PANCE® Question of the Day: Fatigued and cold

Prepare for the PANCE® with this challenging clinical scenario involving a 32-year-old woman reporting fatigue and weight gain. What’s the most likely diagnosis?

A 32-year-old woman presents to the primary care office for evaluation of four months of fatigue and weight gain. She frequently feels cold, even when others in the room are comfortable, and her menstrual cycles have been irregular the last few months. She also has been experiencing constipation and dryness of her skin. She has no significant past medical history and takes no medications. Temperature is 37.0°C (98.6°F), pulse is 58/min, respirations are 16/min, and blood pressure is 118/80 mmHg. On exam, her skin appears dry and her hair is brittle. There are no palpable masses at the anterior neck. Abdominal exam is unremarkable. Initial lab results can be seen below.

Which of the following tests should be ordered next to help make the diagnosis?

A. TSH receptor antibodies

B. Anti-centromere antibodies

C. Thyrotropin-releasing hormone level

D. Thyroid peroxidase antibodies

E. Serum glucose level

Scroll down to find the answer!                       

The correct answer to today’s PANCE® Question is…

D. Thyroid peroxidase antibodies

Correct: See Main Explanation.

Incorrect Answer Explanations

A. TSH receptor antibodies

Incorrect: TSH receptor antibodies can be seen in Grave disease, which leads to hyperthyroidism. TSH would be low and serum-free T4 high.

B. Anti-centromere antibodies

Incorrect: Anti-centromere antibodies may be seen in scleroderma which can lead to hypothyroidism and skin changes; however, Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient parts of the world, and patients should first be tested for this.

C. Thyrotropin-releasing hormone level

Incorrect: TRH is the hormone released by the hypothalamus to stimulate TSH from the pituitary and is typically assessed indirectly through TRH stimulation testing. TSH would typically be low when there is a problem with the hypothalamus leading to hypothyroidism.

E. Serum glucose level

Incorrect: Hypoglycemia can be a rare manifestation of thyroid disease but would not help determine the definitive diagnosis in this case. 

Main Explanation

This patient presents with signs, symptoms, and laboratory results consistent with primary hypothyroidism. Hashimoto thyroiditis is the most common cause of primary hypothyroidism in iodine-sufficient parts of the world. It can be diagnosed with findings of antibodies to thyroid peroxidase. Anti-thyroglobulin antibodies may also be present.

For patients with suspected hypothyroidism, testing should begin with TSH and serum-free T4. If TSH is high and serum-free T4 is low, then the patient can be diagnosed with primary hypothyroidism. The next step is to test for anti-thyroid peroxidase and anti-thyroglobulin antibodies which, if positive, can be used to diagnose Hashimoto thyroiditis. If antibody testing is negative, then the patient should be evaluated for other causes of primary hypothyroidism including iatrogenic causes (e.g., thyroidectomy, radioactive iodine treatment, external neck radiation), iodine deficiency or excess, drugs, and infiltrative diseases.

If both TSH and serum-free T4 are low, then the patient should be evaluated for central hypothyroidism which can occur when thyroid hormone deficiency is due to a disorder of the pituitary, hypothalamus, or hypothalamic-pituitary circulation. Pituitary causes include pituitary adenomas, prior radiation or surgery for pituitary adenomas, as well as infections, inflammation, and infarction (Sheehan syndrome). Infiltrative processes like sarcoidosis and brain injury can also affect the hypothalamic-pituitary axis.

When TSH is high but the serum-free T4 is within normal limits, this is referred to as subclinical hypothyroidism. A significant portion of these patients will eventually go on to develop clinical hypothyroidism. 

Major Takeaway

Patients with suspected hypothyroidism should have TSH and serum-free T4 checked. If TSH is elevated and serum-free T4 is low, primary hypothyroidism can be diagnosed. Patients should be tested for antibodies to thyroid peroxidase and anti-thyroglobulin to determine if Hashimoto thyroiditis is the cause.

Want to learn more about this topic?

Watch this Osmosis video: Hypothyroidism

References 

• Klubo-Gwiezdzinska J, Wartofsky L. Hashimoto thyroiditis: an evidence-based guide to etiology, diagnosis and treatment. Pol Arch Intern Med. 2022 Mar 30;132(3):16222. doi: 10.20452/pamw.16222. Epub 2022 Mar 3. PMID: 35243857; PMCID: PMC9478900.

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