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294 Cards in this Set
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Stimulation test: Used to test___?
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Mainly to test HYPOfunction
ACTH stimulation test |
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Suppression test: Used to test____?
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Mainly to test HYPERfunction
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Most hyper functions can/cannot be suppressed? exceptions to the rule?
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CANNOT be suppressed
Exceptions- 1. Prolactinoma 2. Pituitary Cushing syndrome |
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Causes of hyper function?
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1. Inflammation-acute
2. Adenoma 3. Hyperplasia 4. Cancer |
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Hyperfunction of pituitary: Causes?
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1. Pituitary adenoma
2. Craniopharyngioma 3. Midline hamartoma 4. Langerhans histiocytosis |
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Sarcoidosis causes pituitary: hypo/hyperfunction?
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Hypofunction.
sarcOidOsis= hypOfunctiOn |
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True precocious puberty implies: CNS/peripheral origin?
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CNS origin
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Pseudoprecocious puberty implies CNS/peripheral origin?
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Peripheral origin
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Precocious puberty?
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Onset of puberty before:
9 years of age (boys) 8 years of age (girls) |
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MCC cause of precocious puberty?
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#1 Idiopathic
#2 Midline hamartoma in hypothalamus |
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Hypothalamic dysfunction: Clinical features?
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1. Secondary hypopituitarism
2. Central Diabetes Insipidus: ADH synthesis reduced 3. Hyperprolactinemia: Loss of dopamine inhibition 4. Precocious puberty 5. Visual field disturbances : bitemporal hemianopia 6. Mass effect--> obstructive hydrocephalus 7. Growth hormone disorders--> dwarfism 8. Kallmann's syndrome(hypothalamic hypogonadism) |
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Location of pineal gland?
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Above "qaudrigeminal plate"
(Superior + Inferior colliculi= Corpora quadrigemina) |
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Major fn of pineal gland?
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Melatonin production
Side#3 Stimulus for release of melatonin? |
From superior cervical ganglia.
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Fate of pineal gland across progressing age?
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Undergoes dystrophic calcification.
(begins in childhood) Side#3 Use of pineal gland for medical purposes? |
Helps to detect shifts due to mass lesions in brain.
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Pineal tumors?
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Germinomas
Teratomas |
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Effects of pineal tumors?
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Parinaud's syndrome: "Sunsetting sign"
Obstructive hydrocephalus- compression of 3rd ventricle |
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Increase in size of pituitary gland during pregnancy: reason?
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Due to inhibition of 'release' of prolactin by estrogen and progesterone
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Anterior lobe of pituitary derived from?
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Rathke's pouch
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Loss of secretion of hormones:
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Infarctions of pituitary-->panhypopituitarism
Pituitary infarctions |
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Primary Hypopituitarism?
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Pituitary dysfunction
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Secondary Hypopituitarism?
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Hypothalamic dysfunction
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Hypopituitarism: causes?
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1. Pituitary adenoma
2. Craniopharyngioma 3. Sheehan's syndrome 4. Pituitary apoplexy 5. Sickle cell anemia 6. Lymphocytic hypophysitis 7. Empty sella turcica syndrome 8. Hypothalamic dysfunction |
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MCC of pituitary hypo function in adults?
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Adenoma
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MCC of pituitary hypo function in children?
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Craniopharyngioma
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Craniopharyngioma derived from ____?
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Rathke's pouch
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Location of pituitary?
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In sella turcica:
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Sella turcica:Clinical significance?
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ST forms the base on which pituitary rests
Tumors affecting pituitary can only extend rostrally Rostral structure: Optic chiasma Effect: Bitemporal hemianopsia |
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Craniopharyngioma: Associated dz?
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Diabetes insipidus
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Sheehan's postpartum necrosis? symptoms? reason?
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Hypovolemic shock produces infarction of pituitary- postpartum
Symptoms: sudden loss of lactation secondary to shock reason: loss of prolactin |
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Pituitary apoplexy?
cause? risk factors? Clinical findings? |
Sudden onset of hypopituitarism
Cause: Hemorrhage/infarction of preexisting adenoma Risk factors: Trauma Pregnancy Rx of prolactinoma with bromocriptine Clinical findings: Headache (Raised ICP from stroke) MS alteration (Hemorrhage into other cortical areas) VISUAL DEFECTS HORMONAL DYSFUNCTION |
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Craniopharyngioma: Gross findings?
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1. Cystic tumor
2. Hemorrhagic 3. Calcified- Blue black color on h and e |
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Pituitary adenoma: types?
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Prolactinoma- MC
Corticotroph cell adenoma--> Cushing's disease Somatotroph cell adenoma--> Gonadotroph adenoma Thyrotroph adenoma |
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MCC pituitary adenoma?
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Prolactinoma
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Adenoma: Classification on basis of size?
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Micro: < 10 mm
Macro: > 10 mm |
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Micro adenoma: Disease association?
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MEN I
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MEN I?
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1. Pituitary adenoma
2. Hyperparathyroidism 3. Pancreatic tumor |
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MEN I: clinical features?
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PPP:
1. Parathyroid- hyperfn--> Kidney stones, Osteitis fibrotic cystica 2. Pituitary- adenoma- Prolactinoma 3. Pancreatic- tumor- a. ZE syndrome--> Peptic ulcers b. Insulinoma c. VIPoma d. Glucagonoma |
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Nelson's syndrome?
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Pituitary adenoma following removal of adrenal glands-->
d/t b/l surgical removal of adrenals--> inhibited negative feed back loops--> pituitary gland hyperplsia--> mass effect |
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Lymphocytic hypophysitis?
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Female autoimmune destruction of pituitary gland.
Occurs during or after pregnancy |
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Empty sella syndrome?
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Primary: Subarachnoid space extends into sella-->
CSF pressure compresses the gland |
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Patient population affected by Prim sella syndrome?
