Diagnostic Tests - Identifying Common Endocrine Disorders

The Endocrine System

Have you ever wondered how your body is able to regulate its metabolism, mood, growth, temperature, heart rate, and even fertility? The endocrine system gets the credit and is able to regulate all of these functions via a system of glands, which are small excretory organs in charge of the release of hormones.^{[1][2][3][4][5]} Disorders of the endocrine system result when there is an imbalance and/or lack of one or several hormones.^[1][2]

Hormonal imbalances can manifest in a variety of signs and symptoms via various disease processes, such as diabetes mellitus, hypothyroidism, hyperthyroidism, polycystic ovary syndrome (PCOS), adrenal insufficiency, and low testosterone.^{[1][2][3][4][5][6]} There are many types of endocrine disorders, but these are some of the more commonly diagnosed ones, with diabetes at the top of the list. Patients who develop thyroid and cardiovascular disorders are also predisposed to develop diabetes.[3] Thus, proper diagnosis and management is necessary to prevent the progression of several endocrine (and other system) disorders. How do hormonal imbalances occur? Common causes are linked to injured glands, tumours, one gland failing to stimulate another gland (e.g. hypothalamus to stimulate pituitary to release hormones), infections, diseases, and genetics.^{[1][2][3][4][5]} Identifying the cause is often part of the cure, whether a simple fix like adding a supplement is needed or a more complex fix such as referring a patient for possible surgery is indicated.

Diagnosing Endocrine Disorders

Patients cannot be diagnosed with an endocrine disorder based upon signs and symptoms alone. The signs and symptoms present will be based upon the specific glands being impacted. Further screening will be indicated in order to determine a course of treatment based upon initially obtaining a proper diagnosis. Serum blood tests are the mainstay of endocrine diagnostic tests, in addition to the use of urine and/ or imaging tests when indicated.^[4] With cost containment and time as major variables to consider, your practitioner will order tests based upon presenting signs and symptoms in addition to predisposing risk factors. Common risk factors for endocrine disorders include genetics; lifestyle; diet; gender; body mass index (BMI); and exposure to endocrine-disrupting chemicals from food, environment, medications, personal-care products, and home products. Let’s further discuss the common endocrine disorders and commonly ordered diagnostic tests.^[4][6]

Diabetes

Serum blood tests are the mainstay of diagnosing diabetes mellitus, along with clinical signs and symptoms such as excessive urination (polyuria), thirst (polydipsia), and hunger (polyphagia). Diabetes results when the pancreas makes no or little insulin (type 1), or when the body is unable to use insulin properly to absorb glucose into the cells, resulting in insulin resistance (type  2). Both scenarios result in elevated blood sugar levels, called hyperglycemia. The three typical serum blood tests for diabetes include random blood sugar, fasting blood sugar, and hemoglobin A1c (HbA1c) test.^[3][4] A random blood glucose test is done at any time regardless of when you last ate. A level of 200 mg/dl or more is positive for diabetes.^[4] A fasting blood glucose test is done after fasting through the night. Results indicate as follows: Normal is less than 100 mg/dl, prediabetes is 100–125 mg/dl, and diabetes is 126 mg/dl or greater. A diagnosis of diabetes is confirmed via two separate fasting blood glucose tests.^[4] Finally, the HbA1c test measures the percentage of blood glucose molecules bound to hemoglobin over a two- to three-month window. Results indicate as follows: Normal is less than 5.7%, prediabetes is 5.7–6.4%, and diabetes is 6.5% or greater.^[4]

Hypothyroidism and Hyperthyroidism

Disorders of the thyroid are initially and primarily diagnosed via serum blood tests. There are several common thyroid tests, commonly called the “thyroid panel,” your provider will order with suspected thyroid disorders, including free triiodothyronine (T3) or total T3, free thyroxine (T4), and thyroid-stimulating hormone (TSH). In order to help diagnose if the cause of thyroid dysfunction is autoimmune in nature, your provider should also order a thyroid antibodies or autoantibodies test to help with the diagnosis of Graves’ disease (autoimmune hyperthyroidism) or Hashimoto’s disease (autoimmune hypothyroidism).^[3][4]

