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Medicines Q&As
Q&A 56.7
What clinical evidence is there to support the use of “Armour thyroid” or
other desiccated thyroid extract products?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: February 2016
Summary
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Desiccated thyroid extract is derived from porcine thyroid gland. One grain contains 38mcg levothyroxine
(T4) and 9mcg liothyronine (T3) per 65mg of the labelled amount of thyroid. Prescribers and patients
should be aware that the amount of thyroid hormone in the thyroid gland can vary from animal to animal
and between batches of product so a consistent effect cannot be guaranteed with desiccated thyroid
extract products.
Products such as Armour® Thyroid (AT), which contain thyroid extract, are not licensed in the UK.
However, for historical reasons, these products are available in the US but they have not been approved
by the US FDA as new drugs and have therefore not undergone rigorous clinical trials evaluating safety
and efficacy. The FDA has urged companies who market unapproved drug products, including thyroid
products, to carry out such studies and submit applications for their approval as new drugs.
The Royal College of Physicians (RCP), the British Thyroid Association and the European Thyroid
Association all recommend that, for the vast majority of patients, levothyroxine alone is used in the
treatment of hypothyroidism for underactivity of the thyroid gland. Routine use of thyroid extracts including
AT is not recommended because this is inconsistent with normal physiology, they have not been
unequivocally proven to be of any benefit to patients and they may be harmful in the long term. Most
liothyronine (80%) is generated from the de-iodination of circulating T4, so a preparation of levothyroxine
should provide T3 in a physiological and appropriate concentration.
There is a lack of good quality evidence to support the use of desiccated thyroid. Studies vary in design,
size, duration and outcomes.
There is only one small randomised, controlled, crossover trial which has compared the efficacy of
desiccated thyroid with levothyroxine.
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Seventy patients were treated with one treatment for a period of 16 weeks, then crossed over to the
other treatment for another 16 weeks. There was no difference in general health and all patients
had TSH levels within range.
Patients who preferred desiccated thyroid (49%) tended to have greater weight loss and
improvement in subjective symptoms such as concentration, memory and energy.
In a retrospective practice-based review, the use of desiccated thyroid improved symptoms in 89 patients
who were previously uncontrolled on levothyroxine (median dose 76-100mcg). No dose titration of
levothyroxine had been carried out prior to switching to desiccated thyroid to see if a dose increase could
help with symptom control.
Another retrospective practice-based review found that switching to AT improved symptoms in 154
(euthyroid) patients who reported persistent symptoms despite taking levothyroxine. However, the
patients studied were already dissatisfied with their levothyroxine which would have led to selection bias.
There is limited information regarding adverse events. Product information for desiccated thyroid
products state that adverse reactions, other than those indicative of hyperthyroidism because of
therapeutic overdosage, are rare. In a small study in which 40 patients had their treatment switched to
levothyroxine from desiccated thyroid, abnormally high liothyronine concentrations, measured 2-5 hours
post-dose were seen in 90% of patients taking 90mg-180mg desiccated thyroid. Most tolerated this well
but six patients had symptoms of hyperthyroidism (nervousness, palpitations and tremor post-dose) and
benefited from switching to levothyroxine. Abnormally high liothyronine levels were also seen in a smaller
(n=21) case series.
