[ ] endocrine final.doc
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Endocrine Diseases
Hypercorticism(Cushing’s Disease)
Gigantism Acromegaly
Type of DiseaseHyperpituitarism
PathologyOverproduction of ACTH from pituitary
Over production of GH in a child
Overproduction of GH in an adult
CausePituitary: Tumor or hyperplasia
Functioning adenoma of anterior pituitary
Signs & SymptomsHirtuism, masculinization/virilization (indicative of adrenal tumor due to androgens), striae, central obesity, round face, hyperpigmentation (indicative of pit or ectopic production of ACTH), severe proximal myopathy, psychological disturbances, osteoporosis, buffalo hump, DM, HTN, facial plethora, acne, menstrual disorders
Eunuchoid habitus, elongated arms and legs, deficient genital and secondary sex characteristics
Course facial features, prominent eyebrow, massive scalloped tongue, myopathy, nerve entrapment, prognathism, spade-shaped hands and feet, osteoporosis, HTN, hypertrophied viscera
DiagnosisHypokalemia, alkalosis, CRH assay (differentiate Cushing Ds from ectopic ACTH)
cortisol
GH Level GH level
TreatmentSurgical removal of producing tumor
High doses of hydrocortisone 1 day prior to surgery and 300mg continuous IV on the day of surgery
Iatrogenic Cushing’s Disease: Hydrocortisone 100mg QD, metyrapone (Metopirone), Aminogluthemide (Cytadren) in combination w/ Ketoconazole
**Octreotide (Sandostatin)
Bromocriptine (Parlodel)
DiseaseProlactinoma
(Amenorrhea-Galactorrhea Syndrome) Simmond’s Disease Craniopharyngioma
**most common functional pituitary tumor**
(Pituitary Cachexia)
Type of Disease Hyperpituitarism Hypopituitarism
PathologyOverproduction of prolactin Underproduction of pituitary
tropic hormonesPressure on pituitary thus decreasing output of tropic hormones
Cause
Functioning adenoma of anterior pituitary
Destruction of pituitary gland from:Non-secretory adenomaMetastases to pituitaryAdjacent tumor placing
pressure on pituitaryInfarction after deliveryInflammatory Granulomatous
DsAutoimmune pituitary
destructionIrradiationEmpty Sella Tursica SxInfiltration: sarcoidosis,
histocytosis, hemachromatosis
Lesions of Hypothalamus from:Craniopharyngioma,GliomaGerminoma
Vestigial remnants of Rathke’s pouch form slow growing cystic tumors along craniopharyngeal canal
Signs & Symptoms Women
GalactorrheaAmenorrheaOligomenorrheaInfertilityEarly manifestations
MalesVisual defectsImpotenceHeadachesEOM paralysisLate manifestations
Pressure on pituitary – erosion of surrounding bones, hypothalamus – hydrocephalus, optic nerves – bitemporal hemianopia
Diagnosis prolactin level tropic hormones tropic hormones
Treatment
Bromocriptine (Parlodel)
Sheehan’s Syndrome (Post-partum Pituitary
Necrosis)
Diabetes Insipidus Inappropriate ADH Secretion(SIADH)
Type of Disease
Hypopituitarism Hypopituitarism of posterior pituitary
Hyperpituitarism of posterior pituitary
PathologyEnlargement of pituitary during pregnancy followed by sudden hypotension precipitates necrosis leading to decreased pituitary secretionORDIC, cavernous sinus thrombosis, DM
Underproduction of ADH Overproduction of ADH
CauseSudden infarction of anterior lobe due to hemorrhage or shock during delivery or traumatic abortion
Acquired:Compression or destruction of hypothalamus OR posterior pituitary by inflammatory and infiltrative lesions, tumors, radiation, trauma or surgery
**Cranial: familial
Intracranial trauma (hemorrhage), infection (meningitis), cytotoxic drugsOREctopic ADH secretion
Signs & SymptomsFailure of lactation, gonadotropic deficiency, ACTH, TSH, MSH deficiency
Empty sella turcica
Large volumes of dilute urine (polyuria), excessive thirst (polydipsia), and hypernaturemia, prefer ice cold water
DiagnosisWater Depravation Test
TreatmentVasopressinLypressin (Diapid)Desmopressin Acetate (DDAVP, concentraid)
Cretinism Myxedema Hashimoto’s Thyroiditis(Autoimmune Thyroiditis)
Type of DiseaseHypothyroidism
PathologyUnderproduction of thyroid hormones during infancy
Usually due to iodine deficiency
Underproduction of thyroid hormones in older children or adults
Circulating autoantibodies to thyroglobulin, follicular cell membranes and surface receptors.
