Familial hypocalciuric hypercalcemia

Familial hypocalciuric hypercalcemia

Does not have elevated serum calcium level

Treatment: stop intake / steroids reduce GI absorption of calcium

Status post surgical removal of thyroid (with inadvertent PTH gland removal), autoimmune (e.g. as part of polyglandular syndrome) / Wilson’s / iron-storage disease / others

PTH receptor not working / Albright’s / low calcium

1. 
   iatrogenic
   
2. 
   ectopic ACTH (bronchogenic ca) or (pituitary adenoma)
   
3. 
   adrenal tumor (adenoma, carcinoma)
   

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  overnight dexamethasone suppression test (supposedly is able to suppress a pituitary tumor secreting ACTH, but not an adrenal tumor) / fair amount of false positives on dexamethasone suppression test /
  
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  best test to see if patient has elevated cortisol is 24 hr urine cortisol level
  
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  can measure corticotropin levels (best in AM)  < 10 suggests corticotropin-independent tumor
  

young women / 65% of endogenous / single pituitary adenoma or (more often) multiple microadenomas / adrenal glands show bilateral nodules of clear cells with hyperplasia of intervening parenchyma

15% of endogenous Cushing’s syndrome / 50 yrs, men / small cell carcinoma and carcinoid of lung

bilateral adrenalectomy / skin pigment from increased ACTH (POMC) / pituitary adenoma grows from loss of cortisol negative feedback

50 yrs, women / compact and clear cells (fasciculata), eosinophilic cells (reticularis) / contralateral gland atrophic / less in children / 2% of autopsies have non-functional versions / workup for incidentally discovered adrenal mass [NEJM]

40 yrs / 50% of childhood Cushing’s syndrome / 80% function / contralateral gland atrophic / invasive

Always check adrenal function before mechanical manipulation

FNA to distinguish infection vs. primary vs. mets (may or may not obviate open biopsy)

Treatment: doxorubicin, vincristine, prednisone

Prognosis: usually < 1 yr
Primary hyperaldosteronism (PHA)

adrenal adenoma (Conn’s syndrome) (70%) or hyperplastic adrenal gland (30%) / women, 40s / uninvolved cortex is normal (not atrophic) / < 5% will be from carcinoma and ectopic aldosterone production

Note: escape from renal sodium retention limits fluid gain to 1.5 to 2 L (no escape in CHF)

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  plasma aldosterone/renin ratio: taken at 8AM (> 30-50 diagnostic) / spot aldosterone is too variable
  
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  24 hr urine aldosterone is most sensitive, specific to confirm hyperaldosteronism (after 2 wks of no ACE  oral salt loading (saline loading) would normally suppress aldosterone; if not, then positive for primary hyperaldosteronism)
  

may present at puberty (very mild form) / rare in blacks / complete block is fatal

Mechanism: defective p450c21 cannot convert 17-hydroxyprogesterone to 11-deoxycortisol causing ↑ androgens, ↓aldosterone (also increased ACTH and adrenal hyperplasia)

Findings: hyponatremia, hyperkalemia, hypotension, elevated 17-hydroxyprogesterone

girls  stunted growth, virilization (pseudohermaphrodites), infertility

boys  precocious puberty, not-infertile

Treatment: steroids and IV fluids immediately
11-B-hydroxylase

5 % of cases / ↑ androgen, ↑ aldosterone

children / familial / AD / unilateral / glands of normal size / hyperplasia of intranodular area, remaining tissue is normal / diffuse cortical hyperplasia is uncommon

1^st in US (autoimmune, cortex only) / world: Tb / Other causes: sarcoidosis, histoplasma, cocci, CMV/MAI (HIV patients), hemorrhage, adrenal mets (lungs, breast, stomach), lymphoma, leukemia, X-linked adrenoleukodystrophy, myelipoma, cysts

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  Acute: may need D₅NS infusion / hydrocortisone 100 mg q 6-8 hrs
  
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  Long-term: hydrocortisone 20/10 mg/day or solumedrol (methylprednisolone) / may also need mineralocorticoid replacement (fludrocortisone) 0.1-0.2 mg/d
  

stress, abrupt corticosteroid withdrawal, Waterhouse-Friederichsen syndrome (infarction from sepsis, birth-trauma, DIC) / rapid, progressive hypotension leading to shock

? hyponatremia without hypokalemia?

does not have increased pigmentation as POMC is not increased

does not have hyperkalemia as renin-aldosterone axis preserved
Tertiary adrenal insufficiency

impaired secretion of CRH from the hypothalamus

Disorder	Aldosterone	Cortisol	Renin
Primary hyperaldosteronism (Conn’s syndrome)	High	Normal	Low
Secondary hyperaldosteronism	High	Normal	High
Cushing’s syndrome	Low-normal	High	Low
Adrenal insufficiency (Addison’s disease)	Low	Low	High
Pituitary disease	Normal	Low	Normal

chromaffin cells (Zenker’s solution oxidizes catecholamines to brown-black)

40s / (rule of 10s)  10% extra-adrenal, bilateral, mets, familial (MEN II, III)

Pathology: rarely may secrete ACTH more than E, NE / hard to distinguish benign from malignant by appearance / pleomorphism, but infrequent mitoses

Presentation: hypertension may be constant with paroxysmal or intermittent attacks (may be precipitated by a number of events including palpation of the tumor!) or hypotension (from pressure induced natriuresis), headaches, diaphoresis, hyperglycemia (catecholamine suppression of insulin and stimulation of glycogenolysis)

Associations: associated with neurofibromatosis, von Hippel-Lindau (VHL gene), Sturge-Weber and McCune-Albright syndrome / in MEN, there is diffuse or nodular hyperplasia (RET protooncogene)

