Low Free Thyroxine Levels Research Articles

Decreasing Prostate Specific Antigen Value Leading to the Diagnosis of a Pituitary Adenoma

A 77-year-old white man had been followed since December 1995 for an elevated PSA of 10 ng./ml. Two transrectal ultrasound guided needle biopsies of the prostate in 1995 and 1997 were negative for carcinoma. Between April 1999 and July 2001 the PSA value decreased precipitously from 9.4 to less than 0.3 ng./ml. (fig. 1, A). The patient was neither taking medications nor consuming a diet known to cause a decrease in PSA value. He had been impotent for 5 years and had noticed no change in libido. He had noticed mild hot flashes for several years. Free and total testosterone levels had also decreased during the preceding several years (fig. 1, B). Further workup revealed that luteinizing hormone and follicle-stimulating hormone levels were low, at less than 1.0 and 1.2 mu./ml., respectively. Thyroid function tests demonstrated a normal level of thyrotropin at 2.1 U./ml., and low levels of free and total thyroxine at 0.5 ng./dl. and 4.7 g./dl., respectively. Prolactin was normal at 17 ng./ml. Evaluation for hypopituitarism with magnetic resonance imaging (MRI) of the brain showed a pituitary macroadenoma measuring 1.9 by 2.5 cm. invading the right cavernous sinus (fig. 2). The patient had elected to undergo resection of the pituitary tumor when several days before surgery he presented to the emergency department with severe headache, diplopia and right ophthalmoplegia. Repeat brain MRI revealed no change in the pituitary tumor, and an angiogram revealed no intracranial hemorrhage. The patient underwent uncomplicated transsphenoidal resection of the pituitary tumor. Pathological examination demonstrated pituitary adenoma.

Apparent Increase in Type I 5’-Deiodinase Activity Induced by Antiepileptic Medication in Mentally Retarded Subjects

Background/Objectives: Thyroid function measurements in 3 mentally retarded patients treated with antiepileptic drugs (phenytoin or carbamazepine) showed normal thyroid-stimulating hormone (TSH) responses in spite of markedly low levels of total thyroxine (T₄), triiodothyronine (T₃), and free thyroxine (FT₄) concentrations; free triiodothyronine (FT₃), as well as mean thyroxine-binding globulin (TBG) concentrations were normal. The objective of the present investigations was to determine if antiepileptic medication in these patients contributed to the disparate TSH and thyroid hormone (TH) levels. Methods: Thyroid tests and other laboratory parameters were measured by conventional techniques. Results: Circulating TH changes noted in retarded patients were similar to those observed in control subjects receiving carbamazepine alone. Reverse T₃ (rT₃) levels in all patients were either undetectable or below the normal range. Conclusions: As type I 5′-deiodinase has a higher affinity for rT₃ than T₄, an increased activity of this enzyme would enhance rT₃ deiodination and reduce serum rT₃ concentration whereas enhanced T₄ deiodination would aid in normalizing intracellular FT₃ concentration. The finding of normal serum FT₃ concentration was consistent with normal TSH response and clinical euthyroidism in both retarded and control subjects. While phenytoin-induced increase in type I 5′-deiodinase has been previously noted, the present studies demonstrate a similar effect of carbamazepine on 5′-deiodinase.

Investigation and outcome of neonatal hepatitis in infants with hypopituitarism.

Congenital hypopituitarism is a recognized cause of neonatal hepatitis, but the diagnosis may be difficult to establish even if clinically suspected. In order to determine the natural history of this disorder, the outcome of 12 infants with neonatal hepatitis secondary to hypopituitarism is reviewed. The clinical diagnosis of hypopituitarism was established on a combination of features, which include dysmorphism (4 infants), optic nerve hypoplasia (8 infants), micropenis (5 male infants) and recurrent hypoglycaemia (blood glucose < 2.4 mmol/l (8 infants)). Endocrine investigation revealed low free thyroxine (T4) levels (< 10 pmol/l), with normal thyroid stimulating hormone (TSH) levels (0.4-4.5 mU/l) (11 infants), and serum cortisol levels which were inappropriately low (< 200 nmol/l). In 9 of 12 infants, liver disease resolved within 6 wk following treatment with thyroxine, hydrocortisone and, where appropriate, growth hormone, including Cases 9 and 1 in whom diagnosis and treatment were delayed until 3 mo and 3 y of age, respectively. Liver disease resolved spontaneously in two infants prior to starting hormone replacement therapy (Cases 11, 12), and one male infant (Case 10), in whom the diagnosis and hormone replacement therapy were delayed until 5 y of age, developed cirrhosis and portal hypertension and later underwent liver transplantation. The diagnosis of hypopituitarism should always be considered in infants with unexplained neonatal hepatitis. Delay in diagnosis and appropriate treatment was associated with persistently abnormal liver function tests and may lead to irreversible liver disease.

