Endocrine Final[1]

Endocrine Diseases Hypercorticism (Cushing’s Disease) Type of Disease

Pathology

Cause

Signs & Symptoms

Diagnosis

Gigantism

Acromegaly

Hyperpituitarism

Overproduction of ACTH from pituitary

Over production of GH in a child

Pituitary: Tumor or hyperplasia

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

Hypokalemia, alkalosis, CRH assay (differentiate Cushing Ds from ectopic ACTH)

Overproduction of GH in an adult

Functioning adenoma of anterior pituitary

Eunuchoid habitus, elongated arms and legs, deficient genital and secondary sex characteristics

Course facial features, prominent eyebrow, massive scalloped tongue, myopathy, nerve entrapment, prognathism, spadeshaped hands and feet, osteoporosis, HTN, hypertrophied viscera

GH Level

GH level

↑ cortisol Treatment

Surgical removal of producing tumor High doses of hydrocortisone 1 day prior to surgery and 300mg continuous IV on the day of surgery

**Octreotide (Sandostatin) Bromocriptine (Parlodel)

Iatrogenic Cushing’s Disease: Hydrocortisone 100mg QD, metyrapone (Metopirone), Aminogluthemide (Cytadren) in combination w/ Ketoconazole

Disease

Prolactinoma (Amenorrhea-Galactorrhea Syndrome)

Simmond’s Disease

Craniopharyngioma

**most common functional pituitary tumor** Type of Disease Pathology

(Pituitary Cachexia)

Hyperpituitarism

Hypopituitarism

Overproduction of prolactin

Underproduction of pituitary tropic hormones

Pressure on pituitary thus decreasing output of tropic hormones

Functioning adenoma of anterior pituitary

Destruction of pituitary gland from: Non-secretory adenoma Metastases to pituitary Adjacent tumor placing pressure on pituitary Infarction after delivery Inflammatory Granulomatous Ds Autoimmune pituitary destruction Irradiation Empty Sella Tursica Sx Infiltration: sarcoidosis, histocytosis, hemachromatosis

Vestigial remnants of Rathke’s pouch form slow growing cystic tumors along craniopharyngeal canal

Cause

Lesions of Hypothalamus from: Craniopharyngioma, Glioma Germinoma Signs & Symptoms

Diagnosis

Women Galactorrhea Amenorrhea Oligomenorrhea Infertility Early manifestations

Males Visual defects Impotence Headaches EOM paralysis Late manifestations

↑ prolactin level

Pressure on pituitary – erosion of surrounding bones, hypothalamus – hydrocephalus, optic nerves – bitemporal hemianopia

↓ tropic hormones

↓ tropic hormones

Treatment Bromocriptine (Parlodel)

Sheehan’s Syndrome (Post-partum Pituitary Necrosis)

Diabetes Insipidus

Inappropriate ADH Secretion (SIADH)

Type of Disease

Pathology

Cause

Signs & Symptoms

Hypopituitarism

Hypopituitarism of posterior pituitary

Hyperpituitarism of posterior pituitary

Enlargement of pituitary during pregnancy followed by sudden hypotension precipitates necrosis leading to decreased pituitary secretion OR DIC, cavernous sinus thrombosis, DM

Underproduction of ADH

Overproduction of ADH

Sudden infarction of anterior lobe due to hemorrhage or shock during delivery or traumatic abortion

Acquired: Compression or destruction of hypothalamu s OR posterior pituitary by inflammatory and infiltrative lesions, tumors, radiation, trauma or surgery

Intracranial trauma (hemorrhage), infection (meningitis), cytotoxic drugs OR Ectopic ADH secretion

Failure of lactation, gonadotropic deficiency, ACTH, TSH, MSH deficiency

Large volumes of dilute urine (polyuria), excessive thirst (polydipsia), and hypernaturemia, prefer ice cold water

Empty sella turcica

Diagnosis

**Cranial: familial

Water Depravation Test

Treatment

Vasopressin Lypressin (Diapid) Desmopressin Acetate (DDAVP, concentraid)

Cretinism

Myxedema

Hashimoto’s Thyroiditis (Autoimmune Thyroiditis)

Type of Disease Pathology

Hypothyroidism Underproduction of thyroid hormones during infancy

Underproduction of thyroid hormones in older children or adults

Usually due to iodine deficiency

Circulating autoantibodies to thyroglobulin, follicular cell membranes and surface receptors.

