Endocrine – Thyroid and Parathyroid Glands

Endocrine – Thyroid and Parathyroid Glands
Dr. Geoffrey Pollack October 10, 2007

Endocrine - Thyroid Embryology
Median thyroid anlage forms at base of tongue in region of foramen cecum during 3rd week of gestation Endodermal pocket Originates from primitive alimentary tract protruding between first pair of pharyngeal pouches Subsequently descends in the midline to reach its normal anatomic location developing into a bi-lobed organ

Endocrine - Thyroid Embryology
Iodine trapping occurs as thyroid hormones are first seen in the 3rd month of gestation The principle cells of the thyroid form thyroid follicles and produce thyroglobulin Lateral anlagen develop from the 4th pharyngeal pouch and fuse with the median anlagen at about the 7th week of gestation Ultimobranchial bodies which may orignate from the 4th pharyngeal pouch may give rise to parafollicular or C cells C cells secrete calcitonin C cells originate from neural crest and are of ectodermal origin

Endocrine - Thyroid Embryology – Thyroglossal Duct Cyst (TGDC)
TGDC are the most common non-odontogenic cysts occurring in the neck TGDC are second only to benign lymphadenopathy of all cervical masses in children (70% of all congenital neck cysts) TGD represents the original attachment of the thyroid mass to the oropharynx TGD is normally resorbed by the 6th week of gestation Distal end of duct may be retained as the pyramidal lobe of thyroid

TGDC are located at or near midline between base of tongue and suprasternal notch 75% of TGDC are located just inferior to the hyoid bone The importance of TGDC is related to High incidence of infection Recurrence after inadequate surgery Possible neoplastic change One-third are detected in first year of life; 50% are detected by age 10 They present as painless midline lesions that grow slowly They can increase in size after a URI

TGDC contains thyroid tissue (and perhaps only functioning thyroid tissue in body – obtain sonogram in an adult prior to OR) Rarely a source of thyroid carcinoma (usually papillary) Treatment: surgery via Sistrunk procedure This includes midportion of hyoid bone Must excise entire cyst/tract/fistula up to base of tongue Recurrence rate with Sistrunk procedure is low (less than 4% compared with 50% when not done using this procedure)

Endocrine - Thyroid Embryology – Thyroglossal Duct Cyst (TGDC)

Endocrine - Thyroid Embryology – Lingual Tonsil
Failure of thyroid anlage to migrate can result in persistence of a functional lingual thyroid gland May represent only functional thyroid tissue Excision may be necessary for airway obstruction, swallowing difficulty, or hemorrhage

Endocrine - Thyroid Anatomy Normal gland weights between 20-30 grams
Thyroid lobes lie subadjacent to thyroid cartilage, anterior to larynx and trachea 2 lobes connected by the isthmus Midline pyramidal process, distal remnant of TGD is present in 40-50% of adults Anterior aspect covered by strap muscles Posterolaterally lie common carotid arteries, internal jugular veins and Vagus nerves Gland is covered by connective tissue layer derived from pre-tracheal fascia Fascia connects thyroid to upper tracheal rings and cricoid posteromedially (Berry’s ligament)

Endocrine - Thyroid Anatomy

Endocrine - Thyroid

Endocrine - Thyroid Anatomy - Recurrent laryngeal nerve (RLN)
Arises in the chest as a branch of the Vagus nerve The right nerve loops under the right subclavian artery The left nerve loops under the aortic arch The right can be non-recurrent in a small number of cases As it ascends in the neck from the chest, the recurrent nerve usually runs just under Berry’s ligament before entering the larynx (posterior to the thyroid at the level of the cricothyroid junction)

Endocrine - Thyroid Anatomy - RLN
Motor nerve to intrinsic muscles of larynx except cricothyroid Sensory to mucosa below vocal cords Unilateral injury to the nerve can result in a weakened voice and can lead to shortness of breath Bilateral injury is a devastating complication causing airway obstruction RLN must be identified by a surgeon during any procedure performed on the thyroid gland

Endocrine - Thyroid RLN

Endocrine - Thyroid Anatomy – Superior laryngeal nerve (SLN)
Arises from the Vagus nerve at the skull base and descends along the carotid artery in the neck 2 branches Internal branch is sensory to the larynx above the vocal cords. It enters the larynx at the level of the thyrohyoid membrane External branch is motor to the cricothyroid muscle (tenses the vocal cord) and inferior constrictor muscle. It enters the larynx behind the cricothyroid muscle. Injury to this nerve will produce hoarseness. Injury can be devastating to professional singers

Endocrine - Thyroid SLN Internal branch External branch

Endocrine - Thyroid Anatomy
4 parathyroid glands are associated with the thyroid gland 2 superior 2 inferior The parathyroid glands must be identified by the surgeon during any procedure performed on the thyroid gland

