Endocrinology - Pocket medicine

133 terms by aidajoon 

Create a new folder

Advertisement Upgrade to remove ads

source Pocket Medicine

What are the etiologies of panhypopituatarism?

PRIMARY CAUSES
surgery, radiation, tumors (primary,mets), infection, infiltration (sarcoid,hemachromatosis), autoimmune, ischemia (inc Sheehan's syndrome), carotid aneursym, cavernous sinus thrombosis, trauma

SECONDARY (i.e. causes affecting hypothalamic or stalk), tumor (craniopharyngioma), infection, infiltration, radiation, surgery, trauma

How does panhypopituatarism clinically present?

HORMONAL (acute): fatiguable, hypotension, polyuria, polydipsia, (chronic): wt. loss, bradycardia, sexual dysfxn, loss of axillary & pubic, amenorrhea
MASS EFFECT: HA, visual field changes, cranial nerve palsies, galactorrhea
APOPLEXY: sudden HA, N/V, visual field changes, cranial nerve palsies, meningismus, AMS, hypoglycemia, hyptotension

How do you work up hypopituatarism?

HORMONAL STUDIES
chronic: dec target gland hormone, dec/nl pit hormone
acute: target gland hormone may be nl
(partial more common than panhypopit)
PITUATARY MRI

How do you treat hypopituatarism?

Replace deficient hormones (most importantly, adrenal insufficiency and hypothyroidism. If both, give glucocorticoids first, then thyroid to avoid risk of adrenal crisis)

What are the hormones of hypopituatarism?

(1) Dec ACTH (compared to primary: aldosterone preserved, no hyperpigmentation)
(2) Dec TSH (compared to primary: no goiter, dx with both TSH and T4, as TSH may be low, inapprop normal)
(3) Dec Prl
(4) Dec GH (chronic - fatigue, weight gain, osteoperosis. dx with failure of inc GH with stimulus like insulin tolerance test, glucagon stim)
(5) Dec FSH, LH (Sx: dec libido, impotence, a- or oligomenorrhea, infertility. Sx: dec testicular size, lose off axillary, pubic hair. Dx: dec a.m. testoseterone or estradiol, dec FSH/LH - also dec in any acute illness)
(6) Dec ADH (usually in hypothalamic, stalk disease- diabetes insipidus: severe polyuria, mild hyponatremia - Dx: Posm, Uosm, volume status)

What is the etiology of hyperpituatarism?

Adenoma - 60-70% are functional. May cause deficiencies in some trophic hormones via compression.

How does hyperpituatarism present clinically?

Hormone oversecretion: hyperprolicnemia, acromegaly, Cushing's disease, central hyperthyroidism (v. rare)
Mass Effect: HA, visual changes, diplopia, crania neuropathies.

How do you work up hyperpituatitary syndrome?

hormone levels: (PRL, IGF-1, suppression of GH in response to OGT test, ACTH)
MRI
consider: visual field testing, MEN1 testing
watch and wait if: <10mm, no mass effect, no hormonal effects, f/u in 3-6 months

How does hyperprolactinemia present? How do you work it up?

(1) Presents with: amenorrhea, galoctorrhea, infertility, decreased libido, impotence
(2) Work up: PRL, r/o pregnancy, exogenous estrogen, hypothyroidsm, dopamine agonists (psych meds, antiemetic), renal failure (dec clearance), cirrhosis, stress, inc carb diet.
MRI, visual field testing

How do you treat hyperprolactinemia?

(1) if asx, <10mm, follow with MRI
(2) if sx, >10mm
-medical: bromocriptine, cabergoline (dopamine agonist). side effects: n/v, orthostasis, nasal congestion
-surgical: if failed medical, GH co-secretion, neuro sx not improving- transhenoidal surgery
-radiation: if above failed/not tolerable

What is the clinical manifestation of excess GH? How do you work it up?

inc IGF-1-> acromegaly
P/W increased soft tissue, arthralgias, jaw enlarged, HA, carpal tunnel syndrome, macroglossia, hoarse, sleep apnea, amenorrhea, impotence, DM, acanthosis/skin tags, inc sweating, HTN, colonic polyps
W/U: IGF-1 inc, GH not suppressed to OGT

What is the treatment and prognosis for Acromegaly?

TREATMENT: surgery, octreotide, dopamine agonists (if also Prl consecration) pegvisotmant (GH receptor antagonist), radiation
PROGNOSIS: w/o tx, 2-3x inc in mortality, r/o pituatary insufficiency, colon cancer.

What is MEN Type I?

genetics: inactivation of MENIN
Parathyroid (hyperplasia/adenoma->hypercalcemia)
Pancreatic islet Cell (neoplasia-> gastrin, VIP, insulin, glucagon)
Pituatary adenoma (fxn or not)

What is MEN Type 2A?

genetics: RET proto-oncogene
Medullary thyroid carcinoma
Pheochromocytoma
Parathyroid hyperplasia

What is MEN Type 2B?

genetics: RET proto-oncogene
Medullary thyroid carcinoma
Pheochromocytoma
Mucosal & gastrointestinal neuromas

What is PGA Syndrome Type 1?

Polyglandular Autoimmune Syndrome - children
Mucocutaneous candidiasis
hypoparathyroidism
adrenal insufficiency

What is PGA syndrome Type II

Polyglandular Autoimmune Syndrome - adults
adrenal insufficiency
autoimmunte thyroid disease
DM type 1

TSH: what is best for? what may interfere with its interpretation?

Best for primary hypo and hyperthyroidism
(inappropriately normal in central etiologies)
Decreased by dopamine, steroids, severe illness

What does T3 and T4 immunoassays immunoassays measure? What is it influenced by?

Measures the total* serum concentration.
It is influenced by TBG.

What is TBG, and what increases or decreases it?

THyroxine-binding globulin, will cause correlating inc or dec in T4
inc from: estrogens, OCP, pregnancy, hepatitis, opioids, hereditary
dec from: androgens, glucocorticoids, nephritic syndrome, cirrhosis, acromegaly, nicotinic acid, hereditary.

