Endocrine Disorders Flashcards
How common is a supernumerary parathyroid gland, and where is the supernumerary gland most likely to be found?
Incidence of up to 15%. Most often found in the thymus, thyrothymic tract and carotid sheath
Where do the superior and inferior parathyroid glands obtain their blood supply?
Most blood supply comes from inferior thyroid artery, occasionally the superior glands may get supply from superior thyroid artery in 15% of cases.
How can PTH levels be use intraoperatively to determine the completeness of a parathyroidectomy?
PTH has a half life of 2-5 minutes. PTH levels can be drawn from the patient before incision and then 5-10 minutes after excision. If there is at least a 50% decrease in the PTH level into the normal or near normal range, the excised gland was likely the offending gland.
What structures are landmarks in identifying the superior parathyroid gland?
80% of superior parathyroid glands are found on the posterior aspect of the thyroid gland within a 1cm diameter centered 1cm superior to the intersection of the RLN and inferior thyroid artery
What branchial pouch gives rise to the superior and inferior parathyroid glands
- 4th pouch gives rise to superior parathyroid gland and C cells
- 3rd pouch gives rise to inferior parathyroid gland and thymus
How does PTH maintain calcium levels?
PTH increases calcium absorption from the gut, mobilizes calcium from the bones, inhibits calcium excretion from the kidneys, and simulates renal hydroxylase to maintain activated vitamin D levels
What is the most potent regulator of PTH release?
serum calcium levels
Where are PTH receptors located and what downstream effects do they have in each location?
PTH binds to PTH receptors on bone and in the kidneys.
- PTH on osteoblasts case release of receptor activity of nuclear factor K ligand which then activates osteoclasts, which break down bone to increase serum calcium.
- In the kidney, PTH binds to renal tubule cells and induces reabsorption of calcium and decreases reabsorption of phosphate from the filtrate. It also induces the expression of an enzyme that converts the inactive form of vitamin D to the active form.
When monitoring total calcium levels in a patient what factor do you also need to note?
Albumin level
- Corrected calcium: (4-albumin level)0.8 + total calcium
What test results support the diagnosis of familial hypocalciuric hypercalcemia?
Hypercalcemia with 24 hr urinary calcium:creatine clearance ratio below 0.01, as well as one or more first degree relatives with hypercalcemia
Most common symptoms of chronic hypercalcemia?
“bones, stones, abdominal groans and psychiatric moans”
- renal calculi, bone pains, abdominal pains, depression, anxiety, cognitive dysfunction
Testing necessary to diagnose primary hyperparathyroidism?
Elevated albumin-corrected serum calcium or ionized calcium and elevated PTH
Most common cause of hypercalcemia in an outpatient setting?
Parathyroid adenoma
Most common cause of hypercalcemia in an inpatient setting?
Underlying malignancy
A patient has hypercalcemia and low or undetectable PTH levels. What is the likely diagnosis?
Paraneoplastic induced hypercalcemia mediated by PTH related protein. Primary hyperparathyroidism is ruled OUT by low PTH levels
What is the incidence of primary hyperparathyroidism in Western countries?
22: 100,000 persons per year. Incidence is higher in postmenopausal women
- Most cases occur in women (74%); incidence peaks in the 7th decade of life. Before age 45, incidence in men and women is similar.
What are the different types of parathyroid hyperplasia?
Parathyroid hyperplasia is predominantly caused by proliferation of chief cells within the gland. Rarely, water clear cell hyperplasia, which is a proliferation of vacuolated water clear cells, can be found. The water clear cell variant is clinically more severe and predominantly occurs in females.
Causative factors are associated with primary hyperparathyroidism?
- head and neck radiation in childhood
- long term lithium therapy
- genetic predisposition
Guidelines for surgical treatment in an asymptomatic patient with primary hyperparathyroidism?