Investigation and outcome of neonatal hepatitis in infants with hypopituitarism

Congenital hypopituitarism is a recognized cause of neonatal hepatitis, but the diagnosis may be difficult to establish even if clinically suspected. In order to determine the natural history of this disorder, the outcome of 12 infants with neonatal hepatitis secondary to hypopituitarism is reviewed. The clinical diagnosis of hypopituitarism was established on a combination of features, which include dysmorphism (4 infants), optic nerve hypoplasia (8 infants), micropenis (5 male infants) and recurrent hypoglycaemia (blood glucose &lt; 2.4 mmol/l (8 infants)). Endocrine investigation revealed low free thyroxine (T4) levels (&lt;10 pmol/l), with normal thyroid stimulating hormone (TSH) levels (0.4‐4.5 mU/l) (11 infants), and serum cortisol levels which were inappropriately low (&lt; 200 nmol/l). In 9 of 12 infants, liver disease resolved within 6 wk following treatment with thyroxine, hydrocortisone and, where appropriate, growth hormone, including Cases 9 and 1 in whom diagnosis and treatment were delayed until 3 mo and 3 y of age, respectively. Liver disease resolved spontaneously in two infants prior to starting hormone replacement therapy (Cases 11, 12), and one male infant (Case 10), in whom the diagnosis and hormone replacement therapy were delayed until 5 y of age, developed cirrhosis and portal hypertension and later underwent liver transplantation. Conclusion: The diagnosis of hypopituitarism should always be considered in infants with unexplained neonatal hepatitis. Delay in diagnosis and appropriate treatment was associated with persistently abnormal liver function tests and may lead to irreversible liver disease.

Low free-thyroxine levels are a risk factor for subclinical atherosclerosis in euthyroid hyperlipidemic patients.

Patients displaying overt and subclinical hypothyroidism have more cardiovascular risk factors. Consequently, they are more likely to develop atherosclerosis and cardiovascular diseases. To analyze whether low free-thyroxine levels (FTL) would also be associated with atherosclerosis in euthyroid patients. We selected a group of 1434 healthy euthyroid male patients without known histories of thyroid disease and with levels of thyroid-stimulating hormone values within the normal range (mean 1.70+/-0.76 mUl/l, range 0.13-4.01 mUl/l). Mean age of these patients who had been referred for assessment of hyperlipidemia was 44.6 years and mean FTL was 14.25+/-3.06 pmol/l. We divided the population according to the degree of atherosclerosis in the carotid arteries. Mean age, body mass index, systolic blood pressure, cigarettes/day, blood level of glucose, cholesterol levels, and fibrinogen levels were significantly higher for the patients with atherosclerotic lesions whereas mean FTL was lower for patients with carotid atherosclerosis (P = 0.0002). The relationship between FTL and carotid atherosclerosis was independent from the following cardiovascular risk factors: age, hypertension, amount of excess weight, cholesterol level, fibrinogen level, smoking status, and presence versus absence of diabetes mellitus. Low FTL is a risk factor for atherosclerosis in male euthyroid hyperlipidemic patients.

Cardiac function at rest in hypothyroidism evaluated by equilibrium radionuclide angiography.

