Calcified basal ganglia after thyroidectomy

A 66-year-old Peruvian man visiting the United States for the past 6 months was admitted for evaluation of near syncope and possible transient ischemic attack. He noted two episodes of slurred speech, weakness and difficulty walking that lasted 1 hour.

His past medical history was significant for a history of papillary thyroid carcinoma treated in Peru in 1985 by total thyroidectomy, radical neck dissection with removal of his right sternocleidomastoid muscle followed by external cobalt radiation. He denied radioactive iodine scans or treatment for his thyroid cancer. His only medication was levothyroxine 100 mg twice daily. At home, in Peru, he did not take any vitamins or calcium but ate five to six servings of dairy products daily and spent many hours each day outside without sunblock. During his visit to Boston, he had not been eating any dairy products or taking any vitamin supplements.

Stephanie L. Lee

He denied paresthesias, muscle cramps or any problems with breathing or eating. Although his exam in the ED revealed a hoarse voice, his neurological exam was non-focal with normal movement, and he was alert and oriented. The patient was not checked in the ED for a Chvostek�s or Trousseau�s sign.

A CT scan of the head without contrast in the ED did not show evidence of cerebral vascular accident, hemorrhage or mass, but it showed dense bilateral symmetric calcifications in the distribution of the basal ganglia (Figures 1 and 2); subcortical white matter; and dentate nuclei of the cerebellum (Figure 3). His chemistry panel revealed a calcium of 5.7 mg/dL (reference range 8.4-10.2); albumin of 4 g/dL; phosphorus of 4 mg/dL (reference range 1.6-2.6); parathyroid hormone (PTH) of 4 pg/mL (reference range 11-80); magnesium of 1.7 mg/dL; alkaline phosphatases of 95 IU/L; creatinine of 0.87 mg/dL; thyroid-stimulating hormone of less than 0.01 uU/mL (reference range 0.4-4); triiodothyronine of 82 ng/dL; and free thyroxine of 2.16 mcg/dL. His electrocardiogram showed a normal sinus rhythm and a significant prolongation of QT interval with a QTc of 0.537 ms (Figure 4). A diagnosis of hypocalcemia caused by surgical hypoparathyroidism was made based on this past medical history and lab tests showing a low serum calcium, low PTH, high phosphorus and normal magnesium levels.

The patient was discharged on elemental calcium 1,000 mg three times daily plus calcitriol 0.25 mcg twice daily. He saw the endocrine service for the first time as an outpatient 2 weeks later. He had no symptoms of low calcium levels. His exam was negative for a Chvostek�s or Trousseau�s sign. He had not started the calcitriol because of the expense, but was taking the oral calcium with a repeat calcium level of 7.8 mg/dL. He was instructed to continue the calcium but to take over-the-counter vitamin D 50,000 units weekly. He refused further evaluation for thyroid carcinoma because of the expense.

Bilateral symmetric basal ganglia and intracerebellar calcifications are referred to as Fahr�s disease, which can be accompanied by signs and symptoms of severe hypocalcemia with symmetrical basal ganglia calcifications and neuropsychiatric manifestations, including extrapyramidal movement disorders such as Parkinsonism, hemiballismus, choreoathetoid movement, seizures and mental retardation. Basal ganglia calcifications have been described with chronic hypocalcemia, carbon monoxide poisoning, anoxia, tuberous sclerosis, cytomegalic inclusion disease, toxoplasmosis, therapeutic radiation, epilepsy and methotrexate treatment, but may also be idiopathic. The calcifications occur symmetrically in the basal ganglia, affecting the putamen, globus pallidus and the cerebellar dentate nucleus (Figures 1, 2 and 3).

Figure 1. Coronal CT scan without contrast. Basal ganglia (red) is shown in the illustration. The basal ganglia calcification (red arrows) appears intensely hyperintense in a symmetrical distribution within the putamen, globus pallidus and caudate nucleus.

Figure 2. Axial CT scan without contrast. Basal ganglia (red) is shown in the illustration. The basal ganglia calcification (red arrows) is in a symmetrical distribution within the putamen, globus pallidus and caudate nucleus.

Figure 3. Axial CT scan without contrast. The dentate nucleus of the cerebellum is shown in the illustration. The dentate nucleus calcification is symmetric within the cerebellum (red arrows).

Figure 4. Electrocardiogram. This patient�s electrocardiogram shows QT/QTc prolongation that occurs with hypocalcemia. Photos courtesy of: Stephanie L. Lee, MD, PhD

This patient likely had a long-standing hypoparathyroidism as a result of the neck dissection for thyroid cancer. The hypocalcemia is unlikely related to autoimmune parathyroid destruction (polyglandular autoimmune disease), hypomagnesemia, autoimmune activation of the calcium sensing receptor or idiopathic DiGeorge syndrome.

Parathyroid glands are relatively resistant to the effects of radiation, making it unlikely that the parathyroid hypofunction was related to his prior radiation treatment. Other rare causes of hypoparathyroidism include infiltrative destruction by hemochromatosis, Wilson�s disease (copper deposition), granulomas or metastatic cancer.

This patient had relatively few symptoms at presentation, suggesting that he developed adaptations over a long period to the hypocalcemia and the cerebral calcification.

In addition, his high dairy intake and significant sun exposure in Peru likely maintained an adequate level of vitamin D and calcium intake to prevent hypocalcemic symptoms. Symptoms of acute hypocalcemia include perioral paresthesias, neuromuscular irritability (positive Chvostek�s or Trousseau�s signs), strider with laryngeal spasm, prolonged QT/QTc interval on ECG and seizures. Chronic hypocalcemia, as demonstrated by this patient, is associated with basal ganglia and cerebellar dentate nuclei (Figures 1, 2 and 3) on CT scan, prolonged QT/QTc interval on ECG (Figure 4) and osteoporosis. Of note, calcification cannot be seen on MRI scan; CT is the best imaging modality to see brain calcifications. Mental retardation may occur in children with chronic hypocalcemia. This patient�s symptoms only became manifested when he reduced his high intake of calcium and moved to an environment of reduced sun exposure and development of lower serum vitamin D levels.

Long-term treatment of hypocalcemia will reduce the progression of the calcifications, and case reports suggest that the basal ganglia calcifications may completely resolve. Treatment of hypocalcemia may reverse some of the neurological disorders, but the Parkinsonism associated with basal ganglia calcification is resistant to treatment.

Stephanie L. Lee, MD, PhD, is associate professor of medicine and associate chief in the section of endocrinology, diabetes and nutrition at Boston Medical Center.

For more information:

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• Puvanendran K. Act Neural Scand. 1982;66:309-315.
• Uncanny A. J Neurol. 1985;232:109-111.