Cause
1. Deficiency of thyroid tissue: agenesis or hypoplasia, surgery, radiation
2. Goiter: iodine deficiency, goitrogenic agents, Hashimoto’s Thyroiditis
3. Hypothalamic lesions and hypopituitarism4. Peripheral resistance to thyroid hormones
1. Autoimmune disease of humoral and CMI
2. Familial3. HLA DR5
**Most common form of hypothyroidism**
Signs & Symptoms
Failure of normal mental and bodily development, short stature, wide-set eyes, protuberant tongue, dry skin, coarse facial features
Neurologic: spasticity deafness, severe mental retardation
Cold, lethargic, mentally dull, coarse features, puffy skin, hair loss, accumulation of mucinous ground substance within dermis (myxedema)
CVS: cardiomegaly, bradycardia
CNS: mental slowing, stupor, coma
Features of hypothyroidism, progressive painless moderate enlargement of thyroid
Increased incidence of lymphoma
Often associated with other autoimmune disorders (SLE, RA, Graves Ds)
Diagnosis fT3 and fT4, sTSH >5 (except hypothalamic lesions and hypopituitarism)
Test for AbTSH, T4ESR
Treatment
Levothyroxine (T4) (Synthroid)Tx must start w/in 2-3mo to reverse sx
Levothyroxine (T4) (Synthroid)Infants (1-6mo) 1-1.5mgAdult .017mgRecheck after 6-8 weeks
Subacute Granulomatous
Thyroiditis (DeQuervain’s
Thyroiditis)
Post Partum Thyroiditis (PPT)
(Silent Thyroiditis)
Subclinical Hypothyroidism
Type of Disease
Hypothyroidism
PathologyGranulomas develop in thyroid gland resulting in enlargement
Cause
Uncertain, viral infection suggested
Uncertain, response to pregnancy
Hashimotos, Tx Grave’s Ds, Lithium, inadequate thyroid replacement, Iodine-containing rx, pulsatile TSH, Adrenal insufficiency, drugs, TSH producing tumor
Signs & Symptoms
Painful enlargement of thyroid, self limited ds, recovery in about 3-6 monthsPhase I: hyperthyroid, to nl TSH, fT3&T4, RAIUPhase II: T3&T4, TSH, RAIUPhase III : TSH, T3, T4 wnl
NONPainful enlargement of thyroid, self limited dsPhase I: hyperthyroid, to nl TSH, fT3&T4, RAIUPhase II: T3&T4, TSH, RAIUPhase III : TSH, T3, T4 wnlCan mimic pp depression
some asymptomatic, Some symptomatic: cardiac, lipid, neurobehavior (esp. depression)
DiagnosisTSHT4
RAIU
TSH, nl T4, fT4
Treatment
Hyperthyroid state: sx:beta-blockersAsx: monitorHypothyroid state:Sx: Levothyroxine for 6 – 12 mo.Asx: monitor
Tx symptomatic as well as asymptomatic w/ LevothyroxineRecheck 6 weeks
Multinodular Goiter(Plummer’s Ds)
Graves’ Disease(Toxic Diffuse Goiter)
**Most common form of hyperthyroidism**
Diffuse Nontoxic Goiter(Simple Goiter)
Type of DiseaseHyperthyroidism
Pathology
Irregular nodular enlargement of thyroid due to distended follicles with marked colloid accumulation, fibrosis, hemorrhage
Excessive stimulation by thyroid stimulating immunoglobulins
Diffuse enlargement of thyroid
CauseTransformation from long-standing Simple Goiter
Uncertain, probably caused by immunologic mechanism and defect in Ag-specific suppressor T-cells
Associated w/ HLA-DR3 and autoimmune Ds (SLE, Hashimoto’s Disease)
Iodine deficiency due to: 1. Deficiency in food
and water 2. Goitrogens3. Physiologic demand
Signs & Symptoms
Might be sx-free
Complication include: pressure on trachea, esophagus occasional Obstruction of SVC w/ retrosternal extension of goiter.
