27. skin Flashcards
1
Q
ant. pituitary pathologies include
A
pit. adenoma
hypopituitarism
2
Q
Pituitary Adenoma type size and causes
A
6-10% of all symptomatic intracraneal neoplasms
Most common cause of hyperpitutarism
Functional (hyperpituitarism) or nonfunctional
Childhood to old age (peak 35-60yrs)
Microadenoma <1cm and macroadenoma >1cm
Circumscribed to invasive (30%)
3
Q
Clinical Manifestations of Pituitary adenoma
A
Hyperpituitarism or hypopituitarism
Mass effects (tumors)
Sellar expansion, bony erosion, disruption of diaphragma sella), visual field abnormalities (optic chiasm compression), raised intracranial pressure (headache, nausea, vomiting)
Pitutary apoplexy
4
Q
Pituitary apoplexy
A
Ancient Greek ἀποπληξία (apoplexia) ‘a striking away’) is rupture of an internal organ
“sudden death” of the pituitary gland, usually caused by an acute ischemic infarction or hemorrhage.
“ pituitary stroke”
A pre-existing pituitary adenoma
Neurosurgical emergency
5
Q
Prolactinoma
A
Composed of lactotropic cells
~ 30% of all pituitary tumors
Women may present with oligomenorrhea, amenorrhea, galactorrhea, loss of libido or infertility
Men often have less symptoms than women (sexual dysfunction, visual problems, or headache)
6
Q
Somatotropic adenomas
causes what 2
metabolic causes and why
A
Growth hormone
Gigantism (BEFORE epiphyseal closure) or Acromegaly (AFTER epiphyseal closure)
75% of clinically apparent are macroadenoma
Causes metabolic disturbances, such as hyperglycemia (secondary diabetes mellitus) and hypercalcemia
7
Q
why GH/somatotropic adenoma causes secondary DM
A
GH induce liver gluconeogenesis
8
Q
somatotropic adenoma diagnosed by
A
Diagnosed by ↑GH and IGF-1, lack of GH suppression by oral glucose
9
Q
acromegaly symptoms
A
teeth gapping
increased hands size
mandibulat enlargement
10
Q
Pituitary dwarfism
cause
and differential
A
Severe deficiency of GH in children before growth is completed
Isolated GH deficiency is commonly the result of an inherited AR disorder
Inherited pituitary dwarfism appear after one year of age; retardation in growth of bones and episodes of hypoglycaemia
cretinism
plus mental retardation
11
Q
HYPOPITUITARISM
A
A, Insufficient production ol hormones by the anterior pituitary gland; symptoms arise when > 75% of the pituitary parenchyma is lost,
B, Causes include
Pituitary adenomas (adults) or craniopharyngioma (children)—due to mass
effect or pituitary apoplexy (bleeding into an adenoma)
12
Q
Sheehan syndrome—
define
pathogenesis
A
pregnancy-related infarction of the pituitary gland
i. Gland doubles in size during pregnancy, but blood supply does not increase
significantly; blood loss during parturition precipitates infarction.
13
Q
Simmond’s disease
A
without preceding pregnancy and/or in males
infarction of pit.
14
Q
Empty sella syndrome—
define
types
A
congenital defect of the sella
Cause panhypopituitarism
Primary is due to incomplete diaphragma sella (congenital defect of the sella)herniation of subarachnoid space into the sella turcica
Secondary is a result of Sheehan’s syndrome, infarction and scarring in an adenoma, irradiation damage, or surgical removal of the gland
Pituitary gland is “absent” (empy sella) on imaging
15
Q
Craniopharyngioma
define
age
causes
benign/mal
gene mutation
fluid within looks like
A
Derived from remnants of Rathke pouch (odontogenic epithelium)
Commonly affects children and young adults
Headache, hypopituitarism, and visual field disturbances
Benign but tends to recur after resection
β-catenin (CTNNB1) gene mutations
“motor oil”-like
fluid within tumor
16
Q
Posterior pituitary pathology
A
Syndrome of inappropriate antidiuretic hormone(SIADH)
Diabetes insipidus (DI)
17
Q
Syndrome of inappropriate antidiuretic hormone(SIADH)
define
cause
complication
A
Syndrome of inappropriate antidiuretic hormone(SIADH)
Excessive production of ADH
Retention of water results in hyponatremia and low serum osmolality neuronal swelling and cerebral edema (Mental status changes and seizures)
Cause; any lung disease(like infection), any CNS diseases(like trauma), small cell lung carcinoma and drug (oxytocin ,TCAD)
18
Q
Diabetes insipidus (DI)
define type
A
Neurogenic or central DI
Insufficient secretion of ADH
Causes; Tumor, Multifocal LCH, tuberculosis meningitis, trauma, surgery
Nephrogenic DI
Inadequate response of the renal tubules to ADH
Cause; drug like Li and demeclocycline, genetic disorder (X linked recessive), Chronic renal disease, sickle cell anemia
19
Q
to check for DI
A
Water deprivation test fails to increase urine osmolality in central DI.
