Endocrine System

Dr. I Made Naris Pujawan, M.Biomed, Sp.PA

Endocrine System
 The endocrine system is highly integrated that orchestrate a state of
metabolic equilibrium or homeostasis among the various tissue of the body
 Signaling can be classified as :
 Autocrine
 Paracrine
 Endocrine

 An endocrine hormone is carried by the blood from its site of release and
release to itd targer  feed back inhibition
 Endocrine disease can be classified as :
 Underproduction or overproduction
 Mass lesions
Pituitary
 Hyperpituitarism:
 Arising from excess secretion of trophic hormones
 The causes of hyperpituitarism include pituitary adenoma, hyperplasia and
carcinomas of the anterior pituitary, secretion of hormones by nonpituitary
tumors, and certain hypothalamic disorders
 Hypopituitarism:
 Arising from deficiency of trophic hormones
 This may be caused by destructive processes, including ischemic injury,
surgery or radiation, inflammatory reactions, and nonfunctional pituitary
adenomas

 Local mass effects

 Diseases of the posterior pituitary often come to clinical attention
because of increased or decreased secretion of ADH.
THYROID GLAND
 The thyroid gland consists of two
bulky lateral lobes connected by
a relatively thin isthmus, usually
located below and anterior to
the larynx
 The thyroid is divided by thin fibrous
septae into lobules composed of
about 20 to 40 evenly dispersed
follicles, lined by a cuboidal to low
columnar epithelium, and filled
with PAS-positive thyroglobulin
Hyperthyroidism
 Thyrotoxicosis is a hypermetabolic state caused by elevated
circulating levels of free T3 and T4
 Because it is caused most commonly by hyperfunction of the
thyroid gland, it is often referred to as hyperthyroidism
 The three most common causes of thyrotoxicosis are also
associated with hyperfunction of the gland and include the
following
 Diffuse hyperplasia of the thyroid associated with Graves
disease (accounts for 85% of cases)
 Hyperfunctional multinodular goiter
 Hyperfunctional adenoma of the thyroid
The clinical manifestations of hyperthyroidism are protean and include
changes referable to the hypermetabolic state induced by excess thyroid
hormone and to overactivity of the sympathetic nervous system (i.e., an
increase in the β-adrenergic “tone”)

