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.
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Stephanie L. Lee
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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).
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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.
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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.
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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).
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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:
- Forman MB. Clinical Endocrinology.
1980;12:385-390.
- Mamdani N. Endocr Pract. 2007;13:487-492.
- Puvanendran K. Act Neural Scand. 1982;66:309-315.
- Uncanny A. J Neurol. 1985;232:109-111.