SEVERE REFRACTORY HYPOTHYROIDISM IN A 48 - YEAR -
OLD FEMALE: ROLE OF LOW - DOSE THYROXINE
ABSORPTION TEST IN ESTABLISHING DIAGNOSIS OF
NONCOMPLIANCE
Abstract
A 48-year-old female presented with severe chronic hypothyroidism despite progressively
increasing doses of levothyroxine. Poor adherence was suspected based on previous laboratory
investigations. A low dose thyroxine absorption test using 400 µg of levothyroxine taken orally
, was performed. FT4 increased by 4.7 pmol/L at 3 hours and 6.6 pmol/L at 5 hours, following
ingestion, effectively ruling out malabsorption. Her cardiac hemodynamic profile, measured
noninvasively, also improved following levothyroxine intake, further supporting our diagnosis.
Poor adherence was successfully managed by implementing twice weekly visits by a registered
nurse and an improvement in both thyroid function tests and cardiac parameters was seen at the
one-month follow-up visit. We suggest using a lower dose thyroxine absorption test, owing to its
efficacy in establishing diagnosis and a safer alternative compared to higher doses in particular in
high-risk cardiac patients.
Keywords: Refractory hypothyroidism, T4 absorption test, hemodynamics
INTRODUCTION
We present the case of a 48-year-old female diagnosed with hypothyroidism secondary to total
thyroidectomy for a papillary thyroid carcinoma at age 38. She had no other relevant medical
history. Prior to thyroidectomy, she had normal thyroid function tests (TFTs). Her TSH levels
were appropriately suppressed on 175 µg of levothyroxine following thyroidectomy until august
2014, when TSH above 100 mIU/L and undetectable thyroid hormone levels were first
documented despite claimed compliance to progressively higher doses of levothyroxine therapy.
There were no interfering medications. The patient was adamant that she was taking her
levothyroxine every morning on an empty stomach. Antibodies specific to celiac disease (anti-
transglutaminase IgA and anti-gliadin IgG) were negative, and B12 deficiency was excluded. An
upper endoscopy revealed neither atrophic gastritis nor villous atrophy. She was successfully
treated for Helicobacter pylori infection. Antibodies directed against T3 and T4 were negative on
two separate occasions. She was then switched to triiodothyronine pills then to levothyroxine
drops without success. A regimen based on in-hospital intravenous levothyroxine at doses
ranging between 200 and 400 µg with cardiac monitoring every 2 weeks was successful in
normalizing thyroid hormone levels.
Subsequently, she was lost to follow-up for 2 years until December 2020 when she presented
with severe hypothyroidism: puffy face, periorbital edema, excessive daytime fatigue and
somnolence, proximal myopathy, diffuse arthralgia, diastolic hypertension, bradycardia and
diminished Achilles and patellar reflexes. Her blood work revealed severe hypocalcemia (1.72
mmol/L [2.15-2.5]), hypoproteinemia (57 g/L [62-81], hypercholesterolemia (LDL-cholesterol
5.71 mmol/L), normal CK and serum sodium levels. TFTs were as follows: undetectable serum
thyroglobulin < 0.1 µg/L and negative antibodies to thyroglobulin (20.5 IU/mL, Normal <115)
confirming thyroid carcinoma remission, TSH >100 mIU/L with undetectable FT4 and FT3
while taking (she said) 475 µg of levothyroxine. We also diagnosed her with severe sleep apnea
syndrome with an apnea-hypopnea index of 72/hour. Her ECG showed sinus bradycardia at 45
beats/min. She had no hypothermia. Her cognitive capacity was not altered but she did complain
of memory deficits and concentrating difficulties. Transthoracic ultrasound examination showed
isolated diastolic dysfunction, with a preserved systolic function (left ventricle ejection fraction
59%) and no pericardial effusion.
