Endocrine, Pituitary, Adrenal ABSITE flashcards

Addison's disease:
-low aldosterone and glucocorticoids -> low Na, high K, hypoglycemia
-Crisis presents similar to sepsis with hypotension, fever
-Steroids are diagnostic and therapeutic

Phenylethanolamine N-methyltransferase (PNMT) in adrenal medulla converts NE to epi.
increased by cortisol (from adrenal cortex)
-S-adenosyl-L-methionine ('SAM') is a required cofactor

ipsilateral adrenelectomy
In patients with non-functional adrenal masses, adrenalectomy should be performed if the tumor is more than 6 cm or if the CT and/or MRI scanning are atypical for an adenoma.
Non-functional lesions smaller than 4cm may be safely observed with interval CT or MRI scanning at 3 months and 1 year. Between 4 and 6 cm are controversial

Breast cancer mets to bone release PTHrp -> hypercalcemia
-Sm cell lung ca, other non-hematologic cancers do this as well. Hyper-ca NOT 2/2 bone destruction.
-increased urine cAMP 2/2 effect of PTHrp on kidney (unlike low urine cAMP in hematologic malignancies, which increase Ca by bone destruction)

Parafollicular C cells:
-derived from neural crest
-produce calcitonin => decrease serum Ca

CAH: 21-hydroxylase defic (90%): high 17-OH progesterone -> high testosterone, salt wasting -> HYPOtension, precocious puberty (M), virilization (F). Tx = cortisol, genitoplasty
-11-hydroxylase defic: high 11-deoxycortisone -> salt saving, HYPERtension, precoc. puberty, virilization. Tx = same
-17-hydroxylase defic: ambiguous genitalia in males @ birth. salt saving

CAH: 21-hydroxylase defic (90%): high 17-OH progesterone -> high testosterone, salt wasting -> HYPOtension, precocious puberty (M), virilization (F). Tx = cortisol, genitoplasty
-11-hydroxylase defic: high 11-deoxycortisone -> salt saving, HYPERtension, precoc. puberty, virilization. Tx = same
-17-hydroxylase defic: ambiguous genitalia in males @ birth. salt saving

CAH:
21-hydroxylase defic (90%): high 17-OH progesterone ->
high testosterone, salt wasting ->
HYPOtension, precocious puberty (M), virilization (F).
Tx = cortisol, genitoplasty

11-hydroxylase defic: high 11-deoxycortisone ->
salt saving, HYPERtension, precoc. puberty, virilization.
Tx = same

17-hydroxylase defic: ambiguous genitalia in males @ birth.
salt saving

Conn's syndrome = hyperaldosteronism
-Primary (low renin, A:R ratio >400): 80% adenoma, 20% bilateral hyperplasia (see with postural stimulation test)
-[Secondary (high renin): more common. CHF, renal artery stenosis, liver failure, pregnancy, diuretics, Barter's syn (renin-secreting tumor)]
-HTN, low K, high Na
-Captopril test =>aldosterone decreases if 2/2 hyperplasia (vs. tumor) or Upright sitting test (slight increase in aldosterone and renin if hyperplasia)
-18-OH corticosterone is high (>100 ug/dL) c/ cancer, low c/ hyperplasia
- if Adenoma => responds well to surgery.
- if Hyperplasia => 1st try spironolactone, Ca channel blocker, K
- needs postop fludrocortisone if bilat resection done

Cricothyroid muscle is ennervated by the superior laryngeal nerve

Cushing's syndrome:
-#1 cause = iatrogenic
1. 24-hr urine cortisol = most sensitive
2. low-dose overnight dex supp test: low cortisol means pituitary adenoma is supressed = Cushing's dz
3. serum ACTH: high => ectopic ACTH or pituitary tumor not suppressed by low-dose test (go to #4). low=> hypercortisol 2/2 adrenal tumor or hyperplasia
4. high-dose overnight dex supp test. (+) = pituitary origin. (-) = ectopic ACTH. if can't tell, proceed to CRH test (pituitary adenoma will make increased ACTH but ectopic production won't respond.)
-MRI useful. NP-59 scintigraphy localizes adrenal tumors, differentiates from hyperplasia

Cushing's syndrome:
1.24-hr urine cortisol = most sensitive
2. low-dose overnight dex supp test: low cortisol means PITUITARY ADENOMA (high ACTH) is supressed = CUSHING'S DZ
3. serum ACTH: low=> hypercortisol 2/2 adrenal tumor or hyperplasia. high => ectopic ACTH or pituitary tumor not suppressed by low-dose test (go to #4).
4. high-dose overnight dex supp test. (+) = pituitary origin. (-) = ectopic ACTH. if can't tell, proceed to CRH test (pituitary adenoma will make increased ACTH but ectopic production won't respond.)

Pituitary adenoma: mostly MICROadenomas. Need petrosal sampling to figure out which side. MRI also helpful. Vertical incision to find adenoma. Most resected c/ transsphenoidal approach. XRT if unresectable.

Cushing's syndrome:
1. 24-hr urine cortisol = most sensitive
2. low-dose overnight dex supp test: low cortisol => pituitary adenoma = Cushing's dz
3. serum ACTH: high => ectopic ACTH or pituitary tumor (go to #4). low=> hypercortisol 2/2 ADRENAL ADENOMA OR HYPERPLASIA (15% of cases, low ACTH)
4. high-dose overnight dex supp test. (+) = pituitary origin. (-) = ectopic ACTH. if can't tell, proceed to CRH test (pituitary adenoma will make increased ACTH but ectopic production won't respond.)
-MRI useful. NP-59 scintigraphy localizes adrenal tumors, differentiates from hyperplasia

Cushing's syndrome:
1. 24-hr urine cortisol = most sensitive
2. low-dose overnight dex supp test: low cortisol => pituitary adenoma = Cushing's dz
3. serum ACTH: high => ectopic ACTH or pituitary tumor (go to #4). low=> hypercortisol 2/2 adrenal adenoma or hyperplasia
4. high-dose overnight dex supp test. (+) = pituitary origin. (-) = ECTOPIC ACTH (most commonly sm cell ca). if can't tell, proceed to CRH test (pituitary adenoma will make increased ACTH but ectopic production won't respond.)
-MRI useful. NP-59 scintigraphy localizes adrenal tumors, differentiates from hyperplasia

Cushing's Syndrome = central obesity, glucose intolerance, hypertension, plethora, hirsutism, osteoporosis, nephrolithiasis, menstrual irregularity, muscle weakness, and emotional lability.
The most common cause of non-iatrogenic Cushing syndrome is Cushing disease, ACTH secreting pituitary adenoma (68%).
Adrenal adenoma accounts for 10% of non-iatrogenic cases.
Ectopic CRH syndrome accounts for <1%.

