Severe hypothyroidism presenting as reversible proteinuria: two case reports

Case 1

A 72-year-old Sinhalese man, a paddy farmer from Western Province, Sri Lanka, presented with complaints of facial puffiness and body aches during exertion. He was a healthy man with no history of long-term medications, he did not consume alcohol, and he did not smoke tobacco. On further questioning he complained of cold intolerance; he had no frothy urine and no features of a connective tissue or autoimmune disorder. He had good exercise tolerance and had never experienced ischemic-type chest pains. We excluded the history of recent trauma or seizures by careful detailed questioning. He has no family history of renal disease. He was from a rural area of the Western Province, with access to clean water and sanitation. He gave a history of exposure to various pesticides and weedicides that he has used for nearly 45 years as a farmer. On examination a hoarse voice was noted, with puffy swelling of his body. A mild pallor was noted on examination. His blood pressure was 117/74 mmHg and pulse rate was 62/minute. Other than for sluggishness of reflexes, a neurological examination was unremarkable. A clinical diagnosis of hypothyroidism was made and he was followed up with blood investigations. A TSH > 100 U/L confirmed the diagnosis. In addition, a serum creatinine of 167 umol/L was noted with a urine analysis showing 250 mg/dL albuminuria, and blood urea of 4.6 mmol/L. His urine protein to creatinine ratio (UPCR) was 3.4. He had elevated lipid levels. An extremely low blood urea to creatinine ratio prompted us to exclude coexisting liver disease or myopathy. Liver function tests were normal, but creatinine kinase (CK) was grossly elevated to 4473 U/L. A normal 9.00 a.m. cortisol level ruled out coexisting hypoadrenalism. He was started on an escalating dose of thyroxine, starting with 25 μg daily, with 25 μg increments every fortnight, up to 100 μg/day. Hepatitis B, hepatitis C, and HIV serology were negative. His erythrocyte sedimentation rate (ESR) was 25, and serum protein electrophoresis was normal. An ultrasound scan of his abdomen revealed normal-looking kidneys and did not demonstrate any lymphadenopathy. Antinuclear factor, C3 level, and C4 level were unremarkable. A renal biopsy was not performed initially as rhabdomyolysis was not a likely diagnosis, and was not performed later due to rapid resolution with thyroxine. An ultrasound scan plus duplex of his thyroid revealed a multinodular goiter with no prominent or vascular nodules.

He was followed up at 2, 4, and 6 months. His proteinuria disappeared by 16 weeks, creatinine gradually dropped down to 88 umol/L, and CK normalized to 125 U/L. TSH at 6 months was 1.20 U/L. Omega 3 fatty acids were started to counter the hyperlipidemia, and was converted at 4 months to rosuvastatin 5 mg daily, which was omitted at 6 months.

Case 2

A 47-year-old Tamil woman from Northern Sri Lanka was referred by a peripheral clinic for further evaluation of elevated serum creatinine. She had been hypertensive for 5 years; she did not have a history of diabetes or ischemic heart disease. She was on treatment for hypertension and hypercholesterolemia with enalapril 5 mg daily and fenofibrate 200 mg daily. She did not have a history suggestive of renal disease, autoimmune disorder, or connective tissue disorder. She failed to recall any history of major trauma, dehydration, ingestion of drugs and/or toxins, or seizures within the last few weeks. She is a housewife and mother of two children. Similar to many Asian women, she did not consume alcohol and she did not smoke tobacco. She was married to a hospital clerk, and did not recall exposure to toxins. She was not living in an endemic area of chronic interstitial nephritis in agricultural communities (CINAC).

She had a blood pressure of 150/100 mmHg, with normal cardiovascular examination. She was not pale. She did not have any edema on examination. Her serum creatinine was 126 umol/L, with a blood urea of 3.2 mmol/L. Urine analysis revealed bland sediment with 100 mg/dL of protein, but no hemoglobin or myoglobin. A full blood count showed hemoglobin of 112 g/L, with a mean corpuscular volume of 98 fl. This raised the possibility of hypothyroidism. Further investigations showed a UPCR of 1.6, elevated serum lipids, TSH of > 100 U/L, and CK of 3980 U/L. Her liver profile showed alanine transferase (ALT) of 45 (reference range < 30), aspartate transferase (AST) of 56 (reference range < 30), and alkaline phosphatase (ALP) of 122 (reference range < 245), slight derangement. An initial diagnosis of fenofibrate-induced rhabdomyolysis was made, and fenofibrate was withdrawn from the treatment. She was initiated on management of rhabdomyolysis with alkaline diuresis. An ultrasound scan of her abdomen revealed normal-looking kidneys and no lymphadenopathy. Hepatitis B, hepatitis C, HIV, antinuclear factor, C3 level, and C4 level, were all within reference ranges. Urine myoglobin and urine hemosiderin deposits were negative. However, there was no change in her CK levels (3870 U/L) or creatinine (133 umol/L) levels after a lapse of 2 weeks, and we decided her elevated CK levels were unlikely to be due to fenofibrate-induced rhabdomyolysis. We assumed it was due to hypothyroidism and started an escalating dose of thyroxine at 25 μg/day, with increments of 25 μg each 2 weeks, up to 75 μg/day. A renal biopsy was not performed initially as rhabdomyolysis was not likely, and it was not performed later due to rapid resolution with thyroxine. An ultrasound plus duplex of her thyroid revealed a multinodular goiter with no prominent or vascular nodules. Her CK gradually dropped over the next 12 weeks, with her creatinine, to 93 umol/L. Her UPCR reduced to 0.6 after 6 months of treatment. At the end of 6 months of follow-up her renal function and thyroid functions normalized, and proteinuria was absent.

In both patients, thyroglobulin antibodies tests were not performed due to economic constraints. A summary of the investigations is given in Table 1. Figure 1gives a graphical representation of change of renal functions and CK levels with TSH.