Hypopituitarism

The pituitary gland, often referred to as the master gland, controls the function of multiple endocrine glands. It can be damaged by trauma, internal insult (loss of blood flow), and external insult such as radiation therapy. Hypopituitarism is defined as either partial or complete deficiency of anterior or posterior pituitary hormone secretion. Hormones secreted by the pituitary gland include growth hormone (GH); thyroid stimulating hormone (TSH); the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH); prolactin (PRL); adrenocorticotropic hormone (ACTH); oxytocin; and vasopressin (antidiuretic hormone). Evaluation of pituitary function and determination of the site of pathology often require testing of hormones released as well as end products.

Diagnosis

Indications for Testing

  • Anterior pituitary – symptoms compatible with multiple pituitary hormone deficiencies
    • Fatigue, depression, and other endocrine disorders
  • Posterior pituitary – symptoms of central diabetes insipidus
    • Polydipsia, polyuria, and nocturia
    • Children – fever, weight loss, irritability, delayed growth
  • Incidental pituitary lesion noted on imaging

Laboratory Testing

  • Anterior pituitary testing
    • Adrenocorticotropic hormone (ACTH) deficiency testing – see Adrenal Insufficiency
      • Use to determine presence of deficiency and pituitary origin
      • Initial testing
        • Measure early morning serum cortisol
          • Cortisol ≥5 µg/dL makes primary adrenal insufficiency less likely
            • If serious consideration is given to this diagnosis, perform stimulation testing
        • Follow abnormal cortisol results with ACTH testing
          • If ACTH >300 pg/dL – adrenal failure likely
          • If ACTH <10 pg/dL – pituitary failure likely
          • If ACTH 10-300 pg/dL – administer ACTH (cosyntropin) stimulation test
      • Testing based on ACTH result
        • ACTH stimulation test (cosyntropin)
          • Measures cortisol response to cosyntropin (250 µg using serial cortisol measures at 0, 30, and 60 minutes)
            • Cortisol <5 µg/dL – primary severe adrenal failure
            • Cortisol >18 µg/dL – normal; adrenal insufficiency unlikely
            • Cortisol ≤18 µg/dL but ≥5 µg/dL – evaluate for pituitary failure; secondary adrenal insufficiency likely
          • Evaluation for pituitary failure
            • Insulin tolerance testing (ITT)
              • Not recommended in children <6 years
            • Metyrapone overnight testing
              • If 11 deoxycortisol >7 µg/dL – adrenal failure unlikely; magnetic resonance imaging (MRI)/computed tomography (CT) of adrenal glands
              • If 11 deoxycortisol ≤7 µg/dL – pituitary failure likely; order MRI/CT
                • If still not clear – corticotropin releasing hormone (CRH) stimulus testing
                  • If ACTH <10 pg/mL – pituitary failure likely
    • Thyroid stimulating hormone (TSH) deficiency testing
      • TSH and free T4 (thyroxine)
      • Normal TSH and normal free T4
        • Repeat testing if high suspicion
        • No hypothyroidism – does not rule out insufficiency of other pituitary hormones
      • High TSH and low free T4
      • Low TSH and low free T4
        • Central hypothyroidism (anterior pituitary or hypothalamus etiology)
      • Normal TSH and low free T4
        • Suggests central hypopituitarism (anterior pituitary or hypothalamus)​
    • Gonadotropin deficiency testing
      • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and testosterone or estrogen
        • Normal LH/FSH, normal testosterone or estrogen
          • No gonadotropin deficiency
          • Repeat testing if high suspicion
        • Low LH/FSH, low testosterone or estrogen
          • Gonadotropin deficiency, hypopituitarism
        • High LH/FSH, low testosterone or estrogen
          • Primary hypogonadism (defect at level of gland, not central)
    • Prolactin (PRL) testing
      • Low PRL
        • Indicates anterior pituitary hypopituitarism
      • High PRL
        • Causes PRL-induced hypogonadism
        • May indicate PRL-secreting adenoma or idiopathic hypersecretion
    • Growth hormone (GH) deficiency testing
      • Perform after other hormone deficiencies have been corrected
      • Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3)  – see Growth Hormone Deficiency
  • Posterior pituitary testing (vasopressin/antidiuretic hormone testing)
    • Urine osmolality (UO) and/or serum/plasma osmolality (SO) and serum/plasma sodium (Na)
      • UO<SO and high Na – central diabetes insipidus
      • UO<250 mOsm/kg and low Na – primary polydipsia
      • UO<SO and normal Na – perform water deprivation test in hospital and order SO
        • SO>290 mOsm/kg, Na>140 mmol/L, and weight loss nearing 3% – diabetes insipidus
          • Order antidiuretic hormone (ADH)/arginine vasopressin hormone (AVH) plasma
            • High ADH/AVH– nephrogenic diabetes insipidus
            • Low ADH/AVH – central diabetes insipidus
          • Alternatively, administer vasopressin and order UO 1-2 hours post administration
            • >50% increased UO – central diabetes insipidus
            • <50% increased UO – nephrogenic diabetes insipidus

Histology

  • If pituitary adenoma is present, immunohistochemistry and pathologist examination may be required
  • Consider prolactin, growth hormone, or ACTH
  • For detailed descriptions, refer to ARUP’s Immunohistochemistry Stain Offerings

Imaging Studies

Magnetic resonance imaging (MRI) brain scan is the imaging of choice for pituitary masses.