Excessive levels of thyroid

hormone result in an increase
in the basal metabolic rate
 Thyroid storm is used to designate the abrupt onset of severe
hyperthyroidism
 This condition occurs most commonly in patients with underlying
Graves disease and probably results from an acute elevation in
catecholamine levels, as might be encountered during infection,
surgery, cessation of antithyroid medication, or any form of stress
 Patients are often febrile and present with tachycardia out of
proportion to the fever
 Thyroid storm is a medical emergency: A significant number of
untreated patients die of cardiac arrhythmias
 A diagnosis of hyperthyroidism is made using both clinical and
laboratory findings
Hypothyroidism
 Hypothyroidism is caused by any structural or functional derangement that
interferes with the production of adequate levels of thyroid hormone
 Cretinism refers to hypothyroidism that develops in infancy or early
childhood
 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 term myxedema is applied to hypothyroidism developing in the older
child or adult
 Clinical features of myxedema are characterized by a slowing of physical
and mental activity. The initial symptoms include generalized fatigue,
apathy, and mental sluggishness, which may mimic depression in the early
stages of the disease
Thyroiditis
 Thyroiditis, or inflammation of the thyroid gland, encompasses a diverse group of
disorders characterized by some form of thyroid inflammation
 Whatever the cause, the inflammatory involvement may cause sudden onset of neck
pain and tenderness in the area of the gland and is accompanied by fever, chills, and
other signs of infection
 Thyroid function is usually not significantly affected, and there are few residual
effects except for possible small foci of scarring
 This section focuses on the more common and clinically significant types of thyroiditis:
 Hashimoto thyroiditis,
 Granulomatous (de Quervain) thyroiditis
 Subacute lymphocytic thyroiditis
HASHIMOTO THYROIDITIS
 The name Hashimoto thyroiditis is derived from the 1912 report
by Hashimoto describing patients with goiter and intense
lymphocytic infiltration of the thyroid (struma lymphomatosa)
 Hashimoto thyroiditis is characterized by gradual thyroid failure
because of autoimmune destruction of the thyroid gland
 This disorder is most prevalent between 45 and 65 years of age and
is more common in women than in men, with a female
predominance of 10 : 1 to 20 : 1
 Increased susceptibility to Hashimoto thyroiditis is associated with
polymorphisms in multiple immune regulation–associated genes,
the most significant of which is the linkage to cytotoxic T
lymphocyte–associated antigen-4 (CTLA4) polymorphisms
Graves Disease
 Graves disease is the most common cause of endogenous
hyperthyroidism
 It is characterized by a triad of clinical findings
 Hyperthyroidism due to diffuse, hyperfunctional enlargement of
the thyroid
 Infiltrative ophthalmopathy with resultant exophthalmos
 Localized, infiltrative dermopathy, sometimes called pretibial
myxedema, which is present in a minority of patients
 Graves disease has a peak incidence between 20 and 40 years of age
 Women are affected as much as 10 times more frequently than men
Pathogenesis
 Graves disease is characterized by a breakdown in self-
tolerance to thyroid auto-antigens, most importantly the
TSH receptor
 Autoimmunity also plays a role in the development of the
infiltrative ophthalmopathy that is characteristic of
Graves disease
 These changes displace the eyeball forward and can
interfere with the function of the extraocular muscles
 Morphology : The thyroid gland is usually symmetrically
enlarged because of diffuse hypertrophy and hyperplasia
of thyroid follicular epithelial cells
Diffuse and Multinodular Goiters
 Enlargement of the thyroid, or goiter, is the most common
manifestation of thyroid disease
 Diffuse and multinodular goiters reflect impaired synthesis of thyroid
hormone, which is most often caused by dietary iodine deficiency.
Impairment of thyroid hormone synthesis leads to a compensatory rise
in the serum TSH level, which, in turn, causes hypertrophy and
hyperplasia of thyroid follicular cells and, ultimately, gross enlargement
of the thyroid gland
 The compensatory increase in functional mass of the gland is able to
overcome the hormone deficiency, ensuring a euthyroid metabolic state
in most individuals
DIFFUSE NONTOXIC (SIMPLE) GOITER
 Diffuse nontoxic (simple) goiter causes enlargement of the entire gland
without producing nodularity
 Because the enlarged follicles are filled with colloid, the term colloid
goiter has been applied to this condition
 This disorder occurs in both an endemic and a sporadic distribution
 Two phases can be identified in the evolution of diffuse nontoxic goiter:
the hyperplastic phase and the phase of colloid involution
 The vast majority of persons with simple goiters are clinically euthyroid
MULTINODULAR GOITER
 Multinodular goiters produce the most extreme thyroid enlargements
and are more frequently mistaken for neoplastic involvement than any
other form of thyroid disease
 It is believed that multinodular goiters arise because of variations
among follicular cells in their response to external stimuli, such as
trophic hormones
 If some cells in a follicle have a growth advantage, perhaps because
of intrinsic genetic abnormalities similar to those that give rise to
adenomas, those cells can give rise to clones of proliferating cells
 This may result in the formation of a nodule whose continued growth
is autonomous, without the external stimulus
 The dominant clinical features of multinodular goiter are
those caused by the mass effects of the enlarged gland
 Goiters may cause airway obstruction, dysphagia, and
compression of large vessels in the neck and upper thorax
(superior vena cava syndrome)
 substantial minority of patients an autonomous nodule
may develop within a long-standing goiter and produce
hyperthyroidism (toxic multinodular goiter)  Plummer
syndrome
 The incidence of malignancy in long-standing multinodular
goiters is low (<5%) but not zero, and concern for
malignancy arises in goiters that demonstrate sudden
changes in size or symptoms (e.g., hoarseness)
Neoplasms of the Thyroid
 Several clinical criteria provide clues to the nature of a given
thyroid nodule:
 Solitary nodules, in general, are more likely to be neoplastic than are
multiple nodules
 Nodules in younger patients are more likely to be neoplastic than are
those in older patients
 Nodules in males are more likely to be neoplastic than are those in
females
 A history of radiation treatment to the head and neck region is
associated with an increased incidence of thyroid malignancy
 Functional nodules that take up radioactive iodine in imaging studies
(hot nodules) are significantly more likely to be benign than
malignant
 ADENOMAS
 Adenomas of the thyroid are typically discrete, solitary masses, derived from
follicular epithelium, and hence they are also known as follicular adenomas
 Clinically, can be difficult to distinguish from dominant nodules of follicular
hyperplasia or from the less common follicular carcinomas
 Although the vast majority of adenomas are nonfunctional, a small proportion
produces thyroid hormones and causes clinically apparent thyrotoxicosis
 Hormone production in functional adenomas (“toxic adenomas”) is independent of
TSH stimulation and represents another example of thyroid autonomy, analogous
to toxic multinodular goiters
 minority (<20%) of nonfunctioning follicular adenomas have mutations of RAS or
phosphotidylinositol-3-kinase subunit (PIK3CA),[17] or bear a PAX8-PPARG fusion
gene,[18] all of which are genetic alterations shared with follicular carcinomas
CARCINOMAS
 Carcinomas of the thyroid are relatively uncommon in the United States,
accounting for about 1.5% of all cancers
 A female predominance has been noted among patients who develop
thyroid carcinoma in the early and middle adult years
 Most thyroid carcinomas (except medullary carcinomas) are derived from
the thyroid follicular epithelium, and of these, the vast majority are well-
differentiated lesion
 The major subtypes of thyroid carcinoma and their relative frequencies
include the following:
 Papillary carcinoma (>85% of cases)
 Follicular carcinoma (5% to 15% of cases)
 Anaplastic (undifferentiated) carcinoma (<5% of cases)
 Medullary carcinoma (5% of cases)
Pathogenesis
PARATHYROID GLANDS
 The four parathyroid glands are composed mainly of chief cells
 The chief cells vary from light to dark pink with hematoxylin and
eosin stains, depending on their glycogen content
 They are polygonal, 12 to 20 μm in diameter, and have central,
round, uniform nuclei. In addition, they have secretory granules
containing parathyroid hormone (PTH)
 Oxyphil cells and transitional oxyphils are found throughout the
normal parathyroid, either singly or in small clusters
 They are slightly larger than the chief cells, have acidophilic
cytoplasm, and are tightly packed with mitochondria
 The activity of the parathyroid glands is controlled by the level of free (ionized) calcium in
the bloodstream rather than by trophic hormones secreted by the hypothalamus and
pituitary.
 Normally, decreased levels of free calcium stimulate the synthesis and secretion of PTH
 The metabolic functions of PTH in regulating serum calcium levels can be summarized as
follows:
 It increases the renal tubular reabsorption of calcium, thereby conserving free calcium
 It increases the conversion of vitamin D to its active dihydroxy form in the kidneys.
 It increases urinary phosphate excretion, thereby lowering serum phosphate levels
 It augments gastrointestinal calcium absorption

 Similar to the other endocrine organs, abnormalities of the parathyroid glands include both
hyperfunction and hypofunction
 Tumors of the parathyroid glands, in contrast to thyroid tumors, usually come to attention
because of excessive secretion of PTH rather than mass effects.