The Diagnosis and Treatment of Hypothyroidism
1. Diagnosis
Hypothyroidism is a clinical diagnosis based on evidence of suboptimal thyroid effect in the brain and/or
body. The vast majority of hypothyroidism is not due to disease of the thyroid gland or hypothalamicpituitary system, but instead is due to a dysfunction of the HP-thyroid system. The TSH is usually normal
initially, and is of little use for either diagnosis and treatment. The diagnosis is made according to the
presence of hypothyroid symptoms (see chapter) and low-in-range or low FT4 and/or FT3 levels. The FT4
is the usually the most important single measurement, but an above-mid-range FT4 with a low-in-range
FT3 can represent hypothyroidism. 95% of apparently healthy adults who are not screened for
hypothyroid symptoms have a FT4 of 1.0 to 1.7ng/dl—the true population range. So a person with a FT4
of 1.1 is at the 14th percentile of the unscreened population. The FT3 should usually be above 3.5pg/ml
(range 2.0-4.4pg/ml). A person with both FT4 and FT3 low the lab’s ranges can be severely hypothyroid.
The person’s cortisol status affects their thyroid requirement. More cortisol reduces T4-to-T3 conversion
so a person with higher cortisol levels requires higher thyroid levels, and vice versa.
2. Treatment
The therapeutic goal is simple: The elimination, as much as possible, of all symptoms and signs of
hypothyroidism without producing any signs or symptoms of thyrotoxicosis (see chapter). T3
(liothyronine) must be included with T4 to produce a physiological treatment regimen—especially as the
TSH will be suppressed on therapy, thereby reducing thyroidal T3 production and T4-to-T3 conversion
throughout the body. The ideal T4:T3 ratio for therapy is unknown and certainly varies with the person.
For most persons, NDT (e.g. Erfa Thyroid) with its 4:1 T4:T3 ratio works well. With NDT therapy FT4
levels will be lower and FT3 levels higher than in the untreated state.
Start the cortisol-sufficient patient with a 30mg NDT tablet upon awakening. Increase by one tablet
every week or two up to 3 to 4 tablets, adjusting the frequency and final dose according to the weight
and health of the patient. To use synthetic T4 and T3 instead, prescribe a 25mcg levothyroxine tablet
and 5mcg liothyronine tablet to be taken together, and also increase each by one tablet every week or
two up to 3 tablets each (75mcg T4+15mcg T3). Describe for the patient the negative symptoms that
may arise due to a too rapid or great increase in thyroid levels or due to insufficient cortisol. These
would require a lowering of the dose. Urge the patient to contact the clinic with any persisting negative
symptoms.
If the patient is already on TSH-normalizing levothyroxine therapy and has hypothyroid symptoms, check
add 5mcg T3 to the T4 dose in the morning. Increase by 5mcg every two weeks up to 15mcg/day.
3. Follow-up
The first blood test will be done after 2 months on the full thyroid dose, in the morning prior to taking
the tablets. The TSH will most likely be low. With optimal replacement, the FT4 is usually mid-range to
low-in-range (1 to 1.3ng/dL) and the FT3 mid-range to slightly high (3.3 to 5pg/ml). Early in replacement
therapy, the patient’s thyroid gland adds substantial hormone to the exogenous dose, but this
contribution declines with time when TSH is suppressed. Initial test levels may appear high, but if there
are no symptoms of thyrotoxicosis it is best to continue the same dose as levels will fall with time. If
there has been good therapeutic effect, continue the dose and recheck levels in 2 months. On a given
dose, thyroid levels will gradually fall over the first 2 yrs of treatment, requiring a periodic increase in
dose. When indicated by symptoms and levels, the dose can usually be increased by 30mg NDT or
equivalent, but at times a smaller increase may be considered. Overtreatment is suggested if the FT4 is
high in its range and FT3 also high-in-range or high. Remember that the average FT3 level is much higher
than the 24hr. trough level.
4. Troubleshooting thyroid optimization therapy
Swallowing one’s thyroid hormone once daily is unnatural. With a 4:1 or 5:1 T4:T3 ratio, T3 levels peak
at 3hrs at superphysiological levels, then fall gradually until the next dose. Some persons will need to
split the dose if they have excessive jitteriness in the morning or have night-time awakening or
palpitations (as T3 levels drop). See the thyroid chapter for a discussion of the possibility of atrial
fibrillation and of other concerns surrounding thyroid optimization therapy.
It is a well-known medical principle that thyroid replacement worsens adrenal insufficiency. In fact,
almost the only problem that arises with thyroid optimization is cortisol deficiency—which is quite
common among women with fatigue, achiness, brain fog, depression, etc. These symptoms can also be
due to hypothyroidism. Thyroid replacement is easy and beneficial unless there is cortisol deficiency.
Effective thyroid optimization increases cortisol metabolism and cortisol requirement, and thus worsens
an existing cortisol deficiency. A person with insufficient cortisol will react negatively to effective thyroid
optimization—sometimes with the first dose, sometimes after feeling better for months. If this occurs,
one can try lowering the thyroid dose to find a workable compromise. One can also ask the patient to
take the NDT in the middle of the night, 3.5 hrs prior to awakening for the day. The T3 thus peaks when
cortisol is naturally highest, and also stimulates more cortisol production during the early-AM rise. If no
alterations in the thyroid regimen will allow the person to feel and function well, the physician must
offer the patient a trial of cortisol replacement.