We again suspected poor compliance to medication and thus opted to perform an adjusted low
dose levothyroxine absorption test, using approximately the same dose of 400 µg she was
OLD FEMALE: ROLE OF LOW - DOSE THYROXINE
ABSORPTION TEST IN ESTABLISHING DIAGNOSIS OF
NONCOMPLIANCE
Abstract
A 48-year-old female presented with severe chronic hypothyroidism despite progressively
increasing doses of levothyroxine. Poor adherence was suspected based on previous laboratory
investigations. A low dose thyroxine absorption test using 400 µg of levothyroxine taken orally
, was performed. FT4 increased by 4.7 pmol/L at 3 hours and 6.6 pmol/L at 5 hours, following
ingestion, effectively ruling out malabsorption. Her cardiac hemodynamic profile, measured
noninvasively, also improved following levothyroxine intake, further supporting our diagnosis.
Poor adherence was successfully managed by implementing twice weekly visits by a registered
nurse and an improvement in both thyroid function tests and cardiac parameters was seen at the
one-month follow-up visit. We suggest using a lower dose thyroxine absorption test, owing to its
efficacy in establishing diagnosis and a safer alternative compared to higher doses in particular in
high-risk cardiac patients.
Keywords: Refractory hypothyroidism, T4 absorption test, hemodynamics
INTRODUCTION
We present the case of a 48-year-old female diagnosed with hypothyroidism secondary to total
thyroidectomy for a papillary thyroid carcinoma at age 38. She had no other relevant medical
history. Prior to thyroidectomy, she had normal thyroid function tests (TFTs). Her TSH levels
were appropriately suppressed on 175 µg of levothyroxine following thyroidectomy until august
2014, when TSH above 100 mIU/L and undetectable thyroid hormone levels were first
documented despite claimed compliance to progressively higher doses of levothyroxine therapy.
There were no interfering medications. The patient was adamant that she was taking her
levothyroxine every morning on an empty stomach. Antibodies specific to celiac disease (anti-
transglutaminase IgA and anti-gliadin IgG) were negative, and B12 deficiency was excluded. An
upper endoscopy revealed neither atrophic gastritis nor villous atrophy. She was successfully
treated for Helicobacter pylori infection. Antibodies directed against T3 and T4 were negative on
two separate occasions. She was then switched to triiodothyronine pills then to levothyroxine
drops without success. A regimen based on in-hospital intravenous levothyroxine at doses
ranging between 200 and 400 µg with cardiac monitoring every 2 weeks was successful in
normalizing thyroid hormone levels.
Subsequently, she was lost to follow-up for 2 years until December 2020 when she presented
with severe hypothyroidism: puffy face, periorbital edema, excessive daytime fatigue and
somnolence, proximal myopathy, diffuse arthralgia, diastolic hypertension, bradycardia and
diminished Achilles and patellar reflexes. Her blood work revealed severe hypocalcemia (1.72
mmol/L [2.15-2.5]), hypoproteinemia (57 g/L [62-81], hypercholesterolemia (LDL-cholesterol
5.71 mmol/L), normal CK and serum sodium levels. TFTs were as follows: undetectable serum
thyroglobulin < 0.1 µg/L and negative antibodies to thyroglobulin (20.5 IU/mL, Normal <115)
confirming thyroid carcinoma remission, TSH >100 mIU/L with undetectable FT4 and FT3
while taking (she said) 475 µg of levothyroxine. We also diagnosed her with severe sleep apnea
syndrome with an apnea-hypopnea index of 72/hour. Her ECG showed sinus bradycardia at 45
beats/min. She had no hypothermia. Her cognitive capacity was not altered but she did complain
of memory deficits and concentrating difficulties. Transthoracic ultrasound examination showed
isolated diastolic dysfunction, with a preserved systolic function (left ventricle ejection fraction
59%) and no pericardial effusion.
We again suspected poor compliance to medication and thus opted to perform an adjusted low
dose levothyroxine absorption test, using approximately the same dose of 400 µg she was