Features of hyperthyroidism: nervousness, restlessness, emotional lability, tachycardia, palpitations, arrythmias, dyspnea, heat intolerance, sweating, fatigue, tremor, hair loss, lid lag and stare, atrial fibrillation, thyromegaly, exophthalmos
Thyroid Storm
Self limited in 30%
Diffuse enlarged thyroid
Diagnosis fT3 & fT4, sTSHT3RIA, Thyroid Ab fT3 & fT4, TSH
Treatment
Propylthiouracil Methimazole*Radioactive iodide
Propylthiouracil Methimazole*Radioactive iodideSurgery: Subtotal Thyroidectomy
Subclinical Hyperthyroidism
Primary Hyperparathyroidism
**most common cause of hypercalcemia
Secondary Hyperparathyroidism
Type of DiseaseHyperthyroidism Hyperparathyroidism
PathologyCompensatory hyperplasia in response to hypocalemic state
CauseEuthyroid Graves, autonomous adenoma, Excessive THR Tx, Thyroid Hormone suppressive therapy
Parathyroid adenomaCarcinomahyperplasia
**Chronic renal failureMalabsorption SxVit D deficiency
Signs & SymptomsAsymptomatic or symptomatic: atrial fibrillation, osteoporosis
Osteitis Fibrosa Cystica (cysts formed from resorption of Ca – leads to pathologic fx and “Brown tumors”) BONESNephrolithiasis, gallstones – STONESPancreatitis – GRONESPeptic Ulcers – MONESAssoc. w/ MEN
DiagnosisNl fT4, FTI, T3RIA TSH
serum Ca (3 consec. Tests;unless >12) serum phosphatePTHurinary Ca in 24hr urineALPcAMP in serum or urine radiograph (find brown turmors)
serum Ca serum phosphatePTHALP
TreatmentIf on suppression therapy: RxAsx: repeat TSH 3-6mo, 24hr RAIU – if use beta blocker or antithyroid rx
CA or adenoma: surgeryAcute Ds: excretion w/ saline & furosemide, Mithramycin, Calcitonin, Diphosphates, Hydrocortisone, Gallium NitrateModerate Ds : hydration, diuresis, phosphates, calcitonin, indocin, ASA, Disodium EtdronateCrisis: hopitlization, hydration Mithramycin, Disodium Etidronate
Hypoparathyroidism
**VERY RARE***
Thyroid Cancer
Type of DiseaseHypoparathyroidism Papillary (most commom), Follicular,
mixed, anaplastic, medullary (can be assoc w/ MEN)
PathologyInadequate secretion of PTH or end-organ resistance
Cause
Idiopathic, post surgical, radiation therapy, autoimmune ds, parathyroid aplasia associated w/ DiGeorge’s
Recurrent thyroid CA, hx of radiation exposure
Signs & Symptoms
Severe cases: cardiac arrhythmias, tetany, intracranial pressure w/ papilledema, cataracts, diarrhea, epilepsy, Trousseau’s Sign, numbness, tingling, Chvestek sign
VaryDysphagia, hoarseness, firm and immobile nodules, cervical lymphadenopathy
Suspect nodules in males >40 and females >50 and ALL nodules in children
Diagnosis
Serum Caphosphate levelsPTH
sTSH, Ab, Tg (+ in malignancy)Thyroid scan (cold nodules),Calcitonin levelU/SFNA biopsy
Treatment
Thyroidectomy (suspect CA, compression, cosmetic)RIA(inoperable, residual ds in neck, invasion, metastasis)ChemotherapyT4 suppressive therapy of TSH
Disease
Cushing SyndromeConn’s Syndrome
(Primary Hyperaldosteronism)
Type of DiseaseHyperadrenalism
Pathology
**Pituitary: Tumor or hyperplasia (Cushing Disease)
Adrenal: Tumor
Ectopic production of ACTH or CRH (usually carcinoid tumor of lung or pancreas)
Iatrogenic
Hypersecretion of aldosterone
CauseOverproduction of ACTH from pituitary(Cushing Ds) OR overproduction of CRF from hypothalamus OR ectopic ACTH production OR Adrenal tumor producing cortisol
