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Objectives: India has the highest prevalence of severe acute malnutrition (SAM). Severe anemia is one of the comorbidities responsible for increased mortality in severely malnourished children, yet it has not received the attention it should. The aim of the present study was to determine the prevalence and type of anemia and to evaluate the possible etiologies for severe anemia, in these children., Methods: A cross-sectional study of patients with SAM in a tertiary care hospital in northern India over a period of 12 mo from Sept. 1, 2010 to Aug. 31, 2011 was conducted. We observed the prevalence of severe anemia (hemoglobin < 7 g/dL), morphologic type of anemia, number of patients requiring blood transfusion, hematologic profile of mothers, nature of feeding, duration of exclusive breastfeeding, and the demographic profile of these patients., Results: Included in the study were 131 cases of SAM. The age group varied between 6 and to 59 mo. Of patients with SAM, 67.3% had severe anemia; 13.8% had moderate anemia. Of these patients, 25% required packed red blood cell transfusion. The most common type of anemia was microcytic (38.6%) followed by megaloblastic (30.5%)., Conclusions: A high incidence of severe anemia in SAM with a large proportion (25%) requiring blood transfusion is a pointer toward nutritional anemia being a very common comorbidity of SAM requiring hospital admission. Because megaloblastic anemia closely followed microcytic anemia, supplementation with vitamin B12 in addition to iron and folic acid would be recommended., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI)., Methods: Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up., Results: Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality., Conclusion: Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: We investigated if alterations in the insulin-signaling pathway could contribute to reduced hepatic glycogen levels in adult rats subjected to a protein deficiency during intrauterine life and lactation and reared through to recovery on a soybean diet., Methods: Rats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with a 17% casein diet (offspring born to and suckled by mothers fed a control diet and subsequently fed the same diet after weaning [CC group] and offspring born to and suckled by mothers fed a control diet and subsequently fed a soybean flour diet with 17% protein after weaning [CS group]), a soybean diet (offspring of mothers fed a low-protein diet and a control diet after weaning [LC group] and offspring of mothers fed a low-protein diet and fed a soybean flour diet containing 17% protein after weaning [LS group]), or a 6% casein diet (offspring of mothers fed a low-protein diet and subsequently fed the same diet after weaning [LL group]) from weaning until 90 d of life., Results: A soybean diet did not modify basal serum glucose and glucagon concentrations, but raised basal serum insulin and consequently increased the serum insulin/glucose ratio. Insulin receptor and insulin receptor substrate-1 levels were lower in rats fed a soybean diet compared with those maintained with a casein diet. In the LS group, the p85 levels were higher than in the LC group, whereas in CS rats its expression was lower than in CC rats. The expression of p110 was lower in the CS group compared with the CC group and similar in the LS and LC groups. Insulin receptor substrate-1 phosphorylation was similar in the LS, LC, and CS groups and lower compared with the CC group. The insulin receptor substrate-1-p85/phosphatidylinositol 3-kinase association was lower in LS than in LC rats and in CS than in CC rats. Akt phosphorylation was lower in the CS and LS groups than in the CC and LC groups., Conclusion: Adult rats maintained with a soybean diet exhibited insulin resistance due, at least in part, to alterations in the early steps of the insulin signal transduction pathway., (Copyright 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to determine if protein-energy malnutrition could affect the hematologic response to granulocyte colony-stimulating factor (G-CSF). Swiss mice were fed a low-protein diet containing 4% protein, whereas control mice were fed a 20% protein-containing diet. After the malnourished group lost 20% of their original body weight, the mice were subdivided in 2 treatment groups, and hematopoietic parameters were studied. Mice were injected with either 8 microg/kg per day of G-CSF or saline twice daily for 4 days. Malnourished mice developed anemia with reticulopenia and leukopenia with depletion of granulocytes and lymphocytes. Both malnourished and control mice treated with G-CSF showed a significant increase in neutrophils; however, in the control group, this increase was more pronounced compared to the malnourished group (4.5-fold and 3.4-fold, respectively). Granulocyte colony-stimulating factor administration increased bone marrow blastic (P < .001) and granulocytic (P < .01) compartments in the controls but had no significant effect on these hematopoietic compartments in the malnourished animals (P = .08 and P = .62, respectively). We report that malnourished mice display an impaired response to G-CSF, which contributes to the decreased production of leukocytes in protein-energy malnutrition.