Familial hypercalcemic hypocalciuria:
-2/2 increased binding of PTH to defective PTH receptor in distal convoluted tubule -> increased Ca resorption
-Tx: do nothing. NO parathyroidectomy (Ca not very elevated)

Thyroid mass c/ FNA (+) for follicular cells:
5-10% malignancy risk => lobectomy (or thyroidectomy)

Thyroid lobectomy (+) for follicular CA => proceed to total thyroidectomy if >1 cm or extrathyroidal disease (capsule invasion, clinical or pos. nodes, mets)
-Clinically (+) cervical LNs or extrathyroidal dz => ipsilateral MRND
-Lesion >1 cm or capsular invasion => I-131 x 6 weeks post-op
-Microinvasive (<1 cm), rare nodal spread (<10%), then usually incidental finding on path and lobectomy is sufficient as long as margins (-)
-Thyroid hormone replacement postop to reduce TSH, suppress future growth
-70% 5-yr survival, prognosis depends on stage

Follicular thyroid CA:
-50-60% metastatic @ presentation, more aggressive than papillary CA
-Hematogenous spread (BONE most common)
-Typicaly age 50's-60's, F:M 3:1
-If FNA shows follicular cells => 10% malignancy risk
-Path (+) for adenoma or follicular hyperplasia => lobectomy only
-typically requires total thyroidectomy + postop RI ablation
-Follicular Ca >1 cm or extrathyroidal dz => total thyroidectomy
-Clinically (+) cervical nodes or extrathyroidal dz => ipsilateral MRND
-Lesion >1 cm or extrathyroidal dz/capsular invasion => I-131 x 6 weeks post-op
-Microinvasive (<1 cm), rare nodal spread (<10%), then usually incidental finding on path => lobectomy suffiicient as long as margins (-)
-70% 5-year survival, prognosis based on stage

FNA can't distinguish malignant/benign with follicular or Hurthle cell (subtype of follicular) => need TISSUE
-10% cahnge of malignancy if FNA shows follicular cells

Excess gastrin production
Excess acid inactivation of small bowel enzymes causes malabsorption leading to diarrhea.

Total thyroidectomy
-Hurthle cell ca = subtype of follicular thyroid ca.
-Similar tx, prognosis
-early nodal spread if malignant
-mets to bone, lung
-< 2cm + contained in 1 thyoid lobe => lobectomy or isthmectomy.
-2-4 cm + high risk patient (e.g. advanced age) => total thyroidectomy
- > 4cm => total thyroidectomy must be done b/c 50% risk of cancer.
-MRND if clinically (+) nodes

Hypercalcemia:
-Confusion, somnolence, shortened QT
-Tx: NS @ 200-300/hr, Furosemide
-NO LR or thiazides!

THIAZIDES cause hypercalcemia

1% rate of persistant hyperparathyroidism after parathyroidectomy
-Usually 2/2 missed adenoma in the neck

Hyperthyroid in pregnancy:
-1st line = propylthiouracil (does not cross placenta)
-Persistant sx-=> thyroidectomy in 2nd trimester (decreased risk of adverse events, premature labor)
-I-131 would ablate fetal thyroid
-Methimazole causes cretinism
-Don't mask sx c/ beta blocker b/c hyperthroidism still present, still increased risk of stillbirth, cause fetal growth retardation in 3rd trimester

Hypoparathyroidism:
#1 cause = previous thyroid surgery
-Numbness/tingling in cirumoral area, fingers -> anxiety, confusion -> Tetany (carpopedal spasms, convusions, laryngospam which can be deadly
-Concomitant hypo-Mg can make correction of Ca difficult

Give thyroid hormone replacement following I-131 for papillary or follicular thyroid ca
-Suppresses TSH -> suppress growth of residual cancer tissue

Radioactive I:
-for well-differentiated tumors (papillary, follicular)

must be hypothyroid for I-131 scan =>
stop levothyroxine (T4) 6 weeks before, liothyroxine (T3) 3 weeks before

insulinoma = #1 endocrine pancreatic tumor overall
(but not part of a MEN subgroup; gastrinoma = #1 endocrine pancreatic tumor in MEN)

Medullary thyroid ca:
-from parafollicular C cells. Ret proto-oncogene = diagnostiic
-20% have MEN2 (tend to be bilat, younger, worse prognosis)
Path: AMYLOID pathognomonic
-Provocative test: administer GASTRIN -> increases calcitonin
-Tx: total thyroidectomy. add neck dissection if node (+)

MEN I syndrome include parathyroid hyperplasia (causing hypercalcemia), pancreatic and duodenal neuroendocrine tumors, and pituitary tumors.
1. total parathyroidectomy or 3 1/2 with autotransplantation for hypercalcemia. If pt has ZE syn, should improve the symptoms. 2. gastrinoma resection if sx not improved c/ PPIs and parathyroidectomy

MEN 1:
Pancreatic islet cell tumor (Gastrinoma = #1, 50% multiple, 50% malignant, #1 morbidity of MEN 1)
Pituitary tumor (Prolactinoma = #1)
hyper-Parathyroidism (usually 1st to have sx, fix this 1st)
MENIN gene

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. Prolactinoma = #1

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. Prolactinoma = #1

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. Prolactinoma = #1

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. PROLACTINOMA = #1

MEN 2a:
hyper-Parathyroidism
Medullary thyroid ca (in nearly all pts, 1st to be symptomatic - usually diarrhea, #1 cause of death in MEN 2a)
Pheochromocytoma (often bilateral, almost always benign, fix this 1st)
-RET protooncogene

MEN 2a: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia in 5-20%
-Pheochromocytoma in 10-60%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in ~100%, often bilateral. #1 cause of death in MEN2. Usually 1st part to be symptomatic = diarrhea 2/2 calcitonin

MEN 2a: RET proto-oncogene, from APUD (amine precursor uptake decorboxylase) cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia in 5-20%
-Pheochromocytoma in 10-60%. Often bilateral, benign. corrected 1st.
-Medullary ca of thyroid in ~100%, often bilateral. #1 cause of death in MEN2. 1st to be symptomatic usually: => diarrhea 2/2 calcitonin most common.

MEN 2a: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia in 5-20%
-Pheochromocytoma in 10-60%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in ~100%, often bilateral. #1 cause of death in MEN2. Usually 1st part to be symptomatic: => diarrhea 2/2 calcitonin most common.