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Obese women with hypertension
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Secondary hypopituitarism
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d/t -
radiation/trauma/sx GnRH- 1. Delayed puberty 2. Impotence 3. Amenorrhea/Osteoporosis/hot flashes GH- 1. Growth delay- Delayed fusion of epiphyses 2. Hyoglycemia 3. Muscle loss 4. Fat deposition (around waist) TSH- Hypothyroidism symptoms ACTH- 1. Hypoglycemia- reduced gluconeogenesis 2. Hyponatremia from SIADH |
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Dx of hypopituitarism
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1. GnRH stimulation test:
No increase in FSH/LH in hypopituitarism Eventual increase in FSH/LH in hypothalamic dz 2. Metyrapone test: Metyrapone inhibits 11-hydroxylase--> Normally: Increase in ACTH(from reduced cortisol- negative feedback loop) Accumulation of 11-deoxycortisol (product proximal to 11-hydroxylase) Hypopituitarism- No increase in ACTH No increase in 11-deoxycortisol (after metyrapone administration) 3. Arginine and sleep stimulation test Hypo: No increase in GH or IGF-1 (normally released at 5am in morning) 4. TRF stimulation- No rise in TSH 5. Short ACTH stimulation test: No increase over baseline cortisol levels 6. Long ACTH stimulation test Eventual/gradual increase in baseline levels |
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Posterior pituitary functions?
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ADH-
Urine concentration <Aqueous Distention hormone> Oxytocin- milk ejection uterine contraction |
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Prolactinoma:
Hormones secreted/reduced? Clinical findings? |
Hormones secreted:
Prolactin--> Suppresses GnRH Growth hormone Reduced levels of: FSH and LH Clinical features: Secondary amenorrhea(F) Galactorrhea(F) Impotence(M) Headache(M) Prolactinoma: Levels of prolactin in blood? >200ng/ml |
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Growth hormone - effects/functions?
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1. IGF-1 production in liver
2. Gluconeogenesis 3. +ve nitrogen metab 4. Na retention |
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Effect of IGF-1?
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Growth of:
1. Bone 2. Cartilage 3. Soft tissue |
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Growth hormone adenoma:
Clinical features? |
1. Gigantism
2. Acromegaly |
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Gigantism?
Acromegaly? |
Gigantism:
Increased linear/lateral bone growth (Epiphyses not fused) Acromegaly: 1. Increased lateral bone growth a. Prominent jaw- space between teeth increased b. Big hands c. Feet d. Frontal bossing- Enlarged frontal sinus 2. Hyperglycemia 3. Hypertension 4. Organomegaly- Cardio, Hepato, Reno, Thyro 5. Myopathy 6. Headache 7. Visual field defects |
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Growth hormone adenoma:
Dx? Rx? |
Rx-
Transsphenoidal Sx Medical- 1. Somatostatin and dopamine analogs; 2. GH receptor a/agonist |
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Thyroxine synthesis in thyroid?
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1. Trapping(TSH)
2. Oxidation(Peroxidase) 3. Organification(TSH) 4. Coupling(Peroxidase) 5. Storage 6. Proteolysis(TSH) |
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Active thyroid form: t3/t4?
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T3
T Three= acTive |
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Feedback mechanism of thyroid hormones on TSH?
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FT4: FT3 ratio:
enhanced ratio inhibits TSH |
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T4--> T3: mediated by?
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Outer ring de-iodinase
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TSH mediated effects in thyroid?
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Trapping
Organification Proteolysis |
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Thyroid hormone functions?
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1. Metabolism
2. Growth/maturation 3. Hormone/vitamin turnover 4. Cell regeneration 4Bs- Brain maturation B-receptor stimulation(permissive role) Bone growth BMR |
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Thyroid hormone: MOA?
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Na/K pump stimulation: increases BMI
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TSH levels are directly associated with:
1. FT3 2. FT4 3. TT4 4. TT3? |
FT4
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Conditions associated with increased TT4, normal FT4 ?
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1. Anabolic steroids
2. Nephrotic syndrome |
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Best screening test for thyroid dysfunction?
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TSH
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Conditions associated with increased TT4, normal FT4 ?
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Estrogen
(Pregnancy, OC pills) |
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Test to evaluate synthetic activity of thyroid gland?
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I131
Increased uptake indicates increased activity |
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Decreased I131 uptake seen in?
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Cold nodule
Thyroiditis Pt on thyroid hormone |
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Increased I131 uptake seen in?
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Hot nodule
Grave's disease |
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Marker for thyroid cancer?
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Thyroglobulin
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Hypothyroidism+
Dysphagia for solid foods? |
Lingual thyroid: BASE of tongue
(Represents the only thyroid tissue in body- hypo functional) |
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Dx of lingual thyroid?
Rx? |
I131 scan
Ablation with radioactive iodine |
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Thyroglossal duct? Rx?
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Cystic midline mass: close to hyoid bone
Rx: Surgical removal |
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Thyroiditis: types?
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1. Acute
2. Subacute 3. Hashimoto's 4. Riedel's 5. Lymphocytic |
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Acute thyroiditis: MC assoc microorganism?
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S.Aureus
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Most common cause of a painful thyroid gland?
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Subacute granulomatous thyroiditis
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Thyroiditis associated with :Granulomatous inflammation/multinucleated giant cells?
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Subacute thyroiditis
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Subacute granulomatous thyroiditis: Associated microorganisms?
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1. Coxsackie
2. Mumps |
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Thyroiditis associated with URTI?
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Subacute granulomatous thyroiditis
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Fever+hypothyroidism?
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Acute hypothyroidism
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Subacute and acute thyroiditis: differentiating point?
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1. Acute thyroiditis:
Cervical adenopathy Bacterial involvement 2. Subacute thyroiditis: Viral involvement Granulomatous |
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Common features:Acute and subacute thyroiditis?
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1. Painful conditions
2. Initial thyrotoxicosis (increased T4 ad decreased serum TSH) 3. Decreased I131 intake 4. Reversible(hypothyroidism not permanent) |
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Rx for acute thyroiditis?
Rx for subacute thyroiditis? |
Acute thyroiditis: Penicillin/ampicillin
Subacute thyroiditis: None reqd |
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Granulomatous dzs:
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1. Tb
2. Leprosy 3. Sarcoidosis 4. Crohn's disease 5. Schistosomiasis 6. Histoplasmosis 7. Cryptococcosis 8. Cat scratch 9. Pneumocystis pneumonia 10. Aspiration pneumonia 11. Vasculitis: a. Wegener's b. Churg-Strauss |
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Hashimoto's thyroiditis: HLA-association?
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HLA DR3
HLA DR5 |
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Hashimoto's thyroiditis: Associated conditions?
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1. Turner's
2. Down's 3. Klinefelter's 4. Perinicious anemia 5. Most autoimmune diseases 6. Type I DM |
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Hashimoto's thyroiditis:
Histology? |
1. Hurthle cells:
Epithelial cells with abundant eosinophilic granular cytoplasm 2. Lymphocytic infiltrate with germinal centers |
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Hashimoto's thyroiditis: pathology/Autoimmune type?