- serum calcium > 1mg/dl above the upper limit of normal
- creatine clearance less than 60ml/min
- bone density T score less than -2.5 or previous fragility fracture
- Younger than 50
Typical laboratory values of calcium, PTH, and phosphate in secondary hyperparathyroidism
- low-normal calcium
- elevated PTH
- phosphate levels vary based on etiology (high in renal insufficiency, low in vitamin D deficiency)
Possible causes of secondary hyperparathyroidism
- Situations where low calcium levels triggers secretion of PTH and growth of parathyroid glands
- Renal failure (causes a decline in the formation of activated vitamin D and calcium absorption in the gut, impaired phosphate excretion all resulting in low calcium)
- Vitamin D deficiency
- Short gut syndrome or history of gastric bypass (risk of secondary disease resulting from malabsorption of both calcium and vitamin D)
Treatment of secondary hyperparathyroidism
- Correction of underlying cause
- Symptoms may improve with cincalcet or bisphosphates
- Role for subtotal parathyroidectomy if medical therapy fails
What is tertiary hyperparathyroidism?
A state of excess secretion of PTH after long standing secondary hyperparathyroidism. Phosphate levels in tertiary hyperparathyroidism are decreased. Renal dysfunction may lead to hyperphosphatemia despite elevated levels of PTH. Classic example is hyperparathyroidism persisting after renal transplantation.
Pathophysiology of tertiary hyperparathyroidism
Hypertrophied parathyroid glands become autonomous in their function and secrete PTH, leading to hypercalcemia despite withdrawal of calcium and calcitriol. High calcium levels can cause diffuse calcinosis.
Treatment of tertiary hyperparathyroidism
Total parathyroidectomy with autotransplantation or subtotal parathyroidectomy (3 and 1/2 gland resection)
What are the components of hyperparathyroidism-jaw tumor syndrome
Recurrent parathyroid adenomas, fibro-osseous tumors of the mandible, Wilms tumors
How do symptoms of acute and chronic hypoparathyroidism differ?
- Acute: dramatic hypocalcemia and associated paresthesias, muscle spasms, tetany and seizures
- Chronic: gradual in onset and may not present until patient develops blurry vision from cataracts
Most common causes of hypoparathyroidism
- Iatrogenic (after surgery)
- Congenital (third and 4th arches fail to develop properly)
Histologic description of a parathyroid adenoma?
Hypercellular gland consisting of chief and oncocytic cells with decreased intercellular fat
What is the most sensitive imaging study for identifying location of a parathyroid adenoma?
- Technetium 99m sestamibi with single photon emission CT (SPECT)
- Ultrasound can be helpful but is highly user dependent
How frequently is primary hyperparthyroidism caused by a single adenoma vs four gland hyperplasia?
- A single parathyroid adenoma is the cause in 80-85% of cases
- 4 gland hyperplasia is cause in 10-15% of cases
- Other causes include double adenomas (5%)
- Parathyroid carcinoma (<1%)
What features of a patient with hypercalcemia and elevated PTH are more concerning for a parathyroid carcinoma compared with benign parathyroid adenoma?
- Palpable neck mass
- Markedly elevated serum calcium levels (>14)
- Markedly elevated PTH
- Concomitant renal and bone disease
- Symptoms consistent with severe hypercalcemia
- Evidence of invasions such as vocal cord paralysis due to involvement of RLN
What is the gross pathologic description of a parathyroid carcinoma compared with a benign adenoma?
- Benign adenomas are generally soft, round or oval and reddish brown
- Parathyroid carcinoma is frequently large, lobulated and firm to stony hard mass, with a grayish white capsule that is frequently adherent or invasive to surrounding tissues
What is the most common cause of death in patients with parathyroid carcinoma?
Patients often diet from the effects of excessive PTH secretion and uncontrolled hypercalcemia rather than growth from tumor mass.
From what brachial structures does the thyroid develop?
