PCOS (Polycystic Ovary Syndrome) is a syndrome whose diagnosis is given by exclusion. A "Syndrome" is defined as “a group of symptoms that together are characteristic of a specific disorder, disease, or the like”. Often in medicine when something is characterized as a “syndrome” it is also a “diagnosis by exclusion” which is defined as “a diagnosis made by excluding those diseases to which only some of the patient's
symptoms might belong, leaving one disease as the most likely diagnosis, although no definitive tests or findings
establish that diagnosis.” This, again, means that for a physician to diagnose a woman with PCOS, he/she must first exclude other conditions that mimic PCOS. This is called Differential Diagnosis.
Differential diagnosis, by definition, is ”The process of weighing the probability of one disease versus that of other diseases possibly accounting for a patient's illness.” In theory, when a woman presents with the common complaints of PCOS, a clinician would need to rule out all the other conditions that mimic PCOS and present with one or more of the same symptoms. In another post I listed the most common signs and symptoms of PCOS presented to clinicians and their prevalence in women with PCOS. Also noted previously, is the importance of establishing the proper diagnostic protocol to determine who and how many women are afflicted by PCOS, an thereafter the appropriate treatment plan.
PCOS is a disorder with heterogenous causative factors which presents with clinical and physical symptoms, as well as hormonal, metabolic, and reproductive features. These features, however, are not exclusive to PCOS. Some other diseases also present with some of these physical and/or endocrine (hormonal) features. Conditions such as “ … prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made.” Further, “…nonclassic adrenal hyperplasia, Cushing’s syndrome, androgen-producing tumors, … drug-induced androgen excess…, as well as pregnancy …” also need to be excluded. Some of these very serious conditions, “that exhibit PCOS-like features may elude diagnosis and proper management if not considered.” In practice, I am not sure if this (proper Differential Diagnosis) happens 100% of the time. A woman would have to undergo an extensive check up, including blood, imaging and other diagnostic and screening tests. In my case, this didn’t happen. “In contrast to PCOS, some of these latter conditions can be life threatening or associated with increased morbidity if left undiagnosed”. Luckily, many of these other disorders do have gold-standard testing for its diagnosis, whereas PCOS does not, hence, a diagnosis of exclusion.
Let’s look at some of the Differential Diagnosis mentioned above and analyse their signs and symptoms and overlap with PCOS.
Nonclassic Congenital Adrenal Hyperplasia (NCAH)
NCAH is a genetic disorder presenting with clinical features of androgen (male hormone) excess, similar to PCOS, which become apparent in young girls, adolescents and adult women. Irregular menstruation, hirsutism, and acne are the most prominent clinical signs and focus of treatment. “…besides the presence of some features that may help distinguishing these two conditions, the gold standard in cases of doubt remains the 17-OH-PG response to ACTH stimulation” which if elevated would indicate NCAH rather than PCOS.
Cushing’s Syndrome (CS)
CS is condition of glucocorticoid excess, either endogenous or exogenous. It is rare and highly variable in its clinical presentation and sometimes difficult to diagnose. The overlap with PCOS is found in its propensity to weight gain, menstrual irregularities and infertility, whereas there may be many serious differential concerns such as muscle weakness and atrophy, sensitivity to infections, decrease in bone density and severe psychiatric and cognitive dysfunction, among others.
Androgen Excess (Drug/Tumour induced)
“Androgen-secreting neoplasms, mostly arising from the adrenals or ovaries, are relatively rare and potentially life-threatening and may be associated with virilization (clitoromegaly, deepening of the voice, frontal balding and muscle hypertrophy)”. Both the tumour-induced and drug-induced cases present with clinical signs of hyperandrogenemia (acne, hirsutism, androgenic alopecia, menstrual irregularity and infertility) similar to PCOS. Blood and/or imaging must be used to rule out this serious condition.
Pregnancy is the most common cause of amenorrhea and anovulation in women of reproductive age. A pregnancy test (at-home/lab) is necessary during the diagnostic protocol.
Disorders which may affect thyroid function such as nodules, tumours, autoimmunity, Primary Hypothyroidism, and others, may at times present with a PCOS-like phenotype. Namely, from a clinical perspective, excess weight gain, in some cases enlarged ovaries with or without cysts, hair-loss, and possible menstrual irregularities and infertility. Thyroid hormones (TSH, T3, T4) can be tested in blood.
States of prolactin excess (hyperprolactinemia) present due to tumours or other conditions which may cause serum prolactin levels to be elevated. Prolactin’s main function is to develop breasts during pregnancy and prepare for lactation. “However, prolactin also binds to specific receptors in the gonads, lymphoid cells, and liver.” In an elevated state, prolactin may produce unwanted signs and symptoms outside of lactation. High levels of prolactin inhibit ovulation and menstruation, may cause painful intercourse, acne and hirsutism and galactorrhea (milky discharge from breast). Prolactin is a hormone that can be tested for and ruled out.
Other Insulin Resistant Conditions
“Acanthosis nigricans is a skin lesion characterized clinically by velvety, papillomatous, brownish-black, hyperkeratotic plaques, typically on the intertriginous surfaces (body folds) and neck.” AC is a clinical finding in people with hyperandrogenemia (high levels of male hormones) and Insulin Resistance. “Its severity is directly correlated with the degree of insulin resistance” in other words, the more insulin resistant the person, the bigger and darker the skin patches found in the skin folds.
“In the HAIR-AN syndrome [hyperandrogenism (HA), IR and acanthosis nigricans (AN)] the degree of IR (insulin resistance) and subsequent hyperinsulinemia lead to increased ovarian androgen production … In addition, in a number of common disorders associated with hyperinsulinemia and IR, such as type 2 diabetes mellitus, gestational diabetes and obesity, the prevalence of PCO/PCOS is substantially increased.”