20
Q
congenital thyroid pathologies
A
Thyroid dysgenesis
Dyshormonogenetic goiter
Thyroglossal duct cysts and sinus
21
Q
Thyroid dysgenesis
define and percentage
A
Anomalies in the anatomic development of the thyroid, including thyroid gland proper abnormalities (agenesis, hemiagenesis and hypoplasia) and ectopic thyroid tissue.
~ 80% of cases of 1ᵒ congenital hypothyroidism
22
Q
Dyshormonogenetic goiter
sex
cause by or due to
A
Inborn errors of thyroid hormone synthesis most frequent due to TPO and TG genes mutation
~ 20% of primary congenital hypothyroidism
F > M (2:1)
23
Q
Thyroglossal duct cysts and sinus
A
Cystic dilation of thyroglossal duct remnant
24
Q
thyroditis types
A
hashimoto
reidels fibrosing thyroditis
subacute granulomatous/ dequervain thyroditis
25
Hashimoto thyroiditis
define
age
sex
gene mutations
assoc. with
pathogenesis
Chronic autoimmune disease characterized by immune destruction of the thyroid gland and hypothyroidism.
1st described by the Japanese physician Hakaru Hashimoto in 1912.
Peak age 45 - 65 years
F:M= 10 - 20 : 1
HLA-DR3, HLA-DR5
Associated with other autoimmune disease such as SLE, Sjögren's syndrome, Type I DM and rheumatoid arthritis, Addison disease or pernicious anemia
Antithyroglobulin (TG)
Antithyroid peroxidase(TPO)
Antimicrosomal antibodies (AMA)
26
what is seen in histology of hashimoto that differentiates it from subacute lymphocytic
hurthle cells and fibrosis
esosinophilic metaplasia of cells of the follicle
27
Most common cause of hypothyroidism in iodine-sufficient regions
hashimoto
28
......................... presents as an enlarged thyroid gland in late stage
marginal zone lymphoma
29
Subacute Lymphocytic (Painless) Thyroiditis
define
seen in
Autoimmune disease with pathologic features that resemble Hashimoto thyroiditis
Unlike Hashimoto thyroiditis, fibrosis and Hürthle cell metaplasia are not prominent
~ 5% of women in postpartum period (postpartum thyroiditis)
30
Subacute granulomatous thyroiditis (de Quervain)
define
age
sex
granulomatous thyroditis that follow viral infection
Self-limited disease often following a flu-like illness (eg, viral infection)
Peak ages of 40 – 50 years
F:M =4 : 1
The most common cause of thyroid pain (de Quervain is associated with pain)
31
................... May be thyrotoxic early in course, followed by hypothyroidism (permanent in ~15% of cases).
de quervain
32
Riedel thyroiditis
define
associated with
thyroid presentation
differential
and how to cancel that ddx
chronic inflammation with extensive fibrosis of the thyroid gland
IgG4-related rare disease Shows a
slight predilection for females with most patients being middle-aged.
Hard ('hard as wood’, ‘stony hard’, or ‘iron hard’), and fixed thyroid mass clinically simulates a thyroid carcinoma. but patients are younger (40s), and malignant cells are absent.
Associated with fibrosis in other sites in the body, such as the retroperitoneum
33
hypothyroidism causes 2
primary
genetic
iodine deficiency
drugs
and secondary central
34
Iodine deficiency
Occurs in highland area far from sea water.
Deficiency of iodine in food and water is worldwide still the most common cause of hypothyroidism.
200 million people worldwide continue to be at risk for severe iodine deficiency.
