Theofilus de Bruin, M.D.
A 39-year-old African-American man presented with a two-month history of dysarthria, hoarseness, inter-mittent left eye ptosis, dysphagia, periorbital and eye lid swelling, periorbital hypopigmentation, and electric shock paresthesias of arms and legs. He also had noted some hair loss, weight loss, reduced energy level and depression. The patient had been treated for depression in the past and had been on and off parox-etine and buspirone several times in the last 5 years. He had not seen his psychiatrist in over a year and had been off his antidepressants for 2 years. He indicated that his depression had worsened recently because his companion had died. He denied any cardiovascular symptoms including angina and had no history of prior myocardial infarction.
The patient's past medical history was significant for hepatitis C and geographic tongue. He had a remote history of polysubstance abuse and alcoholism. He stopped using drugs 17 years prior to presentation and quit alcohol 5 years prior to presentation. He had not seen an internist in 6 years. His family history was significant for thyroid disease in his mother, brother, and nephew.
Initial physical examination demonstrated periorbital and eyelid swelling with mild hypopigmentation in periorbital regions. Speech was mildly dysarthric and there was some psychomotor retardation. The thyroid gland was not enlarged. Deep tendon reflexes showed delay in the relaxation phase. Right calf atrophy was noted with reduced right knee jerk that was felt to be related to a back injury at age 14 years that had required surgery. His neurological exam was other-wise normal. A small indentation was noted on his scalp, which was related to prior trauma. Pulmonary, cardiovascular and abdominal examinations were normal. He appeared mildly depressed.
Initial laboratory studies were as follows: thyrotropin 125.03; free thyroxine
0.2; total triiodothyronine 23 (60-181); anti-thyroid peroxidase antibody 647.6;
alanine aminotransferase 54; antithyroglobulin antibody 3906; vitamin B12 and
folate levels normal; hemoglobin 12.4; hematocrit 36.2; serum creatinine 1.6.
Magnetic resonance image of the head was normal.
The patient was diagnosed with profound hypothyroidism and was started on levothyroxine 0.025 mg a day. Over the next 11 months, the levothyroxine dosage has been gradually increased to 0.15 mg a day. His most recent blood tests showed thyrotropin 6.12 and free thyroxine 1.24. His anemia and renal insufficiency also resolved.
The patient was evaluated by a neurologist 4 and 9 months after initiation of levothyroxine. At the first visit, the neurologist noted that most of his presenting symptoms had resolved, including the left eye ptosis. Nevertheless he underwent further evaluation, including a computed tomographic scan of the chest, acetylcholine receptor antibodies, erythrocyte sedi-mentation rate, and anti-nuclear antibodies blood test. All tests were normal or negative. At his follow-up neurology visit, all neurologic and depressive symptoms had resolved. The patient's multiple neuro-muscular complaints and signs were attributed to profound hypothyroidism. He was subsequently seen by a dermatologist who felt that the periorbital pigmentary changes were also related to his thyroid disease. He was prescribed hydroxyquinone 4% cream to apply to these areas.
Iodine deficiency is the most common cause of hypothyroidism and goiter worldwide. Hashimoto's thyroiditis (HT), the most common form of chronic autoimmune thyroid disease (AITD) in areas of iodine sufficiency, is caused by T-cell-mediated disease with a strong genetic component. There is cell- and antibody-mediated destruction of the gland. The disease can be associated with goiter or gland atrophy. Chronic autoimmune thyroid disease is more common in women, especially later in life, and in children.1,2
Patients with HT may initially present only with psychiatric
illness without any other symptoms of the disease. This patient's diagnosis
was preceded by a 6-year history of waxing and waning depression, requiring
medications. Hypothyroidism-related psychiatric illness includes organic mental
disorder, apathy, depression, and psychosis with paranoia. These manifestations
generally abate with adequate hormone replacement therapy. However, if hypothy-roidism
is sufficiently prolonged and severe, the brain damage may be irreversible.3
The patient's neuromuscular symptoms are not unusual in HT. Duyff and colleagues4 evaluated neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism. The study showed 79% of patients had neuromuscular complaints, 39% had clinical weakness of one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy and 29% had carpal tunnel syndrome. After a year of treatment, 13% of patients still had some muscle weakness related to myopathy. In our patient, neuro-muscular complaints were relatively mild and were fully resolved in 7 to 8 months.
As expected, the thyroid replacement therapy resulted in improvement in symptoms during the first 3 months. Geographic tongue has been associated with AITD.5 The patient did not exhibit macroglossia. The dysarthria most likely was related to mucinous deposits in the vocal cords.6 Severe or prolonged autoimmune hypothyroidism results in the accumula-tion of hydrophillic mucopolysaccharides.1,7 Mucoprotein deposits in the subendothelial layer of vessels disrupt the barrier function of capillaries, resulting in loss of extracellular fluid and plasma proteins. Lymphatic vessels are also affected by this process, leading to edema of the hands, face and eyelids with subsequent impairment of fluid and protein drainage.8 In this patient, periorbital and eyelid swelling also related to this process.
The pathogenesis of the ophthalmopathy and dermopathy in HT is unclear, but may be explained by the cross-specificity of thyroid peroxidase and thyroglobulin antibodies with orbital and dermal fibroblasts leading to accumulations of glycosaminoglycans.9 The left eye intermittent ptosis may have related to these processes as well as myopathic and neuropathic changes. Our patient had surprisingly little cardiovascular, pulmonary, or gastrointestinal symptoms.
As this case illustrates, hypothyroidism is a multifaceted disease and the initial presentation may be challenging. Symptoms of depression, including fatigue, reduced energy level, and weight loss may be readily attributed to depression rather than hypothyroidism. Indeed, this patient also had situational causes for depression. Because early recognition is important for successful treatment and reversal of hypothy-roidism-related signs and symptoms, all patients diag-nosed with depression should have their thyroid function tests evaluated. With correction of this patient's hypothyroidism, most of his presenting problems resolved, including the depression.
- Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: etiology, pathogenesis and dermatologic manifestations. J Am Acad Dermatol 2003 May;48(5):641-659.
- Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4 and thyroid antibodies in the United States population (1988-1999): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489.
- McGaffee J, Barnes MA, Lippmann S. Psychiatric presentations of hypothyroidism. Am Fam Physician. 1981 May;23(5):129-133.
- Duyff RF, van den Bosch J, Laman DM, van Loon BJP, Linssen WH. Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study. J Neurol Neurosurg Psychiatry. 2000 Jun;68(6):750-755.
- Fatourechi V. Demystifying autoimmune disease. Post Grad Med 2000;107:127-134.
- Smith, TJ, Bahn RS, Gorman CA. Connective tissue glycosamino-glycans, and diseases of the thyroid. Endocr Rev. 1989;10:366-391.
- Shagam JY. Thyroid disease: an overview. Radiol Technol. 2001;73:25-40.
- Hierholzer K, Finke R. Myxedema. Kidney Int. Suppl. 1997;59:S82-89.
- Singh SK, Singh KK, Sahay RK. Images in medicine: Hashimoto's Thyroiditis with orbitopathy and dermopathy. J Postgrad Med. 2000;46:286-287.
Originally submitted on May 26, 2005