What is the general lab work up approach to thyroid disorders?

TSH-> (if high or low)-> Free T4
if primary hyperthyroidism (low TSH, high FT4)-> RAIU. if no RAIU take up- > serum thyroglobulin

You suspect thyroid disease, but TSH is normal

Consider secondary (central) disease

Decreased TSH, decreased FT4

Central hypOthyroidism

Decreased TSH, normal FT4

subclinical hypERthyroidism

Decreased TSH, increased FT4?

Primary hypERthyroidism -> RAUI
if diffuse, homogeneous take up: Graves
if diffuse, heterogeneous take up: Toxic multi nodular goiter
If focal take up: functioning adenoma
if no take up-> serum thyroglobulin -
if dec: thyrotoxicosis factitia
if inc: thyroiditis strum avarii or Iodine load

Increased TSH, decreased FT4

primary hypOthyroidism
- consider anti-TPO, anti-Tg Abs for Hashimoto's

Increased TSH, normal FT4

subclinical hypOthyroidism

Increased TSH, increased FT4

TSH secreting adenoma (central hypERthyroidism)
or - thyroid hormone resistance

What are causes of hypothyroidism?

PRIMARY (>90%) - dec FT4, inc TSH
- Goitrous: Hashimoto's, s/p thyroiditis, iodine deficiency, Li, amiodarone
- Nongoitrous: surgical destruction, s/p radioactive iodine or XRT, amiodarone

CENTRAL- dec FT4, nl or slight inc TSH
-hypothalamic or pituitary failure (TSH can be of any level, but functionally inactive due to abnormal glycosylation)

How do you test for Hashimoto's thyroiditis?

positive anti-TPO, anti-Tg Abs in most cases

How does hypothyroidism present clinically?

EARLY
weakness, fatigue, arthralagias, myalgias, HA, depression, cold intolerance, weight gain, constipation, menorrhagia, dry skin, coarse hair, brittle nails, carpal tunnel syndrome, delayed DTR, diastolic HTN, hyperlipidemia
LATE
slow speech, hoarseness, loss of outer third of eyebrows, myxedema (inc glycosominoglycans), periorbital puffiness, bradycardia, pleural, pericardial and peritoneal effusions, atherosclerosis.
MYXEDEMA COMA
hypothermia, hypotension, hypoventilation, AMS
LABS
possible hyponatremia, hypoglycemia, anemia, inc LDL, dec HDL, and inc CK

How do you treat overt hypothyroidism?

Levothyroxine, f/u in 5-6 weeks to titrate
Sx can take months to resolve
start low if risk of ischemic heart disease
inc dose for: pregnancy, HRT, dec GI absorption (Fe/Ca supplements, PPI, sucrasulfate, celiac dz, IBD)

MYXEDEMA COMA: First adrenal replacement therapy, T4 IV load then daily, consider T3 if unstable

What are the causes of Hyperthyroidism?

- Graves Disease
- Thyroiditis (subacute/granulomatous, painless/lymphocytic)
- Toxic adenoma (single or multi nodular)
- TSH-secreting pituatary tumor/pituatary resistance to thyroid hormone
- MEDS: amiodarone, iodine-induced, thyrotoxicosis factitia,
- OTHER TUMORS: struma ovarii (3% ovarian dermoid, teratomas), hCG-secreting tumors (e.g. choriocarcinoma), large deposits of metastatic follicular thyroid tumors

What are the specific clinical manifestation of Grave's disease? What are the antibodies involved?

CLINICAL
usually women, usually 40-60
-goiter: diffuse, nontender, w/ bruit
-ophthalmopathy: periorbital edema, lid retraction, proptosis, conjunctivitis, diplopia. A/w smokig.
-pretibial myxedema (infiltrative dermopathy)

ANTIBODIES
TSI or TBII, anti-TPO, anti-thyroglobulin, ANA

What is the clinical presentation of hyperthyroidism? What lab work up would you do?

weight loss, restlessness, sweating, tremor, moist warm skin, fine air, tachycardia, AF, inc frequency of stools, menstrual irregularities, hypereflexia, osteoporosis, stare and lid lag (sympathetic overactivity.
APATHETIC THYROTOXICOSIS - elderly may present with lethargy
THYROID STORM (rare) - delirium, fever, tachycardia, systolic htn w/ wide pulse pressure and dec MAP, GI sx, 20-50% mortality

WORKUP: TSH, FT3, FT4, RAIU scan. Antibodies only in pregnancy
may see hypercalciuria, maybe hypercalcemia, increased AP, anemia

How would you treat hyperthyroidism?

Beta blockers (dec tachy, propanolol dec conversion of T4 to T3)
GRAVES DZ: - methimazole (MMI)- side effects pururitis, rash, arthralgia, fever, N/V, agranulocytosis
- propylthiouracil (PTU) -2nd line, slower, TID. side effects hepatocellular necrosis.
both - high risk of recurrence, check LFTs, WBC, TSH baseline and f/u
- RAI, surgery

TOXIC ADENOMA/TMG - RAI, surgery

THYROID STORM - beta blocker, PTU, iopanoic acid or iodine (using Wolff-Chaikoff effect - thyroid hormone reduced after large iodine load)

OPTHALMOPATHY- ca worsen after RAI, pretreat with prednisone in high risk

SUBCLINICAL- controversial, consider if TSH < 0.1, inc risk for CV dz, osteoporosis

What are causes of thyroiditis?

ACUTE: bacterial infection (rare in US)

SUBACUTE: transient thyrotoxicosis -> transient hypothyroidism -> nl fx
-painful: viral, granulomatouss, de Quervaine (inc ESR, tx NSAIDs, ASA, steroids)
-silent: postpartum, autoimmune, lymphocytic (+anti-TPO)
-other: amiodarone, radiation, palpation thyroiditis (from mechanical damage)

CHRONIC: Hashimoto's, Riedel's (idiopathic fibrosis)

What is Sick Euthyroid Syndrome?