Some patients do request treatment with desiccated thyroid, such as AT because they do not feel as well
when treated with levothyroxine, but there is a lack of robust evidence supporting the clinical
effectiveness of desiccated thyroid.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
Background
Hypothyroidism is underactivity of the thyroid gland. The aim of treatment is to render the patient ‘euthyroid’,
or with a normal thyroid state.(1) The Royal College of Physicians (RCP) recommend that, due to
overwhelming evidence supporting its use, levothyroxine (tetra-iodothyronine, or T4) alone is used in the
treatment of hypothyroidism.(1) Levothyroxine has a long half-life (1 week), giving relatively stable blood
levels with minimal daily fluctuations in T4. Most liothyronine, T3, (80%), is generated from the de-iodination of
circulating T4, so a preparation of levothyroxine should provide T 3 in a physiological and appropriate
concentration. (2) Liothyronine has a quicker onset (a few hours) and shorter duration of action than
levothyroxine (half-life is 24-48 hours). (3-8)
The Royal College of Physicians (RCP), the British Thyroid Association (BTA) and the European Thyroid
Association (ETA) all recommend that, for the vast majority of patients, levothyroxine alone is used in the
treatment of hypothyroidism for underactivity of the thyroid gland. Routine use of thyroid extracts including AT
is not generally recommended as this is inconsistent with normal physiology, has not been unequivocally
proven to be of any benefit to patients and may be harmful in the long term. Furthermore, there are risks from
T3 therapy, such as osteoporosis and arrhythmias (which can also occur with over-treatment of T4) and AT
contains an excessive amount of T3 in relation to T4 (excessive compared to the normal physiological ratio of
T3:T4 in human). (1,7,8)
Desiccated thyroid extracts, such as AT, NP Thyroid and Nature-Throid®, are natural preparations derived
from porcine thyroid glands. One grain of thyroid contains 38 micrograms (mcg) levothyroxine and 9mcg
liothyronine per 65mg of the labelled amount of thyroid. (3-5) The amount of thyroid hormone in the thyroid
gland can vary from animal to animal and between batches (6) so a consistent effect cannot be guaranteed
with desiccated thyroid extract products. These products are not licensed in the UK and while they are
available in the US, (3-5) they have not been approved by the US FDA as new drugs and have therefore not
undergone rigorous clinical trials evaluating safety and efficacy. Notably, the FDA have urged all companies
who market unapproved drug products, including thyroid products, to carry out such studies and submit
applications for approval but to date; no such applications have been submitted at the time of writing.
The use of desiccated thyroid is considered by some to be obsolete and is not supported by the RCP due to
the lack of supporting validated research in published in peer-reviewed journals.(1,6,9-11). There is also
some concern that symptoms of hyperthyroidism, due to high T3 levels post-dose, can occur. (2;6,9,10)
However, some patients do request treatment with desiccated thyroid, such as AT because they do not feel as
well when treated with levothyroxine (12), but are there any robust data to support the clinical effectiveness of
desiccated thyroid?
Answer
Few robust studies of desiccated thyroid have been carried out in the last 10 years. Most data are pre-1980
and many studies date from the 1950s to 1970s. These tend to be uncontrolled, open-label studies which
compared desiccated thyroid with levothyroxine, not in terms of efficacy and safety but comparative potency,
onset and duration of action, and effects on serum lipids; these have not been included in this Q&A.(13-16) It
is not clear whether studies comparing levothyroxine alone with levothyroxine/T3 combination can be
extrapolated to desiccated thyroid. These studies have not been reviewed because they do not provide
information supporting the clinical effectiveness of natural desiccated thyroid.
Randomised, double-blind trial
There is only one randomised, prospective, double-blind study comparing the effectiveness of desiccated
thyroid extract (DTE) with levothyroxine (n=70). (12) Patients with primary hypothyroidism on a stable dose of
levothyroxine were randomised to treatment with either DTE or levothyroxine in identical appearing capsules.
Each grain (65mg) of DTE (as AT) provided 38mcg levothyroxine and 9mcg liothyronine. The initial
desiccated thyroid dose was based on the conversion: 1mg DTE = 1.667mcg levothyroxine. After 6 weeks of
study medication, thyroid stimulating hormone (TSH) levels were checked and medication adjusted to maintain
TSH between 0.5 and 3.0microIU/mL. Once the TSH was within range, medication was continued for at least
another 12 weeks. Patients were then crossed over to the other treatment arm for 16 weeks, with TSH
checked at 6 weeks as during the first treatment period.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
The primary outcome measures were the changes from baseline to endpoint of a number of assessments,
including the Thyroid Symptom Questionnaire (TSQ), the quality of life General Health Questionnaire (GHQ)12, the Wechsler memory scale (WMS-IV) and the Beck Depression Inventory (BDI). The WMS-IV included
the auditory memory index (AMI) and the visual working memory index (VWMI). Subgroup analyses were
carried out on patients who preferred desiccated thyroid or levothyroxine or who had no preference. A sample
size of 67 was required to provide 80% power to detect a difference of 8 points on the TSQ.
a)
b)
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d)
Primary outcome measures. Overall, the patients showed no difference in symptom scores, general
health questionnaires or neuropsychological testing. During the DTE treatment period, there was a
trend towards greater improvements in GHQ-12, TSQ and AMI and there was a reduction of 2.86lb in
weight (p<0.001) compared to the levothyroxine treatment period. No study patient had a TSH level
outside of the reference range. No adverse events were reported with any of the treatments; both were
tolerated equally well. Patients had higher T3 serum levels during the DTE treatment period but no
cardiovascular adverse events occurred.
