2Thyroidarises as an outpouching of the primitive foregut around the third week of gestationoriginates at the base of the tongue at the foramen cecumDuring its descent, the anlage remains connected to the foramen cecum via an epithelial-lined tube known as the thyroglossal ductpaired lateral anlages originate from the fourth branchial pouch and fuse with the median anlage at approximately the fifth week of gestation. The lateral anlages are neuroectodermal in origin (ultimobranchial bodies) and provide the calcitonin producing parafollicular or C cells
3Developmental Abnormalities Thyroglossal Duct Cyst and Sinusmay occur anywhere along the migratory path of the thyroid80% are found in juxtaposition to the hyoid boneusually asymptomatic but occasionally become infected by oral bacteria, prompting the patient to seek medical advicemidline neck mass that moves upward with protrusion of the tongue.Sistrunk = which consists of en bloc cystectomy and excision of the central hyoid boneLingual Thyroidfailure of the median thyroid anlage to descend normallyIntervention necessary for obstructive symptoms such as choking, dysphagia, airway obstruction, or hemorrhageSurgical excision rarely needed should be preceded by an evaluation of normal thyroid tissue in the neck to avoid inadvertently rendering the patient hypothyroid.
4Evaluation TSH is only necessary test Thyrotropin-Releasing Hormone to evaluate pituitary functionThyroid antibodiesRadionuclide ImagingUltrasoundCT or MRI scans
5Benign Thyroid Disorders Diffuse Toxic Goiter (Graves' Disease)Antibodies against TSH receptorMCC of hyperthyroidism in USStrong familial predispositionConditions such as the postpartum state, iodine excess, lithium therapy, and bacterial and viral infections have been suggested as possible triggersSx: palpitations, nervousness, fatigue, emotional lability, hyperkinesis, GI complaintsSuppressed TSH with elevated T3, T4Tx: antithryroid drugs, radioactive idoine, ablation, surgery when others fail or contraindicated or suspicious noduleToxic Multinodular Goiteroften have a prior history of a nontoxic multinodular goiterthyroid nodules become autonomous to cause hyperthyroidism.See suppressed TSH level and elevated free T4 or T3 levelsRAI uptake also is increased, showing multiple nodules with increased uptake and suppression of the remaining gland.Subtotal thyroidectomy is the gold standard
6Thyroid StormHyperthyroidism accompanied by fever, central nervous system agitation or depression, cardiovascular dysfunctionBeta blockersreduce peripheral T4 to T3 conversiondecrease the hyperthyroid symptoms.Oxygen supplementation and hemodynamic supportLugol's iodinedecrease iodine uptake and thyroid hormone secretion.PTU blocks the formation of new thyroid hormone
7Acute Thyroiditis = Suppurative Thyroiditis Infectious agents can seed it from thehematogenous or lymphatic routevia direct spread from persistent pyriform sinus fistulae or thyroglossal duct cystspenetrating trauma to the thyroid glanddue to immunosuppression.Streptococcus and anaerobes account for about 70% of cases;Acute suppurative thyroiditis is more common in childrenpreceded by an upper respiratory tract infection or otitis mediaTreatment consists of IV antibiotics and drainage of abscesses.
8Subacute Thyroiditis Painful or painless forms Painful thyroiditis thought to be viral in originThyroiditis most commonly occurs in 30- to 40-year-old womenHistory of a preceding upper respiratory tract infection often can be elicited.In the early stages of the disease, TSH is decreased, and T4 , and T3 levels are elevated due to the release of preformed thyroid hormone from destroyed follicles.Painless thyroiditis is considered to be autoimmune in origin
9Chronic ThyroiditisThe most common inflammatory disorder of the thyroid and the leading cause of hypothyroidism.Hashimoto's thyroiditis = autoimmune process thatactivation of CD4+ T (helper) lymphocytes with specificity for thyroid antigensT cells can recruit cytotoxic CD8+ T cells to the thyroidautoantibodies, which lead to complement fixation and killing by natural killer cellsMore common in women between the ages of 30 and 50 years old.An elevated TSH and the presence of thyroid autoantibodiesFNAB is indicated in patients who present with a solitary suspicious nodule or a rapidly enlarging goiter.TreatmentThyroid hormone replacement therapy is indicated in overtly hypothyroid patients, with a goal of maintaining normal TSH levels.
