Transcript Chronic bloating and polyuria plus new onset of “Spells”

44 yo Female with Chronic
Polyuria and New Onset
“Spells”
K Steffen, MD 2/11/04
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Past Medical History
• Anxiety/Depression
• Irritable Bowel
Syndrome
• Tension Headaches
• Genital Herpes
• Allergic rhinitis
• Female Sexual
Dysfunction (low
libido)
• Uncomplicated UTI
approx 1998
• Chronic polyuria
• PMS
Past Surgical History
• Breast Augmentation 1992 with silicone
implants
• Removal and replacement of silicone
implants
• Liposuction of hips, abdomen, thighs
Medications
• Wellbutrin SR 150/75
qod
• Celexa 20 mg qd
• Allegra 60 mg prn
• Rhinocort Nasal spray
• Valtrex 5 mg bid
• Estroven OTC
• Testosterone topical
ointment
• Naprosyn prn
• Tylenol prn
• Livostin eye gtts prn
• Bentyl prn
Allergies
• Sulfa causes hives
• Alesse exacerbates headaches
Social History
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Married, no children
Self-employed consultant
Spends winter months at 2nd home in Florida
3-4X/week curves, walks, bikes, watches weight
carefully
• “Former” (20 pack-yr) smoker, now
“occasionally”
• Wine 5-8/week, no illicit drugs
Family History
• Brother: Diabetes (pt worried she has this)
• Brother: Down’s syndrome
• Father: EtOHism, died of liver cancer
Visit to UW Health 8/28/02
• CC: urinary frequency with abdominal
bloating (Add’l: PMS symptoms, testosterone not
helping libido, vaginal dryness)
Urinalysis:pH 8, 6-10 rbc, neg leuk est, neg
nitrite, 0 wbc, 1 epi, bact +, no culture
HbA1C: 4.6
Glucose: 89
RX: Antibiotic for “UTI”
Visit to UW Health 9/18/02
• CC: f/u UTI and PMS, wants progesterone
cream
UA: pH 7.5, neg leu est, neg nitrite, 0-1 wbc,
11-20 rbc, bact +. >5 epi, no culture
Total testosterone 2 (4-70), free testosterone
0.2 (0.6-6.8)
Rx: Macrobid (different abx from 8/02)
1st Visit with Me 10/10/02
• CC: 1 1/2 mth h/o urinary frequency without
dysuria, abd/R flank pain, now having had “spell”
3 days prior :
– 4-blanket-chills, rigors, flu-like symptoms
– Fever to 102
– Anorexia, vomited once, polydipsia
Exam: P72, BP 112/78 mid-epigastric tender, rest
WNL
DDx? Next step?
10/10/02 Results
RX: Levofloxacin
UA:pH 7, neg leu est, neg nitrite, 6-10 rbc, 0-1 wbc,
1 epi, bact+, culture neg
Blood culture: neg
CBC: wbc 5.6, Hb 12.5, Hct 35, MCV 92
Cr: 0.8
RX: D/C levofloxacin
Ddx? What next?
10/14/02-12/02
• Phone update (10/14): Pt feeling much better
• Cancelled CT scan, changed to IVP for work up of
hematuria ( in part per patient preference -didn’t
think she really needed it- felt she was just
overreacting to symptoms)
• IVP (10/17): normal
• UA: pH 7.5, leu est neg, nitrite neg, 11-20 rbc, 2-5
wbc, 5 epi, bact+
• Cytoscopy/Wash cytology/ 12/02 Urology wrapup: normal
Dx:?menstrual blood contaminant, f/u 3 mths
12/05/02 Clinic Visit with Me
• CC: 3 nights ago: recurrent fevers, 3-4 blanketchills, rigors, temp to 100F, shaking, diaphoresis
with feeling hot after she broke a sweat, full body
aches, HA the next day. 2 nights ago: same sx,
temp to 102. One night ago: fine. Yesterday:
chiropractor found cervical lymph nodes on exam.
Stress, brother died 3 weeks ago.
• Exam: NAD, P 60, BP 110/70, few small cervical
nodes, 5 small lymph nodes R groin, nonimpressive.
• Ddx?? What next??
