Endo-Diabetes Flashcards
Differentiate Type 1a and Type 1b diabetes
Type 1a: autoimmune destruction of beta cells
Type 1b: Non-autoimmune destruction of beta cells
Most reliable and convenient tests for identifying DM in asymptomatic individuals
HbA1c or FPG
Key regulator in insulin secretion
Glucose
Glucose level that stimulates insulin synthesis
> 70mg/dL
Rate limiting step that controls glucose-regulated insulin secretion
Glucokinase (liver)
Hexokinase(everywhere else)
Most potent incretin
Glucagon-like peptide 1(GLP-1)
Major portion of postprandial glucose utilized by
Skeletal muscle
Features of diabetes do not become evident until how much beta cells are destroyed?
70-80%
Major susceptibility gene in T1DM
HLA region on chromosome 6
Central to the development of T2DM
Insulin resistance and abnormal insulin secretion
Predominantly accounts for increased FPG levels
Increased hepatic glucose output
Results in postprandial hyperglycemia
Decreased peripheral glucose usage
Honeymoon phase
Time when glycemic control is achieved with modest doses of insulin
Ketone bodies
Acetoacetate(excreted in the urine)
B-hydroxybutyrate
Acetone(not used as source of energy)
Preferred method for detecting ketones that more accurately reflect the true ketone level
Serum or plasma assays for B hydroxybutyrate
Preferentially detected by a commonly used ketosis detection reagent (nitroprusside)
Acetoacetate
Consistent finding in DKA and distinguishes it from simple hyperglycemia
Ketonemia
Etiology of hyperglycemic hyperosmotic state(HHS)
Relative insulin deficiency & inadequate fluid intake
Prominent features of both HHS and DKA
Volume depletion and hyperglycemia
Confirm a patient’s need for insulin
Low c-peptide level
Symptoms of diabetes usually resolve when glucose is
<200mg/dl
Standard of care in diabetes management
Self monitoring of blood glucose
Standard method for long term glycemic control
Measurement of Hba1c
Most serious complication of therapy of DM
Hypoglycemia
Microvascular manifestations of DM
Retinopathy, neuropathy, nephropathy
Macrovascular manifestations of DM
CAD, PAD, CVD
Leading cause of blindness between ages 20 and 74
DM retinopthy
Non-proliferative DM retinopathy
Retinal vascular microaneuryms, blot hemorrhages, and cotton wool spots
Hallmark of proliferative DM retinopathy
Neovascularization in response to retinal hypoxia
Most effective therapy for DM retinopathy
Prevention
Treatment of proliferative retinopathy
Panretinal laser photocoagulation
Treatment of macular edema
Focal laser photocoagulation
Optimal therapy for DM nephropathy
Prevention by control of glycemia
Preferred therapy for DM nephropathy
Renal transplantation from a living related donor
Most common site of foot ulcers
Great toe or metatarsophalangeal(MTP) areas
Optimal therapy for foot ulcers and amputation
Prevention
Most common site of ulceration
Plantar surface of foot
Most common form of diabetic neuropathy
Distal symmetric polyneuropathy(commonly sensory)
Most commonly involved nerve in mononeuropathy
CN III(heralded by diplopia)
Most prominent GI symptoms in DM
Delayed gastric emptying and altered small- and large-bowel motility
Most common pattern of DM dyslipidemia
Hypertryglyceridemia and reduced HDL
Type 1 DM
usually <30 yo autoimmune cause DKA is the most common complication HLA-DR3, -DR4 Depleted beta cells Islet leukocytic infiltrate
Type 2 DM
Strong polygenic genetic predisposition
Islet amyloid deposit
Defense against hypoglycemia
1st line: decreased insulin
2nd line: increased glucagon
3rd line: increased epinephrine
Compromises physiologic defense against hypoglycemia
Defective glucose counterregulation
Compromises behavioral defense against hypoglycemia
Hypoglycemia unawareness
Hypoglycemia in non-beta cell tumors is due to
Overproduction of insulin like growth factor II
Prototypical cause of endogenous hyperinsulinism
Insulinoma
Ingestion of an insulin secretagogue
Hypoglycemia with increased C-peptide levels
Exogenous insulin
Causes hypoglycemia with low C-peptide levels
Hormones derived from proopiomelanocortin(POMC)
MSH, ACTH, B-lipoprotein, B-endorphin
Main site of ADH/Vasopressin synthesis
Supraoptic nuclei of the anterior hypothalamus
Main site of oxytocin synthesis
Paraventricular nuclei of the anterior hypothalamus
Site of oxytocin and ADH/vasopressin storage and secretion
Posterior pituitary
3 parts of the adrenal cortex