**Adrenocortical adenomaHyperplasiaCarcinoma (rarely)
Signs & Symptoms
Hirtuism, masculinization/virilization (indicative of adrenal tumor due to androgens), striae, central obesity, round face, hyperpigmentation (indicative of pit or ectopic production of ACTH), severe proximal myopathy, psychological disturbances, osteoporosis, buffalo hump, DM, HTN, facial plethora, acne, menstrual disorders, bruising, CHF, edema, polyuria, polydipsia
Polyuria, polydypsia, muscle weakness, renal K loss
HTN but hyporeninemia (due to feedback from aldosterone)
Diagnosis
Hypokalemia, alkalosis, CRH assay (differentiate Cushing Ds from ectopic ACTH) (pituitary or ectopic) or (adrenal adenoma) ACTH depending on cause, or MSH depending on cause, serum and 24 urine cortisol, serum glucoseDexamethasone Suppression Test
Pituitary MRI to confirm
Aldosterone level Renin LevelMetabolic alkalosisExessive K in urine serum KSaline Suppression Test
CT , then Venous/Arterial sampling
Treatment
Surgical removal of producing tumor, irradiation or resection of hyperplastic adrenalsHigh doses of hydrocortisone 1 day prior to surgery and 300mg continuous IV on the day of surgery
Iatrogenic Cushing’s Disease: Hydrocortisone 100mg QD, metyrapone (Metopirone), Aminogluthemide (Cytadren) in combination w/ Ketoconazole
Spironolactone (Aldactone)Or Diuretics
Disease
Glucocorticoid Remediable
Aldosteronism(GRA)
Adrenogenital Syndrome Secondary Adrenal
Insufficiency
Type of Disease
Hyperadrenalism Hypoadrenalism
PathologyHypersecretion of aldosterone/glucocorticoid suppression
Congenital Adrenal Hyperplasia (CAH): inborn enzyme defect which inhibits cortisol thus ACTH causing adrenal hyperplasia and overproduction of androgens
Adrenal Virilization:Tumor or hyperplasia resulting in anoverproduction of androgens
Decreased production of ACTH
CauseAbnl hybrid gene results in stimulation of aldosterone by ACTH
Congenital Adrenocortical, hyperplasia, adenoma or carcinoma
Destructive pituitary or lesions of the hypothalamus
Signs & SymptomsHTN Present @ brith
w/ virilization of female
Salt wasting
Virilization of female
Diagnosis aldosterone level cortisol level
ACTH cortisol levelandrogens
ACTH cortisol levelnl aldosterone
TreatmentDexamethasone given to predisposed mother to prevent fetus from genital deformation
IV HydrocortisoneMineralcorticoids
Corticotropin (only parenteral)Hydrocortisone (oral)
DiseaseAddison’s Disease
(Primary Adrenocortical Insufficiency)Pheochromocytoma
Type of DiseaseHypoadrenalism Ds of Hypersecretion of the
Adrenal Medulla
PathologyDestruction of adrenal cortex resulting in cortisol production and aldosterone
Tumor arising from chromaffin cells of adrenal medulla secreting catecholamines(outside the adrenals: paragangliomas)
Cause***Idiopathic adrenalitis (autoimmune)*TB*HistoplasmosisAmyloidosis, metastatic carcinoma, hemochromatosis
(all resulting in damage to the pituitary or hypothalamus)
SporaticFamilial
Some associated w/ MEN II, MEN III
Signs & SymptomsAcute: rapid progression, shock, septicemia, Waterhouse-Friderichsen, DIC w/ widespread hemorrhage in skin and organs, dehydration, hypotension, weakness, hypothermia, abd pain, N/V
