Levothyroxine malabsorption following sleeve gastrectomy

in Endocrinology, Diabetes & Metabolism Case Reports
Authors:
Elodie Gruneisen Division of Endocrinology, McGill University Health Centre, Montreal, Canada
Division of Endocrinology, Diabetology and Metabolism, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

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Ji Wei Yang Division of Endocrinology, McGill University Health Centre, Montreal, Canada

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Melissa-Rosina Pasqua Division of Endocrinology, McGill University Health Centre, Montreal, Canada

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Correspondence should be addressed to E Gruneisen: elodie.gruneisen@chuv.ch
Open access

Summary

Oral levothyroxine (LT4) is prescribed worldwide for hypothyroidism. Bariatric surgery for patients with obesity has shown a substantial, long-term weight loss and considerable improvement of obesity-related diseases. LT4 malabsorption represents a significant cause of refractory hypothyroidism, well known after malabsorptive bariatric surgery such as Roux-en-Y gastric bypass. However, few studies have shown an increase in oral LT4 needed after sleeve gastrectomy. We present a 47-year-old woman with class III obesity and a history of papillary thyroid cancer, with an excellent biochemical and structural response after total thyroidectomy and radioactive iodine. She underwent sleeve gastrectomy 3 years later and developed refractory hypothyroidism despite taking high doses of oral LT4 and ensuring compliance. The T4 absorption test confirmed gastrointestinal LT4 malabsorption. She was initiated on intramuscular LT4 and oral T3 (liothyronine) with improving symptoms and levels of thyroid-stimulating hormone.

Learning points

  • Monitoring thyroid function tests is essential after bariatric surgery, including sleeve gastrectomy.

  • Oral LT4 malabsorption should be considered in cases of refractory hypothyroidism.

  • The T4 absorption test is a useful tool for distinguishing true malabsorption from pseudo-malabsorption.

  • Decreased LT4 absorption after bariatric surgery might be explained by higher gastric pH and reduced stomach volume (impaired dissolution) and by interference with food, vitamin/mineral supplements or other drugs.

  • When LT4 malabsorption is confirmed, a trial of other oral formulations (LT4 tablet crushed, soft gel or liquid preparation) or parenteral administrations is suggested.

Abstract

Summary

Oral levothyroxine (LT4) is prescribed worldwide for hypothyroidism. Bariatric surgery for patients with obesity has shown a substantial, long-term weight loss and considerable improvement of obesity-related diseases. LT4 malabsorption represents a significant cause of refractory hypothyroidism, well known after malabsorptive bariatric surgery such as Roux-en-Y gastric bypass. However, few studies have shown an increase in oral LT4 needed after sleeve gastrectomy. We present a 47-year-old woman with class III obesity and a history of papillary thyroid cancer, with an excellent biochemical and structural response after total thyroidectomy and radioactive iodine. She underwent sleeve gastrectomy 3 years later and developed refractory hypothyroidism despite taking high doses of oral LT4 and ensuring compliance. The T4 absorption test confirmed gastrointestinal LT4 malabsorption. She was initiated on intramuscular LT4 and oral T3 (liothyronine) with improving symptoms and levels of thyroid-stimulating hormone.

Learning points

  • Monitoring thyroid function tests is essential after bariatric surgery, including sleeve gastrectomy.

  • Oral LT4 malabsorption should be considered in cases of refractory hypothyroidism.

  • The T4 absorption test is a useful tool for distinguishing true malabsorption from pseudo-malabsorption.

  • Decreased LT4 absorption after bariatric surgery might be explained by higher gastric pH and reduced stomach volume (impaired dissolution) and by interference with food, vitamin/mineral supplements or other drugs.

  • When LT4 malabsorption is confirmed, a trial of other oral formulations (LT4 tablet crushed, soft gel or liquid preparation) or parenteral administrations is suggested.

Background

Primary hypothyroidism, defined by a high serum thyroid-stimulating hormone (TSH) concentration and a low serum free thyroxine (T4) concentration, has a prevalence rate of 12% in patients with obesity class III (1).

Bariatric surgery is becoming more frequent over the past few decades (2). This is in part due to its efficacy and increasing safety, which lead to long-term weight loss and possible remission of adipose-based complications such as type 2 diabetes, obstructive sleep apnea, metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (3, 4, 5).

