Autoimmune Hypothyroidism and Nephrotic Syndrome

Gutch Manish1, Kumar Sukriti2, Rao Somendra Singh3, Annesh Bhattacharya4, Rajendra Pahan5 1Assistant Professor, Department Of Medicine, King George’s Medical College, Lucknow, Uttar Pradesh, India. 2Assistant Professor, Department Of Radiodiagnosis, King George’s Medical College, Lucknow, Uttar Pradesh, India. 3Senior Resident, Department of Medicine, King George’s Medical College, Lucknow, Uttar Pradesh, India. 4Senior Resident, Department of Cardiology, Rml Hospital, Lucknow, Uttar Pradesh, India. 5Junior Resident, Department of Medicine, King George’s Medical College, Lucknow, Uttar Pradesh, India.


INTRODUCTION
2][3] Autoimmune thyroiditis resulting in hypothyroidism (Hashimoto's) can rarely be associated with concomitant autoimmune glomerular involvement resulting in the development of Nephrotic syndrome. 2The development of overt proteinuria results in loss of thyroid hormones bound to its carrier proteins. 5This results in hypothyroidism in a patient with a compromised thyroid gland.This is one of the rare reversible association between autoimmune hypothyroidism and Nephrotic syndrome which is amenable to Levothyroxine therapy and carries a good prognosis.Very few cases showing the association of hypothyroidism and Nephrotic syndrome have been reported so far. 7,8The clinician should have a high index of suspicion in patients presenting with overlapping features of both hypothyroidism & Nephrotic syndrome and order necessary investigations to rule out underlying hypothyroidism as a treatable cause of Nephrotic syndrome.

CASE SUMMARY
A 25 year old businessman visited the medicine outpatient department with complains of generalised body swelling since last 6 months.Initially he experienced prominent facial puffiness which seemed more prominent in the early morning hours.His symptoms followed a gradually progressive course over the next 6 months finally resulting in generalised anasarca.Besides he also experienced fatigue and lethargy, associated with cold intolerance, which occasionally interfered with his daily activities.He denied any history of breathlessness, cough, decreased urine output, change in voice or neck swelling.Family and medication history was unrewarding.
On examination his vitals were stable with pulse rate of 68/min and respiratory rate of 18/min.He had diastolic hypertension (blood pressure = 130/100 mmHg) with no postural variation.He weighed 76 kg and his height was 165 cm; hence his BMI was 27.92 kg/m 2 .He did not appear pale, although facial and periorbital swelling was prominent with bilateral pedal oedema.There were no signs of goitre or engorgement of neck veins; JVP was within normal limits.We also noticed prominent swelling in bilateral calf regions which was firm and non-tender (Pseudohypertrophy).Abdominal examination revealed no hepato-splenomegaly with mild ascites as perceived by percussion over bilateral flank regions.Higher mental functions and nervous system examination was mostly normal save for the delayed relaxation of ankle reflex bilaterally (grade 1+).Examination of the cardiovascular and respiratory systems did not reveal any significant abnormality.On further investigating, his Haemoglobin was 10.5 g/dl with normocytic normochromic peripheral blood picture.Serum electrolytes and creatinine were within normal limits while liver function tests showed reduced total protein (4.7 g/dl) and albumin (2.2 g/ dl) values.He had deranged fasting lipid profile (total cholesterol = 380 mg/dl, LDL = 180 mg/dl, HDL = 36 mg/dl) while his random blood glucose level was 76 mg/dl.Urine routine examination revealed significant proteinuria (3+) without any RBC casts or pus cells.24 h urinary protein excretion was 6000 mg.We ordered a thyroid function test and obtained results concordant with primary hypothyroidism (T3 = 45 ng/dl, T4 = 3.8 µg/dl, TSH > 100 µIU/ml).Anti TPO antibodies were positive.Kidney biopsy before the start of treatment showed Glomeruli having mesangiocapillary proliferation with oedematous tubules filled with proteinaceous material (Figure 1 and 2).

DISCUSSION
Autoimmune hypothyroidism is the commonest cause of hypothyroidism in iodine-sufficient regions of the world.It generally causes autoimmune thyroid destruction, goitre and a variety of systemic manifestations.Renal involvement as isolated proteinuria is commonly seen in 10-30% of hypothyroid individuals. 1Glomerular involvement with autoimmune thyroiditis is a rare entity.Studies have revealed that the lesion most commonly associated is Membranous Glomerulonephritis (MGN) followed by Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD). 2 Several mechanisms have been proposed to explain these associations.Features suggesting a common autoimmune disorder are immune-complex deposition 3 in the glomerular and thyroid basement membrane and association with other autoimmune diseases like type 1 diabetes mellitus. 4The development of nephrotic syndrome results in urinary loss of thyroid hormones bound to its binding proteins like TBG, transthyretin, prealbumin and albumin. 5Normal thyroid compensates for these changes by increasing synthesis of thyroid hormones.Patients with com-Hence we made a provisional diagnosis of Primary Autoimmune (Hashimoto's) Hypothyroidism with nephrotic syndrome and dyslipidemia.
We began treating him with oral prednisone (40 mg/day) and rosuvastatin (10 mg/day) with advice for low salt and liberal protein intake.Subsequently we added levothyroxine at a dose of 1.6 µg/kg BW/day.His physical condition and symptoms improved gradually with the passage of time and we were able to taper and stop both prednisone and rosuvastatin.Presently at the end of 2 years of treatment, he is only on Levothyroxine while his 24 h urinary protein excretion has reduced to 10 mg.Investigation are mentioned in Table 1.promised thyroid functions may subsequently develop hypothyroidism due to urinary loss of thyroid hormones.Primary hypothyroidism has also been reported to occur in association with congenital nephrotic syndrome. 6hyroid function tests reveal variable results in the nephrotic syndrome, primarily depending upon the level of protein losses in the urine.0][11][12] Serum triiodothyronine (T3) concentrations may also be low due also to decreased binding.0][11][12] Serum reverse T3 (rT3) concentrations are also low.Similar mechanism also seen in patient with metabolic syndrome associated with thyroid dysfunction. 14he association of nephrotic syndrome with hypothyroidism is a rare entity with only a few cases reported so far in medical literature.A 63 year old Japanese man had co-existent minimal change disease and autoimmune hypothyroidism which was proven by biopsy and the presence of anti-microsomal and anti-thyroid peroxidase autoantibodies. 7Similarly a Turkish individual was reported to have co-existent autoimmune hypothyroidism and membranoproliferative glomerulonephritis. 8Nephrotic syndrome associated with autoimmune hypothyroidism is a treatable and reversible condition with a good prognosis, hence clinicians must rule out hypothyroidism when any patient with Nephrotic syndrome presents with compatible clinical features.

CONCLUSION
Untreated Hypothyroidism is a rare but reversible cause of Nephrotic Syndrome which is amenable to treatment with Levothyroxine and has an overall good prognosis.The clinician should have a high index of suspicion in patients presenting with overlapping features of both hypothyroidism and Nephrotic syndrome and order necessary investigations to rule out underlying hypothyroidism as a treatable cause of Nephrotic syndrome.