Common Diseases of the Endocrine System
Objective
 To identify the organs of the Endocrine system
and discuss common surgical diseases
 To review the anatomy and physiology of the
Thyroid, parathyroid and adrenal glands
 To determine the clinical features and pathology
of the common diseases of above endocrine
glands
 To discuss the diagnosis, treatment and surgical
management of these common diseases
The Endocrine System
*The endocrine system is the collection of glands of an
organism that secrete hormones directly into the
circulatory system to be carried towards distant target
organs
Special features of endocrine glands are, in general, their
ductless nature, their vascularity, and commonly the
presence of intracellular vacuoles or granules that store
their hormones
Thyroid Gland
*The adult thyroid gland is brown in color and firm in
consistency, the 2 thyroid lobes are located adjacent to the
thyroid cartilage and connected in the midline by an
isthmus that is located just inferior to the cricoid cartilage.
The normal thyroid gland weighs approx 20gms. A
pyramidal lobe is present in about 50% of pxs.
The superior thyroid arteries arise from the ipsilateral
external carotid arteries and divide into anterior and
posterior branches at the apices of the thyroid lobes. The
inferior thyroid arteries arise from the thyrocervical trunk
shortly after their origin from the subclavian arteries. The
inferior thyroid ateries travel upward in the neck posterior
to the carotid sheath to enter the thyroid lobes at their
midpoint. The thyroidea ima artery arise directly from the
aorta or innominate in 1% to 4% of individuals to enter the
isthmus or replace a missing inferior thyroid artery. The
venous drainage of thyroid gland occurs via multiple surface
veins, which coalesce to form three sets of veins- the
superior, middle and inferior thyroid veins.
Thyroid Histology
*The thyroid is divided into lobules that contain 20 to 40
follicles. There are about 3x106 follicles in the adult male
thyroid gland. Each follicle is lined by cuboidal epithelial
cells and contains a central store of colloid secreted from
the epithelial cells under the influence of the pituitary
hormone TSH. The second group of thyroid secretory cells
is the C cells or parafollicular cells, which contain and
secrete the hormone calcitonin.
Thyroid Physiology
*Iodine Metabolism – in the stomach and jejunum, iodine is
rapidly converted to iodide and absorbed into the
bloodstream and from there it is distributed throughout the
extracellular space. Iodide is actively transported into the
thyroid follicular cells by an ATP dependent process. The
thyroid is the storage site of >90% of the body’s iodine.
Thyroid hormone synthesis, secretion and transport – it
consist of several steps
1. Iodide trapping – involves active transport of
iodide across the basement membrane of the
thyrocyte via an intrinsic membrane protein,
sodium/iodide symporter.
2. Oxidation of iodide to iodine and iodination of
tyrosine residue on THYROGLOBULIN (a large
glycoprotein, which is present in thyroid follicles
and has four tyrosyl residues – to form
monoiodotyrosines (MIT) and diiodotyrosines
(DIT). Both processes are catalyzed by thyroid
peroxidase (TPO)
3. Coupling of two DIT molecule to form 3,5,3’-
triiodothyronine (T3) or 3,3’,5’-triiodothyronine
revese (rT3).
4. Thyroglobulin is hydrolyzed to release free
iodothyronines (T3 and T4) and mono- and
diiodotyrosines.
5. The mono- and diiodotyrosines are diodinated to
yield iodide, which is reused in the thyrocyte
Thyroid Hormone Synthesis
1. Iodide trapping
2. Oxidation of iodide to iodine and iodination of
tyrosine residue on thyroglobulin (MIT) and
diiodotyrosines (DIT)
3. Coupling of two DIT molecule to form 3,5,3’-
triiodothyronine (T3) or 3,3’,5’-triiodothyronine
reverse (rT3).
4. Hydrolysis to Thyroglobulin to release free
iodothyronines (T3 and T4) and mono- and
diiodotyrosines.
5. The mono- and diiodotyrosines are diodinated
to yield iodide
Hypothalamic-Pituitary-Thyroid Axis
*The secretion of thyroid hormone is controlled by the
