J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website http://www.jofem.org

Case Report

Volume 8, Number 2-3, May 2018, pages 47-51

Non-Anti-Neutrophil Anti-Cytoplasmic Antibodies Associated Methimazole-Induced Nephritis: Case and Review of Literature

Figure 1. Representative images from the kidney biopsy demonstrate glomerular crescents. (a) An epithelial crescent is seen in the lower half of the glomerular area (H&E stain). (b) The PAS stain highlights the glomerular tufts and the Bowman’s capsule. The urinary space between these structures contains an epithelial crescent (asterisks). (c) The Jones silver stain highlights an organizing crescent (fibro-epithelial crescent) in the left and lower glomerular areas. The glomerular tufts appear compressed.

**Table 1.** Significant Lab Values on Admission Compared to Baseline
Lab and normal range	Baseline	On hospital admission
H: high.
Creatinine (0.66 - 1.25 mg/dL)	0.84	21.9 (H)
BUN (6 - 20 mg/dL)	10	28 (H)
Urine analysis
Protein (trace) (10 - 20 mg/dL)	Trace	3+ (H)
WBC (0 - 5/hpf)	0 - 5	26 - 50 (H)
RBC (0 - 2/hpf)	0 - 2	3 - 5 (H)

Table 1. Significant Lab Values on Admission Compared to Baseline

Lab and normal range

Baseline

On hospital admission

H: high.

Creatinine (0.66 - 1.25 mg/dL)

0.84

21.9 (H)

BUN (6 - 20 mg/dL)

28 (H)

Urine analysis

Protein (trace) (10 - 20 mg/dL)

Trace

3+ (H)

WBC (0 - 5/hpf)

0 - 5

26 - 50 (H)

RBC (0 - 2/hpf)

0 - 2

3 - 5 (H)

**Table 2.** Significant Lab Values on Admission With No Baseline Comparison
Lab and normal range	On hospital admission
H: high.
SSA AB (0 - 0.9 ZZ)	> 8.0 (H)
SSB AB (0 - 0.9 ZZ)	> 8.0 (H)
TSH (0.47 - 4.68 mIU/L)	0.005 (L)
Free thyroxine (0.7 - 1.9 ng/dL)	2.41 (H)
Total T4 (5.1 - 13.8 µg/dL)	7.5
Urea (9 - 20 mg/dL)	211 (H)
C-reactive protein (0 - 10 mg/dL)	11 (H)
CRP high sensitivity (< 3.00 mg/L)	> 15.00 (H)
Erythrocyte sedimentation rate (0 - 15 mm/h)	119 (H)
LDH (313 - 618 units/L)	778 (H)
Amylase (48 - 133 units/L)	269 (H)
Lipase (23 - 300 units/L)	402 (H)
C3 (90 - 165 mg/dL)	85 (L)
C4 (10 - 40 mg/dL)	28
Total complement CH50 (42 - 62 U/mL)	66 (H)
Histopathological IgG4 plasma cells (> 10/hpf)	19 (H)
Gamma globulin fraction (0.4 - 1.6 g/dL)	2.0 (H)

Table 2. Significant Lab Values on Admission With No Baseline Comparison

Lab and normal range

On hospital admission

H: high.

SSA AB (0 - 0.9 ZZ)

> 8.0 (H)

SSB AB (0 - 0.9 ZZ)

> 8.0 (H)

TSH (0.47 - 4.68 mIU/L)

0.005 (L)

Free thyroxine (0.7 - 1.9 ng/dL)

2.41 (H)

Total T4 (5.1 - 13.8 µg/dL)

7.5

Urea (9 - 20 mg/dL)

211 (H)

C-reactive protein (0 - 10 mg/dL)

11 (H)

CRP high sensitivity (< 3.00 mg/L)

> 15.00 (H)

Erythrocyte sedimentation rate (0 - 15 mm/h)

119 (H)

LDH (313 - 618 units/L)

778 (H)

Amylase (48 - 133 units/L)

269 (H)

Lipase (23 - 300 units/L)

402 (H)

C3 (90 - 165 mg/dL)

85 (L)

C4 (10 - 40 mg/dL)

Total complement CH50 (42 - 62 U/mL)

66 (H)

Histopathological IgG4 plasma cells (> 10/hpf)

19 (H)