10Riedel’s Thyroiditisreplacement of all or part of the thyroid parenchyma by fibrous tissueetiology of this disorder is controversialpredominantly in women between the ages of 30 to 60 years oldpresents as a painless, hard anterior neck mass, which progresses over weeks to years to produce symptoms of compression, including dysphagia, dyspnea, choking, and hoarseness.Patients may present with symptoms of hypothyroidism and hypoparathyroidism as the gland is replaced by fibrous tissueSurgery is mainstay of treatment
11Solitary Nodule 4% of individuals in the United States Assess symptoms Determine family historyrisk factor for the development of both medullary and nonmedullary thyroid cancerDo PEbest palpated from behind the patient and with the neck in mild extension.Then proceed to further tests…
13Papillary Cancer 80% of all thyroid malignancies predominant thyroid cancer in children and individuals exposed to external radiation.Lymph node metastases are common,Orphan Annie nucleiPsammoma bodiesExcellent prognosis with a >95% 10-year survival rate.AGES scoring systemAge,histologic Grade,Extrathyroidal invasionmetastases and tumor SizeLow versus High risk patientsIf any high-risk factors total or near-total thyroidectomy.If minimal papillary thyroid carcinoma in removed for other reasons, unilateral thyroid lobectomy and isthmusectomy is usually enough.
14Follicular Cancer 10% of thyroid cancers Limitations inherent to FNAB diagnosisUsually are solitary lesions, and the majority are surrounded by a capsule.TreatmentThyroid lobectomy because at least 80% of these patients will have benign adenomas.Intraoperative frozen-section examination usually is not helpfulTotal thyroidectomy should be performed when thyroid cancer is diagnosed
15Postop Management Stop T4 therapy for 4-6 weeks Radioactive Iodine Scan look for hot spotAdjuvant treatment with radioactive iodineThen resume thyroid replacement therapy, will help supressCan follow thyroglobulin measurement as markerScreening ultrasound periodically to evaluate central and lateral neck compartments
16Medullary Carcinoma5% of thyroid malignancies and arises from the parafollicular or C cells of the thyroid,25% occur within the spectrum of several inherited syndromes such as familial MTC, MEN2A, and MEN2B.germline mutations in the RET proto-oncogene.Present with neck mass, lymphadenopathy in 15-20%Hematogenous spreadUnilateral if sporadic, multifocal if familialAmyloid on slidesScreen for MEN!Treat pheochromocytoma firstTotal thyroidectomy with bilateral central neck dissectionFollowup measure calcitonin and cEA10 yr survival 80%Perform prophylactic thyroidectomy for MEN2 with RET
17Anaplastic Thyroid Cancer 1 % of thyroid malignancies in USWomen more commonClassic: long standing neck mass that rapidly enlarges and becomes painfulSx: dysphonia, dysphagia, and dyspneaMay be fixed to surrounding structures or may be ulcerated with areas of necrosisConfirmed by FNAIsthmusectomy with or without a tracheostomy may be needed to alleviate tracheal obstruction.Treatment and Prognosismost aggressive thyroid malignancyfew patients surviving 6 monthsCombined radiation and chemotherapy in patients with resectable disease has been associated with prolonged
18ParathyroidSuperior glands from the fourth branchial pouch (also thyroid gland)Inferior glands form third branchial pouch (also thymus)The position of normal superior parathyroid glands is more consistentwith 80% of these glands being found near the posterior aspect of the upper and middle thyroid lobes,Approximately 15% of inferior glands are found in the thymus.Undescended inferior glands may be foundnear the skull base,angle of the mandible,frequency of intrathyroidal glands is about 2%.
