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PATOLOGI

Sistem

Endokrin-2
dr. Muhammad Inam Ilmiawan, M.Biomed
PSPD-FK UNTAN
2016
Parathyroid
Stimulus utama:
HIPOKALSEMIA
(9-10.5 mg/dl)

Antagonis Kalsitonin
Parathyroid hormone (PtH)-calcium feedback loop that controls calcium homeostasis.
four organsthe parathyroid glands, intestine, kidney, and bonetogether
determine the parameters of calcium homeostasis. +, positive effect; , negative
effect; 1,25 D, 1,25-dihydroxyvitamin D 3; eCf,extracellular fluid.
Gangguan paratiroid
HIPER-
Primer (umumnya adenoma; hiperplasia;
karsinoma)
Sekunder (Ca2+ rendah pada gagal ginjal)

HIPO- : Pembedahan, kongenital, familial, idiopatik

PSEUDO-HIPO-
Resistensi organ target
Hiperparatiroid
Hiperkalsemia =
Nyeri tulang, fraktur
Batu ginjal
Konstipasi, mual, ulkus peptik, pankreatitis, batu
empedu
Depresi, letargi, kejang
Kelemahan otot, hipotonia
Poliuri dan polidipsi
QT interval pendek dan T melebar
Kalsifikasi
Hipoparatiroid
Hipokalsemia =
Neuromuskular (kesemutan, spasme otot, facial
grimacing, carpopedal spasm atau tetani)
Perubahan status mental
Parkinsonism like effects
Lens calcification/katarak
Aritmia , QT interval melebar
Gangguan pertumbuhan gigi, karies
Korteks adrenal
Glomerulosa (Salt), mineralocorticoids
ALDOSTERONE

Fasciculata (Sugar), glucocorticoids


CORTISOL

Reticularis (Sex), gonadocorticoids


ANDROGENS, ESTROGENS
4 g.
SALT

SUGAR

SEX

STRESS
Hiperadrenalisme
(1) Hyperaldosteronism (G)

(2) Cushing syndrome, Hypercortisolism


(F) ~ paling sering

(3) Adrenogenital (virilizing) syndrome


(R)
Cushing Syndrome
CENTRAL OBESITY
MOON FACIES
WEAKNESS
HIRSUTISM
HYPERTENSION
DIABETES
OSTEOPOROSIS
STRIAE
STRIAE

MOON BUFFALO
FACIES HUMP
Etiology:
PITUITARY ACTH INCREASE, TUMOR ACTH INCREASE
HYPERPLASIA OF CORTEX, ADENOMA OF CORTEX
CARCINOMA OF CORTEX, EXOGENOUS STEROIDS (90%)
Hyperaldosteronism

Na+ RETENTION
K+ EXCRETION

HYPERTENSION
HYPOKALEMIA
PRIMER SEKUNDER
Neoplasma korteks Penurunan perfusi ginjal

Edema (jantung, hati,


Hiperplasia korteks ginjal)

Overactivity of the Kehamilan


aldosterone synthase
gene, CYP11B2
Adrenogenital Syndromes
VIRILIZATION/feminization
CORTICAL NEOPLASM
CORTICAL HYPERPLASIA
21-Hydroxylase Deficiency, with buildup of 17-
hydroxy progesterone
Hypoadrenalism
ADRENAL INSUFFICIENCY

1. Acute

2. Chronic (Addison Disease)

3. Secondary
Clinical
Progressive weakness, easy fatigability

Abdominal pain, anorexia, nausea, vomiting, weight loss,


diarrhea

Decreased aldosterone (K+ retention , Na+ loss, volume depletion,


hypotension)

Deficient cortisol, androgen, hypoglycemia

Coma, vascular collapse death


Acute
Sudden withdrawal of long-term corticosteroid therapy

Massive adrenal hemorrhage (Waterhouse-


Friderichsen syndrome [if it follows infection [Neisseria
meningitidis , Pseudomonas , pneumococci, H. Influenzae],
anticoagulant therapy, DIC, and shock