Levothyroxine (LT4) is the primary treatment for hypothyroidism. After thyroidectomy, the initial dose of oral LT4 prescribed is often based on body weight: from 1.6 to 1.8 μg/kg for thyroid replacement and up to 2.1–2.7 μg/kg for thyroid cancer patients requiring TSH suppression (6). Its absorption occurs predominantly in the small intestine (jejunum and ileum) with a bioavailability ranging from 60 to 80% in healthy individuals (7). However, the latter can be affected by many factors, including the variations of gastric juice pH, food and drugs interfering or gastrointestinal disease (8).

Refractory primary hypothyroidism is defined by biochemical or clinical evidence of hypothyroidism (TSH level above the upper target level, usually 4.5 mU/L) persistent at least 6 weeks after the last dose increase, despite a daily LT4 dose ≥1.9 μg/kg (9). In these circumstances, physicians should confirm compliance and search for causes for decreased absorption or increased need or metabolism of oral LT4.

Initially, it is important to exclude incorrect administration of the drug, interfering food or medications, weight gain and pregnancy, which can potentially result in an increased demand for LT4. Oral LT4 should be ideally taken on an empty stomach, 60 min before a meal and 4 h apart from other interfering drugs, such as calcium or iron supplements and bile acid sequestrants (6). In addition, antacid drugs such as proton pump inhibitors (PPIs) may decrease gastric pH and consequently impair dissolution of the tablet, normally allowing for intestinal absorption (8).

Alternatively, physicians should exclude noncompliance with treatment (pseudo-malabsorption). Pseudo-malabsorption is a classic cause of refractory hypothyroidism. A medically supervised oral T4 absorption test may be useful to distinguish impaired bioavailability of oral LT4 from pseudo-malabsorption (7). After an overnight fast, a weight-based weekly oral dose of LT4 (e.g. 1.6 μg/kg/body weight × 7) is administered with a glass of water, under medical supervision. Free T4 is measured at times 0, 60 and 120 min (when a peak value of T4 is commonly seen). Values well below 54% at 120 min suggest impaired bioavailability of the tablet, whereas values similar to or greater than this suggest pseudo-malabsorption (10). If a reduced bioavailability of LT4 is documented, immunoassay interference should be excluded by collecting TSH using a different assay.

Afterwards, investigations for gastrointestinal diseases or disorders should be considered: impaired dissolution (maldigestion of LT4) may be related to hypochlorhydria (mainly in the context of PPI therapy), atrophic gastritis or Helicobacter pylori infection. Inadequate delivery (intestinal malabsorption) of LT4 may be documented after taking interfering food or medications, but also in the context of short bowel syndrome, lactose intolerance, coeliac disease, inflammatory bowel disease, infiltrative enteropathy and parasitosis (Giardia) (11).

In case of negative screening tests for LT4 maldigestion and malabsorption, other factors that can increase the need for LT4 should be considered, such as Addison’s disease or impaired regulation of the hypothalamic–pituitary–thyroid axis (11).

Bariatric surgery comprises a variety of surgical techniques to achieve weight loss, where sleeve gastrectomy is the only surgery without deviations in the gastrointestinal pathway. Roux-en-Y gastric bypass has been shown to change the need for LT4 therapy in hypothyroid patients (12). However, most reports showed unchanged or decreased doses of LT4 needed by patients after sleeve gastrectomy (1, 13, 14). In fact, sleeve gastrectomy may potentially also affect LT4 absorption in hypothyroid patients, due to changes to the gastric environment, which include a rise in pH, less gastric secretions and faster gastric motility. We present a rare case of severe primary hypothyroidism refractory to oral LT4 replacement following sleeve gastrectomy.

Case presentation

A 47-year-old woman, known for obesity class III, diabetes mellitus, MASLD, hypertension and non-Hodgkin’s lymphoma in remission, underwent total thyroidectomy with radioactive iodine postoperatively for papillary thyroid cancer, resulting in an excellent biochemical and structural response. Three years following the thyroid surgery, she underwent sleeve gastrectomy.