MEN 2b:
mucosal neuromas, Marfan's habitus, musculoskel abnormalities
Medullary thyroid ca (in nearly all pts, 1st to be symptomatic - usually diarrhea, #1 cause of death in MEN 2a)
Pheochromocytoma (often bilateral, almost always benign, fix this 1st)
RET protooncogene

MEN 2b: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Mucosal neuromas (gut), ganglioneuromatosis in 100%
-Marfanoid habitus, musculoskel abnormalities
-Pheochromocytoma in 50%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in~100%, often bilateral. #1 cause of death in MEN2, more aggressive in MEN2b. Usually 1st part to be symptomatic = diarrhea 2/2 calcitonin

MEN 2b: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Mucosal neuromas (gut), ganglioneuromatosis in 100%
-Marfanoid habitus, musculoskel abnormalities
-Pheochromocytoma in 50%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in~100%, often bilateral. #1 cause of death in MEN2, more aggressive in MEN2b. Usually 1st part to be symptomatic => diarrhea most common.

MEN 2b: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Mucosal neuromas (gut), ganglioneuromatosis in 100%
-Marfanoid habitus, musculoskel abnormalities
-Pheochromocytoma in 50%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in~100%, often bilateral. #1 cause of death in MEN2, more aggressive in MEN2b. Usually 1st part to be symptomatic => diarrhea most common.

Methimazole:
-Prevents peripheral conversion of T4-> T3
(unlike PTU, doesn't also prevent creation of thyroid hormone in gland)
-high relapse rate => continue x6 mo before stopping, or before starting radioactive iodine

solitary neck mass => do FNA (don't need to get imaging 1st)

Nelson syndrome:
-after bilateral adrenalectomy (10%)
-Increased CRH -> pituitary enlargement ->
ACTH, amenorrhea, pigmentation (2/2 beta-MSH = melanocyte stim. hormone = peptide byproduct of ACTH), bitemporal hemianopsia
-Tx = steroids

Primary hyperparathyroidism
-PTH >40 pg/mL, Ca >10.5, Cl:PO4 ratio >33, +/-hyperchloremic met acidosis,
-PRAD-1 oncogene, radiation exposure increase risk of adenoma
-Older women
-OSTEITIS FIBROSA CYSTICA (brown tumors) = bone lesions 2/2 Ca resorption
-Most pts asymptomatic
-Sx: muscle weakness, myalgia, nephrolithiasis, pacreatitis, PUD, depression, bone pain, pathologic fx, MS change, constipation, N/V, anorexia
-Can get HTN 2/2 renal impairment

Insulinoma = #1 endocrine pancreatic tumor overall
(but not part of a MEN subgroup)

Papillary thyroid ca:
-Total thyroidectomy for: >1 cm, bilateral lesions, multicentricity, hx XRT, extra-thyroidal dz (capsular invasion, (+) margins, mets, clincal or (+) LNs)

Papillary thyroid ca = most Popular = 85% of thyroid cancer
-Lymphatic spread but nodes don't predict survival
-20% of adults, 80% of children are node (+) on presentation, 80% are multicentric.
-F:M 3:1. 50% before age 40
-Path:PSAMMOMA bodies represent deposited Ca
-RF = radiation exposure
-MACIS criteria: Mets, Age M>50 or F>40, Completeness of resection, Invasiveness, Size >1.5 cm

inferior thyroid artery supplies the parathyroids

missed adenoma = #1 reason for persistent primary hyperparathyroidism
-5% of pts have multiple adenomas @ time of surgery

#1 location for a missed parathyroid gland @ reexploration =
normal anatomic position

INFERIOR THYROID artery = blood supply to superior and inferior parathyroid glands

Superior parathyroids: 4th pouch, ass'd c/ thyroid complex. lateral to RLN. above inf thyroid art.

Inferior parathyroids + thymus: 3rd pharyngeal pouch. inferior more variable position.. medial to RLN. below inf thyroid art #1 ectopic site = tail of thymus.

#1 location for ectopic parathyroid gland =
inferior parathyroids in TAIL OF THYMUS, can migrate to the anterior mediastinum
-Other ectopic sites: intrathyroid, mediastinum, near tracheoesophageal groove

4-gland parathryoid hyperplasia is treated c/ 4-gland resection + forearm re-implant or 3.5-gland resection
(only do reimplant into the SCM if parathryroid accidentally injured during thyroidectomy)
1. inside carotid sheath + look there
2. tracheoesophageal groove
3. transcervical thymectomy
4. ipsilateral thyroid lobectomy

-if intra-op PTH being measured, can confirm that 4th parathryoid is out (should drop 50% in 10-15 min)

The vascular supply to the parathyroid glands is mainly from the inferior thyroid artery. However, it can also arise from superior thyroid artery (20% of superior parathyroids), the lowest thyroid artery (thyroidea ima), and the arteries of larynx, trachea, esophagus or mediastinum

Parathyroid carcinoma:
-Rare. Presents c/ similar sx to parathyroid adenoma (hyper-Ca)
-Suspect if Ca >15 or palpable neck mass + primary hyperparathyoid
-Unlike adnenoma, more likely to be locally invasive (not "shell out") on excision
-Tx: en bloc resection of gland c/ surrounding structures (usually ipsilateral thyoid lobectomy)

Parathyroid hormone:
-Normal level 5-40 pg/mL (also sae 10-60 pg/mL)
1/2 life 18 min
Ca reabsorbtion in DCT, PO4 secretion
-Increases osteoclasts in bone to release Ca, Po4
N terminal active, C terminal inactive (like insulin)
-1-OH-hydroxylation of VitD in kidney -> more Ca-binding protein in intestine

Parathyroid hormone:
increases 1-OH hydroxylation of vit D in kidney -> increases Ca binding protein -> increases Ca and PO4-absorption in gut
-increases Ca absorption in DCT of kidney, decreases PO4 absorption
-promotes Ca and PO4- release by osteoclasts

Pheochromocytoma:
Hypotension following removal is 2/2 hypovolemia
-Treat c/ IV fluid bolus

Phenoxybenzamine will worsen vasodilation, hypotension
Epi (alpha 1, beta 1/2), phenylephrine (alpha 1 agonist) will work only transiently

Pheochromocytoma pre-op prep:
1. PHENOXYBENZAMINE or prazosin (long-acting alpha blockade) x 1-3 weeks
2. Fluid loading (pt should gain fluid weight)
3.Propranolol (beta blockade) x 48 hrs

-Start beta blockade AFTER alpha blockade confirmed by normal orthostatic changes, fluid loading complete.
-Unopposed alpha adrenergic activity can cuase MI, hypertensive crisis, pulm edema-

Pheochromocytoma: -
Rare, slow-growing, R>L
-CHROMAFFIN cells: symp ganglia or neural crest cells
-10% rule: malignant, bilateral, in children, familial, extra-adrenal
-EXTRAadrenal more likely malignant, don't make epi. #1 location = Organ of Zuckerkandl @ aortic bifurcation
-Ass'd c/ MEN2a/b, von Recklinghausen's, tuberous sclerosis, Sturge-Weber
-Sx: episodic HT, headache, diaphoresis, palpitations
-Dx: 24-hr urine VMA (most sensitive), metanephrines = breakdown products of epi, NE
-MIBG scan (131-metaiodobenzylguanine = NE analogue) (or CT, MRI) => locate. Still can't localize => laparotomy
-Clonidine supression test (a tumor doesn't respond)
-DON'T do venography => can cause hypertensive crisis