The thyroid develops from an endodermal diverticulum of the floor of the primitive pharynx. The medial primordia is derived from the first and second pharyngeal pouches. The lateral primordia is derived from the fourth and fifth pharyngeal pouches.
The ultimobranchial bodies develop into what structures?
The parafollicular (c cells) cells which release calcitonin - Develop from the 4th pharyngeal pouch neural crest cells
What is the most common pattern of descent of the thyroid gland in relation to the hyoid bone?
The thyroid gland descends anterior to the hyoid bone during gestational weeks 4-7
Most common location of ectopic thyroid tissue?
Base of tongue (lingual thyroid)
What does the proximal portion of the the thyroglossal duct form?
foramen cecum of the tongue
What does the caudal remnant of the thyroglossal duct form?
pyramidal lobe of the thyroid (present in 40-55% of patients
Most common path of right and left recurrent laryngeal nerves
- Right: wraps around and passes deep to the right subclavian artery, then travels in a more oblique path to enter the larynx just posterior to the cricothyroid joint
- Left: wraps around and passes deep to the arch of the aorta, then travels in a more medial path within the tracheoesophageal groove
What is the relationship of the RLN and the cricothyroid joint?
The RLN enters the larynx posterior to the cricothyroid joint
What does the external branch of the superior laryngeal nerve innervate?
cricothyroid muscle (increases pitch)
What does the internal branch of the superior laryngeal nerve innervate?
Provides sensation of the supraglottic structures and shares sensation of the glottis with the RLN
Where does the superior laryngeal nerve branch off from the vagus?
Immediately below the nodose ganglion (inferior ganglion) of the vagus nerve, located just inferior to the jugular foramen
What is the name of the prelaryngeal lymph node?
Delphian node
Boundaries of level VI cervical lymph nodes (central neck compartment)?
Hyoid superiorly, brachiocephalic vein inferiorly, carotid arteries laterally
What is the name of the naturally occuring thyroidal enlargement on the lateral portion of the thyroid gland?
The tubercle of Zuckerkandl
What is the name of the posterior suspensory ligament of the thyroid?
Berry ligmanent
Define the borders of Simon triangle
The space between the esophagus (tracheoesophageal groove) medially , the carotid laterally, and the inferior thyroid artery superiorly
Define the borders of the Joll triangle
The space between the inferior pharyngeal constrictor and the cricothyroid muscle medially, the sternothyroid muscle laterally, and the superior thyroid pole inferiorly
What is the active form of thyroid hormone?
T3. T4 must be deiodinated to T3 to act on peripheral tissue
Describe the internal regulatory pathway of thyroid hormogenesis
- Hypothalamus releases thyroid releasing hormone (TRH)
- TRH binds a receptor in the anterior pituitary that increases production and release of thyroid stimulating hormone (TSH)
- TSH stimulates release of stored T3 and T4, increases production of T3 in relation to T4, increases production of thyroglobulin and thyroperoxidase (TPO)
- Entire system is controlled by negative feedback loop
What is the Wolff-Chaikoff effect?
Describes the decreased thyroid hormone production as a result of excess iodine ingestion (such as Lugol iodine administration in patients with Graves disease)
What hormones are produced by the thyroid gland?
T3 and T4
What medications are the mainstay of treatment in the acute setting of thyroid storm?
- Propranolol to control tachyarrhythmias
- Methimazole to reduce thyroid hormone production
- An hour after methimazole has been given, potassium iodide can be given to decrease hormone release and vascularity of thyroid gland if surgery is considered
What are the key components of thyroid hormone?
Iodine and thyroglobulin
What is the key enzyme required for thyroid hormonogenesis?
TPO - an enzyme that performs the iodination of thyroglobulin and coupling of monoiodotyrosine and diiodotyrosine to form T3 and T4
What is the most common cause of unilateral proptosis?
Graves opthalmopathy, due to deposition of glycosaminoglycans and lipogenesis in the orbit
What are the two ways in which amiodarone can cause hyperthyroidism?
