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Aetna Aetna
Clinical Policy Bulletin:
Salivary Tests
Number: 0608


Aetna considers salivary tests of dehydroepiandrosterone (DHEA), estrogen, melatonin, progesterone, or testosterone experimental and investigational for the screening, diagnosis, or monitoring of menopause or diseases related to aging, or any other indications because these tests have not been proven to be valid alternatives to serum tests.

Aetna considers late night salivary cortisol medically necessary for diagnosing Cushing's syndrome.

Aetna considers salivary tests of cortisol experimental and investigational for the screening, diagnosis, or monitoring of menopause or diseases related to aging, or any other indications (e.g., diagnosis of bipolar disorder, depression, or eating disorders) because the effectiveness of salivary tests of cortisol for indications other than Cushing's syndrome has not been established.

Aetna considers measurement of salivary level of CYFRA 21-1, interleukin-8, or mRNAs of dual specificity phosphatase 1 (DUSP1), ornithin decarboxylase antizyme 1 (OAZ1), and S100 calcium-binding protein P (S100P) as biomarkers for oral pre-cancer and oral squamous cell carcinoma experimental and investigational because the effectiveness of this approach has not been established.

Aetna considers salivary testing for anti-tissue transglutaminase for the diagnosis of celiac disease experimental and investigational because the effectiveness of this approach has not been established.

Aetna considers salivary antibody testing (IgA, IgG, IgM) for the diagnosis of Sicca syndrome experimental and investigational because the effectiveness of this approach has not been established.

Note:  In addition, laboratory tests are not covered unless they are ordered by a physician or other qualified health professional.  Please check benefit plan descriptions.


Salivary tests of estrogen, progesterone, testosterone, melatonin, cortisol and dehydroepiandrosterone (DHEA) have become available to consumers over the Internet.  Some of these websites include a questionnaire to allow consumers to determine whether they need saliva testing, and a form that allows consumers to order these tests online.  The results of these tests are purportedly used to determine the need prescriptions of DHEA, vitamins, herbs, phytoestrogens, and other anti-aging regimens.

The medical literature on salivary testing correlates salivary levels with serum levels, the gold standard measurement.  However, the medical literature fails to demonstrate that salivary tests are appropriate for screening, diagnosing, or monitoring patients with menopause, osteoporosis, or other consequences of aging.

Evidence-based clinical practice guidelines from the American Association of Clinical Endocrinologists outline the appropriate methods of screening and diagnosing menopause and osteoporosis.  The primary test for menopause screening is serum follicle-stimulating hormone, for thyroid dysfunction serum thyroid-stimulating hormone, and bone density measurement is the primary method of screening for osteoporosis.  None of these guidelines indicates salivary testing as an appropriate method of screening, diagnosing, or monitoring these disorders.

According to available guidelines, primary hypoadrenalism (Addison’s disease) is suggested by a markedly elevated plasma adrenocorticotrophic hormone (ACTH) with low or normal serum cortisol.  The diagnosis of adrenocortical insufficiency is established primarily by use of the rapid ACTH stimulation test, which involves assessment of the response of serum aldosterone and cortisol to ACTH infusion.

Furthermore, there is inadequate evidence of the value of measuring salivary components to guide prescription of "anti-aging" regimens.  The clinical value of these tests depends not only on how well the salivary testing corresponds to some gold standard (i.e., a serum test), but also upon the evidence of the effectiveness of the particular intervention (anti-aging regimen) that would be prescribed based on the results of the salivary test.  Meta-analyses of the literature have questioned the value of supplementation with DHEA and melatonin on improving patient outcomes.

According to a committee opinion by the American College of Obstetricians and Gynecologists (ACOG, 2005), there is no scientific evidence to support claims of increased safety or effectiveness for individualized estrogen or progesterone regimens prepared by compounding pharmacies.  Furthermore, hormone therapy does not belong to a class of drugs with an indication for individualized dosing.  The opinion by ACOG also pointed out that salivary hormone level testing used by proponents to "tailor" this therapy isn't meaningful because salivary hormone levels vary within each woman depending on her diet, the time of day, the specific hormone being tested, and other variables.

