Hospital Medicine

Anterior pituitary disorders

Anterior pituitary disorders

I. Problem/Condition.

The pituitary gland is often thought of as the "master gland," coordinating the complex functions of multiple endocrine glands along with the hypothalamus. The anterior pituitary secretes hormones that affect the thyroid, adrenal gland, ovaries and testes, the liver, and mammary glands. It makes up more than 80% of the pituitary gland and secretes six major hormones:

  • Growth hormone (GH), also known as somatotropin

  • Prolactin

  • Adrenocorticotropin hormone (ACTH)

  • Thyroid-stimulating hormone (TSH), also known as thyrotropin

  • Luteinizing hormone (LH)

  • Follicle-stimulating hormone (FSH)

The hormones secreted by the anterior pituitary act on target organs to release the appropriate hormone (see Table I). The hormones secreted by the target organs have inhibitory control at the levels of the hypothalamus and the anterior pituitary.

Table I.

Hormones secreted by the anterior pituitary
Hormone secreted by hypothalamus Anterior pituitary Target organ Hormone secreted by target organ Function of hormone
GHRH GH Liver IGF-1 Bone and organ growth
CRH ACTH Adrenal cortex Glucocorticoids Cell homeostasis and function
GnRH FSH, LH Ovaries or testes Estrogen or progesterone in females, testosterone in males Reproduction (spermatogenesis or ovulation)
TRH TSH Thyroid T3,T4 Thermogenesis and metabolism
Dopamine** Prolactin Mammary glands Milk Lactation

Presenting signs and symptoms will be determined by the hormones that are deficient or in excess. Patients can experience partial (hypopituitarism) or complete (panhypopituitarism) loss of their anterior pituitary function. Patients can also experience visual field deficits due to mass effect of a pituitary lesion on the optic nerve or optic chiasm, headache, and more rarely ophthalmoplegia due to mass effect on cranial nerves.

In the inpatient setting, however, it is important to keep in mind that patients may not present with complaints related to pituitary hormone dysfunction or neurological symptoms, or if they do, symptoms can be vague. It is more likely that hospitalists will encounter an incidental finding of a pituitary lesion during workup for other reasons. Treatment of a pituitary lesion is largely dependent on various features, including the size of the pituitary lesion and its rate of growth; the presence of neurological symptoms from local mass effect; and either excessive or insufficient hormone production.

II. Diagnostic Approach

A. Describe a diagnostic approach/method to the patient with this problem.

The simplest way to consider anterior pituitary dysfunction is to first think about the clinical syndrome that would be produced by either the over- or under-production of the hormones. See Table II for an overview (more details in "History" section below).

Table II.

Clinical syndromes associated with abnormal production of anterior pituitary hormones
Hormone Overproduction Underproduction
Growth hormone Acromegaly (gigantism) Growth retardation
ACTH Cushing’s disease Addison’s disease (often, mineralocorticoid function is not affected)
TSH Hyperthyroidism Hypothyroidism
LH and FSH Polycystic ovary syndrome, precocious puberty Infertility, amenorrhea, decreased libido (males)
Prolactin Infertility, amenorrhea, decreased libido (males) Inability to lactate

Further details regarding the approach and treatment of syndromes due to the underproduction of anterior pituitary hormones can be found in the hypopituitarism chapter.

B. What is the differential diagnosis for this problem?

After determining that the underlying problem is excessive versus insufficient hormone production, it is then important to consider whether the underlying problem resides within the pituitary gland itself or outside of the pituitary. Again, it is important to consider each hormone separately as pathology in target organs can also affect the secretion of the associated hormone.

When considering pathology related to the pituitary itself, the most common etiology of either over- or under-production of pituitary hormones in adults is a pituitary lesion. The most common lesion is a pituitary adenoma, which can be categorized based on its size and the presence of hormone hypersecretion or hyposecretion. However, other etiologies of a pituitary lesion can include:

  • Pituitary adenomas (symptoms can also be related to mass effect)

    • Hypersecreting (in order of most to least common hormone overproduced): prolactin, growth hormone, ACTH, glycopeptides (LH, FSH, TSH, a-subunit)

    • Non-secreting

    • Hyposecreting (in order of most to least common hormone underproduced): gonadotropins (LH, FSH), TSH, growth hormone, ACTH

