Endocrinology Made Simple : Papillary Thyroid Carcinoma

Papillary Thyroid Carcinoma

Papillary carcinoma  is the most common form of well-differentiated thyroid cancer.

Etiology And Pathogenesis:

Genetics play an important role in pathogenesis of Papillary Thyroid Carcinoma of Thyroid.

Papillary thyroid carcinoma seems closely related to the activation of the trk and ret proto-oncogenes, both acting by amplifying and rearranging mechanisms

There is also a clear association between prior neck irradiation and incidence of PTC.

Other predisposing factors include the following:

Iodine deficiency

Oral contraceptive use

Benign thyroid nodules

Late menarche

Late age at first birth

Tobacco smoking

Patients with a history of Hashimoto thyroiditis are at increased risk for papillary thyroid cancer.

Gender:

Thyroid cancer is approximately three times more common in females than males.

Age:

Thyroid carcinoma is common in persons of all ages, with a mean age of 49 years and an age range of 15-84 years.

Metastasis:

Papillary tumors have a propensity to invade lymphatics but are less likely to invade blood vessels.

Clinical Presentation:

The most common presentation of thyroid CANCER is an asymptomatic thyroid mass or a nodule that can be felt in the neck.

For any patient with a thyroid lump that has developed recently, record a thorough medical history to identify any risk factors or symptoms.

In particular, obtain a history regarding every prior exposure to ionizing radiation and the lifetime duration of the radiation exposure.

Consider a family history of thyroid cancer.

Thyroid ca may present with following symptoms:

Persistent cough,

Difficulty breathing, or

Difficulty swallowing.

Pain is seldom an early warning sign of thyroid cancer.

Other symptoms (eg, pain, stridor, vocal cord paralysis, hemoptysis, rapid enlargement) are rare, and can be caused by less serious problems.

Metastasis:

At the time of diagnosis, 10-15% of patients with papillary thyroid carcinoma have distant metastases to the bones and lungs. Initially, these patients are evaluated for pulmonary or osteoarticular manifestations (eg, pathologic fracture, spontaneous fracture).

Physical Examination

The clinician should palpate the patient's neck to evaluate the size and firmness of the thyroid and to check for any thyroid nodules. The principal sign of thyroid carcinoma is a palpable nodule, usually solitary, in the thyroid area that has the following characteristics:

Painless

Hard consistency

Average size of less than 5 cm

Ill-defined borders

Fixed in respect to surrounding tissues

Moves with the trachea at swallowing

If cervical lymphadenopathy is present, it may be palpable on either the ipsilateral or contralateral side.

Some patients have a tight or full feeling in the neck, hoarseness, or signs of tracheal or esophageal compression.

Diagnosis:

The following workup should be considered for the diagnosis of papillary carcinoma, a relatively common well-differentiated thyroid cancer:

Thyroid function studies

TSH suppression test

Thyroid ultrasound

Fine-needle aspiration biopsy (FNAB)

Procedures

FNAB is considered the best first-line diagnostic procedure for a thyroid nodule.

Imaging studies

Thyroid Ultrasound

Thyroid ultrasound is the first imaging study to perform in any patient with possible thyroid malignancy. 

Ultrasound is noninvasive and inexpensive, and it represents the most sensitive procedure for identifying thyroid lesions and for determining the diameters of a nodule.

Ultrasound is also useful for localizing lesions when a nodule is difficult to palpate or is deeply seated. The images can help determine if a lesion is solid or cystic and can help detect the presence of calcifications.

Ultrasound may be used to help direct a fine-needle aspiration biopsy (FNAB).

Pulsed and power Doppler ultrasound may provide important information about the vascular pattern and the velocimetric parameters.

Such information can be useful preoperatively to reach a correct differential diagnosis of malignant or benign thyroid lesion.

Scintigraphy

Before the advent of fine-needle aspiration biopsy (FNAB), thyroid scintigraphy (or thyroid scanning) performed with technetium Tc 99m pertechnetate (99mTc) or radioactive iodine (I131 or I123) was the initial diagnostic procedure of choice for a thyroid evaluation.

Malignant nodules usually appear as cold because they are not functioning.

