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Case Report

A curious case of refractory hypothyroidism due to

selective malabsorption of oral thyroxine
Nishikant Damle, Chandrasekhar Bal, Ramya Soundararajan, Praveen Kumar, Prashant Durgapal1
Departments of Nuclear Medicine and 1Pathology, All India Institute of Medical Sciences, New Delhi, India

A B S T R A C T

There are very few cases in the literature in which refractory persistent hypothyroidism responded only to parenteral doses of
levothyroxine and no evidence of any malabsorptive disorder could be identified. Here, we present a rare case of a 35-year-old woman
with refractory hypothyroidism who responded only to intravenous doses of levothyroxine. We also discuss possible causes for the same.

Key words: Refractory hypothyroidism, selective malabsorption, thyroxine

Introduction Here, we present a rare case of a 35-year-old woman

with refractory hypothyroidism who responded only
Oral levothyroxine sodium (LT4) remains the mainstay to intravenous doses of levothyroxine. We also discuss
of treatment of hypothyroidism to achieve physiological possible causes for the same.
thyroid hormone levels. The mean treatment dosage is 1.6
g/kg bodyweight per day.[1] Intestinal absorption ranges Case Report
from 70% to 80% of the administered dose and it differs
A 35-year-old female presented to the physician with
from patient to patient.[2] In addition, absorption is higher
complaints of gradual increase in weight, loss of
in the fasting state. However, hypothyroidism persists and
appetite, lethargy, and weakness over the past 4 years. On
euthyroid state cannot be achieved in a few cases even
examination, she had dry scaly skin, peripheral edema, and
after supplementing adequate or excessive doses of oral
a blood pressure of 140/100 mm Hg. She was incidentally
thyroxine. In such cases of refractory hypothyroidism, the
diagnosed to be hypothyroid during her third pregnancy
main differentials to be considered are (a) poor patient and treatment started on 100 g thyroxine 4 years ago.
compliance to oral thyroxine, (b) deiodinase deficiency, The delivery was uneventful and the baby also had normal
and (c) various malabsorption disorders. Of these thyroid profile. Her symptoms gradually worsened and her
poor compliance is very commonly seen in refractory thyroid-stimulating hormone (TSH) levels reached 651.4
hypothyroidism.[3-5] There are very few cases in the literature IU/ml 1 year ago. The dose of thyroxine was gradually
in which refractory persistent hypothyroidism responded increased upto 400 g/day. Patient was compliant to the
only to parenteral doses of levothyroxine and no evidence intake of thyroxine. Repeated thyroid profiles on thyroxine
of any malabsorptive disorder could be identified. doses between 100 and 400 g showed TSH ranging from
270 to 360 IU/ml. Her free T3 and free T4 were also
very low. Oral intake under physician supervision did not
Access this article online
help. Her serum cholesterol was elevated upto 338 mg/
Quick Response Code:
dl. The patient was additionally administered 25 g of tri-
Website:
www.ijem.in iodothyronine twice daily. Even after such a high dose of T4
and addition of oral T3, her serum T3, T4, and TSH did not
DOI: normalize. She was thoroughly investigated for refractory
10.4103/2230-8210.95716 primary hypothyroidism. Her antithyroglobulin antibody
level was 261 IU/ml and anti-TPO antibody was 974 IU/

Corresponding Author: Dr. Nishikant A. Damle, Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi 110 029, India.
E-mail: [email protected]

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Damle, et al: Selective malabsorption of oral thyroxine

