Hypopituitarism

Indications for Testing

Symptoms compatible with multiple pituitary hormone deficiencies

Laboratory Testing

Anterior pituitary testing
- 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 11-deoxycortisol
    - Low ACTH and 11-deoxycortisol – pituitary adrenocorticotropic hormone deficiency
    - High ACTH and low 11-deoxycortisol – 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 are normal – no gonadotropin deficiency
  - 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 are normal – no growth hormone component to insufficiency
  - IGF-1 and IGFBP-3 low – order GH stimulation with insulin-induced hypoglycemia
    - GH <4 ng/mL (adults) and <5 ng/mL (children) – growth hormone deficiency
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 SO
    - SO>290 mOsm/kg, Na>140 mmol/L and weight loss nearing 3%
      - Yes – 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
      - No – not diabetes insipidus

Histology

Immunohistochemistry – for pituitary adenomas, consider prolactin, growth hormone, ACTH or TSH

Imaging Studies

MRI usually required to identify sellar and parasellar masses

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
Connective tissue 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/AVH)
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
- Weakness
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 – seizures, 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

Tests generally appear in the order most useful for common clinical situations

Test name: Cortisol, Serum or Plasma

ARUP #: 0070030

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Diagnose adrenal insufficiency (may be primary or secondary)

Test name: Adrenocorticotropic Hormone

ARUP #: 0070010

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Diagnose adrenal insufficiency (may be primary or secondary)

Test name: 11-Deoxycortisol Quantitative by LC-MS/MS, Serum or Plasma

ARUP #: 0092331

Methodology: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Use:

GH <5 ng/mL (adults) and <10 ng/mL (children)

Test name: Thyroid Stimulating Hormone

ARUP #: 0070145

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Diagnose thyroid deficiency

Test name: Thyroxine, Free (Free T4)

ARUP #: 0070138

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Diagnose thyroid deficiency

Test name: Luteinizing Hormone and Follicle Stimulating Hormone

ARUP #: 0070193

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Diagnose gonadotropin deficiency

Test name: Testosterone, Free & Total (Includes Sex Hormone Binding Globulin), Adult Male

ARUP #: 0070109

Methodology: Quantitative 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.

Use:

Diagnose gonadotropin deficiency

Test name: Estradiol, Adult Premenopausal Female, Serum or Plasma

ARUP #: 0070045

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Diagnose gonadotropin deficiency

Test name: Estrogens, Fractionated by Tandem Mass Spectrometry

ARUP #: 0093248

Methodology: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Use:

Diagnose gonadotropin deficiency

Test name: Prolactin

ARUP #: 0070115

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Diagnose prolactin excess

Test name: IGF-1 (Insulin-Like Growth Factor 1)

ARUP #: 0070125

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Diagnose GH deficiency

Test name: IGF Binding Protein-3

ARUP #: 0070060

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Diagnose GJH deficiency

Test name: Growth Hormone

ARUP #: 0070080

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Diagnose GH deficiency

Test name: Osmolality, Urine

ARUP #: 0020228

Methodology: Freezing Point

Use:

Diagnose ADH/AVH deficiency

Test name: Osmolality, Serum or Plasma

ARUP #: 0020046

Methodology: Freezing Point

Use:

Diagnose ADH/AVH deficiency

Test name: Sodium, Plasma or Serum

ARUP #: 0020001

Methodology: Quantitative Ion-Selective Electrode

Use:

Diagnose ADH/AVH deficiency

Test name: ACTH by Immunohistochemistry

ARUP #: 2003427

Methodology: Immunohistochemistry

Use:

Aid in histologic diagnosis of pituitary tumors

Stained and returned to client pathologist; consultation available if needed

Test name: Growth Hormone by Immunohistochemistry

ARUP #: 2003929

Methodology: Immunohistochemistry

Use:

Aid in histologic diagnosis of pituitary tumors

Stained and returned to client pathologist; consultation available if needed

Test name: Prolactin by Immunohistochemistry

ARUP #: 2004109

Methodology: Immunohistochemistry

Use:

Aid in histologic diagnosis of pituitary tumors

Stained and returned to client pathologist; consultation available if needed

Additional Tests Available

Test name: Testosterone Free, Adult Male

ARUP #: 0070111

Methodology: Quantitative 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.

Comments:

Test name: Follicle Stimulating Hormone, Serum

ARUP #: 0070055

Methodology: Quantitative Electrochemiluminescent Immunoassay

Comments:

Test name: Luteinizing Hormone, Serum

ARUP #: 0070093

Methodology: Quantitative Electrochemiluminescent Immunoassay

Comments:

Test name: Adrenocorticotropic Hormone Stimulation, 0 Minutes

ARUP #: 0070031

Methodology: Quantitative Chemiluminescent Immunoassay