Cause 1. 2. 3. 4.

Deficiency of thyroid tissue: agenesis or hypoplasia, surgery, radiation Goiter: iodine deficiency, goitrogenic agents, Hashimoto’s Thyroiditis Hypothalamic lesions and hypopituitarism Peripheral resistance to thyroid hormones

1.

2. 3.

Autoimmune disease of humoral and CMI Familial 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

Diagnosis

↓ fT3 and fT4, ↑ sTSH >5 (except hypothalamic lesions and hypopituitarism)

Features of hypothyroidism, progressive painless moderate enlargement of thyroid Increased incidence of lymphoma Often associated with other autoimmune disorders (SLE, RA, Graves Ds)

Test for Ab TSH, T4 ESR

Treatment Levothyroxine (T4) (Synthroid) Tx must start w/in 23mo to reverse sx

Subacute Granulomatous Thyroiditis (DeQuervain’s Thyroiditis)

Levothyroxine (T4) (Synthroid) Infants (1-6mo) 1-1.5mg Adult .017mg Recheck after 6-8 weeks

Post Partum Thyroiditis (PPT) (Silent Thyroiditis)

Subclinical Hypothyroidism

Type of Disease Hypothyroidism Pathology

Granulomas 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

Painful enlargement of thyroid, self limited ds, recovery in about 3-6 months Phase I: hyperthyroid, ↓ to nl TSH, ↑ fT3&T4, ↓ RAIU Phase II: ↓ T3&T4, ↑ TSH, ↑ RAIU Phase III : TSH, T3, T4 wnl

NONPainful enlargement of thyroid, self limited ds Phase I: hyperthyroid, ↓ to nl TSH, ↑ fT3&T4, ↓ RAIU Phase II: ↓ T3&T4, ↑ TSH, ↑ RAIU Phase III : TSH, T3, T4 wnl Can mimic pp depression

some asymptomatic, Some symptomatic: cardiac, lipid, neurobehavior (esp. depression)

Signs & Symptoms

Diagnosis

TSH T4 RAIU

↑ TSH, nl T4, fT4

Treatment Hyperthyroid state: sx:beta-blockers Asx: monitor Hypothyroid state: Sx: Levothyroxine for 6 – 12 mo. Asx: monitor

Tx symptomatic as well as asymptomatic w/ Levothyroxine Recheck 6 weeks

Multinodular Goiter (Plummer’s Ds)

Type of Disease

Graves’ Disease (Toxic Diffuse Goiter)

Diffuse Nontoxic Goiter (Simple Goiter)

**Most common form of hyperthyroidism** Hyperthyroidism

Pathology

Cause

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

Transformation from long-standing Simple Goiter

Uncertain, probably caused by immunologic mechanism and defect in Ag-specific suppressor T-cells

Iodine deficiency due to: 1. Deficiency in food and water 2. Goitrogens 3. Physiologic demand

Associated w/ HLA-DR3 and autoimmune Ds (SLE, Hashimoto’s Disease) 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

Diffuse enlarged thyroid

Thyroid Storm Self limited in 30% Diagnosis

↑ fT3 & fT4, ↓ sTSH ↑T3RIA, Thyroid Ab

Treatment Propylthiouracil Methimazole *Radioactive iodide

Propylthiouracil Methimazole *Radioactive iodide Surgery: Subtotal Thyroidectomy

↑ fT3 & fT4, ↓ TSH

Subclinical Hyperthyroidism

Primary Hyperparathyroidism **most common cause of hypercalcemia

Type of Disease

Hyperthyroidism

Hyperparathyroidism

Pathology

Cause

Signs & Symptoms

Diagnosis

Treatment

Secondary Hyperparathyroidism

Compensatory hyperplasia in response to hypocalemic state

Euthyroid Graves, autonomous adenoma, Excessive THR Tx, Thyroid Hormone suppressive therapy

