SHBG: Broadening the Scope of Hypothyroid Testing

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Once a diagnostic and treatment protocol has been established, it becomes difficult to modify when new information challenges the norm. Few situations highlight this more than the reliance on TSH (thyroid-stimulating hormone) for hypothyroidism. Since the 1980s, TSH has been the gold standard for thyroid testing even though it fails to provide a complete and accurate assessment. Considering TSH is just one of many hormones involved in thyroid function, it is not surprising there are numerous shortcomings to this approach. SHBG (sex-hormone binding globulin) is one important factor in regulating hormonal balance that is widely overlooked. Research and clinical evidence suggests implementing a more comprehensive assessment protocol, which includes SHBG as a means to improve patient outcome.


The thyroid gland was originally named by the Greeks who called it thyros, meaning “shield” after its shape. The gland is the master regulator of functions i.e. body temperature, immunity, metabolism, and so on. It is often compared to an engine that keeps the body running at the proper speed. The thyroid senses changes within the body and responds by adjusting hormone levels as appropriate. When a hypothyroid condition exists, the thyroid doesn’t keep up with the demands of the body. More specifically, it means T3 isn’t active in the body tissues as it should be.


Overall health requires thyroid hormone transport into the cell tissue, which is an energy dependent process. Since energy is produced in the mitochondria it’s no wonder mitochondrial dysfunction is a factor in conditions where thyroid transport is reduced. Transporter activity is also hindered by outside influences such as toxins. In contrast, the pituitary gland (where TSH is produced) has transporters that run on a separate system that isn’t influenced by energy or outside factors. As a result, thyroid transport in the body can be impaired while the pituitary has increased transport activity. Pituitary receptors can also become saturated and signal TSH to stop signaling the thyroid to release more hormone regardless of levels in body tissues. Ultimately the TSH test is indicative of TSH in the pituitary but not necessarily reflective of thyroid hormone levels in the rest of the body.

Conditions with reduced thyroid transport:

Hypothyroid Test Methods Fall Short

Conventional hypothyroid testing generally relies on TSH level for diagnosis, with T3, reverse T3 (RT3) and T4 as supporting determinants. Some physicians will base treatment solely on TSH levels. Either way, inaccuracies abound. For instance, TSH didn’t become the lead biomarker because it’s the most critical, rather because the analytical lab test was working so well. Unfortunately the test fails to reflect how much thyroid hormone is actually in the tissues. A person can have normal serum (blood) levels of TSH, T3 and T4, yet continue to have hypothyroid symptoms because active has T3 failed to enter the cells (or it wasn’t converted to its active form by T4). The tests are based on bloodstream levels, which don’t reflect the activity of cellular transporters and tissue hormone levels. Including RT3 test along with the T3/RT3 ratio can offer insight as to what is happening in the tissues.

TSH test fails to identify:

  • If hypothyroidism is causing the problems
  • If pituitary gland is functioning properly
  • If thyroid hormones are functioning properly in the body
  • If thyroid hormones are successfully transported into the cell (or if they are remaining in the bloodstream)
  • If an autoimmune condition exists, i.e. Hashimoto’s disease.

SHBG: Regulator and Indicator

The endocrine system, which encompasses hormone functioning, is known for its synchronicity. Yet factors such as stress, diet, pharmaceuticals, and environmental toxins can all disrupt hormonal balance. Because of its integral role as a hormone transporter, SHBG can be used as an indicator of how the system is functioning.

The role of SHBG is to protect regulate, and transport sex hormones, estrogen and testosterone. Produced primarily in the liver, SHBG binds to the hormones and shuttles them to tissues in body. When bound to SHBG the hormone, i.e. estrogen, it isn’t “free” or available. It’s important for the body to maintain the right amount of available estrogen, relative to the bound estrogen, as well as to the other hormones. Balance and synchronicity are key. An imbalance, along with low SHBG levels is frequently found in conditions with low thyroid transport (previously listed).

SHBG production responds to thyroid and estrogen hormones, which is why it’s considered to be a good indicator of thyroid tissue levels. In general it is a better marker for women than men. If estrogen levels are satisfactory, SHBG can act as a marker for tissue levels of T3 unless a woman is taking oral estrogen hormone replacement therapy (HRT). In this case, SHBG levels will elevate in response to increased estrogen levels in the liver caused by metabolizing the HRT. SHBG testing would therefore not be a true indicator, unless transdermal patches or creams are used. Simply put, SHBG levels impact estrogen and estrogen affects the thyroid. Thyroid hormones also affect SHBG levels by increasing its production and often diminishing free estrogen. Confused? Here is a gauge:

SHBG for women with adequate estrogen levels should be above 70 nmol/L, and men above 25 nmol/L. For those using thyroid replacement and are below these SHBG levels, it can signify ineffective treatment. SHBG levels are expected to increase when thyroid hormone medications are implemented.

Widening the lens of hypothyroid test methods

Hypothyroid testing remains controversial in the medical community. Although TSH testing is useful for indicating when a hypothyroid dysfunction exists (when levels are elevated), the problem lies in overreliance on it in ways contradicted by research. To best assess status of an individual exhibiting hypothyroid symptoms, both symptoms and lab results should be considered. Lab testing offers a more comprehensive diagnosis when T3/reverseT3 ratio, along with SHBG, is included with a thyroid panel (TSH, T3, T4, RT3). Finally, TPO antibody testing is also important for determining autoimmune hypothyroid, or Hashimoto’s disease, which accounts for the majority of hypothyroid cases.


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2. Hoermann, R. Midgley, J. Larisch R. Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. Front Endocrinol (Lausanne). 2015; 6: 177.

3. Holtorf K. Thyroid Hormone Transport into Cellular Tissue. J of Restorative Med. Aug 2014; 3: 55-68. Available at:

4. Selva, D. Hammond, G. Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4α. J Mol Endocrinol. 2009 Jul 9; (43): 19-27.

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6. White, Z. Do you know your hormone status? Life Extension Magazine.

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