HYPOTHALAMIC-PITUITARY-THYROID AXIS.
The hypothalamus produces a peptide, the thyrotropin-
releasing hormone (TRH), which stimulate the pituitary to
release TSH or thyrotropin. TRH reaches the pituitary via
the portovenous circulation. TSH mediates iodide trapping,
secretion, and release of thyroid hormones, it also
increase the cellularity and vascularity of the thyroid gland.
TSH secretion by the anterior pituitary is also regulated via
a negative feedback loop by T4 and T3. T3 is thought to be
more important in this feedback control and it inhibits the
release of TRH.
Thyroid hormone function
• Important for fetal brain development and
skeletal maturation
• T3 increases oxygen consumption, basal
metabolic rate, and heat production by
stimulation of Na+/K+ ATPase
• Has positive inotropic and chronotropic effects
on the heart
• Maintains normal hypoxic and hypercapnic drive
in the respiratory center of the brain
• Increase gastrointestinal motility
• Increase bone and protein turnover and the
speed of muscle contraction and relaxation
• Increase glycogenolysis, hepatic
gluconeogenesis, intestinal glucose absorption
and cholesterol synthesis and degradation
I. Hyperthyroidism
The clinical manifestations result from an excess of
circulating thyroid hormone.
*It is important to distinguish disorders that result
from increased production of thyroid hormone from
those disorders that lead to a release of stored
hormone from injury to the thyroid gland or from
other nonthyroid gland-related conditions.
Diffuse Toxic Goiter (Grave’s Disease)
• Most common cause of hyperthyroidism
• Autoimmune disease with a strong familial
predisposition, female preponderance (5:1), and
peak incidence between the age 40 and 60 years
• Characterized by thyrotoxicosis, diffuse goiter
and extrathyroidal conditions including
ophthalmopathy, dermopathy (pretibial
myxedema), thyroid acropachy and
gynecomastia
Etiology:
• Postpartum state, iodine excess, lithium therapy
and bacterial and viral infections are possible
trigger of the autoimmune process
• Genetic factors plays a role, it is associated with
certain human leukocyte antigen (HLA)
haplotypes
• Polymorphisms of the cytotoxic T-lymphocyte
antigen 4(CTLA-4) gene
Pathogenesis:
• sensitized T-helper lymphocytes stimulate B
lymphocytes, which produce antibodies directed
against the thyroid hormone receptor.
• The thyroid-stimulating antibodies stimulate the
thyrocytes to grow and synthesize excess thyroid
hormone, which is a hallmark of Grave’s disease
Pathology
• Macroscopically, the gland is diffusely and
smoothly enlarged, with a concomitant increase
in vascularity.
• Microscopically, the gland is hyperplastic and the
epithelium is columnar with minimal colloid
present
Clinical features
• Hyperthyroidism symptoms:
- heat intolerance
- increased sweating and thirst
- weight loss despite adequate caloric intake
- increased adrenergic stimulation include
palpatations,
nervousness, fatique, emotional lability,
hyperkinesis and tremors
- increased frequency of bowel movement and
diarrhea
- amenorrhea, decreased fertility and increase
miscarriage
*Can be divided into those related to hyperthyroidism and
those specific to Grave’s disease.
Physical examination
- weight loss and facial flushing
- tachycardia or atrial fibrillation
- widening of pulse pressure and a collapse pulse
- fine tremor, muscle wasting, and proximal
muscle group weakness with hyperactive tendon reflex
• 50% of patients with Grave’s Disease also
develop clinically evident ophthalmopathy, and
dermopathy occurs in 1% to 2% of patients
*Eye symptoms include lid lag (Von Grafe’s sign), spasm of
the upper eyelid revealing the sclera above the
(Dalrymple’s sign) and a prominent stare due to
catecholamine excess
True infiltrative eye disease results in periorbital edema,
conjunctival swelling and congestion (chemosis), proptosis,
limitation of upward and lateral gaze, keratitis, and even
blindness due to optic nerve involvement
Etiology is not completely known, however orbital
fibroblast and muscles are thought to share common
antigen, the TSH-R

