Hypopituitarism laboratory findings
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A subnormal or reduced concentration of pituitary hormones is diagnostic of hypopituitarism. Patients with complete hormonal deficiencies are mostly symptomatic and have low serum concentrations of both, the pituitary hormones as well as the target-organ hormones. Patients having partial hormonal deficiencies are detected by dynamic tests/stimulatory tests such as corticotropin stimulation, insulin-induced hypoglycemia and metyrapone test. Corticotropin deficiency is detected by assessing basal cortisol secretion. Patients with intermediate cortisol levels need to be tested for adrenocorticotrophic hormone (ACTH) reserve. There are several tests to check the ACTH reserve. Metyrapone test is preferred over others as it is applicable to all adults with no age restriction and has good correlation with stress related cortisol response. Patients with hypopituitarism are screened for hypothyroidism by measuring thyroxine, total thyroxine (T4) and triiodothyronine (T3) uptake, and free T4. Gonadotropin deficiency is confirmed with low estradiol, low testosterone, and low/normal serum FSH/LH. Growth hormone deficiency is confirmed with provocative tests (insulin induced hypoglycemia and arginine and GHRH combination) for growth hormone (GH) secretion resulting in subnormal levels of serum GH levels, serum insulin-like growth factor-1 levels lower than the age-specific lower limit of normal and deficiency of more than one pituitary hormones, such as ACTH, TSH, and gonadotropins. ADH deficiency is assessed by water deprivation test and ADH suppression test. Prolactin deficiency can be confirmed by directly measuring prolactin levels on more than one occasion as its secretion is episodic but it is not done routinely as it is not clinically significant.
- Patients with complete hormonal deficiencies are mostly symptomatic and have low serum concentrations of both, the pituitary hormones (thyrotropin, corticotropin, and luteinizing hormone) as well as the target-organ hormones (thyroxine, cortisol, and testosterone)
- Patients having partial hormonal deficiencies are detected by dynamic tests/stimulatory tests, such as corticotropin stimulation, insulin-induced hypoglycemia, and metyrapone test
- A subnormal or reduced concentration of pituitary hormones is diagnostic of hypopituitarism. Amongst all pituitary hormones, the first and the most common hormonal deficiency seen in hypopituitarism is growth hormone deficiency followed by deficiencies of gonadotropins (FSH, LH), TSH, ACTH, and prolactin.
- Any history of a lesion causing hypopituitarism or a symptom suggestive of hypopituitarism is an indication for testing for hypopituitarism.
- Laboratory findings consistent with laboratory diagnosis of panhypopituitarism depends upon the specific hormonal deficiency and may include:
Dynamic tests for making a diagnosis of hypopituitarism
|Growth hormone||Insulin tolerance||
|GHRH + arginine|
|Corticotropin standard dose (250 μg)||
|Corticotropin low dose (1 μg)|
|ADH||Water deprivation test||
||Diabetes insipidus (DI): Plasma osmolality >295 mOsm/L with inappropriately hypotonic urine (urine osmolality/plasma osmolality ratio <2) during the fluid deprivation confirms DI (test is discontinued)
Partial/primary polydipsia: With partial DI or primary polydipsia, urine concentrates partially during the water deprivation test (300–800 mOsm/kg), and further investigation is required including a prolonged water deprivation test or DDAVP therapeutic trial
Notes for water deprivation test:
- If plasma osmolality > 305 mOsm/kg or if 3% loss of body weight with plasma osmolality > 305 mOsm/kg, proceed to DDAVP administration earlier. If urine output has not decreased and/or urine osmolality/plasma osmolality ratio < 2, but the plasma osmolality has not concentrated to >295 mOsm/kg, continue water deprivation for a further hour and measure plasma and urine osmolality. Offer DDAVP after this.
- Continue measuring urine osmolality hourly for the next 4 h (after DDVAP administration) and measure hourly urine volumes.
- Stop test if >3% weight loss occurs.