35
Iatrogenic
Surgical removal of thyroid
Drugs that cause unwanted hypothyroidism, such as sulphonylureas, resorcinol, lithium and amiodarone
36
Surprisingly enough, iodides in large quantities inhibit the organic binding of iodine (i.e hypothyroidism) and produce an iodide goiter called
Wolff–Chaikoff effect
37
Clinical presentation of hypothyroidsm
in children and adults
Neonate and infant develop critinism
Older child and adult develop myxedema
38
Myxedema
clinical features are based on decreased basal metabolic rate and sympathetic nervous system activity
loss of lateral eyebrow hair
puffy skin due to accumulation of mucopolysacharides
carpal tunnel syndrome
39
Myxedema coma
Severe hypothyroidism in long standing untreated disease precipitated mainly by infection and cold exposure
Treatment: IV fluid, corticosteroid, T4 and T3 and hot blancket.
40
lab findings of myxedema coma
hypoglycemia
hyponatremia
hypoxemia
hypercapnia
41
Cretinism
Characterized by mental retardation (cretinism), short stature (thyroid dwarfism), coarse facial features, enlarged tongue, and umbilical hernia.
Causes include maternal hypothyroidism during early pregnancy, thyroid dysgenesis, dyshormonogenetic goiter, and iodine deficiency.
42
Thyroid storm
Extreme form of hyperthyroidism
Precipitated by infection, trauma, surgery and stress
Delirium, coma, high grade fever, hypotension, CHF
30% mortality
42
thyroid opthalmology
retraction of upper eye lid
lid lag of upper eyelid
inability to converge
42
Hyperthyroidism (thyrotoxicosis)
define
causes what
and how
Hypermetabolic state that results from an excess of free thyroid hormones (T3 and T4) in blood.
Increases basal metabolic rate (due to increased synthesis of Na+ - K+ ATPase)
Increases sympathetic nervous system activity (due to increased expression of receptors)
43
causes of hyperthyroidism
Graves disease
multinodular goitor
44
Graves disease
define
age
causes what and how
The most common cause of endogenous hyperthyroidism
Autoimmune disorder
90% of patients have Thyroid stimulating immunoglobulin (TSI)
Peak age 20 to 40 years
M:F= 1:10.
Increased risk for other autoimmune diseases, such as SLE, pernicious anemia, type 1 diabetes, and Addison disease.
45
graves triad
dermopathy
opthalmopathy
diffuse goiter
lady seeing grave
46
why exopthalmosis and periorbital myxedema
Fibroblasts behind the orbit and overlying the shin express the TSH receptor. TSI and CD4+ cytokines results in glycosaminoglycan (chondroitin sulfate and hyaluronic acid) accumulation, inflammation, fibrosis, and edema leading to exophthalmos and pretibial myxedema.
47
histologic finding in graves diesease
scalloping of colloid
colloid normally cicle but now irregular
48
The Jod-Basedow effect
Hyperthyroidism following administration of iodine or iodide, either as a dietary supplement or as iodinated contrast for medical imaging.
Does not occur in persons with normal thyroid glands, as thyroid hormone synthesis and release in normal persons is controlled by pituitary TSH secretion
Typically presenting in a patient with endemic goiter, who relocate to an iodine-abundant geographical area.
because receptor upregulation
49
Mass lesion of the thyroid(goiter or goitre)
A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland.
50
Non neoplastic thyroid enlargement (goiter)
2
Diffuse nontoxic goiter (colloid) goiter
Multinodular nontoxic goiter
Two types: Endemic or sporadic.
51
diffuse non toxic goiter
characterizes the early stages of the disease.
Diffuse goiter is frequent in adolescence and during pregnancy
52
multinodular goiter
reflects more chronic disease.
multinodular type usually occurs in persons older than 50 years.
53
Endemic goiter
> 10% of the population is affected
Always related to iodine deficiency
Other causes include regular consumption of goitrogens, eg. Cassava contains a thiocyanate that inhibits iodide transport within the thyroid.
54
Sporadic goiter/ physiologic goiter
Less common than endemic goiter
Striking female preponderance and a peak incidence at puberty or in young adult life usually due to increased physiologic demand for thyroxine (also called physiologic goiter)
In most of the cases the cause is not apparent
Dyshormonogenetic goiter and goitrogens are rare causes
55
10% of patients over a 10-year period develop hyperthyroidism (toxic MNG), also known as
Plummer's disease
56
Thyroid neoplasm
characteristics
Usually presents as a distinct, solitary nodule.