Endocrine - Thyroid Anatomy Thyroid gland supplied by 4 main arteries
2 superior thyroid arteries (branches of external carotid) 2 inferior thyroid arteries (branches of thyrocervical trunk) Superior, middle and inferior thyroid veins drain blood into internal jugular vein and brachiocephalic veins Lymphatic drainage Intraglandular – travels through isthmus (accounts for relative frequency of multifocal tumors) Central compartment (from hyoid to innominate artery) Jugular chain (especially levels II, III, IV, V)

Endocrine - Thyroid Physiology
Thyroid gland converts inorganic iodine into thyroid hormone (TH) Iodine enters thyroid and is trapped by follicular cells TH synthesis takes place at interface of cell and thyroglobulin (THG) THG is a glycoprotein (colloid) Iodine oxidized by thyroid peroxidases to an activated form of iodine that binds the amino acid tyrosine forming T3 and T4 (TH) The newly formed TH is stored in THG Thyroid gland releases T3 and T4 into the circulation 20% of all T3 and the majority of T4 99% of TH is protein-bound (thyroxin binding globulin, prealbumin, albumin) 80% of T3 is formed from T4 in peripheral tissue Thyroid hormone release is regulated by TSH (thyrotropin stimulating hormone) from the pituitary

Endocrine - Thyroid Physiology

Endocrine - Thyroid Physiology Thyroid function tests Direct tests
Radioactive iodine uptake (RAIU) Tests of hormone concentration and binding T4 T3 T3 resin uptake T4 index (Totally T4 + T3 resin uptake) T7 Tests of hypothalamic – pituitary – thyroid axis TSH Other tests Anti-thyroid peroxidase Anti-thyroglobulin

Endocrine - Thyroid

Endocrine - Thyroid 1. Operations on the thyroid account for the largest number of procedures performed for tumors of the head and neck 2. Thyroid carcinoma is unique because of the low-grade nature of the majority of lesions 3. The major problem for surgeons Correct diagnosis of the small number of malignant tumors from the large number of benign growths Selecting the optimal surgical treatment using a safe effective technique

Endocrine - Thyroid Benign conditions
Benign diseases are common and affect women 5 times more than men About 1% of women develop hypo or hyperthyroidism Benign conditions can be categorized as Toxic [toxic multinodular goiter, toxic solitary nodule, diffuse toxic goiter (Graves’ disease)] Non-toxic [diffuse and nodular (solitary or multiple goiter)] Inflammatory diseases consisting of thyroiditis

With the exception of hyperthyroidism, benign thyroid diseases are of significance to the surgeon either because of mechanical constraint on the upper aerodigestive tract or because it is not possible to rule out carcinoma within a nodular or diffuse lesion Nodular increase may be indistinguishable from goiter or cancer Autoimmune disease may cause firm nodular enlargement difficult to distinguish from carcinoma Follicular adenoma is a true neoplasm that may be indistinguishable from follicular carcinoma except by permanent histologic exam after surgery (vascular or capsule invasion)

Endocrine - Thyroid Benign conditions – Hyperthyroidism
Hyperthyroidism – an excess of production and secretion of thyroid hormone with a characteristic hypermetabolism result Thyrotoxicosis – hypermetabolic state that can be caused by hyperthyroidism (or can occur without hyperthyroidism) Lab tests Elevated T4 or T3 Suppressed TSH Normal RAIU

Endocrine – Thyroid Hyperthyroidism

Endocrine - Thyroid Benign conditions – Hyperthyroidism Treatment
Usually medical but surgery may be required if medical treatment has failed or is contraindicated in 3 conditions Graves’ disease Toxic multinodular goiter (TMNG) Toxic solitary nodule (TSN)

Graves’ disease Autoimmune toxic diffuse goiter Antibodies against TSH receptor 6-7 times more common in women Genetic factors play a role Triad Diffuse toxic goiter Infiltrative opthalmopathy Infiltrative dermopathy (pre-tibial myxedema)

Graves’ disease – Treatment Antithyroid drugs Thionamides (PTU, Tapazole) Inhibits organification of iodine and coupling of iodothyronine Must be used for long duration; recurrence can occur if meds discontinued Success correlates inversely with gland size May cause agranulocytosis Beta-blockers – usually in adjuvant setting if patient is symptomatic or pre-surgery Radioactive Iodine Most commonly chosen therapy Hypothyroidism expected complication

Graves’ disease – Treatment: Surgery 10% of patients require surgery Pregnancy (131-I contraindicated) Failure of drug therapy Concurrent nodular disease with positive FNA Pre-op preparation to attain euthyroid state increases safety (PTU, Tapazole, Beta-blockers, Iodine) Controls hypermetabolic state Decreases risk of thyroid storm May decrease vasularity