Patient has TFT abnormalities due to severe nonthyroidal illness (may be acquired transient central hypothyroidism)
if working up thyroid in critically ill patients: TSH not reliable, have to measure T4, FT4, T3.
Replacement thyroxine in critically ill not usually helpful unless other s/s of hypothyroidism

What is the risk of thyroid disease in patients on Amiodarone?

Higher dose has higher risk

HYPOTHYROIDISM: 10%, more common in iodine replete areas

HYPERTHYROIDISM: 3% or 10-20% in iodine deficient areas.

What are the risk factors associated with malignancy in a thyroid nodule?

Age: <20 or >70
Sex: male
h/o nec xrt
Exam: hard, immobile mass, size is large
RAIU: cold
U/S: hypoechoic, solid, irregular borders, microcalcification, central blood flow
cervical LAD.

What are the features associative with benign thyroid nodules?

FHx: autoimmune thyroid dz or goiter
hypo- or hyperthyroidism
nodule tenderness

When would you do a screening U/S for thyroid nodules?

FHx of MEN2 or medullary thyroid cancer
PHMx neck XRT
palpable nodules
Multinodular goiter

When would you do an FNA of a thyroid nodule?

if >10mm (or >8mm with irregular borders), micro calcifications, central vasculature. Hx of neck XRT, FHx of MEN2, MTC

What is the clinical approach to thyroid nodule?

Hx: thyroid sx, h/o neck XRT, FHx of MEN2, MTC, autoimmone thyroid dx, goiter
PExam
TSH
U/S
if TSH Low, RAUI
if TSH normal, RAUI cold, or other RF - FNA

Cold nodules, malignant FNA - surgery
Hot nodules: benign toxic adenoma- ablate, resect, or meds
bening: observe or meds, monitor

What is Cushing syndrome versus Cushing's disease?

CUSHING SYNDROME: cortisol excess
CUSHING'S DISEASE: Cushing's syndrome secondary to pituatary ACTH hypersecretion

What are the etiologies of hypercortisolism?

(1) Iatrogenic-exogenous glucocorticoids (most common)
(2) Cushing's disease: pituitary adenoma or hyperplasia
(3) Adrenal tumor: adenoma, (rarely) carcinoma
(4) Ectopic ACTH: SCLC, islet cell tumors, MTC, pheo

How does hypercortisolism present?

NONSPECIFIC: DM, Htn, obesity, oligomenorrhea, osteoperosis

MORE SPECIFIC: central obesity, extremity wasting, dorsocervical fat, moon fancies

MOST SPECIFIC: easy bruising, proximal myopathy, wide striae, hypokalemia

OTHER: depression, insomnia, psychosis, impaired cognition, facial flushing, acne, hirsutism, hyperpigmentation (if also inc ACTH), fungal skin infxn, nephrolithiasis, polyuria

How do you work up Cushing's Syndrome?

(1) SCREEN - 3 options
-24 hr urine free cortisol
-overnight low dose dexamethasone suppression test
-11pm salivary cortisol

(2) Positive in EtOH, acute illness, depression (possible pseudo-Cushings): recheck after resolution or combine 48 hr LD DST + CRH

(3) Positive, or continued strong clinical suspicion
recheck 24hr UFC, THEN
serum ACTH

(4) ACTH high/nl: ACTH dependent
->48hr o/n HIGH dose DST or CRH test

a. NO supression/neg stim: chest & and RI, somatostatin scan: + (ectopic ACTH) - (->Bilat inferior petrosal sinus vein sampling, assess petrosal: peripheral ACTH ratio - will determine if ectopic ACTH or Cushing disease)

b. YES suppress/pos stim: pituatary MRI: + Cushing Dz, - (->BIPSS)

(5) ACTH low: ACTH independent
adrenal CT/MRI for adrenal tumor

How do you treat Cushing's Syndrome?

(1) Tumors (pituatary, adenoma, adrenal, ectopic) - surgery
(2) if not successful
-pituatary XRT
-medical adrenalectomy w/ mitotane or b/l surgical adrenalectomy
-ketoconazole, +/- metyrapone to dec cortisol
(3) Glucocorticoid replacement therapy 6-36 mo for Transphenoidal, lifetime (+mineralocorticioid) if adrenalectomy)

What are the etiologies of Hyperaldosteronism?

PRIMARY: adrenal d/o, renin independent increases
-adrenal hyperplasia 70%, adenoma (Conn's syndrome) 25%, carcinoma 5%, glucocorticoid-remediable adosteronism (GRA)

SECONDARY: extra-adrena d/o, inc is renin dependent
-primary reninism: rening secreting tumor (rare)
-secondary reninism: renovascular disease (Renal artery stenosis, malignant hypertension), dec arterial volume due to edema (CHF, cirrhosis, nephrosis), hypovolemia, diuretics, DM2, Bartter's (=loop diuretic), Gitelman's (=thiazide diuretic)

NONALDOSTERONE MINERALOCORTICOID EXCESS: mimics hyperaldesteronism
-11Beta-HSD deficiency (hydroxysteroid dehydrogenase)
- black licorice (inhibits, 11Beta-HSD), extreme hypercorisolism (overwhelmed 11beta-HSD
- Liddle syndrome (inc distal tubular renal Na channel)
-exogenous mineralocorticoids, some CAH

How does Hyperaldosteronism present?

Mild to moderate Htn (refractory to 3 drugs)
HA, muscle wekaness, polyuria, polydipsia.
hypokalemia (or nl), metabolic alkalosis, mild hypernatremia

How do you work up hyperaldosteronism?

suspected (esp if Htn + hypokalemia, adrenal mass, or its refractory)
-> AM plasma renin and aldosterone

(1) low renin, low aldosterone: NON-ALDOSTERONE MINERALOCORTICOID EXCESS

(2) low renin, high aldosterone, high aldo:renin ratio: PRIMARY HYPERALDOSTERONISM
-> Adrenal CT/MRI:
(a) unilateral: adenoma or carcinoma
(b) none or bilateral--> adrenal vein sampling (if no localizations: hyperplasia, GRA)

(3) high renin, high aldosterone, low ratio: SECONDARY HYPERALDOSTERONISM

How do you treat hyperaldosteronism?