*Dermopathy is characterized by
deposition of glycosaminoglycans, leading to thickened
skin in the pretibial region and dorsum of the foot
*Gynecomastia is common in young
men
Bony involvement leads to subperiosteal bone formation
and swelling in the metacarpals
Onycholysis, or separation of fingernails from their beds, is
a common finding
Diagnostic test
• Thyroid panel -
- Suppressed TSH with or without an elevated
free T4 or T3 level
• 123I uptake and scan - elevated uptake, with a
diffusely enlarged gland, confirms the diagnosis
• Technetium scintigraphy
• Anti-Tg and anti-TPO antibodies
– elevated in 75%, not specific
• Elevated TSH-R or thyroid
-stimulating antibodies (TSAb) - diagnostic; inc in
90%
*In the absence of eye findings, an 123I uptake and scan
should be performed. An elevated uptake, with a diffusely
enlarged gland, confirms the diagnosis
Treatment
• Antithyroid drugs
Propylthiouracil (PTU 100 to 300mg three times daily)
Methimazole (10 to 30mg three times daily)
- both drugs reduce thyroid hormone production by
inhibiting the organic binding of iodine and the coupling of
iodotyrosines (mediated by TPO)
*May be treated by any of three treatment modalities:
antithyroid drugs, thyroid ablation with radioactive 131I and
thyroidectomy
• Propylthiouracil
- Also inhibits the peripheral conversion of T4 to
T3
- Lower risk of transplacental transfer
• Methimazole
- Associated with congenital aplasia
• Side Effects: reversible granulocytopenia, skin
rashes, fever, peripheral neuritis, polyarteritis,
vasculitis, hepatitis and rarely, agranulocytosis
and aplastic anemia.
• B-blockade should be considered in all patients
with symptomatic thyrotoxicosis and is
recommended for elderly patients, those with
coexistent cardiac disease, and patient with
resting heart rate >90 bpm.
• Propranolol – most commonly prescribe, 20 to
40mg four times daily.
• Radioactive Iodine Therapy (131I)
-forms the mainstay of treatment in north America
- advantage are avoidance of a surgical procedure and its
concomitant risks, reduced overall treatment cost, and
ease of treatment
- dose is calculated after a preliminary scan and usually
consist of 8 to 12 mCI administered orally.
-most oftern used in older patients with small or
moderate-sized goiters, those who have replased after
medical or surgical therapy and those in whom antithyroid
drugs or surger are contraindicated
Absulote contraindications
- women who are pregnant (or planning pregnancy w/in
6mos)
-breastfeeding
Relative contraindication include young patients (children
and adolescents), those with thyroid nodules and
ophthalmopathy
• Surgical Treatment
- surgery is recommended when RAI is
contraindicated as in px:
a. Have confirmed cancer or suspicious thyroid
nodules
b. Are young
c. Desire to conceive soon (<6mos) after treatment
d. Have severe reactions to antithyroid medications
e. Have large goiters (>80g) causing compressive
symptoms
f. Are reluctant to undergo RAI therapy
- Relative indications:
smokers with moderate to severe Grave’s
ophthalmopathy
desiring rapid control of hyperthyroidism with a chance
of euthyroid
those demonstrating poor compliance to medications
pregnancy – best performed in 2nd trimester
- Goal of thyroidectomy should be the complete
and permanent control of the disease with
minimal morbidity
-Based on the current evidence, recently published
guidelines from the American Thyroid Association (ATA)
and the American Association of Clinical Endocrinologist
(AACE) recommend TOTAL OR NEAR TOTAL
THYROIDECTOMY as the procedure of choice for the
surgical management of Grave’s disease
Toxic Multinodular Goiter
• Occur in older individuals, who have prior history
of nontoxic multinodular goiter
• Can be precipitated by iodine containing drugs
such as contrast media and the antiarrhytmic
agent amiodarone (Jod-Basedow
hyperthyroidism)
• Symptoms and signs of hyperthyroidism are
similar to Grave’s disease but extrathyroidal
manifestation are absent
• Diagnostic Studies
- suppressed TSH level and elevated free T4 or T3
levels
-RAI uptake is increased, showing multiple
nodules with increased uptake and suppression of
remaining gland
• Treatment
- hyperthyroidism must be adequately controlled with
antithyroid drugs
-RAI and surgical resection may be used
Near-total or total thyroidectomy is recommended
- to avoid recurrence and the consequence
increased complication rates with repeat surgery
RAI therapy is reserved for elderly patients who represent
very poor operative risk
Toxic Adenoma
• Hyperthyroidism from a single hyperfunctioning
nodule
• Typically occurs in younger patients with recent
growth of a long standing nodule along with the
symptoms of hyperthyroidism
• Characterized by somatic mutations in the TSH-R
gene
• Most thyroid nodule have attained a size of at
least 3cm before hyperthyroidism occurs
• Physical examination reveal a solitary thyroid
nodule without a palpable thyroid tissue on
contralateral side
• RAI scanning shows a “hot” nodule with
suppression of the rest of the thyroid gland
• Smaller nodules may be manage with antithyroid
medication and RAI
• Surgery (lobectomy and isthmusectomy) is
preferred to treat young patient and those with
larger nodules
• Percutaneous ethanol injection (PEI) has been
reported to have reasonable success rate
Thyroid Storm
• Condition of hyperthyroidism accompanied by
