hyperthyroidism. Patients with Graves’ disease produce autoantibodies to
TSH receptors. CD8+-T cells are also generated against the TSH receptors,
leading to their destruction. The result is an increase in TSH produced by
the anterior pituitary with a concomitant increase in thyroid hormone pro-
duction [T4 (tetraiodothyronine, thyroxine) and T3 (tetraiodothyronine)]
from the thyroid. The elevated thyroid hormone secretion leads to the ner-
vousness, weight loss, and extreme mood changes experienced by the
patient.
The thyroid gland is shown in the photomicrograph and is most often
confused histologically with lactating mammary gland, which differs from
the thyroid in the presence of an elaborate duct system. The thyroid is
composed of follicles filled with colloidal material and surrounded by fol-
licular cells with a cuboidal-to-columnar epithelium. The C cells are found
outside the follicular cells and produce calcitonin, synthesized by the inter-
follicular “C” (parafollicular) cells derived embryologically from the ulti-
mobranchial bodies (fourth and possibly fifth pair of branchial pouches).
Calcitonin decreases elevated serum calcium levels by transiently inhibit-
ing osteoclastic activity through receptors on osteoclasts. In Graves’ disease
there are no autoantibodies to the C cells (answer a).Destruction of C cells
would lead to an absence of calcitonin and high serum calcium levels.
Autoantibodies to principal cells of the parathyroid (answer b)would lead
to decreased serum calcium levels as parathyroid hormone (PTH) synthe-
sis and secretion would be reduced. PTH increases osteoclastic resorption
and also stimulates Ca^2 +uptake from the gut and Ca^2 +reabsorption by
the kidneys. The thyroid gland is under the direct regulation of TSH
(thyrotropin) production by the anterior pituitary, which in turn is regu-
lated by TSH-releasing factor (TSH-RF) released from the hypothalamus.
TSH-RF is transported by the hypothalamic-hypophyseal (pituitary)-portal
system to the anterior pituitary. Autoantibodies to TSH-RF (answer c)
would result in elevated TSH and T3 and T4, but the receptors would be
located in the anterior pituitary on thyrotrophs. Autoantibodies to thy-
roglobulin and thyroid peroxidase result in Hashimoto’s thyroiditis
[answer d(see question 233)].
Asthenia is loss of strength and tachycardia is accelerated heart rate.
Pretibial myxedema presents as an orange-peel-like rash on the shins in
some patients with Graves’ disease.
The thyroid follicular epithelial cells import iodide and amino acids
from the capillary lumen. The follicular cells synthesize thyroglobulin from
352 Anatomy, Histology, and Cell Biology