Her oral medications included LT4 500 μg daily, vitamin D3 20,000 IU weekly, calcium citrate: 400 mg combined with vitamin D 500 IU twice daily, vitamin B12 250 μg daily, rosuvastatin 40 mg daily, ezetimibe 10 mg daily, metoprolol 75 mg twice a day, hydralazine 25 mg daily and perindopril 16 mg daily.

One year after sleeve gastrectomy, she presented with symptomatic hypothyroidism despite taking high doses of oral LT4 (500 μg daily) and ensuring compliance. She reported weight gain (15 kg), fatigue, sleep disturbance, cold intolerance and subjective decreased muscle strength with paresthesia of hands over the past 3–4 months. She also described soft stools 2–3 times per day and persistent labile blood pressure despite being on three antihypertensive agents. Her physical examination showed a blood pressure measurement of 156/101 mmHg, mild hypothermia (34–35°C), facial oedema, patchy alopecia, xeroderma and decreased proximal and distal muscle strength (4/5) in the upper limbs. She had no alteration in mental status. She was transferred to the emergency department for monitoring and further investigations.

In the emergency room, her blood pressure was 176/98 mmHg, her pulse was 84/min, and her temperature was 36.7°C, with a physical examination similar to that found in the clinic, notably without neurocognitive impairment that could raise suspicion for myxoedema coma. Her TSH was 58 mIU/L (normal range (NR): 0.4–4.40 mIU/L), and FT4 was less than the detectable limit of 2.50 nmol/L (NR: 8–18 pmol/L) (Table 1). She had a low level of vitamin D at 32 nmol/L (NR: 50–125 nmol/L) and vitamin B12 at 115 pmol/L (NR: ≥133 pmol/L).

Table 1

Thyroid function tests before and after SG.

Reference range 1 month before SG 1 year after SG 4 months after IM LT4
TSH (mIU/L) 0.40–4.40 3.54 58.3 24.68
Free T4 (pmol/L) 8–18 9.6 <2.5 7.30
Free T3 (pmol/L) 3.8–6 5.76 3.66 5.13

SG, sleeve gastrectomy; TSH, thyroid-stimulating hormone; T4, thyroxine; T3, triiodothyronine; and IM, intramuscular.

Investigation

Before hospitalization, the patient was followed in the endocrinology clinic. TSH was elevated with a peak of up to 68 mIU/L in the preceding 3 months. The endocrine work-up for resistant hypertension (Cushing’s syndrome, primary hyperaldosteronism and pheochromocytoma or paraganglioma) was negative, which included the 1-mg overnight dexamethasone suppression test, plasma aldosterone/renin ratio and plasma metanephrines and normetanephrines. Given the gastrointestinal symptoms, the refractory hypertension on three antihypertensive agents, the refractory hypothyroidism with oral LT4 and the vitamin D and B12 deficiencies despite adequate supplementation, a gastrointestinal malabsorption was already suspected.

The history, physical examination and investigations did not highlight a malabsorptive disease or disorder outside of her known gastrectomy. Parietal cell antibodies and gastric biopsies were negative for autoimmune atrophic gastritis or infection with Helicobacter pylori. Transglutaminase antibodies and intestinal biopsies were negative for coeliac disease, short bowel syndrome, inflammatory bowel disease and infiltrative enteropathy. There were no infectious causes found for the diarrhea (negative stool cultures and polymerase chain reaction (PCR test)). The work-up for autoimmune hepatitis, liver failure (anti-smooth muscle, antimitochondrial antibodies, TP and albumin) or exocrine pancreatitis (faecal elastase) was negative as well.

During her hospitalization, a T4 absorption test was performed, which confirmed the diagnosis of gastrointestinal LT4 impaired bioavailability, with an increase in free T4 level of 11% at 120 min (Table 2).

Table 2

T4 absorption test following oral LT4 (1,400 μg) given once at baseline.

FT4 NR
Baseline, pmol/L 5.40 8–18
At 60 min, pmol/L 6.2
At 120 min, pmol/L 6
 % increase 11

T4, thyroxine; NR, normal range; FT4, free thyroxine; LT4, levothyroxine; % increase (from baseline) = serum FT4 at 120 min (pmol/L) − baseline serum FT4 (pmol/L) divided by baseline serum FT4 (pmol/L) × 100.