- Type 1 amiodarone induced thyrotoxicosis: excess iodine (amiodarone is 37% iodine) causes excessive thyroid hormone production and is best treated
- Type 2 amiodarone induced thyrotoxicosis: destructive thyrotoxicosis due to amiodarone best treated with prednisone
Preferred treatment for subacute (de Quervain) thyroiditis in the hyperthyroid stage
Symptomatic treatment with beta blockers and NSAIDs is the standard treatment. Severe cases are treated with high dose prednisone.
A rare cause of thyrotoxicosis is a hydatidiform mole. what is the mechanism?
Hydatidiform moles, a form of gestational trophoblastic disease, produce chorionic gonadotropin, which has TSH likely activity
Where is a hormone producing focus of metastatic follicular carcinoma typically found on radioactive body scan?
Usually in the lungs or bone
In a nongravid woman with thyrotoxicosis, radioactive iodine uptake is found in the pelvis. What is the diagnosis?
Struma ovarii, a teratoma of the ovary that contains function thyroid tissue
Four main classifications of hypothyroidism
- primary: result of dysfunctional thyroid gland
- secondary: caused by a dysfunctional pituitary gland
- tertiary: hypothalamic dysfunction
- peripheral: hormone receptor resistance
Most common cause of hypothyroidism in the world
Iodine deficiency
Most common cause of hypothyroidism in the US
Hashimoto thyroiditis
Cause of myxedema coma
An extreme hypothyroid state typically brought on by some systemic stress, often infection, in a hypothyroid patient
How often should head and neck cancer patients have thyroid functions labs?
After 6 weeks of intervention and then every 6-12 months thereafter. Hypothyroidism is common with head and neck cancer after surgery and particularly radiation therapy.
~ how long does the hypothyroid phase of thyroiditis last?
Thyroiditis typically produces a transient hyperthyroid state and then either recovery or a transient hypothyroid state. When it occurs the hypothyroid state lasts 2-8 weeks.
What is the likely cause of subacute granulomatous thyroiditis (de Quervain thyroiditis)?
- Viral illness such as mumps, influenza, coxsackievirus, adenovirus
What lab values are elevated in patients with Hashimoto’s?
- TSH
- antimicrosomal antibodies (anti-thyroperoxidase antibodies)
- antithyroglobulin antibodies
- 10% of patients with clinical Hashimoto thyroiditis may be antibody negative
What causes the initial hyperthyroid state in some patients with Hashimoto’s?
Transient release of stored thyroid hormone from damaged thyroid cells (hashitoxicosis) causes a temporary surge in serum thyroid hormone
What is the relationship between Hashimoto thyroiditis and thyroid cancer?
Slightly increased incidence of papillary thyroid carcinoma compared with the general population
What are the indications for surgery in a patient with Hashimoto’s
Large goiter with obstructive symptoms, worrisome nodularity
Characteristic physical examination findings of Riedel thyroiditis
Rock hard, fixed, painless goiter. Compressive symptoms including dysphagia, dysphonia, cough, and dyspnea may occur
What organisms most commonly cause acute suppurative thyroiditis
Staph aureus, strep pneumoniae, beta hemolytic strep, occasionally can be caused by fusobacterium and haemophilus species
What criteria for a thyroid FNA must be met in order to be considered diagnostic?
Presence of at least 6 follicular cell groups, each with at least 10 cells, derived from at least two aspirates of the cyst or nodule
Why is FNA of cystic thyroid nodules of low diagnostic yield?
Because of scant cellularity of fluid and the difficulty in obtaining a biopsy of the very thin cyst wall.
What are the false negative and false positive rates of thyroid FNA?
False negative is ~1-6%, false positive rate is <5%
When should a benign thyroid nodule (based on results of previous FNA) undergo repeat FNA?
When it changes in size significantly, a cyst recurs or the nodule changes texture
What is Pemperton sign?