More likely to be benign than malignant 10:1.
Most appear as a cold nodule on RAI uptake scan.
Nodules in younger patients and nodules in males are more likely to be neoplastic.
57
list neoplasms
benign and malignant
Follicular adenoma
Papillary Thyroid Carcinoma
Follicular Carcinoma
Medullary carcinoma
Anaplastic (undifferentiated) Carcinoma
58
Follicular adenoma
define
hormone
Benign proliferation of follicles surrounded by a fibrous capsule.
Rarely secrete thyroid hormone (called toxic adenomas)
In general it not precursor to carcinomas; nevertheless, shared genetic alterations(RAS mutations) raise the possibility that at least a subset of follicular carcinomas arises in preexisting adenomas.
59
Papillary Thyroid Carcinoma
Most common thyroid malignancy
Peak incidence between 20 and 40 years
In most cases cervical lymph node metastasis is the first manifestation
Predisposing factors: Previous exposure to ionizing radiation, Gardner syndrome and Cowden disease.
Ten-year survival 98%
60
papillary thyroid carcinoma 2 histologic findings
psamoma bodies
orphan annie eye nuclei
clear nuclei
61
Follicular Carcinoma
define
age
sex
unique feature
Second most common thyroid carcinoma
Peak age 40 and 50 years; females > males
Incidence higher in areas with iodine deficiency; indicating that follicular carcinoma might arise from nodular goitre
Regional lymph nodes rarely involved; blood vessel invasion common with spread to bones, lungs and liver.
Widely invasive 10-year survival < 50%.
Minimally invasive 10-year survival greater than 90%.
62
FNAC only examines cells and not the capsule; hence, a distinction between follicular adenoma and follicular carcinoma cannot be made by FNAC. The term follicular neoplasm used instead.
63
Anaplastic (undifferentiated) Carcinoma
define
age
prognosis
Rapidly enlarging bulky neck mass, which spread to contiguous structures
Mean age of 65 years
50% with a previous history of MNG
20% with a previous history of a differentiated carcinoma
The most aggressive cancers known; in most cases death occurs in less than 1 year.
64
Medullary carcinoma
define where
presents with
Parafollicular or ‘C cells’
Sporadic lesions are common in adults (40–50 years)
May present as a paraneoplastic syndrome due to secretion of calcitonin (hypocalcaemia), VIP(diarrhea), ACTH(Cushing syndrome), somatostatin, and serotonin.
Prognosis of familial cancers (MEN2 syndrome) is worse than sporadic
Detection of the RET mutation warrants prophylactic thyroidectomy
65
medullary carcinoma presents as ........ and ........... in sporadic and ............ and .................... in familial
solitary and unilateral
multifocal and bilateral
66
Parathyroid pathology
mild hypomagnesimia and severe consequences
mild no pth synthesis
severe no release
67
Hyperparathyroidism
define
types
Increased levels of PTH
> 95% cases are sporadic and < 5% cases are familial (most often MEN1)
68
Primary hyperparathyroidism
Parathyroid lesions with autonomous overproduction of PTH
Most are older than 50 year
F:M = 4:1
69
Pathogenesis
of pth
sporadic and familial
Sporadic parathyroid adenomas are associated with two molecular defects: Parathyroid adenomatosis gene 1 (PRAD1)( new name CCND1) and MEN 1 mutations (30-35%)
Familial in MEN-1 and MEN-2A syndromes, and FHH.
Familial hypocalciuric hypercalcemia (FHH): AD condition a result of mutations in the calcium-sensing receptor (CASR) gene on ch 3q that lead to decreased receptor activity
70
Parathyroid carcinoma
Diagnosis of carcinoma is based on invasion of adjacent tissue or metastases.
71
Parathyroid hyperplasia
types
Primary is idiopathic. Occurs sporadically or as a component of MEN syndrome
Secondary is due to a compensatory mechanism triggered by hypocalcemia and hyperphosphatemia like in ESKD
Usually all four glands are involved
72
Clinical presentation and morphological change
of hyperpth
Due to effect of high PTH level and the resulting hypercalcemia (>10.5 mg/dL)
Most often results asymptomatic hypercalcemia
Osteitis fibrosa cystica (von Recklinghausen disease of bone)
resorption of bone leading to fibrosis
Nephrocalcinosis Nephrolithiasis
73
Laboratory findings 1⁰ Hyperparathyroidism
pth
ca
camp
alp
phosphate
Include high (serum PTH, serum calcium, urinary cAMP, and serum ALP), low Serum phosphate.
