Protirelin (Systemic)


VA CLASSIFICATION
Primary: DX900

Commonly used brand name(s): Relefact TRH.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Diagnostic aid (hypothalamic-pituitary-thyroid axis function)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Thyroid function studies and
Pituitary function studies—Protirelin is indicated as an adjunct in the diagnostic assessment of thyroid function in patients with pituitary or hypothalamic function impairment and to help evaluate the effectiveness or adjust the dosage of thyroid hormone in patients with nodular or diffuse goiter or primary hypothyroidism. {01} {09}
—As an adjunct to other diagnostic procedures, protirelin serves to evaluate pituitary function when hypothalamic or pituitary lesions are suspected. {01} {09} {10}
—[Protirelin is also used to detect inhibition of thyroid-stimulating hormone (TSH) secretion that occurs in hyperthyroidism.]1

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    362.39

Mechanism of action/Effect:

Diagnostic aid (thyroid function)—Like naturally occurring thyrotropin-releasing hormone (TRH), protirelin stimulates release of thyroid-stimulating hormone (TSH) from the anterior pituitary. As a result, protirelin can be used to detect an increase in or blunting of TSH response due to a variety of medical conditions or to confirm adequate suppression of TSH response by administration of thyroid hormones. {01} {10}


Other actions/effects:

Protirelin appears to increase plasma growth hormone concentrations in some acromegalic patients. It also increases serum prolactin concentrations. {01} {09} {10}

Half-life:

5 minutes. {09} {10}

Time to peak TSH concentration

Normal—20 to 30 minutes. {01}

Duration of action:

Approximately 3 hours for TSH concentrations to return to baseline. {01}

Elimination:
    Renal. {10}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Studies in humans have not been done.

Studies in rabbits have shown that protirelin at doses 11/2 and 6 times the human dose caused an increase in the number of resorption sites in the pregnant rabbit. {01}

Breast-feeding

Problems in humans have not been documented; however, breast enlargement and leaking of milk have occurred in lactating women, persisting for up to 2 to 3 days after administration of protirelin. {01} {09}

Pediatrics

Diagnostic studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of protirelin in children.


Geriatrics


Caution in interpreting thyroid-stimulating hormone (TSH) response is recommended in elderly males because of a natural decrease in responsiveness to thyrotropin-releasing hormone (TRH).

Drug interactions and/or related problems
See Laboratory value alterations .


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With results of this test

Due to other medications
Adrenocorticoids, glucocorticoid with mineralocorticoid activity    (physiologic doses have no effect but pharmacologic doses may reduce the thyroid-stimulating hormone [TSH] response to protirelin; in general, however, withdrawal of adrenocorticoids in patients with known hypopituitarism is not recommended {01} {09})


Aspirin    (doses of 2 to 3.6 grams per day may inhibit the TSH response to protirelin; peak TSH concentrations occur at the same time after administration but are reduced {01} {09})


Levodopa, or other dopaminergic medications    (chronic use may inhibit the TSH response to protirelin {01} {09})


Thyroid hormones    (concurrent use decreases the TSH response to protirelin administration; withdrawal of liothyronine 7 days [or of levothyroxine, liotrix, thyroglobulin, or thyroid extract at least 14 days and preferably 4 to 6 weeks] prior to testing is recommended except in patients being evaluated for effectiveness of levothyroxine for nodular or diffuse goiter or when dosage of thyroid hormone for primary hypothyroidism is being adjusted {01} {09})


Due to medical problems or conditions
Renal function impairment    (may produce unreliable test results {09})

With physiology/laboratory test values
Growth hormone    (plasma concentrations may be increased in patients with acromegaly; however, protirelin may also inhibit release of growth hormone caused by levodopa)


Prolactin    (serum concentrations may be increased in euthyroid and also to a lesser extent in hyperthyroid individuals {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

See also Laboratory value alterations .

Risk-benefit should be considered when the following medical problems exist
» Conditions in which sudden changes in blood pressure would be dangerous, such as:{01}{09}
Cerebrovascular disease
Coronary insufficiency
Hypertension
Occlusive vascular disease
Sensitivity to protirelin{08}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood pressure measurements    (recommended prior to and at frequent intervals during the first 15 minutes following administration of protirelin; if a clinically significant change occurs, monitoring should be continued until blood pressure returns to baseline levels {01})


» Thyroid-stimulating hormone (TSH), serum concentrations    (blood samples should be drawn immediately prior to and at specific intervals [30 and 60 minutes; or 20, 40, and 60 minutes] following protirelin administration; because of possible variation, the physician should be familiar with the assay method used and the normal range for the particular laboratory being utilized {01})