Selected 12/05/02 Results
• CBC: wbc 5.6, Hb 12.5, HCT 35
• ESR 16
• NA 145, K 2.0, Cl 96, CO2 34, BUN 12, Cr
0.8, glucose 84
• T prot 6.5, D bili 0.2, ALKP 52, AST 20,
ALT 33
• TSH 1.40
• Ddx? What next??
12/05/02 Further “Results”
• Phone conversation: no eating disorder/excessive
exercise, eats red licorice regularly (but NO black
licorice- yuck), has used diuretics in the past but
denies recent diuretic use, no further
spells/episodes, no known h/o HTN ever
• Review: Ddx Hypokalemia/hypernatremia/
metabolic alkalosis
• RX: KCl supplements
12/02/02 & 12/06/02 Results
• Na 143, K 2.1, Cl 97, CO2 34, BUN 11, Cr 0.6,
Mg 2.3
• Serum Osmolality 298
• Urine Cl 52, Cr 57.0, Na 38, K 38, OSM 358
• Aldosterone 61.1 ng/dl (supine 1-16, upright 4-31)
• Renin activity 2.3 (upper limit of normal)
• CT Abd/pelvis: 1.4x2.4 cm R adrenal mass with
>50% washout on delayed images c/w adenoma,
bilateral ovarian cysts
12/13/02 “Curbside” Endocrine
Consult
• Dr. Shenker confirms findings consistent with
aldosteronoma
• D/C KCl supplement
• Start spironolactone 50 mg po tid
• Q 3week electrolytes faxed from home in Florida
• Refer to Dr. Chen for laparoscopic adrenalectomy
after 6 weeks of spironolactone
• Formal endocrine consult 1/28/03
Follow-Up
• Laparoscopic adrenalectomy 2/05/03
complicated by 1 day post-op ileus,
otherwise successful
• Pt presents for intermittent clinic visits with
nonspecific somatic symptoms (including
dysuria-with normal UA) and psychosocial
issues but has normal labs and no more
spells/episodes
Objectives
• Review the differential diagnosis of hypokalemia
• Review hyperaldosteronism and aldosteronoma
(Conn’s syndrome) presentation and diagnosis;
aldosteronoma treatment
• Reminder to take care in interpreting
urinalyses/use of follow- up cultures
*I have no financial disclosures to report*
DDx:Unexplained Metabolic
Alkalosis and HypoK+ & Nl BP
• Diuretics, vomiting, or Bartter’s
• Examine pt for signs of self-induced vomiting
• Urine Cl- <25 in this setting reflects vomiting or
diuretic therapy
• High urine chloride reflects concurrent diuretic
use or Bartter’s--check urine assay for diuretics to
distinguish
?? Bartter’s Syndrome
• No hypertension
• Hypokalemia due to renal K+ wasting
• Weakness, periodic paralysis, polyuria due to
hypoK+
• Autosomal recessive, often presents in childhood
• Elevated plasma renin activity and aldosterone,
hypomagnesemia
Ddx: Hyperaldosteronism: Other
Secondary Causes
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Licorice
Renin-secreting renal tumor
Renal disease
Non-aldosterone mineralocorticoid excess
Ddx: Primary
Hyperaldosteronism
• Aldosteronoma (Conn’s Syndrome) (60%)
• Idiopathic with bilateral micronodular
hyperplasia (40%)
• Glucocorticoid-remediable
hyperaldosteronism with bilateral adrenal
hyperplasia (rare, familial)
• Aldosterone secreting adrenal carcinoma
(rare)
Evaluation of Suspected Primary
HyperAldosteronism
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Clinical Characteristics of
Aldosteronoma
• Hypertension-almost universal
– Case report from 1999 reported 2 cases and referred to
only 10 known and previously documented cases
• BP often very high (160-180’s/105-110’s), but
malignant HTN is rare
• Females>males
• Middle aged, occasionally young persons
Clinical characteristics, continued
• Hypokalemia symptoms (muscle weakness,
fatigue, cramping, muscle paralysis,
polyuria, polydipsia)
• Lack of lower extremity edema
• Blunted circulatory response (postural
hypotension, bradycardia)
Lab Findings
• Hypokalemia (more severe than in adrenal
hyperplasia)
• Mild hypernatremia
• Mild hypomagnesemia is possible
• Mild metabolic alkalosis
• EKG: prolonged QT, U waves (hypoK+)
• Very low plasma renin activity (PRA)
Diagnostic Findings in Primary
Hyperaldosteronism/ Ald’oma
• Ratio of Plasma Aldosterone Concentration
(PAC in ng/ml) to PRA (in ng/ml/hr) is
typically 30-50 (vs 4-10 in essential HTN)
• PAC> 20 ng/dl plus PAC/PRA>30 has sens
and spec 90% for aldosteronoma
Definitive Biochemical Dx of
Primary Hyperaldosteronism
• Confirmation test used in patients with HTN with
positive PRA/PAC screening test
• 3 day high sodium diet load/IV saline infusion
followed by 24 HR urine collection for
aldosterone, K, Na; serum aldosterone
measurement:
– When Urine NA> 200 mEq, aldosterone>14 ug/24hrs
(39 nmol/d), PAC doesn’t fall below 6 ng/dl
(often>10)--then primary hyperaldo is present
Is it Adenoma or Hyperplasia?
