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Severe Hypothyroidism Causing Minimal Change Nephropathy In Early Pregnancy

Author Information 

Bora A*, Madhva Prasad S**, Gupta AS***

(* Second Year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth GS Medical College and KEM Hospital, Mumbai.)

Abstract

Vulval edema, as a part of pregnancy is a common entity. While hypertension and renal disease are the commonly attributed etiologies, these may be transient also. Here a case of severe hypothyroidism at 16 weeks pregnancy which presented as a transient nephrotic syndrome is described. Complete resolution with correction of thyroid status occurred.  

Introduction 

Occurrence of vulval edema, generalized edema all over the body, high blood pressure and proteinuria in pregnancy usually signifies preeclamptic state. However in this case, the occurrence of proteinuria was probably because of a minimal change nephropathy which can occur in severe hypothyroidism.

Case Report 

A 24 year old primigravida with 16 weeks pregnancy presented with swelling all over the body and decreased urine output. She was antenatally unregistered. She noticed gradual swelling, initially in the feet and vulvar region, around three weeks prior, which gradually progressed to involve entire body. She gave no history of burning micturition, dysuria or increased frequency of micturition or urgency. She had no complaints of breathlessness, palpitations or weakness. She gave no complaints of yellowish discoloration of the body, pruritus, clay colored stools or pain in abdomen.
On examination her blood pressure and pulse were 130/80 mm of Hg and 88 beats per minute respectively. Cardiovascular examination was within normal limits and chest was clear. Bilateral non-pitting pedal edema was present. Abdomen was soft, free fluid was detected and uterus was just palpable. There was gross vulvar edema. On per vaginal examination internal os was closed and uterus was 14 weeks in size. 
Ultrasonography showed a live intrauterine gestation of 14 weeks 6 days, bilateral mild pleural effusion and ascites. She was admitted for evaluation of anasarca. Hemoglobin was 8.6 gm %, white blood cell count was 7600 cells/ cubic mm, platelet count was 3.6 lacs, serum creatinine was 0.7 mg%, blood urea nitrogen was 5.1 mg%, sodium and potassium levels were 143 meq/ l and 4.2 meq/ l respectively. Liver function tests, including serum protein levels were within normal limits.   
Urine routine microscopy was within normal limits, except a trace of albumin. Serum TSH was done, and surprisingly was found to be extremely elevated; 150 mg/dl. The other abnormal investigation was twenty four hour urine protein which was found to be high; 78.7mg/ dl (normal < 10mg/dl). Nephrologist advised to rule out autoimmune causes. Anti-nuclear antibodies and anti dsDNA antibodies, ICT/ DCT were negative; C3 and C4 were within normal limits.  
She was started on oral levothyroxine 150 mcg once a day. During her stay in the hospital, strict blood pressure monitoring was done. In view of a single high blood pressure value (150/100 mm Hg) and in the setting of proteinuria she was started on methyldopa 250 mg BD, and labetalol 50 mg BD; since the nephrologists anticipated rise in blood pressure with progression of pregnancy. For the vulvar edema, regular magnesium sulphate dressings were done. Fundoscopy was done and retina was found to be normal. Ultrasonography for kidney, ureter and bladder was normal. She was discharged with the advise to continue all the above 3 drugs and follow up as an outpatient. However, she presented to the outpatient department only after 2 months.
In her consequent visits, she had no facial puffiness, no pedal edema and the vulvar edema had significantly reduced. Nephrologist stopped the antihypertensive medications. She continued home blood pressure monitoring. Urine for albumin was always nil and obstetric Doppler was normal. She was admitted at 38 weeks for induction of labor for chronic hypertension. Critical review of her case history, her initial clinical presentation of anasarca, hypertension and its subsequent disappearance after starting thyroid replacement therapy enabled us to co-relate her clinical condition to severe hypothyroidism and exclude the differential diagnosis of minimal change nephrotic syndrome or chronic hypertension.  Induction of labor was deferred and she was allowed to go into spontaneous labor at 39 weeks and 4 days gestation. She remained normotensive during labor. She progressed spontaneously and delivered a female child of 2.438 kg, with an Apgar score of 9/10. Course of labor was uneventful. Repeat serum TSH value was 9.2 mg/ dl. She was continued on levothyroxine 150 microgram and discharged.

Discussion 

The occurrence of hypothyroidism ranges from around 3 to 15 % in various population groups.[1] Guidelines for management of hypothyroidism and screening for subclinical disease in pregnancy has now become universally accepted.[2] However, the clinical presentation of hypothyroidism can be varied. Our patient initially presented with gross vulval edema and ascites. Vulvar edema can be due to hypoproteinemia, and may be associated with hypertension in pregnancy.[3]
Hypothyroidism presenting as ascites is a rare but well established entity.[4] Though our patient had normal protein values, she had few readings of elevated blood pressure and anti-hypertensives were started though blood pressure did not reach the usually recommended values of 160/110mm Hg.[5]
However, in 2 months, the antihypertensives required discontinuation and patient did not have any further high blood pressure readings. Such a normotensive state continued throughout pregnancy, labor and her post-partum period. Hence, it was retrospectively considered that the initial presentation of edema was probably not due to the hypertension or related renal disease. De Feudis et al have described ascites as the initial presentation of primary hypothyroidism, albeit in a non-pregnant state.[6] Mizgala et al and Patel et al had also previously reported preeclamptic patients presenting with hypothyroidism.[7,8] However, now recent evidence has convincingly proved that hypothyroid disease is associated with hypertension in pregnancy.[9] This association may be genetically determined also, as reported recently by Procopciuc et al.[10]
Our patient had a TSH value of > 150 mg/dl, which is considered as severe hypothyroidism. This level was detected at the time of evaluation of anasarca during her initial presentation. Inversetti et al have also described a case of severe hypothyroidism which mimicked a preeclamptic state and highlighted the need for correction of thyroid status before any further intervention.[11] Ipadeola et al have also reported a case where hypothyroidism was unmasked by preeclampsia and ascites, almost identical to our case.[12]
The nephrologists were of the opinion that this presentation was similar to Minimal Change renal disease, though biopsy was not done. This is consistent with the case reported by Soh et al wherein minimal change nephrotic syndrome occurred with deterioration of hypothyroidism.[13] Karethimmaiah et al have also reported the need for increased thyroxine supplementation in patients with nephrotic syndrome.[14]
Hence it is retrospectively hypothesized that our patient developed a transient nephrotic syndrome like picture due to severe hypothyroidism, presenting as anasarca, that resolved completely when she achieved the euthyroid state. That a minimal change renal disease or chronic hypertension did not exist is proven by the fact that the patient went till term gestation with no further high blood pressure readings, proteinuria or intrauterine fetal growth retard or fetal compromise. However, this enlightenment occurred only at 38 weeks of gestation during a critical review of her clinical course when we were contemplating induction of labor for chronic hypertension. 
To conclude, hypothyroidism can present in a varied manner. This case report also highlights the fact that clinical decision making is an arduous task requiring correlation of many factors and in spite of superspecialists’ opinions, the judgment of a senior obstetrician is indispensable.  

References
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  14. Karethimmaiah H, Sarathi V. Nephrotic Syndrome Increases the Need for Levothyroxine Replacement in Patients with Hypothyroidism. J Clin Diagn Res; 2016;10(12):OC10-OC12
Citation

Bora A, Madhva Prasad S, Gupta AS. Severe hypothyroidism causing minimal change nephropathy in early pregnancy. JPGO 2017. Volume 4 No.9. Available from: http://www.jpgo.org/2017/08/severe-hypothyroidism-causing-minimal.html