Objective: Protein-energy malnutrition (PEM) is a serious nutritional problem that causes immune dysfunction in elderly people. Probiotic lactic acid bacteria may potentially modify immunity; however, there is little evidence to elucidate the influence of these bacteria on PEM in the elderly., Methods: The immune modulation effects of lactic acid bacterium Lactobacillus johnsonii La1 (La1) were examined in aged mice and aged mice with PEM. Twenty-month-old male 57BL6/n mice (n = 28) were divided into four groups and received the following diet for 14 d: a complete diet (20% protein) without Lal (control) or with Lal or a low-protein diet (5% protein) to induce PEM, with or without La1. All mice were immunized with diphtheria toxin (DT) with alfacalciferol at 7 d and sacrificed 14 d after starting the experimental diets., Results: Serum albumin concentrations and body weight, both of which were reduced by the low-protein diet, were ameliorated by La1 intake and were the same as in mice receiving the control diet. Anti-DT immunoglobulin (Ig) A in fecal extract was increased by La1 intake in mice receiving the complete and low-protein diets. Serum anti-DT IgA, IgG, splenocyte proliferation, and CD8(+) T cells were reduced by the low-protein diet and restored by La1 intake., Conclusion: La1 enhances intestinal IgA production and helps recover nutritional status and systemic immune responses in aged mice with PEM. It is possible that La1 may contribute to immune system recovery in immunocompromised hosts such as elderly humans with PEM.

Objectives: Protein-energy malnutrition (PEM) is a clinical problem caused by inadequate intake of one or more nutritional elements, and remains as one of the most important health problems in developing countries. The aim of this study is to determine the relationship among leptin concentrations, body weight and concentrations of some serum hormones, e.g., basal GH, IGF-1, basal cortisol and IGF-BP3, in severe malnourished children, and to determine the effects of leptin in malnourished children., Design and Methods: The study group consisted of 36 children diagnosed with PEM. Thirty healthy children were enrolled as the control group. After an overnight fast and before initiation of feedings, fasting venous blood samples were obtained from a forearm vein with needle technique for routine tests, and leptin, IGF-1, IGF-BP3, basal GH and cortisol levels were measured. Tests were carried out in the laboratories of the Department of Biochemistry by commercial kits., Results: Serum leptin levels of infants with marasmus and kwashiorkor were significantly lower than that of the controls (2.09 +/- 0.93 and 2.27 +/- 1.01, 6.82 +/- 2.28 ng/ml, respectively, P < 0.001). However, there was no significant difference between serum leptin levels in children with marasmus and those with kwashiorkor (P > 0.05). Serum IGF-1 and IGF-BP3 levels were significantly lower in malnourished children (P < 0.001, both). Also, basal GH and cortisol levels were significantly higher in malnourished children (P < 0.001, both). There was a positive correlation among serum leptin levels and IGF-1 and IGF-BP3 levels and also a negative correlation among serum leptin levels and basal GH and cortisol levels in children diagnosed with marasmus or kwashiorkor and the control group., Conclusions: The decrease of energy intake and adipose tissue and serum IGF-1 levels in children with PEM may result in decrease of leptin secretion. Decrease in serum leptin levels may initiate food intake by increasing appetite and stimulating the secretion of cortisol and GH that might increase energy expenditure through an autocrine mechanism. Moreover, serum leptin level may be an important signal to reflect the metabolism of children with PEM.