From outer to inner: (GFR) Zona glomerulosa(aldosterone secretion) Zona fasciculata(cortisol secretion) Zona reticularis(weak androgen secretion)
2 products of the adrenal medulla
Epinephrine (80%)
Norepinephrine (20%)
Decreases Ca2+ & phosphate excretion but increases urinary Ca2+; increases intestinal Ca2+ absorption
Vitamin D
Stimulated by LH, releases the “libido” hormone testosterone
Leydig cells
Mnemonic: LLL: LH, Leydig, Libido Hormone
Stimulated by FSH, nurse cell for sperm
Sertoli cells
Mnemonic: SSS: FSH, Sertoli cells, Sperm
Increases blood glucose, has direct and indirect effects (via IGF-1)
GH
GHRH -> GH -> IGF-1
CRH -> ACTH ->
Cortisol
ZF (largest area in the AC)
Weak androgens
DHEA, androstenedione (ZR, AC): significantly only in females
Source: beta cells, islets of Langerhans, endocrine pancreas
Insulin
Insulin 2nd messenger
Tyrosine kinase
Insulin precursor
Proinsulin(splits into Insulin and C peptide)
Increases well-fed state pathways: glycolysis, lipid and protein synthesis
Increases K influx in other cells
Insulin
Only insulin mediated transporter
GLUT-4
Insulin counter regulatory hormone
Glucagon(alpha cells)
Most common functioning pituitary adenoma
Prolactinoma
Second most common pituitary adenoma
Somatotroph adenoma
Postpartum necrosis of anterior pituitary gland presenting as sudden cessation of lactation
Sheehan syndrome
Headache, diplopia and hypopituitarism caused by hemorrhage into the pituitary adenoma
Pituitary apoplexy
Most reliable criterion to diagnose pituitary adenoma
Metastases (CSF/Systemic)
Most common type of thyroid malignancy; good prognosis
Orphan Annie nuclei
Papillary Thyroid CA
Thyroid malignancy with capsular and vascular invasion
Follicular Thyroid CA
Thyroid malignancy derived from C cells, MEN-associated, amyloid deposition
Medullary Thyroid CA
Thyroid malignancy with giant cells and highly pleomorphic cells
poor prognosis
Anaplastic Thyroid CA
Most common cause of hypothyroidism in iodine sufficient areas; with germinal centers, fibrosis, and Hurthle cell change
Hashimoto’s Thyroiditis
Most common cause of hypothyroidism worldwide
Iodine deficiency
Condition where normal thyroid tissues are replaced by fibrous tissue
Reidel thyroiditis
Hyperthyroidism, ophthalmopathy, dermopathy
Grave’s disease
Histopathologic finding of Grave’s disease
Diffuse thyroid hypertrophy and hyperplasia
Most common primary thyroid cancer in adults and children
Papillary thyroid cancer
Associated disease with PSaMMoma Bodies
Papillary Thyroid Cancer;
Serous Cystadenoma of the ovaries;
Mesothelioma;
Meningioma (in general, cancers with papillary architecture
Most common cause of primary hyperparathyroidism
Parathyroid adenoma
Elevated PTH, normal calcium levels
Pseudohypoparathyroidism/Tertiary hyperparathyroidism
Elevated PTH occurring in CKD patients
Secondary hyperparathyroidism
Difficult to treat hypertension associated with hypokalemia
Hyperaldosteronism
Most common cause of primary hyperaldosteronism
Bilateral idiopathic hyperaldosteronism
Adrenals are converted to sacs of clotted blood, which virtually obscures all underlying detail
Waterhouse-Friderichsen Syndrome(causes acute adrenal insufficiency)
Common cause of Waterhouse Friderichsen Syndrome
Neisseria meningitidis
Other causes:
GABHS, GBS, Pseudomonas Staphylococcus
Neoplasms composed of chromaffin cells, which synthesize and release catecholamines and in some instances peptide hormones
Pheochromocytoma
~75% parenchymal loss of the pituitary
Hypopituitarism
Tropic hormone failure associated with pituitary compression or destruction usually occurs in this sequelae
GH > FSH > LH > ACTH > Prolactin
Most common presentation of tropic hormone failure in childhood
Growth retardation
Earliest symptom of tropic hormone failure in the adult
Hypogonadism
Most common cause of hypopituitarism in children associated with WNT signaling pathway
Craniopharyngioma
Most common cause of hyperpituitarism
Pituitary adenoma
Cut-off size for microadenoma
<10mm diameter
Most common mechanism where suprasellar extension can lead to bitemporal hemianopsia
compression of the optic chiasm
Early sign of optic tract pressure
loss of red perception
Surgical approach for most pituitary tumors
Transphenoidal surgery
Treatment of choice for prolactinomas
Dopamine agonists(cabergoline and bromocriptine)
Most common pituitary hormone hypersecretion syndrome in both sexes
Hyperprolactinemia
Hallmarks of hyperprolactinemia
Amenorrhea, galactorrhea, infertility