Stress in patients with underlying chronic adrenal insufficiency


(infections, trauma, surgical procedures )
Chronic (Addison Disease)
Auto-immune adrenalitis [ACAs]

INFECTIONS (tuberculosis, AIDS, sarcoidosis, fungi)

METASTASES (preferred site for early lung carcinoma


metastases)

GENETIC DISORDERS
Neoplasm
Adrenocortical adenomas
Adrenocortical carcinomas
Adrenocortical hyperplasia. The
adrenal cortex (bottom) is yellow,
thickened, and multinodular as a
result of hypertrophy and
hyperplasia of the lipid-rich zonae
fasciculata and reticularis. The top
shows a normal adrenal for
comparison
Adrenocortical adenoma. The adenoma is
distinguished from nodular hyperplasia by
its solitary, circumscribed nature. The
functional status of an adrenocortical
adenoma cannot be predicted from its
gross or microscopic appearance
Adrenal cortical adenoma. The neoplastic cells are vacuolated because of the
presence of intracytoplasmic lipid. There is mild nuclear pleomorphism.
Adrenal carcinoma. The bright yellow tumor dwarfs the kidney and compresses
the upper pole. It is largely hemorrhagic and necrotic
Adrenal carcinoma with marked anaplasia
Adrenal Medulla
Chromaffin cells neoplasms
( pheochromocytomas)
Neuronal neoplasms
( neuroblastoma, ganglion cell
tumor)
Pheochromocytoma
"rule of 10s":
10% several familial syndromes
10% extra-adrenal, paraganglioma
10% bilateral
10% biologically malignant

Hypertension
Tachycardia, palpitations, headache, sweating, tremor
Pheochromocytoma. The
tumor is enclosed within an
attenuated cortex and
demonstrates areas of
hemorrhage. The comma-
shaped residual adrenal is
seen below
Pheochromocytoma, demonstrating characteristic nests of cells ("Zellballen") with
abundant cytoplasm.
Neuroblastoma
MEN Multiple Endocrine Neoplasia Syndromes
Proliferative lesions (hyperplasias, adenomas, and carcinomas)

Multiple endocrine organs (in one organ, the tumors are often
multifocal)

Occur at a younger age

Preceded by an asymptomatic stage of endocrine


hyperplasia

More aggressive and recur


MEN-1 Wermer Syndrome "3 P"
(Tumor suppressor gene, inactivation)

Hyper- Parathyroid-ism

Pancreatic endocrine tumors

Pituitary adenoma, usually prolactinoma


MEN-2
(RET protooncogene activation)

Familial Medullary Thyroid Ca

MEN-2A: Pheochromocytomas, Medullary


Ca., Parathyroid hyperplasia

MEN-2B: NO hyperparathyroidism,
ganglioneuromas of mucosal sites (gastrointestinal
tract, lips, tongue)
ENDOCRINE
PANCREAS
Immunoperoxidase staining shows a dark reaction product for insulin in
cells (A), glucagon in cells (B), and somatostatin in cells (C). D, Electron
micrograph of a cell shows the characteristic membrane-bound granules,
each containing a dense, often rectangular core and distinct halo. E,
Portions of an cell (left) and a cell (right) also show granules, but with
closely apportioned membranes.
Diagnosis
Glucosa acak >200