Graves’ disease – Treatment: Surgery Total vs. Subtotal thyroidectomy Total Hypothyroidism expected Risks to nerves and parathyroids Recurrence of hyperthyroidism approaches 0% Subtotal – purposefully leaving tissue behind at poles or laterally Bilateral subtotal Unilateral total with contralateral subtotal 50-60% recurrence rate Recurrence can occur 1-30 years after surgery Re-op much more difficult

Toxic multinodular goiter (TMG) “Hot” nodules take up radioactive tracer at higher than normal levels “Hot” nodules can be Autonomous (not responsive to TSH suppression) Not autonomous (responsive to TSH suppression) Autonomous nodules can be Toxic (thyroid hormone in excess clinically hyperthyroid) Non-toxic Rate of cancer in “hot” nodules is low

Toxic multinodular goiter (TMG) Over age 50 in setting of longstanding nontoxic multinodular goiter Nodules become autonomous and toxic (clinically hyperthyroid) - cannot be suppressed Treatment: Same as Graves’ disease (thionamides, radioiodine, surgery) Radioiodine treatment of choice Surgery performed for large goiters and compressive symptoms after patient made euthyroid. Remove all nodules

Toxic solitary nodule (TSN) Most are follicular adenomas that can have spontaneous infarction Less than 1% are carcinoma Life cycle (“hot” nodule  autonomous “hot” hodules  autonomous TSN) More worrisome in nodules greater than 2.5-3cm Surgery for worrisome nodules otherwise 131-I therapy

Endocrine - Thyroid Benign conditions – Hyperthyroidism

Endocrine - Thyroid Benign conditions – Thyroiditis
Includes heterogeneous mixture of diseases with variable etiologies, presentation and treatment Can result in diffusely enlarged, nodular and even normal gland in appearance May be euthyroid, hypo or hyper Often preceding triggers (partuition, viruses, medication)

Endocrine - Thyroid Benign conditions – Thyroiditis Classified by
Descriptive, subjective history (painful or not painful) Temporal course (acute, subacute, chronic) Histopathology (hyperplastic, lymphocytic, granulomatous or fibrosis) Doctor’s name (Graves, Hashimoto, DeQuervain, Reidel)

Endocrine - Thyroid Thyroiditis

Endocrine - Thyroid 1. Operations on the thyroid account for the largest number of procedures performed for tumors of the head and neck 2. Thyroid carcinoma is unique because of the low-grade nature of the majority of lesions 3. The major problem for surgeons Correct diagnosis of the small number of malignant tumors from the large number of benign growths Selecting the optimal surgical treatment using a safe effective technique

Benign diseases are common and affect women 5 times more than men About 1% of women develop hypo or hyperthyroidism Benign conditions can be categorized as Toxic [toxic multinodular goiter, toxic solitary nodule, diffuse toxic goiter (Graves’ disease)] Non-toxic [diffuse and nodular (solitary or multiple goiter)] Inflammatory diseases consisting of thyroiditis

With the exception of hyperthyroidism, benign thyroid diseases are of significance to the surgeon either because of mechanical constraint on the upper aerodigestive tract or because it is not possible to rule out carcinoma within a nodular or diffuse lesion Nodular increase may be indistinguishable from goiter or cancer Autoimmune disease may cause firm nodular enlargement difficult to distinguish from carcinoma Follicular adenoma is a true neoplasm that may be indistinguishable from follicular carcinoma except by permanent histologic exam after surgery (vascular or capsule invasion)

Endocrine - Thyroid Thyroid Nodule Range of disease for thyroid nodule
Benign cyst Lethal malignancy Need strategy to identify malignant vs. benign

Endocrine - Thyroid Thyroid Nodule Prevalence
5% of adults by palpation (greater than 1.5cm) 30% of adults by sonography Increased risk Female Age History of XRT Endemic iodine deficiency

Endocrine - Thyroid Thyroid Nodule Risk of cancer
New thyroid nodules 275,000 per year 1:20 new nodules are malignant (This represents 5%; however in some studies it can approach 15%) Death from thyroid carcinoma 1,100 per year 1:200 new nodules are lethal cancer

Endocrine - Thyroid Thyroid Nodule – Differential Diagnosis
Colloid nodule – multinodular goiter Adenoma Cyst Focal thyroiditis Carcinoma 95%

Endocrine - Thyroid Thyroid Nodule – Differential Diagnosis
Metastasis to thyroid Lobar hypertrophy status post hemithyroidectomy Non-thyroid Lymph node Laryngeal, esophageal tumor TGDC Cystic hygroma, dermoid, teratoma Laryngocele Nerve sheath tumor

