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
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

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
  • 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

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
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Cortisol, Serum 0070030
Method: Quantitative Chemiluminescent Immunoassay

Adrenocorticotropic Hormone 0070010
Method: Quantitative Chemiluminescent Immunoassay

11-Deoxycortisol Quantitative by HPLC-MS/MS, Serum or Plasma 0092331
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Luteinizing Hormone and Follicle Stimulating Hormone 0070193
Method: Quantitative Electrochemiluminescent Immunoassay

Testosterone, Free and Total (Includes Sex Hormone Binding Globulin), Adult Male 0070109
Method: Quantitative Electrochemiluminescent Immunoassay
The concentration of free testosterone is derived from a mathematical expression based on the constant for the binding of testosterone to sex hormone binding globulin. 

Estradiol, Adult Premenopausal Female, Serum or Plasma 0070045
Method: Quantitative Chemiluminescent Immunoassay

Estrogens, Fractionated by Tandem Mass Spectrometry 0093248
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Prolactin 0070115
Method: Quantitative Chemiluminescent Immunoassay

Insulin-Like Growth Factor 1 (IGF-1) with Calculated Z-Score 2007698
Method: Quantitative Chemiluminescent Immunoassay

Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) 0070060
Method: Quantitative Chemiluminescent Immunoassay

Growth Hormone 0070080
Method: Quantitative Chemiluminescent Immunoassay

Osmolality, Urine 0020228
Method: Freezing Point

Osmolality, Serum or Plasma 0020046
Method: Freezing Point

Sodium, Plasma or Serum 0020001
Method: Quantitative Ion-Selective Electrode

Arginine Vasopressin Hormone 0070027
Method: Quantitative Radioimmunoassay

ACTH by Immunohistochemistry 2003427
Method: Immunohistochemistry

Growth Hormone by Immunohistochemistry 2003929
Method: Immunohistochemistry

Prolactin by Immunohistochemistry 2004109
Method: Immunohistochemistry

Guidelines

Fleseriu M, Bodach ME, Tumialan LM, Bonert V, Oyesiku NM, Patil CG, Litvack Z, Aghi MK, Zada G. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline for Pretreatment Endocrine Evaluation of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016; 79(4): E527-9. PubMed

Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, Vance ML, Endocrine Society. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(4): 894-904. PubMed

Ghigo E, Masel B, Aimaretti G, Léon-Carrión J, Casanueva FF, Dominguez-Morales MR, Elovic E, Perrone K, Stalla G, Thompson C, Urban R. Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj. 2005; 19(9): 711-24. PubMed

General References

Darzy KH, Shalet SM. Hypopituitarism following radiotherapy. Pituitary. 2009; 12(1): 40-50. PubMed

Kargi AY, Merriam GR. Diagnosis and treatment of growth hormone deficiency in adults. Nat Rev Endocrinol. 2013; 9(6): 335-45. PubMed

Kelberman D, Dattani MT. Hypopituitarism oddities: congenital causes. Horm Res. 2007; 68 Suppl 5: 138-44. PubMed

Nakamoto J. Laboratory diagnosis of multiple pituitary hormone deficiencies: issues with testing of the growth and thyroid axes. Pediatr Endocrinol Rev. 2009; 6 Suppl 2: 291-7. PubMed

Prabhakar VK, Shalet SM. Aetiology, diagnosis, and management of hypopituitarism in adult life. Postgrad Med J. 2006; 82(966): 259-66. PubMed

Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla G, Ghigo E. Hypopituitarism. Lancet. 2007; 369(9571): 1461-70. PubMed

Toogood AA, Stewart PM. Hypopituitarism: clinical features, diagnosis, and management. Endocrinol Metab Clin North Am. 2008; 37(1): 235-61, x. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Gronowski AM, Fantz CR, Parvin CA, Sokoll LJ, Wiley CL, Wener MH, Grenache DG. Use of serum FSH to identify perimenopausal women with pituitary hCG. Clin Chem. 2008; 54(4): 652-6. PubMed

Thienpont LM, Van Uytfanghe K, Blincko S, Ramsay CS, Xie H, Doss RC, Keevil BG, Owen LJ, Rockwood AL, Kushnir MM, Chun KY, Chandler DW, Field HP, Sluss PM. State-of-the-art of serum testosterone measurement by isotope dilution-liquid chromatography-tandem mass spectrometry. Clin Chem. 2008; 54(8): 1290-7. PubMed

Medical Reviewers

Content Reviewed: 
September 2017

Last Update: December 2017