Adenoma/carcinoma - surgery
hyperplasia- spironolactone/eplerone
GRA- glucocorticoids +/- spironolactone

What are the etiologies of adrenal insufficiency?

PRIMARY (Addison's Dz - adrenocortical dz)
-vascular (hemorrhage esp in setting of sepsis, thrombosis, trauma)
-infection (TB, CMV, histoplasmosis)
-neoplasm: metastatic
-autoimmune (including PGA)
-infiltrative (sarcoid, amyloid, hemochromatosis)
-tox (ketoconazole, etomidate, rifampin, anticonvulsants

SECONDARY (pituatary, failure of ACTH - aldo is still intact, given RAALS)
-any cause of hypo-pit
-glucocorticoid therapy, megestrol (progestin w/ corticoid activity)

How does adrenal insufficiency present?

weakness, fatigue, anorexia

PRIMARY ONLY (from no aldo, inc ACTH): orthostatic hypotension (vol. depleted), hyperpigmentation, hyperkalemia

SECONDARY ONLY +/- other hypo-pit sx

How do you work up adrenal insufficiency?

(1) Early am serum cortisol
(2) Standard dose cosyntropin stimulation test (assess whether more ACTH increases cortisol-abnl in primary and chronic secondary, where adrenals atrophied)
(3) Specialized tests of HPA axis: insulin-induced hypoglycemia, metyrapone
(4) other lab abnl: hypoglycemia, eosinophilia, lymphocytosis, +/- neutropenia
(5) ACTH levels
(6) consider imaging: pituitary MRI, adrenal CT

CRITICALLY ILL PT
if hypotension + abs adrenal insuf -> ACTH stim test ASAP
-start corticosteroid early

How do you treat Adrenal Insufficiency?

(1) Acute insufficiency: IVF + hydrocortisone IV
(2) Chronic insufficiency: hydrocortisone PO + fludrocortisone PO (only in primary) + back up dexamethasone

What are the clinical manifestations of pheochromocytoma?

THE 5 P'S:
Pressure (htn, paroxysmal, severe, refractory)
Pain (HA, CP)
Palpitation (tachy, tremor, wt loss, fever)
Perspiration
Pallor (vasoconstriction)

RULE OF 10
10% extra adrenal (paraganglioma-more likely to recur, be malignant)
10% in children
10% multiple or bilateral
10% recur
10% malignant
10% familiar
10% incidentaloma

What syndromes are associated with pheochromocytoma?

MEN 2A, 2B
Von Hippel Lindau
Neurofibromatosis type 1
familial paraganglioma

How do you work up Pheochromocytoma?

(1) 24 hr urine fractionated metanephrines & catecholamines (very Se/Sp)
- false + w/ very ill, Renal failure, OSA, labetalol, TCA, meds w/ sympathomimetics

(2) Plasma free metanephrines (lower specificity)
(3) Adrenal CT/MRI, consider MIBG scintigraphy, PET
(4) Consider genetic testing

How do you treat Pheochromocytoma?

First: alpha blockade (phenoxybenzamine)
+/- beta blockade (usually propanolol)
then surgery

What is the differential diagnosis of Adrenal Incidentalomas?

(1) NONFUNCTIONING MASS
-adenoma, cysts, abscesses, granuloma, hemorrhage, lipoma, myelolipoma, primary or metastatic malginancy
(2) FUNCTIONING MASS
-pheochromocytoma, adenoma (cortisol, aldosterone, or sex horones), nonclassical CAH, other endocrine tumor, carcinoma
(3) NONADRENAL MASS
-renal, pancreatic, gastric, artifact

How do you work up an Adrenal incidentaloma?

(1) R/O SUBCLINICAL CUSHINGS IN EVERYONE
- 1 mg o/n Dex test. If abnl, do confirmatory studies
(2) R/O HYPERALDOSTERONISM IF HTN
- plasma aldo and renin
(3) R/O PHEO IN EVERYONE
- 24hr urine fractionated metanephrines and catecholamines, or plasma free metanephrines
(4) R/O METS or INFECTION if suspicious
- history, CT guided biopsy

What are CT and MRI characteristics that may suggest adenoma vs. carcinoma in adrenal incidentalomas?

BENIGN: small (<4cm), smooth margins, homogenous, hypodense. - follow with periodic scans

SUSPICIOUS: large (>4 cm) or expanding in repeat scans, irregular margins, heterogeneous, dense or vascular, h/o malignancy, young age. - FNA biopsy, repeat in 3 months, or resection

What are the the hypercalcemic disorders that correlate to these lab findings?
(1) High Ca, v. High PTH, low PO4
(2) High Ca, hi or nl PTH, low PO4
(3) high Ca, low PTH, low PO4
(4) high Ca, low PTH, high PO4
(5) high Ca, low PTH, unpredictable PO4

(1) Hyperparathoridism, primary and tertiary
(2) Familial hypocalciuric hypercalcemia
(3) Milk-alkali syndrome, thiazides
(4) Increased bone turnover OR Vit D excess
(5) malignancy

What are the hypocalcemic disorders that correlate to these lab findings?
(1) low Ca, v. high PTH, high PO4?
(2) low Ca, high PTH, low PO4
(3) low Ca, high PTH, high PO4
(4) low Ca, low PTH, high PO4
(5) low Ca, variable PTH, variable PO4

(1) Pseudhypoparathyroidsm
(2) Vit D deficiency
(3) chronic renal failure (secondary hyperparathyroidism)
(4) Hypoparathyroidism
(5) acute calcium sequestration

What are limitations in measuring calcium?

(1) Only ionized calcium reflects physiologic Ca. Serum Ca is influenced by albumin (need to correct or measure directly)
(2) alkalosis increases albumin binding

What are etiologies of hyperparathyroidism (primary and secondary?)