Endocrine - Thyroid Thyroid Nodule – History Age <20 or >60
Male (nodular disease is more common in women, but risk of cancer is 2 times greater in men) History of XRT Family history (MTC) Size >4cm Rapid growth Invasion/compression Trachea/larynx: airway, vocal cord paralysis, cough Esophagus: dysphasia Pain (subacute thyroiditis or hemorrhage) Thyroid functional status Hashimoto’s MTNG STN Remember most cancers are euthyroid that is, no functional deficiency

Endocrine - Thyroid Thyroid Nodule – History
Low dose ionizing radiation Tonsils/thymus, acne, tinea (ended approx. 1955), Hodgkin’s, scatter from breast 20-30% develop nodules Patients presenting with such a history have a 30-50% chance of developing cancer

Endocrine - Thyroid Thyroid Nodule – Physical Exam Solitary, dominant
Consistency, fixed Trachea, larynx shift Lymph nodes Vocal cord motion Retrosternal/Pemburton’s sign

Endocrine - Thyroid Thyroid Nodule – Degree of clinical concern for carcinoma based on history and physical exam Less concern Stable exam Evidence of functional disorder Multinodular gland without dominant nodule

Endocrine - Thyroid Thyroid Nodule – Degree of clinical concern for carcinoma based on history and physical exam More concern Age <20 >60 Males Rapid growth, pain History of radiation therapy Family history of thyroid carcinoma Hard fixed lesion Lymphadenopathy Vocal cord paralysis Size >4cm Aerodigestive tract compromise (e.g., stridor, dysphagia) Cyst recurrence after aspiration

Endocrine - Thyroid Thyroid Nodule – Lab Work up
Thyroid function tests TSH, T4, Total T3, resin uptake, T4 index, T7 Hashimoto’s: TPO Malignancy: No effective markers Thyroglobulin Extensive overlap benign vs. malignant Hampered by anti-thyroglobulin autoantibodies Useful in long-term follow-up in patients with thyroid carcinoma

Endocrine - Thyroid Thyroid Nodule – Hashimoto’s Thyroiditis
Can present with small, firm thyroid lobes which can be mistaken for thyroid nodules on exam Common cause of hypothyroidism in females Development of progressively enlarging mass within Hashimoto’s should trigger concern for lymphoma FNA can give false positive findings (microfollicles, Hurthle cells, lymphocytes)

Endocrine - Thyroid Thyroid Nodule – Toxic Nodule
Decreased TSH (rationale for checking TSH prior to FNA) Very low incidence of malignancy High risk of microfollicle false positive FNA

Endocrine - Thyroid Thyroid Nodule – Multinodular Goiter
Dominant nodule is considered as a solitary nodule in terms of malignancy risk

Endocrine - Thyroid Thyroid Nodule – Radiographic Work up
CXR – tracheal deviation, substernal extension, metastasis CT – impact on adjacent cervical viscera, retrosternal extension, adenopathy (cervical or mediastinal), tracheal invasion; caution with use of iodine in multinodular goiter where patient may be subclinically hyperthyroid MR – Retrosternal mediastinal vascular relationship

Endocrine - Thyroid Thyroid Nodule – I123 Scan
95% cold: cold solid nodule, cyst, focal thyroiditis; only 10-15% malignant 5% hot: <4% hot nodules are malignant When to scan: Identification of a functional solitary thyroid nodule when TSH is decreased If an FNA is reported as a follicular neoplasm or suspicious, the finding of a “hot” nodule may decrease the suspicion of a cancer Detecting neck metastasis

Endocrine - Thyroid Thyroid Nodule – Sonography
Does not distinguish between benign vs. malignant Provides a sensitive and objective measure of nodule size prior to FNA, surgery, suppression Provides clear-cut baseline Finds contralateral nodules, lymph nodes which can be helpful at surgery Nonpalpable or difficult to palpate nodules for US-guided FNA Follow-up imaging for solitary nodules that are managed medically or by observation Nondiagnostic fine needle aspirate (as an adjunct to repeat FNA)

Endocrine - Thyroid Thyroid Nodule – Sonography Studies show
70% of nodules are solid  20% are malignant 19% are cystic  7% are malignant 11% are mixed  12% are malignant

Endocrine - Thyroid Thyroid Nodule – Sonography
US features suggesting malignancy Absent “halo” sign Solid or hypoechogenicity Heterogeneous echo structure Irregular margin Fine calcifications Extraglandular extension

Endocrine - Thyroid Thyroid Nodule – Fine Needle Aspiration (FNA)
All palpable lesions of the thyroid require FNA Decreased the percent of patients brought to surgery by 20-50% Increased the percent of carcinoma found in surgical specimens by 10-15% Overall decreases cost of care by 25%

Endocrine - Thyroid FNA

Endocrine - Thyroid Thyroid Nodule – FNA Diagnostic Categories

Endocrine - Thyroid Thyroid Nodule – Fine Needle Aspiration (FNA) “Suspicious”