fever, central nervous system agitation or
depression, and cardiovascular and GI
dysfunction, including hepatic failure
• May be precipated with abrupt cessation of
antithyroid medications, infection, thyroid or
nonthyroid surgery, and trauma in patient with
untreated thyrotoxicosis
Treatment:
• Can be appropriately managed in an ICU setting
• B-blockers
• Oxygen supplementation and hemodynamic
support
• Nonaspirin componds and Lugol’s iodine or
sodium ipodate (IV)
• PTU
• corticosteriods
Hypothyroidism
• Deficiency in circulating levels of thyroid
hormone
• In neonates, leads to cretinism, which is
characterized by neurologc impairment and
mental retardation.
• May occur in Pendred’s syndrome and Turner’s
Syndrome
Clinical features
• Failure of thyroid gland development or function
in utero leads cretinism and characteristic facies
similar to children with Down syndrome and
dwarfism
• Failure to thrive and severe mental retardation
• Immediate testing and treatment with thyroid
hormone at birth can lessen neurologic and
intellectual deficits
• In adults symptoms are nonspecific, includes :
- tiredness
- constipation
-weight gain
- menorrhagia
-cold intolerance
• Patients with severe hypothyroidism or
myxedema develop characteristic facial and
periorbital puffiness
• Skin becomes rough and dry
• Hair becomes dry and brittle
• Loss of the outer two thirds of the eyebrows
• Enlarged tongue
• Nonspecific abdominal pain with distention and
constipation
• Impaired libido and fertility
 • Bradycardia, cardiomegaly, pericardial effusion,
reduced cardiac output and pulmonary effusions
Laboratory findings
- Low circulating levels of T4 and T3
- Raised TSH levels are found in primary thyroid
failure
- Low TSH levels that do not increase following
TRH stimulation is characteristic of secondary
hypothyroidism
- ECG demonstrates decreased voltage with
flattening or inversion of T waves
Treatment
• T4 is the treatment of choice and is administered
in dosages varying from 50mg to 200ug per day
depending on patient’s size and condition
• Elderly patients and those with coexisting heart
disease and profound hypothyroidism should be
started on a considerable lower dose, 25 to 50ug
daily
Common Diseases of the Endocrine System (Part II –
Lecture)
Parathyroid Gland
Anatomy and Histology
• 4 parathyroid glands
Superior glands – usually are dorsal to the RLN at
level of cricoid cartilage
Inferior glands – located ventral to the RLN
• Appear golden yellow to light brown in adults,
ovoid and measures up to 7mm in size and weigh
approximately 40 to 50mg each
• Usually derive their blood supply from branches
of inferior thyroid artery
• Composed of CHIEF cells and OXYPHIL cells
arranged in trabeculae, within a stroma
composed of adipose cells
• Chief cells produce parathyroid hormone (PTH)
• Oxyphil cells, are mitochondria rich, acidophilic –
derive from chief cells
• A third group of cells, known as water-clear cells
are also derive from chief cells
Physiology and Calcium homeostasis
• Calcium is the most abundant cation
• Extracellular Calcium is important for excitation-
contraction coupling in muscle tissue, synaptic
transmission in nervous system, coagulation and
secretion of other hormones
• Intracellular Calcium is an important second
messenger regulating cell division, motility,
membrane trafficking and secretion
• Approximately 50% of the serum calcium is in
IONIZED form, which is the active component
• The remainder is bound to albumin (40%) and
organic anions such as phosphate and citrate
(10%)
• Total serum calcium levels ranges from 8.5 to
10.5mg/dl (2.1 to 2.6mmol/L)
• Ionized calcium levels range from 4.4 to
5.2mg/dl (1.1 to 1.3mmol/L)
• Parathyroid Hormone
- parathyroid cells rely on calcium-sensing
receptor (CASR) to regulate PTH secretion by sensing
extracellular calcium levels
- also stimulated by low levels of 1,25-dihydroxy
vitamin D, cathecolamines and hypomagnesemia
- half life of 2 to 4 minutes
- in the liver, it is metabolized into the active N-
terminal component and the relatively inactive C-terminal
fraction
• Parathyroid Hormone
- regulate calcium levels via its actions on the
three target organs
1. Bone – increases resorption by stimulating
osteoclast and promotes the release of calcium
and phosphate into circulation
2. Kidney – calcium is primarily absorbed in concert
with sodium in the proximal convoluted tubule;
limit calcium excretion at the distal convoluted
tubel via an active transport mechanism
3. Gut – enhance 1-hydroxylation of 25-
hydroxyvitamin D, which is responsible for its
indirect effect of increasing intestinal calcium
absorption
• Calcitonin
- produced by thyroid C cells and functions as an
antihypercalemic hormone by inhibiting osteoclastic
mediated bone resorption
• Vitamin D (vitamin D2 and D3)
- produced by photolysis of naturally occurring
sterol precursors
- further hydroxylation in the kidney results in
1,25-dihydroxy vitamin D, the most metabolically active
form
Hyperparathyroidism (HPT)
• Primary HPT arises from increased PTH
production from abnormal parathyroid glands
and results from a disturbance of normal
feedback control exerted by serum calcium
• Secondary HPT occurs as a compensatory
response to hypocalcemic states resulting from
 chronic renal failure or GI malabsorption of of the middle phalanx of 2nd and 3rd fingers),
calcium bone cyst, and tufting of the distal phalange

