Tutorial 1 Pituitary & Thyroid Disorders 1

Case 1 : James is a 5 –year- old child. He is much smaller than his classmates at school. His growth rate has been monitored and has clearly dropped off markedly in the past year. He is an active. On examination he has normal body proportions. His mother and father are of average height. His bone age is that of a 3- year- old child. What biochemical tests would be appropriate in the investigation of this boy? 2

Answer of case 1: Growth hormone deficiency should be suspected particularly in view of the documented fall-off in the patient’s growth rate over the previous year. Random growth hormone measurement is potentially misleading i.e. false positive and false negative results are frequent. Thus, many endocrinologists measure the following : 1- Exercise- stimulated GH where a result > than 20 mU/l excludes GH deficiency. 2- Also, Clonidine,a potent stimulant of GH secretion can be diagnostic. 3- Response of GH to insulin-induced hypoglycemia can also be used but it has been abandoned by some centers as a diagnostic test for children because of its hazards. 3

Case 2 : A 36 year old man complained of impaired vision while driving, particularly at night. After clinical and initial biochemical assessment, a combined anterior pituitary stimulation test was performed. ( i.v. insulin 0.1 U/Kg, TRH :200 µg, GnRH: 100 µg ) LH U/l Prolactin mU/l GHCortisol nmol/l Glucose mmol/l Time (min) < Reference values fasting glucose 2.8 – 6.0 mmol/l. Cortisol at morning:140 – 690 nmol/l at night : < than 100 nmol/l Growth hormone following glucose: < than 2 mU/l. following stress: > than 20 mU/l. Prolactin mU/l. LH adult male:2 – 10 U/l

2-What is the most likely diagnosis ? 1-A lower than normal dose of insulin was used. Why ? 3-What precautions should be taken before surgery? Questions: 5

Answer of case 2: 1- If hypopituitarism is suspected, a lower dose of insulin should be used. This is because the relative deficiency of glucocorticoids and growth hormone are associated with an increase in insulin sensitivity. 2- The basal prolactin was so high in the case that hyperprolactinoma was the diagnosis until proven otherwise. Also, imaging of the pituitary confirmed the diagnosis. 6

3- The hypoglycemic stress induced in the patient did not cause the expected rise in serum cortisol (it should rise to more than 500 nmol/l in response to insulin stress test) therefore, it is essential that he is commenced on steroid replacement before surgery. 4- As hyperprolactinaemia frequently shrink dramatically in response to dopamine agonists, he should be commenced preoperatively on bromocriptine to reduce the size of the tumor. 7

Case 3 : A 49-year-old woman receiving hormone replacement therapy was found to have a thyroid nodule. No lymphadenopathy was detectable and clinically she appeared to be euthyroid. A technetium scan revealed a cold nodule and an ultrasound scan indicated it was cystic. Biochemistry results in a serum specimen: Reference range: nmol/l. 172T4 (nmol/l) Reference range: 0.3 – 5.0 mU/l. 0.4TSH (mU/l) 8

Questions: 1- Explain why the T4 is elevated ? 2- What other investigations should be performed on this patient ? 9

Answer of case 3: 1- This patient has a high serum T4 because of the estrogen component of hormone replacement therapy stimulates the synthesis of thyroxine-binding globulin. 2- By far the most important investigation for this woman is a fine needle aspiration biopsy of the thyroid nodule. It is important that thyroid epithelium is obtained to enable the diagnosis of thyroid cancer to be excluded or confirmed. 10

Case 4 : Investigation of a 63-year-old woman with effort angina revealed a serum TSH of 96 mU/L (normal=0.3 – 5.0 mU/l) and a serum free T4 of 3.7 pmol/L (normal pmol/l). An ECG showed some evidence of ischemia but was not diagnostic of myocardial infarction. Further biochemical investigation revealed : Reference ranges: < than 5 mmol/L.9.3 Cholesterol (mmol/L) < than 90 U/L.290Creatine kinase (U/L) 10 – 40 U/L35AST (U/L) How should these results be interpreted ? 11

Answer of case 4: 1- The low free T4 and markedly elevated TSH results suggest Primary Hypothyroidism. Skeletal and Cardiac muscles are affected in hypothyroidism causing the release of creatine kinase into the circulation. This, combined with a decrease in the catabolic rate of creatine kinase,will be sufficient to cause the creatine kinase to increase to the levels observed in this case. 2- The AST is at the upper limit of the normal reference and this will fall along with creatine kinase and cholesterol after a few weeks of treatment with thyroxine. 12

Case 5 : A 28-year-old woman with thyrotoxicosis has had two courses of carbimazole. Results from her recent visit to the thyroid clinic now show: Reference range < 0.05TSH (mU/L) Reference range T4 (nmol/L) Reference range free T4 (pmol/l) 1- What has happened ? 2- What other biochemistry tests might be useful here ? 13

Answer of case 5: It is likely that this patient has suffered a relapse of her thyrotoxicosis. The severity of the derangement in her thyroid biochemistry (free T4 : 66 pmol/l) makes it likely that she will be clinically thyrotoxic and symptomatic. Repeated failure of medical therapy may allow us to think of alternative treatment such as radioactive iodine and surgery. N.B. : Radioactive iodine ablates the production of thyroid hormone irreversibly and the patient would need to take replacement thyroxine therapy permanently thereafter. 14