Diagnosis of malignant pheochromocytoma is often difficult. It generally established when there is invasion of adjacent structures or by documenting nodal or distant metastases

Posterior pituitary =neurohypophysis: ADH, oxytocin
Anterior pituitary = adneohypophysis: GH, ACTH, TSH, LH, FSH, prolactin
-Chromophobe pit. adenoma: non-functional. decreased GH, FSH, LH, TSH, ACTH
-Prolactinoma = #1 pituitary adenoma (tx: bromocriptine or transsphenoidal resection)

Posterior pituitary =neurohypophysis: ADH, oxytocin
Anterior pituitary = adneohypophysis: GH, ACTH, TSH, LH, FSH, prolactin
-Chromophobe pit. adenoma: non-functional. decreased GH, FSH, LH, TSH, ACTH

-Prolactinoma = #1 pituitary adenoma
Tx: bromocriptine.
MICROadenomas (most cases): transsphenoidal resection if failure of med mgmt. Pregnancy not an indication.
MACROadenomas: resect if hemorrhage, visual loss, pregnancy, CSF leak

Posterior pituitary =neurohypophysis: ADH, oxytocin
Anterior pituitary = adneohypophysis: GH, ACTH, TSH, LH, FSH, prolactin
-Chromophobe pit. adenoma: non-functional. decreased GH, FSH, LH, TSH, ACTH
-Prolactinoma = #1 pituitary adenoma (tx: bromocriptine or transsphenoidal resection)

Plummers syndrome:
-hyper-functioning nodule develops within a longstanding goiter ->
-Hyperthyroidism without ophthalmologic sx
-Toxic multi or uni-nodular goiters
-Typical population: women over the age of 60
-Indication for thyroidectomy (doesn't respond to meds)

Primary hyperparathyroidism
-Hyperchloremic metabolic acidosis
-PTH >40 pg/mL
-Ca >10.5
-High renal cAMP (effect on PTH R in kidney)
Cl:PO4 ratio >33
-High urine Ca in 70% (normal in 30%)

Primary hyperparathyroidism
-PTH >40 pg/mL, Ca >10.5, high renal cAMP (effect on PTH R in kidney), Cl:PO4 ratio >33, +/- HYPERCHLOREMIC METABOLIC ACIDOSIS,
-PRAD-1 oncogene increases risk for adenomas
-Older women
-Osteitis fibrosa cystica (brown tumors) = bone lesions 2/2 Ca resorption
-Most pts asymptomatic
-Sx: muscle weakness, myalgia, nephrolithiasis, pacreatitis, PUD, depression, bone pain, pathologic fx, MS change, constipation, N/V, anorexia
-Can get HTN 2/2 renal impairment

Primary hyperparathyrodism:
80-85% have single adenoma => resect adenoma, inspect other glands to r/o hyperplasia or another adenoma
4%% have multiple adenomas
15% have diffuse hyperplasia (MEN 1 ot 2a have 4-gland hyperplasia) => don't biopsy all glands b/c risk of hemorrhage, hypo-PTH. resect 3.5 glands or parathyroidectomy + reimplantation
<1% have parathyroid adnenocarcinoma (very high Ca levels) => radical parathyroidecomy including ipsilateral glands

Primary hyperparathyroidism
-PTH >40 pg/mL, Ca >10.5, Cl:PO4 ratio >33, +/-hyperchloremic met acidosis,
-PRAD-1 oncogene, RADIATION exposure increase risk of adenoma
-Older women
-Osteitis fibrosa cystica (brown tumors) = bone lesions 2/2 Ca resorption
-Most pts asymptomatic
-Sx: muscle weakness, myalgia, nephrolithiasis, pacreatitis, PUD, depression, bone pain, pathologic fx, MS change, constipation, N/V, anorexia
-Can get HTN 2/2 renal impairment

Primary hyperparathyroidism - 5 indications for surgery:
1.Symptomatic dz
2.Asymptomatic + Ca>13
3. Decreased Cr clearance
4. Nephrolithiasis
5. Significantly decreased bone mass

Adenoma (84%). PRAD-1 increases risk => resection; inspect other glands to r/o hyperplasia or multiple adenomas (4%)
-Hyperplasia (15%) => resect 3.5 glands or total parathyroidectomy + autoimplantation (don't biopsy all glands 2/2 risk of hemorrhage + hypoparathyroid)
-Parathyroid adenocarcinoma (<1%) => radical parathyroidectomy (c/ ipsilateral thyroid)
-Pregnancy => surgery in 2nd trimester to avoid risk of 3rd trimester stillbirth

Primary hyperparathyroidism
-Hyperchloremic metabolic acidosis
-PTH >40 pg/mL
-Ca >10.5
-High renal cAMP (effect on PTH R in kidney)
Cl:PO4 ratio >33
-High urine Ca in 70% (normal in 30%)

Propylthiouracil (thionamide, along with methimazole):
-INHIBITS PEROXIDASES, which connect iodine to tyrosine to form DIT, MIT
-PTU, propranolol, and Prednisone also inhibit peripheral conversion of T4 -> T3
-SE: aplasic anemia, AGRANULOCYTOSIS (rare)
-crosses placenta. preferred over methimazole definitely during FIRST trimester, most review books says all of pregnancy

Propylthiouracil:
-Inhibit peroxidases -> prevents DIT, MIT coupling
-SE: aplasic anemia, agranulocytosis (rare)
-PTU preferred in 1st trimester; may change to methimazole in 2nd-3rd trimester. can cause cretinism.