A National Institutes of Health State-of-the-Art Conference Statement on Management of Menopausal Symptoms (2005) reached the following conclusions about salivary hormone testing and bioidential hormones: "Bioidentical hormones, often called "natural" hormones, are treatments with individually compounded recipes of a variety of steroids in various dosage forms, with the composition and dosages based on a person’s salivary hormone concentration.  These steroids may include estrone, estradiol, estriol, DHEA, progesterone, pregnenolone, and testosterone.  There is a paucity of data on the benefits and adverse effects of these compounds."

An assessment by the Institute for Clinical Systems Improvement (2006) concluded: "Currently, there is insufficient evidence in the published scientific literature to permit conclusions concerning the use of salivary hormone testing for the diagnosis, treatment or monitoring of menopause and aging."

The North American Menopause Society (2005) has concluded: "Salivary testing is not considered to be a reliable measure of testosterone levels."

Flyckt and colleagues (2009) compared salivary versus serum measurements of total testosterone (TT), bioavailable testosterone (BT; consisting of free testosterone [FT] and albumin-bound testosterone), and FT from samples collected simultaneously in women who were either receiving transdermal testosterone patch supplementation (300 microg/d) or a placebo patch.  Naturally and surgically post-menopausal women receiving concomitant hormone therapy were recruited to participate in a 24- to 52-week phase III trial of a 300 microg/day transdermal testosterone patch for the treatment of hypoactive sexual desire disorder.  Initial analysis demonstrated high correlations between TT, BT, and FT levels (r = 0.776 to 0.855).  However, there was no correlation with salivary testosterone levels for any of the serum testosterone subtypes (r = 0.170 to 0.261).  After log transformation, salivary testosterone correlated modestly with BT (r = 0.436, p < 0.001), FT (r = 0.452, p < 0.001), and TT (r = 0.438, p < 0.001).  The authors concluded that although salivary testing of testosterone concentrations is an appealing alternative because it is inexpensive and non-invasive, these findings do not support the routine use of salivary testosterone levels in post-menopausal women.

Klebanoff and colleagues (2008) examined if salivary progesterone (P) or estriol (E3) concentration at 16 to 20 weeks' gestation predicts preterm birth or the response to 17alpha-hydroxyprogesterone caproate (17OHPC).  Baseline saliva was assayed for P and E3.  Weekly salivary samples were obtained from 40 women who received 17OHPC and 40 who received placebo.  Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth.  However, 17OHPC prevented preterm birth comparably, regardless of baseline salivary hormone concentrations.  Thus, salivary P or E3 does not appear to predict preterm birth.

Groschl (2008) provided an overview of the current applications of salivary hormone analysis.  The author noted that although saliva has not yet become a mainstream sample source for hormone analysis, it has proven to be reliable and, in some cases, even superior to other body fluids.  Nevertheless, much effort will be needed for this approach to receive acceptance over the long-term, especially by clinicians.  Such effort entails the development of specific and standardized analytical tools, the establishment of defined reference intervals, and implementation of round-robin trials.  One major obstacle is the lack of compliance sometimes observed in outpatient saliva donors.  Moreover, the author stated that there is a need for standardization of both collection and analysis methods in order to attain better comparability and evaluation of published salivary hormone data.