Asymptomatic or symptomatic: atrial fibrillation, osteoporosis

Parathyroid adenoma Carcinoma hyperplasia

**Chronic renal failure Malabsorption Sx Vit D deficiency

Osteitis Fibrosa Cystica (cysts formed from resorption of Ca – leads to pathologic fx and “Brown tumors”) BONES Nephrolithiasis, gallstones – STONES Pancreatitis – GRONES Peptic Ulcers – MONES Assoc. w/ MEN

Nl fT4, FTI, T3RIA ↓ TSH

↑serum Ca (3 consec. Tests;unless >12) ↓ serum phosphate ↑PTH ↑urinary Ca in 24hr urine ↑ALP ↑cAMP in serum or urine radiograph (find brown turmors)

↓ serum Ca ↑ serum phosphate ↑PTH ↑ALP

If on suppression therapy: ↓ Rx Asx: repeat TSH 36mo, 24hr RAIU – if ↑ use beta blocker or antithyroid rx

CA or adenoma: surgery Acute Ds: ↑ excretion w/ saline & furosemide, Mithramycin, Calcitonin, Diphosphates, Hydrocortisone, Gallium Nitrate Moderate Ds : hydration, diuresis, phosphates, calcitonin, indocin, ASA, Disodium Etdronate Crisis: hopitlization, hydration Mithramycin, Disodium Etidronate

Hypoparathyroidism

Thyroid Cancer

**VERY RARE*** Type of Disease

Pathology

Hypoparathyroidism

Papillary (most commom), Follicular, mixed, anaplastic, medullary (can be assoc w/ MEN)

Inadequate secretion of PTH or endorgan resistance

Cause Idiopathic, post surgical, radiation therapy, autoimmune ds, parathyroid aplasia associated w/ DiGeorge’s

Recurrent thyroid CA, hx of radiation exposure

Severe cases: cardiac arrhythmias, tetany, ↑ intracranial pressure w/ papilledema, cataracts, diarrhea, epilepsy, Trousseau’s Sign, numbness, tingling, Chvestek sign

Vary Dysphagia, hoarseness, firm and immobile nodules, cervical lymphadenopathy

↓ Serum Ca ↑phosphate levels ↓PTH

sTSH, Ab, Tg (+ in malignancy) Thyroid scan (cold nodules), Calcitonin level U/S FNA biopsy

Signs & Symptoms

Suspect nodules in males >40 and females >50 and ALL nodules in children

Diagnosis

Treatment Thyroidectomy (suspect CA, compression, cosmetic) RIA(inoperable, residual ds in neck, invasion, metastasis) Chemotherapy T4 suppressive therapy of TSH

Disease Cushing Syndrome

Type of Disease

Conn’s Syndrome (Primary Hyperaldosteronism)

Hyperadrenalism

Pathology **Pituitary: Tumor or hyperplasia (Cushing Disease) Adrenal: Tumor

Hypersecretion of aldosterone

Ectopic production of ACTH or CRH (usually carcinoid tumor of lung or pancreas) Iatrogenic Cause

Overproduction of ACTH from pituitary(Cushing Ds) OR overproduction of CRF from hypothalamus OR ectopic ACTH production OR Adrenal tumor producing cortisol

**Adrenocortical adenoma Hyperplasia Carcinoma (rarely)

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

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 glucose Dexamethasone Suppression Test

↑ Aldosterone level ↓ Renin Level Metabolic alkalosis Exessive K in urine ↓ serum K Saline Suppression Test

Signs & Symptoms

HTN but hyporeninemia (due to feedback from aldosterone)

Diagnosis

Pituitary MRI to confirm Treatment Surgical removal of producing tumor, irradiation or resection of hyperplastic adrenals 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

CT , then Venous/Arterial sampling Spironolactone (Aldactone) Or Diuretics

Disease Glucocorticoid Remediable Aldosteronism (GRA)

Adrenogenital Syndrome

Secondary Adrenal Insufficiency

Type of Disease Hyperadrenalism

Pathology

Cause

Signs & Symptoms

Hypoadrenalism

Hypersecretion 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 an overproductio n of androgens

