NUR 6400 Module 5 Endocrine Case: Graves Disease and Orbitopathy in a Smoker Example

An Antibody That Acts Like a Hormone: Thyrotoxicosis and Eye Disease in a 34-Year-Old Hairstylist Who Smokes

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Master of Science in Nursing, Thomas Edison State University

NUR-6400: Advanced Pathophysiology

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An Antibody That Acts Like a Hormone: Thyrotoxicosis and Eye Disease in a 34-Year-Old Hairstylist Who Smokes

Introduction

Ms. T. is a composite patient, a 34-year-old hairstylist who saw a nurse practitioner because her hands shook enough to make precise cuts difficult. In eight weeks she had dropped six kilograms despite second helpings, kept the salon fan on while coworkers wore sweaters, woke at 3 a.m. and felt her heart racing while she sat. Her clients had commented that her eyes looked wide and staring. She smokes about 20 cigarettes a day. Examination found a heart rate of 112, a fine tremor, a smooth, diffusely enlarged thyroid with a bruit and mild bulging of both eyes. Her thyroid-stimulating hormone was undetectable, her free thyroxine was three times the upper limit and her TSH receptor antibodies were positive. This paper explains her illness as an autoimmune disorder whose effects spread through the whole body.

Normal Control of the Thyroid

Normally the chain starts with thyrotropin-releasing hormone from the hypothalamus, which prompts the anterior pituitary to secrete TSH. TSH binds its receptor on thyroid follicular cells, stimulating iodine uptake, hormone synthesis and growth of the gland. Thyroxine and triiodothyronine then feed back on the pituitary and hypothalamus to lower TSH. The loop keeps hormone levels within a narrow range. Ms. T.'s undetectable TSH shows the loop was still working at the pituitary: her pituitary had sensed the excess and stopped. Something other than TSH was driving her gland. The pattern of her other results points the same way. A diffuse goiter with a bruit and positive receptor antibodies is typical of an antibody-driven gland, whereas a single hot nodule or a tender gland after a viral illness would suggest a different cause of thyrotoxicosis, and Ross et al. (2016) list these alternatives because each needs different treatment. Triiodothyronine is often raised more than thyroxine in Graves disease, since the stimulated gland converts more of its output to the active form.

The Autoimmune Mechanism

That driver was an antibody. In Graves disease, B cells produce IgG antibodies that bind the TSH receptor and activate it the way TSH does (Smith & Hegedüs, 2016). Because the antibodies are not subject to feedback, the gland is stimulated continuously. Follicular cells take up more iodine, make more hormone and multiply, producing the smooth, diffuse goiter. Increased blood flow through the enlarged gland explains the bruit. This is a stimulatory form of type II hypersensitivity: antibodies against a cell surface receptor change the cell's function instead of destroying it.

Why tolerance fails is only partly known. Davies et al. (2020) describe a combination of genetic susceptibility, including variants in HLA genes and in immune regulatory genes such as CTLA4, with environmental triggers, so that self-reactive B and T cells escape the controls that normally keep them silent. The thyroid itself becomes a site of immune activity, with lymphocytes in the gland and local antibody production.

Every Symptom From One Hormone

Thyroid hormone acts on almost every tissue, which is why one gland can produce such a range of symptoms. It raises the basal metabolic rate by increasing mitochondrial activity and sodium-potassium pump turnover, so Ms. T. burned more energy than she ate and lost weight despite a greater appetite, and she produced more heat. Her heart muscle also carried more beta receptors, and each one answered adrenaline more strongly, so her pulse sat at 112 and every beat thumped against her ribs. The same adrenergic sensitivity produces the fine tremor and anxiety. Faster gut transit causes more frequent stools, and disturbed sleep reflects central nervous system arousal. Untreated, the excess hormone can also cause atrial fibrillation and bone loss, the two complications most important in older patients.

The Eyes: A Second Target

Not all of Ms. T.'s findings come from thyroid hormone. Some of the stare is caused by adrenergic retraction of the upper lid, which improves when hormone levels fall. Her bulging eyes are different. Orbital fibroblasts carry TSH receptors and receptors for insulin-like growth factor 1, and the same antibodies activate them (Smith & Hegedüs, 2016). Activated fibroblasts produce hyaluronan, which draws in water, and some become fat cells, so the tissue behind the eye and the eye muscles swell inside the bony orbit. The eyes are pushed forward, causing proptosis, and in severe cases the swelling compresses the optic nerve.

Of all the things Ms. T. could change, her cigarettes matter most to her eyes. Smokers are more likely to develop it, have more severe disease and respond less well to treatment, and the effect increases with the number of cigarettes smoked (Davies et al., 2020). Proposed mechanisms include low oxygen in the orbit and chemicals in smoke that stimulate fibroblasts to make more hyaluronan and fat. For Ms. T., stopping smoking is part of treating her eyes, not general health advice.

Predisposing Factors Across the Lifespan

Graves disease is five to ten times more common in women and usually appears between the ages of 30 and 50 (Davies et al., 2020). Estrogen effects on immune function and the X chromosome, which carries several immune genes, may explain part of this difference. The postpartum period is a time of increased risk, as immune tolerance established during pregnancy resets after delivery. Stress, high iodine intake and some medicines that affect immune function have also been associated with onset. In older adults the disease may present with weight loss or atrial fibrillation and few of the classic symptoms, which delays diagnosis.

Conclusion

Ms. T.'s illness came from antibodies that switched on her TSH receptors without feedback. Her gland grew and produced excess hormone, and the hormone raised her metabolic rate and adrenergic sensitivity, producing weight loss, heat intolerance, palpitations and tremor. The same antibodies reached her orbital fibroblasts, and smoking worsened the swelling behind her eyes. Her sex, age and probably her genes made her susceptible. Treatment options, including antithyroid drugs, radioactive iodine and surgery, follow from the mechanism, and the American Thyroid Association guideline (Ross et al., 2016) sets out how to choose among them, with smoking cessation part of every plan.

References

Davies, T. F., Andersen, S., Latif, R., Nagayama, Y., Barbesino, G., Brito, M., Eckstein, A. K., Stagnaro-Green, A., & Kahaly, G. J. (2020). Graves' disease. Nature Reviews Disease Primers, 6(1), 52. https://doi.org/10.1038/s41572-020-0184-y

Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., & Walter, M. A. (2016). 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid, 26(10), 1343-1421. https://doi.org/10.1089/thy.2016.0229

Smith, T. J., & Hegedüs, L. (2016). Graves' disease. New England Journal of Medicine, 375(16), 1552-1565. https://doi.org/10.1056/NEJMra1510030