Measurement of late-night and/or midnight salivary cortisol currently used in the United States and European countries is a simple and convenient screening test for the initial diagnosis of Cushing's syndrome (CS).  Carroll et al (2008) stated that making a definite diagnosis of CS is a challenging problem.  Unsuspected CS occurs in 2 to 3 % of patients with poorly controlled diabetes, 0.5 to 1 % with hypertension, 6 to 9 % with incidental adrenal masses, and 11 % with unexplained osteoporosis and vertebral fractures.  The increasing recognition of this syndrome highlights the need for a simple, sensitive, and specific diagnostic test.  Patients with CS consistently do not reach a normal nadir of cortisol secretion at night.  The measurement of late-night salivary cortisol levels might, therefore, provide a new diagnostic approach for this disorder.  Salivary cortisol concentrations reflect those of active free cortisol in plasma and saliva samples can easily be obtained in a non-stressful environment (e.g., at home).  Late-night salivary cortisol measurement yields excellent overall diagnostic accuracy for CS, with a sensitivity of 92 to 100 % and a specificity of 93 to 100 %.  Several factors can, however, make interpretation of results difficult; these factors include disturbed sleep-wake cycles, contamination of samples (particularly by topical corticosteroids), and illnesses known to cause physiologic activation of the pituitary-adrenal axis.

Elamin et al (2008) summarized the evidence on the accuracy of common tests for diagnosing CS.  These investigators searched electronic databases (Medline, Embase, Web of Science, Scopus, and citation search for key articles) from 1975 through September 2007 and sought additional references from experts.  Eligible studies reported on the accuracy of urinary free cortisol (UFC), dexamethasone suppression test (DST), and midnight cortisol assays versus reference standard in patients suspected of CS.  Reviewers working in duplicate and independently extracted study characteristics and quality and data to estimate the likelihood ratio (LR) and the 95 % confidence interval (CI) for each result.  These researchers found 27 eligible studies, with a high prevalence [794 (9.2 %) of 8,631 patients had CS] and severity of CS.  The tests had similar accuracy: UFC (n = 14 studies; LR+ 10.6, CI: 5.5 to 20.5; LR- 0.16, CI: 0.08 to 0.33), salivary midnight cortisol (n = 4; LR+ 8.8, CI: 3.5 to 21.8; LR- 0.07, CI: 0 to 1.2), and the 1-mg overnight DST (n = 14; LR+ 16.4, CI: 9.3 to 28.8; LR- 0.06, CI: 0.03 to 0.14).  Combined testing strategies (e.g., a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n = 3; LR+ 15.4, CI: 0.7 to 358; LR- 0.11, CI: 0.007 to 1.57).  The authors concluded that commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS.

Doi et al (2008) assessed the usefulness of the measurement of late-night salivary cortisol as a screening test for the diagnosis of CS in Japan.  These investigators studied 27 patients with various causes of CS, consisting of  ACTH-dependent Cushing's disease (n = 5) and ectopic ACTH syndrome (n = 4) and ACTH-independent adrenal CS (n = 11) and subclinical CS (n = 7).  Eleven patients with type 2 diabetes and obesity and 16 normal subjects served as control group.  Saliva samples were collected at late-night (23:00) in a commercially available device and assayed for cortisol by radioimmunoassay.  There were highly significant correlations (p < 0.0001) between late-night serum and salivary cortisol levels in normal subjects (r = 0.861) and in patients with CS (r = 0.788).  Late-night salivary cortisol levels in CS patients (0.975 +/- 1.56 microg/dL) were significantly higher than those in normal subjects (0.124 +/- 0.031 microg/dL) and in obese diabetic patients (0.146 +/- 0.043 microg/dL), respectively.  Twenty-five out of 27 CS patients had late-night salivary cortisol concentrations greater than 0.21 microg/dL, whereas those in control group were less than 0.2 microg/dL.  Receiver operating characteristic curve (ROC) analysis showed that the cut-off point of 0.21 microg/dL provides a sensitivity of 93 % and a specificity of 100 %.  The authors concluded that the measurement of late-night salivary cortisol is an easy and reliable non-invasive screening test for the initial diagnosis of CS, especially useful for large high-risk populations, such as diabetes and obesity.