Endocrine - Thyroid Thyroid Nodules - Management of the Thyroid Cyst

Endocrine - Thyroid Thyroid Nodule Suppression
Exogenous T4 suppresses TSH and withdraws stimulatory influence on the thyroid and nodules within it Goal and length of treatment are unclear Controversy regarding whether suppressive therapy is superior to placebo Risks Suppressive therapy promotes osteoporosis and in an elderly population increases atrial fibrillation

Endocrine - Thyroid Thyroid Nodule Algorithm

Endocrine - Thyroid Nontoxic Goiter
Goiter is defined as any benign enlargement of the thyroid gland Iodine deficiency is most common cause (endemic goiter) In response to iodine deficiency  increase TSH Epithelial hyperplagia of thyroid gland followed by focal nodular hyperplagia Can grow extremely large In US, most goiters are nonendemic 3-4% of US population Cause unknown

Endocrine - Thyroid Nontoxic Goiter – Indications for Surgery
Symptoms of airway, esophageal, or superior vena caval obstruction Thyroid enlargement despite nonoperative treatment FNA biopsy positive or suspicious for malignancy Radiologic finding of tracheal deviation or compression Susternal goiter Cosmetic deformity/patient preference

Endocrine - Thyroid Nontoxic Goiter – Surgery: Controversy
Patients with unilateral thyroid enlargement lobectomy and isthmusectomy Patients with diffuse or multinodule goiter Total on one side and subtotal on the other Total Bilateral subtotal High recurrence rate (up to 25%) Need for reoperation

Endocrine - Thyroid Thyroid Cancer – Statistics
1.5% of all cancers in the US Most common endocrine malignancy (95% of all endocrine cancers) Approx. 22,000 new cases each year 74% occur in women

Endocrine - Thyroid Thyroid Cancer – Pathology

Endocrine - Thyroid Thyroid Cancer – Papillary Carcinoma
75-80% of all thyroid cancers Consists of pure papillary, follicular, tall cell*, columnar cell*, oxyphilic*, diffuse sclerosing, and encapsulated variants Accounts for 90% of radiation-induced thyroid ca. Familial in 3% of patients (Cowden’s syndrome and Gardner’s syndrome) * Aggressive forms of papillary carcinoma

Endocrine - Thyroid Thyroid Cancer – Papillary Carcinoma
Histological features Psammoma bodies Intranuclear grooves Cytoplasmic inclusions Multicentric in 30-50% of tumors Spreads via lymphatics Cervical metastasis is not uncommon on initial presentation (in one study, microscopic mets present in 90% of elective neck dissection specimens)

Endocrine - Thyroid Thyroid Cancer – Papillary Carcinoma Treatment
Papillary carcinoma <1cm in size “microcarcinoma”  lobectomy and isthmusectomy Papillary carcinoma >1cm in low-risk group  lobectomy and isthmusectomy (low-risk have recurrence rate of 5-11%; mortality rate .07-5%) Papillary carcinoma >1cm in high-risk group  total thyroidectomy (high-risk have recurrence rate of 48%; mortality rate 48%) Patients with history of head and neck irradiation  total thyroidectomy (high incidence of ca. at sites other than nodule and increased lifetime risk of developing thyroid carcinoma)

Endocrine - Thyroid Thyroid Cancer – Papillary Carcinoma

Total thyroidectomy – Advantages Associated with lowest incidence of local and regional occurrence When combined with post-op 131I ablation there is improved survival Allows use of serum thyroglobulin (Tg) and radioiodine for early detection and treatment of metastatic disease Avoids possible future re-op surgery Total thyroidectomy – Disadvantages Injury to recurrent laryngeal nerves and parathyroid glands

Lymph nodes Prophylactic lymph node dissection not warranted Enlarged lymph nodes in central and lateral neck should be removed and submitted for frozen section If FS+ in central neck  central neck dissection performed If FS+ in lateral neck  modified radical neck dissection (functional neck) performed

Endocrine - Thyroid Thyroid Cancer – Papillary Carcinoma Treatment –
Lymph Nodes

Endocrine - Thyroid Thyroid Cancer – Follicular Carcinoma
10% of all thyroid cancers Spreads hematogenously (lungs and bones) Only 10% spread to cervical lymph nodes FNA cannot distinguish benign from malignant follicular neoplasm (capsule or vascular invasion are determining factors) FNA report “consistent with follicular neoplasm” has 20% chance of malignancy These patients should undergo lobectomy and isthmusectomy If permanent section is positive for carcinoma, then completion thyroidectomy is done

Endocrine - Thyroid Thyroid Cancer – Hurthle Cell Carcinoma
5% of thyroid cancers Similar to follicular carcinoma but more aggressive tumor 10-year survival 30%