74
osteoblast hace pth receptor and produce ALP
75
Secondary hyperparathyroidism
Exces production of PTH due to a disease process extrinsic to the parathyroid gland
Caused by any condition which is associated with chronic hypocalcaemia: Renal failure, Inadequate dietary intake of calcium, Vitamin D deficiency (lack of sun light, liver, kidney and malabsorbsion)
76
lab findings in secondary hyper pth
renal and non renal
High serum (PTH, ALP, and phosphate) and low calcium in renal failure
High serum (PTH and ALP) and low serum (calcium and phosphate) in non renal causes.
77
Tertiary hyperparathyroidism
Autonomous parathyroid hyperplasia after long-standing secondary hyperplasia of renal failure
May not regress after renal transplantation
Parathyroidectomy is required
2/3 of patients with long-standing uremia
78
Hypoparathyroidism
Decrease level of PTH
Less common than hyperparathyroidism
Lab low PTH and Ca⁺⁺, and high Phosphate
79
Causes of hypoparathyroidism
Absence of PTH: DiGeorge syndrome, Hereditary hypoparathyroidism (very rare, autoimmune polyendocrine syndrome), Surgical removal of the parathyroid glands (common cause) and ideopathic/Autoimmune (60% have anti CASR)
Defective release of PTH: severe hypomagnesemia (Mg++<0.4mmol/L)
End organ resistance for PTH: Pseudohypoparathyroidism
80
Pseudohypoparathyroidism
End-organ resistance to PTH
Autosomal dominant form is associated with short stature and short 4th and 5th digits GNAS1-inactivating mutation.
Labs reveal hypocalcemia with increase PTH levels
81
Clinical features
of hypopth
Due to hypocalcaemia (Serum total calcium < 9.0 mg/dL and ionized < 5.5 mg/dL)
Tetany, circumoral numbness, paraesthesias of the distal extremities, carpopedal spasm, laryngospasm and generalized seizures
Mental status changes including emotional instability, anxiety, depression, confusion, hallucinations and frank psychosis
Prolonged QT interval on ECG
Dental abnormalities (dental hypoplasia, failure of eruption, defective enamel and root formation and abraded carious teeth)
82
Signs of hypocalcemia
clinical exam 2
Chvostek sign—tapping of facial nerve (tap the Cheek) contraction of facial muscles.
Trousseau sign—occlusion of brachial artery with BP cuff (cuff the Triceps) carpal spasm.
83
Hypercortisolism (Cushing Syndrome)
types
Increased glucocorticoid levels
Exogenous (iatrogenic) -90%
Endogenous
ACTH dependent: Pituitary (2⁰), hypothalamus (3⁰),
ectopic ACTH, or ectopic CRH
ACTH independent: Adrenal (1⁰), ectopic cortisol
84
cushings disease
Osteoporosis and skin striate (catabolic effect on proteins causing loss of collagen and resorption of bone)
Weakness and fatigability due to selective atrophy of fast twitch (Type II) myofibrils and decreased muscle mass
Cushing syndrome can cause facial roundness, weight gain around the middle body and upper back, thinning of the arms and legs, easy bruising, and stretch marks. Cushing syndrome happens when the body has too much of the hormone cortisol for a long time.
85
cortisol level suppression by dexamethasone
86
Hyperaldosteronism
Excessive aldosterone secretion
Causes sodium retention (hypertension) and potassium excretion (hypokalaemia)
87
types of hyper aldosteronism
plus aka
1⁰(Conn syndrome)-Autonomous overproduction of aldosterone by adrenal
2⁰(renin dependent hyperaldosteronism)- Aldosterone release occurs secondary to activation of RAAS
88
Symptoms of hypokalemia
mild moderate severe
Mild ( 3 - 3.5 mmol/l) – Asymptomatic
Moderate( 2.5 – 3 mmol/l) – Muscle weakness, cramp (paralytic ileus)
Severe( < 2.5 mmol/l) – Cardiac arrhythmia
89
Hypersecretion of sex steroids
= Adrenogenital syndrome (adrenal virilism) is a rare disease
Due to excess sex steroids
Can affect neonates or adults
In neonates (i.e., present at birth) related to congenital adrenal hyperplasia.
