Hypothyroidism presenting as reversible renal impairment: an interesting case report

Abstract

We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

• Acute kidney injury
• chronic kidney disease
• glomerular filtration rate
• hypothyroidism
• renal impairment
• thyroid hormone replacement therapy

Introduction

Renal impairment is a common finding in clinical practice and is increasingly recognized with the routine use of estimated glomerular filtration rates. Clinical assessment is essential to determine which of the many possible investigations are appropriate. Thyroid hormones regulate many cellular functions, and abnormalities of the active thyroid hormones, thyroxine (T4) and triiodothyronine (T3) can influence serum creatinine levels. Evaluation of thyroid function is easily overlooked, but important in this context, as hypothyroidism is common and can cause renal impairment, which is typically reversible.1

Hypothyroidism is an underappreciated cause of renal impairment. The classical clinical signs and symptoms may be subtle or absent, even in severe hypothyroidism. In patients with hypothyroidism, clarification of whether an elevated serum creatinine represents true renal impairment, that is, reduced glomerular filtration rate (GFR) or simply increased generation and tubular secretion of creatinine, therefore requires further analysis by the way of isotope GFR studies.2 We report a case of reversible renal impairment secondary to hypothyroidism. 99mTc DTPA renal scans done before and after thyroid hormone replacement therapy (THRT) suggested hypothyroidism responsible for this renal impairment

Case report

A 57-year-old man was referred from a sub divisional hospital for evaluation of elevated serum creatinine found during investigations for vague complaints of weakness, lethargy and muscle aches. He had these symptoms for about two years. There were no urinary complaints. His past medical history was unremarkable. He was not on any medications prior to the investigations. He had a heart rate 58 beats/min, blood pressure of 130/80 mmHg, a dry scaly skin, puffiness around eyes, pallor, a husky voice, mild non-pitting edema over lower extremities and slow-relaxing ankle reflexes. Thyroid gland was not palpable.

Investigations included hemoglobin 8.2 g/dL, white cell count 6.8 × 10³/dL, erythrocyte sedimentation rate 70 mm 1st hr, microcytic hypochromic anemia on peripheral blood film, serum urea 63 mg/dL, creatinine 2.7 mg/dL, estimated GFR (eGFR) 26 mL/min/1.73 m² by Cockcroft--Gault equation, sodium 138 mEq/L, potassium 4.2 mEq/L, chloride 106 mEq/L, calcium 8.8 mg/dL, phosphorous 3.2 mg/dL, uric acid 6.3 mg/dL, protein 7 gm/dL, albumin 4.3 gm/dL, bilirubin 0.8 mg/dL, aspartate aminotransferase 81 IU/L, alanine aminotransferase 29 IU/L, alkaline phosphatase 78 U/L, random blood sugar 81 mg/dL, cholesterol 424 mg/dL, triglycerides 756 mg/dL serum creatine phosphokinase 270 U/L (normal range <190 U/L). Urine examination showed no albumin or sugar, had 6–8 pus cells per high field and culture was sterile. Urinary myoglobin was not detected and 24-hour urine protein levels were 81 mg (normal 50–150 mg). Ultrasound evaluation showed left kidney 9.8 × 3.8 cm and right kidney 9 × 3.5 cm and normal patent renal arteries on both sides on Doppler. There was minimal pericardial effusion and a normal left ventricular function on echocardiography. 99mTcDTPA renal scan showed severely compromised cortical function with adequate clearance of right kidney and compromised cortical function with adequate clearance of left kidney. Patient was found to be hypothyroid and his thyroid profile was: thyroid-stimulating hormone (TSH) >40 mIU/L (normal range 0.3–6.0 mIU/L), free T3 1.9 pg/mL (normal range 1.4–4.2 pg/dL), free T4 (FT4) was undetectable (normal range 0.8–2.0 ng/dL), antithyroid peroxidase (anti-TPO) antibodies >500 IU/mL (normal <40 IU/mL).

The patient was treated with 100 microgram of levothyroxine daily and advised to follow-up for renal dysfunction. The serum creatinine had normalized at 2-month follow-up visit. After six months of THRT, the patient became totally asymptomatic and had the following test results: hemoglobin 11.2 g/urea 23 mg/dL, creatinine 0.8 mg/dL, eGFR of 86 mL/min/1.73 m² by Cockcroft--Gault equation, serum cholesterol 164 mg/dL, triglycerides 153 mg/dL and a normal thyroid function (TSH 2.55 mIU/L and FT4 1.0 ng/dL). A repeat 99mTcDTPA renal scan revealed a mildly compromised cortical function with adequate clearance of right kidney and adequate cortical function with adequate clearance of left kidney, showing a remarkable recovery of renal function with THRT.