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1. T cell mediated destruction- Typer IV hypersensitivity
2. IgG autoAB: Block TSH receptor: Type II (Mainly Type IV) |
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Hashimotos thyroiditis: antibodies found in the blood?
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1. A/microsomal ABs
2. Thyroglobulin ABs 3. A/peroxidase ABs |
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Hashimoto's: clinical findings?
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Initial thyrotoxicosis
Hypothyroidism |
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MCC of primary hypothyroidism?
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Hashimoto's thyroiditis
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Hashimoto's: associated malignancy?
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B cell malignant lymphoma of thyroid
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Riedel's thyroiditis? complication? Rx?
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Fibrous replacement of thyroid tissue
Complication: tracheal obstruction Rx: #1. Steroids #2. Tamoxifen #3. Sx |
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Riedel's thyroiditis: Dx? clinical features?
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Fibrosis with gland destruction
Hard painless- "rock like" Hypothyroidism features Dysphagia Dyspnea |
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Autoimmune thyroiditis associated with postpartum state?
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Subacute lymphocytic thyroiditis
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Sudden onset of thyrotoxicosis following/after pregnancy?
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Subacute lymphocytic thyroiditis
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Hypothyroidism following pregnancy?
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Lymphocytic thyroiditis
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Subacute lymphocytic thyroiditisLab findings?
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A/microsomal ABs
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A/microsomal AB related thyroiditis?
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1. Hashimoto's
2. Subacute painless lymphocytic thyroiditis |
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Subacute painless lymphocytic thyroiditis: rx?
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Levothyroxine
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Hypothyroidism:
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1. Hashimoto's
2. Lymphocytic thyroiditis 3. Hypopituitarism 4. Iodine deficiency 5. Enzyme deficiency 6. Drugs- (a. Amiodarone, b. Lithium, c. Sulfonamides, d. Phenylbutazone) 7. Congenital 8. Acute/subacute(viral/bacterial) - reversible |
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Clinical findings:
differences between- pituitary dwarfism and cretinism? |
Cretinism:
Increased weight and short stature Dwarfism: Decreased weight and short stature |
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Cretinism: cause?
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maternal hypothyroidism
before fetal thyroid maturation |
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Adult hypothyroidism: clinical findings.
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1. Proximal muscle myopathy
(increased serum creatine kinase) 2. Delayed recovery of achilles reflex 3. Weight gain- hypo metabolism and Na / water retention 4. Periorbital puffiness- increased hyaluronic acid/chondroitin sulphate 5. Hoarse voice- increased hyaluronic acid/chondroitin sulphate 6. Coarse yellow skin- failure to breakdown b-carotenes--->retinoic acid 7. Dry brittle hair- loss of outer 1/3rd eyebrow 8. Cold intolerance 9. Fatigue 10. Menorrhagia 11. Diastolic hypertension 12. Bradycardia 13. Congestive/dilated cardiomyopathy- biventricular failure 14. Atherosclerotic coronary artery disease 15. Mental slowness 16. Dementia |
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Primary hypothyroidism: Rx?
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Levothyroxine increment every 6-8 wks
(target TSH should be brought back to normal) |
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Primary hypothyroidism:Laboratory findings?
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1. Decreased T4
2. A/microsomal 3. A/peroxidase 4. A/thyroglobulin ABs 5. Hypercholesterolemia |
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Myxedema coma: causes?
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1. Idiopathic
2. Cold exposure 3. Sedatives 4. Opiates 5. Acute illness |
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Myxedema coma: clinical findings?
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1. Hypoventilation
2. Hypocortisolism 3. Hypoglycemia 4. Hypothermia 5. Stupor 6. Bradycardia 7. SIADH |
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Myxedema coma: Rx?
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1. IV levothyroxine
2. High dose corticosteroids 3. Rx hypothermia 4. Ventilatory support |
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Myxedema coma : prognosis?
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20-50% survival rate
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Hyperthyroidism?
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Hormone from increased SYNTHESIS of thyroxine
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Thyrotoxicosis?
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Hormone excess from any cause(?)
(Grave's disease, toxic nodular goiter) |
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MCC of hyperthyroidism?
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Grave's disease
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Grave's disease: HLA association?
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HLA-B8
HLA-DR3 |
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Grave's disease: Autoimmune type?
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Type II
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Grave's disease: A/bodies associated?
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Anti-thyroglobulin
Anti-Microsomal |
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Grave's disease: Risk/triggering factors?
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1. Infection
2. Steroid withdrawal 3. Iodide excess 4. Post partum |
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Grave's disease:Thyroid-gross/microscopic features?
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Symmetric enlargement
Nontender Scant colloid Papillary infolding of the glands |
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Grave's features: Clinical features unique to grave's disease?
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1. Exophthalmos
2. Pretibial myxedema 3. Thyroid acropachy |
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Thyroid acropachy?
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1. Digital swelling(Clubbing of fingers)
2. Nails seperating from nailbeds |
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Grave's disease: Exophthalmos?
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Muscle weakness
Adipose and GAG deposition |
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Grave's disease:Pretibial myxedema?
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GAG deposition in DERMIS
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Grave's disease: Findings in elderly?
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1. A-fib(deposition of GAG in valvular tissue)
2. CHF 3. Muscle weakness 4. Weakness/apathetic face |
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Toxic multi nodular goitre/Plummer's disease: pathology?
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1/>1 nodule turns independent of TSH stimulation
"hot nodule" |
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Toxic multi nodular goitre: rx?
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Rx: Sx
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All findings in thyrotoxicosis from any cause? Findings result from ____?
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1. Weight loss
2. Fine tremors 3. Brisk reflexes 4. Heat intolerance 5. Diarrhea 6. Anxiety 7. Oligomenorrhea 8. Lid stare 9. Sinus tachycardia 10. Atrial fibrillation 11. Systolic hypertension 12. High output 13. Osteoporosis Result from increased synthesis of B-receptors |
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Lab findings in hyperthyroidism?
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Increased t4
decreased TSH Increased I131 uptake Hyperglycemia Hypercalcemia Lymphocytosis Hypocholesterolemia |
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Thyroid storm: rx?
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Rx:
Propylthiouracil/iodide: Inhibit hormone synthesis B blockers Hydrocortisone Cooling blanket |
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Euthyroid sick syndrome?