Recurrent laryngeal nerve injury (e.g. during total thyroidectomy) -> hoarseness
(R injury more common than L but R less likely to be recurrent)

Recurrent laryngeal nerve:
-Innervates all of larynx except CRICOTHYROID muscle
-Run posterior to thyroid lobes in tracheoesophageal groove
-Can tract c/ inferior thyroid artery, but variable
-L RLN loops around aorta
-R RLN loops around R subclavian = innominate artery, but R is more lateral, more likely than L to be non-recurrent (e.g. 2/2 replaced R subclavian off the descending aorta)
-Risk of injury to non-recurrent laryngeal nerve during surgery
-Unilateral injury -> hoarseness; Bilat injury -> airway obstruction 2/2 medialization of cords, requires emergent tracheostomy

replaced R subclavian off the descending aorta

RIGHT recurrent laryngeal nerve => loops around R subclavain (or innominate) artery. More likely than L to not be recurrent
LEFT recurrent laryngeal nerve = loops around aorta

Bilateral recurrent laryngeal nerve injury during total thyroidectomy -> medialization of cords -> severe resp stridor, possibe resp arrest, very difficult to reintubate
-Do TRACHEOSTOMY via the COLLAR INCISION that was used for thyroidectomy

Adrenal cortical ca:
-bimodal age distribution: before age 5, after age 50. F >M
-50% functioning tumors: cortisol, aldosterone, sex steroids
-children have virilization in 90%. feminization in men. masculinization in women
CT findings: heterogeneous enhancement, slow washout. MRI hypointense on T1, high-intermediate signal on T2. if >4 cm, likely malignant
-Sx: abn pain, wt loss, weakness
-80% have advanced dz @ time of diagnosis
-Tx: radical adrenalectomy. Mitotane (AKA Op-DDD = adrenal-lytic) for residual or recurrent dz
-20% 5-yr survival

Renal osteodystrophy causes hyper-parathryroidism by 2 mechanisms:
1. Kidney loses Ca2+, retains PO4-. (main mechanism)
2. Decreased vitamin D 1-hydroxylation

Renin-angiotensin-aldosterone system:
low NaCl -> sensed by the macula densa -> produces renin ->
converts angiotensinogen to A-1 -> which is converted to A-2 in the lung ->
A-2 = vasoconstrictor, increases Aldosterone ->
retains Na, loses K and H+ in urine

RET proto-oncogene
-60% have MEN 2a
-5% have MEN 2b
-35% have familial medullary thyroid ca

Secondary hyperparathyroidism:
-Usually dialysis pts c/ chronic Ca loss
-Elevated PTH, normal Ca
-Rarely requires surgery
-Most common surgery indication = bone pain 2/2 Ca resorption

Sheehan syndrome: post-partum lack of lactation, persistent amenorrhea
+/- adrenal insuff, hypothyroidism
-2/2 pituitary ischemia 2/2 hemorrhage, hypotension

Small cell lung ca = most common tumor to cause paraneoplastic hyper-Ca
(distinguish from parathryroid dz by normal/low PTH)
-primary tx = osteoclast inhibitor = bisphosphonate

Sturge-Weber = cephalotrigeminal angiomatosis:
-NOT inherited, presents by age ~2
-Bridging veins absent on one side of brain -> that side develops central venous drainage -> venous HTN after birth -> increased risk of thrombosis, multiple tiny infarcts -> atrophy, calcification of one hemisphere

Port-wine angioma can trigger w/up, especially if it involves medial canthus (but is an isolated finding in 90% of cases)
-increased risk of pheochromocytoma

This is a typical presentation of Subacute Thyroiditis, the exact cause of which is unknown. This is generally a self-limiting process, however, treatment with corticosteroids or NSAIDS is effective in relieving symptoms.

Superior laryngeal nerve injury (e.g. during thyroidectomy) -> loss of pitch
(motor to cricothyroid. Injury => loss of projection, high pitch)

Superior laryngeal nerve:
Vagus -> Sup laryngeal nerve -> internal + external branches -> EXTERNAL branch travels c/ SUP. THYROID ARTERY to CRICOTHYROID muscle
(only laryngeal muscle innervated by the nerve)
-injury (e.g. during thyroidectomy) -> weak voice, loss of voice quality @ higher ranges

T3: 3x as active as T4
-1/2 life = 3 days

Thyroidectomy for hyperthyroid if:
-Pregnant (beta block then operate)
-Plummer's syndrome = autonomously functioning nodule
-Compressive sx
-Failed medical tx

open wound and place emergent trach,
-Very difficult to intubate c/ bilateral RLN injury and medialization of both cords

Thyroid CA + palpable LNs =>
total thyroidectomy + modified radical neck dissection

Indications for MRND = extra-thyroidal dz: capsule invasion, clinical or (+) nodal dz, or mets

Thyroid storm:
-Sx: increased HR, numbness, irritability, vomiting, diarrhea
High-output cardiac failure = #1 cause of death
-Post-op pt c/ undiagnosed GRAVE'S > precipitated by anxiety, excessive gland palpation, adrenergic stimulants
-Inital tx: beta blockers (ESMOLOL drip), PTU, Lugol's soln (KI), cooling blanketsl O2, lucose, fluid
-Emergent thyroidectomy rarely indicated
-WOLFF-CHAIKOFF effect = give pt high doses of I (Lugol's soln, KI) -> inhibit TSH action on thyroid -> inhibit organic coupling of iodide -> less T3, T4 release

Thyroid storm:
-Sx: increased HR, numbness, irritability, vomiting, diarrhea
High-output cardiac failure = #1 cause of death
-Post-op pt c/ undiagnosed GRAVE'S > precipitated by anxiety, excessive gland palpation, adrenergic stimulants
-Inital tx = beta blockers (ESMOLOL drip) -> PTU, Lugol's soln (KI), cooling blanketsl O2, lucose, fluid
-Emergent thyroidectomy rarely indicated
-WOLFF-CHAIKOFF effect = give pt high doses of I (Lugol's soln, KI) -> inhibit TSH action on thyroid -> inhibit organic coupling of iodide -> less T3, T4 release

Thyroid ca worse prognostic factors: AGES
Age: women >50, men >40
Grade (poorly diff)
Extebnt: extracapsular extension, regional LN dz
Size >4 cm or Sex Male

I-131 - for PAPILLARY & FOLLICULAR thyroid ca. Indications:
-recurrent dz
-primary inoperable tumors 2/2 local invasion
-Papillary c/ extranodal dz
-Follicular >1 cm OR extranodal dz
-For metastatic dz, thyroidectomy facilitates entry of I-131 into metastatic lesions

-can cure bone and lung mets
-done 6 weeks post-op
-SE: sialoadenitis, GI sx, infertility, BM suppression, parathyroid dysfx, leukemia

Follow serum THYROGLOBULIN levels s/p total thyroidectomy for papillary or follicular thyroid ca to detect recurrence

Thyroid hormone binds a receptor located at the NUCLEUS

thyroid lobectomy

thyroid storm:
-tachycardia, fever, numbness, irritability, N/V, diarrhea
-#1 cause of death = high output cardiac failure
-most common post-op in pt c/ undiagnosed Grave's. also 2/2 anxiety, excess palpation of gland, adrenergic stimulants
-Tx: beta blocker, PTU, Lugol's (KI), steroids, cooling, oxygen, glucose, fluid
Rarely need emergent thyroidectomy
-Wolff-Chaikoff effect: give high doses of Lugols= KI to inhibit TSH action -> inhibit organic coupling of iodide ->less T3, T4

