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