Endocrine System - Part 2 (Robbins)

Pathology (dr. Yabut) Endocrine Pathology ( from Book) 09 January 08

Clinical Features of Diabetes Type I -

-

Type II

Occur at at an any ag age Honeymoon Period: in the initial 1-2 years following manifestation of  overt overt type type 1 diabet diabetes es the exoge exogenous nous insulin insulin requi requirem rement ent may be minimal to none Dominated by signs of altered metabolism: polyuria, polydipsia, polyphagia Despite increased appetite, catabolic effects prevail  weight loss and weakness Chemical Chemical indices indices: ketoa ketoacid cidosi osis, s, low or absent absent plasma plasma insulin insulin,, elevated plasma glucose Metab Metaboli olic c dera derang ngem emen entt and insul insulin in need are direc directl tly y relat related ed to physiologic stress

-

-

Complications of Both Types Types of Diabetes Cardiovascular Di Disease Diabetic Ne Nephropathy Lead Le adin ing g cause cau se of endend-st stag age e rena renall renal vascula vascularr insuffi insufficie ciency, ncy, - MI, renal -

CVA are the most common cause of death Appear ≈ 15-20 years after hypoglycaemic onset Acco Account unts s for for 80% 80% of dea deaths ths in typ type e 2 diabetes

-

-

Ol de der th an an ag age 40 With With poly polydi dips psia, ia, pol polyur yuria, ia, obe obesi sity ty Metabo Metabolic lic derange derangemen ments ts are usually usually mild mild Dx is made afte afterr routine routine blood blood or urine urine testi testing ng in asympt asymptom omat atic ic persons Non-ketotic Hyperosmolar Coma: elderly individuals who become dehydrated secondary to osmotic dieresis and lack adequate water intake

disease Earl Earlie iest st mani manife fest stat atio ion n is the the appe appear aranc ance e of low amoun amounts ts of  albumin in the urine (≥30mg/day) or microalbuminuria 80% of type1 and 20-40% of type nephropathy  2 develo develop p overt nephropathy  w it ith macro al albu mi minu ri ria (≥300mg/day) over the next 10-15 years usually accompanied by the appearance of hypertension

Diabetic Re Retinopathy -

-

Infections

60-8 60-80% 0% of of pxs pxs deve develo lop p this this 15-20 years after diagnosis 4th leading cause of acquired blindness Have Have a pred predis ispo posi siti tion on to cataracts and glaucoma

-

Enha Enhanc nced ed sus susce cept ptib ibil ilit ity y to infections of the skin and to TB, pneu pneumo monia nia,, and and pyelonephritis

Pancreatic Endocrine Neoplasms Incidence Insuli Insulinom noma a (β-cel (β-celll tumor) most co common of pancre pancreati atic c endocrine neoplasms responsible for the

Clinical Features -

-

2b1 (joy, shar, cams, yna) at goldie

clin ic ical triad: Attacks of   hypoglycemia oc cu r with blood glucose glucose leve levels ls belo below w 50 mg/d mg/dL L of  serum

Morphology general ly ly be benign solitary lesions, although multipl multiple e tumors tumors or tumors ecto ectopi pic c to the the pancreas may be encountered

Pathogenesis/Etiol ogy - Diffuse hyperp hyperplas lasia ia of  the islets . in neonates and infants. - previously known as nesidioblasto

Lab Finduings high circulatin g leve levels ls of insulin and a high insulinglucose

1 of 6

Treatment -

Surgical removal of  the tumor

Pathology – Endocrine Pathology by  Pathology  by  Dr.  Dr. Yabut 

Page 2 of 6

elaboration elaboration of  sufficient insulin to induce clinically significant hypoglycemia

-

-

th e attacks consist princip principally ally of  such such cent centra rall nervous system manifestations as confusio confusion, n, s sttup upor or,, and and loss of   consciousness ; th e attacks are precipitated by fastin fasting g or exer exercis cise e and are promp promptly tly relie elieve ved d by feeding or parenteral administration of glucose

-

Zollinger-Ellison Syndrome (Gastrinomas)

-

Triad of: Recalcitrant pept peptic ic ulce ulcerr disease Gastric hypersecretion Endocrine ce cell tumor elaborating gastrin Ulcers: Duodenal and - Duodenal -

-

-

smal l (often le less than 2 cm in diameter) encapsulated pale to redbrown brown nodul nodules es located anywhere in the pancreas Histo: look remark remarkably ably like like giant islets, with prese preservat rvation ion of  the regular cords of monot monotono onous us cell cells s and and thei theirr orie orient ntat atio ion n to the vasculature. Immuno: insulin can be localized localized in the tumor cells EM: neoplastic β cells display distinctive distinctive round granu ranule les s that that contain polygonal or rectangular dens dense e crys crystal tals s separa separated ted from from the the enclo nclosi sing ng membra membrane ne by a distinct halo. Arise in th e duod duoden enum um and peripancreatic soft tissues, e.g., pancreas (gastrinoma triangle) 25% aris arises es in conjunction conjunction with other other endocr endocrine ine tumors  MEN1 syndrome

-

sis may re r esult fr f rom maternal diabetes, BeckwithWiedemann synd syndro rome me,, and rare rare meta metabo bolic lic disorders.

ratio

-

Surgical removal but with recurrence

Pathology – Endocrine Pathology by  Pathology  by  Dr.  Dr. Yabut 

Page 3 of 6

-

-

-

α cell tumors (Glucagonomas)

-

Perian d postmenopausal women

-

-

-

δ cell tumors

-

VIPoma (Diarrheogenic Islet Tumor Cell) Pancreatic Carcinoid Tumors Pancreatic PolypeptideSecreting Islet Cell Tumors

