Hypopituitarism

Diagnosis

Indications for Testing

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

Laboratory Testing

  • Anterior pituitary testing
    • Adrenocorticotropic hormone (ACTH) deficiency testing
      • ACTH and serum/plasma cortisol
        • Normal ACTH and cortisol – repeat testing if high suspicion
          • Normal repeat test results– no adrenal component to insufficiency
          • Low cortisol and low/normal ACTH – perform metyrapone testing or insulin-induced hypoglycemia with repeat ACTH and 11-deoxycortisol
            • Low ACTH and 11-deoxycortisol – pituitary ACTH deficiency
            • High ACTH and low 11-deoxycortisol – adrenal etiology
        • Low or normal ACTH and low cortisol – see above
      Thyroid stimulating hormone (TSH) deficiency testing
      • TSH and free T4 (thyroxine)
        • Low or normal results
          • Repeat testing if high suspicion
            • Normal TSH and free T4 – no thyroid component to insufficiency
            • High TSH, low free T4 – primary hypothyroidism
            • Normal/low TSH, low free T4 – TSH deficiency
        • High – suggests primary hypothyroidism; see Thyroid Disease
      Gonadotropin deficiency testing
      • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and testosterone or estrogen
        • Normal LH/FSH, normal testosterone or estrogen – repeat testing if high suspicion
          • Normal results – no gonadotropin deficiency
          • Low LH/FSH, low testosterone or estrogen – gonadotropin deficiency
        • Low LH/FSH, low testosterone or estrogen – gonadotropin deficiency
        • High LH/FSH, low testosterone or estrogen – primary hypogonadism
      Prolactin (PRL) testing
      • Prolactin
        • High PRL – prolactin-induced hypogonadism
        • Low PRL – FSH deficiency
      Growth hormone (GH) deficiency testing
      • Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3)
        • Normal IGF-1 and IGFBP-3 – repeat testing if high suspicion
          • Normal results – no growth hormone component to insufficiency
          • Low IGF-1/IGFBP-3 – insulin-induced hypoglycemia testing with serial GH measurement
        • Low IGF-1 and IGFBP-3 – see above
  • Posterior pituitary 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 ADH/AVH plasma
              • Low ADH/AVH – central diabetes insipidus
              • High ADH/AVH– nephrogenic 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

  • Immunohistochemistry if pituitary adenoma is present – consider prolactin, growth hormone, ACTH, or TSH

Imaging Studies

  • MRI usually required to identify sellar and parasellar masses

Clinical Background

The pituitary gland, often referred to as the master gland, controls the function of multiple endocrine glands. Hypopituitarism is defined as either partial or complete deficiency of anterior or posterior pituitary hormone secretion.

Epidemiology

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

Etiology

Pathophysiology

  • Anterior pituitary produces 6 major hormones
  • Posterior pituitary produces
    •  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 will produce 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
    • 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

Treatment

  • Hormone replacement based on deficiencies

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Cortisol, Serum or Plasma 0070030
Method: Quantitative Chemiluminescent Immunoassay

Aid in the diagnosis of adrenal insufficiency

   
Adrenocorticotropic Hormone 0070010
Method: Quantitative Chemiluminescent Immunoassay

Aid in the diagnosis of adrenal insufficiency

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

Aid in the diagnosis of adrenal insufficiency

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

Diagnose thyroid deficiency

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

Aid in the diagnosis of gonadotropin deficiency

   
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. 

Aid in the diagnosis of gonadotropin deficiency

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

Aid in the diagnosis of gonadotropin deficiency

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

Aid in the diagnosis of gonadotropin deficiency

   
Prolactin 0070115
Method: Quantitative Chemiluminescent Immunoassay

Diagnose gonadal disorders

   
IGF-1 (Insulin-Like Growth Factor 1) 0070125
Method: Quantitative Chemiluminescent Immunoassay

Aid in the diagnosis of GH deficiency

   
IGF Binding Protein-3 0070060
Method: Quantitative Chemiluminescent Immunoassay

Aid in the diagnosis of GH deficiency

   
Growth Hormone 0070080
Method: Quantitative Chemiluminescent Immunoassay

Aid in the diagnosis of GH deficiency

   
Osmolality, Urine 0020228
Method: Freezing Point

Aid in the diagnosis of posterior pituitary function deficiency

   
Osmolality, Serum or Plasma 0020046
Method: Freezing Point

Aid in the diagnosis of posterior pituitary function deficiency

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

Aid in the diagnosis of posterior pituitary function deficiency

   
Arginine Vasopressin Hormone 0070027
Method: Quantitative Radioimmunoassay

Aid in the diagnosis of posterior pituitary function deficiency

   
ACTH by Immunohistochemistry 2003427
Method: Immunohistochemistry

Aid in histologic diagnosis of pituitary tumors

Stained and returned to client pathologist; consultation available if needed

   
Growth Hormone by Immunohistochemistry 2003929
Method: Immunohistochemistry

Aid in histologic diagnosis of pituitary tumors

Stained and returned to client pathologist; consultation available if needed

   
Prolactin by Immunohistochemistry 2004109
Method: Immunohistochemistry

Aid in histologic diagnosis of pituitary tumors

Stained and returned to client pathologist; consultation available if needed

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay
Thyroxine, Free (Free T4) 0070138
Method: Quantitative Electrochemiluminescent Immunoassay
Testosterone Free, Adult Male 0070111
Method: Quantitative Electrochemiluminescent Immunoassay
Total Testosterone and SHBG are measured and free testosterone is estimated from these measurements.
Follicle Stimulating Hormone, Serum 0070055
Method: Quantitative Electrochemiluminescent Immunoassay
Luteinizing Hormone, Serum 0070093
Method: Quantitative Electrochemiluminescent Immunoassay
Adrenocorticotropic Hormone Stimulation, 0 Minutes 0070031
Method: Quantitative Chemiluminescent Immunoassay