Patient preference. At the end of the study, 34 patients (49%) preferred DTE treatment, 13 (19%)
preferred levothyroxine and 23 (33%) had no preference. The higher preference for DTE therapy was
due to an average of 4lb weight loss during the DTE treatment compared with levothyroxine (p<0.001),
(note that on average, these patients were 16lbs heavier at baseline than those patients who preferred
levothyroxine), and improvements in subjective symptoms such as concentration, memory, sleep,
decision-making capability, happiness and energy levels. Patients preferring DTE therapy did better on
their neuropsychological measures compared with baseline [TSQ, GHQ-12 WMS-IV and BDI], while
those preferring levothyroxine did better only on the WMS-IV.
Predictors of preference for DTE. The best predictor for clinical preference for DTE was a lower TSQ
score at endpoint. Patients with lower VWMI values on DTE were also more likely to favour DTE.
Doses. The mean levothyroxine dose during the study was 119.2mcg and the mean DTE dose was
80.6mg.
For the patients who preferred DTE treatment, their general well-being and thyroid symptoms were better
controlled than with levothyroxine. It is possible that DTE may provide subtle improvements for some patients.
The study is limited by its small size, low sensitivity of some of the neuropsychological tests and biochemical
measures, no genetic testing for deiodinase polymorphisms and the lack of a washout period, although this
may not have been deemed appropriate. Studies with a longer duration are required to clarify the efficacy and
safety of desiccated thyroid extract.
Switching from desiccated thyroid to levothyroxine
Thyroid hormone levels were compared in 40 patients who had their therapy switched from desiccated thyroid
to levothyroxine and clinical benefits were assessed.(6) Seventeen patients had been treated for
hypothyroidism and 23 patients received thyroid as medical therapy for thyroid gland suppression. The most
common desiccated thyroid doses were 120mg-180mg per day (in 35/40 patients), which were switched to
150mcg to 200mcg levothyroxine daily. Serum thyroid hormone levels were measured while the patients were
taking desiccated thyroid, and then at least 6 weeks after changing to levothyroxine. The mean T3 levels with
desiccated thyroid were significantly higher than with levothyroxine: 289ng/dL vs. 176ng/dL, p<0.0005 [normal
range, 70-180ng/dL]. The mean T4 level was significantly lower with desiccated thyroid than with
levothyroxine: 7.4mcg/dL vs. 11.6mcg/dL, p<0.01 [normal range, 5-13mcg/dL].
a) When treated with desiccated thyroid, most patients (36/38) had T3 levels above the normal range and
39/40 had T4 levels in the low normal or normal range; raised T4 level was seen in a pregnant patient.
One patient had a T3 level of 540ng/dL 3 hours post-dose, falling to 240ng/dL at 24 hours;
supraphysiological levels of T3 have also been reported in a case series of 21 patients experiencing
nervousness, palpitations and tremor post-dose.(9)
b) When treated with levothyroxine, 17/40 patients had elevated T3 levels (two of the 17 patients had
previously been taking 60mg desiccated thyroid) and 8/40 had raised T4 levels; three of the raised T3
and one of the raised T4 could be accounted for by pregnancy and all of the raised levels occurred in
patients taking 200mcg, which may have been too high a dose.
What this study showed is that symptoms of hyperthyroidism may occur following a daily dose of 120-180mg
desiccated thyroid. Abnormally high T3 concentrations, measured 2-5 hours post-dose were seen in 90% of
patients taking 90mg-180mg desiccated thyroid; while most tolerated this well, six patients had symptoms of
hyperthyroidism and benefited from switching to levothyroxine. Raised T3 levels may be hazardous in some
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
patients, especially those with cardiac disease. Changing to levothyroxine resulted in lower T3 and higher T4
levels, resembling those seen in normal subjects.