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Abnormal T3 and T4; normal gland function
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ESS: Associations?
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1. Malignancy
2. Heart failure 3. Renal failure 4. Sepsis 5. Myocardial infarction |
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ESS: Pathology?
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Peripheral ring deiodinase gets deactivated-->
T4 gets converted to inactive reverse T3 |
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ESS: Rx?
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No treatment
Levothyroxine if severe |
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Goitre?
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Excess colloid-->thyroid enlargement
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Goitre Types:?
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Endemic: iodide deficiency
Sporadic: 1. Goitrogens(cabbage), 2. Enzyme deficiency, 3. Puberty 4. Pregnancy |
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Scant colloid observed in?
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Hashimoto's thyroiditis
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Goitre: Pathogenesis?
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1. Initial hyperplasia/hypertrophy---> Hypoplasia/involution
2. Thyromegaly--> Multinodular goitre |
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Goitre: Complications?
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1. Hemorrhage into cyst: Painful(sudden) gland enlargement
2. Edema face: Jugular vein compression. (Pemberton 's sign) 3. Primary hypothyroidism 4. Hoarseness: Laryngeal nerve compression 5. Dyspnea: Tracheal compression |
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Goitre: Rx?
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Levothyroxine
Sx if compression. |
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Solitary thyroid nodules: Causes?
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1. Goiters
2. Follicular adenoma 3. Malignant(prior hx of radiation) 4. Euthyroid |
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Solitary thyroid nodules: in women malignant/ benign?
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Benign and Euthyroid
15% are malignant |
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Solitary thyroid nodules in men/children: malignant/benign?
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Malignant
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Solitary thyroid nodule: 1st step in management?
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#1 FNAC
#2 Thyroid hormone studies |
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Solitary thyroid nodules: Rx?
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Malignant: Sx removal
Benign: Periodic follow up |
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Thyroid tumors: Name em.
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1. Follicular adenoma
2. Follicular carcinoma 3. Medullary carcinoma 4. Papillary adenocarcinoma 5. Primary b cell lymphoma 6. Anaplastic thyroid cancer. |
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MC benign thyroid tumor?
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Follicular adenoma
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Follicular adenoma: prognosis?
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1. Benign condition
2. 10% chance of progressing to follicular ca. |
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Follicular adenoma: common presentation?
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Solitary cold nodule
may produce pressure symptoms |
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Follicular carcinoma: common presentation?
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Solitary cold nodule
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Follicular carcinoma: female/male dominant?
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Female dominant
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Follicular carcinoma: Gross/microscopic findings?
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Encapsulated or Invasive(either)
Neoplastic follicles invade blood vessels NO LN involvement(rare) |
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Follicular carcinoma: Metastatic sites?
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Lung
Bone |
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Follicular carcinoma: Rx?
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Rx:
1. Subtotal/total thyroidectomy 2. Followed by radiotherapy 3. Suppressive therapy with thyroid hormone (Tumor - TSH dependent) |
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Follicular carcinoma: symptoms?
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Pressure related:
dyspnea dysphagia hoarseness cough |
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MC endocrine cancer?
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Paipllary adenocarcinoma
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MC thyroid cancer?
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Papillary adenocarcinoma
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Papillary adenocarcinoma: patient population affected?
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Females
2nd and 3rd decade **Radiation exposure** |
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Papillary adenocarcinoma: Gross/microscopic features?
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1. Multifocal
2. Psammoma bodies 3. "Orphan-Annie nuclei" (Empty appearing nuclei) 4. Lymphatic invasion 5. Papillary branching pattern mixed with follicles |
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Papillary adenocarcinoma: metastasis?
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Cervical LN
Lung |
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Papillary adenocarcinoma: Dx?
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FNA
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Papillary adenocarcinoma: Rx? prognosis?
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Rx:
1. Subtotal/total thyroidectomy 2. Followed by radiotherapy 3. Suppressive therapy with thyroid hormone (Tumor - TSH dependent) |
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Medullary carcinoma: types?
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Sporadic(80%)
Familial(20%) |
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Medullary carcinoma thyroid:
Associations? |
1. MEN IIa- Medullary carcinoma, HPTH, Pheochromocytoma
2. MEN IIb(III) syndrome: Medullary carcinoma, Neuromas, pheochromocytomas 3. Ectopic hormones: ACTH- Cushing's syndrome |
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Medullary carcinoma thyroid:
Pathogenesis? |
1. Tumors derived from parafollicular cells-->calcitonin-->
amyloid Hypocalcemia 2. C cell hyperplasia |
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Medullary Ca of thyroid: Dx?
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1. FNA
2. Sr. calcitonin |
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Medullary Ca of thyroid: Dx?
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Genetic testing: RET mutation
if +ve--> thyroidectomy |
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Primary B cell malignant lymphoma: Derives from?
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Hashimoto's thyroiditis
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Anaplastic thyroid ca: Risk factors?
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Multinodular goitres
history of follicular cancer |
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Anaplastic thyroid ca: rx?
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Palliative sx
radiation/ chemotherapy |
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Superior parathyroid derived from?
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Fourth pharyngeal pouch
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Inferior parathyroid derived from?
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Third pharyngeal pouch
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PTH functions/actions?
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1. Increased absorption of Ca from distal tubule
2. Increased bone resorption 3. Decreased PO4 and HCO3 absorption from prox tubule 4. Induces 1-alpha-hydroxylase in prox tubule 5. Inhibits 25-hydroxylase in prox tubule |
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PTH actions in prox tubule?
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1. Induces 1-alpha-hydroxylase
2. Inhibits 25-hydroxylase 3. Inhibits HCO3 and PO4 absorption |
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Vit D sources?
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Ergocalciferol from plants
Cholecalciferol from fish 7-Dehydrocholesterol--> cholecalciferol (sunlight) |
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Vit D processing in body?
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Cholecalciferol--> 25 hydroxyCC(Liver- Cyt P450)
25-OH-CC-->1,25-DHCC(prox tubules: 1-alpha-hydroxylase) |
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In Absence of PTH:
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25-HCC-->24, 25 DHCC(prox tubules: 24-hydroxylase)
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Vit D: actions?
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1. Absorption of Ca from duodenum
2. Absorption of PO4 from ileum and jejunum 3. Increased bone resorption. (Induction of stem cells-->osteoclasts) |
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Effect of Ca on:
24hydroxylase 1-alpha-hydroxylase decreased ca? |
Increased Ca:
24-hyd:activation 1-a-hyd:inhibition 24-hy:inhibition 1-a-hyd: activation |
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Total Sr Ca: bound form distribution?