Endocrine - Thyroid Thyroid Cancer – Staging
Papillary and Follicular carcinoma are considered well-differentiated thyroid tumors Both Papillary and Follicular ca have good prognoses 20-year survival rates are 90% and 70% respectively Most important prognostic factor is age

Endocrine - Thyroid Thyroid Cancer – Staging

Endocrine - Thyroid Thyroid Cancer – Post-op Treatment of Well-Differentiated Thyroid Carcinoma Thyroid remnant ablation destroys residual thyroid tissue after surgery using 131I Destroys microscopic disease Allows for detection of recurrent disease by radioiodine scanning Allows for improved sensitivity of serum thyroglobulin (Tg) measurements during follow-up Used for: Papillary ca. >1.5cm Papillary ca. with mets Invasive follicular or Hurthle Cell ca. Patient should be off thyroid hormone for weeks (or T3 for 2 weeks) to allow for maximal TSH levels

Endocrine - Thyroid Thyroid Cancer – Post-op Treatment of Well-Differentiated Thyroid Carcinoma Thyroid hormone given post-ablation to suppress TSH (TSH stimulates tumor growth, invasion, angiogenesis, Tg secretion) Long-term follow-up using serum Tg and 131I whole-body scans

Endocrine - Thyroid Thyroid Cancer – Medullary Carcinoma (MTC)
Parafollicular cells of neuroectoderm origin 5% of all thyroid cancers (75% sporadic; 25% hereditary) FNA can be characteristic along with special staining for calcitonin Hereditary Part of multiple endocrine neoplasia syndromes type IIA and IIB (IIA – hyperparathyroidism and pheochromocytoma, lichen planus amyloidosis, Hirschprung’s disease; IIB – pheochromocytoma, marfanoid body habitus, mucosal neuromas, ganglioneuromatosis of the GI tract) RET proto-oncogene is currently primary factor implicated This allows for screening, early detection and treatment

Endocrine - Thyroid Thyroid Cancer – Medullary Carcinoma (MTC)
Treatment Surgery is main modality of treatment Total thyroidectomy with central neck dissection Modified radical neck dissection is performed for cervical lymph node metastasis These tumors are not amenable to radioiodine therapy or other adjuvant therapy Post-treatment Monitor serum calcitonin levels

Endocrine - Thyroid Thyroid Cancer – Anaplastic Cancer
A most aggressive cancer Overall 5-year survival; 3.6% with median survival of 4 months No adequate therapy known; complete surgical resection is difficult because of tumor size, extra thyroid growth and invasion into surrounding tissues. Besides attempted resection, surgery may be indicated for airway management (e.g., tracheotomy) Surgery, radiation therapy, chemotherapy combined may improve local control

Endocrine - Thyroid Thyroid Cancer – Lymphoma
Less than 1% of thyroid cancers Usually non-Hodgkin’s B-cell type Associated with Hashimoto’s thyroiditis Usually in older women Presents as rapidly enlarging painless neck mass FNA 80% accurate Occasional biopsy is necessary for tissue diagnosis 50-70% 5-year survival

Endocrine - Thyroid Thyroid Cancer – Surgery: Complications
2 primary potential complications that must be considered in performing thyroid surgery are RLN injury and hypoparathyroidism With total thyroidectomy, incidence of temporary hypoparathyroidism ranges from 5-40% With total thyroidectoy, the incidence of permanent hypoparathyroidism ranges from 1-5% in some studies to 8-32% in other studies The rate of temporary RLN injury is 3-7% With total thyroidectomy the incidence of permanent RLN injury is 0-3% per side in some studies, and up to 11% in other studies Lastly, injury to the superior laryngeal nerve can be a devastating complication to professional singers

Endocrine - Thyroid Thyroid Cancer – Surgery: Complications
Hypoparathyroidism (hypocalcemia) Circumoralparasthesia Mental status change Carpopedal spasm Seizures QT interval prolongation Cardiac arrest Most common after total thyroidectomy but can occur in patients with hyperparathyroidism who undergo parathyroid surgery, especially when the calcium is extremely elevated preoperatively, with significant bone disease (hungry bone syndrome) Should be treated as a general rule when serum calcium falls below 7 and / or patient is symptomatic

Endocrine - Thyroid Surgery – Technique

Endocrine – Parathyroid
84% of adults have 4 parathyroids Autopsy results reveal 13% have greater than 4 and 3% have less than 4 84% of adults have 4 parathyroids Autopsy results reveal 13% have greater than 4 and 3% have less than 4

Endocrine - Parathyroid

Anatomy and Embryology Inferior glands are derived from the 3rd branchial pouch and migrate caudally with the thymus. They then separate at the level of the inferior thyroid pole Superior glands are derived from the 4th branchial pouch and follow the migration of the ultimobranchial bodies at the lateral part of the thyroid anlage