Retrospective, practice-based reviews
Two retrospective practice based reviews assessing the symptomatic effects of switching from levothyroxine
to a desiccated thyroid treatment were identified.
In the first, published in 1997, the records of 89 patients with hypothyroidism treated with levothyroxine but still
symptomatic were compared with those of 832 untreated hypothyroid patients.(17) Forty of the previously
treated patients and 278 of the untreated patients were followed-up after treatment with natural desiccated
thyroid. The investigators monitored eight main symptoms, (constipation, headache, muscle cramps,
depression, Achilles, rheumatoid, cold, fatigue), scored as 0=no symptoms and 2=full-blown symptoms, giving
a maximum score of 16.
a) In the levothyroxine-treated patients prior to switching to desiccated thyroid (n=40), the prevalence of
symptoms was comparable to that of the main group of untreated patients, with a mean symptom
score of 10.7. The mean 24-hour urine free T3* level was 797.5pmol. The mean levothyroxine dose
was 99.7mcg, given for a mean 33.2 months; most patients were taking between 76-100mcg/day.
b) After switching to desiccated thyroid treatment, the mean symptom score fell from 10.7 to 3.6 and the
mean 24-hour urine T3 rose from 767 to 1990pmol. Mean desiccated thyroid dose was 233mg, given
for a mean 26.9 months.
c) For the previously untreated patients, the mean symptom score fell from 10.1 to 3.6 and the 24-hour
urine T3 rose from 752 to 1900pmol. The mean desiccated thyroid dose was 200mg, given for a mean
23 months.
The investigators acknowledge that levothyroxine treatment can adequately treat patients with hypothyroidism.
They also state that reliance on serum tests (thyroid stimulating hormone and free T4) than on clinical signs
and 24-hour urine free T3 may lead to an insufficient dose of thyroid hormone to obtain satisfactory results.
But, the investigators did not appear to consider the possibility that the 89 patients still symptomatic on
levothyroxine may have simply required a dose increase to control their symptoms, but instead switched them
to desiccated thyroid. For all patients, the 24-hour urine free T3 levels were low but were within the reference
range. The study is limited by its retrospective nature, lack of control group and lack of titration of
levothyroxine to control symptoms.
* A 24-hour urine free T3 measured below the reference range indicates functional hypothyroidism. Free T3
measures the biologically active fraction of total T3, the majority of which is bound by protein carriers and is
therefore inactive. The normal range is 592 – 1850pmol/24 hours.
Another retrospective review (described as a retrospective observational study) was published in 2014. (18) It
investigated the observed preference for AT over levothyroxine in a subgroup of patients with hypothyroidism
who reported dissatisfaction with levothyroxine monotherapy. Of the 450 patients treated at a single outpatient
endocrinology practice over 3 months, 154 patients (34%, average age 53 years) self-reported failure of
levothyroxine monotherapy. Despite having normal thyroid hormone levels, they reported persistent fatigue,
cold intolerance, constipation, myalgia and unexplained weight gain. (17)
They were switched from levothyroxine (average dose prior to switch not documented) to AT (mean dose post
switch 92.3 +/- 28.6mg), excluding those with thyroid cancer or nodular thyroid therapy. It is not clear from the
manuscript whether the dose of levothyroxine was optimised prior to switching. After at least 4 weeks on AT,
patients were asked to compare AT and levothyroxine using a 5 point patient Satisfaction Rating Scale (=SRS,
where 1 means that AT is definitely worse than levothyroxine and 5 means that AT is definitely better than
levothyroxine).
Of the 154 patients switched, 78% scored >3 and they were classed as responders. Thirty three patients
(21%) scored ≤3; they were classed as non-responders. The average mean SRS scores for responders vs.
non responders was 4.79 vs. 2.70, p<0.001. TSH levels checked after the switch did not differ to levels taken
before the switch (1.30 vs. 1.34 mIU/L, p=ns). T3 levels, however, increased after the switch (1.18 vs. 1.50
pmol/L, p<0.003) and the T4:T3 ratio was lowered when patients were switched (4.70 vs. 8.45, p<0.001).
