Ward Round - Seizures, tremor and muscle weakness 20 years after thyroid surgery

Clinical presentation

A 32 year-old carpenter was admitted to the medical ward at QECH with a 1 month history of fever, weight loss, a sore mouth and pain on swallowing. He had recently tested HIV positive but was not taking antiretroviral therapy or cotrimoxazole prophylaxis. On Initial examination he was sweating, febrile, temperature 38.2°C and tachypnoeic, RR 32/min. Other vital signs were unremarkable; BP 120/80 mmHg, PR 84/min, regular, O₂ saturations on room air 95%. His oral mucosa was erythematous with 2 small ulcers on the palate. There were no physical signs suggestive of a focus of infection. According to local guidelines he was treated with intravenous penicillin and gentamicin for presumed sepsis, fluconazole for possible oral/oesophageal candida and started on cotrimoxazole prophylaxis. He remained febrile, his antibiotic regime was changed to ceftriaxone but his fever persisted

On subsequent review a more detailed history and examination were taken which revealed that he also had neurological problems. He described the onset of a coarse tremor 3 months previously, at the same time he developed generalized body pain, numbness of the hands and feet, muscle weakness and fatigue which had become so severe he was now unable to stand or even sit unaided. He had had 3 grand mal convulsions prior to admission and further convulsions were witnessed on the ward. He had long standing anorexia, constipation, cold intolerance and poor libido. He had a thyroidectomy at the age of 12 years for goiter and had no contact with clinical services between then and the current admission. He left school at the age of 16 years, and reported he was a good performer at school. He was married with seven children, occasionally drank locally made beer (chibuku and kachasu), and smoked 3 cigars per day. There was no history of TB contact.

On examination he was pale with facial and periorbital oedema and a husky voice. There were no cataracts. He had a neck scar consistent with thyroidectomy. Cardiovascular, respiratory and abdominal examinations were unremarkable. He was mentally alert. There was no nystagmus or dysarthria. There was proximal muscle wasting and muscle tone appeared low- he was unable to sit unsupported or stand despite relatively preserved muscle power (4/5 in all limbs). Tendon reflexes were normal and were not slow relaxing. He had spasmodic involuntary movements of the limbs, both at rest and on movement. Chvostek's (facial twitching in response to tapping of the facial nerve) and Trousseaus's signs (carpopedal spasm when a blood pressure cough is inflated above systolic pressure for 3 minutes) were positive.

Investigations

Investigations were directed towards possible neurological, metabolic and endocrine diseases, as well as the cause of his fever.

• FBC: Hb 8.6 g/dl, MCV 90 fl, WBC 8.6 X109/l, platelet 610 X109/l

• Urea 23 mg/dl (5–13), creatinine 1.6 mg/dl (0.6–1.2),

• Serum calcium (corrected) 1.95 mmol/L (2.2–2.4), phosphorus 5.2 mg/dl (2.1–3.8)

• Thyroid function: TSH 23.4 mu/l (0.3–6.4), fT3 0.3 ng/ml, fT4 4.3 ug/dl (4.8–11.6).

• Blood culture- no growth, malaria parasites- negative, LP- failed attempt

• CXR- enlarged cardiac silhouette, clear lung fields,

• Transthoracic echocardiogram: 2cm pericardial effusion with fibrinous strands and no cardiac tamponade

• CT scan brain (figure 1a and ​and1b)1b) Calcification of basal ganglia and subcortical white matter

  

  Figure 1a

  CT brain scan

  

  Figure 1b

  CT brain scan

Discussion

The persistent fever despite broad spectrum antibiotics, lack of positive identification of infection elsewhere and finding of pericardial effusion with strands on echocardiogram led to a diagnosis of presumed TB pericarditis¹. He was treated empirically with anti-tuberculous drugs and prednisolone and made an excellent response. He continued with cotrimoxazole prophylaxis.