The Endocrine Society's clinical practice guideline on the diagnosis of CS (Nieman et al, 2008) stated that after excluding exogenous glucocorticoid use, testing for CS in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma is recommended.  It recommends the initial use of one test with high diagnostic accuracy such as urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-hr DST.  The guideline also recommends that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-corticotropin-releasing hormone test.  Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome.  Patients with concordant normal results should not undergo further evaluation.  The guideline also recommends additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.

Knorr et al (2010) examined if salivary cortisol differs for patients with depression and control persons.  These investigators performed a systematic review with sequential meta-analysis and meta-regression according to the PRISMA Statement based on comprehensive database searches for studies of depressed patients compared to control persons in whom salivary cortisol was measured.  A total of 20 case-control studies, including 1,354 patients with depression and 1,052 control persons were identified.  In a random-effects meta-analysis salivary cortisol was increased for depressed patients as compared to control persons on average 2.58 nmol/L (95 % CI: 0.95 to 4.21; p = 0.002) in the morning and on average 0.27 nmol/L (95 % CI: 0.03 to 0.51; p=0.03) in the evening.  In a fixed-effects model the mean difference was 0.58 nmol/L (95 % CI).  Study sequential cumulative meta-analyses suggested random error for the finding of this rather small difference between groups.  The reference intervals for morning salivary cortisol in depressed patients (0 to 29 nmol/L) and control persons (1 to 23 nmol/L) showed substantial overlap suggesting lack of discriminative capacity.  These results should be interpreted with caution as the heterogeneity for the morning analysis was large and a funnel plot, suggested presence of bias.  Further, in meta-regression analyses higher intra-assay coefficients of variation in cortisol kits (p = 0.07) and mean age (p = 0.08) were associated with a higher mean difference of morning salivary cortisol between depressed and controls, while gender and depression severity were not.  The authors concluded that based on the available studies, there is not firm evidence for a difference of salivary cortisol in depressed patients and control persons and salivary cortisol is unable to discriminate between persons with and without depression.

Monteleone and colleagues (2011) noted that the stress response involves the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS).  As a role for stress in determining of the onset and the natural course of eating disorders has been proposed, the study of the psychobiology of the stress response in patients with anorexia nervosa (AN) and bulimia nervosa (BN) should be helpful in understanding the pathophysiology of these disorders.  The 2 neurobiological components of the stress response can be easily explored in humans by the measurement of salivary cortisol and α-amylase response to a stressor.  Thus, these researchers assessed salivary cortisol and α-amylase responses to the Trier Social Stress Test (TSST) in symptomatic patients with AN (n = 7) and BN (n = 8) compared to age-matched healthy females (n = 8).  Subjects underwent the TSST between 1530 and 1700 hr.  Salivary cortisol and α-amylase levels were measured by an enzyme-linked immunosorbent assay (ELISA).  Compared to healthy women, AN patients showed a normal cortisol response to the TSST, although this occurred at significantly increased hormone levels, and an almost complete absence of response of α-amylase.  BN women, however, exhibited enhanced pre-stress levels of salivary α-amylase but a normal response of the enzyme and cortisol to the TSST.  The authors concluded that these findings demonstrated, for the first time, the occurrence of an asymmetry between the HPA axis and SNS components of the stress response in the acute phase of AN but not in BN.  Moreover, they stated that pathophysiological significance of this asymmetry remains to be determined.