Tuberous sclerosis = Bourneville's Dz: autosomal D neurocutaneous dz, xsomes 9,11
-"Zits, Fits, + Nitwits"
-Skin lesions, hamartomas
-Myoclonic seizures (90%, start at age 1-2)
-Mental retardation (50%)

Von Hipple Lindau:
multifocal and recureent renal cell ca, renal cysts, CNS tumors, pheochromocytoma

von Recklinghausen's = Neurofibromatosis type 1 = #1 phakomatosis.
-Autosomal D, xsome 17. Defined by 2/7 criteria
Cutaneous lesions: 1. CAFE-AU-LAIT SPOTS, 2. neurofibromas, schwannomas, 3. axillary/inguinal/intertriginous freckling
PERIPHERAL NEURAL TUMORS: 4. optic glioma, 5. lisch nodules
Skeletal deformaties: 6. sphenoid dysplasia, long bone cortical thickening
7. 1st deg relative c/ NF1
also have PHEOCHROMOCYTOMA

Waterhouse-Friderichsen syndrome:
-adrenal hemorrhage 2/2 meningococcal sepsis -> can cause adrenal insuff

Wolk Chaikoff effect:
-High I-doses (lugol's, KI) inhibit TSH
-Useful in thyroid storm

Parafollicular C cells:
-derived from neural crest
-produce calcitonin => decrease serum Ca

Cricothyroid muscle is ennervated by the superior laryngeal nerve

Familial hypercalcemic hypocalciuria:
-2/2 increased binding of PTH to defective PTH receptor in distal convoluted tubule -> increased Ca resorption
-Tx: do nothing. NO parathyroidectomy (Ca not very elevated)

Thyroid mass c/ FNA (+) for follicular cells:
5-10% malignancy risk => lobectomy or thyroidectomy

Thyroid lobectomy (+) for follicular CA => proceed to total thyroidectomy if >1 cm or extrathyroidal disease
-Extrathyroidal involvement or clinically (+) cervical LNs => ipsilateral MRND
-Lesion >1 cm or capsular invasion => I-131 x 6 weeks post-op
-Microinvasive (<1 cm), rare nodal spread (<10%), then usually incidental finding on path and lobectomy is sufficient as long as margins (-)
-70% 5-yr survival, prognosis depends on stage
- 50% metastatic on presentation. bone mets most common.

Follicular thyroid CA:
-50-60% metastatic @ presentation, more aggressive than papillary CA
-Hematogenous spread (BONE most common)
-Typically age 50's-60's, F:M 3:1
-If FNA shows follicular cells => 10% malignancy risk
-Path (+) for adenoma or follicular hyperplasia => lobectomy only
-typically requires total thyroidectomy + postop RI ablation
-Follicular Ca >1 cm or extrathyroidal dz => total thyroidectomy
-Clinically (+) cervical nodes or extrathyroidal dz => ipsilateral MRND
-Lesion >1 cm or extrathyroidal dz/capsular invasion => I-131 x 6 weeks post-op
-Microinvasive (<1 cm), rare nodal spread (<10%), then usually incidental finding on path => lobectomy suffiicient as long as margins (-)
-70% 5-year survival, prognosis based on stage

FNA can't distinguish malignant/benign with follicular or Hurthle cell (subtype of follicular) => need TISSUE
-10% cahnge of malignancy if FNA shows follicular cells

Total thyroidectomy
-Hurthle cell carcinoma of the thyroid is a subtype of follicular ca
- Tx, prognosis are similar with small differences (Sabiston, p619). Most are benign. Usually older pts
- <2 cm, contained in 1 lobe=> lobectomy or isthmectomy.
- MOST CASES: 2-4 cm and patient is high risk (e.g. advanced age)=> TOTAL THYROIDECTOMY
- > 4cm => total thyroidectomy for sure - 50% risk of cancer.

Hypercalcemia:
-Confusion, somnolence, shortened QT
-Tx: NS @ 200-300/hr, Furosemide
-NO LR or thiazides!

1% rate of persistant hyperparathyroidism after parathyroidectomy
-Usually 2/2 missed adenoma in the neck

Hyperthyroid in pregnancy:
-1st line = propylthiouracil (does not cross placenta)
-Persistant sx-=> thyroidectomy in 2nd trimester (decreased risk of adverse events, premature labor)
-I-131 would ablate fetal thyroid
-Methimazole causes cretinism
-Don't mask sx c/ beta blocker b/c hyperthroidism still present, still increased risk of stillbirth, cause fetal growth retardation in 3rd trimester

Hypoparathyroidism:
#1 cause = previous thyroid surgery
-Numbness/tingling in cirumoral area, fingers -> anxiety, confusion -> Tetany (carpopedal spasms, convusions, laryngospam which can be deadly
-Concomitant hypo-Mg can make correction of Ca difficult

Give thyroid hormone replacement following I-131 for papillary or follicular thyroid ca
-Suppresses TSH -> suppress growth of residual cancer tissue

I-131 if:
- starts 6 weeks post-op
- (I-131 scan to r/o mets also best done 4-6 wks postop when PTH highest)
- Papillary, follicular ca only
- can cure bone and lung mets

- Indications: recurrent pr metastatic papillary/follicular ca (if mets, do total thyroidectomy 1st), primary inoperable tumors 2/2 local invasion, papillary + extrathyroidal dz, follicular >1 cm + extrathyroidal dz

Medullary thyroid ca:
-from parafollicular C cells. Ret proto-oncogene = diagnostiic
-20% have MEN2 (tend to be bilat, younger, worse prognosis)
Path: AMYLOID pathognomonic
-Provocative test: administer GASTRIN -> increases calcitonin
-Tx: total thyroidectomy. add neck dissection if node (+)

MEN 1:
Pancreatic islet cell tumor (Gastrinoma = #1, 50% multiple, 50% malignant, #1 morbidity of MEN 1)
Pituitary tumor (Prolactinoma = #1)
hyper-Parathyroidism (usually 1st to have sx, fix this 1st)
MENIN gene

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. Prolactinoma = #1

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. Prolactinoma = #1

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. Prolactinoma = #1

MEN 1: MENIN gene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia => urinary sx, usually the 1st part to be symptomatic, needs to be corrected before the others. Tx = 4-gland resection c/ autotransplantation
-Pancreatic islet cell tumors => the major MEN1 morbidity. Gastrinoma = #1. 50% multiple, 50% malignant.
-Pituitary adenoma. PROLACTINOMA = #1

MEN 2a:
hyper-Parathyroidism
Medullary thyroid ca (in nearly all pts, 1st to be symptomatic - usually diarrhea, #1 cause of death in MEN 2a)
Pheochromocytoma (often bilateral, almost always benign, fix this 1st)
-RET protooncogene

MEN 2a: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia in 5-20%
-Pheochromocytoma in 10-60%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in ~100%, often bilateral. #1 cause of death in MEN2. Usually 1st part to be symptomatic: => diarrhea 2/2 calcitonin most common.