Findings from thyroid scanning are helpful and specific in the preoperative and immediate postoperative periods for localization of cancer or residual thyroid tissue and in observing for tumor recurrence or metastasis. 

Thyroid scanning can also be useful for diagnosing benign lesions (by FNAB) or solid lesions (by echography).

Fine-Needle Aspiration Biopsy

Fine-needle aspiration biopsy (FNAB) is considered the best first-line diagnostic procedure for a thyroid nodule. FNAB is a safe and minimally invasive procedure.

The accuracy of FNAB results is better than any other test for detecting papillary thyroid carcinoma. The sensitivity of the procedure is near 80%, the specificity is near 100%, and errors can be diminished using ultrasonographic guidance.

Fine-needle aspiration biopsy (FNAB) is considered the best first-line diagnostic procedure for a thyroid 

nodule

Management

Surgery is the definitive management of papillary thyroid cancer. Approximately 4-6 weeks after surgical thyroid removal, patients may have radioiodine therapy to detect and destroy any metastasis and residual tissue in the thyroid.

Lobectomy with isthmectomy is the minimal operation for a potentially malignant thyroid nodule. It is an option for patients younger than 40 years who have papillary thyroid carcinoma nodules that are smaller than 1 cm, well-defined, minimally invasive, and isolated.

However, an important consideration in considering this approach is that approximately 10% of patients who

have had only a lobectomy develop a recurrence in the contralateral lobe, and residual tissue has the potential to dedifferentiate to anaplastic cancer.

Subtotal thyroidectomy is a near-total thyroidectomy. The argument for this form of surgical intervention is that total thyroidectomy does not improve long-term prognosis, and subtotal thyroidectomy has a lower incidence of complications (eg, hypoparathyroidism, superior and/or recurrent laryngeal nerve injury) than total thyroidectomy.

Total thyroidectomy

Total thyroidectomy (removal of all thyroid tissue but preservation of the parathyroid glands) is commonly performed for patients with papillary carcinoma who are older than 40 years and in any patient with bilateral disease. In addition, total thyroidectomy is used in most patients with a thyroid nodule and a history of irradiation.

National Comprehensive Cancer Network guidelines recommend total thyroidectomy for patients who meet any of the following criteria

Radiation history

Known distant metastases

Bilateral nodularity

Extrathyroidal extension

Tumor > 4 cm in diameter

Cervical lymph node metastases

Poorly differentiated tumor

Total thyroidectomy is considered by many to be the surgical treatment of choice for papillary tumors of the thyroid, for a number of reasons. Papillary foci involving both lobes are found in some 60-85% of patients. 

About 5-10% of patients who have had a lobectomy develop recurrences in the remaining lobe. Also, at 20 years after initial surgery, patients who had undergone total thyroidectomy had a recurrence rate of 8%, whereas those who had received lobectomy only had a recurrence rate of 22%. Survival rates were, however, comparable.

External beam radiotherapy has been used as adjuvant therapy in patients with papillary thyroid cancer who were older than 45 years and had locally invasive disease. Some improvements in 10-year survival rates have been reported with this approach.

Patients require lifelong thyroid hormone replacement therapy, especially after total thyroidectomy. Treatment consists of levothyroxine in a dosage of 2.5-3.5 mcg/kg/d.

Surgical Care

Surgery is the definitive management of thyroid cancer. Various types of operations may be performed, ranging from lobectomy with isthmectomy to total thyroidectomy.

After thyroidectomy, patients are given thyroid replacement therapy for approximately 4-6 weeks. Thyroid replacement is then discontinued, to induce a hypothyroid state and promote high serum thyroid-stimulating hormone (TSH) levels.

A diagnostic dose of radioiodine (131 I or123 I) is then given, and a whole-body scintiscan is performed to detect any tissue taking up radioiodine. If any normal thyroid remnant or metastatic disease is detected, a therapeutic dose of131 I is administered to ablate the tissue. The patient is then placed back on thyroid hormone replacement (levothyroxine) therapy.

Therapy is administered until radioiodine uptake is completely absent. Radioiodine treatment may be used again 6-12 months after initial treatment of metastatic disease, for cases in which disease recurs or has not fully responded.