Kamali and associates (2012) compared HPA axis activity in bipolar individuals with and without suicidal behavior and unaffected healthy controls through measurement of salivary cortisol.  Salivary cortisol was collected for 3 consecutive days in 29 controls, 80 bipolar individuals without a history of suicide and 56 bipolar individuals with a past history of suicide.  Clinical factors that affect salivary cortisol were also examined.  A past history of suicide was associated with a 7.4 % higher bedtime salivary cortisol level in bipolar individuals.  There was no statistical difference between non-suicidal bipolar individuals and controls in bedtime salivary cortisol, and awakening salivary cortisol was not different between the 3 groups.  The authors concluded that bipolar individuals with a past history of suicidal behavior exhibit hyperactivity in the HPA axis.  This biological marker remains significant regardless of demographic factors, mood state, severity and course of illness.  This finding in bipolar disorder is consistent with the evidence for altered HPA axis functioning in suicide and mood disorders and is associated with a clinical subgroup of bipolar patients at elevated risk for suicide based on their history, and in need of further attention and study.  The drawbacks of this study were (i) measure of salivary cortisol was a home-based collection by the study subjects, and (ii) the retrospective clinical data was primarily based on their historical account.

The American Association of Clinical Endocrinologists (AACE) Reproductive Medicine Committee’s position statement on bioidentical hormones (2007) noted that “Salivary hormone level testing is recommended by many BH proponents as a way of providing patients with “individualized” therapy.  Such tests are available to consumers over the Internet.  Some of the websites include elaborate questionnaires supposedly designed to establish the type of saliva testing needed.  The results of these tests are subsequently used to determine the type and dosage of compounded formulations.  Only a few types of salivary hormone testing methods are FDA/CLIA approved.  In fact, the vast majority of the salivary hormone tests results contain the disclaimer that those tests are not FDA/CLIA approved and should be used only for research purposes.  Yet such tests are still utilized to support clinical decisions by some supporters of BH …. the limited research, although interesting, does not prove that salivary testing can be used as reliable ancillary tests for clinical purposes …. the evidence often quoted by Salivary Test promoters simply do not pass the muster of the level 1 or even 2 of the Level of Evidences (LOE) as endorsed by AACE ”.

The North American Menopause Society’s position statement on “Hormone Therapy” (2012) stated that “Use of BHT (bioidentical hormone therapy) has escalated in recent years, along with the use of salivary hormone testing, which has been proven to be inaccurate and unreliable …. The Food and Drug Administration also states that there is no scientific basis for using saliva testing to adjust hormone levels”.

Bonamico et al (2011) stated that the high prevalence of celiac disease (CD) prompted them to evaluate a new, non-invasive disease screening strategy.  The aim was to identify CD in 6- to 8-year old children for a timely diagnosis, start gluten-free diet (GFD) in compliant subjects, achieve the growth target, and prevent CD complications.  A total of 5,0000 subjects were invited to participate in the study; 4,048 saliva samples were tested for anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A using a fluid-phase radioimmunoprecipitation method.  Positive children were tested for serum radioimmunoassay tTG IgA, ELISA tTG IgA, and anti-endomysium IgA.  Children confirmed as positive by serum assays underwent endoscopy with duodenal biopsies and, at the diagnosis of CD, were suggested to start GFD.  Consent was obtained from 4,242 parents (84.8 %) for the screening to be performed, and adequate saliva samples were collected from 4,048 children (95.4 %).  Thirty-two children were found to be salivary tTG IgA positive and 9 with borderline autoantibody levels; 31 of the 32 and 3 of the 9 subjects were also serum positive.  Twenty-eight children showed villous atrophy when undergoing intestinal biopsy, whereas 1 had Marsh 1 lesions; 3 children were suggested to start GFD without performing endoscopy.  Celiac disease prevalence in the population investigated (including 19 CD known cases) was 1.16 %.  The ratio between screening-detected patients and those diagnosed before the screening was 3:2.  The ratio between symptomatic and asymptomatic patients was 1:1.6.  The authors concluded that it is possible to perform a simple and sensitive CD screening using saliva.