(a) Basal ACTH secretion:
|Serum cortisol||Basal adrenocorticotrophic hormone (ACTH)|
|Low: ≤3 mcg/dL (83 nmol/L)||Cortisol deficiency|
|High: ≥18 mcg/dL (497 nmol/L)||No cortisol deficiency even in times of stress|
|Intermediate: >3 mcg/dL (83 nmol/L)
<18 mcg/dL (497 nmol/L)
|Needs evaluation for ACTH reserve|
(b) ACTH reserve:
- Patients with intermediate cortisol levels need to be tested for ACTH reserve. There are several tests to check the ACTH reserve. Metyrapone test is preferred over others as it is applicable to all adults with no age restriction and has good correlation with stress related cortisol response. The major disadvantage of the test is that it needs inpatient observation for blood pressure and pulse monitoring to prevent postural hypotension.
- Insulin-induced hypoglycemia test is not preferred as it needs continuous monitoring for hypoglycemic symptoms during the first hour of insulin administration in patients who are elderly and have cardiovascular or cerebrovascular issues or a seizure disorder. Hypoglycemia is treated with intravenous glucose.↵The standard or low dose cosynotropin stimulation test is not recommended as it can give falsely normal results. The corticotropin-releasing hormone test indicates pituitary-adrenal function and is as reliable as insulin-induced hypoglycemia test but has a limitation that only a small number of patients can be evaluated and may cause transient nausea.
Metyrapone blocks 11-beta-hydroxylase (CYP11B1), an enzyme that catalyzes the last step in cortisol production resulting in decreased cortisol and increased 11-deoxycortisol concentration. In this test 750 mg of Metyrapone is administered orally every 4 hours for 24 hours. Serum cortisol and 11-deoxycortisol concentration are checked at 8 am after 24 hours and the results are interpreted as follows:
|Subject||Cortisol level||11-deoxycortisol level|
|Normal subjects||< 7 mcg/dL (172 nmol/L)||≥10 mcg/dL (289 nmol/L)|
|Patients with decreased ACTH reserve||<7 mcg/dL (172 nmol/L)||<10 mcg/dL (289 nmol/L)|
- Thyroxine (T4)
- Total thyroxine (T4) and triiodothyronine (T3) uptake
- Free T4
- Thyrotropin-releasing hormone test may be used to confirm thyrotropin deficiency but reduced response is commonly seen in normal elderly subjects and it may cause transient urge to urinate, metallic taste in mouth, arrhythmia and hypotension
|Condition||Serum T3||Serum free T4||Serum TSH|
|Central hypothyroidism||Low or normal||Low or low-normal||Low, normal, or slightly high|
Gonadotropin-releasing hormone test may be used to detect serum levels for gonadotropins (follicle stimulating hormones and luteinizing hormones) but repeated stimulations by gonadotropin-releasing hormone are required to make a diagnosis.
- Low testosterone
|GH provocative tests||Serum GH levels|
|Insulin induced hypoglycemia||<5.1 ng/mL|
|Arginine and GHRH combination||<4.1 ng/mL|
(b) Serum insulin-like growth factor-1 levels lower than the age-specific lower limit of normal. This test is useful in children but not in adults as up to 1/3rd of adults with confirmed GH deficiency have normal IGF-1 levels.
5.Antidiuretic hormone (ADH) deficiency
(a) Water deprivation test:
It is used to differentiate psychogenic polydipsia from diabetes insipidus. Water intake is restricted with continuous monitoring (as patients with psychogenic polydipsia try even to drink the toilet water) and hourly measurements of serum and urine osmolalities. Results are interpreted as follows:
|Condition||Serum osmolality||Urine osmolality|
(b) Vasopressin stimulation test:
This test is used to differentiate central from nephrogenic diabetes insipidus. Serum and urine osmolalities are measured 1 hour after administration of either subcutaneous 1-2mcg of desmopressin (DDAVP) or 5 units of aqueous vasopressin. The results are interpreted as follows:
|Diabetes insipidus||Serum osmolality||Urine osmolality|
|Nephrogenic||no change||no change|
Prolactin deficiency can be confirmed by directly measuring prolactin levels on more than 1 occasion as its secretion is episodic. Serum prolactin level may be increased in a patient with hypothalamic or pituitary lesion but is rarely low. The following are the salient features associated with prolactin level testing:
- Hypoprolactinemia is a marker of severe pituitary damage in patients having structural pituitary disease
- It is important to measure serum prolactin level as it can give an idea about the location of lesion
- Routine testing is not done because:
- Thyrotropin-releasing hormone test is not very useful as it can't differentiate between prolactinomas and other causes of hyperprolactinemia.
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