Despite this, reported patient satisfaction and biochemistry did not correlate and there was no significant
change in average weight after switching (75.9kg vs. 74.4kg).No adverse reactions were reported.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
This study suggests that in patients already dissatisfied with their hypothyroid symptom management with
levothyroxine despite being biochemically euthyroid, switching to AT increases their level of perceived
satisfaction. Larger, prospective studies with a suitable control group are needed to clarify whether AT has a
role in the management of hypothyroidism. There were several limitations; although a relatively high proportion
of patients (78%) reported satisfaction with the switch from levothyroxine to AT, this is the expected result of a
selection bias for patients already dissatisfied with levothyroxine treatment. The study did not involve any
blinding which would have compounded this bias. The study was relatively small and of short duration and the
five point SRS scale used is not a validated scale. Furthermore, the paper is published in an open access
journal and there are small discrepancies between the numerical results published in the abstract and the
main text. Given the discrepancies and noting that such journals often charge authors a fee for publication,
there is concern about whether the manuscript of the study was adequately peer reviewed prior to publication.
(18,19)
Limitations
 This Q&A focuses solely on the use of desiccated thyroid for the treatment of hypothyroidism, not
euthyroid hypometabolism.
 This Q&A focuses on evidence that shows clinical effectiveness and safety of AT compared with that
of levothyroxine.
 There may be articles that were not found via the three databases searched (Embase, Medline and
AltMedDex). This may be because either the journal is not included in the 3,500+ journals indexed by
these databases, or that the article was published prior to 1950 and as such, that practice may be
considered obsolete.
References
(1) The diagnosis and management of primary hypothyroidism. Royal College of Physicians.
http://www.rcplondon.ac.uk/sites/default/files/the-diagnosis-and-management-of-primary-hypothyroidism-revisedstatement-14-june-2011_2.pdf Accessed 08/01/2016.
(2) Cooper DS. Thyroid hormone treatment: new insights into an old therapy. Journal of the American Medical
Association 1989; 261(18):2694-2695.
(3) Armour thyroid (thyroid tablets, USP). Forest Pharmaceuticals, Inc.
http://pi.actavis.com/data_stream.asp?product_group=1924&p=pi&language=E Accessed 08/01/2016.
(4) NP Thyroid (thyroid tablets, USP). Acella Pharmaceuticals, LLC. http://www.npthyroid.com/assets/ace-15666-pi.pdf
Accessed 08/01/2016.
(5) Nature-Throid (thyroid USP) tablets. RLC Labs http://getrealthyroid.com/wp-content/uploads/2014/11/Nature-ThroidPrescribing-Information.pdf Accessed 19/2/16
(6) Jackson IM, Cobb WE. Why does anyone still use desiccated thyroxine USP? Am J Med 1978; 1978(64):-284.
(7) Wiersinga WM, Duntas L, Fadeyev V et al. 2012 ETA Guidelines: The use of L-T4 + L-T3 in the treatment of
hypothyroidism. European Thyroid Journal 2010; 1: 55-71
(8) Okosieme O, Gilbert J, Abraham P et al. Management of primary hypothyroidism: statement by the British Thyroid
Association Executive Committee. Clinical Endocrinology 2015; 0: 1-10
(9) Lev-Ran A. Part-of-the-day hypertriiodothryoninemia caused by desiccated thyroid. Journal of the American Medical
Association 1983; 250(20):2790-2791.
(10) Smith SR. Desiccated thyroid preparations. Obsolete therapy. Arch Intern Med 1984; 144:926-927.
(11) Vaidya B, Pearce SHS. Management of hypothyroidism in adults. Br Med J 2008; 337:284-289.
(12) Hoang TD, Olsen CH, Mai VQ et al. Desiccated thyroid extract compared with levothyroxine in the treatment of
hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab 2013; 98(5):1982-1990.
(13) Sawin CT, Hershman JM, Fernandez-Garcia R et al. A comparison of thyroxine and desiccated thyroid in patients with
primary hypothyrodism. Metabolism 1978; 27(10):1518-1525.