Decreased production of ACTH

Abnl hybrid gene results in stimulation of aldosterone by ACTH

Congenital

Adrenocortical, hyperplasia, adenoma or carcinoma

Destructive pituitary or lesions of the hypothalamus

HTN

Present @ brith w/ virilization of female

Virilization of female

Salt wasting Diagnosis ↑ aldosterone level ↓ cortisol level

Treatment

↑ ACTH ↓ cortisol level ↑androgens

↓ ACTH ↓ cortisol level nl aldosterone

Dexamethasone given to predisposed mother to prevent fetus from genital deformation

Corticotropin (only parenteral) Hydrocortisone (oral)

IV Hydrocortisone Mineralcorticoids

Disease

Addison’s Disease (Primary Adrenocortical Insufficiency)

Pheochromocytoma

Hypoadrenalism

Ds of Hypersecretion of the Adrenal Medulla

Type of Disease

Pathology

Cause

Destruction of adrenal cortex resulting in ↓ cortisol production and aldosterone

Tumor arising from chromaffin cells of adrenal medulla secreting catecholamines (outside the adrenals: paragangliomas)

***Idiopathic adrenalitis (autoimmune) *TB *Histoplasmosis Amyloidosis, metastatic carcinoma, hemochromatosis

Sporatic Familial Some associated w/ MEN II, MEN III

(all resulting in damage to the pituitary or hypothalamus) Signs & Symptoms

Acute: rapid progression, shock, septicemia, WaterhouseFriderichsen, 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

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

Idiopathic often assoc. w/ other autoimmune diseases

Diagnosis ↓ ↓ ↓ ↑ ↑ Treatment

↑ catecholamines in serum and urine Presence of VMA (Vanillylmandelic acid)in 24° urine **pathnomonic MRI to confirm

cortisol Na+ glucose K+ ACTH

Acute: Cortisol 100mg IV Q 6-8° until stable Reduce over 5d to maintenance dose of 50mg/d IV saline Glucose

Chronic: Hydrocortisone 2030mg QD 2/3 given in am 1/3 given in afternoon Fludrocortisone

Alpha adrenergic blockers w/ Beta Blockers Surgery

Disease

Type of Disease Pathology

Cause

Signs & Symptoms

Ganglioneuroma/ Neuroblastoma

Type I Diabetes Mellitus

Ds of Hypersecretion of the Adrenal Medulla Ganglioneuroma Benign tumor of ganglion cells

Neuroblastom a Highly malignant tumor from neural crest

Tumor

Neuroblastoma: common in childhood, abdominal mass, anemia, fever, wt loss Commonly metastasizes to bone of skull and orbit (Hutchison-type) To liver (Pepper Syndrome)

Metabolic Disorder of the Pancreas

Ab against beta cells destroy islet cells resulting in a decreased production of insulin

Target tissue develops insulin resistance

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

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

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 disease

Diagnosis

Treatment

Type II Diabetes Mellitus

↓ insulin ↑ HbA1c Ab to islet cells or insulin Fasting glucose >126mg/dL Random glucose >200mg/dL 1.

NPH BID w/ premeal Lispro 2. Glargine Q HS w/ premeal Lispro Pt education Goal: HbA1C 7% or lower DKA tx: hydration, insulin

Chronic Complications: CAD, MI, stroke, gangrene, cataracts, artherosclerosis, retinopathy, nephropathy, neuropathy, vascular Ds ↓ insulin ↑ HbA1c Fasting glucose >126mg/dL Random glucose >200mg/dL Diet, exercise, wt loss Sulfonylureas Glucophage Insulin (occas.) Tx hyperlipidemia Pt education

Disease Insulinoma

Type of Disease

Pathology

Cause

Signs & Symptoms

Pancreatic Tumor

Gastrinoma (Zollinger-Ellison Syndrome)

Pancreatic Tumor

Insulin producing tumor of the islet cells

Gastrin Producing tumor of islet cells

Tumor

Tumor

Dizziness, confusion, bizarre behavior, seizure, coma

Triad: gastrinoma, gastric acid hypersecretion, peptic ulcer disease

10% malignant Assoc. w/ MEN I

Diarrhea, fluid electrolyte imbalance 60% malignant Assoc w/ MEN I

Diagnosis

Treatment

↑ insulin ↓ glucose