Discussion

In the reported case, the initial finding of renal impairment guided further investigations, leading to the diagnosis of hypothyroidism and THRT brought about complete recovery of renal function. Most reports documenting hypothyroidism with renal impairment have described patients with unexplained worsening of pre-existing renal disease of an alternative etiology; descriptions of renal impairment solely attributable to hypothyroidism, as in our cases, are less common.

The classical clinical signs and symptoms may be subtle or absent, even in severe hypothyroidism and when renal impairment coexists, these signs and symptoms may be attributed to uremia. In hindsight, the patient’s presentation, anemia (more pronounced than might have been expected given the degree of renal impairment), hypercholesterolemia and raised transaminases were perhaps clues to the underlying diagnosis in our patient.

Primary hypothyroidism is associated with a reversible elevation of serum creatinine. This increase is observed in more than half (>55%) of adults with hypothyroidism.3 Moreover, some authors have reported an elevation of serum creatinine associated with subclinical hypothyroidism.4

Thyroid hormone (TH) affects nearly all organ systems in the body. In the kidney, it is involved in renal development and growth, renal hemodynamics and sodium and water homeostasis.5 GFR is also known to be influenced by thyroid dysfunction.6 Hypothyroidism-associated kidney dysfunction seems to be more related with the decline in TH levels rather than with thyroid autoimmunity.7 The pathophysiology of impaired renal function in hypothyroidism is multifactorial. Among the mechanisms involved are direct effects of TH on the cardiovascular system (lead to lower cardiac output and renal blood flow (RBF) resulting in reduction in GFR) and metabolism (hyperlipidemia), and indirect effects through paracrine or endocrine mediators, such as insulin-like growth factor type 1 (IGF-1) and vascular endothelial growth factor.8,9

Primary hypothyroidism is associated with a reduction of GFR and RBF that are normalized following levothyroxine administration.3,8,10–12 Similarly, normalization of circulating TH concentrations with replacement therapy in hypothyroid patients with chronic kidney disease (CKD) can significantly improve GFR.13

Although hypothyroid myopathy is usually limited to myalgias, rhabdomyolysis leading to acute kidney injury is a rare complication of hypothyroidism.14 Our patient did not show any evidence of rhabdomyolysis.

Recent epidemiological studies, identifying a high prevalence of thyroid dysfunction among patients with renal impairment, lend a new importance to the phenomenon of reversible hypothyroidism-induced renal impairment. Subclinical hypothyroidism (elevated TSH levels with normal FT4 levels) and clinically apparent hypothyroidism occur in ∼18–20% of patients with chronic kidney disease not requiring renal replacement therapy, with the prevalence rising as the degree of renal impairment worsens.15,16

THTR for subclinical hypothyroidism has been found to significantly decrease the rate of decline in eGFR, preserve renal function and is predictor of renal outcome in patients with stage 2–4 CKD.17 Hypothyroidism contributes to the reduction in eGFR in CKD patients. THTR for primary hypothyroidism leads to significant improvement of renal function in chronic kidney disease patients. It increases eGFR by about 30% in CKD patients. Therefore, patients with CKD should positively be examined for thyroid function, and appropriate THRT should be started if needed.18

Diagnosing signs of hypothyroidism and therapy with TH in progressive CKD could be very important in delaying the need for renal replacement therapy.13 The development of primary hypothyroidism seemed to worsen the already impaired renal function in this case. We suggest the assessment of thyroid function in patients with unexplained deterioration of renal failure.19

Hypothyroidism is an underappreciated cause of renal impairment. The classical clinical signs and symptoms may be subtle or absent, even in severe hypothyroidism. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation. Thyroid function should be assessed in patients with deteriorating renal function, including those with known renal impairment in whom the deterioration is unexpected. It is worthwhile to examine the thyroid function in known CKD patients and institute appropriate THRT to correct the reversible hypothyroidism-induced renal impairment.

Declaration of interest

All the authors declared no competing interests.