Treatment

In this context, she received intravenous LT4, initial dosage based on her weight and estimated by 75% of the oral dose (1.6 μg/kg × 0.75), followed by an increase in the level of free T4 and normalisation of free T3 after 1 week (6).

Outcome and follow-up

At discharge, a short trial of crushed T4 tablet daily formulation and then liquid gel capsules was done, without significant changes in her symptoms and with persistent biochemical hypothyroidism. She was started on oral liothyronine (T3) 15 μg twice a day and weekly intramuscular LT4 (300 to 500 μg per week), with ongoing clinical and biochemical improvement (Table 1).

Discussion

LT4 malabsorption has been described after bariatric surgery (15), especially after gastric bypass procedures, due to its anatomic and physiological changes. Surgical involvement of the stomach and the length of the intestinal limb principally involved in nutrient absorption are the main differences between gastric bypass (such as the Roux-en-Y surgery) and sleeve gastrectomy. Both procedures can affect LT4 absorption by several mechanisms, including gastric pH variations (reduced gastric fluid and number of parietal cells due to reduced stomach volume, and common use of PPIs and antacids), use of vitamin and mineral supplements and increased gastrointestinal hormone secretion (PYY and GLP-1) (12). Indeed, a physiological gastric pH (1.0–2.0) is required for tablet dissolution of T4 from a solid form, to allow its conversion into a lipophilic form, and increases the absorption of the drug (16).

Only one case report has shown the development of iatrogenic hypothyroidism after sleeve gastrectomy (17).

The T4 absorption test is a useful tool for distinguishing true malabsorption from pseudo-malabsorption: administration of the weight-based weekly oral dose of T4 is accompanied by measurement of free T4 at baseline, 60 and 120 min. Values below a 54% increment of T4 at 120 min are compatible with gastrointestinal LT4 malabsorption, whereas values similar or above suggest poor compliance (10).

When LT4 malabsorption is confirmed, a trial of other oral formulations (LT4 tablet crushed, soft gel or liquid preparation) or parenteral administrations (intramuscular, subcutaneous and intravenous) is advised. Switching to crushed powder has been shown to resolve hypothyroidism, also after sleeve gastrectomy (17). Soft gel capsules or liquid formulations are less dependent on gastric pH, resulting in higher bioavailability compared to LT4 tablets (15), and may normalize TSH values in hypothyroidism, even without gastrointestinal disorders (18). Parenteral administrations of LT4 (intramuscular, subcutaneous and intravenous) could be another option, in weekly or biweekly doses, also among patients with poor adherence or those unable to take oral treatment (19). Combination LT4 and LT3 therapy might be used as an experimental trial in case of persistent symptoms attributed to hypothyroidism in compliant LT4-treated individuals, as in our case. Indeed, liothyronine is more rapidly metabolised and has a more rapid effect (peak in 2–4 h after administration) than LT4 in cases of severe hypothyroidism (20). In healthy individuals, T3 production comes mainly from the peripheral conversion of T4 to T3, and this conversion is decreased in cases of severe chronic illness, such as in significant hypothyroidism. This could suggest potential benefits of using LT3 as monotherapy or combined with LT4, to improve symptoms and normalize biochemical abnormalities. In our case, liothyronine was added in this context of severe hypothyroid state when there is a possibility that T4 conversion to triiodothyronine may be decreased (21).

Despite the many factors that may modify the absorption of T4 replacement therapy in those post-sleeve gastrectomy, complete malabsorption is still rare. Most patients post-sleeve gastrectomy still benefit from oral supplementation, albeit at different doses, due to ease of administration. However, alternate administration of medication should be a next step if oral medications are insufficient.

Conclusion

Monitoring thyroid function tests is essential not only after malabsorptive bariatric surgery but also after sleeve gastrectomy, given the weight variations and the potential impairment of LT4 absorption. Gastrointestinal malabsorption of LT4 should be investigated in case of refractory hypothyroidism despite an adequate dose of oral LT4 after ensuring good compliance and absence of drug or food interference. Switching to other oral formulations or parenteral administrations may normalize TSH values, given the absence of dissolution required for most of them.

Declaration of interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. Internal funds from the post-graduate medical education office and the university’s division of endocrinology were used for publication.

