We report a rare case of an elderly lady who presented with severe dementia (mini-mental score of 8/30), with dramatic improvement, following replacement of thyroid hormone. Mini-mental score of 30/30 on discharge.

The History

A 65 year old female, was sent by her G.P with one week history of cough, wheeze, visual hallucinations and increasing confusion.. She reported seeing objects on her body and floor. She had a past medical history of controlled Atrial fibrillation, impaired renal function, mild cognitive impairment, hypertension and coronary artery bypass graft. She was on Risperidone 0.5 mg daily, Quetiapine 25 mg, Digoxin 0.125 mg daily, Clopidrogil 75 mg daily, Warfarin, Pravastatin 40 mg daily, Donepezil 10 mg and Sertraline 100 mg.

She was comfortable at rest and her vital signs were stable. Examinations, showed wheeze and scattered crepitations in the mid and lower zone of the right lung. Pulse 55 irregular, normal JVP, heart sounds and no peripheral oedema. She was disoriented in time, place, with mini-mental state examination score of 8 /30.

She had ECG, chest X-ray and urinalysis in casualty and all were normal, apart from Atrial fibrillation with a heart rate of 55/minute. Full blood count, urea & electrolytes, inflammatory markers, B12, folate and liver function test were all normal.

An initial diagnosis of lower respiratory tract infection and medication induced hallucinations was made. She was started on antibiotic, Sertraline and Resperidone were withheld. But the hallucinations persisted .She had episodes of laughing and uncontrolled crying. She also had episodes of confusion and agitation and physically hitting family members. There were moments when she was lucid. Her speech remained clear. She was mobile but unsteady with broad-based gait. According to family, she was a quiet and shy person, there was no history of weight gain or loss and no history of constipation. She had bradycardia but we felt that could be related to the B blocker. We stopped the drug but she remained bradycardic. She had CT Brain, which was normal.

Over the next five days she continued to deteriorate and became sleepier and developed mild facial puffiness .At this stage, a Thyroid function test (TFT) was ordered. We routinely do TFT in this hospital for dementia screen but because she had a previous history of dementia, this was not done. Thyroid function test showed TSH of more than 100 (0.35-5.5), free T4 of 3.3 (11.5-23.) The treatment plan was discussed with the Endocrinologist, following which, the patient was started on intravenous triiodthyronine, intravenous hydrocortisone and oral Levothyroxine.As she has history of heart disease, the dose of oral Levothyroxine was started slowly and gradually increased. In the next five days, the patient showed dramatic response to thyroid hormone with improvement in all symptoms.

The confusion, agitation and hallucination all disappeared. We stopped her Donipezil, as we feel that she may have been suffering from hypothyroid for some time which may have been misdiagnosed as dementia. She was discharged after two weeks of treatment. The T3 was stopped and oral Levothyroxine was continued. Her mini-mental score was 30/30 on discharge. We will review her in the OPD and intend to repeat her TFT in four weeks.

Discussion:

Hypothyroidism is a clinical disease that is characterized by decreased thyroxin production. The prevalence of hypothyroidism increases with age, ranging from 0.5% to 6% for overt hypothyroidism and from 4- 15% for sub-clinical hypothyroidism. It is more frequent in elderly Caucasian women, and is more commonly observed in hospitalised, as compared to free-living, subjects.

Causes:
The most common cause is autoimmune thyroid disease. Treatment of Grave's disease is another common cause of hypothyroidism in the elderly population. Iodine-containing drugs such as radiographic contrast agents and the anti-arrhythmic amiodarone may precipitate the development of hypothyroidism. Similarly recombinant interleukin-2A16 and recombinant interferon-alpha17 may precipitate hypothyroidism especially in patients with underlying autoimmune thyroiditis. A significant number of patients receiving long-term lithium therapy develop an elevation of TSH, a response to the inhibition of thyroid hormone release by this drug, and some develop overt hypothyroidism. Hypothyroidism caused by pituitary or hypothalamic disease is very rare and is usually the result of tumours or surgery

Effect of age on the thyroid gland:
As a person ages, the structure of the thyroid gland changes. Some studies have shown an increase and others a decrease in the size of the gland with aging. This discrepancy is probably related to dietary iodine intake. At the same time, however, there is a decrease in the number and size of the follicles as well as in colloid content. Histopathologic examination shows lymphocytic infiltration and fibrosis of the connective tissue. The gland also becomes increasingly nodular with age.

In spite of these structural changes, results of thyroid function tests are normal in most patients. Serum levels of free thyroxin (T4) remain constant with aging, because a decline in production is offset by slower metabolism. Although initial studies in heterogeneous populations suggested a decline in triiodothyronine (T3) levels with aging, later studies in selected healthy persons showed that the levels are unaffected. Thyrotropin (i.e.TSH) levels typically remain normal, except for a mild decrease in extreme senescence (i.e. octogenarians). A blunting of diurnal variation in thyrotropin levels and the thyrotropin response to thyrotropin-releasing hormone may occur, especially in elderly men, but this effect is rarely clinically significant. Some studies also have shown an elevation in thyroid auto antibodies with aging, but the increase seems to be the effect of age-associated disease rather than aging per se.

