prolactin that are measured by the prolactin assay but that do not exert any biological effects). The laboratory can help assess for these issues. 

Clinical symptoms and signs:

• women: oligomenorrhea, infertility, and galactorrhea

• men: hypogonadism, decreased libido, erectile dysfunction, gynecomastia, and galactorrhea

Diagnosis: evaluation of physiologic causes of hyperprolactinemia with labs tests (pregnancy test, TSH, free thyroxine [fT4], and renal function)

Treatment:

• minimal symptoms or microadenomas: observation

• oligomenorrhea or amenorrhea presentation in a woman who does not wish to get pregnant: consider oral contraceptive

• symptomatic woman considering pregnancy: dopamine agonists

• • Cabergoline is the most effective dopamine agonist for both decreasing prolactin level and reducing tumor size and has a better side-effect profile than the other available agent, bromocriptine.

Acromegaly

Presentation: This growth hormone–secreting tumor is characterized by the following clinical features:

• change in appearance with frontal bossing

• soft tissue swelling of extremities

• systemic complications including hypertension, diabetes, arthritis, and sleep apnea

Diagnosis:

• Average time to diagnosis is 7 years.

• Screening test consists of insulin-like growth factor 1 (IGF-1) with confirmation testing with oral glucose–tolerance test to look for suppression of growth hormone.

• Random growth-hormone level is not clinically diagnostic because secretion is pulsatile.

• MRI helps assess tumor size; tumors are usually large.

Treatment:

• Transsphenoidal surgery is the primary therapy.

• Further control can be achieved with somatostatin analogues and the growth hormone receptor antagonist pegvisomant.

Acromegaly in a 50-Year-Old Man

Panel A shows identical twins; the twin on the left has acromegaly caused by a growth hormone–hypersecreting pituitary macroadenoma. He presented with headaches, enlargement of feet, increased sweating, and joint stiffness and had coarse facial features, including acral enlargement (nose and lips) and enlargement of the facial soft tissue. Panel B shows a coronal section and Panel C a sagittal section of the macroadenoma on magnetic resonance imaging.
(Source: Medical Mystery — The Answer. N Engl J Med 2004.)

Cushing Disease

Presentation: Presentation of this condition, caused by an ACTH-producing tumor includes:

• features of hypercortisolism (including weight gain, centripetal obesity, supraclavicular and dorsocervical fat pads, facial rounding, plethora, pigmented striae, easy bruising)

Diagnosis:

• Initial evaluation can start with late-night salivary cortisol, overnight 1-mg dexamethasone test, or 24-hour urinary free cortisol measurement.

• If abnormal, the next step is to determine cause of hypercortisolism based on ACTH levels.

• • If elevated, ACTH-secreting pituitary adenoma needs to be differentiated from an ectopic source of ACTH.

  • The majority of ACTH-producing adenomas are microadenomas, and MRI may be normal. In these cases, inferior petrosal sinus sampling can help differentiate a pituitary adenoma from an ectopic source of ACTH.

Treatment:

• Transsphenoidal surgery is primary treatment.

• Medical therapy options can be considered in patients who are not good surgical candidates or patients whose cortisol levels are not well controlled after surgery. These include:

• • mifepristone: blocks cortisol action at the glucocorticoid receptor

  • ketoconazole, mitotane: blocks cortisol synthesis in the adrenal glands

  • dopamine agonists and somatostatin analogs: blocks ATCH secretion from the pituitary gland

• Other treatment options include bilateral, laparoscopic adrenalectomy, and pituitary irradiation.

Abdominal Striae in a Patient with Cushing syndrome

**(Source: Ectopic Cushing’s Syndrome. N Engl J Med 2011.)**Physical Evidence of Cushing syndrome

(Source: Mutation in PDE8B, a Cyclic AMP–Phosphodiesterase in Adrenal Hyperplasia. N Engl J Med 2008.)

Nonfunctioning Pituitary Adenomas

One-third of pituitary adenomas do not secrete hormones. Given the lack of hormone secretion, most patients present with symptoms from mass effect or incidentally due to a mass on imaging.

Evaluation:

• Incidentalomas: Patients should be evaluated for hormone secretion.

• Incidentalomas and symptoms from mass effect: Patients should be evaluated for hypopituitarism. (Note: Prolactin can increase modestly due to stalk pressure, but the prolactin level usually is not above the 200 ng/mL seen in patients with prolactinomas.)

• Visual field testing is indicated if there is evidence either clinically or on imaging that the tumor is abutting the optic chiasm.

Treatment:

• Transsphenoidal surgery is the main treatment for symptomatic tumors with mass effect.

• Observation with MRI monitoring for tumor enlargement is sufficient in patients with incidentalomas (only 10% experience tumor growth).

Hypopituitarism

Inadequate production of hormones in the anterior or posterior pituitary gland leads to hypopituitarism. It can result from inherited disorders but more commonly is caused by acquired disorders, including tumors (breast and lung are the most common tumors to metastasize to the pituitary), infiltrative lesions (sarcoidosis, histiocytosis X), infarction, lymphocytic hypophysitis (including hypophysitis due to use of immune checkpoint inhibitors), medications, apoplexy, trauma, and infection. Hypopituitarism is associated with increased mortality due to ACTH deficiency.

Clinical presentation:

• acute onset: sudden-onset headache, nausea, vomiting, increasing thirst and urination

• chronic onset: depends on hormone deficiency

Diagnosis: based on serum TSH, gonadotrophin, prolactin, ACTH deficiencies

Treatment: hormone replacement therapy

Posterior Pituitary

The posterior pituitary, formed by axons that originate in the supraoptic and paraventricular nuclei of the hypothalamus, produces two hormones — arginine vasopressin (AVP) or antidiuretic hormone (ADH) and oxytocin. Deficiency in AVP results in a syndrome characterized by large amounts of dilute urine (diabetes insipidus) while excess AVP impairs water excretion and causes hyponatremia.

inbox