Hypopituitarism

Last Literature Review: April 2023 Last Update:

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Hypopituitarism is the partial or total deficiency of at least one of the hormones produced by the pituitary gland.  Panhypopituitarism occurs when the production of all pituitary hormones has decreased, and patients may transition from hypopituitarism to panhypopituitarism over time. The anterior lobe of the pituitary gland produces adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone, prolactin, and gonadotropins (ie, luteinizing hormone [LH] and follicle-stimulating hormone [FSH]). The posterior lobe produces oxytocin and arginine vasopressin (AVP).  A decrease in the production of various pituitary hormones often, though not always, occurs in the following order: growth hormone and gonadotropins, TSH, then ACTH and prolactin.  Laboratory testing for the diagnosis of hypopituitarism may include an assessment of hormones produced by the pituitary gland as well as hormones produced by the glands stimulated by the pituitary gland (eg, thyroxine and cortisol, which are produced by the thyroid and adrenal glands, respectively). 

Quick Answers for Clinicians

What are the common causes of hypopituitarism?

Hypopituitarism and panhypopituitarism are most commonly caused by benign pituitary tumors or the treatment of such tumors by pituitary surgery radiotherapy.  Other causes include traumatic brain injuries (TBIs), pituitary apoplexy, hemochromatosis, and certain infectious diseases.  In children, hypopituitarism may be congenital and may be caused by structural abnormalities of the pituitary gland or by certain craniofacial defects. 

Which hormonal interactions need to be considered when assessing pituitary hormones?

The various hormones produced or regulated by the pituitary gland, including hormones of the hypothalamic-pituitary-adrenal (HPA) axis, affect one another to various degrees. These interactions have clinical implications and entail additional testing considerations in individuals with adrenal insufficiency, central hypothyroidism, growth hormone deficiency, hypogonadism, and diabetes insipidus.  

Because of the complex interactions among these hormones, the following should be considered when evaluating specific conditions associated with hypopituitarism:

Condition Laboratory Testing Considerations

Central adrenal insufficiency

Assess HPA axis functionality before and after growth hormone replacement therapy

Monitor for diabetes insipidus in individuals being treated for adrenal insufficiency

If diabetes insipidus improves in patients without an adrenal insufficiency diagnosis, perform adrenal insufficiency testing

Estrogen replacement therapy can elevate serum cortisol levels, which may affect adrenal evaluation

Central hypothyroidism

Monitor thyroid function in patients receiving therapy for growth hormone deficiency

Treat central hypothyroidism before assessing for growth hormone deficiency

Growth hormone deficiency

Assess HPA axis functionality before and after starting growth hormone replacement therapy

Monitor thyroid function in patients receiving therapy for growth hormone deficiency

Treat central hypothyroidism before assessing for growth hormone deficiency

Hypogonadotropic hypogonadism

 

Estrogen replacement therapy can elevate serum cortisol levels, which may affect adrenal evaluation

Diabetes insipidus

Monitor for diabetes insipidus in individuals being treated for adrenal insufficiency

If diabetes insipidus improves in patients without an adrenal deficiency diagnosis, test for adrenal insufficiency

Sources: Fleseriu, 2016 ; Feldt-Rasmussen, 2018 

Indications for Testing

Testing for hypopituitarism should be performed if clinical suspicion for a pituitary hormone deficiency exists, if deficiency of at least one pituitary hormone has been documented, or if a condition that is known to cause hypopituitarism is present (eg, pituitary incidentaloma, traumatic brain injury, treatment of pituitary adenomas through surgery or radiotherapy).    Symptoms may help guide initial testing.

Hormone Deficiencies Caused by Hypopituitarism
Deficient Hormone(s) Associated Disorder Common Symptoms Other ARUP Consult Resources

ACTH

Central adrenal insufficiency

Chronic: lethargy, weight loss, tiredness

Acute: nausea, hypotension, hyponatremia, vomiting

Adrenal Insufficiency topic

Adrenal Insufficiency Testing Algorithm

Growth hormone

Growth hormone deficiency

Children: reduced growth

Adults: low energy, increased fat mass, decreased muscle mass

Growth Hormone Deficiency topic

Growth Hormone Testing in Pediatric Patients Testing Algorithm

Growth Hormone Testing in Transition Patients Testing Algorithm

Growth Hormone Testing in Adult Patients Testing Algorithm

TSH

Central hypothyroidism

Fatigue, cold intolerance, weight gain (with reduced severity compared to primary hypothyroidism)

Hypothyroidism topic

Thyroid Disease Testing Algorithm

LH and FSH (gonadotropins)

Hypogonadism (male and female)

Premenopausal individuals with ovaries: amenorrhea or irregular menstruation, fertility issues

Individuals with testes: testosterone deficiency, infertility

Male Hypogonadism topic

Hypogonadism Testing Algorithm

Amenorrhea topic

Amenorrhea Testing Algorithm

Prolactin

Hyperprolactinemia (leading to hypogonadism)

Premenopausal individuals with ovaries: amenorrhea or irregular menstruation, fertility issues

Individuals with testes: testosterone deficiency, infertility

Male Hypogonadism topic

Hypogonadism Testing Algorithm

Amenorrhea topic

Amenorrhea Testing Algorithm

Hypoprolactinemia

Inadequate lactation

AVP

Central diabetes insipidus

Excessive urine production, excessive thirst

Central Diabetes Insipidus (Posterior Pituitary) Testing Algorithm

Sources: Fleseriu, 2016 ; Higham, 2016 

Pituitary Hormone Testing

If hypopituitarism is suspected, evaluations should be performed for all hormones released by the pituitary gland. Because some analytes (particularly estradiol, testosterone, growth hormone, and free thyroxine) have large interassay variability, the same assay from the same laboratory should be used for all serial measurements. 