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1)albumin- 40%
2)Phosphorus Citrate-13% 3) Free- 47% |
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Albumin binding to calcium?
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At pH 7.4: COO- groups freely available: bind to albumin.
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MCC of hypocalcemia?
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Hypoalbuminemia
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Hypocalcemia due to hypoalbuminemia?
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Total Ca drops
Free Ca normal Normal PTH No evidence of tetany |
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Effect of respiratory alkalosis on Ca levels in blood? Reason?
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Free Ca drops-->increased PTH
Bound form rises. TOTAL Ca= NORMAL TETANY Reason: Increased negative charge on albumin: Therefore more binding of Ca (-COOH groups of ACIDS in albumin ionize in alkaline medium) COOH--> COO- and H+ COO- attracts H+ |
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Tetany: cause?
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Decreased ionized Ca levels-->
Partial depolarization of nerves and muscles--> |
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Tetany: clinical effect?
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Carpopedal spasm: Thumb flexes in palm
Chvostek sign: facial twitch after tapping facial nerve |
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Hypoparathyroidism: MCC?
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Autoimmune hypoparathyroidism
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Hypoparathyroidism: Causes?
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1. Autoimmune
2. Previous thyroid Sx 3. DiGeorge syndrome: Thymic aplasia + Absent parathyroid (Failure of 3rd and 4th pharyngeal pouch to descend) 4. Hypomagnesemia (Causes of hypomagnesemia: Diuretics Diarrhea Aminoglycosides Alcohol) cAMP required for PTH activation Mg : cofactor for cAMP |
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Hypoparathyroidism: clinical findings?
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a. Tetany
b. Basal ganglia calcification c. Cataracts d. Candida infections (?) Hypocalcemia Hyperphosphatemia Drop in PTH |
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Hypocalcemia: causes?
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1. Acute pancreatitis- Calcium binds to fatty acids in enzymatic fat necrosis-->indicates poor prognosis
2. Hypovitaminosis D-->decreased ca absorption-->decreased sr.ca---> PTH---> increased 1,25 DHCC-->increased PO4 absorption 3.Lack of sunlight: decreased conversion of vit D 4. Cirrhosis: decreased synthesis of 25-OH 5. Drugs: phenytoin, alcohol: induction of cyt p450 6. Chronic renal failure: Decreased 7. Enzyme defects/Vit-D dependent rickets: AR type I: Absent 1-alpha-hydroxylase 8. AR type II: Absent receptors for calcitriol 9. Pseudohypoparathyroidism: AD dz End organ resistance |
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Hypovitaminosis D: causes
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1. Lack of sunlight
2. Malabsorption 3. Cirrhosis 4. Drugs: alcohol, phenytoin 5. CRF |
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Pseudohypoparathyroidism: cause? clinical signs?
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Cause:
End organ Resistance 1. Mental retardation 2. Knuckle knuckle dimple dimple sign- small 4th and 5th metacarpals 3. Basal ganglia calcification |
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Hypocalcemia due to hypoalbuminemia?
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Total Ca drops
Free Ca normal Normal PTH No evidence of tetany |
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Effect of respiratory alkalosis on Ca levels in blood? Reason?
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Free Ca drops-->increased PTH
Bound form rises. TOTAL Ca= NORMAL TETANY Reason: Increased negative charge on albumin: Therefore more binding of Ca (-COOH groups of ACIDS in albumin ionize in alkaline medium) COOH--> COO- and H+ COO- attracts H+ |
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Tetany: cause?
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Decreased ionized Ca levels-->
Partial depolarization of nerves and muscles--> |
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Tetany: clinical effect?
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Carpopedal spasm: Thumb flexes in palm
Chvostek sign: facial twitch after tapping facial nerve |
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Hypoparathyroidism: MCC?
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Autoimmune hypoparathyroidism
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Hypoparathyroidism: Causes?
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1. Autoimmune
2. Previous thyroid Sx 3. DiGeorge syndrome: Thymic aplasia + Absent parathyroid (Failure of 3rd and 4th pharyngeal pouch to descend) 4. Hypomagnesemia (Causes of hypomagnesemia: Diuretics Diarrhea Aminoglycosides Alcohol) cAMP required for PTH activation Mg : cofactor for cAMP |
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Hypoparathyroidism: clinical findings?
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a. Tetany
b. Basal ganglia calcification c. Cataracts d. Candida infections (?) Hypocalcemia Hyperphosphatemia Drop in PTH |
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Hypocalcemia: causes?
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1. Acute pancreatitis- Calcium binds to fatty acids in enzymatic fat necrosis-->indicates poor prognosis
2. Hypovitaminosis D-->decreased ca absorption-->decreased sr.ca---> PTH---> increased 1,25 DHCC-->increased PO4 absorption 3.Lack of sunlight: decreased conversion of vit D 4. Cirrhosis: decreased synthesis of 25-OH 5. Drugs: phenytoin, alcohol: induction of cyt p450 6. Chronic renal failure: Decreased 7. Enzyme defects/Vit-D dependent rickets: AR type I: Absent 1-alpha-hydroxylase 8. AR type II: Absent receptors for calcitriol 9. Pseudohypoparathyroidism: AD dz End organ resistance |
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Hypovitaminosis D: causes
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1. Lack of sunlight
2. Malabsorption 3. Cirrhosis 4. Drugs: alcohol, phenytoin 5. CRF |
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Pseudohypoparathyroidism: cause? clinical signs?
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Cause:
End organ Resistance 1. Mental retardation 2. Knuckle knuckle dimple dimple sign- small 4th and 5th metacarpals 3. Basal ganglia calcification |
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Primary: Hyperparathyroidism: cause?
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1. MCC: adenoma
2. Hyperplasia- ALL FOUR GLANDS 3. Carcinoma |
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Hyperparathyroidism:
glands involvement(site/no)- in - hyperplasia? adenoma? |
Hyerplasia: All 4 glands- chief cells involved
Adenoma: Right inferior gland involved. |
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Primary hyperparathyroidism: Pt population affected?
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Postmenopausal women:
Associated with MENI and MENII(a) |
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Primary hyperparathyroidism: clinical findings/associations?