Distension of the jugular veins, facial edema or erythema when a patient extends both arms above the head, indicating cervicothoracic inlet obstruction seen in patients with a substernal goiter
What is Chvostek sign?
Seen in cases of hypocalcemia and is positive when tapping a finger on a patient’s cheek over the course of the facial nerve results in contraction of the ipsilateral facial muscles
What is Trousseau sign?
Seen in cases of hypocalcemia where inflation of a blood pressure cuff above systolic blood pressure for 3 minutes results in ipsilateral spasm of the wrist and hand muscles
What are the main complications of thyroid surgery?
Hematoma, infection, superior laryngeal nerve injury, recurrent laryngeal nerve injury, hypocalcemia
Name 4 main types of thyroid surgeries and define each one
- Thyroid lobectomy: removal of a single lobe with or without the isthmus
- Subtotal thyroidectomy: incomplete removal of thyroid tissue, leaving more than 1gram of thyroid remaining
- Near total thyroidectomy: incomplete removal of thyroid tissue, leaving behind a small amount of tissue adjacent to RLN
- Total thyroidecomy: removal of all grossly visible thyroid tissue
At what point in the thyroid dissection should one be aware of of the SLN?
The external branch of the SLN supplies the cricothyroid muscle and lies near the superior pole vessels. Special care should be undertaken during division of superior pole.
How common are thyroid nodules?
Incidence is 50% in adults
Most common pathology of a thyroid nodule
Benign follicular adneoma
Why are thyroid nodules often found during pregnancy?
The incidence of thyroid nodules during pregnancy is 5-20%. Increased hormones and relative iodine deficiency may be associated with increased thyroid nodularity.
How often are thyroid nodules cancerous?
~5% in adults. 20-50% malignancy in children
Is a thyroid cyst always benign?
No. PTC and parathyroid carcinoma can be cystic
What factors increase suspicion of malignancy in a patient with thyroid nodule?
Age younger than 20, male sex, family history of thyroid cancer, pheochromocytoma, hyperparathyroidism, Gardner syndrome, Cowden disease, history of head and neck radiation
Most common cause of thyroid nodule in pediatric population?
Follicular adenoma
Signs and symptoms in patient with thyroid nodule worrisome for cancer
Rapid growth, solid and fixed lesion, lymphadenopathy, pain, compressive symptoms (dysphagia or stridor), dysphonia, invasion of RLN
What is most common presentation of a patient with thyroid cancer?
Nontender, palpable thyroid mass
What are the ultrasound characteristics of a lymph node concerning for metastatic thyroid cancer?
Loss of fatty hilum, increased vascularity, rounded node configuration rather than ovoid, hypoechogenicity of a solid nodule, microcalcifications, peripheral vascularity
Subtypes of well differentiated thyroid cancer
- Papillary thyroid cancer
- Follicular thyroid cancer
- Hurthle cell thyroid cancer
T staging for thyroid cancer
- TX - Primary tumor cannot be assessed
- T0 - No evidence of primary tumor is found
- T1 - Tumor size ≤ 2 cm in greatest dimension and is limited to the thyroid
T1a - Tumor ≤ 1 cm, limited to the thyroid
T1b - Tumor > 1 cm but ≤ 2 cm in greatest dimension, limited to the thyroid - T2 - Tumor size > 2 cm but ≤ 4 cm, limited to the thyroid.
