Reversible acute renal failure associated with hypothyroidism: report of four cases with a brief review of literature

SUMMARY:   We present four adult cases of acute renal failure associated with hypothyroidism. All patients presented with symptoms suggestive of moderate to severe hypothyroidism, such as cold intolerance, constipation, muscle weakness, and lower extremity oedema. Initial serum creatinine levels ranged between 115 and 203 µmol/L (1.3 and 2.3 mg/dL), with creatinine clearances (CrCl) ranging between 0.58 and 0.97 mL/s (34.5 and 58 mL/min). After 6–12 weeks of treatment with levothyroxin, serum creatinine levels decreased to the range of 80 and 124 µmol/L (0.9 and 1.4 mg/dL) and CrCl increased to 0.74–1.64 mL/s (44–98 mL/min). One patient had proteinuria of 800 mg/day, which decreased to the normal range (<200 mg/day) after levothyroxin treatment. One patient developed acute gouty arthritis before normalization of thyroid-stimulating hormone (TSH), which was successfully managed with prednisone therapy. All of our patients had increased creatine kinase (CK), ranging between 1000 and 2360 U/L (normal range, 22–165 U/L), which normalized after 6 weeks of levothyroxin treatment.     

Hypoandrogenaemia is associated with subclinical hypothyroidism in men

Hypothyroidism has been shown to be associated with a reduction in serum testosterone level in males. This reduction in testosterone is reversible by thyroxine replacement therapy. However, to the best of our knowledge, it is not yet known, whether a similar reduction in serum testosterone level is observed in subclinically hypothyroid males [thyroid-stimulating hormone (TSH) < 10 mIU/L] in whom the benefits of thyroxine replacement therapy are still controversial. Our goal was to investigate the putative connections between subclinical hypothyroidism and the circulating levels of gonadotrophins and gonadal steroids in males (mean age +/- SEM, 34.67 +/- 1.52 years; ranging from 20 to 54 years). The serum samples from patients showing normal euthyroid and subclinical hypothyroid profiles (TSH < 10 mIU/L) were further analysed for the levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, progesterone and oestradiol. Subclinical hypothyroidism was associated with a decrease in the levels of serum testosterone and its precursor progesterone. The data suggest that serum testosterone declines because of the non-availability of its precursor progesterone. The level of oestradiol was similar in both the groups, suggesting a greater conversion rate of testosterone to oestradiol in subclinically hypothyroid males, in order to maintain the oestradiol levels. Prolactin levels were slightly but significantly increased in subclinical hypothyroidism. To the best of our information this is a novel report, which shows a direct association between subclinical hypothyroidism and hypoandrogenaemia. Testosterone deficiency and its symptoms should be kept in view while managing subclinical hypothyroidism in male patients. Further studies are needed in order to reveal the physiological and molecular mechanisms leading to hypoandrogenaemia in subclinical hypothyroidism (TSH < 10 mIU/L).     

Risk factors associated with hypothyroidism after laryngectomy.

Hypothyroidism is a well-documented complication after treatment of head and neck cancer and is particularly significant among patients undergoing laryngectomy. The objective of this study was the identification of factors associated with the development of hypothyroidism in this population. Records of 136 patients treated with laryngectomy were retrospectively reviewed in an attempt to define a risk factor profile for patients in whom hypothyroidism is most likely to develop after laryngectomy. The Cox proportional hazards model was used to identify factors significantly related to an increased risk for development of hypothyroidism. The actuarial method was used to estimate the period of greatest risk for the development of hypothyroidism. Increased risks were found for patients who were female (P = 0.0049), received preoperative radiation therapy (P = 0.0022), had invasion of the thyroid gland by tumor (P = 0.0003), had presence of cervical metastases (P = 0.0022), and had postoperative fistula (P = 0.0095). From the actuarial method, we estimated that the period of time when patients were at greatest risk for development of hypothyroidism was between 0 and 14 months after surgical intervention. Wound complications were twice as frequent in hypothyroid patients. Perioperative awareness of risk factors associated with the development of hypothyroidism in patients undergoing laryngectomy allows for early recognition and management of hypothyroidism and may reduce the number of complications related to wound healing and fistula.     

