Age-specific, gender-specific, and, for women, menstrual cycle phase–specific reference intervals have been established for follicle-stimulating hormone (FSH). (However, depending on the laboratory method used, variations in values can occur.)
Child (age 1-10 years) [1]
Conditions associated with increased FSH include primary hypogonadism, either congenital or acquired:
Other chromosomal disorders Disorders of androgen biosynthesis FSH receptor mutations Myotonic dystrophy Infection (eg, mumps, orchitis)Medication (antineoplastic agents such as cyclophosphamide, chlorambucil, cisplatin, carboplatin, glucocorticoids, Ketoconazole, suramin)
Chemicals (eg, dibromochloropropane) Chronic systemic disease (eg, cirrhosis, chronic renal failure, HIV disease) Pituitary gonadotroph macroadenomasConditions associated with decreased FSH include the following secondary or tertiary causes of hypogonadism, either congenital or acquired:
Isolated idiopathic hypogonadotropic hypogonadism (GnRH deficiency)Idiopathic hypogonadotropic hypogonadism associated with intellectual disability (eg, Prader-Willi syndrome)
Combined pituitary hormone deficiency Mass lesions (eg, pituitary adenomas, cysts, metastatic disease) Hypothalamic/pituitary surgery or radiation Infiltrative disease (eg, sarcoidosis, hemochromatosis, histiocytosis) Meningitis (especially tuberculous meningitis) Glucocorticoid excess (endogenous or exogenous) Sex steroid–secreting tumors Chronic systemic disease (eg, cirrhosis, chronic renal failure, HIV disease)Preferred specimen and acceptable tubes:
Serum (red top tube, SST) Plasma (green top tube - sodium heparin, ammonium heparin, lithium heparin; PST)Specimen volume: 0.5 mL plasma or serum (0.1 mL minimum volume)
Centrifuge specimens and remove serum or plasma from the cells within 2 hours of the collectionStore at room temperature for 8 hours, or refrigerate at 2-8 degrees Celsius (36-46 degrees Fahrenheit) up to 5 days.
If assays are not completed within 48 hours, or the separated sample is to be stored beyond 48 hours, samples should be frozen at -20 degrees Celsius or colder. Frozen samples should be thawed only once. Analyte deterioration may occur in samples that are repeatedly frozen and thawed.
Because of the cyclic and circadian variations in the secretion of gonadotropins, a meaningful evaluation of FSH and LH requires either testing of a pool of blood specimens collected 20-30 min apart or average the hormone measurements of multiple blood samples collected 20-30 min apart.
Total estrogens TestosteroneUsually, for a better and rapid evaluation of hypothalamic-pituitary-gonadal axis, both FSH and LH are evaluated together in the same sample and in the same time and most of the modern assays are using cocktails of antibodies for both FSH and LH, allowing their concurrent evaluation.
Measurement of FSH
There are 2 major ways in which FSH is currently evaluated: radioimmunoassay (RIA) and chemiluminescence immunoassays.
In the RIA, endogenous FSH present in the sample is competing with iodine radiolabeled FSH for a limited amount of FSH-specific antibodies (“competitive assay”). The measured signal is inversely proportional with the amount of TSH present in the sample.
The chemiluminescence assay is using two antibodies (“sandwich immunoassay”). The “capture antibody” is usually binding the alpha subunit of FSH, while the “detection antibody” is always binding within the FSH-specific beta-subunit. The measured signal is directly proportional with the amount of FSH present in the sample. The chemiluminescence assay is significantly more sensitive than RIA. [3]
As all immunoassays, these assays are prone to specific interferences, especially heterophilic antibodies. Hook effect is rarely seen. Interferences from other hormones with similar biochemical structure (eg, LH, TSH, hCG) and from free alpha subunits produced by some pituitary tumors were eliminated by using antibodies specifically directed against beta-subunit epitopes of FSH. However, epitope specificity was not yet achieved, and intense efforts are placed into standardization of the FSH assay. [5]
Measurement of FSH in urine
Because of the cyclic and circadian variations in the secretion of gonadotropins, it is difficult to overcome the issue of detection sensitivity using randomly collected blood samples, especially in children and prepubertal teens. Therefore, more and more pediatric endocrinologists support the idea of FSH and LH evaluation 3-hour urine collection. The kidneys integrate the episodic secretion of these hormones and the urine samples can be further concentrated, so the issue of detection sensitivity and variability can be overcome. [5]
In women with PCOS, the concentration of FSH is low relative to the concentration of LH, with an increased ratio of LH to FSH. A ratio LH to FSH greater than 2.5 is often used for the diagnosis of PCOS. [6]