MEN 2a: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia in 5-20%
-Pheochromocytoma in 10-60%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in ~100%, often bilateral. #1 cause of death in MEN2. Usually 1st part to be symptomatic: => diarrhea 2/2 calcitonin most common.

MEN 2a: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Parathyroid hyperplasia in 5-20%
-Pheochromocytoma in 10-60%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in ~100%, often bilateral. #1 cause of death in MEN2. Usually 1st part to be symptomatic: => diarrhea 2/2 calcitonin most common.

MEN 2b:
mucosal neuromas, Marfan's habitus, musculoskel abnormalities
Medullary thyroid ca (in nearly all pts, 1st to be symptomatic - usually diarrhea, #1 cause of death in MEN 2a)
Pheochromocytoma (often bilateral, almost always benign, fix this 1st)
RET protooncogene

MEN 2b: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Mucosal neuromas (gut), ganglioneuromatosis in 100%
-Marfanoid habitus, musculoskel abnormalities
-Pheochromocytoma in 50%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in~100%, often bilateral. #1 cause of death in MEN2, more aggressive in MEN2b. Usually 1st part to be symptomatic => diarrhea most common.

MEN 2b: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Mucosal neuromas (gut), ganglioneuromatosis in 100%
-Marfanoid habitus, musculoskel abnormalities
-Pheochromocytoma in 50%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in~100%, often bilateral. #1 cause of death in MEN2, more aggressive in MEN2b. Usually 1st part to be symptomatic => diarrhea most common.

MEN 2b: RET proto-oncogene, from APUD cells, autosomal D, 100% penetrance, variable expressivity
-Mucosal neuromas (gut), ganglioneuromatosis in 100%
-Marfanoid habitus, musculoskel abnormalities
-Pheochromocytoma in 50%. Often bilateral, benign but needs to be corrected 1st.
-Medullary ca of thyroid in~100%, often bilateral. #1 cause of death in MEN2, more aggressive in MEN2b. Usually 1st part to be symptomatic => diarrhea most common.

Primary hyperparathyroidism
-PTH >40 pg/mL, Ca >10.5, Cl:PO4 ratio >33, +/-hyperchloremic met acidosis,
-PRAD-1 oncogene, radiation exposure increase risk of adenoma
-Older women
-OSTEITIS FIBROSA CYSTICA (brown tumors) = bone lesions 2/2 Ca resorption
-Most pts asymptomatic
-Sx: muscle weakness, myalgia, nephrolithiasis, pacreatitis, PUD, depression, bone pain, pathologic fx, MS change, constipation, N/V, anorexia
-Can get HTN 2/2 renal impairment

Insulinoma = #1 endocrine pancreatic tumor overall
(but not part of a MEN subgroup)

Papillary thyroid ca:
-Total thyroidectomy for: >1 cm, bilateral lesions, multicentricity, hx XRT, extra-thyroidal dz (capsular invasion, (+) margins, mets, clincal or (+) LNs)

Papillary thyroid ca = most Popular = 85% of thyroid cancer
-Lymphatic spread but nodes don't predict survival
-20% of adults, 80% of children are node (+) on presentation, 80% are multicentric.
-F:M 3:1. 50% before age 40
-Path:PSAMMOMA bodies represent deposited Ca
-RF = radiation exposure
-MACIS criteria: Mets, Age M>50 or F>40, Completeness of resection, Invasiveness, Size >1.5 cm

#1 location for a missed parathyroid gland @ reexploration =
normal anatomic position
Superior: lateral to RLN. above inf thyroid artery
Inferior: medial to RLN. more anterior and below inf thyroid artery. more likely to be ectopic. occasionally in tail of thymus, can migrate to anterior mediastinum (other ectopic sites: intrathyroid, mediastinal, near TE groove)

INFERIOR THYROID artery = blood supply to superior and inferior parathyroid glands

Superior parathyroids: 4th pouch, ass'd c/ thyroid complex. lateral to RLN. above inf thyroid art.

Inferior parathyroids + thymus: 3rd pharyngeal pouch. inferior more variable position.. medial to RLN. below inf thyroid art #1 ectopic site = tail of thymus.

#1 location for ectopic parathyroid gland =
inferior parathyroids in TAIL OF THYMUS, can migrate to the anterior mediastinum
-Other ectopic sites: intrathyroid, mediastinum, near tracheoesophageal groove

Parathyroid hormone:
-Normal level 5-40 pg/mL
1/2 life 18 min
Ca reabsorbtion in DCT, PO4 secretion
-Increases osteoclasts in bone to release Ca, Po4
N terminal active, C terminal inactive (like insulin)
-1-OH-hydroxylation of VitD in kidney -> more Ca-binding protein in intestine

Parathyroid hormone:
increases 1-OH hydroxylation of vit D in kidney -> increases Ca binding protein -> increases Ca and PO4-absorption in gut
-increases Ca absorption in DCT of kidney, decreases PO4 absorption
-promotes Ca and PO4- release by osteoclasts

Primary hyperparathyroidism
-Hyperchloremic metabolic acidosis
-PTH >40 pg/mL
-Ca >10.5
-High renal cAMP (effect on PTH R in kidney)
Cl:PO4 ratio >33
-High urine Ca in 70% (normal in 30%)

Primary hyperparathyroidism
-PTH >40 pg/mL, Ca >10.5, high renal cAMP (effect on PTH R in kidney), Cl:PO4 ratio >33, +/- HYPERCHLOREMIC METABOLIC ACIDOSIS,
-PRAD-1 oncogene increases risk for adenomas
-Older women
-Osteitis fibrosa cystica (brown tumors) = bone lesions 2/2 Ca resorption
-Most pts asymptomatic
-Sx: muscle weakness, myalgia, nephrolithiasis, pacreatitis, PUD, depression, bone pain, pathologic fx, MS change, constipation, N/V, anorexia
-Can get HTN 2/2 renal impairment

Primary hyperparathyrodism:
80-85% have single adenoma => resect adenoma, inspect other glands to r/o hyperplasia or another adenoma
4%% have multiple adenomas
15% have diffuse hyperplasia (MEN 1 ot 2a have 4-gland hyperplasia) => don't biopsy all glands b/c risk of hemorrhage, hypo-PTH. resect 3.5 glands or parathyroidectomy + reimplantation
<1% have parathyroid adnenocarcinoma (very high Ca levels) => radical parathyroidecomy including ipsilateral glands