Anatomy and Embryology The inferior glands vary more in their location than the superior glands The superior glands are generally located superior to the inferior thyroid artery and posterior to the recurrent laryngeal nerve (classically described as lying 1cm above the intersection of the RLN and inferior thyroid artery

Anatomy and Embryology Common ectopic location for the superior gland includes paraesophageal or retroesophageal areas (superior posterior mediastinum) and intrathyroid The inferior glands usually lie near the inferior pole of the thyroid and are inferior to the inferior thyroid artery and anterior to the RLN The inferior glands are more variable in location. Ectopic locations include in or around the thymus (anterior mediastinum)

Anatomy and Embryology: Ectopic locations

Anatomy Glands are usually oval, bean-shaped or oblong Weigh 30-65mg Average 5x3x2mm Light yellow to caramel color Blood supply to the superior and inferior glands is from the inferior thyroid artery in 86% of patients. In the remainder, both glands are supplied by the superior thyroid artery or by anastomotic arch from both vessels

Anatomy

Physiology Parathyroid hormone (PTH) is an 84-amino acid peptide with the biologic activity residing at its amino terminal PTH regulates serum calcium concentration and bone metabolism (affects bone, kidney and intestine particularly) Serum calcium concentration in turn regulates PTH secretion high calcium  PTH secretion low calcium  PTH secretion

Physiology PTH Increase in renal calcium absorption Increase in enzyme activity converting Vitamin D to its active form and thereby increasing intestinal absorption of calcium Increases osteoclast activity which increases bone resorption and bone remodeling Decreased phosphorous excretion, mild metabolic acidosis and decrease in GFR also occur

Physiology

Primary hyperparathyroidism (PHPT) Syndrome of inappropriate secretion of PTH by one or more abnormal glands Most cases are sporadic with female to male 4:1 Familial syndrome are relatively rare and include: MEN Types I and II Familial isolated HPT Hereditary HPT jaw tumor syndrome 85-90% are caused by a single adenoma Multiple gland disease either as multiple adenomas or hyperplasia of all 4 glands 10-15% <1% parathyroid carcinoma

Parathyroid Adenoma – Right inferior

Primary hyperparathyroidism (PHPT) Classic presentation: “renal stones, painful bones, abdominal groans, psychic moans and fatigue overtones” Severe symptoms which are uncommon include: osteitis fibrosis cystica, osteoclastomas (Brown tumors) and nephrocalcinosis Most patients today are “asymptomatic” with increased calcium found in routine blood tests “Asymptomatic” patients may have subtle symptoms such as neuropsych disorders, dyspepsia, constipation and high blood pressure

Primary hyperparathyroidism (PHPT) Diagnosis made by blood test of increased calcium and increased circulating intact PTH Other causes of hypercalcemia should be ruled out Familial hypocalciuric hypercalcemia (FHH) Autosomal dominant <1% of patients with hypercalcemia PTH usually normal or slightly elevated Urinary calcium secretion NOT usually elevated (in contrast to PHPT) so the fasting urinary calcium to creatnine ratio is less than 0.01

Differential diagnosis of hypercalcemia

Primary hyperparathyroidism (PHPT) Indications for surgery Virtually all patients with symptomatic PHPT and selected patients with asymptomatic PHPT should undergo surgery Guidelines have been liberalized over the years; that is, more people who are asymptomatic now come to surgery (in one study, 25% of asymptomatic patients develop some form of metabolic complication within 5 years of diagnosis Asymptomatic patients not meeting criteria for surgery should have serum calcium checked twice a year and bone densitometry and serum creatnine checked yearly

Primary hyperparathyroidism (PHPT)

Primary hyperparathyroidism (PHPT) Conventional parathyroidectomy Bilateral neck exploration with identification of all 4 glands Removal of enlarged gland(s) (+ / - biopsy of normal glands) 95% success rate This operation is indicated when localization studies fail; when diagnosis of hyperplasia is suspected; and for cases of secondary and tertiary hyperparathyroidism

Primary hyperparathyroidism (PHPT) New approaches to surgery Localization studies Technetium-99 –labeled sestamibi Absorbed and retained by parathyroid disease but rapidly washed out from thyroid Accuracy enhanced by combining it with single photon emission CT (SPECT) Picks up 85% of adenomas Sensitivity decreases with multiple gland disease

Primary hyperparathyroidism (PHPT) New approaches to surgery Localization studies Cervical USG – 60-70% of abnormal glands MRI / CT 75% sensitivity but usually reserved for reoperation

Primary hyperparathyroidism (PHPT) New approaches to surgery Directed parathyroidectomy Makes use of localization studies to allow for unilateral neck dissection on the side of the positive localization Methylene blue, when used preoperatively, can enhance success of localization intraoperatively. Abnormal tissue turns dark blue in color

