Hypopituitarism

Diagnostic Algorithm

  Hypopituitarism (Anterior Pituitary) Testing Algorithm

  Central Diabetes Insipidus (Posterior Pituitary) Testing Algorithm

Clinical Background

The pituitary gland is often referred to as the master gland because it orchestrates 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's syndrome), sickle cell disease
• Infections – histoplasmosis, tuberculosis, toxoplasmosis
• Infiltrative disease – sarcoidosis, hemochromatosis
• Genetic disease – Kallmann syndrome, Prader-Willi syndrome, Laurence-Moon-Bardet-Biedl 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 which part of the pituitary gland is involved and the age at which hypopituitarism occurs
• Nonspecific
  • Headache
  • Visual disturbances
• Anterior pituitary
  • Gonadotropic hormones
    • Adults – sexual dysfunction and amenorrhea
    • Infants – cryptorchidism, microphallus
    • Children – failure of pubertal development
  • Growth hormone
    • Adults – fatigue, decreased muscle mass and strength, reduced bone marrow density
    • Infants – convulsions, hypoglycemia
    • Children – short stature, failure to thrive
  • Adrenal corticotrophic hormone
    • Adults – fatigue, nausea, vomiting
    • Infants – acute adrenal crises with shock
  • Thyroid hormone
    • 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
  • PRL deficiency – basal measurement of PRL
  • GH deficiency – basal morning measurement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3)
    • In addition, test response to insulin-induced hypoglycemia (insulin tolerance test)
  • ACTH deficiency (primary adrenal insufficiency) – basal measurement, ACTH and cortisol
    • Metyrapone testing if ACTH deficiency is consideration
      • ACTH stimulation testing if primary adrenal insufficiency is a consideration
  • Gonadotropin deficiency (GTD) – basal measurement LH, FSH, estradiol (female) or testosterone (male)
  • TSH deficiency – basal thyroid function testing
    • Thyroid stimulating hormone (TSH), free T4
  • ADH deficiency –  Diabetes insipidus testing
    • Urine osmolality and serum/urine sodium, serum antidiuretic hormone (ADH)
    • May require water deprivation testing
  • Releasing hormone stimulation is not recommended for use in initial testing
• Imaging studies – MRI usually required to identify sellar and parasellar masses

Pharmacogenetics and Therapeutic Drug Monitoring

Screening

Monitoring

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
Cyclic AMP, Plasma 0070180 Method: Radioimmunoassay
Arginine Vasopressin Hormone 0070027 Method: Radioimmunoassay

Guidelines

General References

References from the ARUP Institute for Clinical and Experimental Pathology®