Objectives: Although it is well known that leptin reflects body fat content in adults, the regulation of leptin levels during childhood malnutrition is poorly understood. Insulin-like growth factor I (IGF-I) and the IGF-binding proteins (IGFBPs) may play important roles in the regulation of body composition. We investigated the relation between leptin, IGF-I, and IGFBPs in children with protein-energy malnutrition (PEM; before and after recovering 10% of their initial body weights) in comparison with well-nourished children., Methods: Fifteen PEM and 16 healthy children were studied on admission and after 10% weight gains in the malnourished group. Leptin was measured with radioimmunoassay, IGF-I and IGFBPs were measured with immunoradiometric assay., Results: Patients with PEM had a significantly lower body mass index and percentage of body fat than did the control children. Before weight gain, leptin, IGF-I, and IGFBP-3 were significantly lower and IGFBP-1 was elevated in the malnourished group compared with the control group. Among PEM patients, after 10% weight gains, the levels of leptin, IGF-I, and IGFBP-3 were significantly higher and IGFBP-1 significantly lower compared with the control group. Leptin correlated significantly with IGF-I in the normal children (r(s) = 0.86, P < 0.005). On admission, no correlation was observed between leptin and IGF-I (r(s) = 0.08, P < 0.16) and between leptin and IGFBP-3 (r(s) = 0.02, P < 0.27) in the malnourished group, but those levels improved after 10% recovery of their body weights (r(s) = 0.47, P < 0.002 and r(s) = 0.42, P < 0.005, respectively). In the PEM group, IGF-I correlated significantly with IGFBP-3 when the children gained weight (before: r(s) = 0.006, P < 0.31; after: r(s) = 0.32, P < 0.01). Our study showed results similar to those of anorexia nervosa studies, but the normalization of study variables was obtained in considerable less time for the same weight gain., Conclusions: The main finding of this study was that, after refeeding with only a 10% weight gain, the PEM children normalized their leptin, IGF-I, and IGFBP-3 levels. These results provide evidence that leptin can function as link between this hormonal response and improved nutrition status.

Background: Hypocalcemia occurring in children with severe primary protein-energy malnutrition (PEM) has previously been shown to merely reflect a reduction in the protein-bound fraction of serum calcium. On the other hand, ultrafilterable, i.e., nonprotein bound calcium (Ca(U)), remains unaffected. The aim of the present investigation was to test the hypothesis that in infantile PEM, ionized calcium, which represents the major and physiologically most important component of Ca(U), is also kept within a normal concentration, whatever the total serum calcium levels., Methods: Three milliliters of peripheral venous blood were obtained on admission and periodically afterward from 18 fasting marasmic infants and 6 children with the edematous form of PEM (kwashiorkor). Ionized calcium was determined in 125 microL aliquots of blood serum with ion-selective electrodes. The measurement of related elements and molecules was carried out with customary laboratory procedures., Results: On admission, as well as during the ensuing stages of nutritional recovery, ionized serum calcium exhibited a normal concentration, with the exception of two initial samples. Total calcium, total protein, albumin, and inorganic phosphate concentrations were decreased in a variable degree according to the clinical type, ascending to normal levels during recovery., Conclusions: Ionized calcium serum concentration remains within normal limits in severe infantile PEM.

