Question

Case 2 Hypothyroidism: Autoimmune Thyroiditis
Shirley Tai is a 43-year-old elementary school teacher. At her annual checkup, Shirley complained that,
despite eating less, she had gained 16 lb. in the past year. Her physician might have attributed this
weight gain to “getting older” except that Shirley also complained that she has very little energy, always
feels cold (when everyone else is hot), is constipated, and has heavy menstrual flow every month. In
addition, the physician noticed that Shirley’s neck was very full. The physician suspected that Shirley
had hypothyroidism and ordered laboratory tests (Table 2).
Table 2 Shirley Tai’s Laboratory Values and Test Results
T 4 3.1 ug/dL (normal 5-12 ug/dL)
TSH 85 mU/L (normal, 1.3 – 5 mU/L)
T 3 resin uptake Decreased
Thyroid antimicrosomal antibodies Increased
Based on the physical findings and laboratory results, Shirley’s physician concluded that Shirley had
autoimmune (Hashimoto) thyroiditis and prescribed oral administration of synthetic T 4 (L-thyroxine).
The physician planned to determine the correct dosage of T 4 by monitoring the TSH level in Shirley’s
blood.
Questions
1. Sketch the diagram for the regulation of thyroid hormone secretion by the hypothalamic –
anterior pituitary – thyroid axis. List the two potential mechanisms that could result in
decreased secretion of thyroid hormones and indicate where the problem for each lies on the
diagram. How might you distinguish between these mechanisms as potential causes for
Shirley’s hypothyroidism

Answer 1

Answer :- The hypothalamus secretes a tripeptide [thyrotropin-releasing hormone (TRH)that stimulates the thyrotrophs of the anterior pituitary to secrete TSH. TSH (a
glycoprotein) circulates to the thyroid gland, where it has two actions.

(1) It increases the synthesis and secretion of thyroid hormones (T4 and T,) by stimulating each step in the biosynthetic process.

(2) It causes hypertrophy and hyperplasia of the thyroid gland.
The system is regulated primarily through negative feedback effects of thyroid hormone on
TSH secretion. Specifically, T3 down-regulates TRH receptors on the thyrotrophs of the anterior
pituitary, decreasing their responsiveness to TRH. Thus, when thyroid hormone levels are
increased, TSH secretion is inhibited. Conversely, when thyroid hormone levels are decreased,
TSH secretion is stimulated.
Three potential mechanisms for decreased thyroid hor-
mone secretion:

(1) primary failure of the hypothalamus to secrete TRH, which would decrease
TSH secretion by the anterior pituitary;

(2) primary failure of the anterior pituitary to secrete TSH; and

(3) a primary defect in the thyroid gland itself (e.g., autoimmune destruction or
removal of the thyroid).
The three mechanisms that cause hypothyroidism are not distinguishable by their effects on
circulating thyroid hormone levels or by their symptoms. In each case, circulating levels of T3
and T4 are decreased, and symptoms of hypothyroidism occur. However, the mechanisms are
distinguishable by the circulating levels of TRH and TSH. In hypothalamic failure (very rare),
secretion of both TRH and TSH is decreased, leading to decreased secretion of thyroid hormones.
In anterior pituitary failure, secretion of TSH is decreased, leading to decreased secretion of
thyroid hormones. In primary failure of the thyroid gland (most common), secretion of thy-
roid hormones is decreased, but secretion of TSH by the anterior pituitary is increased. In this
scenario, the anterior pituitary gland is normal; TSH secretion is increased because of dimin-
ished feedback inhibition by thyroid hormones.
Thus, the most common cause of hypothyroidism (a primary defect in the thyroid gland) is
clearly distinguishable from the second most common cause (a defect in the anterior pituitary) by
their respective TSH levels. If the defect is in the anterior pituitary, TSH levels are decreased; if the
defect is in the thyroid, TSH levels are increased.