• Tertiary HPT result from chronically stimulated • Gastrointestinal complications

glands becoming autonomous, resulting in
persistence or recurrence of hypercalcemia - Associated with peptic ulcer disease

Primary Hyperparathyroidism - Increased incidence of pancreatitis, although this

• Increased PTH production leads to ypercalcemia
via increased GI absorption of calcium, increased
production of vitamin D3, and reduced renal
calcium clearance.
• Characterizeby increased parathyroid cell
proliferation and PTH secretion that is
independent of calcium levels
• Exact cause is unknown, although exposure to
low-dose therapeutic ionizing radiation and
familial predisposition account for some cases
appears to occur only in patets with profound
hypercalcemia
- Increased incidence of cholelithiasis
• Neuropyschiatric complications
- Severe hypercalcemia may lead to florid
psychosis, obtundation or coma
- Mild hypercalcemia, may have depression,
anxiety and fatigue
• Other feature

• Result from the enlargement of a single gland or - Can lead to fatigue and muscle weakness which is
parathyroid adenoma in 80%, multiple adenoma prominent in the proximal muscle group
or hyperplasia in 15 to 20% and parathyroid
carcinoma in 1% Physical findings

• Most cases are sporadic • Parathyroid tumors are seldom palpable

• Also occurs within the spectrum of a number of • May demonstrate evidence of band keratopathy,
inherited disorders such as MEN1, MEN2A, a deposition of calcium in Bowman’s membrane
isolated familial HPT, and familial HPT with jaw- just inside the iris of the
tumor syndrome