Primary hyperparathyroidism
-PTH >40 pg/mL, Ca >10.5, Cl:PO4 ratio >33, +/-hyperchloremic met acidosis,
-PRAD-1 oncogene, RADIATION exposure increase risk of adenoma
-Older women
-Osteitis fibrosa cystica (brown tumors) = bone lesions 2/2 Ca resorption
-Most pts asymptomatic
-Sx: muscle weakness, myalgia, nephrolithiasis, pacreatitis, PUD, depression, bone pain, pathologic fx, MS change, constipation, N/V, anorexia
-Can get HTN 2/2 renal impairment

Primary hyperparathyroidism - 5 indications for surgery:
1.Symptomatic dz
2.Asymptomatic + Ca>13
3. Decreased Cr clearance
4. Nephrolithiasis
5. Significantly decreased bone mass

Adenoma (84%) => resection; inspect other glands to r/o hyperplasia or multiple adenomas (4%)
-Hyperplasia (15%) => resect 3.5 glands or total parathyroidectomy + autoimplantation (don't biopsy all glands 2/2 risk of hemorrhage + hypoparathyroid)
-Parathyroid adenocarcinoma (<1%) => radical parathyroidectomy (c/ ipsilateral thyroid)
-Pregnancy => surgery in 2nd trimester to avoid risk of 3rd trimester stillbirth

Primary hyperparathyroidism
-Hyperchloremic metabolic acidosis
-PTH >40 pg/mL
-Ca >10.5
-High renal cAMP (effect on PTH R in kidney)
Cl:PO4 ratio >33
-High urine Ca in 70% (normal in 30%)

Propylthiouracil (thionamide, along with methimazole):
-Inhibits peroxidases, which connect iodine to tyrosine to form DIT, MIT
-PTU, Propranolol, and Prednisone (steroid) inhibit peripheral conversion of T4 -> T3
-SE: aplasic anemia, agranulocytosis (rare)
-crosses placenta. preferred over methimazole during FIRST trimester only

Propylthiouracil, Methimazole (thionamides):
-Inhibit peroxidases -> prevents DIT, MIT coupling
-SE: aplasic anemia, agranulocytosis (rare)
-PTU preferred in 1st trimester; may change to methimazole in 2nd-3rd trimester. can cause cretinism.

Recurrent laryngeal nerve injury (e.g. during total thyroidectomy) -> hoarseness

Recurrent laryngeal nerve:
-Innervates all of larynx except CRICOTHYROID muscle
-Run posterior to thyroid lobes in tracheoesophageal groove
-Can tract c/ inferior thyroid artery, but variable
-L RLN loops around aorta
-R RLN loops around R subclavian = innominate artery, but R is more lateral, more likely than L to be non-recurrent (e.g. 2/2 replaced R subclavian off the descending aorta)
-Risk of injury to non-recurrent laryngeal nerve during surgery
-Unilateral injury -> hoarseness; Bilat injury -> airway obstruction 2/2 medialization of cords, requires emergent tracheostomy

Bilateral recurrent laryngeal nerve injury during total thyroidectomy -> medialization of cords -> severe resp stridor, possibe resp arrest, very difficult to reintubate
-Do TRACHEOSTOMY via the COLLAR INCISION that was used for thyroidectomy

RET proto-oncogene
-60% have MEN 2a
-5% have MEN 2b
-35% have familial medullary thyroid ca

Secondary hyperparathyroidism:
-Usually dialysis pts c/ chronic Ca loss. Renal osteodystrophy = Al accumulates in bones -> osteomalacia after dialysis x several yrs.
-Elevated PTH, normal Ca
-Rarely requires surgery (subtotal thyroidectomy or total parathyroidectomy + autotransplant)
-Most common surgery indication = bone pain 2/2 Ca resorption
-Tx: control PO4, Ca supplement, vit D. l

This is a typical presentation of Subacute Thyroiditis, the exact cause of which is unknown. This is generally a self-limiting process, however, treatment with corticosteroids or NSAIDS is effective in relieving symptoms.

Superior laryngeal nerve injury (e.g. during thyroidectomy) -> loss of pitch
(motor to cricothyroid. Injury => loss of projection, high pitch)

T3: 3x as active as T4
-1/2 life = 3 days

Thyroid CA + palpable LNs =>
total thyroidectomy + modified radical neck dissection

Indications for MRND = extra-thyroidal dz: capsule invasion, clinical or (+) nodal dz, or mets

Thyroid storm:
-Sx: increased HR, numbness, irritability, vomiting, diarrhea
High-output cardiac failure = #1 cause of death
-Post-op pt c/ undiagnosed GRAVE'S > precipitated by anxiety, excessive gland palpation, adrenergic stimulants
-Inital tx: beta blockers (ESMOLOL drip), PTU, Lugol's soln (KI), cooling blanketsl O2, lucose, fluid
-Emergent thyroidectomy rarely indicated
-WOLFF-CHAIKOFF effect = give pt high doses of I (Lugol's soln, KI) -> inhibit TSH action on thyroid -> inhibit organic coupling of iodide -> less T3, T4 release

Thyroid storm:
-Sx: increased HR, numbness, irritability, vomiting, diarrhea
High-output cardiac failure = #1 cause of death
-Post-op pt c/ undiagnosed GRAVE'S > precipitated by anxiety, excessive gland palpation, adrenergic stimulants
-Inital tx = beta blockers (ESMOLOL drip) -> PTU, Lugol's soln (KI), cooling blanketsl O2, lucose, fluid
-Emergent thyroidectomy rarely indicated
-WOLFF-CHAIKOFF effect = give pt high doses of I (Lugol's soln, KI) -> inhibit TSH action on thyroid -> inhibit organic coupling of iodide -> less T3, T4 release

I-131 - for PAPILLARY & FOLLICULAR thyroid ca. Indications:
-recurrent dz
-primary inoperable tumors 2/2 local invasion
-Papillary c/ extranodal dz
-Follicular >1 cm OR extranodal dz
-For metastatic dz, thyroidectomy facilitates entry of I-131 into metastatic lesions

-can cure bone and lung mets
-done 6 weeks post-op
-SE: sialoadenitis, GI sx, infertility, BM suppression, parathyroid dysfx, leukemia

Follow serum thyroglobulin levels s/p total thyroidectomy for papillary or follicular thyroid ca to detect recurrence

von Recklinghausen's = Neurofibromatosis type 1 = #1 phakomatosis.
-Autosomal D, xsome 17. Defined by 2/7 criteria
Cutaneous lesions: 1. CAFE-AU-LAIT SPOTS, 2. neurofibromas, schwannomas, 3. axillary/inguinal/intertriginous freckling
PERIPHERAL NEURAL TUMORS: 4. optic glioma, 5. lisch nodules
Skeletal deformaties: 6. sphenoid dysplasia, long bone cortical thickening
7. 1st deg relative c/ NF1
also have PHEOCHROMOCYTOMA

Wolk Chaikoff effect:
-High I-doses (lugol's, KI) inhibit TSH
-Useful in thyroid storm