Primary hyperparathyroidism (PHPT) New approaches to surgery Directed parathyroidectomy Intraoperative PTH monitoring iPTH has short half-life Serial measurement of serum iPTH before, during and at 5 and 10 minutes after removal of enlarged gland will show fall in iPTH Reduction in iPTH greater than of equal to 50% of pre-surgery level indicates success Absolute level of iPTH should fall to normal Success exceeds 90%

Primary hyperparathyroidism (PHPT) New approaches to surgery Directed parathyroidectomy Radioguided parathyroidectomy Employs injection of 99-Tc sestamibi immediately before OR Using gamma probe to detect area of greatest radioactivity Can combine techniques Minimally invasive parathyroidectomy – requires proper localization studies Open minimal access parathyroidectomy Endoscopic parathyroidectomy

Primary hyperparathyroidism (PHPT) Results Parathyroidectomy is curative in 95% of cases of PHPT Persistent PHPT usually results from a missed adenoma Recurrent PHPT (occurs 6 months or more post-op) may develop 5-10% of time, probably due to a second adenoma or hyperplasia of remaining glands

Primary hyperparathyroidism (PHPT) Complications Temporary hypocalcemia (20-30%) Cervical hematoma (less than 1%) Recurrent nerve palsy (1-2%) Recurrent nerve injury (less than 1%)

Primary hyperparathyroidism (PHPT) Parathyroid hyperplasia Consider this diagnosis when localization studies are not helpful 15% of all PHPT Diagnosis in 37% of patients undergoing re-op Pathology found in secondary and tertiary hyperparathyroidism and MEN syndromes Requires bilateral neck exploration In PHPT – perform either 3 ½ gland resection making sure remnant left is viable and marking remnant with vascular clip in case of need for re-exploration or total parathyroidectomy with autotransplantation

Secondary and Tertiary Hyperparathyroidism Secondary hyperparathyroidism Result of chronic overstimulation leading to hyper secretion and hyperplasia of normal parathyroid glands, i.e., chronic hypocalcemic stimulation Seen most commonly in chronic renal failure Surgery is associated with end-stage renal failure, only 1% usually require surgery Bilateral exploration either performing subtotal parathyroidectomy or total parathyroidectomy with immediate autotransplantation

Secondary and Tertiary Hyperparathyroidism Tertiary hyperparathyroidism Occurs in setting of longstanding 2HPT Longstanding parathyroid hyperplasia leads to autonomous function Bilateral exploration either performing subtotal parathyroidectomy or total parathyroidectomy with immediate autotransplantation

Secondary and Tertiary Hyperparathyroidism Indications for surgery Bone and joint pain Intractable pruritis Muscle weakness Malaise X-ray signs of renal osteodystrophy Uncontrolled hypercalcemia Uncontrolled hyperphosphatemia Extraskeletal nonvascular calcifications calciphylaxis

Secondary and Tertiary Hyperparathyroidism

Persistent or Recurrent Hyperparathyroidism Re-operation surgery includes surgery for persistent HPT when the previous operation has failed, and recurrent HPT following initially successful surgery Main causes of recurrent or persistent PHT is missing an adenoma on initial surgery (e.g., failure to locate an ectopic gland), multiglandular disease, multiple adenomas or hyperplasia of the remaining glands, or transplanted parathyroid tissue

Persistent or Recurrent Hyperparathyroidism

Bibliography

Bibliography Kreisel, D. et al. The Surgical Review: An integrated basic and clinical science study guide. Lippincott, 2001. Randolph, G. Management of the Thyroid Nodule. American Academy of Otolaryngology – Head and Neck Surgery Foundation, Inc., 1999. Silver, C. and Rubin, J. Atlas of Head and Neck Surgery. Churchill Livingston, 1999. Cummings, C. et al. Otolaryngology Head and Neck Surgery. Mosby, 1993. Bailey. Head and Neck Surgery – Otolaryngology. Lippincott Greenfield. Surgery – Scientific Principles and Practice. Lippincott Harvey, H. The Otolaryngologic Clinics of North America: Disorders of the thyroid and parathyroid. Vol I. April 1990. Harvey, H. The Otolaryngologic Clinics of North America: Disorders of the thyroid and parathyroid. Vol II. June 1990. Shindo, M., and Singer, P. The Otolaryngologic Clinics of North America: Current concepts in the management of thyroid and parathyroid disorders. August 1996. Miller, F., and Otto, R. The Otolaryngologic Clinics of North America: Disorders of the thyroid. February 2003. Stack, B. The Otolaryngologic Clinics of North America: Parathyroids. August 2004

Endocrine – Thyroid and Parathyroid Glands

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Endocrine – Thyroid and Parathyroid Glands

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