Most abundant anterior pituitary hormone and major determinant of hepatic IGF-I synthesis
GH
Most validated test to distinguish pituitary-sufficient patients from AGHD
Liver
Confirmed by demonstrating failure of GH suppression to <0.4 g/L within 1-2h of a 75g oral glucose
Acromegaly
Most common cause of GHRH-mediated acromegaly
Chest or abdominal carcinoid tumor
Most significant cause of mortality with acromegaly
Cardiovascular
Provides a useful screening measure when clinical features raise the possibility of acromegaly
IGF-I
Initial treatment for most patients with acromegaly
Surgical resection of GH-secreting adenomas
Drug that acts by competitve inhibition of GH
Pegvisomant
Features that make pathologic causes of hypercortisolism more likely
Central redistribution of fat
Thin skin with striae and bruising
Proximal muscle weakness
Primary cause of death in Cushing’s syndrome
Cardiovascular disease
Size of most ACTH-secreting pituitary tumors
<5mm in diameter(half undetectable by MRI)
Origin of most nonfunctioning adenomas
Gonadotrope cells
Most important, if not the only, physiologic action of AVP
Reabsorb water and promote concentration of water
Syndrome characterized by abnormally large volumes of dilute urine (24hr urine >50mL/kg body weight and osmolarity <300mosmol/L)
Diabetes insipidus
Excessive urination from insensitivity of renal tubules to ADH
Nephrogenic DI
Excessive urination secondary to lack of ADH
Central DI
Differentiates central vs peripheral DI
Fluid deprivation test
Most common cause of preventable mental retardation
Iodine deficiency
Hypothyroidism in infancy or early childhood
Cretinism
Method of choice in determining thyroid size accurately
Ultrasound
First test in the approach of thyroid testing
TSH levels
There is no convincing evidence for a role of infection in autoimmune hypothyroidism, except
Congenital rubella syndrome
Thyroid cell destruction in autoimmune thyroiditis is primarily mediated by
CD8+ cytotoxic T cells
Major role in pathogenesis in myxedema coma, leading to hypoxia and hypercapnia
Hypoventilation
Indication for external warming in hypothermia of myxedema
Temperature <30C
Major etiologies of hyperthyroidism
Graves disease
Toxic multinodular goiter
Toxic adenoma
Apathetic thyrotoxicosis in elderly present as
Fatigue and weight loss
Most common cardiovascular manifestation of hyperthyroidism
Sinus tachycardia(associated with palpitations)
Earliest manifestations of Grave’s ophthalmopathy
Sensation of grittiness, eye discomfort, and excess tearing
Most serious manifestation of Grave’s ophthalmopathy
Compression of optic nerve at apex of the orbit
Most frequent site of of thyroid dermopathy
Anterior or Lateral aspects of lower leg( pretibial myedema)
Time of major risk of relapse in Graves disease in pregnancy
Postpartum period
Duration of carbimazole or methimazole - free period prior to radioiodine therapy
At least 2 days before
Duration of PTU free period prior to radioiodine therapy
several weeks before
Absolute contraindications to radioiodine
Pregnancy and breast feeding
Most common cause of acute thyroiditis in children and young adults
Presence of a pyriform sinus(predominantly left-sided)
Most common clinically apparent cause of chronic thyroiditis
Hashimoto thyroiditis
Major cause of sick euthyroid syndrome
release of cytokines
Most common pattern of sick euthyroid syndrome
Decrease in total and unbound T3 levels(low T3 syndrome) with normal levels of T4 and TSH
Venous distention over the neck and difficulty breathing especially when the arms are raised(in large retrosternal goiters)
Pemberton sign
Most frequent cause of acquired hypoparathyroidism in the past
Surgery for hyperthyroidism
Hypoparathyroidism now usually occurs after
Surfery for hyperparathyroidism
Sonographic characteristics of thyroid nodules suggestive of malignancy
Microcalcifications, hypoechogenicity, increased vascularity
Most common malignancy of the endocrine system
Thyroid CA
Most common type of thyroid cancer
Papillary thyroid carcinoma
More common in iodine-deficient regions
Follicular thyroid carcinoma
Surgical treatment in almost all patients with well-differentiated cancer
Near-Total thyroidectomy
Most common type of thyroid lymphoma
Diffuse large-cell lymphoma
Provides a marker of residual or recurrent disease in medullary thyroid carcinoma
Elevated serum calcitonin
Primary management of medullary thyroid carcinoma
Surgery
Size of most palpable thyroid nodules
> 1cm