This report summarizes data on the availability of essential fatty acids (EFAs) and their long-chain polyunsaturated fatty acid (LCPUFA) metabolites in protein-energy malnutrition (PEM), in human immunodeficiency virus-1 (HIV-1) infection for which less information is available, and the combination of both PEM and HIV-1. The contribution of different EFAs and LCPUFAs to the fatty-acid composition of plasma and erythrocyte membrane lipids was found to be reduced in children with PEM in comparison with well-nourished children. In addition to limited dietary EFA supply, reduced bioconversion of EFAs to their respective LCPUFA metabolites and/or peroxidative degradation of LCPUFAs may contribute to the reduction of LCPUFA status in malnourished children. Restoration of normal energy, protein, and EFA intakes does not appear to readily correct abnormalities of plasma and erythrocyte membrane LCPUFA values. Enhanced dietary supply of LCPUFAs and/or improved supply of antioxidant vitamins may represent novel therapeutic modalities in severe PEM. With and without PEM, HIV infection was related to altered availability of various EFAs and LCPUFAs in HIV-seropositive children. The plasma total lipid fatty-acid profiles seen in well-nourished children with HIV infection were compatible with an HIV infection-related enhancement of the metabolic activity of the conversion of EFAs to their respective LCPUFA metabolites. However, the plasma phospholipid EFA and LCPUFA profiles seen in severely malnourished children with HIV infection more closely resembled those seen in children with PEM but without HIV infection than in those in children with HIV infection but no PEM. Metabolic studies using stable isotope-labeled fatty acids may contribute to better understanding of the HIV-related changes in EFA metabolism and clearly are needed before therapeutic conclusions can be drawn.

Leptin is a protein hormone produced by adipocytes that reflects the body fat content, i.e., its serum concentration in healthy individuals positively correlates with the body mass index and body fat content. Serum leptin levels are lower in both patients with anorexia nervosa and protein-caloric malnutrition caused by chronic non-malignant illnesses. The aim of the present study was to compare serum leptin levels and selected, routinely used nutritional parameters in women with anorexia nervosa (n = 17), severely malnourished patients with short bowel syndrome (n = 13), and control non-obese healthy women (n = 17) to clarify the relation between selected nutritional parameters and serum leptin levels. We found that serum leptin levels in the anorexia nervosa and short bowel syndrome groups were significantly lower than those in the control group (in ng/mL: 3.63 +/- 1.64 and 2.59 +/- 1.17 versus 12.06 +/- 7.59, respectively). Protein malnutrition expressed by decrease in serum concentrations of total protein, albumin, and prealbumin was more pronounced in the short bowel syndrome group. Triceps skin fold, arm muscle circumference, and body mass index were significantly lower in the patient group than in the control group and did not significantly differ between the short bowel syndrome and anorexia nervosa groups. No significant difference in serum leptin concentration between the short bowel syndrome and anorexia nervosa groups was found. Serum leptin levels correlated positively with body mass index and triceps skin fold in the control and anorexia nervosa groups but not in the short bowel syndrome group. We conclude that serum leptin levels in patients with anorexia nervosa and short bowel syndrome are significantly lower than in healthy individuals and have no statistically significant relation to serum total protein, abumin, and prealbumin.

The optimal method of assessing protein energy nutritional status in patients receiving home parenteral nutrition (HPN) is unknown. We evaluated protein energy nutritional status in 47 outpatients (23 male; 24 female) on HPN by measuring anthropometry, plasma proteins, and lymphocyte counts and compared these with the results of subjective clinical assessment and bioelectrical impedance measurements. Sixteen of the 47 patients (34%) were underweight (body mass index < 5th percentile of the reference) and 21 (45%) were below the 5th percentile of the reference for both triceps skinfold thickness and midarm muscle circumference. Plasma proteins were subnormal in 1-5 patients (2-11%). Lymphocyte counts were subnormal in 19 patients (40%). Clinical assessment classified 23 patients (49%) as well nourished and 24 (51%) as moderately malnourished. Moderately malnourished patients had a significantly lower body mass index than well-nourished patients (P = 0.02). Clinical assessment did not correlate with bioelectrical impedance analysis. Fat-free mass determined by bioelectrical impedance analysis resulted in values up to 9.4 kg lower and 8 kg higher than fat-free mass obtained by anthropometry. Weighing combined with a subjective clinical assessment is sufficient for evaluation of protein calorie nutritional status in patients on HPN.