PRIMARY
adenomas (85%), hyperplasia (spont vs MEN 1/2A), carcinoma (<1%)
TERTIARY
after long standing secondary hyperpara (renal failure)-> autonomous nodule (require surgery)
Lithium (inc PTH)

What are the etiologies of familial hypocalciuric hypercalcemia (FHH)?

(1) Inactivating mutation in Ca sensing rec in parathyroid and kidney--> inc Ca set point +/- inc PTH (to a lesser degree than primary hyperpara)
(2) Acquired from autoAb to Ca sensing rec (rare)

FEca <0.01

What are the etiologies of malignancy leading to hypercalcemia?

(1) PTH-related peptide (PTHrP)--> humoral inc Ca of malignancy (e.g. squamous cell cancers, renal, breast bladder)
(2) Cytokines and 1,25 (OH)2D3 (hematological malignancies)
(3) local osteolysis (breast, myeloma)

What are the etiologies of Vitamin D excess hypercalcemia?

grandulomas (sarcoid, TB, histo, Wegener's)--> Inc 1-OH-> inc 1,25 (OH)2D
Vit D intoxication

What is the cause of hypercalcemia due to increased bone turnover?

hyperthyroidism
immobilization + Paget's Dz
Vitamin A

What are the etiologies of Hypercalcemia? What is most common in the inpatient population?

Hyperparathyroidism (primary and tertiary)
Familial Hypocalciuric hypercalcemia (FHH)
Malignancy
Vitamin D excess
Inc Bone Turnover
Thiazides,
Milk Alkali Syndrome
Adrenal Insufficiency

Inpatients: 45% cancer, 25% primary hyperpara, 10% chronic kidney disease--> tertiary hyperapara

What is the clinical manifestation of of hypercalcemia?

BONES, STONES, ABD GROANS, PSYCHIATRIC OVERTONES
(1) bones: osteopenia, fractures, oseitis fibrosa cystic (if severe, inc osetoclast activity->cysts, fibrous nodules, "salt and pepper" on x ray)
(2) stones: nephrolithiasis, nephrocalcinosis, nephrogenic DI
(3) Abd groans: pain, anorexia, N/V/C, pancreatitis, PUD
(4) Psych: fatigue, weakness, depression, confusion, coma, Dec DTR, short QT interval

HYPERCALCEMIC CRISIS: (Ca>13-15): polyuria, dehydration, AMS (Ca toxic to renal tubules, blocks ADH-> vasoconstriction->dec GFR->polyuria but with inc Ca reabsorption-> inc serum Ca-> inc nephrotoxicity and CNS sx)

CALCIPHYLAXIS (calcific uremic arteriopathy): calcification fo media of small-med vessels of dermis & SC fat--> ischemia and skin necrosis
a/w uremia, inc PTH, inc Ca, inc PO4
dx biopsy, poor prognosis
tx: wound care, keep Ca & PO4 nl, avoid supplements

What are the diagnostic studies for Hypercalcemia?

Ca, albumin, ionized Ca, PTH, PO4.
perhaps: PTHrP, 25(OH)2D, Alk Phos, Uca, SPEP, UPEP, ACE, CXR/CT, mammogram

What are the treatments for Hypercalcemia?

(1) NL SALINE (onset hours, duration during Rx, natriuresis inc renal Ca excretion)
(2) FUROSEMIDE (hours, duration during Rx, use only if volume overloaded)
(3) BISPHOSPHONATES (onset 1-2d, lasts 2-3d, inhibits osteoclasts, good for malignancy, careful in renal failure, risk of jaw osteonecrosis)
(4) CALCITONIN (onset hours, lasts 2-3 d, quickly develop tachyphylaxis)
(5) GLUCOCORTICOIDS (onset ays, lasts days, maybe useful in some malignancy, granulomatous disorders and vit D intox)

What is the treatment for asymptomatic primary hyperparathyroidism?

Surgery if young (<50), high serum Ca (>1mg/dL), low kidney function (Cr Cl <60), low bone density (DEXA T score < -2.5)

What are the etiologies of Hypocalcemia?

(1) HYPOPARATHYROIDISM
-sporadic, familial, iatrogenic (thyroid surgery, radiation), Wilson's, hemochromatosis, hypoMg, activating Ca-sensing rec auto-Ab

(2) PSEUDOHYPOPARATHYROIDISM
-Ia and Ib (PTH end organ resistance, thus inc serum PTH), Ia (skeletal abnl, short stature, retardation)
-pseudopseudohypoparathyroidism (1a syndrome but nl Ca & PTH)

(3) VIT D DEFICIENCY (or RESISTANCE)
-nutritional/sunlight, GI dz/fat malabs, drugs (anticonvulsants, rifampin, ketoconazole, 5-FU/leucovorin), genetic (1alpha-hydroxylase, VDR mutations)

(4) CHRONIC RENAL FAILURE (low 1,25(OH)2D production, high PO4 from low clearance)

(5) ACCELERATED NET BONE FORMATION
-postparathyroidectomy, Rx of severe vit D deficiency or Paget's dz, osteoblastic mets

(6) CALCIUM SEQUESTRATION
-pancreatitis, citrate excess (after blood transfusion), acute and severe inc PO4 (ARF, rhabdo, tumor lysis) bisphosphonates

What are the clinical manifestations of Hypocalcemia?

(1) Neuromuscular irritability: perioral paresthesis, cramps, Chvostek's sign (tap facial nerve->contract facial muscles), Trousseau's sign (inflate BP cuff->carpal spasm), laryngospasm; irritibility, depression, psychosis, inc ICP, seizures, inc QT

(2) Rickets/Osteomalacia: chronic dec Vit D-> dec Ca, PO4-> dec bone mineralization, growth failure, bone pain, muscle weakness

(3) Renal osteodystrophy (dec Vit D, inc PTH in renal failure), osteomalacia, and osteitis fibrosa cystica (due to inc PTH)

What are the diagnostic studio for hypocalcemia?

Ca, alb, ionized Ca, PTH, 25-(OH)-D, 25-(OH)2-D (if renal failure or rickets), Cr, Mg, PO4, Alk Phos, Uca

How do you treat hypocalcemia?