However, the American College of Gastroenterology’s clinical guideline on “Diagnosis and management of celiac disease” (Rubio-Tapia et al, 2013) stated that “Stool studies or salivary tests are neither validated nor recommended for use in the diagnosis of CD”

Punyani and Sathawane (2013) noted that due to the pro-angiogenic characteristic of interleukin 8 (IL-8), it may play a vital role in tumor angiogenesis and progression.  These researchers estimated the levels of salivary IL-8 in oral pre-cancer and oral squamous cell carcinoma (OSCC) patients and compared them with healthy controls.  The aim was to evaluate its effectiveness as a potential biomarker for these diseases.  Each group comprised 25 individuals.  The salivary IL-8 levels were determined by ELISA.  The levels of salivary IL-8 were found to be significantly elevated in patients with OSCC as compared to the pre-cancer group (p < 0.0001) and healthy controls (p < 0.0001).  However, the difference in salivary IL-8 concentrations among the pre-cancer group and controls was statistically non-significant (p = 0.738).  The authors concluded that these findings suggested that salivary IL-8 can be utilized as a potential biomarker for OSCC.  Salivary IL-8 was found to be non-conclusive for oral pre-malignancy in this preliminary study.  Hence, its possible role in transition from pre-malignancy to malignancy needs further research with larger sample sizes.  They stated that the role of IL-8 in oral cancer if validated further by future research can provide an easy diagnostic test as well as a prognostic indicator for patients undergoing treatment.  Thus, if the role of Il-8 in tumor genesis can be sufficiently assessed, it could open up new avenues to find out novel treatment modalities for oral cancer.

Rajkumar et al (2013) stated that CYFRA 21-1, a constituent of the intermediate filament proteins of epithelial cells, is known to be increased in many cancers.  These investigators estimated the levels of salivary and serum CYFRA 21-1 in patients with oral pre-cancer and OSCC and compared them with healthy controls.  Each group comprised of 100 subjects.  Saliva and blood samples were collected from patients with OSCC, pre-malignant (PML) subjects, and normal healthy subjects.  Serum and salivary CYFRA 21-1 levels were measured by ELISA.  Appropriate statistical tests were employed to assess diagnostic potency of CYFRA 21-1.  These researchers found a significant increase in CYFRA 21-1 level in OSCC compared with PML and healthy subjects.  Salivary CYFRA 21-1 levels in OSCC was 3-fold higher when compared to serum levels.  Pre-malignant group showed increased salivary CYFRA 21-1 when compared to control subjects, but it was significantly lower compared with OSCC.  Receiver operator characteristic curve analysis showed salivary CYFRA 21-1 to have superior sensitivity in detecting OSCC compared with serum CYFRA 21-1.  The authors concluded that the outcome of this study suggested that salivary CYFRA 21-1 can be utilized as a biomarker in early detection of oral cancer.  These findings need to be validated by well-designed studies.

Cheng and colleagues (2014) gathered preliminary data concerning the feasibility of using 7 salivary mRNAs: IL-8; IL-1β; dual specificity phosphatase 1 (DUSP1); H3 histone family 3A (H3F3A); ornithin decarboxylase antizyme 1 (OAZ1); S100 calcium-binding protein P (S100P); and spermidine/spermine N1-acetyltransferase 1 (SAT1) for detecting development of OSCC in oral lichen planus (OLP) patients and OSCC patients whose disease was in remission.  Saliva samples were collected from 5 study groups (25 subjects per group): newly diagnosed OSCC, OSCC-in-remission, disease-active OLP, disease-inactive OLP, and normal controls.  The salivary mRNA levels were determined by a pre-amplification reverse transcription quantitative polymerase chain reaction (RT-qPCR) approach with nested gene-specific primers.  Mean fold changes between each pair of study groups were analyzed by the Mann-Whitney U test.  Salivary levels of OAZ1, S100P, and DUSP1 mRNAs were significantly higher in newly diagnosed OSCC patients, compared to: (i) normal controls (p = 0.003; p = 0.003; and p < 0.001, respectively); (ii) OSCC-in-remission (p < 0.001; p = 0.001; and p < 0.001, respectively); (iii) disease-active OLP (p < 0.001; p = 0.016; and p < 0.001, respectively); and (iv) disease-inactive OLP (p = 0.043; p < 0.001; and p < 0.001, respectively).  No significant differences were found in the levels of salivary IL-8, IL-1β, H3F3A, and SAT1 mRNAs between newly diagnosed OSCC patients and the normal controls (p = 0.093, 0.327, 0.764, and 0.560, respectively).  The authors concluded that salivary OAZ1, S100P, and DUSP1 mRNAs are candidate biomarkers for detecting OSCC development in OSCC patients in remission and in OLP patients.  Moreover, they state that these findings serve as the basis for a further large-scale study that may lead to a non-invasive screening method for early detection of OSCC.