• ? Is positive PRA/PAC plus nonsuppression
with saline, plus unilateral adenoma enough
to distinguish aldosteronoma from
hyperplasia?
– Probably in patients less than age 40-50 with
characteristic findings.
– PAC/PRA >32 100% sens, 61 spec for adenoma
in one study/ PAC>20 +PAC/PRA>30, 90%
sens and spec
Adenoma vs. hyperplasia
• Postural test: aldosterone level decreases or
stays the same in aldosteronoma
• Increased levels of aldosterone precursors in
aldosteronoma (18-OH- corticosterone &
18-oxocortisol)
Further Tests
• If no adrenal mass found:
– DEXA suppression test for GRA
– 131-I-iodocholesterol radionuclide scintigraphy (incr
unilateral uptake with aldosteronoma)
– Adrenal vein sampling (absence of mass does not
exclude adenoma (<1cm may not be detected on CT))
• If adrenal mass found but patient over 40 or 50
– Adrenal vein sampling
– 131-I-iodocholesterol scintigraphy
Treatment of Aldosteronoma
• Laparoscopic adrenalectomy
• Non-surgical candidates:
– Spironolactone
– Dietary sodium restriction (<100mEq/day)
– Amiloride if spironlactone intolerant
References
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Biglieiri, E. Spectrum of mineralcorticoid hypertension. Hypertension 1991;17:251-261.
Blumenfeld, J. Diagnosis and Treatment of Primary Hyperaldosteronism. Ann Intern
Med 1994;121:877-885.
Bravo, E et al. The changing clinical spectrum of primary aldosteronism. Am J Med
1983;74:641-651.
Frasert R et al. Conn’s syndrome: no longer a needle in a haystack. Clinical
Endocrinology 1998; 49:709-710.
Ganguly, A. Primary aldosteronism. NEJM 1998;339:1828-1833.
George et al. The Syndrome of Primary Aldosteronism.
Shenker, Yoram. Medical Treatment of Low-Renin Aldosteronism. Endo and Metab
Clinics of North America 1989;18:414-442.
Vantyghem, M et al. Aldosterone-producing adenoma without hypertension: a report of
two cases. European J of Endocrinology 1999;141:279-285.
Young, W et al. Primary aldosteronism: diagnosis and treatment. Mayo Clin Proc
1990;65:96-110.
References, continued
Online:
• Up to Date: ”Approach to the patient with HTN and hypokalemia,” “Urine
Electrolytes in diagnosis of metabolic alkalosis,” “Glucocorticoid-remediable
aldosteronism,” “Licorice and the syndrome of apparent mineralocorticoid
excess, “Unexplained metabolic alkalosis and hypokalemia: Vomiting;
diuretics;Gitelman’s or Barrter’s syndrome
Books:
• Harrison’s Principles of Internal Medicine: “Hypokalemia,” “Aldosteronism”
• Manual of Endocrinology and Metabolism, Lavin Ed.