Adrenocorticotropic Hormone

Because ACTH regulates the production of cortisol, decreased ACTH production may result in adrenal insufficiency.  High ACTH concentrations are associated with primary adrenal insufficiency. For detailed information on the diagnosis of primary adrenal insufficiency, refer to the ARUP Consult Adrenal Insufficiency topic.

Because low to normal levels of ACTH do not necessarily indicate central adrenal insufficiency, the initial test for the assessment of central adrenal insufficiency is serum cortisol, measured in the morning.  Low cortisol concentrations indicate adrenal insufficiency, whereas high cortisol concentrations likely rule it out. 

When initial serum cortisol concentrations are indeterminate, a corticotropin stimulation test should be performed, and cortisol should be measured 30 or 60 minutes after the administration of cosyntropin.  A high result suggests a diagnosis of central adrenal insufficiency, whereas a low result suggests primary adrenal insufficiency.  Either a high-dose or low-dose test may be used.  This test has a low specificity, which should be considered along with the pretest probability of the disease when approaching diagnosis. 

For individuals taking hydrocortisone or glucocorticoids, any testing of the hypothalamus-pituitary-adrenal (HPA) axis should be performed at least 18-24 hours after the last dose of hydrocortisone and longer after the last dose of synthetic glucocorticoids. 

Growth Hormone

When a strong clinical suspicion of growth hormone deficiency (GHD) exists in conjunction with deficits in at least three other pituitary hormones, biochemical testing for GHD is not recommended.  For detailed information on the diagnosis of GHD, refer to the ARUP Consult Growth Hormone Deficiency topic.

After the initiation of GH replacement therapy, thyroid function and adrenal function should be assessed. 

Thyroid-Stimulating Hormone

Central hypothyroidism usually occurs in the presence of other pituitary hormone deficiencies.  For detailed information on the diagnosis of hypothyroidism, refer to the ARUP Consult Hypothyroidism topic.

Luteinizing Hormone and Follicle-Stimulating Hormone

Deficiencies in the pituitary gonadotropins (LH and FSH) result in central hypogonadotropic hypogonadism in both individuals with testes and individuals with ovaries. 

Individuals With Testes

In individuals with testes, hypogonadotropic hypogonadism may result in low testosterone and/or impaired spermatogenesis.  For detailed information about the diagnosis of hypogonadism in individuals with testes, refer to the ARUP Consult Male Hypogonadism topic.

Individuals With Ovaries

In individuals with ovaries, hypogonadotropic hypogonadism may result in amenorrhea or oligomenorrhea.  In individuals with these symptoms, other causes of impaired ovulation (eg, thyroid disease and hyperandrogenism) should be ruled out, especially in individuals without deficiencies in other pituitary hormones.  Refer to the ARUP Consult Amenorrhea topic for the appropriate workup.

Serum estradiol, FSH, and LH should be measured when assessing for hypogonadotropic hypogonadism in individuals with ovaries.  In premenopausal individuals, low serum estradiol combined with low LH and low FSH concentrations suggests a diagnosis of hypogonadotropic hypogonadism, although the results must take the menstrual cycle phase into account.  In postmenopausal individuals, an absence of elevated FSH and LH confirms a diagnosis of hypogonadism, as long as the patient is not receiving hormone replacement therapy. 

Dynamic testing for gonadotropin-releasing hormone (GnRH) does not provide useful diagnostic information. 

Prolactin

Hypopituitarism may be associated with either hypoprolactinemia or hyperprolactinemia (which can cause hypogonadism).   A single elevated serum prolactin measurement establishes the diagnosis of hyperprolactinemia unless there is high venipuncture stress.  For more information on the appropriate follow-up to a diagnosis of hyperprolactinemia, refer to the Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline. 

Arginine Vasopressin

A deficiency in AVP, also referred to as antidiuretic hormone (ADH) or arginine vasopressin hormone (AVH), can result in diabetes insipidus.   Testing is used to differentiate between primary polydipsia (in which excessive thirst and fluid consumption lead to dilute urine), central diabetes insipidus (caused by low AVP secretion due to damage of the hypothalamus or pituitary gland), and nephrogenic diabetes insipidus (caused by impaired kidney function that results in the ability to concentrate urine).  

Initial Testing

Initial testing for diabetes insipidus should include measurements for urine osmolality, serum osmolality, and sodium levels.  

Interpretation of Urine and Serum Osmolality Test Results
Urine Osmolality Serum Osmolality Interpretation

Low

Low

Suggests primary polydipsia

Low

High

Suggests diabetes insipidus

Source: Gubbi, 2019 

Water Deprivation Test

If results are inconclusive or suggest diabetes insipidus, a water deprivation test, long considered the standard diagnostic test for diabetes insipidus, should be performed.  Urine osmolarity, serum osmolarity, and sodium levels are measured after a period of dehydration; the results of this test can often definitively differentiate between diabetes insipidus and primary polydipsia. 

Central diabetes insipidus and nephrogenic diabetes insipidus can be differentiated by measuring urine osmolarity after administration of desmopressin. 

ARUP Laboratory Tests

Testing for Central Adrenal Insufficiency
Testing for Growth Hormone Insufficiency
Testing for Central Hypothyroidism
Testing for Central Hypogonadism
Testing for Hypo- or Hyperprolactinemia
Testing for Central Diabetes Insipidus

References