(1) SYMPTOMATIC
-IV Ca gluconate + calcitriol (most effective in acute, but takes hrs) +/- Mg

(2) ASYMPTOMATIC OR CHRONIC
-oral Ca + Vit D. If +calcitriol, consider thiazide

(3) CHRONIC RENAL FAILURE
-phosphate binder + oral Ca, calcitriol or analog (calcimimetic later to prevent hypercalcemia)

What is the definition of Diabetes Mellitus?

(1) Fasting glc >/= 126
(2) random glc >/= 200 x 2 (or once if very high + metabolic decompensation)
(3) 75 g OGTT w/ 2h glc >/= 200 (not the routine OGTT)
(4) NOT OFFICIAL: HbA1C>6.5

What is the definition of "prediabetes"? How do you proven progression to dm?

(1) impaired fasting glc: 100-125
(2) impaired glc tolerance: 140-199 2h after 75 g OGTT

Diet and exercise (58% dec), metformin (31% dec), TZD (60% dec)

What are the categories of Diabetes?

(1) Type I: islet cell destruction, abs insulin deficiency, ketosis if no insulin, inc risk with FHx, HLA associations, usually childhood onset (not always), have anti-GAD, anti-islet cell, anti-insulin autoantibodies. Prevalence is 0.4%

(2) Type II: insulin resistance + relative insulin deficiency; gradual onset later in life; inc risk if +FHx, obesity, sedentary, no HLA association. prevalence is 8%

(3) Type II DM p/w DKA (ketosis prone type 2 diabetes): most often i nonwhite, +/- anti-GAD Ab, eventually may not need insulin

(4) MODY (mature onset diabetes of the young): autosomal dominant, forms of DM due to defects in insulin secretion genes, heterogeneous

(5) Secondary causes of DM: exogenous glucocorticoids, glucogonoma (3Ds: DM, DVT, diarrhea), pancreatic (pancreatitis, hemochromatosis, CF, resection), endocrinopathies (Cushing's, acromegaly), gestational, drugs (PI, atypical antipsychotics)

What are the diabetes treatment options?

(1) Diet (carb counting, wt reduction, exercise)
(2) Metformin
(3) Sulfonylureas
(4) Thiozolididnediones (PPAR gama agonists)
(5) glinides
(6) exenatide
(7) alpha-glucosidase inhibitors
(8) pramlinitide
(9) DPP-4 inhibitor
(10) insulin

Metformin: what is its effect, adverse effects, contraindication, general use?

EFFECT: dec hepatic gluconeogenesis, dec HbA1C ~1.5%
ADVERSE: weight neutral, N/V/D, rare lactic acidosis
CONTRA: renal (Cr > 1.5) or liver failure
USE: first line Rx with lifestyle for all T2D wit HA1C>7%

Sulfonylureas: what is its effect, adverse outcomes?

EFFECT: inc insulin secretion, dec HbA1C 1.5%
ADVERSE: weight gain, hypoglycemia

Thiazolidinediones (PPAR gamma agonists): what is its effect, adverse effects, contraindication?

EFFECT: inc insulin sensitivity in muscle, adipose, dec HbA1C 1%
ADVERSE: Weight gain, hepatotoxicity, fluid retention, CHF, bone factures, ?inc risk of MI (rosiglitazone, not pioglitazone)
CONTRA: liver disease, NYHA III-IV, monitor LFTs

Glinides: effect, adverse effects?

EFFECTS: inc insulin secriteion, dec HbA1C 1.5%
ADVERSE: hypoglycemia (less than SU), wt gain

Exenatide: effect, adverse effects?

EFFECTS: inc glc depend insulin secretion (GLP-agonist), dec HbA1C 0.5%
ADVERSE: wt loss, N/V/D, pancreatitis (rare)

alpha-glucosidase inhibitor: effect, general use?

EFFECTS: dec intestinal CHO absorption, dec HbA1C 0.5-0.8%
GENERAL USE: as adjunctive Rx w/ insulin in T1D or T2D

DPP-4 inhibitor: effect?

blocks degradation of GLP-1 and GIP-> inc insulin, dec HbA1c 0.5%

Insulin: adverse effects, use?

ADVERSE: hypoglycemia, weight gain
USE: T1D - intermed/long acting (NPH or glargine) and short/rapid (regular or lispro)
T2D- consider if mono oral Rx not adequate (esp if high HbA1C), start if combo oral Rx not adequate

What is the onset, peak, duration and time of use of Lispro and aspart?

ONSET: 5-15 min
PEAK: 60-90 min
DURATION: 2-4 h
USE: immediate before a meal

What is the onset, peak, duration and time of use of Regular insulin?

ONSET: 30-60 min
PEAK: 2-4 hr
DURATION: 5-8 h
USE: 30 min before a meal

What is the onset, peak, duration and adverse effects of use of NPH?

ONSET: 1-2 h
PEAK: 4-8 h
DURATION: 12-18 h
SIDE EFFECT: can cause protamine Ab production

What is the onset, peak, duration and time of use of glargine?

ONSET: 2 h
PEAK: no peak
DURATION: 20-24 h
USE: Once daily (am or pm)

What are the types, presentation of diabetic retinopathy? What is the treatment?

(1) Non-proliferative
-"dot & blot", retinal hemorrhages, cotton-wool/protein exudates

(2) proliferative
- neovascularizations, vitreious hemorrhage, retinal detachment, blindness

TREATMENT: photocoagulation, surgery

What is the usual progression of diabetic nephropahty? What is the histological pattern? How is it related to retinopathy? What is the treatment?

(1) microalbuminuria--> proteinuria +/- nephrotic syndrome -> renal failure
(2) diffuse glomerular basement membrane thickening/nodular pattern (Kimmelstiel-Wilson)
(3) Accompanies retinopathy. If not, suspect other cause
(4) strict BP control with ACEI or ARB, low protein diet, dialysis or transplant.

What are the types of diabetic neuropathy?

