Hypopituitarism

Diagnostic Algorithm

  Hypopituitarism (Anterior Pituitary) Testing Algorithm

  Central Diabetes Insipidus (Posterior Pituitary) Testing Algorithm

Clinical Background

The pituitary gland, often referred to as the master gland, orchestrates the complex functioning 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

• Tumor – adenoma, lymphoma, metastatic infiltration
• Autoimmune disease
• Trauma – surgery, head injury, radiation
• Vascular event – hemorrhagic apoplexy, pregnancy-related (Sheehan syndrome), sickle cell disease
• Infections – histoplasmosis, tuberculosis, toxoplasmosis
• Infiltrative disease – sarcoidosis, hemochromatosis
• Genetic disease – Kallmann syndrome, Prader-Willi syndrome, Laurence-Moon-Bardet-Biedl syndrome
• Other – empty sella syndrome

Pathophysiology

• Anterior pituitary produces 6 major hormones
  • Prolactin (PRL)
  • Growth hormone (GH)
  • Adrenocorticotropic hormone (ACTH)
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
  • Thyroid-stimulating hormone (TSH)
• Posterior pituitary releases oxytocin and antidiuretic hormone (ADH)
• Any insult to gland or vascular supply may cause hypopituitarism
• Loss of any of these hormones will produce specific symptoms based on the particular hormones lost

Clinical Presentation

• Varied – dependent on the part of the pituitary gland involved and the age of the patient
• Nonspecific
  • Headache
  • Visual disturbances
• Anterior pituitary
  • Gonadotropic hormones (FSH, LH, PRL)
    • Adults – sexual dysfunction and amenorrhea
    • Infants – cryptorchidism, microphallus
    • Children – failure of pubertal development
  • GH
    • Adults – fatigue, decreased muscle mass and strength, reduced bone marrow density
    • Infants – convulsions, hypoglycemia
    • Children – short stature, failure to thrive
  • ACTH
    • Adults – fatigue, nausea, vomiting
    • Infants – acute adrenal crises with shock
  • TSH
    • Adults – weight gain, coarse hair, fatigue
    • Children – failure to thrive
  • Nonspecific – fatigue, memory disturbances, depression
• Posterior pituitary (hypothalamic)
  • Central diabetes insipidus
    • Adults – polydipsia, polyuria, nocturia

Treatment

• Hormone replacement based on deficiencies

Diagnosis

Indications for Testing

• Symptoms compatible with multiple pituitary hormone deficiencies

Laboratory Testing

• Based on specific symptoms
  • ACTH deficiency (primary adrenal insufficiency – basal measurement, ACTH and cortisol
    • ACTH and plasma cortisol normal – repeat testing if high suspicion
      • If repeat test results normal – no adrenal component to insufficiency
    • ACTH and cortisol low – metyrapone testing or insulin-induced hypoglycemia with ACTH and cortisol
      • ACTH and cortisol low – pituitary adrenocorticotropic hormone deficiency
      • ACTH high and cortisol low – adrenal etiology
  • TSH deficiency – basal thyroid function testing
    • TSH, and free T4 low or normal – repeat testing if high suspicion
      • Test results
        • Normal – no thyroid component to insufficiency
        • High TSH, low free T4 – primary hypothyroidism
        • Normal or low TSH, low free T4 – TSH deficiency
    • TSH and free T4 low – repeat TSH testing
      • High TSH, low free T4 – primary hypothyroidism
      • Normal or low TSH, low free T4 – TSH deficiency
  • Gonadotropin deficiency (GTD) – basal measurement LH, FSH, estrogen (female) or testosterone (male)
    • LH/FSH and testosterone/estrogen normal – repeat testing if high suspicion
      • If repeat test results not low – no gonadotropin component to insufficiency
    • LH/FSH high and testosterone/estrogen low – primary hypogonadism
    • LH/FSH and testosterone/estrogen low – gonadotropin deficiency
  • PRL deficiency – basal measurement of PRL
    • PRL high – prolactin-induced hypogonadism
    • PRL low – FSH deficiency
  • GH deficiency – basal morning measurement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3)
    • IGF-1 and IGFBP-3 normal – repeat testing if high suspicion
      • If repeat test results not low – no growth hormone component to insufficiency
    • IGF-1 and IGFBP-3 low – order GH stimulation with insulin-induced hypoglycemia
      • No change – growth hormone deficiency
  • ADH deficiency – diabetes insipidus testing
    • Urine osmolality and serum/urine sodium, serum ADH
    • May require water deprivation testing

Imaging Studies

• MRI usually required to identify sellar and parasellar masses

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Testosterone Free, Adult Male  0070111 Method: 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.
Follicle Stimulating Hormone, Serum 0070055 Method: Electrochemiluminescent Immunoassay
Luteinizing Hormone, Serum 0070093 Method: Electrochemiluminescent Immunoassay
Adrenocorticotropic Hormone Stimulation, 0 Minutes 0070031 Method: Chemiluminescent Immunoassay
Arginine Vasopressin Hormone 0070027 Method: Radioimmunoassay