Furthermore, an UpToDate review on “Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma” (DeSimone et al, 2014) does not mention salivary testing of CYFRA 21-1, IL-8, or mRNAs of DUSP1, OAZ1, and S100P, as a management tool.

CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes covered if selection criteria are met:
CPT codes not covered for indications listed in the CPB (not all-inclusive):
HCPCS codes not covered for indications listed in the CPB:
S3650 Saliva test, hormone level; during menopause
ICD-9 codes covered if selection criteria are met:
255.0 Cushing's syndrome
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
140.0 - 146.9 Malignant neoplasm of lip and oral cavity [oral squamous cell carcinoma]
173.02 Squamous cell carcinoma of skin of lip
255.41 - 255.42 Corticoadrenal insufficiency
256.2 Postablative ovarian failure
256.31 Premature menopause
296.00 - 296.06 Bipolar I disorder, single manic episode
296.20 - 296.36 Major depressive disorder
296.40 - 296.89 Bipolar I disorder, most recent episode (or current)
298.0 Depressive type psychosis
300.4 Dysthymic disorder
307.1 Anorexia nervosa
307.50 - 307.59 Other and unspecified disorders of eating
311 Depressive disorder, not elsewhere classified
528.6 Leukoplakia of oral mucosa, including tongue
528.79 Other disturbances of oral epithelium, including tongue [Erythroplakia of mouth or tongue]
579.0 Celiac disease
627.0 - 627.9 Menopausal and postmenopausal disorders
710.0 Sicca syndrome
733.00 - 733.09 Osteoporosis
V07.4 Hormone replacement therapy (postmenopausal)
V49.81 Asymptomatic postmenopausal status (age-related) (natural)
V76.42 Screening for malignant neoplasm of the oral cavity
V82.81 Special screening for osteoporosis