• It is the earliest and most common manifestation

of MEN1 and develops in 80% to 100% of
patients by age 40 years old

Clinical features

• Present with the classic pentad of symptoms

- Kidney stones diagnostic study

- Painful bones
- Abdominal groans • Presence of an elevated serum calcium and
- Psychic moans intact PTH or two-site PTH levels, without
- Fatique overtones hypocalcuria, establishes the diagnosis of PHPT
• Currently, most patients present with weakness,
• Also typically have decrease serum phosphate
fatigue, polydipsia, polyuria, nocturia, bone and
(50%) and elevated 24hour urinary calcium
joint pain, constipation, decreased appetite,
concentrations (60%)
nausea, heart burn, depression and memory loss
• Mild hyperchloremic metabolic acidosis also is
• Renal Disease
present (80%)
- approx. 80% of patients have some degree of
renal dysfunction or symptoms

- Kidney stones occur in 20% to 25%, composed of

calcium phosphate or oxalate

- Nephrocalcinosis is found in <5% of patients and

is more likely to lead to renal dysfunction.

- Chronic hypercalcemial also can impair

concentrating ability, resulting in polyuria,
polydipsia and nocturia

• Bone Disease

- osteopenia, osteoporosis, and osteitis fibrosa

cystica is found in 15% of patients

- Increased bone turnover, as found in patient

with osteitis fibrosa cystica can be determined
by documenting an elevated blood alkaline
phosphate level

- On xray of the hands, there is subperiosteal

resorption (most apparent on the radial aspect
 • Xray of the hand and skull may demonstrate
osteitis fibrosa cystica
• Abdominal ultrasound examination is used
selectively to document renal stones
Treatment
• Most authorities agree that patients who have
developed complications and have “classic
symptoms” of PHPT should undergo
parathyroidectomy
• Medical options for treating PHPT and its
complication include antiresorptive treatment
such as Bisphosphonates, hormone replacement
therapy and selective estrogen receptor
modulators such as raloxifene
Tertiary Hyperparathyrodism
• Renal transplantation is an excellent method of
treating secondary HPT, but some patients
develop autonomous parathyroid gland function
and tertiary HPT
• Can cause pathologic fractures, bone pain and
worsened bone disease, renal stones, peptic
ulcer disease, pancreatitis and mental status
changes
• Many patient is treated with cinacalcet, although
the drug is effective and well tolerated, the long
term effect on kidney allograft function are not
known
• Parathyroidectomy has been shown to lead to a
more immediate and dramatic reduction in
hypercalcemic symptoms

• Operative intervention is indicated for

symptomatic disease or if autonomous PTH
secretion persist for >1 year after a successful
transplat in patients who are operative
candidate

Hypoparathyroidism

• Cause hypocalcemia

• Results in decreased ionized calcium ad

increased neuromuscular excitability

Secondary Hyperparathyrodism

• Occurs in patient with chronic renal failure but

also may occur in those with hypocalcemia
secondary to inadequate calcium or vitamin D
intake or malabsorption

• Pathophysiology of HPT in chronic renal failure is

complex and appears to be related to
hyperphosphatemia, deficiency of 1,25-
dihydroxy vitamin D due to loss of renal tissue,
low calcium intake, decreased calcium
absorption and abnormal parathyroid cell
response to extracellular calcium or vitamin D

• Treated medically with low-phosphate diet,

phosphate binders, adequate intake of calcium
and 1,25-dihydroxy vitamin D and a high-
calcium, low-aluminum dialysis bath
• Calcimemitics have been shown to control
parathyroid hyperplasia and osteitis fibrosa
cystica associated with secondary HPT and
decrease plasma PTH and total and ionized
calcium levels
• Surgical treatment was traditionally
recommended for patients with bone pains,
pruritus and
a. A calcium-phosphate product >=70
b. Calcium >11 mg/dL with markedly elevated PTH
• Hypocalcemia initially develop circumoral and
fingertip numbness and tingling
• Mental symptoms include anxiety, confusion and
depression
• Physical examination reveals chovstek’s sign and
Trousseau’s sign
• Most patient with postoperative hypocalcemia
can be treated with oral calcium and vitamin D
supplements, IV calcium infusion is rarely
required except in patient with preoperative
osteitis fibrosa cystica

c. Caciphylaxis

d. Progressive renal osteodystrophy and

e. Soft tissue calcification and tumoral calcinosis,

despite masimal medical therapy