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1. Renal- Nephrocalcinosis/ renal stones- polyuria and renal failure
2. GI- Peptic ulcer disease- Ca stimulates gastrin 3. Acute pancreatitis- Ca stimulates phospholipase 4. Bones- Osteitis fibrous cystic: increased osteoclastic activity: MC site: jaw Skull shows-"salt and pepper appearance" Osteoporosis Chondrocalcinosis 5. Diastolic hypertension- Ca retention 6. Eyes- Band keratopathy in eye limbus 7. CNS- psychosis, confusion, anxiety, coma |
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Hypercalcemia: best initial screening test?
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Sr. PTH
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Primary hyperparathyroidism: Laboratory findings?
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1. PTH: increased, ca increased
2. Increased Chloride:Phosphorus > 31 decreased chloride:phosphorus<29--excludes Primary HyperPTH as cause. 3. Normal anion gap acidosis: excretion of HCO3 4. Increased calcitriol(vit d) -- d/t increased synthesis of 1-alpha-hydroxylase 5. PROLONGED QT on EKG 6. Technecium-99m- sestamibi radionuclide scan. |
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Primary hyperparathyroidism: Rx?
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1. Sx removal of gland
hypercalcemia: 2. IV hydration, 3. IV furosemide 4. Bisphophonates 5. Cincalcet: Increases PTH receptors(ca sensing to extracellular Ca) |
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Hypercalcemia: causes?
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1. Hypervitaminosis D
2. Malignancy 3. Familial hypocalciuric hypercalcemia: AD (altered set point for detecting calcium in receptors) 4. Sarcoidosis: Macrophages in granulomas synthesize 1-alpha-hydroxylase 5. Thiazides |
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Malignancy associated hypercalcemia? Mechanism?
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1. Activation of osteoclasts:
i. Multiple myeloma ii. Bone mets 2. Ectopic PTH secretion i. Squamous cell carcinoma(lung) ii. Renal cell carcinoma |
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Secondary hyperparathyroidism: cause?
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Hypocalcemia from any cause induces hyperPTH
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IF EITHER PTH OR Ca NORMAL WITH THE OTHER ABNORMAL PARAMETER
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Think about :
hypoalbuminemia or respiratory alkalosis |
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Hypophosphatemia: causes? clinical features?
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1. Hypovitaminosis D
2. HyperPTH 3. Respiratory alkalosis 4. Insulin Rx in DKA 5. Vitamin D resistant rickets Clinical features: RBC lysis Muscle weakness/fatigue--> rhabdomyolysis Osteomalacia(phosphorus needed for bone mineralization) |
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Hyperphosphatemia: causes? clinical features?
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HypoPTH
CRF Normal child PseudohypoPT: AD Clinical features: Metastatic calcification Hypovitaminosis D (Phosphate inhibits 1-alpha-hydroxylase) |
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Enzyme activated by AT-II(converts cortisone-->aldosterone
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18-hydroxylase
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Adrenal cortex: hormones synthesized?
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Glomerulosa: Aldosterone
Fasciculata: Cortisol Reticularis: Androgens |
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End product of catecholamine metabolism?
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Vanillyl mandalic acid(VMA)
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End product of Dopamine metabolism?
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Homovanillic acid(HVA)
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Adrenal medulla derived from?
(embryological structure) |
Neural crest derivative
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Adrenocortical insufficiency: causes?
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1. Steroid withdrawal
2. Waterhouse-Friedrichson syndrome 3. Anticoagulation |
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Waterhouse friedrichson syndrome?
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N.meningitidis
Sepsis-->Endotoxic shock-->Thromboplastin-->DIC-->B/L hemorrhagic infarction |
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Chronic adrenal insufficiency: causes?
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1. Autoimmune
2. Miliary tb 3. HIV 4. Metastatic cancers- primary lung cancer 5. Adrenogenital syndrome |
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Adrenal insufficiency: Clinical findings?
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1. Weakness, hypotension
2. Hyperpigmentation(ACTH) 3. Hypoglycemia 4. Eosinophilia, lymphocytosis, neutropenia 5. Hyponatremia, hyperkalemia, acidosis(Aldosterone enhances proton pump) |
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21-hydroxylase
11-hydroxylase 17-hydroxylase deficits? |
21-hydroxylase: increased androgens
11-hydroxylase: increased androgens and deoxycortisol/sterone 17-hydroxylase: increased deoxycortisol/sterone 21-hydroxylase deficiency--> accumulation of androgens Androstenedione DHEA 11-hydroxylase deficiency--> Androgens 11-DOC accumulation 17-hydroxylase deficiency--> Aldosterone accumulation Rx: replacement |
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Adrenal insufficiency:
Laboratory tests/dx? |
1. Short and prolonged ACTH stimulation--> no effect
2. Metyrapone test: 11-hydroxylase inhibition-->increased ACTH 3. Increased plasma ACTH 4. Hyponatremia, hyperkalemia, metabolic acidosis 5. Hypoglycemia(fasting) 6. Lymphocytosis, eosinophilia, neutropenia |
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Dx of adrenogenital syndrome?
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1. Sr 17-OH-progesterone
(increased in 21 and 11-hydroxylase deficiency) Measured prenatally in chorionic villous sampling 2. Sr. 17-hydroxycorticoids Sr. 17-ketosteroids |
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Hypertension in 17-hydroxylase deficiency due to: associated compound?
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11-DOC
**********NOT aldosterone********* (AT-II activity drops so no 11-doc converted to aldosterone) |
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MCC enzyme defect in adrenogenital syndrome?
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21-OH-ase deficiency
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21-OH-ase deficiency: types?
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Classic: both cortisol and aldoterone deficient
Non-classic: Only cortisol deficient |
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Adrenocortical hyperfunction:
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Cushing syndrome:
1. Prolonged steroid therapy 2. Cushing's dz: i. Pituitary Cushing: adenoma ii. Adrenal cushing: adenoma iii. Ectopic cushing: Small cell lung ca, thyroid, thymus |
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Ectopic cushing's: causes? ACTH levels: increased/decreased?
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Small cell carcinoma of lung
Thymus Thyroid ACTH increased |
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Cushing's syndrome: clinical findings?
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1. Fat deposition
(Cortisol--> hyperglycemia--> hyperinsulinemia--> fat deposition) fat deposited in 1. trunk 2. upper back 3. face 2. Muscle wasting Cortisol--> breaks down muscles--> release of AA for gluconeogenesis) 3. Diastolic hypertension Mineralocorticoid activity enhanced. 4. Hirsutism 5. Striae: Cortisol-->collagen breakdown 6. Osteoporosis Cortisol |
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Cushing's disease: laboratory findings?
