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44 yo Female with Chronic Polyuria and New Onset “Spells”

44 yo Female with Chronic Polyuria and New Onset “Spells”. K Steffen, MD 2/11/04 Suggestion: Wait to look at handout until case presentation complete. Anxiety/Depression Irritable Bowel Syndrome Tension Headaches Genital Herpes Allergic rhinitis. Female Sexual Dysfunction (low libido)

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44 yo Female with Chronic Polyuria and New Onset “Spells”

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  1. 44 yo Female with Chronic Polyuria and New Onset “Spells” K Steffen, MD 2/11/04 Suggestion: Wait to look at handout until case presentation complete

  2. Anxiety/Depression Irritable Bowel Syndrome Tension Headaches Genital Herpes Allergic rhinitis Female Sexual Dysfunction (low libido) Uncomplicated UTI approx 1998 Chronic polyuria PMS Past Medical History

  3. Past Surgical History • Breast Augmentation 1992 with silicone implants • Removal and replacement of silicone implants • Liposuction of hips, abdomen, thighs

  4. 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 Medications

  5. Allergies • Sulfa causes hives • Alesse exacerbates headaches

  6. 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

  7. Family History • Brother: Diabetes (pt worried she has this) • Brother: Down’s syndrome • Father: EtOHism, died of liver cancer

  8. 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”

  9. 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)

  10. 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?

  11. 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?

  12. 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: normal Dx:?menstrual blood contaminant, f/u 3 mths

  13. 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??

  14. 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??

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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*

  20. 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

  21. ?? 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

  22. Ddx: Hyperaldosteronism: Other Secondary Causes • Licorice • Renin-secreting renal tumor • Renal disease • Non-aldosterone mineralocorticoid excess

  23. 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)

  24. Evaluation of Suspected Primary HyperAldosteronism

  25. 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

  26. Clinical characteristics, continued • Hypokalemia symptoms (muscle weakness, fatigue, cramping, muscle paralysis, polyuria, polydipsia) • Lack of lower extremity edema • Blunted circulatory response (postural hypotension, bradycardia)

  27. 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)

  28. 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

  29. 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

  30. 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

  31. 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)

  32. 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

  33. Treatment of Aldosteronoma • Laparoscopic adrenalectomy • Non-surgical candidates: • Spironolactone • Dietary sodium restriction (<100mEq/day) • Amiloride if spironlactone intolerant

  34. 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.

  35. 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.

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