Patient consent

Written informed consent for publication of the clinical details was obtained from the patient.

Author contribution statement

All authors were the members of the treating team. EG, MRP and JWY wrote the main manuscript text, and EG prepared Table 1. All authors reviewed the manuscript.

Acknowledgements

We would like to thank our endocrinologist colleague, Dr Vanessa Tardio, for providing us with her expertise in bariatric endocrinology and recommending the T4 absorption test. We would also like to thank our colleague in internal medicine, Dr Jennifer Wright, for her involvement in patient care.

References

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    Mingrone G , Panunzi S , De Gaetano A , et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 2021 397 293304. (https://doi.org/10.1016/s0140-6736(20)32649-0)

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    Virili C , Brusca N , Capriello S , et al. Levothyroxine therapy in gastric malabsorptive disorders. Front Endocrinol 2021 11 621616. (https://doi.org/10.3389/fendo.2020.621616)

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    Centanni M , Benvenga S & Sachmechi I . Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report. J Endocrinol Invest 2017 40 12891301. (https://doi.org/10.1007/s40618-017-0706-y)

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    Walker JN , Shillo P , Ibbotson V , et al. A thyroxine absorption test followed by weekly thyroxine administration: a method to assess non-adherence to treatment. Eur J Endocrinol 2013 168 913917. (https://doi.org/10.1530/eje-12-1035)

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    Mercado A , Pham A , Wang Z , et al. Effects of bariatric surgery on drug pharmacokinetics-preclinical studies. Front Pharmacol 2023 14 1133415. (https://doi.org/10.3389/fphar.2023.1133415)

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    Neves JS , Castro Oliveira S , Souteiro P , et al. Effect of weight loss after bariatric surgery on thyroid-stimulating hormone levels in patients with morbid obesity and normal thyroid function. Obes Surg 2018 28 97103. (https://doi.org/10.1007/s11695-017-2792-5)

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    Pirola I , Formenti AM , Gandossi E , et al. Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery. Obes Surg 2013 23 14931496. (https://doi.org/10.1007/s11695-013-1015-y)

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    • Search Google Scholar
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    Liu H , Li W , Zhang W , et al. Levothyroxine: conventional and novel drug delivery formulations. Endocr Rev 2023 44 393416. (https://doi.org/10.1210/endrev/bnac030)

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    • Search Google Scholar
    • Export Citation
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    Fain K , Rojas AP & Peiris AN . Hypothyroidism following gastric sleeve surgery resolved by ingesting crushed thyroxine tablets. Proc (Bayl Univ Med Cent) 2020 33 3839. (https://doi.org/10.1080/08998280.2019.1669412)

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    Fallahi P , Ferrari SM , Ruffilli I , et al. Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update. Expert Opin Drug Deliv 2017 14 647655. (https://doi.org/10.1080/17425247.2016.1227782)

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    Ritter MJ , Gupta S & Hennessey JV . Alternative routes of levothyroxine administration for hypothyroidism. Curr Opin Endocrinol Diabetes Obes 2020 27 318322. (https://doi.org/10.1097/med.0000000000000558)

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  • 20

    Ahluwalia R , Baldeweg SE , Boelaert K , et al. Use of liothyronine (T3) in hypothyroidism: joint British Thyroid Association/Society for endocrinology consensus statement. Clin Endocrinol 2023 99 206216. (https://doi.org/10.1111/cen.14935)

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    Ueda K , Kiyota A , Tsuchida M , et al. Successful treatment of myxedema coma with a combination of levothyroxine and liothyronine. Endocr J 2019 66 469474. (https://doi.org/10.1507/endocrj.ej18-0469)

