ENDOC- HYPOTHYROID Flashcards
_____________ is caused by any structural or functional derangement that interferes with the
production of adequate levels of thyroid hormone.
Hypothyroidism
Hypothyroidism is a fairly common disorder,
and by some estimates the population prevalence of overt hypothyroidism is 0.3%, while
subclinical hypothyroidism can be found in greater than 4%. [7]
The prevalence of
hypothyroidism increases with age, and it is nearly tenfold more common in____________
It can result from a defect anywhere in the hypothalamic-pituitary-thyroid axis.
As in the case of
hyperthyroidism, this disorder is divided into primary and secondary categories, depending on
whether the hypothyroidism arises from an intrinsic abnormality in the thyroid itself, or occurs as
a result of pituitary and hypothalamic disease ( Table 24-4 ).
women than in men.
_____________ accounts
for the vast majority of cases of hypothyroidism, and can be accompanied by an enlargement in
the size of the thyroid gland (goiter).
Primary hypothyroidism
Note :Primary hypothyroidism can be congenital, acquired, or
autoimmune
Causes of Hypothyroidism
- Primary
- secondary (central)
Primary Hypothyroidism
- Developmental (thyroid dysgenesis: PAX8, FOXE1, TSH receptormutations)
- Thyroid hormone resistance syndrome (THRB mutations)
- Postablative
Surgery, radioiodine therapy, or external
irradiation - Autoimmune hypothyroidism
Hashimoto
thyroiditis [*] - Iodine deficiency [*]
- Drugs (lithium, iodides, p-aminosalicylic acid) [*]
- Congenital biosynthetic defect (dyshormonogenetic goiter)
SECONDARY (CENTRAL)
- Pituitary failure
- Hypothalamic failure
- (rare)
** ______________**account for the majority of cases of hypothyroidism in developed
countries.
Hashimoto thyroiditis and
postablative hypothyroidism
Associated with enlargement of thyroid (“goitrous hypothyroidism”).
- thyroiditis [*]
- Iodine deficiency [*]
- Drugs (lithium, iodides, p-aminosalicylic acid) [*]
- Congenital biosynthetic defect (dyshormonogenetic goiter) [*]
Worldwide, ______________is most often the result of endemic iodine deficiency in
the diet (see below).
**congenital hypothyroidism **
Other less common forms of congenital hypothyroidism include , such as
- inborn errors of thyroid metabolism (dyshormonogenetic goiter),
- wherein any one of the multiple steps leading to thyroid hormone synthesis may be deficient
What arthye the steps in thyroid hormone synthesis?
(1) iodide transport into
thyrocytes, (2) iodide “organification” (binding of iodide to tyrosine residues of the storage
protein, thyroglobulin), and (3) iodotyrosine coupling to form hormonally active T3 and T4.
_______________ gene are the most common cause of
dyshormonogenetic goiter.
Mutations in the thyroid peroxidase (TPO)
_____________, characterized by hypothyroidism and
sensorineural deafness
Pendred syndrome
Pendred syndrome is due to:
, is caused by mutations in the SLC26A4 gene, whose product, **pendrin, **is an anion transporter expressed on the apical surface of thyrocytes and in the inner ear.
In rare instances there may be complete absence of thyroid parenchyma (thyroid agenesis), or
the gland may be greatly reduced in size (thyroid hypoplasia).
Germline mutations in transcription factors that are expressed in the developing thyroid and regulate follicular differentiation, such as_______________________, have been reported in individuals with thyroid agenesis.
thyroid transcription factor-2 (TTF-2), also known as FOXE1, and
paired box-8 (PAX-8)
What is the typical presentation of patients wit thryoid agenesis?
These patients
typically present with a constellation of extra-thyroidal malformations.
Inactivating germline
mutations of the_____________ is a rare genetic cause of isolated hypothyroidism (note
that activating somatic mutations of TSHR are found in autonomous thyroid nodules, see
below).
TSH receptor (TSHR)
__________ is a rare autosomal-dominant disorder caused
by inherited mutations in the thyroid hormone receptor, which abolish the ability of the receptor
to bind thyroid hormones.