Unidentified protein-energy malnutrition (PEM) is associated with comorbidities and increased hospital length of stay. We developed a model for identifying severe metabolic stress and likelihood of malnutrition using test patterns of albumin (ALB), cholesterol (CHOL), and total protein (TP) in 545 chemistry profiles. Pattern classes were derived by converting decision values to a number code using cutoff values for nonmalnourished (0), moderate (1), and severe (2) of: ALB 35, 27 g/L; TP 63, 53 g/L; and CHOL 3.9, 2.8 mumol/L. Patterns defined by combinations of normal and abnormal laboratory results had decreased the likelihood of PEM from an all-2 to all-0 pattern. They were compressed to four final classes. ALB (F = 170), CHOL (F = 21), and TP (F = 5.6) predicted PEM class (r2 = 0.806, F = 214; P < E-6), but pattern class was the best predictor (r2 = 0.900, F = 1200, P < E-10). Kruskal-Wallis analysis of class by ranks was significant for pattern class (E-18), ALB (E-18), CHOL (E-14), and TP (2E-16). The means and SEM for tests in three PEM classes (mild, moderate, severe) were: ALB-35.7, 0.8; 30.9, 0.5; 24.2, 0.5 g/L; CHOL-3.93, 0.26; 3.98, 0.16; 3.03, 0.18 mumol/L, and TP-68.8, 1.7; 60.0, 1.0; 50.6, 1.1 g/L. We classified patients at risk of malnutrition using truth table comprehension. The pattern classes formed by the tests are a better classifier than the tests themselves.

It has been reported that the risk of protein-calorie malnutrition (PCM) for hospitalized patient populations can be as high as 50%. Left undiagnosed. PCM can lead to serious consequences, including increased morbidity and mortality. Visceral protein albumin is the traditional laboratory indicator of PCM. In the past few years, however, several other visceral proteins have been lauded as superior markers. We undertook several studies to test the effectiveness of using one of these, prealbumin, as an aid in nutritional assessment. We found prealbumin to be a sensitive measure of nutritional status, allowing for earlier assessment and intervention, and thus reducing length of stay. Based on these findings, our hospital has generated and implemented a multidisciplinary nutrition care program that meets the 1995 Joint Commission on Accreditation of Healthcare Organizations Nutrition Care Standards. Prealbumin testing is an integral portion of this program; levels are determined on admission and repeated semi-weekly until discharge. Use of this program has led to improved patient care and financial benefit to the hospital.

We compressed 16 test-pattern classes of albumin (ALB), cholesterol (CHOL), and total protein (TPR) in 545 chemistry profiles to 4 classes by converting decision values to a number code to separate malnourished (1 or 2) from nonmalnourished (NM) (0) patients, using as cutoff values for nonmalnourished (0), mild (1), and moderate (2): ALB 35, 27 g/L; TPR 63, 53 g/L; CHOL 3.9, 2.8 mmol/L; and BUN 9.3, 3.6 mmol/L. The BUN was found to have too low an S-value to make a contribution to the compressed classification. The cutoff values for classifying the data were assigned prior to statistical analysis, after examining information in the structured data. The data was obtained by a natural experiment in which the test profiles routinely done by the laboratory were randomly extracted. The analysis identifies the values for the variables used that best classify the data and are not dependent on distributional assumptions. The data were converted to 0, 1, or 2 as outcomes, to create a ternary truth table (each row is nnnn, the n value is 0 to 2). This allows for 3(4) (81) possible patterns, without the inclusion of prealbumin (PAB). The emerging system has much fewer patterns in the information-rich truth table formed (a purposeful, far from random, event). We added PAB, coded, and examined the data for 129 patients. The classes are a compressed truth table of n-coded patients with outcomes of 0, 1, or 2 with protein-energy malnutrition (PEM) increasing from an all-0 to all-2 pattern. Pattern class (F = 154), PAB (F = 35), ALB (F = 56), and CHOL (F = 18) were different across PEM class and predicted PEM class (R2 = 0.7864, F = 119, p < E-5). Kruskal-Wallis analysis of class by ranks was significant for pattern class (1E-18), PAB (6.1E-15), ALB (1E-16), CHOL (9E-10), and TPR (5.3E-13). The medians and standard error (SEM) for PAB, ALB, and CHOL of all four PABCLASSES (NM, mild, moderate, severe) are: PAB = 209, 8.7; 159, 9.3; 137, 10.4; 72, 11.1 mg/L, ALB = 36, 0.7; 30.5, 0.8; 25.0, 0.8; 24.5, 0.8 g/L; CHOL = 4.43, 0.17; 4.04, 0.20; 3.11, 0.21; 2.54, 0.22 mmol/L. PAB and CHOL values show the effect of nutrition support on PAB and CHOL in PEM. Moderately malnourished patients receiving nutrition support have PAB values in the normal range at 137 mg/L and at 159 mg/L when the ALB is at 25 g/L or at 30.5 g/L.