(1) symmetric peripheral: symmetric distal sensory loss, paresthesias +/- motor loss
(2) Autonomic: gastroparesis, constipation, neurogenic bladder, ED, orthostasis
(3) mononeuropathy: sudden-onset peripheral or CN deficit (e.g. foot drop, CNIII>VI>IV)

What are the common infectious risks of diabetes?

UTI, osteomyelitis of foot, candidiasis, mucormycosis, necrotizing external otitis

What are the dermatologic risks of diabetes?

- necrobiosis lipoidica diabeticorum
-lipodystrophy
-acanthosis nigricans

What are the complications of Diabetes?

RETINOPATHY
NEPHROPATHY
NEUROPATHY
ATHEROSCLEROSIS (coronary, cerebral, peripheral)
INFECTIONS
DERMATOLOGIC

What are the Outpatient screening and treatment goals of Diabetes?

(1) HbA1C <7%
(2) Yearly microalbuminuria test, Spot microalbumin/Cr ratio <30%
(3) Cardiovascular: BP <130/80, LDL <100, TG<150, HDL >40.
(4) Consider: Statins helpful even w/o CAD, ASA if age >50 (men)/>60 (women)
(5) Retinal, foot exam yearly

Overview: What is the management of hyperglycemia in Inpatients?

(1) Reversible causes? (IVF, steroids, post op, carb diet)
(2) Tests: BG (fasting, qAC, qHS or q6h if NPO), HA1C
(3) Goals: avoid hypoglycemia, and extreme hyperglycemia <180
(4) Modify outpatient treatment
- T1D: maintain basal insulin (or risk DKA)
- T2D: stop PO DM meds
(5) Inpt insulin, use outpt as guide. If naive:
- total daily=wt(kg) / 2
- half as basal (long acting), target fasting
- half as short acting (pre-meal, sliding scale) (then adjust)
(6) Discharge plan: keep outpatient unless indication otherwise.

What are the likely precipitants of DKA?

The 6 I's :

INSULIN DEFICIENCY
IATROGENESIS (glucocorticoid)
INFECTION (pna, uti) )
INFLAMMATION (pancreatitis, cholecystitis)
ISCHEMIA/INFARCTION (mi, cerebral, gut)
INTOXICATION (etoh, drugs)

What is the pathophysiology of DKA?

occurs in T1D/ketosis prone T2D
(1) inc glucagon, dec insulin
(2) hyperglycemia: inc glucneogenesis, glycogenolysis, dec uptake into cells
(3) ketsosis: insulin def-> mobilize, oxidize FA, inc substrates for ketogenesis, inc ketogenic state of liver, dec ketone clearance

How does DKA present?

(1) polyuria, polydypsia
(2) dehydration: tachycardia, hypotn, dry
(3) N/V/abd pain (from inc abd pressure, dka), illeus.
(4) Kussmaul respirations (deep, to compensate metabolic acidosis) with acetone odor,
(5) change MS (somnolence, stupor, coma)
- mortality ~1%

What are the things you should track in DKA?

(11 things)
Vital signs
Urine output
pH
HCO3
AG
Ketones (betaOHB, or acetaldehyde by nitroprusside)
Glc
K
PO4
IVF
Insulin

How does DKA present on diagnosistic studies?

(1) anion gap metabolic acidosis (later non-AG from urinary loss of ketones and fluid resusc with chlorine)
(2) ketosis: in urine and serum (beta-OHB, or acetaldehyde if measured by nitroprusside) Urine ket may be + in nl fasting patients
(3) Inc serum glc, BUN/Cr (dehydration)
(4) pseudohyponatremia
(5) inc or dec K (dec* total body K), dec total body phos
(6) inc WBC, amylase

how do you correct for pseudohyponatremia in DKA?

corrected Na= measured Na + [2.4x(measured glc-100)/100]

how do you treat DKA?

(1) r/o precipitants
(2) aggressive hydration: NS 10-14 ml/kg/h (adjust for dehydration and CV)
(3) Insulin (10 U IV push, then 0.1 U/kg/h - cont until AG normal
-if glc <250, AG still high, add dextrose too)
(4) Electrolyte repletion
- K: 20-40meq/L IVF if K <4.5 (note insulin promotes K entry to cells, will see dec in serum K)
-HCO3? if pH<7, cardiac instability
-PO4: if <1

What is the definition of Hyperosmolar hyperglycemic state? precipitants?

(1)
-extreme hyperglycemia, w/o ketoacidosis
-hyperosmolar
-ms changes in T2D (typically elderly)
(2) 6Is, but also, dehydration, renal failure

What is the pathophysiology of hyperosmolar hyperglycemic state?

hyperglycemia-> osmotic diuresis -> vol depeltion ->prerenal azotemia -> inc glc, etc

how does hyperosmolar hyperglycemia present (including studies)?

volume depletion, MS change
inc serum glc (>600)
inc serum osm (>320)
- effective Osm = 2 x Na (mEq/L) + glc (mg/dL)/18
no ketoacidosis (usually inc BUN/Cr)

How do you treat hyperosmolar hyperglycemia?

(1) r/o preciptants (15% mortality from these)
(2) aggressive hydration NS, then 1/2NS, avg body fluid loss is 8-10 L
(3) Insulin (10 u IV push, then 0.05-0.1 u/kg/h)

What are the etiologies of hypoglycemia?

DIABETICS
(1) excess meds, missed meals, renal failure (dec med clearance)
-beta blockers mask sx of hypoglycemia
NONDIABETICS
(2) inc insulin (exogenous, sulfonyureas, insulinoma, anti-insulin antibodies)
(3) dec glucose production: hypopit, AI, glucagon def, heaptic failure, renal failure, CHF, etoh-ism, sepsis
(4) Inc IGF-II: non-islet tumor
(5) post-parandial (esp postgastrectomy, gastric bypasss, excess response to glc load)
(6) low glc w/o sx can be normal

What are the clinical manifestations of hypoglycemia?