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Increased urine cortisol
Low dose dexamethasone suppression- no effect on anything High dose dexamethasone suppression- Suppresses pituitary cushing's |
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Conn's syndrome?
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Primary hyperaldosteronism.
Adenoma in zona glomerulosa |
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Conn's syndrome: clinical findings? laboratory findings?
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Clinical findings:
1. Hypertension 2. Muscle weakness(hypokalemia) 3. Tetany(alkalosis) Laboratory findings: 1. Hypernatremia 2. Hypokalemia 3. Alkalosis 4. Decreased plasma renin activity-----> therefore hypertension due to: 11-DOC(no 18 hydroxylase to convert 11-DOC to aldosterone) |
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Pheochromocytoma: associations?
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1. Neurofibromatosis type 1
2. Von-Hippel Lindau syndrome: VHL gene mutation 3. MENII-a and MENII-b: RET proto-oncogene |
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Pheochromocytoma:
Malignant/benign? |
Benign adenoma
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Pheochromocytoma: Organ sites affected?
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1. Adrenal medulla
2. Organ of zuckerkandl-(bifurcation of aorta) 3. Bladder 4. Posterior medulla |
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Pheochromocytoma: gross appearance?
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1. Hemorrhagic
2. Necrotic 3. Brown |
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Pheochromocytoma: clinical features?
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1. Diastolic hypertension
2. Orthostatic hypotension 3. Episodic bouts of hypertension 4. Absent peristalsis in ileus(?) 5. Hyperhidrosis 6. Chest pain 7. Palpitations 8. Anxiety |
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Pheochromocytoma: Laboratory findings?
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1. Increased plasma free metanephrines
2. Increased plasma free normetanephrine 3. Increased 24-hr urine - metanephrine 4. Increased 24 hr urine- VMA 5. Hyperglycemia 6. Neutrophilic leukocytosis--> Inhibition of adhesion molecules 7. Lack of clonidine suppression |
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Pheochromoctyoma: rx?
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Rx:
Sx Preoperative stabilization: 1. Phenoxybenzamine 2. B-blockers 3. Metyrosine (catecholamine synthesis inhibitor) 4. Liberal fluid and salt intake hypertensive crysis: phentolamine/nitroprusside + b-blocker |
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Effects of pheochromocytoma due to
Norepinephrine/epinephrine? |
Norepinephrine
(tumor produces only NOR) |
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If tumor produces both Nor and Epi: effected sites?
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1. Adrenal medulla
2. Organ of Zuckerkandl |
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Neuroblastoma: organ affected?
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Post sympathetic ganglia
1. adrenal medulla 2. Posterior mediastinum(paraspinal) |
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Neuroblastoma: genetic defect?
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amplification if n-myc oncogene
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Neuroblastoma: sites of metastasis?
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1. Bones
2. Skin |
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Neuroblastoma: Clinical features?
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1. Diastolic htn
2. Palpable abdominal mass Increased VMA and HVA 3. Opsoclonus-myoclonus syndrome: i. Myoclonic jerks ii. Chaotic eye movements |
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Neuroblastoma: Microscopy?
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1. Homer-Wright rosettes
(Neuroblasts around central space) 2. Neurosecretory granules in electron microscopy |
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Neuroblastoma: dx?
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Urine collection- VMA and HVA
Imaging studies: Body scan with I-MIBG(metaiodobenzylguanidine) Bone scans- lytic lesion |
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Neuroblastoma: pt population commonly affected?
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Children < 5years
Mean age of onset 18 months |
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Opsoclonus-myoclonus syndrome: associated dz?
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Neuroblastoma
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Glucagonoma:
Malignant/benign? |
Malignant tumor of alpha cells
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Glucagonoma: clinical features? rx?
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Hyperglycemia(DM)
Necrolytic migratory erythema rx: Sx, octreotide |
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MC islet cell tumor?
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Insulinoma
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Insulinoma:
Malignant/benign? |
Benign
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Insulinoma: Important dz association? clinical features?
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MEN-I
Fasting hypoglycemia Increased sr. insulin, c-peptide |
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Insulinoma: Rx?
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Sx
Streptozotocin |
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Insulinoma vs surreptitious use of insulin?
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Both conditions=
fasting hypoglycemia increased insulin Insulinoma= Increase in C-peptides. Surreptious use= Decrease in C-peptides. |
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Somatostatinoma? effects?
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Inhibition of :
1. Gastrin: Achlorhydria 2. Secretin: Steatorrhea 3. Cholecystokinin: Cholelithiasis, steatorrhea 4. Gastric inhibitory peptide: DM |
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Somatostatinoma: Rx?
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Sx
Streptozotocin |
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Streptozotocin?
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Natural compound toxic to islet b cells
Effective in treating tumors not removable by sx (as a compound has poor curative effect, high toxicity-rarely used) |
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Somatostatinoma: benign/malignant?
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VIPoma? rx?
1. Secretory diarrhea 2. achlorhydria 3. hypokalemia 4. Acidosis- normal anion gap(loss of bicarbonate in stools) Rx: 1. Octreotide 2. Surgery |
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Zollinger ellison syndrome?
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Increased gastrin--> hyperacidity
Peptic ulcers Diarrhea Maldigestion Sr. gastrin> 1000pg/ml |
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ZE: rx?
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PPI
Sx Octreotide |
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ZE syndrome: association?
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MEN-I syndrome
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Diabetes is the MCC of______:
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1. Legal blindness
2. Peripheral neuropathyy 3. CRF 4. BK amputation 5. Multiple CN palsies |
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Diabetes: classification?
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1. Type I
2. Type II 3. IGT 4. GDM 5. MODY 6. Metabolic syndrome |
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Diabetes (secondary): causes?
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1. Pancreatic-
a. cystic fibrosis b. chronic pancreatitis 2. Drugs- a. Glucocorticoids b. pentamidine c. thiazides d. alpha-IFN 3. Endocrine dzs- a. Pheochromocytoma b. glucagonoma c. cushing's syndrome d. somatostatinoma 4. Genetic diseases- a. hemochromatosis b. metabolic syndrome/syndrome X c. MODY 5. Infections- a. Mumps b. CMV |
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MODY: pathology/genetic defect?
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Defect in glucokinase gene(transcription factors expressing such genes)
Impaired glucose induced secretion of insulin |
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MODY- patient population affected?