Chronic: insidious onset, malaise, weight loss, hypotension, loss of body hair, menstrual irregularities, skin hyperpigmentation, weakness, fatigue, anorexia, GI sx, saltcravings, postural hypotension
Idiopathic often assoc. w/ other autoimmune diseases
Paroxysmal or sustained HTN, angina, cardiac arrhythmias leading to CHF, flushing, diaphoresis, palpitations, N/V tachycardia,
Episodic HA, sweating, anxiety, tremor, visual disturbances, ringing in ears, papilledema, heart murmurs, cardiomegaly
Diagnosis cortisol Na+ glucose K+ ACTH
catecholamines in serum and urinePresence of VMA (Vanillylmandelic acid)in 24 urine **pathnomonicMRI to confirm
TreatmentAcute:Cortisol 100mg IV Q 6-8 until stableReduce over 5d to maintenance dose of 50mg/dIV salineGlucose
Chronic:Hydrocortisone 20-30mg QD2/3 given in am1/3 given in afternoon
Fludrocortisone
Alpha adrenergic blockers w/ Beta Blockers
Surgery
DiseaseGanglioneuroma/ Neuroblastoma Type I Diabetes Mellitus Type II Diabetes
Mellitus
Type of Disease Ds of Hypersecretion of the Adrenal
MedullaMetabolic Disorder of the Pancreas
PathologyGanglioneuromaBenign tumor of ganglion cells
NeuroblastomaHighly malignant tumor from neural crest
Ab against beta cells destroy islet cells resulting in a decreased production of insulin
Target tissue develops insulin resistance
CauseTumor Immune
Viral (Cacksackie Virus – molecular mimecry)
Genetic (linked to HLA DR3&4 on Chromosome 6)
Overeating, Obesity, Genetics (large predisposition)Risk factors: aging, sedentary lifestyle
Signs & Symptoms
Neuroblastoma: common in childhood, abdominal mass, anemia, fever, wt loss
Commonly metastasizes to bone of skull and orbit (Hutchison-type)To liver (Pepper Syndrome)
Onset early in life, but can occur at any time, Wt loss, dry skin, weakness, Insulitis, DKA, Hyperglycemia resulting in AGES & sorbitol depositions, eventually coma if untx, insulinopenia, infections, polyuria, polyphagia, polydipsia
Chronic Complications: CAD, MI, stroke, gangrene, cataracts, artherosclerosis, retinopathy, nephropathy, neuropathy, vascular disease
Onset usually >30, but is becoming more common in younger, upper segment obesity, polyuria, abnl insulin secretion, insulin resistance, glucose production from liver, triglycerides d/t inability to activate lipoprotein lipase, hyperlipidemia indicates poor control
Chronic Complications: CAD, MI, stroke, gangrene, cataracts, artherosclerosis, retinopathy, nephropathy, neuropathy, vascular Ds
Diagnosis insulin HbA1cAb to islet cells or insulinFasting glucose >126mg/dLRandom glucose>200mg/dL
insulin HbA1cFasting glucose >126mg/dLRandom glucose>200mg/dL
Treatment 1. NPH BID w/ premeal Lispro
2. Glargine Q HS w/ premeal Lispro
Pt educationGoal: HbA1C 7% or lower
DKA tx: hydration, insulin
Diet, exercise, wt lossSulfonylureasGlucophageInsulin (occas.)
Tx hyperlipidemiaPt education
Disease
Insulinoma Gastrinoma(Zollinger-Ellison
Syndrome)
Type of DiseasePancreatic Tumor Pancreatic Tumor
PathologyInsulin producing tumor of the islet cells
Gastrin Producing tumor of islet cells
CauseTumor Tumor
Signs & SymptomsDizziness, confusion, bizarre behavior, seizure, coma
10% malignant
Assoc. w/ MEN I
Triad: gastrinoma, gastric acid hypersecretion, peptic ulcer disease
Diarrhea, fluid electrolyte imbalance
60% malignant
Assoc w/ MEN I
Diagnosis insulin glucose
Treatment