ENDOCRINOLOGY
ENDOCRINOLOGYcomprehensivePHYSIOLOGY
Insulin Preproinsulin synthesized in RER proinsulin exocytosis
of insulin and C-peptideInsulin and C-peptide are increased in
insulinomaRleased from Pancreatic Beta cellsAnabolic effects of
insulinGlucose transport in skeletal muscle and adipose tissue
Glycogen synthesis and storage Triglyceride synthesisSodium
retentionProtein synthesisGlucagon releaseGlucagonMade by
pancreatic Alpha cellsCatabolic effects of Glucagon:Glycogenolysis,
gluconeogenesisLipolysis and ketone productionSecreted in response
to hypoglycemiaInhibited by insulin, hyperglycemia, and
somatostatin
ProlactinSecreted by Anterior PituitaryStimulates milk
production in breastInhibits ovulation in females and
spermatogenesis in males by inhibiting GnRH synthesis and
releasesInhibited by Dopamine from hypothalamusProlactin in turn
inhibits its secretion by increasing Dopamine synthesis and
secretionTRH prolactin secretionGH (somatotropin)Secreted by
Anterior PituitaryStimulates linear growth and muscle mass through
IGF-1/somatomedin secretion, insulin resistance
(diabetogenic)Releases in pulses in response to the GNRHSecretion
during exercise and sleepInhibited by glucose and
somatostatinExcess secretion = Pituitary AdenomaCause of acromegaly
in adults and gigantism in childrenAntidiuretic hormoneSynthesized
in hypothalamus, released by Posterior PituitaryRegulates serum
osmolarity and BPSerum osmolarity regulation via regulation of
aquaporin channelADH level isin central diabetes inspidus, normal
orin nephrogenic DIDesmopressin (ADH analong) = Tx for Central
DI
CortisolSecreted from Adrenal gland (Zona Fasciculata)BP
(upregulates Alpha-1 receptors on arterioles)Insulin
resistanceGluconeogenesis, lipolysis, proteolysisFibroblast
activity (striae)Inflammatory and Immune responsesBone formation
(osteoblast activity)CRH (hypothalamus) stimulates ACTH (pituitary)
release, causing cortisol productionExcess cortisol CRH, ACTH, and
Cortisol secretion
ParaThyroid HormonePhosphate Trashing Hormone (PTH)Secreted by
Chief cells of parathyroidBone resorption of Ca2+ and PO43-Kidney
reabsorption of Ca2+ in DCTReabsorption of PO43- in PCT1,25-(OH)2D3
(calcitrol)serum Ca2+ PTH secretionserum Mg2+ PTH secretionserum
Mg2+ PTH secretionVitamin D (Cholecalciferol)D3 from sun exposure
in skinD2 ingested from plantsBoth converted to 25-OH in liver and
to 1,25-(OH)2 in kidneyAbsorption of dietary Ca2+ and PO43-Bone
resorption Ca2+ and PO43-CalcitoninSecreted from Parafolicular
cells of Thyroid (C cells)Bone resorption of Ca2+serum Ca2+ causes
calcitonin secretionCalcitonin opposes actions of PTHCalcitonin
tones down Ca2+ levels
Thyroid hormones (T3/T4)Secreted from Follicles of thyroidT3
functions 4 BsBrain maturationBone growthBeta-adrenergic
effectsBasal metabolic rate Beta receptors in heart CO, HR, SV,
ContractilityBasal metabolic rate Na+/KATPaseglycogenolysis,
gluconeogenesis, lipolysisTRH (hypothalamus) stimulates TSH
(pituitary) which stimulates follicular cellsNegative feedback by
free T3, T4 to anterior pituitary decreasing sensitivity to
TRHWolf-Chaikoff effect excess iodine temporarily inhibits thryoid
peroxidase iodine organifications T3/T4
PATHOLOGYCushing Syndromecortisol due to variety of
causes:Exogenous corticosteroids ACTH, bilateral adrenal
atrophyPrimary adrenal adenoma, hyperplasia, or carcinoma ACTH,
atrophy of adrenal gland. Can be present in Conn
syndromeACTH-secreting pituitary adenoma (Cushing disease),
