Endocrine Pathology

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Secondary Cushing's (due to pituitary adenoma)

Result of abnormally elevated ACTH

Cushing's due to adrenal hyperplasia/neoplasia

Hyperadrenocorticism with decreased ACTH

Example and explanation of tumors that cause Cushing's

Small cell lung cancer. Ectopic ACTH production

Iatrogenic Cushing's

Chronic steroid use, asthma meds & prednisone. All decrease ACTH by negative feedback. [Most common Cushing etiology.]

Dexamethasone suppression test in healthy patient

See decreased cortisol after low dose.

DST test with ACTH-producing pituitary adenoma (Cushing's)

Cortisol does not decrease after low dose, does decrease after high dose

Neurofibromatosis-1 (Von Recklinghausen syndrome)

Most common 1-gene defect, an autosomal dominant causing neural fibromas & cafe au lait spots

DST results in patient w/ cortisol producing [adrenal] tumor or patient w/ ectopic ACTH-tumor

Cortisol does not decrease after low dose or high dose

Cushing's findings

HTN, weight gain, moon facies, truncal obesity, buffalo hump, hyperglycemia, skin changes, osteoporosis, amenorrhea and immune suppression

Primary hyperaldosteronism etiology & diagnosis

Aldosterone secreting tumor [glomerulosa], resulting in HTN, hypokalemia, metabolic alkalosis, and low plasma renin

Secondary hyperaldosteronism etiology and results

Low blood volume [e.g., CHF, cirrhosis, dehydration, renal artery stenosis, renal failure]. Results in overactive RAAS & high plasma renin

Primary hyperaldosteronism treatment

Spironolactone, a K-sparing diuretic

Addison's disease cause & findings

Primary adrenal insufficiency, cortisol and aldosterone low. Hypoglycemia, hypotension, hyperkalemia and bronzing.

Secondary adrenal insufficiency

Insufficient ACTH. Mimics Addisons' but no bronzing and no hyperkalemia.

Addison's mnemonic

Adrenal Atrophy and Absence of hormone production; involves All three cortices

Waterhouse-Friderichsen syndrome findings & bacterial cause

Acute adrenocortical insufficiency due to adrenal hemorrhage. Associated with meningococcal septicemia

Sheehan's syndrome

Postpartum hypopituitarism. Enlargement of anterior pitutary during pregnancy without corresponding increase in blood supply leads to increased risk of infarction of the pituitary gland following severe bleeding during delivery.

Sheehan's syndrome symptoms [post- partum hypopituitarism]

Fatigue, amenorrhea, poor lactation, loss of pubic and axillary hair

Pheochromocytoma rule

10% malignant, 10% bilateral, 10% extra-adrenal, 10% calcify, 10% kids, 10% familial


Most common tumor of the adrenal medulla in adults. Derived from chromaffin cells which arise from neural crest.

Pheochromocytoma secretions

Epinephrine, Norepinephrine and Dopamine; can cause episodic hypertension.

Elevated with pheochromocytoma

Urinary VMA (vanillylmandelic acid) and plasma catecholamines.

Pheochromocytoma associations

NF, MEN types 2A and 2B

Pheochromocytoma treatment

Alpha blockers, especially phenoxybenzamine [nonselective, irreversible alpha blocker] "Pheo-Knocks-Ben's Amine"

Episodic hyperadrenergic causes and symptoms

Carcinoid tumors & pheochromocytoma. Hypertension [Pressure], Pain, Perspiration, Palpitations, Pallor


Most common tumor of adrenal medulla in kids. Can occur anywhere along the sympathetic chain. See HVA (DA breakdown product) in urine. N-myc oncogene.

MEN 1 [Multiple Endocrine Neoplasia 1] = Werner's syndrome characteristics

Pancreas tumors [Z-E syndrome, insulinomas]; Pituitary tumors [prolactin or GH]; Parathyroid tumors [hypercalcemia]

MEN 1 (Multiple Endocrine Neoplasia) tumor sites & presentation

Pituitary [prolactinoma], parathyroid [hypercalcemia] & pancreas [gastrinoma]. "Stones, bones & groans"

MEN2A (Multiple Endocrine Neoplasia 2A) (Sipple's syndrome)

Medullary thyroid carcinoma , Pheochromocytoma, Parathyroid tumors [but not oral ganglioneuromas, as MEN2B does]

MEN 2B traits & dx

Medullary thyroid carcinoma [secretes calcitonin], Pheochromocytoma, Oral/intestinal ganglioneuromas. Marfan appearance.

