”FIRST AND FINEST”

Why is my Hyperparathyroid Patient Itching?

LCDR Amie Harvey, MD

LCDR Karen Kaufman, DO

CDR Jason Daily, MD

Naval Medical Center Portsmouth

”FIRST AND FINEST”

Disclaimer• Nothing to disclose• The views expressed in this presentation are

those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense or the United States Government.

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Subjective• 37 year old female with 2 week history of

itchy rash• Fatigue, headaches, nausea, decreased

appetite, constipation

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Medical History• No history of medical problems• No known allergies• No family history of thyroid or parathyroid

disease• No tobacco, alcohol or illicit drug use• No current medications

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Physical Exam• Afebrile; HR 82; BP 125/86; RR 14 • Skin with erythematous, edematous

wheals without central pallor on lower back, chest and upper extremities without facial, periorbital or mucosal swelling

• Thyroid without diffuse enlargement or palpable nodules

• No lymphadenopathy

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Skin Findings

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Laboratory ResultsComplete Blood Count

WBC / mcL 6,000

HgB g/dL 14.1

HCT (%) 41.5

PLT/mcL 188,000

Neutrophils (%) 72.4

Lymphocytes (%) 21.9

Eosinophils (%) 0.0

Basic Metabolic Panel

Na (mmol/L) 141

K (mmol/L) 4.2

Cl (mmol/L) 105

CO2 (mmol/L) 25

BUN (mgl/dL) 12

Cr (mg/dL) 0.8

Ca (mg/dL) 11.4 ♦

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Laboratory Results

Additional Labs

Parathyrin Hormone (pg/mL) 136 ♦ (10-65)

Vitamin D, 25 Hydroxy (ng/mL) 57.3 (30-100)

24 h urine calcium (mg/24h) 366♦ (100-300)

FECA 1.62% ♦Ca ionized (mmol/L) 1.45 ♦ 1.16-1.32

Thyroglobulin AB (IU/mL) <20 <20

Thyroperoxidase AB (IU/mL) 14 <35

Environmental Allergens sIgE Negative

CU index (histamine%) 69 ♦ (<16)

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Diagnosis and Treatment

• Primary Hyperparathyroidism (PHP)– Treatment: Surgical excision

• Chronic Urticaria (CU)– H1 and H2 Antihistamines

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Pathology• 1.2 gram, 3 x 0.9 cm homogenous, light tan

inconspicuous capsule

Parathyroid Adenoma 10x H&E Parathyroid Adenoma 40x H&E

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PHP• Demographics

– Prevalence 1: 1000– More common in

women (2:3)– Most common in 5th or

6th decade

• Symptoms– Skeleton, cortical bone– Nephrolithiasis– Chronic pancreatitis– Polyuria– Polydipsia– Anorexia– Hypertension– Nausea– Vomiting

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CU• Daily, near daily, greater than 6 weeks• Self limited in most patients

– Average duration is 2-5 years– Spontaneous remission at one year for 30%– Persists greater than 5 year in 20%

• Strong Association with Autoimmune disease

Sarbjit S. Saini, Middleton’s Allergy: Principles and Practice 8th edition, 2013: 575-587.Kulthanan K, et al. J Dermatol 2007; 34:294-301.

Kozel MM, et al. J Am Acad Dermatol 2001; 45:387-391.

Toubi E, et al. Allergy 2004; 59:869-873.

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Cutaneous Associations

• Multiple Endocrine Neoplasia Type 1– Angiofibromas (85%)– Collagenomas (70%)– Lipomas– Café-au-lait spots

• Multiple Endocrine Neoplasia Type 2– Cutaneous amyloidosis

• Sporadic Hyperparathyroidism– Metastatic calcification

Fuleihan GE et al : Clinics in Dermatology 2006; 24; 281-288

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PHP and Urticaria

• PHP– Parathyroid hyperplasia (1 case)– Parathyroid Adenoma (3)

• 1st reported case of PHP with urticaria– Reported in JAMA 1983 in 58 year old female

with 1 year of urticaria– 4 gram adenoma

Liechty DR, Firminger HI: JAMA 1983; 250:789-790.

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Previous Theories• 1983 JAMA – “circulating antigen antibody

complexes”– Similar to other necrotic cancers– Hemorrhagic areas, cyst formation, and fibrosis

induce antigen formation• Hypercalcemia

– Induces mast cell degranulation – Induces histamine release

• Calcium infusion did not reproduce urticaria• Urticaria not present in other cases of hypercalcemia

Liechty DR, Firminger HI: JAMA 1983; 250:789-790.

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Subtypes

Urticaria25%

Chronic Urticaria

Chronic Idiopathic

Urticaria (CIU)

Physical Urticaria

Chronic Autoimmune

Urticaria (CAU)

Systemic Disease

Malignancy

Acute Urticaria

EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64:1417-1426.

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• Persuasive, but not conclusive evidence for the existence of autoimmune chronic spontaneous urticaria was found by a European taskforce panel 2013

Konstantinou GN, Asero R, Ferrer M, et al. EAACI taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria. Allergy 2013;68: 27

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CAU Testing• 1986 Autologous Serum Skin Test (ASST)

– Administration and interpretation not standardized

• CU Index testing

Cho , altrich et al. Ann Allergy Asthma Immunol 2013; 110: 29-33.

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CU Index Test• Donor basophils combined with:

– patient’s serum– buffer control – anti-IgE

• Alliquots of cells lysed for histamine content

• Histamine release is measured and compared with total histamine in basophils

Cho , altrich et al. Ann Allergy Asthma Immunol 2013; 110: 29-33.

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CAU

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• Medical Websites• Medical info• http://www.colorectaltumor.com• http://www.genitaldischarge.com• http://www.hepaticcarcinoma.com• http://www.hpvvaccination.com• http://www.ovarydisease.com

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Becky M, et al. Current Allergy and Asthma Reports 2005; 5:270-276.

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Follow up Testing

Postoperative

Calcium 9.0

Parathyroid Hormone

26

CU Index < 16 (negative)

Preoperative

Calcium 11.4 ♦

Parathyroid hormone

136 ♦

CU Index 69 ♦

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Our Case• Resolution of urticaria after adenoma

excision• Resolution of positive index supports IgG

against IgE or IgE receptor is stimulated by parathyroid adenoma

• Further studies of possible subclinical antibody presence in PHP warranted

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Questions?

Thank you.