Previous studies have suggested that hypothyroidism affects both systolic and diastolic cardiac function. We have applied equilibrium radionuclide angiography to the study of heart function at rest in hypothyroidism. A prospective study, evaluating cardiac function at rest in primary hypothyroidism. Cardiac function was studied by means of equilibrium radionuclide angiography. Screening echo-Doppler examinations were performed on each patient. Twenty-six consecutive untreated hypothyroid patients without clinical or echocardiographic cardiac disease and 20 healthy matched controls. Between patients and controls, the time to peak emptying rate (161 +/- 6 msec vs. 144 +/- 6 msec, P < 0.05) and the time to peak filling rate (188 +/- 6 msec vs. 170 +/- 5 msec, P < 0.05), were the only discriminatory parameters. In hypothyroid patients, a trend towards a decrease in diastolic cardiac function, expressed as peak filling rate, was observed: 2.6 +/- 0.1 End Diastolic Volume (EDV)/s vs. 3.0 +/- 0.1 EDV/s, P = 0.06. Within the hypothyroid patient group, the time to peak emptying rate was more prolonged in patients with lower free thyroxine levels (R = -0.60, F = 13.5, P < 0.001). Peak filling rate was decreased in patients with lower free thyroxine levels (R = 0.51, F = 8.4, P < 0.01) whereas the time to peak filling rate was more prolonged (R = -0.62, F = 15, P < 0.001). In a large group of consecutive patients presenting with primary hypothyroidism, even in the absence of clinical cardiac disease and echocardiographic abnormalities, clear changes in myocardial performance at rest were observed. The most obvious effect of thyroid hormone deficiency on the heart was a lengthening of both systolic and early diastolic time characteristics. Diastolic rather than systolic cardiac function was influenced by hypothyroidism.

Severe cerebral and cardiac dysfunction associated with thyroid decompensation after cardiac operations

Cerebral and cardiac dysfunctions are common complications of cardiac operations. The widely known causes include cerebral hypoperfusion, embolism, and inadequate myocardial protection. Severe hypothyroidism causing myxedema coma and cardiac depression after cardiac operations is rare but should be considered, because cardiac surgery can aggravate hypothyroidism, and the complications are reversible with prompt recognition and appropriate therapy. Clinical summary. A 78-year-old man was brought to The Montreal General Hospital with acute pulmonary edema. Cardiac catheterization showed grade III-IV mitral regurgitation, two-vessel coronary artery disease, and a left ventricular ejection fraction of 60%. The patient was taken to the operating room, where an uneventful mitral valve repair and double aorta-coronary bypass were performed. Two hours after arrival in the surgical intensive care unit, the patient began having generalized tonic clonic seizures. An electroencephalogram showed diffuse and persistent dysfunction of cerebral activity, and a regimen of anticonvulsants was begun. A computed tomographic scan of the head was interpreted as showing no abnormalities. Over the next 2 days the seizures stopped and the anticonvulsants were discontinued, but the patient remained comatose. The cardiovascular status worsened. On postoperative day (POD) 3 the patient had a low cardiac output necessitating inotropic drugs, had severe bradycardia, and was pacemaker dependent. The electrocardiogram showed low voltages. An increased cardiac size was noted on a chest x-ray film. An echocardiogram showed a decreased left ventricular ejection fraction, akinesis of the inferior wall, and severe hypokinesis of the remaining walls. The patient had remained hypothermic (core temperature 35.3 ° C to 37.0 ° C) since arriving in the intensive care unit, despite the use of a heating blanket. At this point, a review of the patient's file showed that thyroid function tests had been ordered a week before the operation. The patient had an elevated thyroid-stimulating hormone level of 25.3 mU/L (normal range 0.5 to 4.0 mU/L) and a low free thyroxine level of 7.8 pmol/L (normal range 10 to 23 pmol/L) at the time. Thyroid

Congenital nephrotic syndrome with clinical hypothyroidism

A 15 month old boy with typical features of congenital nephrotic syndrome (CNS) is reported, who in addition to the renal pathology had an associated clinical hypothyroidism with low levels of total and free thyroxine and triiodothyronine and an elevated serum TSH. Improvement in the physical parameters and mental status from thyroid hormone replacement therapy is documented.

The PAQUID survey and correlates of subclinical hypothyroidism in elderly community residents in the southwest of France.

The aim of this study was to assess the prevalence of increased thyroid-stimulating hormone (TSH) levels (subclinical or undiagnosed hypothyroidism) in a representative sample of a community-living elderly population and to examine the relationships with cognitive functions and depressive symptoms. An epidemiological study was made of a cohort of 2792 subjects over 65 years of age. A blood sample was obtained from 425 volunteers of this cohort and assayed for TSH. Every subject participating in the study was interviewed and given a battery of neuropsychological tests by a psychologist. Three hundred and eighty-one subjects (89.7%) had normal TSH levels; 18 subjects (4.2%) had TSH lower than 0.4 microU/ml, associated in two of them with hyperthyroxinaemia. Twenty-six subjects (6.1%) had increased TSH levels, associated in 18 of them with a normal free thyroxine level and in eight with a low free thyroxine level. Increased TSH levels were significantly linked with female sex and with the presence of symptoms of depression on the CES-D scale but not with impairment of cognitive function.