- T3 - Tumor size > 4 cm, limited to the thyroid or any tumor with gross extrathyroidal extension invading only strap muscles
T3a Tumor size > 4 cm, limited to the thyroid
T3b Any size tumor with gross extrathyroidal extension invading only strap muscles (eg, extension to sternothyroid muscle or perithyroid soft tissues) - T4a - Any size tumor with gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve ; or intrathyroidal anaplastic carcinoma
- T4b -Any size tumor with gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels; or anaplastic carcinoma with gross extrathyroidal extension
N Staging for thyroid cancer
- N0 - No regional lymph node metastasis
- N1 - Regional lymph node metastasis
- N1a - Metastases to level VI or VI (pretracheal, paratracheal, or prelaryngeal/Delphian or upper mediastinal) lymph nodes
- N1b - Metastases to unilateral, bilateral, or contralateral neck lymph nodes (levels I, II, III, IV, or V) or retropharyngeal lymph nodes
Thyroid Cancer Staging and Age
- Papillary or follicular carcinoma in a patient younger than 45: stage 1 - any T, any N and M0 ; stage 2 - any T, any N, and M1
- Medullary and anaplastic carcinoma staging do not differ based on age
What is the most significant predictor of overall prognosis for well differentiated thyroid cancer?
Distant metastasis is the most significant prognostic factor
What is the recommended surgical treatment for patients with well differentiated thyroid cancer?
Total thyroidectomy recommended except in cases of PTC of low risk and <1cm in size.
How should local invasion of the esophagus by thyroid carcinoma be treated?
Local invasion of pharynx or esophagus should be resected and then repaired by primary closure of the defect.
What adjuvant forms of treatment exist for well differentiated thyroid carcinoma?
TSH suppression with exogenous thyroid hormone, radioiodine ablation or external beam radiation
What is TSH suppression?
Increased thyroxine levels administered to decrease the concentration of TSH released by the pituitary gland. Side effects of TSH suppression include bone lone, cardiac arrhythmias and symptoms of hyperthyroidism
Complications of radioiodine ablation
Sialadenitis, dental caries, nasolacrimal duct obstruction, xerostomia, rarely secondary malignancies
What is the recommended treatment for a pregnant woman with well differentiated thyroid carcinoma?
Surgical excision is recommended, either during the second trimester or after delivery
Does thyroid cancer discovered during pregnancy differently from disease found in non-pregnant females?
No
What are the recommendations for radioiodine ablation in regard to women of childbearing age?
Pregnancy should be avoided for 12 months after radioiodine ablation
As a general rule what is the best treatment for well differentiated thyroid carcinoma with pulmonary metastasis?
I-131 radioiodine ablation therapy
What are the two most sensitive tests for tumor surveillance after treatment of well differentiated thyroid carcinoma?
- Blood thyroglobulin levels and neck ultrasound
- Thyroglobulin is a reliable marker in patients who don’t produce anti-thyroglobulin antibodies as its production is a marker for functioning thyroid tissue.
How might anti-thyroglobulin antibodies affect posttreatment thyroglobulin levels?
Antibodies can produce a falsely low level of thyroglobulin and its utility as a tumor marker becomes invalid
What histologic features are unique to PTC?
Psammoma bodies which are concentric calcified structures aka “orphan Annie” eyes from large nuclear inclusions and nuclear grooves
In regard to PTV which pathological variants carry a worse prognosis?
Tall cell variant, columnar cell variant and diffuse sclerosing variants
Which thyroid cancer is most common in the pediatric population?
PTC
How does PTC tend to spread?
Via lymphatic channels within thyroid gland leading to frequent multifocal disease as well as to local lymph nodes in the paratracheal and cervical regions.
- Cervical lymph node mets are present in 30-70% of patients
What is the effect of cervical lymph node metastasis on prognosis of PTC?
Topic is debated - most say no decrease in survival with local lymph node involvement but likely increased risk of recurrence after surgical treatment
What is the most common thyroid status of patients with follicular adenomas?
Euthyroid
Are destant mets more common in PTC or follicular thyroid carcinoma?
Follicular because it spreads hematogenously
What is the significance of aneuploid follicular carcinoma?