Diagnosis of hypothyroidism in patients with end-stage renal disease

Hypothyroidism may occur more commonly in patients with end-stage renal disease (ESRD) than in the general population. The signs and symptoms of both hypothyroidism and uremia may be similar. To evaluate the usefulness of clinical and routine laboratory findings in the diagnosis of hypothyroidism in patients with ESRD, we compared 6 patients with documented primary hypothyroidism who had serum thyrotrophin (TSH) levels above 20 microU/ml with 12 euthyroid patients. The euthyroid patients were divided into two groups. The first was matched with the hypothyroid patients for age, renal disease and duration of dialysis, while the second group was matched for serum total thyroxine and free T4 index values. Serum TSH levels were normal (less than 10 microU/ml) in both of these latter groups. There were no significant differences in the clinical manifestations among the three groups of patients, except for hoarseness of voice which was significantly more common in the hypothyroid uremic patients (p = 0.03). No significant differences were noted on electrocardiogram, physical examination, chest x-ray or echocardiography. Routine laboratory values were not different. Therapy of the uremic hypothyroid patients with L-thyroxine was associated with improvement or resolution of many of the symptoms and signs of hypothyroidism that otherwise would have been attributed to the uremic state. Our results indicate that the diagnosis of hypothyroidism in uremic patients cannot be made by clinical or routine laboratory values and rests on the presence of an overtly elevated serum TSH concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary hypothyroidism in chronic renal failure

Serum thyroid hormone concentrations have been measured in 8 patients with chronic renal failure (CRF) who are currently enrolled on a chronic hemodialysis program. Three of these patients were diagnosed to be suffering from coexistent primary hypothyroidism whereas the other 5 were considered euthyroid. There was a variable decline in serum thyroid hormone levels in both groups. However, the serum TSH response to TRH was normal or blunted in the euthyroid group but was characteristically brisk in subjects with CRF and coexistent primary hypothyroidism. The TRH test may be useful in the diagnosis of primary hypothyroidism coexistent with CRF.     

A case of pituitary hyperplasia associated with primary hypothyroidism

A thirteen-year-old girl was admitted complaining of short stature and anemia. The low titers of her serum T3 and T4 and the abnormally high TSH level represented primary hypothyroidism. Although she had normal sellar size, CT demonstrated an intra- and suprasellar round mass with homogeneous enhancement. With thyroid replacement therapy the enhanced mass diminished on CT within 5 months, and her symptoms regressed. Twelve cases with radiological diminution of pituitary mass or visual field improvement after thyroid replacement therapy are reviewed. They were considered to be pituitary hyperplasia, rather than pituitary adenoma, caused by long-standing untreated hypothyroidism. In four of them, the pituitary mass on CT was diminished after the therapy. Characteristic CT findings of pituitary hyperplasia, including our case, was a round isodensity mass with homogeneous enhancement in the midline of the pituitary region. In the experimental studies, pituitary hyperplasia is based on the feedback mechanism of hypothalamic-pituitary-thyroid axis, and ultimately autonomous pituitary adenoma may occur. Pituitary mass with hypothyroidism, visual field defect, amenorrhea or galactorrhea tend to be mistaken for prolactinoma or non-functioning adenoma with pituitary hypothyroidism. Thorough endocrinological examination must be carried out. The first choice of treatment for this type of pituitary mass should be thyroid replacement therapy. If there is no improvement of visual field, no regression of pituitary mass on CT, or continuing high TSH levels, then pituitary surgery must be considered.     

Vitiligo and alopecia areata associated with subclinical/clinical hypothyroidism

The parents of an 18-year-old woman had noticed white hair while combing their daughter's hair 12 years ago. They found tiny white spots on her scalp, but she was asymptomatic. The spots have since progressed. Examination of the affected skin on the scalp was marked by the presence of a chalky/ivory white macule, 8 to 10 cm in diameter, conforming to that of segmental (zosteriformis) vitiligo (Figure 1). The lesions were located on the temporoparietal region of the scalp. The hair over the macules was white (leukotrichia) and dry, coarse, and brittle. The patient's nails were thin and dull. Her thyroid profile revealed the following: triiodothyronine, 1.12 nmol/L (0.95-2.5 nmol/L); thyroxine, 69.21 nmol/L (60.0-120.0 nmol/L); and thyroid-stimulating hormone, 6.26 microIU/mL (0.25-5.00 microIU/mL), indicative of primary hypothyroidism. Liver and renal function tests were within normal limits. A lipid profile revealed the following: total lipids, 503.8 mg% (400-700 mg %); triglycerides, 123.0 mg % (160 mg %); cholesterol, 212.0 mg % (150-250 mg %); high-density lipoprotein, 43.1 mg % (30-63 mg %); and low-density lipoprotein, 144.3 mg % (50 mg %). Electrocardiographic findings were normal. History of tiredness, constipation, depression, sensitivity to cold, weight gain, muscle weakness, cramps, and increased menstrual flow supported the diagnosis. The patient was administered 100 microg of thyroxine once a day along with methoxsalen, the dose of which was calculated at 0.6 mg/kg to 0.7 mg/kg body weight per day given on alternate days, followed 2 hours later by exposure to UV-A (1 J/cm2) irradiation (psoralen-UV-A [PUVA]), supplemented by 1 mg of beta-methasone, 150 mg of levamisole on 2 consecutive days per week, and an antioxidant. During the course of 7 weeks, the macules (13 exposures) had become erythematous, with an appearance of perifollicular/ marginal pigmentation. Repeat examination showed a thyroid profile of total triiodothyronine (T3), 127.3 microg/dL (86-186); total thyroxine (T4), 6.54 microg/dL (4.5-12.5 microg/dL); and thyroid-stimulating hormone (TSH), 0.32 microIU/mL (0.3-5.6 microIU/mL), supplemented by antithyroid microsomal peroxidase antibodies (thyroid microsomal antibody and thyroid peroxidase), 21.9 IU/mL (1-40 IU/mL), and antithyroglobulin antibodies, 78.1 U/mL (1-100 U/mL). During the patient's treatment period, 4 other patients with clinical symptoms and signs of long-standing hypothyroidism developed vitiligo, the duration of which was variable in each patient (Table I). All of the patients were taking thyroxin. Thyroid and lipid profiles were performed periodically to evaluate the progress (Table I). These patients were also treated with PUVA therapy and thyroxin. During the course of treatment, 2 of the patients noticed asymptomatic, progressive, localized, and well-circumscribed hair loss at the temporal region of the scalp that extended to involve the vertex, conforming to findings of alopecia areata (Figure 2A and Figure 2B).     

Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism

A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an autoimmune basis for the pathogenesis of the functional tubular defect. Bicarbonate therapy resulted in a sustained clinical recovery.     

Exercise-induced acute renal failure associated with renal vasoconstriction]

Exercise-induced acute renal failure without rhabdomyolysis is not a rare condition. We experienced 6 cases (5 men and a woman) during last the 8 years. All cases complained of severe loin pain and nausea after mild to moderate exercises (for example, a track race in an athletic meeting). The elevation of serum and urinary myoglobin was undetected. In 4 of 5 patients with abdominal CT, renal patchy vasoconstriction (wedge-shaped low-density lesion) was observed. This was diagnosed as exercise-induced acute renal failure with loin pain (serum creatinine levels: 1.7-8.6 mg/dl). The renal function in 5 of the 6 cases normalized in about three weeks by fluid replacement therapy and hemodialysis support, which one patient received for 3 days. One patient required a long time for improvement of renal function and renal insufficiency persisted (serum creatinine 1.8 mg/dl). In 2 patients, the concentration of serum uric acid became very low after the recovery of renal function. These two patients were diagnosed as an isolated hyperuricosuric hypouricemia. More than half of the 6 patients had previously experienced the same episodes (loin pain and nausea) after exercise. Exercise-induced acute renal failure, probably due to renal patchy vasoconstriction, seems to be not a rare disease. The etiology of renal patchy vasoconstriction after exercises remains to be elucidated. The occurrence of acute renal failure must be taken into consideration when the youngster, especially with renal hypouricemia, complains of severe loin pain and nausea after exercise such as a track race.     

Hidden pathologies associated with (and concealed by) early gestational isolated fetal hydrothorax

Isolated fetal hydrothorax is an uncommon finding on routine prenatal ultrasound and is associated with a variable prognosis. We believe this is the first report of a patient whose antenatal hydrothorax was associated with both congenital diaphragmatic hernia and congenital pulmonary lymphangiectasia. This rare combination caused significant problems in diagnosis and subsequent treatment.     

Ascites associated with end-stage renal disease

Patient characteristics, clinical outcomes, and proposed pathophysiologic mechanisms are reviewed in 138 patients reported in the literature to have had ascites associated with end-stage renal disease. Contributing mechanisms may include fluid overload, peritoneal membrane changes (not necessarily related to peritoneal dialysis), hypoproteinemia, and lymphatic drainage disturbances. In 15% of cases, extensive evaluations may reveal an underlying disease. The most effective therapy may be kidney transplantation.     

Poland syndrome associated with renal agenesis

Poland syndrome is characterized by unilateral aplasia or hypoplasia of the sternocostal portion of the pectoralis major muscle and ipsilateral syndactyly. In some cases other associated anomalies, including renal malformations, dextrocardia, and vertebral abnormalities, have been reported. We report a 7-month-old girl with Poland syndrome who also presented with ipsilateral renal agenesis. This report suggests that renal structural anomaly may be an integral part of this syndrome. We recommend renal imaging studies be performed on all children with Poland syndrome. Received: 23 July 2001 / Revised: 23 October 2001 / Accepted: 23 October 2001     

Hyperglycemia associated with renal cell carcinoma

A case of renal cell carcinoma presenting with uncontrolled diabetes mellitus is reported. After a radical nephrectomy, the diabetic state completely resolved. Laboratory studies failed to reveal any endocrinopathy responsible for the diabetic state. Thus it appears that hyperglycemia and diabetes mellitus can now be included with the other paraneoplastic endocrinopathies associated with renal cell carcinoma.