In adult women usually related to androgen-producing tumors, which cause virilization with hirsutism, deepening of the voice, and loss of menstruation.
90
Congenital adrenal hyperplasia
pathogenesis
Inborn errors of steroid metabolism
All congenital adrenal enzyme deficiencies are AR
21-hydroxylase deficiency is the most common cause
Followed by 11β-hydroxylase and 17α-hydroxylase
Results in low cortisol high ACTH hyperplasia of both adrenal glands
Clinical features depends on the type of enzyme deficiency
91
17α-hydroxylase deficiency
21-hydroxylase deficiency
11β-hydroxylase deficiency
If deficient enzyme starts with 1, it causes hypertension; if deficient enzyme ends with 1, it causes virilization in females
92
Hypofuctioning of adrenal (Adrenal insufficiency)
Lack of adrenal hormones
1⁰ (adrenal diseases) vs 2⁰ (pituitary and hypothalamus disease)
Acute vs Chronic
93
Acute 1⁰ insufficiency (Waterhouse - Friderichsen Syndrome)
Acute hemorrhagic necrosis of the adrenals
Medical emergency (adrenal crises)
Classically caused by Neisseria meningitidis
Hypovolaemic shock and hypoglycaemia
94
Chronic 1⁰ insufficiency (Addison disease)
Due to progressive destruction of the adrenal glands
Common causes include autoimmune destruction (most common cause in the West), TB (most common cause in the developing world), and metastatic carcinoma
95
Lung cancer can cause both of them by ectopic production of ACTH ( Cushing syndrome) and by metastasize to adrenal (Addison disease) you may think it as ” the cancer is trying to correct the mess that it made”
96
Diseases of adrenal medulla
Pheochromocytomas
Neuroblastoma
97
Pheochromocytomas
urine excretion of what increases
Pheochromocytomas
Uncommon neoplasms of chromaffin cells origin
Episodic sympathetic outflow like hypertension
1/3 hypertension is chronic and sustained.
Complications; CHF, pulmonary edema, myocardial infarction, cerebrovascular accidents, and arrhythmias.
Lab: Increased urinary excretion of free catecholamines and their metabolites, eg, vanillylmandelic acid (VMA) and metanephrines
98
Freshly cut tumor surface turns dark brown (right half of image) when immersed in potassium dichromate (K₂Cr₂O₇) solution.
This is due to oxidation of stored catecholamines
99
Multiple pheochromocytomas in a patient with multiple endocrine neoplasia type 2A
100
Pheochromocytomas “rule of 10s”
4
10% extra-adrenal
10% of sporadic adrenal pheochromocytomas are bilateral (vs ≤50% of familial tumor syndromes)
10% of adrenal pheochromocytomas are biologically malignant(vs (20% to 40%) in paragangliomas, and in familial tumor syndromes)
10% of adrenal pheochromocytomas are not associated with hypertension
101
Carotid body tumor
Most common form of paraganglioma in the head and neck.
Mobile horizontally but not vertically
Pulsations can sometimes be distinct.
10 times more frequent in persons of high altitudes
~ 5% follow a malignant course.
102
Neuroblastoma
special clinically seen
Rare and highly malignant tumor found in infants and children
Tumor composed of neuroblasts
May secrete catecholamines and may also originate outside the adrenal medulla
Most metastasized by the time of diagnosis (liver, skin and bones (especially the skull) is common)
May occasionally mature spontaneously to ganglioneuroma (benign tumor)
racoon eye
blue berry muffin skin lesion
103
neuroblastoma ddx
Present as palpable posterior abdominal mass (Ddx – Multicystic renal dysplasia and Wilms’ tumor of the kidney).
104
Diabetes Mellitus (DM)
A heterogeneous metabolic disorder, characterized by chronic hyperglycaemia with disturbance of carbohydrate, fat and protein metabolism (WHO)
The most common endocrine disorder
Literally means sweet siphon “passing though; a large discharge of sweet urine.”