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  • 1

    Azran C , Porat D , Fine-Shamir N , et al. Oral levothyroxine therapy postbariatric surgery: biopharmaceutical aspects and clinical effects. Surg Obes Relat Dis 2019 15 333341. (https://doi.org/10.1016/j.soard.2019.01.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Welbourn R , Hollyman M , Kinsman R , et al. Bariatric surgery worldwide: baseline demographic description and one-year outcomes from the fourth IFSO global registry report 2018. Obes Surg 2019 29 782795. (https://doi.org/10.1007/s11695-018-3593-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Biertho L , Hong D & Gagner M . Bariatric Surgery: Surgical Options and Outcomes. In:. Canadian Adult Obesity Clinical Practice Guidelines 2020. (https://obesitycanada.ca/guidelines/surgeryoptions)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Mingrone G , Panunzi S , De Gaetano A , et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 2021 397 293304. (https://doi.org/10.1016/s0140-6736(20)32649-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Currie AC , Kaur V , Carey I , et al. Obstructive sleep apnea remission following bariatric surgery: a national registry cohort study. Surg Obes Relat Dis 2021 17 15761582. (https://doi.org/10.1016/j.soard.2021.05.021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Jonklaas J , Bianco AC , Bauer AJ , et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014 24 16701751. (https://doi.org/10.1089/thy.2014.0028)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Virili C , Antonelli A , Santaguida MG , et al. Gastrointestinal malabsorption of thyroxine. Endocr Rev 2019 40 118136. (https://doi.org/10.1210/er.2018-00168)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Virili C , Brusca N , Capriello S , et al. Levothyroxine therapy in gastric malabsorptive disorders. Front Endocrinol 2021 11 621616. (https://doi.org/10.3389/fendo.2020.621616)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Centanni M , Benvenga S & Sachmechi I . Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report. J Endocrinol Invest 2017 40 12891301. (https://doi.org/10.1007/s40618-017-0706-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Walker JN , Shillo P , Ibbotson V , et al. A thyroxine absorption test followed by weekly thyroxine administration: a method to assess non-adherence to treatment. Eur J Endocrinol 2013 168 913917. (https://doi.org/10.1530/eje-12-1035)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Ramadhan A & Tamilia M . Treatment-refractory hypothyroidism. CMAJ 2012 184 205209. (https://doi.org/10.1503/cmaj.110994)

  • 12

    Mercado A , Pham A , Wang Z , et al. Effects of bariatric surgery on drug pharmacokinetics-preclinical studies. Front Pharmacol 2023 14 1133415. (https://doi.org/10.3389/fphar.2023.1133415)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Neves JS , Castro Oliveira S , Souteiro P , et al. Effect of weight loss after bariatric surgery on thyroid-stimulating hormone levels in patients with morbid obesity and normal thyroid function. Obes Surg 2018 28 97103. (https://doi.org/10.1007/s11695-017-2792-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Zendel A , Abu-Ghanem Y , Dux J , et al. The impact of bariatric surgery on thyroid function and medication use in patients with hypothyroidism. Obes Surg 2017 27 20002004. (https://doi.org/10.1007/s11695-017-2616-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Pirola I , Formenti AM , Gandossi E , et al. Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery. Obes Surg 2013 23 14931496. (https://doi.org/10.1007/s11695-013-1015-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Liu H , Li W , Zhang W , et al. Levothyroxine: conventional and novel drug delivery formulations. Endocr Rev 2023 44 393416. (https://doi.org/10.1210/endrev/bnac030)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Fain K , Rojas AP & Peiris AN . Hypothyroidism following gastric sleeve surgery resolved by ingesting crushed thyroxine tablets. Proc (Bayl Univ Med Cent) 2020 33 3839. (https://doi.org/10.1080/08998280.2019.1669412)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Fallahi P , Ferrari SM , Ruffilli I , et al. Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update. Expert Opin Drug Deliv 2017 14 647655. (https://doi.org/10.1080/17425247.2016.1227782)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Ritter MJ , Gupta S & Hennessey JV . Alternative routes of levothyroxine administration for hypothyroidism. Curr Opin Endocrinol Diabetes Obes 2020 27 318322. (https://doi.org/10.1097/med.0000000000000558)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Ahluwalia R , Baldeweg SE , Boelaert K , et al. Use of liothyronine (T3) in hypothyroidism: joint British Thyroid Association/Society for endocrinology consensus statement. Clin Endocrinol 2023 99 206216. (https://doi.org/10.1111/cen.14935)

    • PubMed
    • Search Google Scholar
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  • 21

    Ueda K , Kiyota A , Tsuchida M , et al. Successful treatment of myxedema coma with a combination of levothyroxine and liothyronine. Endocr J 2019 66 469474. (https://doi.org/10.1507/endocrj.ej18-0469)

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