Adrenal Cortex

-

-

Associated with neural crest tumors rare

-

-

rare

-

gastri gastric c ulcers ulcers are often multiple Intractable to u su a l modalit modalities ies of  therapy Occur in unusual  locations, locations, e.g., jejunum Diarrhea  presenting symptom in 30% of px 60%  maligna malignant; nt; 40%  benign Extremely high plasma glucagon levels Mild fe features of of   DM Migratory necrotizing necrotizing skin erythema anemia High plasma somatostatin levels Features Features of DM, cholelithiasis, steatorrhea steatorrhea,, and hypochlorhydia Wa te ter y diarrh ea ea Hypokalemia achlorhydia serotoninproducing asymptomatic

multifocal histology a nd ultrastructure similar similar to normal inte intest stin inal al and and gastric G cells

Pathology – Endocrine Pathology by  Pathology  by  Dr.  Dr. Yabut 

Page 4 of 6

A. Adrenocortical Adrenocortical Hyperfunction (Hyperadrenalism)

- Dx: measuring serum level of serum corticotrophin and determining urinary steroid excretion after administration of  dexamethasone to suppress corticotrophin levels - Morphology: depends on the cause Pituitary – Crooke hyaline change with basophils caused by • elevated glucocorticoid levels Diffuse Adrenal Cortical Hyperplasia – glands are • enlarged and affected bilaterally Nodular Adrenal Cortical Hyperplasia – cortex between • nodules is identical to diffuse hyperplasia Adenomas – small, well circumscribed • •

Carcinomas – larger, unencapsulated

•

Zona reticularis and fasciculate – atrophic (both the adjacent and contralateral) Incidence Clinical Features

-

Hypercortisolism (Cushing Syndrome) -

-

Cushing Dse

-

-

Zona glomerulosa – intact Clin Clinic ical al Featur atures es:: Central obesity Moon facies Weakness and fatigability Hirsutism Hypertension Plethora Glucose intolerance/diabetes Osteoporosis Neuropsychiatric abnormalities Menstrual abnormalities Cutaneous striae Delayed wound healing/bruisability

•

• • • • • • • • • • • •

Morphology

Pathogenesis/Etiol ogy

Lab Finduings

Primary Adrenal Neoplasms (Adrenal adenoma, CA, primary cortical hyperplasia) 10-20% of   Independent of   Px with unilateral endogenous corticotrophin neoplasm: Cushing because th e contralateral syndrome a dr dren al als fx n adrenal cortex is autonomously Adults: atrophic vecause aden adenoma omas s and of  costicotropin carcinomas suppression Children: and low levels of  carcinomas corticotropin Ectopic Costicotropin Secretion by Non-Pituitary Tumors Tumors 10% of   Adrenals are Associated Associated with endogenous bil at ateral a nd nd smal smalll cell cell CA Cushing hyoerplastic of the lungs syndrome - Rarely Men, 40 40-60 y/o associated associated with ectopic secr secret etio ion n of  corticotrophin -releasing factor  Young adults Adrenals are Elevated 7 0-80% of   bilaterally serum F:M  5:1 endogenous hyperplastic corticotro hypercortisolism

Treatment

Pathology – Endocrine Pathology by  Pathology  by  Dr.  Dr. Yabut 

Page 5 of 6

-

Primary Hyperaldosteronis m Characterized by - Characterized chroni chronic c exce excess ss aldosterone secretion  Na rete retenti ntion on and K  excretion  HPN and hypokalemia

Women ag aged 30 3050 y/o

-

-

Asoociated Asoociated with a corticotrophi corticotrophinnproducing  pituitary  adenoma Hypokalemia  weakness, paresthesias, visual disturbances, tetany Na retention retention  increas increases es total total body Na and ex pa pands E CF CF volume  hypertension

pin

-

-

-

-

Adrenogenital Syndromes - Androgen-secreting adrenal cortical neoplasms: androgensecreting adrenal CA Congenital adrenal hyperplasia (CAH): autosomal recessive o metabolic errors characterized by a deficiency or total lack of a o particular enzyme involved in the biosynthesis of cortical steroids, i.e., cortisol steroidogenesis is channelled into other pathways  increased o production of androgens  virilization 21-hydroxylase deficiency Defective conversion of progesterone to 11o deoxycorticosterone by 21-hydroxylase (CYP21B)

Solitary, small, encapsulated adenomas occur occurri ring ng more more commonly commonly on the left side May be buried w/in the adrenal adrenal gland land and and not not apparent externally Cut Cut s su urf rfac ace e is bright yellow  high lipid content Lipid l ad aden c el ells resemble resemble cells of  zona fasciculate Presence of PASreactive, eosinophilic, laminated, cytoplasmic inclusions inclusions known as spironolactone bodies 3 distinct o   

-

Autonomous overproductio overproduction n of  aldosterone caused by: Conn syndrome Idiopathic hyperaldoster onism Gluc oc ocor ti ticoi d -remediable hyperaldoster onism

syndromes: Salt-wasting adrenogenitalism adrenogenitalism Simple virilizing adrenogenitalism without salt-wasting Nonclassic adrenogoenitalism

Morphology: Substantial, bilateral adrenal enlargement o Widened cortex and nodular o Appears brown because of lipid depletion o

Pathology – Endocrine Pathology by  Pathology  by  Dr.  Dr. Yabut   Adrenomedullary dysplasia – incomplete migration of the chromaffin cells to the center of the gland Clinical features Determined by specific enzyme deficiency o Abnormalities related to androgen excess vs. o aldosterone and glucocorticoid deficiency  CAH – any neonate with ambiguous genitalia o Severe enzyme deficiency can be life-threatening o with vomiting, dehydration, and salt-wasting Women may present with delayed menarche, o oligomenorrhea, or hirsutism o

-

Page 6 of 6