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 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
            • 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

• Tumor – adenoma, lymphoma, metastatic infiltration
• Autoimmune disorders – connective tissue disease
• Trauma – surgery, head injury, radiation
• Vascular – 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 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)
    • Adults – sexual dysfunction and amenorrhea
    • Children – failure of pubertal development
    • Infants – cryptorchidism, microphallus
  • GH
    • Adults – fatigue, decreased muscle mass and strength, reduced bone marrow density
    • Children – short stature, failure to thrive
    • Infants – seizures, hypoglycemia
  • 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

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

Test Name and Number	Comments
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

Diagnostic Algorithm

  Hypopituitarism (Anterior Pituitary) Testing Algorithm

  Central Diabetes Insipidus (Posterior Pituitary) Testing Algorithm