Primary Hyperthyroidism / Grave’s Disease and Thyroid Gland Enlargement

2. A 40 years old women complained of heat intolerance, excessive sweating,  palpitations, unintentional weight loss despite increased appetite and occasional diarrhoea. On examination , a diffuse enlargement of the thyroid gland and protruding eye balls were noted. Laboratory investigations showed an elevated free plasma thyroxine(T4) undundetectable plasma TSH level with elevated serum TSH receptor antibodies.  

2.1 State the most likely diagnosis of this patient.                                (20 marks)     
2.2 State the reason for.                                                      
2.2.1 Unintentional weight loss.  (15 marks )    
2.2.2.excessive sweating   (15 marks) 
2.3. Explain the physiological basis for enlargement of thyroid gland and hormone levels  in this patient.           

Answers:-

2
2.1  Primary hyperthyroidism / Grave’s disease

2.2

2.2.1  In primary hyperthyroidism there is increased secretion of thryroid hormones – thyroxine (T4) and triiodothyronine (T3) from the thyroid grand. Thyroxine has an action in increasing the basal metabolic rate (BMR) of the body. This occurs by increased production of ATP from food to meet energy demands, by increasing number and size of mitochondria and increasing membrane bound Na+K+ATPase activity. The increased energy demand is due to an overall increase in metabolic functions throughout the body. To meet this energy demand there is increased glucose uptake and glysolysis and gluconeogenesis using stored energy. Thyroxine also increases LDL receptors in liver cells leading to increased cholesterol removal from blood and loss in bile. There is also reduction in blood phospholipids and triglyderides. This increased BMR and utilisation of carbohydrates and fats (and proteins when there is very high thyroid hormone levels) leads to weight loss.

2.2.2  In hyperthryroidism there is an increase in the BMR due to increased metabolic activity in the body and increased Na+K+ATPase activity. This leads to increased production of heat in the body so in order to remove this heat from the body there is increased sweating from the skin. Also due to the anabolic effect of thyroid hormones leading to increased protein synthesis there can be hypertrophy of sweat glands further contributing to the excessive sweating.

 2.3  Grave’s disease is an autoimmune disease where there are antibodies produced in the body called Thyroid stimulating immunoglobins (TSI) which bind to the thyroid stimulating hormone (TSH) receptors on the thyroid gland and mimic the TSH activity which involves,

 Increasing all steps of thyroid hormone production
 Increasing thyroglobin breakdown and release of stored thyroid hormone
 Increasing cell size, number and activity The resulting hypertrophy of the thyroid gland leads to increasing size of the gland which is a condition known as goitre.

The Thyroid hormone production is usually under a hypothalamo-pitutary-thyroid axis. The hypothalamus secretes thyroid releasing hormone (TRH) which acts on the anterior pituitary and stimulates it to secrete TSH which travels through blood and acts on the thyroid gland and stimulates the above mentioned activities which leads to secretion of thyroid hormones. Then the secreted thyroid hormones of which about 93% is T4 has a negative feedback effect on the anterior pituitary and hypothalamus and reduces secretion of TRH and TSH. Here there is high T4 levels due to the TSI stimulation on the thyroid gland. The increased T4 levels has a very high negative feedback effect on the anterior pituitary greatly reducing the TSH secretion. The TSH receptor antibodies are the TSI produces due to the Grave’s autoimmune disease.