Patients demonstrate a **generalized resistance to thyroid hormone, **despite high circulating levels of T3 and T4.
Since the pituitary is also resistant to feedback
from thyroid hormones, TSH levels tend to be high as well.
Thyroid hormone resistance syndrome
Acquired hypothyroidism can be caused by____________ ablation of thyroid
parenchyma.
surgical or radiation-induced
A large resection of the gland ___________ for the treatment of hyperthyroidism of a primary neoplasm can lead to hypothyroidism.
(total thyroidectomy)
The gland may also be
ablated by radiation, whether in the form of radioiodine administered for the treatment of
hyperthyroidism, or exogenous irradiation, such as external radiation therapy to the neck.
What are the Drugs given intentionally to decrease thyroid secretion_____________
can cause acquired hypothyroidism, as can agents used to treat nonthyroid conditions (e.g.,
lithium, p-aminosalicylic acid).
(e.g., methimazole and propylthiouracil)
________________ is the most common cause of hypothyroidism in iodine-sufficient
areas of the world.
Autoimmune hypothyroidism
The vast majority of cases of autoimmune hypothyroidism are due to
_____________.
Hashimoto thyroiditis
Circulating autoantibodies, including\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_,are found in this disorder, and the **thyroid is typically enlarged (goitrous).**
anti-microsomal, anti-thyroid
peroxidase, and anti-thyroglobulin antibodies,
Autoimmune hypothyroidism can occur in isolation or in
conjunction with _________________** (**see discussion in
“Adrenal Glands”).
autoimmune polyendocrine syndrome (APS), types 1 and 2
Secondary (or central) hypothyroidism is caused by___________________
NOTE :Necrosis, trauma, and nonpituitary tumors), or of hypothalamic damage
from tumors, trauma, radiation therapy, or infiltrative diseases can cause central
hypothyroidism
deficiency of TSH, and far more
uncommonly, that of TRH.
Classic clinical manifestations of hypothyroidism include_________ and ________.
cretinism and myxedema.
_______________ refers to hypothyroidism that develops in infancy or early childhood.
Cretinism
TRIVIA: The term cretin
was derived from the French chrétien, meaning “Christian” or “Christlike,” and was applied to
these unfortunates because they were considered to be so mentally retarded as to be
incapable of sinning.
In the past this disorder occurred fairly commonly in areas of the world where dietary iodine deficiency is endemic, such as the Himalayas, inland China, Africa, and
other mountainous areas.
It has become much less frequent in recent years, as a result of the
widespread supplementation of foods with iodine. On rare occasions, cretinism may also result
from inborn errors in metabolismthatinterfere with the biosynthesis of normal levels of thyroid
hormone (dyshormonogenetic goiter, see above)
What are the clinical features of Cretinism?
Clinical features of cretinism include:
- impaired development of the skeletal system and central nervous system, manifested by:
- severe mental retardation,
- short stature,
- coarse facial features,
- a protruding tongue,
- **and umbilical hernia. **
The severity of the mental impairment in cretinism
seems to be related to the_______________.
time at which thyroid deficiency occurs in utero
Normally, maternal
hormones, including T3 and T4, cross the placenta and are critical to fetal brain development.
If
there is maternal thyroid deficiency before the development of the fetal thyroid gland, mental
retardation is severe. In contrast, reduction in maternal thyroid hormones later in pregnancy,after the fetal thyroid has developed, allows normal brain development.
The term____________ is applied to hypothyroidism developing in the older child or adult.
myxedema
_________________was first linked with thyroid dysfunction in 1873 by Sir William Gull
in an article addressing the development of a “cretinoid state” in adults.
Myxedema, or Gull disease,
In myxedeme the clinical
manifestations vary with the age of onset of the deficiency.
The older child shows signs and
symptoms intermediate between those of the cretin and those of the adult with hypothyroidism.
In the adult the condition appears insidiously and may take years to reach the level of clinical
suspicion.