All three lab tests in the thyroid panel interact with one another. The pituitary gland makes TSH, which tells the thyroid gland to make free T3 and free T4. The amounts of circulating free T3 and free T4 determine how much TSH is made. Thus, TSH works on a negative feedback loop, with increased levels indicating hypothyroidism and decreased levels indicating hyperthyroidism.^[1][3][4] In order to confirm hyperthyroidism, both free T3 and free T4 must be tested, because free T4 levels may still be normal while free T3 levels will be increased. Free T4 is not bound to protein molecules in the bloodstream and freely enter body tissues, which makes free T4 preferred over bound T4 molecules. Free T4 results indicate as follows: Hypothyroidism is less than 0.8 ng/dL and hyperthyroidism is greater than 1.8 ng/dL. Further testing may be needed beyond serum blood testing, including thyroid ultrasound imaging and radioactive iodine uptake test.^[4]

Polycystic Ovary Syndrome (PCOS)

The ovaries are responsible for the secretion of estrogen and progesterone, and for the maturation and release of eggs. For a woman to be diagnosed with PCOS, at least two of the following signs and symptoms must be present:

• Menstrual dysfunction
• Elevated androgen (testosterone) levels
• Ultrasound confirmation of polycystic ovaries [1,2,4]

Menstrual dysfunction includes an irregular or absent menstrual cycle with an absence of ovulation. A serum testosterone test showing a level greater than 20 ng/dL will be seen in women with PCOS. A uterine ultrasound will also be ordered to see if at least twelve ovarian follicles are visible, or one or both ovaries have increased in size.[4]

Adrenal Insufficiency

Imbalances of cortisol and/or aldosterone can cause adrenal insufficiency. The adrenal glands control reactions to illness or injury, regulate blood pressure, regulate blood glucose levels, and help with fat and protein metabolism.^[1][4] Addison’s disease can be diagnosed with the adrenocorticotropic hormone (ACTH) stimulation test. The anterior pituitary releases ACTH and tells the adrenal glands to make cortisol. A positive diagnosis of Addison’s disease is made when only a low rise in cortisol is seen after ACTH is intravenously injected.^[4] Cushing syndrome is caused by an excessive release of cortisol and can be diagnosed via three different tests, including corticotropin-releasing hormone (CRH) stimulation test, dexamethasone suppression test, and 24-hour urine-collection test. The hypothalamus releases CRH, which tells the pituitary gland to release ACTH by the anterior portion, and this tells the adrenal glands to make cortisol.^[4] The CRH suppression test helps to identify excessive secretion of ACTH and subsequent hypersecretion of cortisol, which is also seen with Cushing disease and pituitary tumours. The dexamethasone suppression test is done with a blood or urine sample when testing for Cushing syndrome, because dexamethasone normally decreases cortisol levels. A positive diagnosis is made when there are no changes in cortisol levels. Finally, the 24-hour urine collection test measures the amount of cortisol in the urine over a full day, with too much cortisol suggesting Cushing syndrome.^[1][4]

Low Testosterone

The testicles produce testosterone in men and the ovaries, in much smaller amounts, produce testosterone in women. Low testosterone, or hypogonadism, is classified as either primary or secondary. Primary hypogonadism is due to injury, infection, or genetic malfunctioning of the testicles. Secondary hypogonadism has a deeper root in the hypothalamus and, by default, pituitary. This results in a communication breakdown with the brain, causing low testosterone levels by inhibiting follicle-stimulating hormone (FSH) and luteinizing hormone (LH).^[1][4] Normal testosterone levels are between 300 and 1000 ng/dL, thus a level less than 300 ng/dL is indicative of hypogonadism. If secondary hypogonadism is suspected, a cranial CT or MRI scan may be ordered to visualize a pituitary tumour as a source of low testosterone.^[4]

In conclusion, endocrine diagnostic tests are used in conjunction with clinical signs and symptoms in order to diagnoses common conditions of the endocrine system. Most endocrine diagnostic tests are based upon serum blood tests, but some are based upon urine or imaging tests. Your provider will order and interpret the appropriate diagnostic tests, coupled with a physical assessment, before recommending an appropriate course of treatment.