Prognosis

The prognosis of papillary thyroid cancer is related to age, sex, and stage. In general, if the cancer does not extend beyond the capsule of the gland, life expectancy is minimally affected. Prognosis is better in female patients and in patients younger than 40 years. The survival rate is at least 95% with appropriate treatments.

Risk factors for overall survival include the following:

Age older than 45 years

Male sex

Minority race

Node metastases

Extrathyroidal invasion

Distant metastases

If two or more risk factors are present, patients should be considered for more aggressive management.

Staging

The staging of well-differentiated thyroid cancers follows the tumor, node, metastasis (TNM) classification system. Staging differs, depending on whether the patient is younger than 45 years of age.

Staging for patients younger than 45 years is as follows:

Stage I - Any T, any N, M0 (cancer in thyroid only)

Stage II - Any T, any N, M1 (cancer spread cervical lymph nodes or to distant organs)

Staging for patients aged 45 years and older is as follows:

Stage I - T1, N0, M0 (cancer only in thyroid, and less than 2 cm)

Stage II - T2, N0, M0 and T3, N0, M0 (cancer only in thyroid and between 2-4 cm)

Stage III - T4, N0, M0 and any T, N1, M0 (tumor greater than 4 cm or cancer spread outside thyroid but not outside of the central neck compartment)

Stage IV - Any T, any N, M1 (cancer spread to either cervical lymph nodes outside of the central neck or distant organs)

Differential Diagnoses

Differential Diagnosis for Thyroid ca includes the following:

Anaplastic Thyroid Carcinoma

Follicular Thyroid Carcinoma

Goiter

Graves Disease

Hurthle Cell Carcinoma

Medullary Thyroid Carcinoma

Parathyroid Carcinoma

Thyroid Lymphoma

Thyroid Nodule

Computer Studies Made Simple : Data Communication

Data Communication

Data communication is the transfer of data from one region to another in electronic form.

Components of Data Communication:

The following are components of data transmission:

1.Message:

This is the data that needs to be transferred from one region to another.

It may be a file in the form of video,picture or text.

2.Sender or Transmitter:

This is the device that sends the message.

It is usually a  computer.

3.Receiver:

This device receives the message.

Some examples include computer and its components such as printer.

4.Medium:

This is used to transmit the message between sender and receiver.

Examples include : Fibre optic cable

5.Encoder:

This device converts the digital signals into a form that can pass through a transmission medium.

6.Decoder:

This device reconverts the signals that have been transmitted through the medium into a form that canbe understood and accepted by the receiver 

Endocrinology Made Simple : Acute Adrenal Insufficiency

Acute Adrenal Insufficiency:

This is of two main types

Primary adrenal insufficiency

This occurs due to impairment of the adrenal glands.

80% are due to an autoimmune disease called Addison's disease or autoimmune adrenalitis.

One subtype is called idiopathic, or of unknown cause.

Other cases are due to congenital adrenal hyperplasia or an adenoma (tumor) of the adrenal gland.

Secondary adrenal insufficiency

This is caused by impairment of the pituitary gland or hypothalamus.

This also takes place in setting of long term exposure to glucocorticoids medications that can cause chronic suppression of hypothalamic-pituitary adrenal axis resulting in secondary or tertiary adrenal insufficiency due to decrease in plasma ACTH and cortisol levels respectively.

Pathophysiology And Clinical Features:

Signs and symptoms include:

Hypoglycemia

Dehydration

Weight loss

Disorientation.

Weakness

Tiredness

Dizziness

Low blood pressure that falls further when standing (orthostatic hypotension),

Cardiovascular collapse

Muscle aches

Nausea,

Vomiting

Diarrhea.

These problems may develop gradually and insidiously.

ACTH doesnot control release of mineralocorticoids from zona glomerulosa of the adrenal glands and hence patients have normal plasma aldosterone levels and are normotensive.

However such patients can develop vascular collapse under stressful situations such as infection due to decrease in cortisol which is hormone responsible for maintenance of vascular tone.

Cortisol also promotes synthesis of catecholamines in adrenal medulla,cortisol deficient patients are unable to mount a good pressor response during stress.

Hypotension in this patient should respond to fluid repletion and stress dose of corticosteroids.