(14) Singh SP, Feldman EB, Carter AC. Desiccated thryoid and levothyroxine in hypothyroidism. N Y State J Med 1972;
May:1045-1048.
(15) Sturnick MI, Lesses MF. A comparison of the effect of desiccated thyroid and sodium levothyroxine on the serum
protein-bound iodine. N Engl J Med 1961; 264(12):608-609.
(16) McGavack TH, Reckendorf HK. Therapeutic activity of desiccated thyroid substance, sodium L-thyroxine and D,Ltriiodothyronine. A comparative study. Am J Med 1956; May:774-777.
(17) Baisier WV, Hertoghe J, Eeckhaut W. Thyroid insufficiency. Is thyroxine the only valuable drug? J Nutr Environ Med
1997; 11:159-166.
(18) Pepper GM, Casanova-Romero PY. Conversion to Armour Thyroid from Levothyroxine improved patient satisfaction
in the treatment of hypothyroidism. Journal of Endocrinology, Diabetes and Obesity 2014; 2 (3):1055.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
(19) Butler D, The dark side of publishing, Nature 2013; 495: 433-5.
Quality Assurance
Updated by
Sheena Vithlani, Regional MI Manager, London Medicines Information Service, Northwick Park Hospital,
Harrow.
Date Prepared
11/02//2016
Checked by
Elizabeth Uhegwu, Medicines Information Pharmacist, London Medicines Information Service, Northwick Park
Hospital, Harrow.
Date of check
23/02/2016
Contact
[email protected]
Search strategy
NICE Evidence (www.evidence.nhs.uk), NICE (www.nice.org.uk), SIGN (www.sign.ac.uk), Cochrane
Database, Royal College of Physicians (www.rcplondon.ac.uk/) , British Thyroid Association
(www.britishthyroid-association.org), MHRA (www.mhra.gov.uk), FDA (www.fda.gov), Micromedex
(www.micromedexsolutions.com ), BNF, Martindale and AHFS (via www.medicinescomplete.com),
Internet Search: www.google.co.uk, ‘armour thyroid’ ‘desiccated thyroid’, ‘natural thyroid’
Embase (1980-present), Medline (1950-present) and AltMedDex (1985-present): Date of search: 08/10/2013
via NHS Evidence.
1
EMBASE
(armour AND thyroid).af
329
2
EMBASE
"armour thyroid".af (last 2 years)
23 (5)
3
EMBASE
"desiccated porcine thyroid".af (last 2 years)
1 (0)
4
EMBASE
"porcine thyroid".af (last 2 years)
526 (10)
5
EMBASE
4 [Limit to: Human and English Language]
92
6
EMBASE
HYPOTHYROIDISM/ [Limit to: Human and English Language] (last 2 years)
29888 (6858)
7
EMBASE
5 AND 6 [Limit to: Human and English Language] (last 2 years)
23 (11)
8
EMBASE
"dessicated thyroid".af (last 2 years)
11 (0)
9
EMBASE
"desiccated thyroid".af (last 2 years)
103 (6)
10
EMBASE
8 OR 9 (last 2 years)
114 (6)
11
EMBASE
10 [Limit to: Human] (last 2 years)
70 (14)
12
MEDLINE
(desiccated AND thyroid).af
176
13
MEDLINE
"desiccated thyroid".af
132
14
MEDLINE
(dessiccated AND thyroid) OR (dessicated AND thyroid) OR (desicated AND
thyroid) or (armour thyroid) OR (armour thyroid)
25
15
MEDLINE
THYROID HORMONES
17167
16
MEDLINE
HYPOTHYROIDISM/ DT,PC [DT = drug therapy, PC = prevention and
control). (last 2 years)
4152
17
MEDLINE
(12 OR 13 OR 14 OR 15) AND 16 (last 2 years)
196 (1)
18
AMED
"desiccated thyroid".af
1
19
AMED
"armour thyroid".af
1
20
AMED
“armour AND thyroid”.af
1
21
AMED
HYPOTHYROIDISM/ OR THYROID HORMONES/
80
Available through NICE Evidence Search at www.evidence.nhs.uk
6