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Pts<25yrs
Young and NOT obese |
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MODY: features?
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Resistance to ketosis
Impaired glucose induced secretion of insulin |
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MODY: Inheritance?
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AD
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Type 1 DM: Genetics?
Type 2 DM: Genetics? |
Type 1:
HLA-DR3 HLA-DR4 Type 2: None |
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Type 1 DM: associations?
Type 2 DM: associations? |
Type 1 DM:
1. Grave's disease 2. Hashimoto's thyroiditis 3. Perinicious anemia 4. Addison's disease Type 2 DM: None |
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Type 1 DM: Pathogenesis?
Type 2 DM: Pathogenesis? |
Type 1 DM:
T cell mediated destruction of pancreas Autoantibodies against islet cells Type 2 DM: 1. Decreased insulin receptors-->Insulin receptor resistance 2. Post receptor defects: a. Tyrosine kinase defects, b. GLUT-4 defects Early stages have insulinemia--> deficiency of insulin |
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Diabetes type associated with autoantibodies?
Directed against? |
Type I
Directed against: 1. Islet cells 2. Insulin |
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Metabolic syndrome: disease associations?
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1. PCOS
2. Alzheimer's dz 3. Acanthosis nigricans |
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Hyperinsulinemia: effects?
|
1. Hypertriglyceridemia>150 mg/dl
2. Acanthosis nigricans 3. Hypertension- increased sodium retention 4. CAD- direct damage to endothelial cells 5. HDL<40 in men HDL< 50 in women |
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Metabolic syndome: findings?
|
1. Hypertriglyceridemia>150mg/dl
2. Hyperglycemia>110mg/dl(IGT) 3. HDL<40 in M <50 in F 4. Obesity (abdominal girth M>40' F>35') |
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Metabolic syndrome: Rx?
|
1. Statins
2. Htn- ACE inhibitors 3. Weight loss 4. Metformin/thiazolidinediones |
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MCC of death in DM?
|
MI
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Blindness d/t DM- reason?
|
Retinal detachment(?)
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Complications of DM?
|
1. Atherosclerotic dz
2. Renal dz- a. papillary necrosis b. nodular glomerulosclerosis c. Mesangial proliferation and type IV collagen in BM 3. Ocular defects- a. Proliferative retinopathy- Neovascularization Retinal detachment---> blindness b. Non proliferative retinopathy Flame hemorrhages, Microaneurysms Exudates c. Cataracts d. Glaucoma 4. Peripheral neuropathy- a. Sensory- Decreased pinprick sensation Decreased proprioception b. Motor Reduced deep tendon reflexes Muscle weakness 5. Pressure ulcers Rx: Duloxetine Topical capsaicin Amitryptyline 6. Autonomic dysfunction- Gastroparesis Impotence Neurogenic bladder Orthostatic hypotension Rx for gastroparesis: metoclopramide 7. CN affected: CN III, IV, VI 8. Infections- a. UTIs b. Vulvovaginitis- Candida c. Malignant otitis media- P. aeruginosa d. Rhinocerebral mucormycosis e. Cutaneous infections- S. Aureus 9. Necrobiosis Lipoidica Diabeticorum- Fat deposition in the anterior part of leg an dorsum of foot Lipoatrophy- at injection site of insulin(impure) Lipohypertrophy- fat synthesis at insulin inj. site 10. Neuropathic joints (lack of sensation--> joint deformity) |
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Diabetic ketoacidosis: precipitating causes?
|
1. Omission of insulin/ medical illness
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DKA: effects?
|
1. Volume depletion: from Na loss, water(osmotic diuresis)
2. Hyperglycemia: Glucagon and epinephrine 3. Ketone bodies: From acetyl coA(derived from B-oxidation of FAs) 4. Hypertriglyceridemia: Reduced insulin-->reduced LPL activity-->Increased VLDL/Chylomicrons--> Type V hyperlipoproteinemia--> Eruptive xanthoma Acute pancreatitis |
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Acute pancreatitis in DKA due to?
|
Hypertriglyceridemia
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DKA: Laboratory findings?
|
1. Hyperglycemia 250-1000mg/dl
2. Increased HbA1c>6% 3. Dilutional hyponatremia 4. Hyperkalemia (Trans cellular shifts to buffer excess H+ in blood) 5. Anion gap metabolic acidosis: Ketoacidosis/lactic acidosis 6. Prerenal azoteia- vol depletion 7. Hypertriglyceridemia |
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General rx for type I diabetes?
|
Split dose:
Insulin+ NPH 2 doses morning and evening Intensive- Insulin+ NPH in morning Insulin during dinner NPH at bed time Long acting insulin + Lispro |
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Somogyi effect?
|
Hyperglycemia at 3am due to rebound release of
glucagon catecholamines rx by increasing NPH dose |
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Dawn effect?
|
Hyperglycemia at 7am
Due to release of GH at 5am Dividing dose between bedtime and dinner |
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DKA: volume replacement?
|
Vol replacement with 0.9% saline
followed by 0.45% saline + 5% dextrose |
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DKA complication?
|
Respiratory paralysis due to hypokalemia and hypophosphatemia
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Diabetes: lab dx?
|
1. Random blood glucose> 200mg/dl
2. Fasting blood glucose> 126mg/dl 3. 2 hour glucose levels after 75g oral glucose administration>200mg/dl Atleast one of the above should be positive next day for dx. |
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Glycosylated hb?
|
Glycemic control for preceding 8-12 weeks
goal of therapy<7% |
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Gestational diabetes mellitus: cause?
|
HPL
Progesterone Cortisol |
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Gestational diabetes mellitus: screening test?
|
24-28 weeks of gestation
50g glucose-oral--> levels >140mg/dl diagnostic |
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Gestational diabetes mellitus:
Newborn risk factors? Maternal risk? |
Macrosomia: increased fat storage
RDS: insulin inhibits surfactant production NTDs Hypoglycemia Maternal risk: may develop diabetes at a later stage |
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Polyglandular deficiency syndrome?
Types? Inheritance pattern? |
Type I:
AR Addison's dz Prim hypoPTH Mucocutaneous candidiasis Type II: AD HLA DR3, HLA DR4 Addison's Hashimoto's Type I DM |
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Fasting hypoglycemia: causes?
|
1. Alcohol
2. Renal Failure 3. Malnutrition 4. Chronic liver dz 5. Insulinoma 6. Hypopituitarism 7. Ketotic hypoglycemia |
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