In secondary and tertiary adrenal failure,there is no significant abnormal mineralocorticoid levels.

Management

Primary goal of treatment in patients with acute adrenal insufficiency is to reverse the hypotension,correct the electrolyte abnormality and replace cortisol.

Prompt administration of intravenous steroids is indicated without watching for confirmation of the diagnosis.

Intravenous dexamethasone is preferred because it is long acting and doe snot interfere with measurement of serum or urinary steroids during subsequent cosyntropin stimulation test ACTH

Computer Studies Made Simple : Open System Interconnection Model / OSI

Open System Interconnection Model / OSI :

This model allows communications between two systems with different architecture.

Composition of OSI

It consists of seven layers.

These are as follows:

1.       Physical Layer

2.       Data Link Layer

3.       Network Layer

4.       Transport Layer

5.       Session Layer

6.       Presentation Layer

7.       Application Layer

Physical Layer

This is the bottom layer of OSI Model.

It is responsible for transmission of bits and data and determines the control signals.

It also defines the characteristics and type of transmission medium.

It also defines the type of encoding

It determines the data rate or number of bits that should be sent per second.

Data Link Layer

This layer divides stream of bits into small easily handled units called frames.

It ensures system to control rate of transmission of data such that there remains a balance between rate of receiving and transmission of data.

It also detects damaged frames  and prevents duplication of frames.

Network Layer:

This layer manages the establishment,maintenance and termination of network layers.

It determines a path between sender and the receiver and manages the delivery of data from source to destination.

Transport Layer:

This layer is responsible for ensuring efficient data transmission takes place between the sender and the recipient.

It eliminates errors in the messages and divides larger data packets into smaller ones for efficiency in data transmission.

Session layer:

This layer pertains with users management.

It helps in establishing,managing and terminating connections between users.

Presentation Layer

This layer plays a role in changing data and formatting it such that it canbe transmitted between the sender and recipient effectively.

It can also compress a large sized data into smaller size a process called compression.

Application Layer:

This layer provide services to the users such as emails,network sharing etc.

     

   

Endocrinology Made Simple : Normal Functions Of Somatostatin

Normal Functions Of Somatostatin :

Somatostatin has following normal functions in human body:

1. Inhibit the release of growth hormone from Anterior pituitary gland

2. Inhibit the release of thyroid-stimulating hormone (TSH)

3. Suppression of release of following gastrointestinal hormones : Gastrin, Cholecystokinin          (CCK),Secretin,Motilin,Vasoactive intestinal peptide (VIP),Gastric inhibitory polypeptide (GIP),Enteroglucagon

4. Reducing the rate of gastric emptying, and

5. Reducing smooth muscle contractions and blood flow within the intestine

6. Suppressing the release of pancreatic hormones

7. Inhibiting the release of insulin and glucagon

8. Suppressing the exocrine secretory action of pancreas

Endocrinology Made Simple : Somatostatinomas

Somatostatinomas

Theses are tumors arising from Delta cells in the pancreas.

Some tumors may arise from somatostatin secreting cells of duodenum

Clinical features:

Classical triad of somatostatinomas is

Gall stones

Diabetes

Malabsorption

They cause Diabetes by inhibiting insulin secretion.

Gallstones are caused by inhibitory effect of somatostatin on gall bladder motility.

Malabsorption occurs due to inhibition of pancreatic secretion.

Investigations:

Fasting Somatostatin Levels are obtained to confirm a Diagnosis of Somatostatinomas.

Fasting Somatostatin Levels of more than 160 pg/ml are diagnostic of somatostatinomas.

After biochemical diagnosis has been confirmed,next step is localization of tumor by Imaging studies such as CT Scan of abdomen.

Management :

This includes a combination of Chemotherapy and Surgery

Chemotherapy with streptozocin, dacarbazine, doxorubicin

Surgical debulking via Whipple procedure and other resections of other affected  gastrointestinal organs .

Computer Studies Made Simple : Uses and Advantages of Computers

Uses and Advantages of Computers:

1 . Storage of large amounts of information and retrieval of data for subsequent uses.

2 . Work with great speed executing functions rapidly and able to do tasks repeatedly.

3 . Undertake complex calculations with high accuracy.

4. Follow the instructions given with consistency