paraneoplastic ACTH secretion, small cell lung cancer, bronchial
carcinoid ACTH, bilatral adrenal hyperplasiaDexamethasone
suppression test distinguish between Cushing (will decrease) and
ectopic ACTH secretion (wont decrease)HyperaldosteronismPrimary
Caused by adrenal hyperplasia or an aldosterone secreting adrenal
adenoma (CONN SYNDROME) resulting in hypertension, hypokalemia,
metabolic alkalosis, low plasma reninRemove the tumor or
Spironolactone, K+ sparing diureticSecondary Renal perception of
low intravascular volume resulting in overactive RAASIt is due to
Renal Artery Stenosis, CHF, cirrhosisTreatment is
SpironoloctoneAddison diseaseChronic primary adrenal insufficiency
due to adrenal atrophy or destruction by diseaseDeficiency of
aldosterone and cortisol causing hypotension, hyperkalemia,
acidosis, and skin/mucosal hyperpigmentationAdrenal Atrophy and
Absence of hormone productionSecondary adrenal insufficiency, had
no skin/mucosal hyperpigmentation and no hyperkalemiaNeuroblastoma
The most common tumor of adrenal medulla in childrenOriginates from
neural crest cellsPresentation: abdominal distention, and firm,
irregular massHomovanillic acid in urineBombesin +Less likely to
develop hypertensionAssociated with overexpression of N-myc
PheochromocytomaMost common tumor of the adrenal medulla in
adultsDerived from chromaffin cells (arise from neural crest)Rule
of 10s10% malignant10% bilateral10% extra-adrenal10% calcify10%
kidsMost tumors secrete epinephrine, norepinephrine, and dopamine,
which can cause episodic hypertensionAssociated with von
Hippel-Lindau disease, MEN 2A and 2BSymptoms occur in spellsUrinary
VMA and plasma catecholamines are
HYPOTHYROIDISMHashimoto thyroiditisMost common cause in odine
sufficient regionsAnti-thryoid peroxidase antithyroidglobulin
antibodiesAssociated with HLA-DR3Hyperthyroid early due to
thyrotoxicosis during follicular ruptureHisto: Hurthle cells,
lymphoid aggregate with germinal centersEnlarged nontender
thyroid
Congenital hypothyroidism (Cretinism)Severe fetal hypothyroidism
due to maternal hypothyroidism, thyroid agnesis, thyroid
dysgenesis, iodine deficiency, dyshormonogenic goiterFindings: pot
belly, pale, puffy face, protruding umbilicus, protuberant tongue,
poor brain developmentSubacute thyroiditis (de Quervain)Self
limited hypothyroidism often following a flu-like illnessMaybe
hyperthyroid earlierHisto: granulomatous inflammationFindings: ESR,
jaw pain, tender thyroid (de quervain is associated with
pain)Riedel thyroiditisThyroid replaced by fibrous tissue
(hypothyroid)Fibrosis may extend to local structures (airways),
mimicing anaplastic carcinomaConsidered manifestation of IgG
related systemic diseaseHYPERTHYROIDISMToxic multinodular goiter
Focal patches of hyperfunctioning follicular cells working
independently of TSH due to mutation in TSH receptorrelease of T3
and T4Jod Basedow phenomenon refers to when thryrotoxicosis occurs
if a patient with iodine deficiency goiter is made iodine
repleteGraves disease Autoantibodies (IgG) stimulates TSH receptors
on thyroidDiffuse goiter, retro-orbital fibroblasts (exophthalmos),
dermal fibroblasts (pretibial myxedema). Often presents during
stress (childbirth)Thyroid storm Stress induced catecholamine surge
seen in serious complication of Graves disease and other
hyperthyroid disorders.Thyroid cancerPapillary carcinoma most
common, excellent prognosis. Empty appearing nuclei (Orphan Annie
eyes). Psammoma bodies. RET and BRAF mutations.Medullary carcinoma