ml. Family history of hypothyroidism was present.99mTc elevation of TSH and decrease in serum free T4 caused
pertechnetate thyroid scan showed normally located thyroid due to dysfunction of thyroid gland itself. But the same
gland with normal homogenous tracer uptake in both the biochemical picture in spite of adequate or excessive
lobes of thyroid gland. supplementation of oral thyroxine might be due to poor
compliance of the patient which is the most frequent
As a next step, malabsorption of oral thyroxine was cause.[3-5] The other important cause is malabsorption that
kept as one of the differential diagnosis. Although there could be due to GI diseases, pancreatic and liver diseases,
was no history of diarrhea/steatorrhea or other clinical dietary interference, or interference due to medications
findings of malabsorption, further investigations to rule such as antacids, sucralfate, antiepiletics, calcium carbonate
out malabsorption as a cause were done. Hemogram did amongst others, previous GI surgeries, congestive cardiac
not reveal anemia and peripheral smear was normal. Stool failure, and pregnancy.[6]
examination was normal. Upper gastrointestinal (GI)
endoscopy was done which was also normal. Duodenal In the above case, the patient was very much compliant with
biopsy was taken and it did not show pathological oral therapy, and it was also tried under medical supervision
abnormalities consistent with malabsorptive disorder and hence poor compliance with the drug was excluded.
[Figure 1]. Antibodies to gliadin and transglutaminase Defect in the conversion of LT4 to triiodothyronine (T3)
were in normal range. Her D-xylose test was done which because of deiodinase-3 deficiency was also suspected
was also within normal limits, i.e., 4 mmol/L. We tried which was disproved by her reduced free T 4 levels,
supplementation of thyroxine by intravenous route. unresponsiveness even to oral T3, and normalization of
Injection levothyroxine (LT4) 200 g once in 3 days was T3 also after intravenous T4 supplementation. Her duodenal
started. After five doses of Levothyroxine, her TSH levels biopsy was strikingly normal and not consistent with
started improving and reached 68 IU/ml. We continued malabsorptive disease. All other investigations relevant
with the doses of intravenous levothyroxine and after for ruling out intestinal malabsorption were done and all
five more doses her TSH levels reached 28 IU/ml with turned out to be normal.
normalization of T3 and T4 levels. On stopping, the
intravenous thyroxine and maintaining the patient on oral Parenteral levothyroxine (LT4) is commercially available
medication, the TSH started rising again with fall in T3 and in 10 ml flip flop single use in 100 g, 200 g or 500 g
T4 levels within 7 days. This provided us with evidence of vials in lyophilized powder form and it is to be stored
oral malabsorption of thyroxine. at 1530C. After injection, the synthetic levothyroxine
is no way different from endogenous thyroxine. Its
Discussion distribution, metabolism, and elimination properties
are similar to endogenous thyroxine. Replacement or
Primary hypothyroidism can be clearly demonstrated by supplemental therapy by intravenous levothyroxine may
be done in congenital or acquired hypothyroidism of
any etiology when even high doses of oral thyroxine,
given for long enough time, fail to achieve euthyroidism
and the possibility of deiodinase deficiency and patient
noncompliance has been ruled out. Another indication is
when rapid repletion of thyroxine is needed, except in cases
of transient hypothyroidism. Another important indication
is management of myxedema coma using IV levothyroxine.

After enquiry in numerous pharmacies, only one pharmacy

could provide the injection levothyroxine at a cost of Rs.
4700 per vial of 200 g and that was also not routinely
a b available with them. The patient needs to get it by prior
intimation. Thus, we see that in our Indian setup the drug
is difficult to procure and expensive.

Figure 1: (a) Giemsa stained duodenal biopsy (4) shows villus to crypt Our patient responded to 10 doses of parenteral T4, i.e.,
ratio of 3:1,intraepithelial lymphocytes are not increased,no luminal parasite TSH levels decreased from 370 to 28 IU/ml and she
identifed,there is mild chronic inlammatory cell infiltrate in the lamina propria
features are non specific. (b) Giemsa stained duodenal biopsy (20) - one improved symptomatically. In our Indian setup, where most
villus with same features as desribed patients are not covered by insurance, it is highly important

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Damle, et al: Selective malabsorption of oral thyroxine

to assess the efficacy of such a costly therapeutic regimen, such patients may be treated with parenteral doses of
so we repeated the measurement of TSH after five doses levothyroxine.
of levothyroxine (15 days) to have an early idea about the
response. References
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of oral thyroxine, various ideas can be hypothesized. First of levothyroxine. JAMA 1991;266:2118-20.
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9. Tnjes A, Karger S, Koch CA, Paschke R, Tannapfel A, Stumvoll M,
thyroid ablation.[9] Jauk et al. in 2000 reported an unusual et al. Impaired enteral levothyroxine absorption in hypothyroidism
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Still the cause of hypothyroidism remains unclear in our
patient. But in such cases of refractory hypothyroidism
Cite this article as: Damle N, Bal C, Soundararajan R, Kumar P, Durgapal
after verifying the compliance with oral therapy and after P. A curious case of refractory hypothyroidism due to selective malabsorption
ruling out all other causes for malabsorption, selective of oral thyroxine. Indian J Endocr Metab 2012;16:466-8.
malabsorption of oral thyroxine can be considered and Source of Support: Nil, Conflict of Interest: None declared.

468 Indian Journal of Endocrinology and Metabolism / May-Jun 2012 / Vol 16 | Issue 3