Atau

Glukosa puasa >126

Atau

Glukosa Post-prandial > 200, 2 jam setelah OGTT (Oral


Glucose Tolerance Test)
Classification of Diabetes Mellitus
1 Type 1 diabetes (-cell destruction, usually leading to absolute insulin deficiency)
Immune-mediated
Idiopathic
2 Type 2 diabetes (combination of insulin resistance and -cell dysfunction)
3 Genetic defects of -cell function
Maturity-onset diabetes of the young (MODY), caused by mutations in:
Hepatocyte nuclear factor 4 (HNF4A), MODY1
Glucokinase (GCK), MODY2
Hepatocyte nuclear factor 1 (HNF1A), MODY3
Pancreatic and duodenal homeobox 1 (PDX1), MODY4
Hepatocyte nuclear factor 1 (HNF1B), MODY5
Neurogenic differentiation factor 1 (NEUROD1), MODY6
Neonatal diabetes (activating mutations in KCNJ11 and ABCC8, encoding Kir6.2 and
SUR1, respectively)
Maternally inherited diabetes and deafness (MIDD) due to mitochondrial DNA
mutations (m.3243AG)
Defects in proinsulin conversion
Insulin gene mutations
4 Genetic defects in insulin action
Type A insulin resistance
Lipoatrophic diabetes, including mutations in PPARG
5 Exocrine pancreatic defects
Chronic pancreatitis
Pancreatectomy/trauma
Neoplasia
Cystic fibrosis
Hemachromatosis
Fibrocalculous pancreatopathy
6 Endocrinopathies
Acromegaly
Cushing syndrome
Hyperthyroidism
Pheochromocytoma
Glucagonoma
7 Infections
Cytomegalovirus
Coxsackie B virus
Congenital rubella
8 Drugs
Glucocorticoids
Thyroid hormone
Interferon-
Protease inhibitors
-adrenergic agonists
Thiazides
Nicotinic acid
Phenytoin (Dilantin)
Vacor
9 Genetic syndromes associated with diabetes
Down syndrome
Kleinfelter syndrome
Turner syndrome
Prader-Willi syndrome
10 Gestational diabetes mellitus
Fungsi insulin
Kerja insulin
di sel target
Pathogenesis
Type-1 Type-2
T-Lymphocytes reacting Diet
against poorly
Life Style
defined beta cell antigens
Obesity
Inflammatory inflitrate, chronic, i.e.,
INSULIN RESISTANCE
INSULITIS Beta cells UN-able to
adapt to the long
term demands of
insulin resistance
A. Autoimmune insulitis in a rat (BB) model of autoimmune diabetes. This disorder also is
seen in type 1 human diabetes. B,Amyloidosis of a pancreatic islet in type 2 diabetes.
Amyloidosis typically is observed late in the natural history of this form of diabetes, with islet
inflammation noted at earlier observations.
COMPLICATIONS
MACRO-VASCULAR disease, i.e., ASCVD
MICRO-VASCULAR disease, kidneys, retina,
nerves
IMMUNE related problems, INFECTIONS, e.g.,
TB, pneumonia, pyelonephritis, candida, etc.
COMPLICATIONS
ADVANCED GLYCATION
collagen, laminin, polypeptides, GBM
(glomerular basement membrane), Hgb1c
ACTIVATION of PROTEIN KINASE C, VEGF,
endothelin-1, increased ECM, decreased
fibrinolysis, inflam. cytokines
INTRACELLULAR HYPERGLYCEMIA
COMPLICATIONS
MORPHOLOGY
(MACRO-vascular) Atherosclerosis
MICRO-vascular
*Retinopathy
*Nephropathy- glomerular, vascular, KW
*Neuropathy (most common cause of
neuropathy)

Infections
ATHEROSCLEROSIS
ATHEROSCLEROSIS
RETINOPATHY in Dm
Microaneurysms,
Areas of hemorrhage,

Cotton wool spots,


Hard exudates,
venous beading, neovascularization,
retinal detachment, vitreous
detachment, pre retinal hemorrhage
NEPHROPATHY
Kimmelstiel-
Wilson (KW)
Kidneys

IS

Nodular
glomerulosclerosis
NEPHROPATHY
NEPHROSCLEROSIS
NEPHROPATHY
GBM thickening
NEPHROPATHY
Diffuse
Mesangial
Sclerosis
INFECTIONS in Dm
SKIN
TUBERCULOSIS
PNEUMONIA
PYELONEPHRITIS
CANDIDA
NEOPLASMS of the Endocrine
Pancreas
Islet cell tumors
Beta cells INSULINOMAS (NOT rare)
Alpha cells GLUCAGONOMAS (rare)
Delta cells SOMATOSTATINOMAS (rare)

GASTRINOMAS, producing ZOLLINGER-ELLISON


SYNDROME, consisting of increased acid and ulcers
Terima Kasih