  • Non-pituitary tumors (symptoms can also be related to mass effect)

    • Germ cell tumors

    • Craniopharyngioma

    • Meningioma

    • Metastatic disease

  • Vascular lesions

    • Aneurysms

    • Hamartomas

    • Infarctions

    • Pituitary apoplexy (hemorraghic event), including Sheehan’s syndrome, acute shock, hypertension, or diabetes

  • Infiltrative

    • Sarcoidosis

    • Histiocytosis

    • Lymphocytic hypophysitis

    • Eosinophilic granulomas

  • Other

    • Rathke’s cleft cyst

    • Anatomic abnormalities

1. Historical information important in the diagnosis of this problem.

Because signs or symptoms due to pituitary disorders are less commonly the presenting complaint for inpatients, the hospitalist must take a thorough targeted history if an anterior pituitary disorder is suspected, or if an incidental pituitary lesion is found.

Pertinent history will be relevant for the hormone that is over- or under-produced. Note that symptoms related to mass effect from a lesion are also key historical elements and commonly manifest as visual field disturbances and headaches. Specific questions related to hormonal dysfunction are included in Table III.

Table III.

Specific questions for history taking
Hormone Overproduction Underproduction
Growth hormone Coarsening of facial featuresChange in ring or shoe sizeExcess sweatingHypertensionObstructive sleep apneaDiabetes Visceral obesityDecreased muscle massGrowth retardation
ACTH Pituitary Cushing’sExcessive weight gainEasy bruisingMuscle weaknessNew stretch marks Hypocortisolism with relative preserved mineralocorticoid production
TSH Hyperthyroidism Hypothyroidism
LH and FSH Polycystic ovary syndrome, precocious puberty Infertility, amenorrhea, decreased libido (males)
Prolactin Infertility, amenorrhea/galactorrhea (females), decreased libido (males) Oligomenorrhea, inability to lactate (females), decreased sexual function, loss of facial or body hair

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Physical exam findings are useful in identifying the hormones affected.

  • General: anxiety and tachycardia can be signs of hyperthyroidism.

  • Head, eyes, ears, nose, and throat (HEENT): frontal bossing, prognathism and macroglossia can indicate excess growth hormone.

  • Neurological: visual field deficits and cranial nerve palsies can indicate mass effect from a pituitary lesion.

  • Skin: skin tags or oily skin can be a sign of excess growth hormone; supraclavicular fat, wide purple striae, central obesity, moon facies, thin skin, proximal muscle atrophy and multiple bruising can be signs of pituitary Cushing’s.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Laboratory tests are important for assessing hormone production, as these can be under- or over- produced. Radiographic tests are useful in characterizing mass lesions. Again, it is important to remember that an assessment of hormone production is critical to making the diagnosis.

Tests to assess for pituitary sufficiency will attempt to stimulate the production of the desired hormone or measure the level of the target hormone. These can include:

  • GH deficiency:

    • Insulin tolerance test - normal response is GH level greater than 3 μg/L, glucose greater than 40 mg/dL

    • GH-releasing hormone-arginine test (L-arginine test) - normal response is GH level greater than 3 μg/L

    • L-dopa test - normal response is GH level greater than 3 μg/L

  • ACTH deficiency:

    • Metyrapone test - ACTH greater than 75 pg/ML

    • Cosyntropin (ACTH stimulation) test (low or high dose) - Cortisol level greater than 18 μg/dL

  • TSH deficiency:

    • Free T4 levels - low

    • TSH level is NOT useful for secondary hypothyroidism

  • FSH and LH deficiency:

    • Serum levels of FSH, LH - low

    • Testosterone (males) - low

    • Estradiol (females) - low

(See also "Hypopituitarism".)