The above policy is based on the following references:
  1. American Association of Clinical Endocrinologists (AACE). Medical guidelines for clinical practice for management of menopause. Endocrine Pract. 1999;5:355-366. Available at: Accessed February 15, 2002.
  2. Hodgson SF, Watts NB, Bilezikian JP, et al. .American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract. 2003;9(6):544-564..
  3. AACE Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8(6):457-469..
  4. Huppert FA, Van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation for cognitive function. Cochrane Database Syst Rev. 2006:(2):CD000304.
  5. Grimley Evans J, Malouf R, Huppert F, van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev. 2006;(4):CD006221.
  6. Herbert V, Kava R. The miracle of melatonin? Priorities (American Council on Science and Health). 1995;7(4). Available at: Accessed February 15, 2002.
  7. No authors listed. Melatonin: Interesting, but not miraculous. Prescrire Int. 1998;7(38):180-187.
  8. Contreras LN, Arregger AL, Persi GG, et al. A new less-invasive and more informative low-dose ACTH test: Salivary steroids in response to intramuscular corticotrophin. Clin Endocrinol (Oxf). 2004;61(6):675-682.
  9. No authors listed. Chronic hypoadrenalism. GPNotebook. General Practitioner Notebook. Warwickshire, UK: Oxbridge Solutions, Ltd.; 2005. Available at: Accessed September 16, 2005.
  10. Odeke S, Nagelberg SB. Addison disease. eMedicine Endocrinology Topic 42. Omaha, NE:; updated November 25, 2003. Available at: Accessed September 16, 2005.
  11. Rubin GJ, Hotopf M, Papadopoulos A, Cleare A. Salivary cortisol as a predictor of postoperative fatigue. Psychosom Med. 2005;67(3):441-447.
  12. American College of Obstetricians and Gynecologists (ACOG) Committee on Gynecologic Practice. ACOG Committee Opinion #322: Compounded bioidentical hormones. Obstet Gynecol. 2005;106(5 Pt 1):1139-1140.
  13. National Institutes of Health (NIH). NIH State-of-the-Science Conference Statement on Management of Menopause-Related Symptoms. NIH Consensus and State-of-the-Science Statements. Bethesda, MD: NIH: March 21-23; 22(1). 
  14. Institute for Clinical Systems Improvement (ICSI). Menopause and hormone therapy (HT): Collaborative decision-making and management. Bloomington, MN: ICSI; October 2006.
  15. The North American Menopause Society. The role of testosterone therapy in postmenopausal women: Position statement of The North American Menopause Society. Menopause. 2005;12(5):497-511.
  16. Carroll T, Raff H, Findling JW. Late-night salivary cortisol measurement in the diagnosis of Cushing's syndrome. Nat Clin Pract Endocrinol Metab. 2008;4(6):344-350.
  17. Elamin MB, Murad MH, Mullan R, et al. Accuracy of diagnostic tests for Cushing's syndrome: A systematic review and metaanalyses. J Clin Endocrinol Metab. 2008;93(5):1553-1562.
  18. Doi M, Sekizawa N, Tani Y, et al. Late-night salivary cortisol as a screening test for the diagnosis of Cushing's syndrome in Japan. Endocr J. 2008;55(1):121-126.
  19. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540.
  20. Klebanoff MA, Meis PJ, Dombrowski MP, et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Salivary progesterone and estriol among pregnant women treated with 17-alpha-hydroxyprogesterone caproate or placebo. Am J Obstet Gynecol. 2008;199(5):506.e1-e7.
  21. Gröschl M. Current status of salivary hormone analysis. Clin Chem. 2008;54(11):1759-1769.
  22. Carroll T, Raff H, Findling JW. Late-night salivary cortisol for the diagnosis of Cushing syndrome: A meta-analysis. Endocr Pract. 2009;15(4):335-342.
  23. Raff H. Utility of salivary cortisol measurements in Cushing's syndrome and adrenal insufficiency. J Clin Endocrinol Metab. 2009;94(10):3647-3655.
  24. Flyckt RL, Liu J, Frasure H, Wekselman K, et al. Comparison of salivary versus serum testosterone levels in postmenopausal women receiving transdermal testosterone supplementation versus placebo. Menopause. 2009;16(4):680-688.
  25. Alexandraki KI, Grossman AB. Novel insights in the diagnosis of Cushing's syndrome. Neuroendocrinology. 2010;92 Suppl 1:35-43.
  26. Sereg M, Toke J, Patócs A, et al. Diagnostic performance of salivary cortisol and serum osteocalcin measurements in patients with overt and subclinical Cushing's syndrome. Steroids. 2011;76(1-2):38-42.
  27. Knorr U, Vinberg M, Kessing LV, Wetterslev J. Salivary cortisol in depressed patients versus control persons: A systematic review and meta-analysis. Psychoneuroendocrinology. 2010;35(9):1275-1286.
  28. Monteleone P, Scognamiglio P, Canestrelli B, et al. Asymmetry of salivary cortisol and α-amylase responses to psychosocial stress in anorexia nervosa but not in bulimia nervosa. Psychol Med. 2011;41(9):1963-1969.
  29. Kamali M, Saunders EF, Prossin AR, et al. Associations between suicide attempts and elevated bedtime salivary cortisol levels in bipolar disorder. J Affect Disord. 2012;136(3):350-358.
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