Hypothyroidism and associated acute renal failure

Introduction

We report a case of profound hypothyroidism with associated and otherwise unexplained acute renal failure in which replacement of the hormonal deficiency led to correction of the renal dysfunction. Electrolyte disorders are occasionally observed in hypothyroidism but associated renal impairment without any other clear underlying cause is relatively rare. There have been previous case reports documenting this association but it is something that is rarely found in medical textbooks. We describe our case of a middle-aged gentleman who presented with profound clinical hypothyroidism who was found on further investigation to also have significant renal impairment.

Case report

A 54-year-old bus driver was referred with a history of peri-orbital, facial and generalized leg swelling which he reported had come on gradually over a three-week period. There were no other symptoms suggestive of volume overload, particularly no shortness of breath, dyspnoea on exertion and no other cardiac symptoms. He also denied any urinary symptoms or other symptoms suggestive of renal failure. On further questioning this three-week history of swelling was preceded by several months of vague constitutional symptoms including tiredness, lethargy, low mood and leg muscle cramping. He had no significant past medical or surgical history and was on no regular medication. He was an ex-smoker and had no pets. There was no family history of renal or endocrine disorders.

On clinical examination he was overweight (BMI 41) with marked peri-orbital oedema and facial oedema. Vital signs were stable; he was apyrexial, pulse of 72 bpm, blood pressure of 107/68 mmHg, a respiratory rate of 18 breaths/min and oxygen saturations of 100% on room air. Cardiovascular examination was normal; there were no additional heart sounds or murmurs and the JVP was not raised. Respiratory, abdominal and neurological examinations were all unremarkable.

Laboratory results revealed a normal full blood count, sodium of 141 mmol/L (135–145), potassium of 4 mmol/L (3.6–5.3), urea of 9 mmol/L (3.4–8.2) and creatinine of 190 umol/L (78–122). ALT was raised at 68 IU/L (5–40), AST was 103 IU/L (5–40) but other liver function tests, albumin, random cortisol and coagulation screen were all normal. Repeated urinalysis showed no evidence of blood or protein, and this was later confirmed in the laboratory with a normal urine protein/creatinine ratio. The creatinine kinase was markedly elevated at 3322 U/L (0–170) with a normal MB fraction and normal electrocardiogram. An autoantibody screen and serum complement levels were also normal. Renal ultrasound showed normal kidneys bilaterally and no urinary tract abnormalities.

Thyroid function tests revealed a TSH of 211.2 mU/L (0.4–5.0) and Free T4 of <0.3 pmol/L (12–23). TPO antibodies were strongly positive: >600 IU/ml (0–70). A diagnosis of autoimmune thyroiditis was made. The patient was commenced on thyroxine replacement, which resulted in resolution of his symptoms, correction of his TFTs and a gradual improvement in his renal function

Table 1

Trend of blood results

	Admission	4 weeks	10 weeks	14 weeks	8 months	1 year
Sodium (135–145 mmol/L)	141	140	140	141	140	140
Potassium (3.6–5.3 mmol/L)	4	4.4	4.9	4.6	5	4.8
Urea (3.8–4.2 mmol/L)	8.6	9.3	8	10	8	7.5
Creatinine (78–122 mmol/L)	185	158	144	127	123	115
TSH 0.4–5.0 mU/L	211.2	106.5	67.6	55.79	8	2.2
T4 12.0–23.0 pmol/L	<0.3	11.4	12.1	13.2	16	20
CK 0–170 IU/L	3871			156

(Table 1).

Discussion

Hypothyroidism is frequently seen in patients with renal impairment but is rarely determined to be the underlying cause. It is therefore not routinely requested when investigating patients with abnormal renal function. However there have been previous case reports documenting this rare association. The effects of hypothyroidism on the kidney appear to be well established. Histological changes have been demonstrated in both rats and humans. 1 Physiological effects more commonly include water and electrolyte abnormalities especially hyponatreamia and associated with this altered intrarenal haemodynamics, including decreases in both renal blood flow and glomerular filtration rate (GFR). This is believed to be principally due to the hypothyroidism induced hypodynamic state. 2 In rare cases, renal failure can be secondary to rhabdomyolysis, and raised creatinine kinase levels, however this is usually associated with other precipitating factors such as trauma, exercise and lipid-lowering medication. 3, 4

Current evidence is unclear of the timescale required to develop renal impairment and there is also considerable debate as to the degree of reversibility following adequate hormone replacement. In one study the renal failure did not recover fully to previous levels following the initiation of thyroid replacement therapy and correction of the hypothyroidism. 5 However, a more recent study demonstrated abnormalities after two weeks of hypothyroidism, and fully reversed on appropriate thyroid replacement. 6 Whether longer-term untreated hypothyroidism will result in permanent renal impairment is not known. As this is a relatively infrequent association the patient numbers are low and thus it is difficult to prove definitely

It is also important to be aware that hypothyroidism is not only a recognized cause of de novo renal failure but can also precipitate deterioration in patients with stable chronic renal failure. There are reports of improvement in renal failure following treatment of hypothyroidism in these patients. 7 Epidemiologic data also suggests that predialysis patients with advanced chronic renal dysfunction (Chronic Kidney Disease stages 4 and 5) may have an increased risk of hypothyroidism compared to the general population. This is often subclinical and is therefore important to detect, especially in the elderly, as the condition is easily treatable.

Knowledge of the association between thyroid dysfunction and renal impairment is important for the clinician. We suggest that thyroid function tests could become part of the routine screening blood tests for patients with impaired renal function and also that hypothyroidism should be considered as a cause of renal impairment especially in the context of patients with no other clear explanation for their renal dysfunction.

Footnotes

DECLARATIONS

Competing interests None declared

Funding None

Ethical approval Not applicable

Guarantor LG

Contributorship BJ and DJ contributed equally, AR helped edit the initial drafts and LG is the senior author