Screening tests for hormone overproduction can attempt to suppress production of the hormone or measure the serum levels of the hormone. Tests with positive results include:

  • GH:

    • Serum insulin-like growth factor 1 (IGF-1) level – elevated

    • GH level after oral glucose administration - elevated (GH should suppress to less than 1μg/L)

  • TSH:

    • TSH - normal or elevated in setting of elevated free T3 and T4

  • ACTH (Cushing’s syndrome, Cushing’s disease)

    • 24-hour urinary free cortisol - elevated to 250 μg/24 hours

    • Dexamethasone 1 mg at 11 pm and 8 am - fasting plasma cortisol expected to suppress to less than 5 μg/dL

    • Salivary cortisol- elevated to >6 ng/mL at 9 am and >1 ng/mL at 11 pm (differences due to diurnal variation in cortisol levels)

  • Prolactin:

    • Prolactin level - elevated to above 100-200 ng/mL (assumes non-pregnant patient)

Radiologic exams are useful in assessing for the presence of a pituitary lesion. If a pituitary lesion is incidentally identified on computed tomography (CT) scan of the head, magnetic resonance imaging (MRI) is the preferred diagnostic modality for assessing the size and location of a pituitary mass. A patient found to have a pituitary lesion abutting the optic chiasm or optic nerve on imaging should undergo formal visual field examination. A pituitary adenoma, the most common pituitary lesion encountered by hospitalists and which tends to be an incidental finding, is categorized on imaging by size - a macroadenoma is 10 mm in diameter or greater, whereas a microadenoma is less than 10 mm in diameter.

Current recommendations suggest that every pituitary adenoma found on imaging, whether micro- or macro-adenoma, should undergo laboratory evaluation for hormone overproduction or underproduction, regardless of whether a patient is symptomatic or not.

Specifically, all patients should have serum testing for prolactin levels (the most commonly overproduced anterior pituitary hormone), IGF-1 (patients with GH-secreting adenomas can be asymptomatic for prolonged periods before complications arise), and for glucocorticoid excess or deficiency.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Please see section above for related values.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

If a pituitary lesion is incidentally identified on computed tomography (CT) scan of the head, it should be further characterized with an MRI of the pituitary and biochemical testing as detailed above. However, not all hormones need to be reflexively tested as the history and physical can help to delineate, for example, whether testing for gonadotropins is warranted, as well as thyroid function tests. Consultation with an endocrinologist can be helpful.

III. Management while the Diagnostic Process is Proceeding

A. Management of anterior pituitary disorders.

The key steps in management of pituitary lesions are determined by: 1) pituitary function, particularly by determining which hormones are being over- or under-produced; 2) the presence of neurological deficits (visual field disturbances, headache or ophthalmoplegia) that are directly related to a pituitary mass affecting local structures; 3) evidence of pituitary lesion growth on serial imaging. These factors will determine whether medical or surgical management, typically via transsphenoidal resection, should be pursued.

Pituitary lesions that are shown to over- or under-produce hormones should undergo evaluation for surgery. The exception is a prolactin-secreting pituitary lesion, or prolactinoma, which can be medically managed with the use of dopamine agonists (cabergoline and bromocriptine), unless side effects prevent its use. Once hormonal abnormalities are identified, it is suitable to involve endocrine subspecialists.

If a patient with visual field disturbances, ophthalmoplegia, or unremitting headache is found to have a pituitary lesion, surgical consultation is recommended. In addition, patients found to have a pituitary lesion on MRI that is abutting the optic nerve or chiasm should also undergo surgical evaluation, as there is concern that the lesion could progress and lead to neurological deficits.

If a previously identified pituitary lesion is shown to progress in size on serial MRI imaging as indicated by rapid expansion or growth towards the optic chiasm or optic nerve, then surgical consultation is warranted.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

An important pitfall is not assessing for visual field defects or symptoms of mass effect due to a pituitary mass lesion. These symptoms will make surgical therapy more likely.

Side effects of medications depend on the hormone abnormality identified.

Treatment of prolactinomas with dopamine antagonists may be poorly tolerated (among the more common side effects are nausea, emesis, and lethargy), in which case transsphenoidal resection of a prolactinoma may be required.

IV. What’s the evidence?

Freda, P, Beckers, A, Katznelson, L, Molitch, M, Montori, V, Post, K, Vance, M. "Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. vol. 96. 2011. pp. 894-904.

Imran, S. "Analysis and Natural History of Pituitary Incidentalomas". Eur J Endocrinol. vol. 175. 2016. pp. 1-9.

Fernandez-Balsells, MM. "Natural History of Non-functioning Pituitary Adenomas and Incidentalomas: a Systematic Review and Metaanlaysis". J Clin Endocrinol Metab. vol. 96. 2011. pp. 905-912.

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