They are more aggressive in their behavior compared to other follicular carcinomas
Describe the histopathologic findings of Hurthle cell tumors (oncocytic neoplasms)
- Predominance of Hurthle cells, which are large, granular, eosinophilic cells
- Malignancy is determined by the presence or absence of extracapsular spread, lymphovascular invasion or presence of metastasis
How do Hurthle cell carcinomas respond to radioiodine therapy?
They tend to be aggressive and have decreased iodine uptake and are thus resistant to radioiodine therapy
Medullary thyroid carcinoma accounts for what % of thyroid malignancies?
~5%
Medullary thyroid carcinoma originates from what cell type?
Parafollicular cells (C cells) of the thyroid gland which produce calcitonin and are of neuroendocrine origin
What lab abnormalities are associated with medullary thyroid carcinoma?
Elevated calcitonin and often elevated CEA
What is the most common manifestation of medullary thyroid carcinoma?
- Patients with sporadic tumors usually have an enlarging palpable neck mass and cervical lymphadenopathy
- Patients with familial disease are often diagnosed in a presymptomatic state as a result of early screening
What is most important prognostic factor in patients with medullary thyroid carcinoma?
Stage is most important prognostic factor followed by age
How does radioiodine affect medullary thyroid carcinoma?
It does not take up radioiodine because medullary carcinoma originates in the parafollicular cells which aren’t involved in production of thyroid hormone
Standard treatment for medullary thyroid carcinoma
Total thyroidectomy and central neck dissection. If greater than 1cm an ipsilateral lateral neck dissection (levels II-V) should be performed. Chemo and radiation are not effective.
Common initial symptoms of anaplastic thyroid carcinoma
Rapidly enlarging neck mass, often associated with dyspnea, dysphagia, hoarseness and pain
Which of the MEN subtypes includes involvement of parathyroid glands?
- MEN1: multiglandular disease
- MEN2A: parathyroid adenoma and primary hyperparathyroidism
Is familial or sporadic medullary thyroid carcinoma more common?
Sporadic cases represent 75% of cases
What conditions are associated with MEN-2A?
medullary thyroid carcinoma, pheochromocytoma, parathyroid hyperplasia
What conditions are associated with MEN-2B
medullary thyroid carcinoma, pheochromocytoma, marfanoid body habitus, mucosal neuromas (on the surface of the tongue, palate or pharynx, prominent “blubbery” lips, submucosal nodules on vermillion border of lips, eyelid neuromas)
What is the inheritance pattern of familial medullary thyroid carcinoma?
Autosomal dominant
What gene mutations are responsible for familial medullary thyroid carcinoma?
Gain of function mutations of the RET proto-oncogene
What is the recommended treatment for patients with RET mutation and/or family history of medullary thyroid carcinoma?
For children, prophylactic thyroidectomy. In general, early intervention improves outcome by preventing metastasis. In MEN-2A thyroidectomy is recommended in pre-teenage patients whereas in MEN-2B resection is recommended in infancy before age of 1.
How frequently do individuals with MEN-2A develop the various clinical manifestations of this syndrome?
About 70-95% develop medullary thyroid carcinoma, 50% develop pheochromocytoma, 15-30% develop primary hyperparathyroidism
How frequently are cervical lymph node metastases present on presentation of medullary thyroid carcinoma in MEN-2A
up to 70%
What is the incidence of pheochromocytoma in MEN-2B?
50%, approximately half are bilateral
What is essential before surgery in any patient with MEN-2A, MEN-2B or medullary thyroid carcinoma?
Screening for the presence of a functioning pheochromocytoma. Adrenalectomy should be performed before thyroidectomy to avoid intraoperative hypertensive crisis. Calcium and parathyroid levels should be checked for possible primary hyperparathyroidism
What is the rate of recurrence of medullary thyroid carcinoma in patients with MEN-2 who have undergone total thyroidectomy and cervical lymph node dissections?
~50%
In patients with MEN-2 who have undergone prophylactic thyroidectomy what is the recommended screening protocol for medullary thyroid carcinoma?
Yearly serum calcitonin levels
