Malabsorption of Thyroid Hormone After Small Bowel Resection

Abstract

Hypothyroid patients on stable long-term oral levothyroxine (T4) dosage are at risk of developing overt hypothyroidism after small bowel (SB) resection. This can happen despite equivalent peri-operative intravenous (IV) supplementation and resumption of preoperative oral T4 dosage when post-operative oral medication is tolerated. This situation is not specifically addressed in any of the major guidelines for T4 oral replacement in this setting and may be underrecognized, leading to diagnostic and management challenges.

1. Introduction

Primary hypothyroidism is managed through daily oral levothyroxine (T4) replacement therapy. Patients require adequate hormone absorption to maintain appropriate thyroid function and overall health as monitored by normalization of thyroid stimulating hormone (TSH). Complications of inadequate hormone replacement therapy include fatigue, metabolic disorders, depression, and myxedema coma.

Oral T4 is predominantly absorbed in the jejunum and proximal ileum.1 In small bowel (SB) resection, the intestinal surface area available for absorption is reduced, and the transit time through the small intestine may be shortened, leading to malabsorption of the hormone.2,3 We present a case of a patient on stable oral T4 who clinically developed overt hypothyroidism after emergency SB resection. Currently, there are no published guidelines regarding close monitoring for hypothyroid symptoms and thyroid function tests (TFTs) following small bowel resection in patients tolerating T4 orally. This case may suggest close monitoring of TFTs and readjustment of T4 replacement therapy following small bowel resection in patients taking oral thyroid hormone replacement.

2. Case report

An 87-year-old female with controlled primary hypothyroidism on a stable oral dose of 125 mcg T4 presented to the ED with a 1-day complaint of upper abdominal pain and tenderness associated with nausea, vomiting, and diminished oral intake. Medical history included complex partial seizures (controlled on stable doses of divalproex, levetiracetam, zonisamide), mild neurocognitive disorder, and hysterectomy. At baseline, she lived at home, ambulated with a walker, managed personal care independently, and appropriately conversed with her family.

Initial exam revealed normal vital signs. She was alert and conversant, with dry oral mucous membranes and decreased skin turgor. Abdominal exam revealed diffuse tenderness without rebound, rigidity or masses. Rectal exam was normal with brown stool. White blood cell (WBC) count was mildly elevated without a left shift. Red blood cell count, hemoglobin, and hematocrit were mildly elevated, attributed to dehydration and hemoconcentration. Blood urea nitrogen (BUN) was 28 mg/dL (normal: <8 mg/dL), and serum creatinine was normal. TSH was 0.79 μIU/mL (normal: 0.27–4.2 μIU/mL). Computed tomography (CT) scan of abdomen and pelvis revealed mild diffuse colonic-wall thickening. Treatment with IV fluids and a single empiric dose of ciprofloxacin and metronidazole were administered. However, abdominal distension with hyperactive bowel sounds developed over several hours without a bowel movement. This prompted an emergent repeat CT scan, now revealing closed loop SB obstruction (Fig. 1).

Fig. 1.

Enhanced coronal and transverse computed tomography with oral contrast revealed closed loop small bowel obstruction in the pelvis with two transition points (green arrows pointing one transition point located at level of femoral heads on coronal imaging and second green arrow pointing towards second transition point located below femoral heads on transverse imaging). No illumination in intraluminal bowel with oral contrast is seen indicating obstruction. Mesenteric hyper-attenuation is seen in blue arrow indicating mesenteric pathology as a sequelae of small bowl obstruction. Bowel wall hypoattenuation is seen in orange arrow representing arterial ischemia.

Home medications were administered parenterally at equivalent doses. Emergent exploratory laparotomy revealed a closed loop obstruction. Two feet of necrotic jejunal-ileal segment were resected with anastomosis and lysis of adhesions. On the 2^nd post-operative day, she resumed oral home medications. On the 3^rd post-operative day, clinical and chest x-ray (CXR) findings were consistent with aspiration pneumonia. IV piperacillin/tazobactam for 7 days course was initiated. On the 7^th postoperative day, she was afebrile and transferred to Transitional Care Unit (TCU) for rehabilitation and completion of remaining antibiotic course.

After 3 days in the TCU (On 10^th post-operative day), patient’s vigilant family and staff noted she was withdrawn and fatigued, taking frequent naps. She appeared lethargic. There were no focal motor or speech deficits. She had diminished deep tendon reflexes and delayed relaxation phase in the knee jerk reflex. Goiter was not present. No evidence of her complex partial seizure disorder or unwitnessed grand mal seizure with post-ictal state were noted.

Urgent laboratory studies including repeat complete blood count, complete metabolic panel, and urinalysis were unrevealing. Repeat CXR showed resolving post-operative pneumonia. Considering her recent surgery, an urgent CT scan of the head, abdomen, and pelvis was thought necessary to evaluate for post-operative non-focal stroke, intracranial lesions/inflammation, or intraabdominal abscess. Images were unrevealing, and lumbar puncture was thought not to be indicated.