Thyroid function tests confirmed primary hypothyroidism with raised TSH and low fT3 and fT4. The low calcium, raised phosphorus and intracranial calcifications are all highly suggestive of hypoparathyroidism. We were unable to measure parathyroid hormone levels to confirm this. Both hypothyroidism and hypoparathyroidism are likely to have occurred secondary to the thyroidectomy he had 20 years ago. Intracranial calcification, particularly of the basal ganglia is a common occurrence in hypoparathyroidism. It increases with the duration of hypoparathyroidism and is rarely visible on plain X-rays but can be seen on a CT scan². The most common site is the globus pallidus but it can also occur in the cerebellum, subcortical white matter, corona radiata and thalamus³. The mechanisms behind this paradoxical intracranial calcification are still unknown but some have speculated that it may be a function of hyperphosphataemia promoting ectopic calcification⁴. The cerebral calcification is associated with neurological damage, most commonly Parkinsonism, but other extra-pyramidal syndromes, cerebellar and pyramidal signs have been described⁵. The neurological problems are usually irreversible or only partially improve when hypoparathyroidism is treated.

The incidence of hypothyroidism following thyroidectomy varies depending on the underlying thyroid problem and the amount of thyroid removed but can be as high as 50%⁶. We assume our patient must have had an extensive thyroidectomy in order to have lost all 4 parathyroid glands. In such situations, thyroid function and calcium levels should be routinely monitored postoperatively.

The reported incidence of permanent hypoparathyroidism following thyroid surgery varies between 0.5 and 4% depending on the extent of operation, the surgical technique and the surgeon's experience. Symptoms of hypoparathyroidism post thyroid surgery generally begin 1 or 2 days after the procedure. In approximately 50% of cases this abnormality is transient and caused by oedema and glandular haemorrhage while the rest is permanent because of the removed parathyroid glands⁷.

His problems seem to originate from his thyroidectomy 20 years ago, at the age of 12. The indication for this is not known. It is unlikely that he was thyrotoxic or had thyroid malignancy, as he was not aware of these diagnoses, so we speculate that it was done for treatment of goiter. There is no conclusive local data for the national prevalence of childhood and adult endemic or other causes of goiter, but iodine deficiency may cause childhood endemic goiter especially in people living in mountainous areas and not using iodised salt. This patient comes from a mountainous district, and although iodised salt use is widely used in Malawi these days we are not sure if it was the same 20 years ago.

His neuromuscular problems on presentation were complex. Hypocalcaemia can cause neuromuscular excitability, indicated by parasthesia, tetany, positive Chvostek and Trousseau's signs, and in the most extreme cases, seizures, as in this case. In addition he had muscular complications of hypothyroidism including weakness and poor muscle tone. We also suspect that, although he did not have typical Parkinsonism, he had involuntary movements due to the basal ganglia calcification.

The patient also had renal impairment which normalized on subsequent tests which may have exacerbated the high phosphorus and low calcium and may be the reason he developed symptomatic hypocalcaemia at this time, having been asymptomatic for 20 years. He was treated with calcium/vitamin D supplements and thyroxine. Ideally activated Vitamin D (1,25-hydroxylated) should be used, because of its greater potency, however, it was not available so he was given the 25-hydroxylated form only.

One month after starting treatment, all the neurological and neuromuscular abnormalities had disappeared, his facial oedema and pallor had improved and his voice was normal. He continues to attend the medical department for review and repeat prescriptions- his thyroxine, calcium and vitamin D supplements will be life-long. He is yet to finish tuberculosis treatment and will start anti-retroviral therapy in March this year (2008).

Final diagnoses

• TB pericarditis (presumed)

• Hypothyroidism - post thyroidectomy

• Hypocalcaemia, hyperphosphataemia, and basal ganglia calcification- due to hypoparathyroidism

• Normochromic anaemia- multiple possible contributory factors

• Mild intercurrent renal impairment

• HIV infection: WHO clinical stage IV (Extra-pulmonary tuberculosis and oesophageal candidiasis), AIDS

Like many of the patients we see on the medical wards this patient presented with opportunistic infection (Tuberculosis) in the context of HIV. It was only after thorough clinical assessment he was found to have other serious and potentially life threatening diagnoses; hypothyroidism and hypoparathyroidism.

This case highlights the value of taking a detailed history for more accurate diagnosis at first patient's review. It also illustrates how treatment of one problem can lead to the development of another problem. Where it is difficult to follow patients up long term, or to monitor patients for the development of metabolic and endocrine problems, thyroidectomy should only be undertaken where there is a strong indication and care should be taken not to remove all of the thyroid gland or the parathyroid glands to minimize the risk of these postoperative complications.