Symptoms and signs of hypothyroidism in elderly:

Older patients had fewer symptoms, and some of the classic signs (e.g. cold intolerance, weight gain) were often absent. Moreover, the common clinical features of hypothyroidism (e.g. fatigue, constipation, cognitive loss) are often attributed to normal aging. These factors, along with the fact that hypothyroidism has an insidious onset and affects multiple organ systems, may cause considerable delay and difficulty in diagnosis. Therefore, it is important to have a high index of suspicion and a low threshold for screening for thyroid dysfunction in elderly patients who present with vague, non-specific symptoms.

Atypical signs and symptoms in elderly patients:
Confusion
Behavioural changes
Macrocytic anaemia
Peripheral neuropathy
Dementia-like behaviour
Memory impairment
Myopathy
Depressed affect
Muscle weakness

Diagnosis:

The single best diagnostic test for primary hypothyroidism is an increased serum thyroid stimulating hormone concentration, but, compared to young hypothyroid patients, old individuals with primary hypothyroidism may have significantly lower basal serum thyroid-stimulating hormone levels. Test for anti-thyroid antibody help to identify patients with autoimmune thyroiditis, but don't provide direct information on thyroid function and an hypo-echogenic pattern of the thyroid by ultra-sonography helps in identifying auto-immune thyroiditis.

Myxoedema coma:

Is defined as severe hypothyroidism leading to decreased mental status, hypothermia, and other symptoms. It is a medical emergency with a high mortality rate. Fortunately, it is now a rare presentation of hypothyroidism, probably because of earlier diagnosis. The demographics of patients who develop myxoedema coma are those of hypothyroidism in general, with older women being most often affected. Myxoedema coma can result from any of the usual causes of hypothyroidism, particularly chronic autoimmune thyroiditis, because of its often-insidious course compared with post-surgical or -ablative hypothyroidism. It can occur in patients with secondary hypothyroidism, and there are case reports of its occurrence in patients with lithium- or amiodarone-induced hypothyroidism.

The hallmarks of myxoedema coma are decreased mental status and hypothermia, but hypotension, bradycardia, hyponatremia, hypoglycaemia, and hypoventilation are often present as well. The possibility of a precipitating infection or other acute illness should always be considered; it is important to appreciate, however, that the patient may not have a febrile response to infection.

Despite the name, myxoedema coma, patients frequently do not present in coma, but do manifest lesser degrees of altered consciousness. This usually takes the form of confusion with lethargy and obtundation. Alternatively, a more activated presentation may occur with prominent psychotic features, so-called myxoedema madness. Untreated, patients will progress to coma.

Treatment:

The goal of therapy is restoration of the euthyroid state, which can be readily accomplished in almost all patients by oral administration of synthetic thyroxin (T4). However, some patients may benefit from a combination of T4 and T3. The average daily replacement dose of L-Thyroxin (L-T4) in adults is 1.6 mcg/kg, but elderly hypothyroid patients require a dose of 20-30% lower, and they display a narrow therapeutic range and require close monitoring of serum thyroid stimulating hormone to avoid over-treatment. It is important to "start low and go slow," because the half-life of circulating levels of T4 increases with age.

L-T4 therapy should be initiated with a dose of 12.5-25 mcg/day, followed by careful increments of 12.5-25 mcg/day every 4-8 weeks, to reach the full replacement dose in several months. Particular attention should be paid in patients with co-existent or suspected cardiac disease, since L-T4 substitution may precipitate angina or myocardial infarction. On the other hand, L-T4 substitution ameliorates reversible hypothyroid heart dysfunction and produces beneficial effects on hyperlipidaemia.

Myxoedema coma - Patients with myxoedema coma should be treated aggressively, because the mortality rate approaches 80 percent. If the diagnosis is suspected, a blood sample should be drawn for measurement of serum T4, TSH, and cortisol before therapy with a glucocorticoid and thyroid hormone, which are then given immediately, before laboratory confirmation of the diagnosis. The serum T4 concentration is usually very low.

The serum TSH concentration may be high, indicating primary hypothyroidism, or low, normal, or slightly high, indicating central hypothyroidism.

Whether patients with myxoedema coma should be treated with T4 or T3, or both, is controversial. Some experts favour administration of T3, while others favour T4, preferring that T3 production be governed by the activity of 5'-deiodinase in the patient. What is important is that a substantial dose of thyroid hormone be given, even though there may be some risk of precipitating a cardiac arrhythmia or myocardial infarction.

Combined therapy is recommend in most patients. An initial dose of 200 to 300 mcg T4 intravenously, depending upon body weight, followed by daily intravenous doses of 50 to 100 mcg until the patient can take T4 orally. T3 is given intravenously at the same time; the initial dose is 5 to 20 mcg, followed by 2.5 to 10 mcg every eight hours depending upon the patient's age and coexisting cardiovascular disease. T3 is continued if there is clinical improvement and the patient is stable.

Supportive measures are extremely important, including mechanical ventilation, appropriate fluid replacement, and correction of hyponatremia and hypothermia. In addition, there is often an associated illness that must be treated, such as infection, or gastrointestinal bleeding. Until coexisting adrenal insufficiency can be excluded, the patient should be given high-dose glucocorticoid therapy (hydrocortisone 100 mg intravenously every eight to twelve hours for two days, then lower doses).