Upon further workup, repeat thyroid function tests (TFTs) were drawn on the 12th post-operative day (10 days after resuming oral T4), which revealed overt hypothyroidism (Table 1). The patient’s oral T4 was converted to IV T4 at 62.5 mcg (50 % of oral dose) due to suspected malabsorption of oral T4. She demonstrated clinical return to her baseline within 24 h and improvement of TFTs by the 5^th day after being on IV replacement therapy (Table 2).

Table 1.

Thyroid function test drawn 12 days after small bowel resection (10 days after resumption of oral T4).

Test	Result	Normal Range	Interpretation
Thyroid Stimulating Hormone before Small Bowel Resection	0.79 μIU/mL	0.27–4.2 μIU/mL	Within normal limits
Thyroid Stimulating Hormone 12 days after Small Bowel Resection (10 days after resumption of Oral T4)	13.5 μIU/mL	0.27–4.2 μIU/mL	Elevated (above upper limit normal)
Total Thyroxine 12 days after Small Bowel Resection	4.37 μg/dL	4.5–11.7 μug/dL	Low (below lower limit normal)
Free Thyroxine 12 days after Small Bowel Resection	0.71 ng/dL	0.93–1.7 ng/dL	Low (below lower limit normal)
Total Triiodothyronine 12 days after Small Bowel Resection	38.3 ng/dL	80–200 ng/dL	Low (below lower limit normal)

Table 2.

TFT drawn 5 days after switching oral T4 to IV T4 due to suspected oral T4 malabsorption from small bowel resection.

Test	Result	Normal Range	Interpretation
Thyroid Stimulating Hormone	12.5 μIU/mL	0.27–4.2 μIU/mL	Elevated (above upper limit normal)
Free T4	1.07 ng/dL	0.93–1.7 ng/dL	Within normal limits

3. Discussion

We attributed our patient’s hypothyroidism to diminished surface absorption of oral T4 due to SB resection. Several other confounders were considered in our differential diagnosis.

Hypothyroidism induced by her anti-seizure medications was thought less likely because of normal TSH on admission and no dosage adjustments of these medications during her stay.

Nonthyroidal illness was considered for our patient’s thyroid abnormalities. Laboratory testing for reverse T3 (rT3) was unavailable, though previous studies have suggested that rT3 is not generally reliable to distinguish hypothyroid sick patients from euthyroid sick patients.4 According to the American Thyroid Association, a rise in TSH during worsening stages of critical illness can be indicative of thyroid hormone deficiency in patients with preexisting hypothyroidism, and IV T4 may be given to patients with gastrointestinal disease in the intensive care setting.5 However, current guidelines do not provide specific recommendations on SB resection as a scenario for IV T4 or increasing dosage of oral T4 replacement therapy in a non-ICU setting.

Due to our patient’s worsening free T4 (fT4) levels during the hospital course, as well as high degree of suspicion for malabsorption, decision was made to switch the patient to IV T4. After temporary treatment with IV T4 and improvement of symptoms and fT4 levels, we resumed the oral thyroid replacement dose patient took prior to admission, 125 mcg oral daily. On 25^TH post-operative day, she was stable for discharge. Arrangements were made for close outpatient monitoring.

Previous studies have demonstrated T4 malabsorption after SB resection.1–3 One case study highlighted a 59-year-old male who required significantly higher doses of oral T4 following multiple SB resections and an ileostomy.1 Despite increasing the dose to 350 μg daily, his TSH levels remained elevated until the ileostomy was closed, after which his T4 requirement decreased. This underscores the impact of intestinal surgeries on thyroid hormone absorption and the necessity for individualized dosing in such patients. Previous studies have also compared the absorption of radioactive L-Thyroxine in normal patients versus patients with SB resections and showed reduced peak radioactivity of L-Thyroxine in the serum of short bowel patients.3

The rapid onset of our patient’s hypothyroid state may be explained by additional factors. Gut microbiota are involved in synthesis of thyroid hormone.6 They absorb minerals such as iodine, iron, copper, zinc, and selenium. Iodine, iron, and copper are crucial for synthesizing thyroid hormone whereas selenium and zinc play a role in conversion of T4 to T3. Alterations in gut microbiota, or gut dysbiosis, may impact the bioavailability of dietary minerals needed for T4 synthesis or T3 conversion. In addition to SB resection, we speculate that her antibiotics for aspiration pneumonia may have also contributed to gut dysbiosis. Since the half-life of endogenous T4 is typically 9–10 days for people with hypothyroidism, we surmise that increased metabolism of T4 from gut dysbiosis was likely a contributing factor for our patient to develop overt hypothyroidism 12 days after SB resection.

Based on this patient, we demonstrate that small bowel resection can impact T4 absorption and metabolism in hypothyroid patients on stable oral T4 replacement therapy. We found no prospective studies of similar patients which compared those requiring adjustments to their oral T4 dose to those who did not. Although current guidelines have no specific recommendations for this scenario, we suggest close monitoring for hypothyroid symptoms and TFTs (especially free T4 levels) in patients undergoing small bowel resection who are on oral thyroxine replacement therapy.