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

• 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 cultureHbA1C: 4.6Glucose: 89RX: 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 wrap-up:

normalDx:?menstrual blood contaminant, f/u 3 mths

12/05/02 Clinic Visit with Me

• CC: 3 nights ago: recurrent fevers, 3-4 blanket-chills, 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, non-impressive.

• 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

• 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

• 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.