Form of inheritance of MEN syndromes

Autosomal Dominant

MEN 2A and 2B gene defect (name gene)

RET proto-oncogene activation

Hypothyroidism findings

Cold intolerance, hypoactivity, weight gain, fatigue, decreased appetite, constipation, weakness, decreased reflexes, dry cool skin, corase brittle hair

Primary hypothyroidism labs

Increased TSH, decreased total T4, decreased free T4, decreased T3 uptake

Hyperthyroidism signs & symptoms

Heat intolerance, hyperactivity, weight loss, palpitations, arrhythmias, diarrhea, exophthalmos, warm moist skin, fine hair

Primary hyperthyroidism labs (Graves, thyroid adenoma)

Decreased TSH, increased total T4, & free T4, increased T3 uptake

Hashimoto's thyroiditis

Autoimmune hypothyroidism. Moderately enlarged, nontender thyroid produces anti-thyroglobulin antibodies.

Subacute thyroiditis [de Quervain's] symptoms & diagnosis

Self-limited hypothyroidism often following a flulike illness. Elevated ESR, jaw pain, tender thyroid. Granulomatous inflammation.

Riedel's thyroiditis

Thyroid replaced by fibrous tissue. Presents with fixed, hard, painless goiter.

Grave's disease

Autoimmune hyperthyroidism with thyroid-stimulating TSH receptor antibodies. Exophthalmia, pretibial myxedema, diffuse goiter. Often presents during stress.

Thyroid storm & Grave's disease

Stress-induced thyrotoxicosis with high fever, cardiovascular and nervous system dysfunction. Possible death by arrhythmia.

Toxic multinodular goiter causes & appearance

Cause: Iodine deprivation followed by iodine restoration. Causes release of T3 and T4. Non malignant.

Jod-Basedow phenomenon

Thyrotoxicosis in a iodine deficiency goiter treated with iodine

Papillary thyroid carcinoma frequency & diagnosis

Most common thyroid cancer. Good prognosis. Ground glass nuclei, "Orphan Annie eyes"[Daddy Warbucks=Papa-lary] and psamomma [Papa & Momma] bodies, nuclear grooves, increased risk with childhood irradiation.

Follicular carcinoma

Most common thyroid cancer. Good prognosis. Uniform follicles.

Medullary carcinoma

Thyroid cancer of parafollicular "C" cells. Produces calcitonin. Sheets of cells in amyloid stroma. Associated with MEN types 2A and 2B.

Undifferentiated/anaplastic thyroid cancer

Older patients, very poor prognosis.


Associated with Hashimoto's thyroiditis


Due to severe fetal hypothyroidism. May be due to endemic lack of iodine, defect in T4 formation, or development failure in thyroid formation.

Cretinism signs & symptoms

MR, pot-bellied, hypotonic with protruding umbilicus and tongue


Excess GH in adults

Acromegaly signs & symptoms

Large tongue with deep furrows, deep voice, large hands and feet, coarse facial features, impaired glucose tolerance [insulin resistance]

Acromegaly treatment

Pituitary adenoma resection followed by octreotide

Acromegaly diagnosis

Increased serum IGF-1; failure to suppress serum GH following oral glucose tolerance test

Primary hyper-parathyroidism cause & signs & symptoms

1. Parathyroid adenoma increases PTH
2. Hypercalcemia, hypercalciuria (renal stones), hypophosphatemia. Classic presentation includes weakness and constipation with "stones, bones, and groans"

Osteitis fibrosa cystica (von Recklinghausen's syndrome)

Cystic bone spaces filled with brown fibrous tissue, found in primary hyperparathyroidism

Secondary hyperparathyroidism symptoms & causes

1. Hypocalcemia from decreased Ca absorption in chronic renal failure --> stimulus of parathyroids --> hyperphosphatemia. Ends in osteodystrophy
2. Squamous cell lung cancer [paraneoplastic secretion of PTH]

Renal osteodystrophy

Bone lesions due to secondary hyperparathyroidism in end-stage renal disease. Hyperphosphatemia and hypocalcemia.

Hypoparathyroidism causes & effects

Causes: Surgical excision, autoimmune destruction, or DiGeorge syndrome. Effects: Hypocalcemia, tetany.

Chvostek's sign from hypocalcemia

Found in hypoparathyroidism. "Tetany-on-demand." Tap CN-7 [facial nerve] --> contraction of facial muscles.

Trousseau's sign-- hypocalcemia

Found in hypoparathyroidism. Occlusion of brachial artery with BP cuff --> carpal spasm


AD kidney unresponsiveness to PTH. Hypocalcemia, shortened 4th/5th digits, short stature

All are causes of hypercalcemia--"bones, groans, stones"

Ca2+ ingestion, Parathyroid tumor, Hyperparathyroidism, Squamous cell lung cancer, Thiazide diuretics, Lithium use, Paget's, Addison's, Z-E, Excess vit D.