Gamma globulin fraction (0.4 - 1.6 g/dL)

2.0 (H)

**Table 3.** A Comparison of Findings Among the Three Papers
Case number	1 [8]	2 [9]	Present case
ANA: anti-neutrophil; ANCA: anti-neutrophil anti-cytoplasmic antibodies; C: complement; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; N/A: presence or absence of finding not specified.
Presence of rash	Yes	Yes	No
ANCA positivity	No	No	No
ANA positivity	No	N/A	Yes
Anti-dsDNA positivity	No	N/A	No
Anti-glomerular basement membrane positivity	N/A	No	No
Serum cryoglobulin	N/A	Yes	No
Hepatitis C	N/A	No	No
C3 levels	N/A	Low	Low
C4 levels	N/A	Low	WNL
Other findings	CRP 23.7 (H) ESR WNL	CRP 114 mg/L (H) ESR 25 mm/h (H) Creatinine 6.32 mg/dL (H)	CRP 14 mg/L (H) ESR 119 mm/h (H) Creatinine 21.9 mg/dL (H) SSA/SSB negative IgG4 plasma cells 19/hpf (H)

Table 3. A Comparison of Findings Among the Three Papers

Case number

1 [8]

2 [9]

Present case

ANA: anti-neutrophil; ANCA: anti-neutrophil anti-cytoplasmic antibodies; C: complement; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; N/A: presence or absence of finding not specified.

Presence of rash

Yes

ANCA positivity

ANA positivity

N/A

Yes

Anti-dsDNA positivity

N/A

Anti-glomerular basement membrane positivity

N/A

Serum cryoglobulin

N/A

Yes

Hepatitis C

N/A

C3 levels

N/A

Low

C4 levels

N/A

Low

WNL

Other findings

CRP 23.7 (H)
ESR WNL

CRP 114 mg/L (H)
ESR 25 mm/h (H)
Creatinine 6.32 mg/dL (H)

CRP 14 mg/L (H)
ESR 119 mm/h (H)
Creatinine 21.9 mg/dL (H)
SSA/SSB negative
IgG4 plasma cells 19/hpf (H)

**Table 4.** Summary of Causes and Outcomes of Vasculitis or Interstitial Nephritis Induced by Methimazole or Its Pro-Drug Form Carbimazole in Reported Cases
Case number	1	2	3
HD: hemodialysis; MMI: methimazole.
Author	Kanat et al [8]	Day et al [9]	Present case
Patient age (years)/sex	56/M	72/M	27/M
Etiology of underlying hyperthyroidism	Unspecified	Unspecified	Graves’ disease
Medication dosage/duration	MMI 20 mg daily/1 week	Carbimazole 20 mg daily/2 weeks	MMI 10 mg daily/6 months
Biopsy findings	1) Cutaneous leukocytoclastic vasculitis	1) Cutaneous leukocytoclastic vasculitis 2) Interstitial nephritis w/eosinophils	1) Chronic tubulointerstitial nephritis w/crescentic changes
Cessation of offending drug and commencement of steroids	Yes	Yes	Yes
Thyroidectomy	No	No	Yes
Outcome	1) Cutaneous rashes resolved	1) Cutaneous rash improved 2) HD dependent	1) Pleural effusions resolved 2) HD dependent

Table 4. Summary of Causes and Outcomes of Vasculitis or Interstitial Nephritis Induced by Methimazole or Its Pro-Drug Form Carbimazole in Reported Cases

Case number

HD: hemodialysis; MMI: methimazole.

Author

Kanat et al [8]

Day et al [9]

Present case

Patient age (years)/sex

56/M

72/M

27/M

Etiology of underlying hyperthyroidism

Unspecified

Graves’ disease

Medication dosage/duration

MMI 20 mg daily/1 week

Carbimazole 20 mg daily/2 weeks

MMI 10 mg daily/6 months

Biopsy findings

1) Cutaneous leukocytoclastic vasculitis

1) Cutaneous leukocytoclastic vasculitis
2) Interstitial nephritis w/eosinophils

1) Chronic tubulointerstitial nephritis w/crescentic changes

Cessation of offending drug and commencement of steroids

Yes

Thyroidectomy

Yes

Outcome

1) Cutaneous rashes resolved

1) Cutaneous rash improved
2) HD dependent

1) Pleural effusions resolved
2) HD dependent