19Parathyroid Physiology Rely on a G-protein coupled membrane receptor to regulate PTH secretion by sensing extracellular calcium levelsPTH secretion also stimulated by low levels of 1,25-dihydroxy vitamin D, catecholamines, and hypomagnesemia.Secreted PTH has a half-life of 2 to 4 minutes.PTH functions to regulate calcium levels via its actions on three target organs:BoneKidneyGutCalcitonin produced by thyroid C cells antihypercalcemic hormoneinhibits osteoclast-mediated bone resorption.Vitamin D refers to vitamin D2 and vitamin D3 ,both produced by photolysis of naturally occurring sterol precursorsVitamin D is metabolized in the liver to its primary circulating form, 25-hydroxyvitamin D.Further hydroxylation 1,25-dihydroxy vitamin D most metabolically activeVitamin D stimulates the absorption of calcium and phosphate from the gut and the resorption of calcium from the bone.
20Primary Hyperparathyroidism Most cases of PHPT are sporadic.Occurs within the spectrum of a number o inherited disorders such as MEN1, MEN2A, isolated familial HPTHyperplasia, Adenoma, CarcinomaPHPT is the earliest and most common manifestation of MEN180 to 100% of patients by age 40 years oldSx: kidney stones, painful bones, abdominal groans, psychic moans, and fatigue overtonesMore likely to be asymptomatic and picked up on blood testsMeasure PTH to decide between the 2 causes of hypercalcemiaSurgery for complications, classic symptoms, age < 50Total versus focusedLocalization studies: ultrasound, Sestamibi scan
21Parathyroid Carcinoma 1% of PHPT cases.Suspect by preoperatively by the presence of severe symptomsserum calcium levels >14 mg/dLsignificantly elevated PTH levels (5 x normal)palpable parathyroid glandLocal invasion is most commonTreatmentbilateral neck exploration, with en bloc excision of the tumor and the ipsilateral thyroid lobe.Modified radical neck dissection if lymphadeonopathy
22Hypercalcemic Crisis Uncontrolled PTH secretion, worsened by polyuria, dehydration, and reduced kidney functionTreatment consists of therapies to lower serum calcium levels followed by surgeryThe mainstay of therapy involves rehydrationdiuresis with furosemideFurther bisphosphonates, etc
23Parathyroid Surgery Asymptomatic Patient Serum Ca > 1 mg/dl Above upper limits of normalLife threatening hypercalcemic episodeReduced creatinine clearanceRenal stones on xrayMarkedley elevated 24 hour urine CaSubstantially decreased bone mineral density
24Secondary Hyperparathyroidism commonly occurs in patients with chronic renal failure but also may occur in those with hypocalcemia secondary to inadequate calcium or vitamin D intake, or malabsorption.The pathophysiology 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 responsegenerally hypocalcemic or normocalcemic.treated medically with a low-phosphate diet, phosphate binders, adequate intake of calcium and 1,25-dihydroxy vitamin D and a high calcium, low-aluminum dialysis bath.Surgery if:bone pain, pruritus, calcium >11 mg/dL with markedly elevated PTH, calciphylaxisA bilateral neck exploration is indicatedConsider subtotal resection with autotransplant
25Tertiary Hyperparathyroidism some patients develop autonomous parathyroid gland function and tertiary HPT after renal transplantpathologic fractures, bone pain, renal stones, mental status changes.Surgery if persists 1 year after transplant
26Parathyroid Complications HypocalcemiaVocal cord paralysisHypoparathyroidismPermanent if > 6 mths
27Adrenal Outer cortex and an inner medulla The cortex originates from mesodermal tissue near the gonadsEctopic adrenocortical tissue may be found in the ovaries, spermatic cord, and testes.Adrenal medulla is ectodermal in origin and arises from the neural crest.Most extra-adrenal neural tissue regresses but may persist at several sites.The largest of these ia left of the aortic bifurcation near the inferior mesenteric artery origin and is designated as the organ of Zuckerkandl.