Background

Epidemiology

  • Incidence  – 4-5/100,000
  • Age – incidence increases with age

Etiology

Pathophysiology

  • Anterior pituitary produces 6 major hormones
  • Posterior pituitary produces 2 major hormones
    • Oxytocin
    • Antidiuretic hormone/arginine vasopressin hormone (ADH/AVH)
  • Any insult to gland or vascular supply may cause hormone deficiency (hypopituitarism)
    • Loss of any of these hormones produces symptoms based on the hormones lost

Clinical Presentation

  • Varied – dependent on the region of pituitary gland involved and age of patient
  • Nonspecific
    • Headache
    • Visual disturbances
    • Weakness
  • Anterior pituitary
    • Gonadotropic hormones (FSH, LH, PRL)
    • GH
      • Adults – fatigue, decreased muscle mass and strength, reduced bone marrow density
      • Children – short stature, failure to thrive
      • Infants – seizures, hypoglycemia
    • ACTH
      • Adults – fatigue, nausea, vomiting
      • Children/infants – acute adrenal crises with shock
    • TSH
      • Adults – weight gain, coarse hair, fatigue
      • Children/infants – failure to thrive
  • Posterior pituitary (hypothalamic)
    • Central diabetes insipidus
      • Adults – polydipsia, polyuria, nocturia
      • Children – vomiting, diarrhea, dry skin, weight loss, irritability
      • Infants – fever, unusually wet diapers (polyuria), delayed growth, irritability

ARUP Laboratory Tests

Differential diagnosis of Cushing syndrome

Screen and diagnose primary and secondary adrenal insufficiency

Aid in diagnosis of adrenal insufficiency and determining the presence of anterior pituitary tumors

Aid in diagnosis of adrenocorticotropic hormone (ACTH) deficiency in the evaluation of hypopituitarism

Assess thyroid function

Identify risk in patients with palpable thyroid nodules

Reflex: if TSH is outside the reference interval, then Free T4 testing will be added

Aid in diagnosis of gonadotropin deficiency

Provides a calculated value for free testosterone concentration using total testosterone measured by immunoassay

 
Use to evaluate hypogonadism in cisgender males with a total testosterone concentration at the lower limit of normal 


May be used to evaluate testosterone status in individuals with protein-binding abnormalities or to monitor testosterone hormone therapies 


Not recommended when low testosterone concentrations, such as those found in children and cisgender females, are expected; for these individuals, testing by mass spectrometry is recommended; refer to Testosterone, Free and Total, Includes Sex Hormone-Binding Globulin (Adult Females, Children, or Individuals on Testosterone-Suppressing Hormone Therapy) (0081056)

Use this immunoassay to measure estradiol in adult premenopausal cisgender females and individuals on estrogen hormone therapies

Not recommended when low estradiol concentrations, such as those found in children, cisgender males, and postmenopausal females, are expected, or for monitoring antiestrogen (eg, aromatase inhibitor) therapy; the preferred estradiol test in these cases is Estradiol (Adult Males, Children, Postmenopausal Females, or Individuals on Estrogen-Suppressing Hormone Therapy) (0093247) 

Not recommended in the evaluation of estradiol status for individuals with protein-binding abnormalities or individuals on hormonal contraception; the preferred estradiol test for these individuals is Estradiol, Free, by Dialysis and Mass Spectrometry (2006160) 

Use to evaluate estrogen status in children, cisgender males, and postmenopausal cisgender females

Most useful when low estrogen concentrations are expected, regardless of the patient’s sex assigned at birth

Screening for anterior pituitary tumor

Aid in diagnosis of growth hormone excess or deficiency disorders

Not a first-line test in the evaluation of growth disorders

Aid in workup of suspected anterior hypopituitarism

Aid in histologic diagnosis of pituitary tumors

Stained and returned to client pathologist; consultation available if needed

Related Tests

Preferred test for screening and monitoring of thyroid function

Not the preferred initial thyroid disorder screening test

Order following an abnormal thyroid stimulating hormone (TSH) result to diagnose thyroid disease

Order in conjunction with TSH in cases of suspected secondary hypothyroidism

Provides a calculated value for free testosterone concentration using total testosterone measured by immunoassay 

Use to evaluate hypogonadism in cisgender males with a total testosterone concentration at the lower limit of normal 

May be used to evaluate testosterone status in individuals with protein-binding abnormalities or to monitor testosterone hormone therapies 

Not recommended when low testosterone concentrations, such as those found in children and cisgender females, are expected; for these individuals, testing by mass spectrometry is recommended; refer to Testosterone, Free (Adult Females, Children, or Individuals on Testosterone-Suppressing Hormone Therapy) (0081059)

Use to screen, diagnose, and monitor diseases associated with excess or deficient cortisol production

May be useful for monitoring certain pituitary tumors

References

Additional Resources
  • 17467517

    Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I , et al. Hypopituitarism. Lancet. 2007;369(9571):1461-1470.

  • Medical Experts

    Contributor

    Lehman

    Christopher M. Lehman, MD
    Associate Professor of Pathology (Clinical), University of Utah
    Medical Director, University of Utah Health Hospital Clinical Laboratory, ARUP Laboratories
    Contributor