Common pituitary adenoma & its treatment

Prolactinoma. Dopamine agonists [bromocriptine & cabergoline] cause shrinkage. Tumor may impinge on optic chiasm --> temporal hemianopia

Cushing's sexual findings

Amenorrhea, galactorrhea, low libido, infertility

Acute manifestations of DM

Polydipsia, polyphagia, weight loss, DKA (type I), hyperosmolar coma (type 2), unopposed secretion of GH and epi (exacerbating hyperglycemia)

Chronic manifestations of DM due to nonenzymatic glycosylation

Small vessel diease (diffuse thickening of BM) --> retinopathy, glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to HTN, Kimmelsteil-Wilson nodules). Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease and gangrene, cerebrovascular disease.

Chronic manifestations of DM due to osmotic damage

Neuropathy [motor, sensory and autonomic dysfunction]; and cataracts [sorbitol accumulation]

DM tests

Fasting serum glucose, glucose tolerance test, HbA1c (measures long term diabetic control)

Type I DM

Juvenile onset, due to viral or immune destruction of beta cells. Always require insulin. Genetic predisposition. Ketoacidosis is common. Polyuria, polydipsia, weight loss.

Type II DM

Adult onset. Increased resistance to insulin. Insulin is sometimes neccessary in tx. Age is >40y at onset. Strong polygenic genetic predisposition. No association with HLA. Mild to moderate glucose intolderance. Ketoacidosis is rare. Beta cell numbers in islets are variable, serum insulin levels are variable. poly sx & weight loss occur sometimes.


One of most important complications of Type I DM. Usually due to increased insulin requirements from increased stress (eg infection). Excess fat breakdown and increased ketogenesis from increased FFAs which are then made into ketone bodies.

DKA signs and sx

Kussmaul respirations (rapid/deep breathing), N/V, abd pain, psychosis, dehydration, fruity breath

DKA (diabetic ketoacidosis) labs

Hyperglycemia, acidosis, decreased HCO3- (anion gap), increased blood ketone levels, leukocytosis, hyperkalemia but depleted intracellular K due to transcellular shift.

DKA complications

Complications: Life-threatening mucormycosis, cerebral edema, cardiac arrhythmias, heart failure

DKA treatment

Monitor/adjust fluids, insulin, K+ [to replace intracellular stores]; glucose if neccessary to prevent hypoglycemia

Diabetes insipidus

Intense thirst and polyuria together with an inability to concentrate urine owing to lack of ADH (central) or to a lack of renal response (nephrogenic)

Causes of central diabetes insipidus

Poserior pituitary tumor, trauma, surgery, & histiocytosis X

Causes of nephrogenic diabetes insipidus

Hereditary or secondary to hypercalcemia, lithium, demeclocycline [ADH antagonist]

Diabetes insipidus diagnosis

H2O deprivation test - urine osmolality unaffected [remains very low]. Response to desmopressin distinguishes central type [responds] from nephrogenic type [no response].

Diabetes insipidus findings

Urine specific gravity < 1.006; serum osmolality >290 mOsm/L

Diabetes insipidus treatment

ALL: Adequate fluid intake. Central: intranasal desmopressin (ADH analog). Nephrogenic: diuretics (Hydrochlorothiazide or amiloride)

SIADH signs & symptoms

Excessive water retention, hyponatremia[Na is diluted by reabsorbed H2O], urine osmolarity > serum osmolarity

Most dangerous SIADH complication

Complication : Extreme hyponatremia [central pontine myelinolysis]. Can lead to seizures [correct slowly!]

SIADH treatment

Water restriction, then Demeclocycline [a tetracycline derivative!]; add furosemide in severe cases. Never correct Na faster than 10 mEq in 24 hr!

SIADH causes

Ectopic ADH [small cell lung cancer], CNS disorders/head trauma; pulmonary disease [pneumonia, TB]; or drugs [cyclophosphamide]

Carcinoid syndrome causes, signs & symptoms

Tumors of neuroendocrine cells in gut and in lungs . Secrete high levels of 5-HT (serotonin). Paroxysmal flushing, wheezing asthma, diarrhea & RCHF

Reason why carcinoid syndrome is not seen in primary GI tumors

5-HT (serotonin) undergoes first-pass metabolism in liver

Carcinoid syndrome signs & symptoms

Diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease.

Carcinoid syndrome treatment


Zollinger-Ellison syndrome

Gastrin-secreting tumor of pancreas. Causes recurrent ulcers. May be associated with MEN type I

MEN-1 tumor sites

Parathyroid [hypercalcemia], pituitary medulla [calcitonin], pancreas [gastrinoma--> ulcers-Zollinger Ellison]

Central and Nephrogenic

The two types of diabetes insipidus

Central diabetes insipidus cause

Deficient production of ADH

Nephrogenic diabetes insipidus cause

Renal ADH receptor defect

DiGeorge syndrome

Cardiac Abnormality [especially Fallot's Tetralogy]
Abnormal facies
Thymic aplasia [T-cell deficiency]
Cleft palate
Hypocalcemia [Parathyroid aplasia]
22-- chromosome

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