(1) CNS: ha, visual change, ms change, weakness, sz, LOC (neuroglycopenic sx)
(2) Autonomic: diaphoresis, palpitations, tremor (adrenergic)

How do you evaluate hypoglycemia? (nondiabetic)

CLINICALLY ILL
check BUN, Cr, LFTs, TFTs, IGF-I/II ratio as needed

OTHERWISe
-72h fast with monitored glc (stop for neurolgycopenic sx)
-At time of hypoglycemia, check insulin, C peptide (up w/insulinoma, sulfonylureas, down w/ exogenous insulin), beta-OHB, solfonylurea
-at end of fast, give 1 mg glucagon IV, measure plasma glc response before feeding

How do you treat hypoglycemia?

(1) POs: juice, paste, glc tablets
(2) IV 25-50g D50
(3) no IV: glucagon 0.5-1 mg IM or SC (side effect N/V)

What is a lipoprotein?

lipids (cholesterol esters & trigycerideds)
+ phospholipids
+ proteins
include: chylomicron, VLDL, IDL, LDL, HDL, Lp(a)

How is cholesterol measured and what are some relevant considerations?

(1) measure after 12 hr fast
(2) LDL is calculated = TC - HDL - (TG/5) but if LDL >400, order direct since calc is inaccurate.
(3) lipid levels stable up to 24 hr after ACS/acute illness, then dec (up to 6wk to normalize)

What are the criteria for metabolic syndrome?

At least 3 of these:
(1) waist >/= 40" (m) or 35" (w)
(2) TG >/=150, HDL <40 (m) or <50 (w)
(3) BP >/= 130/85
(4) FBG >/= 100

What are the secondary dyslipidemias?

ENDOCRINOPATHIES
-DM2 (high TG, low HDL)
-hypothyroidism ( inc LDL, inc TG)
-hyperthyroidism (dec LDL)
-cushing/exogenous steroids (inc TG)

RENAL DISEASE
-RF (inc TG)
-nephrotic syndrome (inc LDL)

HEPATIC DZ
-cholestasis, PBC (inc LDL)
-Liver failure (dec LDL)
-acute hepatitis (inc TG)

LIFESTYLE
-obesity (inc TG, dec HDL)
-sedentary (dec HDL)
-etoh (inc TG, inc HDL)
-tobacco (dec HDL)

MEDICATIONS
-thiazides (inc LDL)
-beta blockers (inc TG, dec HDL)
-estrogens (inc TG, inc HDL)
-protease inhibitors (inc TG)

What are they primary dyslipidemias?

(1) FH - familial hypercholesterolemia (1:500) deffective LDL rec, super high chol, nl TG, inc CAD

(2) FDB- familial defective apoB100 (1:1000) similar

(3) FCH - familial combined hyperlipidemia (1:2000) polygenic, inc chol, TG, CAD, dec HDL

(4) FDBL - familial dysbetaliproteinemia (1:10K) apo E eta2/eta2 + DM, obesity, renal dz, etc - inc chol, TG, CAD; tuberoeruptive and palmar striated xanthomas

(5) FHTG - familial hypertriglyceridemia (1:500): inc TG, +/- inc chol, dec HDL, pancreatitis

What are the physical exam findings in lipid disorders?

(1) Tendon xanthomas-achilles, elblows hands (LDL >300)
(2) eruptive xanthomas: pimple like lesions on extensor surface (TG>1000)
(3) xanthelesma: yellowish streaks on eyelids in various dyslipidemias
(4) corneal arcus: esp in older peeps, if in younger implies hyperlipidemia

What is the pay off for reducing LDL? What are the goals?

Every 39mg/dL dec LDL-> 21% redux major vascular event (CV death, MI, stroke, revasc)

GOALS -from NCEP guidelines, framingham 10 yr CHD risk

HIGH RISK (chd, cvd, pad, aaa, dm, or >/= 2RF & 10y risk>20%)
goal LDL <100 or <70 if very high risk

MOD HIGH >/=2RF &10y risk 10-20%
goal LDL <130 (optional 100)

MODERATE >/=2RF &10y risk <10%
goal LDL <130

Lower 0-1RFs
goal LDL <160

RF: >/=45 yo (m), 55yo (w); smoking; htn; +FH; HDL <40. If HDL>60 -1RF

What is the expected effect and side effects, other considerations of statins?

dec LDL: 20-60%
inc HDL: 5-10%
dec TG: 10-25%

inc aminotransferases 05-3% of peep, risk dose dependent
(check LFTs before, 8-12 wks, the q6mo)

myalgias <10% (not always inc CK), myositis 0.5%, rhabdo <0.1%, dose dependent

dbl dose -> 6% dec in LDL

What is the expected effect and side effects, other considerations of ezetimibe?

dec LDL: 15-20%

well tolerated

What is the expected effect and side effects, other considerations of fibrates?

dec LDL: 5-15%
inc HDL: 5-15%
dec TG: 35-50%

myopathy risk increases w/ statin

What is the expected effect and side effects, other considerations of niacin?

dec LDL: 10-25%
inc HDL: ~30%
dec TG: 40%

flushing (tx w/ASA)
pruritis
inc glc
goute
nausea
severe hepatitis (rare)

What is the expected effect and side effects, other considerations of resins?

dec LDL: 20%
inc HDL: 3-5%
dec TG: ?inc

bloating, binds other meds

What is the expected effect and side effects, other considerations of omega3 FAs?

dec LDL: inc 5%
inc HDL: 3%
dec TG: 25-30%

dyspepsia, diarrhea

Please allow access to your computer’s microphone to use Voice Recording.

Having trouble? Click here for help.

We can’t access your microphone!

Click the icon above to update your browser permissions above and try again

Example:

Reload the page to try again!

Reload

Press Cmd-0 to reset your zoom

Press Ctrl-0 to reset your zoom

It looks like your browser might be zoomed in or out. Your browser needs to be zoomed to a normal size to record audio.

Please upgrade Flash or install Chrome
to use Voice Recording.

For more help, see our troubleshooting page.

Your microphone is muted

For help fixing this issue, see this FAQ.

Star this term

You can study starred terms together

NEW! Voice Recording

Create Set