Diagnosis: urine markers, clonidine suppression test / CT scan / ¹²³I-MIBG

Lab markers (24 hr urine): VMA (may be elevated even without acute hypertension), metanephrines (most sensitive), catecholamines / yield increased if collected during episode / should discontinue any alpha or B-blockers / spot serum levels not a good test due to fluctuations/false positives (if you must use this, patient should rest 30 mins before and must use indwelling catheter to collect venous sample)

Treatment:

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  alpha then beta blockade (avoids crises of hypoperfusion with excess peripheral vascular resistance while heart rate is being b-blocked)
  
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  phenoxybenzamine (irreversible a-blocker begun 1 wk prior to surgical resection)
  
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  may need to give IV nitroprusside for acute HTN
  
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  may need to give volume (if volume depleted)
  

extra-adrenal pheochromocytoma, but does not produce catecholamines / 30s to 60s, sporadic or familial, usually recur / usually have mets (especially retroperitoneal versions) / mitoses absent / encapsulated but adherent, difficult to excise

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  nonfunctioning adrenal mass > 6 cm (35% to 98% carcinoma)  resect
  
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  between 3 and 6 cm  MRI
  
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  smaller than 4 to 6 cm  could be incidentaloma (unknown adrenal mass) [NEJM]
  
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  work up to r/o other primary – includes timed urine catecholamines, dexamethasone (1 mg) suppression test, and androgen/estrogen levels
  
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  unifocal adrenal mets from unknown primary is rare (0.2%), so no need for FNA with no history (lung, breast, stomach, kidney, colon, melanoma, lymphoma), signs, symptoms, radiographic or laboratory findings suggesting an occult malignancy / can follow with serial clinical examinations and abdominal imaging
  

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  For details on specific organisms, please see microbiology or a folder full of bugs
  
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  Case Presentations from Johns Hopkins Infectious Diseases
  

Note: either Ga or In concentrates more in GI, thus making it worse for GI lesions (increased background noise)

septic splenitis, bacteremia, body temperature dysregulation, leukocytosis/leukocytopenia, hypotension, DIC, end-organ damage (DAD, acute renal failure, ATN, heart failure, liver failure)

cerebral malaria, toxic shock syndrome (TSS), C difficile colitis

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  Volume repletion: fluids + PRBC if Hct low
  
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  Hemodynamic support: pressor (levafed for low SVR, may add dopamine for contractility)
  
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  Antibiotics: broad spectrum such as vanc/zosyn, meropenem, etc.
  
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  Steroids: trend toward empirically treating for relative adrenal insufficiency; do cosyntropin stim test 0, 30, 60 upon admission then empirically add hydrocortisone 50 mg q 6 and fludrocortisone 50 ug qd for total 7 days (decreases mortality in some trials)
  
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  Nutrition: Harris-Benedict for caloric intake in a male 66 + (13.7 x wt) + (5 x ht) – (6.8 ? age)
  
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  Other: activated protein C (reduces mortality by 10%)
  

Lactic acid > 4 mmol/L / increased anion gap in only 50% / Type A or B / late marker of ischemic gut

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  make sure they get 2 inches of cath tip for CFU count to determine if primary or secondary catheter infection
  
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  some evidence suggests utility of drawing simultaneous cultures from peripheral and through catheter; if catheter culture grows faster, it suggests infection is line related
  

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  Asymptomatic bacteriuria (50% women, 30% men > 65 yrs): should treat pregnant and immunosuppressed patients (including diabetics)
  

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  Candida in urine / if asymptomatic, changing catheter clears in 40% / treatment with fluconazole or ampho B recommended for immunocompromised, neutropenic, obstruction, invasion of upper pole / bladder washings is only a temporary measure
  

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  Acute uncomplicated cystitis: empiric treatment for women with symptoms of acute cystitis and positive dipstick / fluoroquinolone x 3 days
  
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  Pyelonephritis: IV ceftriaxone then fluoroquinolone (or other) to complete 10 days (change to PO when appropriate)
  
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  Urosepsis: supportive as for any sepsis / ampicillin + gentamicin or imipenem or Zosyn
  

erythema, warmth, and tenderness

distinguished by indurated, elevated margin [dermis]; lymphatic involvement and vesicle formation are common / face and legs; facial may follow URI strep infection

Differentiated from erysipelas by nonelevated, poorly demarcated margins

Local tenderness and regional adenopathy are common; up to 85% of cases occur on the legs and feet (look for sign of entry such as chronic athlete’s foot)

Treatment: nafcillin IV (1 to 2 g q 4-6hrs) for a while (~few days) followed by PO dicloxacillin 250 to 500 mg qid (for another few days or as needed, but with lymphatic/venous insufficiency, you can expect your patient to come back and need more IV nafcillin because you sent them home too early on PO)

Alternative: PO augmentin or Cephalosporins (cephalothin, cephalexin, cephradine)

Vancomycin for MRSA or penicillin allergy

Area involved has a blue-red-purple-red color

mainly in children (face) and sometimes adults (neck or upper chest)

Blood cultures frequently positive

Higher incidence in patients with liver disease (75%) and in immunocompromised hosts (corticosteroids, diabetes mellitus, leukemia, renal failure)

History of exposure to salt water or eating raw seafood

Large hemorrhagic bullae, cellulitis, lymphadenitis, myositis, DIC and septic shock occur frequently / mortality rate over 50% in septic shock

deep-seeded subcutaneous infection  progressive destruction of fascia and fat

diffuse swelling of an arm or leg, followed by bullae filled with clear fluid (maroon or violaceous in color)

Systemic symptoms may include shock and organ failure

CT or MRI is useful in locating the site and depth of infection

Treatment: surgical debridement and antibiotics
Panniculitis

Inflammation of subcutaneous tissue, occasionally complicates alpha-1-antitrypsin deficiency