Side/Adverse Effects

Note: Hypotension or hypertension, which rarely may be severe (including possible syncope), occurs frequently immediately after injection, usually persisting for no more than 15 minutes following administration. {01} {10}
Most side effects persist for only a few minutes following administration. {01} {09}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Amaurosis, in patients with pituitary tumors (temporary loss of vision){01}
    
hypotension, severe (fainting){01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Flushing or redness of skin
    
frequent urge to urinate
    
headache, sometimes severe
    
lightheadedness
    
nausea
    
stomach pain
    
unpleasant taste in mouth or dryness of mouth
{01}{09}{10}
Incidence less frequent
    
Anxiety
    
drowsiness
    
pressure in the chest or tightness in throat
    
sweating
    
tingling
{01}{09}{10}




Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Protirelin (Diagnostic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Test procedure: Blood sample taken; injection given; one or more blood samples taken again; lying down before, during, and for at least 15 minutes after administration to avoid dizziness or lightheadedness

Before having this test
»   Conditions affecting use, especially:
Sensitivity to protirelin





Breast-feeding—Breast enlargement and leaking of milk possible; may persist for 2 to 3 days after administration





Use in the elderly—Decreased response in males to thyrotropin-releasing hormone; caution in interpreting test results
Other medical problems, especially cerebrovascular disease, coronary insufficiency, hypertension, occlusive vascular disease

Preparation for this test
» Physician may recommend fasting or a low-fat meal prior to the test; following instructions carefully


Side/adverse effects
Signs of potential side effects, especially amaurosis and severe hypotension


General Dosing Information
Results of the protirelin test should be interpreted by someone familiar with thyroid-pituitary-hypothalamic physiology and the clinical status of the patient. The physician should also be familiar with the thyroid-stimulating hormone (TSH) assay method used and the normal range for the laboratory performing the assay. {01}

Fasting for 6 hours prior to the test or a low-fat meal prior to the test is recommended for patients (except those with hypopituitarism) to prevent interference with the TSH test by elevated serum lipids. {01}

It is recommended that the patient be supine before, during, and for at least 15 minutes following administration of protirelin to reduce the risk or severity of hypotension. {01} {09} {10}

Protirelin is administered as an intravenous injection over 15 to 30 seconds. {01}

Because repeated administration of protirelin leads to a reduced TSH response, an interval of at least 7 days is recommended between tests with protirelin. {01}


Parenteral Dosage Forms

PROTIRELIN INJECTION

Usual adult dose
Diagnostic aid (thyroid function)
Intravenous, 500 mcg (0.5 mg). {01}


Usual pediatric dose
Diagnostic aid (thyroid function)
Children up to 6 years of age: Experience is limited with the use of protirelin in this age group; however, doses of 7 mcg (0.007 mg) per kg of body weight administered intravenously have been used.

Children 6 to 16 years of age: Intravenous, 7 mcg (0.007 mg) per kg of body weight, up to 500 mcg (0.5 mg).


Strength(s) usually available
U.S.—


500 mcg (0.5 mg) per mL (Rx) [Relefact TRH]

Canada—


200 mcg (0.2 mg) per mL (Rx) [Relefact TRH]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.



Revised: 07/05/1994



References
  1. Relefact TRH package insert (Hoechst-Roussel—US), Rev 6/86.
  1. Munsat TL, Taft J, Jackson I. Pharmacokinetics of intrathecal thyrotropin-releasing hormone. Neurology 1987 Apr; 37: 597-601.
  1. Mitsumoto H, Salgado ED, Negroski D, et al. Amyotrophic lateral sclerosis: effects of acute intravenous and chronic subcutaneous administration of thyrotropin-releasing hormone in controlled trials. Neurology 1986 Feb; 36: 152-9.
  1. Brooke MH, Florence JM, Heller SL, et al. Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis. Neurology 1986 Feb; 36: 146-51.
  1. Sharif NA. Diverse roles of thyrotropin-releasing hormone in brain, pituitary and spinal function. TIPS 1985 Mar; 119-22.
  1. Imoto K, Saida K, Iwamura K, et al. Amyotrophic lateral sclerosis: a double-blind crossover trial of thyrotropin-releasing hormone. J Neurol Neurosurg Psychiatry 1984; 47: 1332-4.
  1. Holaday JW, Bernton EW. Protirelin (TRH): a potent neuromodulator with therapeutic potential [editorial]. Arch Intern Med 1984 Jun; 144: 1138-9.
  1. Precaution included in all USP DI monographs, 1990 revision, per DID policy.
  1. AMA Drug evaluations. 6th ed. Chicago: American Medical Association, September 1986: 757-8.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 29th ed. London: The Pharmaceutical Press, 1989: 1152-3.
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