from parafollicular C cells. Produces cacitonin. Sheets of cells in
an amyloid stroma. Associated with MEN 2A and 2B (RET gene)
Follicular carcnimoma good prognosis. Invades thyroid capsule,
uniform folliclesUndifferentiated/anaplastic carcioma older
patients. Invades local structures. Very poor prognosisLymphoma
associated with Hashimoto thyroiditisHyperparathyroidism
Primary stones, bones, groans, psychtriac overtones Usually an
adenomaHypercalcemia, hypercalciuria (renal stones),
hypophosphatemiaPTH, ALP, cAMP in urineMay present with weakness
and constipation, abdominal/flank pain (kidney stones, acute
pancreatitis), depressionOstitis fibrosa cystica cystic bone spaces
filled with brown fibrous tissue (bone pain)Secondary Due to gut
Ca2+ absorption and PO43- Hypocalcemia, hyperphosphatemia in
chronic renal failure (vs hypophosphatemia with most other
causes)ALP, PTHRenal osteodystrophy bone lesions due to 2o or 3o
hypeparathyroidism in turn to renal diseaseHypoparathyroidismDue to
accidental surgical excision of parathyroid glands, autoimmune
destruction, or DiGeorge syndromeHypocalcemia, tetanyChvostek sign
taping of facial nerve (tap the Cheek) leading to contraction of
facial musclesTrousseau sign occlusion of brachial artery with BP
cuff (cuff the triceps) leading to carpal spasmDiabetes
InsipidusIntense thirst and polyuria, with inability to concentrate
urine due to lack of ADH
SIADHSyndrome of Inappropriate ADH secretionExcessive water
retentionHyponatremiaUrine osmolarity > serum osmolarityBody
response:aldosterone to maintain near-normal volume statusCan lead
to edema, seizures due to low NaCauses:Ectopic ADH (small lung
cancer)CNS disorders/head traumaPulmonary diseaseDrugs like
CyclophosphamideTx: IV hypertonic saline
HypopituitarismUndersecretion of pituitary hormones due
to:Nonsecreting pituitary adenoma, cranipharyngiomaSheehan syndrome
ischemic infarct of pituitary following postpartum bleeding (due to
lack of collateral circulation)Empty sella syndrome atrophy or
compression of pituitary, often idiopathic, common in obese
women35Diabetes mellitusPolydipsia, polyuria, polyphagia, weight
loss, DKA (type 1), hyperosmolar coma (type 2)Rarely can be caused
by unopposed secretion of GH and epinephrineNonenzymatic
glycosylation:Small vessel disease (diffuse thickening of basement
membrane) retinopathy (hemorrhage, exudates, microaneurysms, vessel
proliferation), glaucoma, nephropathyKimmelstiel-Wilson nodules due
to arteriosclorsisOsmotic damage (sorbitol accumulation in rogans
with aldose reductase)Neuropathy, cataractsTests: fasting serum
glucose, oral glucose tolerance test, HbAic
Diabetic ketoacidosisOne of the most important complications of
diabetes (usually Type 1)Excess fat breakdown and increased
ketogensis from fatty acids ketone bodiesSigns: Kussmaul
respirations, nausea, abdominal pain, psychosis/delirium,
dehydration, fruity breath (acetone)Labs: hyperglycemia, H+,
HCO3-Life threatning murcormycosis (rhizopus infection), cerebral
edema, cardiac arrhythmiasTx: IV fluids/insulinCarcinoid
syndromeCaused by carcinoid tumors, which secrete high levels of
serotoninNot seen if tumor limited to GI tractResults in recurrent
diarrhea, cutaneous flushing, asthmatic wheezing, right sided
valvular disease5-HIAA in urineTx: resection, somatostatin analong
(ocreotide)Zollinger Ellison syndromeGastrin secreting tumor of
pancreas or dueodenumAcid hypersecretion causes recurrent ulcers in
distal duodenum and jejunumAbdominal pain, diarrheaMay be
associated with MEN 1
