Hypopituitarism

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 >20 µg/dL – normal; adrenal insufficiency unlikely
          • Cortisol ≤20 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
        • Primary hypothyroidism – disease is at the level of the thyroid gland (see Thyroid Disease)
      • 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.