Hypopituitarism

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
• Hypothalamic disease (eg. tumor)

Laboratory Testing

• Anterior pituitary testing
  • Adrenocorticotropic hormone (ACTH) deficiency testing

    • ACTH and serum 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

    • 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)
      • 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 (alternate tests include arginine plus GHRH stimulation or glucagon stimulation)
          • GH <4 ng/mL (adults) or <5 ng/mL (children) – growth hormone deficiency
      • 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
          • 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

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

Imaging Studies

• MRI usually required to identify sellar and parasellar masses