Results from defects in insulin secretion, insulin action or, most commonly both
105
primary and secondary dm
primary type 1 and 2
secondary gestational
106
Type I DM
5-10% of diabetics
Autoimmune and idiopathic situations associated with β- cell destruction, and an absolute deficiency of insulin
Insulin-dependent diabetes mellitus (IDDM)
"Juvenile DM" most common type in < 30 years
ketoacidosis prone
107
Pathogenesis of Type I DM
Molecular mimicry (Mumps, Coxsackie B4, retroviruses, CMV and EBV). Dietary nitrosamines and Bovine serum albumin (BSA), and β cell sequestered antigen
~ 95% HLA DR3 or DR4
Identical twins 50% chance
108
Type II DM
90-95% of diabetics
Impaired insulin action/insulin resistance
Vast majority are overweight (obesity)
Non-insulin dependent diabetes NIDDM (Most don’t require insulin)
Adult-onset diabetes (>30 years)
Rarely associated with ketoacidosis (normal or increased insulin secretion)
109
Adipocytokines
Prohyperglycaemic (like retinol-binding protein 4 (RBP 4)and resistin)
Antihyperglycaemic (leptin and adiponectin)
110
Clinical presentation Type I DM
Manifest after 80% of β -cell mass has been destroyed
More symptomatic than type 2 diabetic patients
Polyuria, polydipsia , polyphagia progressive loss of weight and muscle weakness
Increased ketone synthesis leading to ketonaemia, ketonuria and ultimately diabetic ketoacidosis (presents with severe nausea, vomiting and respiratory difficulty)
111
Type II DM
Majority asymptomatic and ~50% present with chronic complications
High portal insulin levels in Type II DM prevent unrestricted hepatic fatty acid oxidation and keep ketone body production in check
Osmotic diuresis and resulting dehydration can induce hyperosmolar nonketotic coma especially in case of poor fluid intake
112
Diabetic Ketoacidosis(DKA)
State of absolute or relative insulin deficiency aggravated by hyperglycaemia, dehydration and acidosis.
Caused by infection, disruption of insulin treatment and new onset of diabetes.
Biochemically DKA is defined as: serum ketones >5 mEq/L, blood glucose > 250 mg/L, arterial blood pH < 7.3
Bicarbonate level ≤18 mEq/L (severe DKA)
113
Hyperglycaemic hyperosmolar non-ketotic syndrome (HHNS)
= Hyperosmolar hyperglycemic state (HHS), Non ketotic Hyperosmolar Coma
More often associated with a Type 2 DM
Due to severe dehydration resulting from prolonged hyperglycaemia-induced diuresis
Intracellular dehydration occurs as hyperglycaemia and water loss leads to increased plasma tonicity, causing a shift of water out of cells. This is associated with movement of potassium from the cell to extracellular compartment.
114
Pancreatic tumours of endocrine origin
Insulinoma (β-cell tumor)
Gastrinoma (G-cell tumor)
Glucagonoma (α-cell tumor)
Somatostatinoma (δ-cell tumor)
vipoma
115
Insulinoma (β-cell tumor)
Most common type of islet cell tumor
Produces insulin hypoglycemia (insulin coma)
Surgical excision is curative
116
Gastrinoma (G-cell tumor)
Produces gastrin
Zollinger-Ellison syndrome (thick gastric folds, elevated serum gastrin, gastric hyperacidity, and intractable peptic ulcers)
May arise outside the pancreas
May be associated with MEN I
117
Glucagonoma (α-cell tumor)
define
5 d
Produces glucagon
Excess glucagon causes hyperglycemia (diabetes), anemia, and skin rash
dermatitis
depression
dm
dvt
diarhea
118
Somatostatinoma (δ-cell tumor)
Produces somatostatin
Inhibits insulin secretion, leading to diabetes
Can also inhibit gastrin secretion (leading to hypochlorhydria) and cholecystokinin secretion (leading to gallstones and steatorrhea)
Prognosis is poor
119
Polyglandular autoimmune syndrome (PGA)
= Autoimmune polyendocrine syndromes (APS)
Functional impairment of multiple endocrine glands due to loss of immune tolerance
120
Multiple endocrine neoplasia (MEN) syndromes
Inherited diseases resulting in proliferative lesions (hyperplasia, adenomas, and carcinomas) of multiple endocrine organs
Characteristics by younger age, multiple endocrine, multifocal, usually preceded by hyperplasia, and usually more aggressive and recur
121
men1
men2a
men2b
pitutary adenoma
pth hyperplasia
pancreatic tumors
pth hyperplasia
medullary thyroid carcinoma
pheochromocytoma
mucosal neuroma
marfanoid body
medullary thyroid carcinoma
pheochromocytoma
122