28HyperaldosteronismSecondary causes from stimulation of the renin-angiotensin system from renal artery stenosis and to low-flow states such as congestive heart failure and cirrhosis.Primary hyperaldosteronism results from autonomous aldosterone secretion which, Ileads to suppression of renin secretion.1% of hypertension cases.HypokalemiaCauses:Adenoma 70%Hyperplasia 30%Carcinoma rareSx: hypertension difficult to control despite multiple-drug therapy, muscle weakness, polydipsia, polyuria, nocturia, headaches, and fatigue.Labs: K+. Measure renin-aldosteroneCT scan can localize with sensitivity of 90%Selective venous samplingTxs:spironolactone (aldosterone antagonist)amiloride (a potassium-sparing diuretic that blocks sodium channels in the distal nephronnifedipineCaptoprilUnilateral tumors producing aldosterone are best managed by adrenalectomy
29Cushing Syndrome Hypercortisolism Most common cause iatrogenic 70% are pituitary tumor, 20% adrenal tumor, 10% ectopic ACTH producing tumorSx: wt gain, buffalo hump, central obesity, striae, acne, hypertension, neurologic or pyschiatric disorderselevated glucocorticoid levels that are not suppressible by exogenous hormone administration and loss of diurnal variationovernight low-dose dexamethasone suppression test. In this testCushing's syndrome patients do not suppressMeasure ACTH to determine if ACTH dependent;If ACTH dependent do high dose dexamethoasone test; if no supression then likely ectopicLaparoscopic adrenalectomy is the treatment of choice for patients with adrenal adenomas.Open adrenalectomy for large tumors (≥6 cm) or those suspected to be adrenocortical cancersCushing disease treatment is transsphenoidal excisionMay need mineralocorticoid and glucocorticoid replacement therapy
30Congenital Adrenal Hyperplasia Deficiencies or complete absence of enzymes involved in adrenal steroidogenesis.21-Hydroxylase deficiency is the most common enzymatic defect (>90% of cases)overproduction of adrenal androgens and corticosteroid precursors such as 17-hydroxyprogesterone and androstenedione.converted to testosterone in the peripheral tissues, thereby leading to virilization.Complete deficiency of 21-hydroxylase presents at birth with: virilization, diarrhea, hypovolemia, hyponatremia, hyperkalemia, and hyperpigmentation.Dx: karyotype and measurement of plasma and urinary steroidsTx: traditionally have been managed medically with cortisol and mineralocorticoid replacement to suppress the hypothalamic-pituitary-adrenal axis.teroids required often are supraphysiologic lead to iatrogenic hypercortisolism lap adrenalectomy gaining momentum
31PheochromocytomaDisorders of the Adrenal Medulla; paraganglioma if extra adrenal10 percent tumor because10% are bilateral, 10% are malignant, 10% occur in pediatric patients, 10% are extra-adrenal, and 10% are familial.Pheochromocytomas occur in families with MEN2A and MEN2BSx: Headache, palpitations, and diaphoresisDx: 24 hr urine for catecholamines and plasma metanephrinesCT to localize tumorNeed alpha blocker first, titrate to orthostatic hypotensionAdrenalectomy is treatment of choice12-29% are malignant, and these tumors are associated with decreased
32Adrenal Insufficiency May be primary, resulting from adrenal disease, or secondary, due to a deficiency of ACTHThe most commonly encountered causes of primary adrenal insufficiency are autoimmune disease, infections, and metastatic deposits.fulminant meningococcal septicemia (Waterhouse-Friderichsen syndrome).Bilateral adrenal hemorrhage also can occur secondary to trauma, severe stress, infection, and coagulopathies and, if unrecognized, is lethal.Suspect in stressed patients with any of the relevant risk factorslaboratory findings: hyponatremia, hyperkalemia, fasting or reactive hypoglycemiaACTH stim testPeak cortisol levels <20 g/dL suggest adrenal insufficiencyReplace glucocorticoids and mineralocorticoids