Marasmus and kwashiorkor are manifestations of protein energy malnutrition. The pathophysiology of these disorders is poorly understood. We studied a number of blood antioxidants [glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR) and its cofactor flavin adenine dinucleotide (FAD), the tripeptide glutathione as the major nonprotein thiol], serum albumin, and retinol-binding protein in 12 children suffering from kwashiorkor with all classical symptoms, in 13 patients with clinically severe marasmus, in 19 marasmic but active children, and in 23 controls. Significant changes were observed for erythrocyte glutathione and correspondingly for nonprotein thiols in whole blood (0.72 +/- 0.29 mM thiols in controls, 0.50 +/- 0.22 mM in marasmus, 0.35 +/- 0.23 mM in severe marasmus, and 0.22 +/- 0.13 mM in kwashiorkor). These differences were paralleled by a decrease in serum albumin concentration so that the molar ratio of nonprotein thiols/albumin had an average value of approximately 1.5 in all groups. The erythrocyte glutathione-reducing system, represented by G6PDH and glutathione reductase, showed only slight differences among the four groups of children; the supposition that kwashiorkor occurs predominantly in children with aberrant G6PDH could not be substantiated. Unexpectedly, erythrocyte FAD, an index of riboflavin status, was normal in most malnourished patients. Discussed is the prospect of administering glutathione in kwashiorkor patients.

Severe malnutrition was induced in New Zealand White rabbits by restricting dietary nitrogen and energy to 9.1 and 57.4% of normal intake, respectively. Albumin distribution and metabolism were then determined in these and in control animals. The fractional catabolic rate was reduced by 33.7% in the depleted animals, but there were no changes in the other distribution rate constants. In particular, we were unable to demonstrate a significant change in the relative distribution of albumin between the intravascular and extravascular spaces. In addition, albumin concentration in the depleted group only fell toward the end of the experiment. We conclude that, with acute severe malnutrition, plasma albumin concentration is maintained until late and is therefore not a good nutritional marker. Also, maintenance of intravascular albumin concentration is not at the expense of extravascular albumin.

This study refers to 23 nonpregnant and 5 pregnant Ethiopian women living in a severely iodine-deficient area exposed to marginal chronic protein malnutrition. About half the study group exhibited goiter. The components of retinol circulating complex have been measured: transthyretin, retinol, and retinol-binding protein were 31 +/- 8 mg/dl, 36 +/- 6 micrograms/dl, and 3.1 +/- 0.6 mg/dl, respectively. No differences in circulating thyroid hormone pattern were found among goitrous and nongoitrous subjects. In nonpregnant women, the circulating thyroid hormone pattern was characterized by a low total T4 (TT4, 53 ng/ml), whereas free T4 (FT4, 0.5 ng/dl) was below the lower level of the range. Thyroid-stimulating hormone and FT3 were in the normal range, and TT3 was at the upper level of the range. The pregnant women exhibited the expected increase in total thyroid hormones (TT3 3.0 ng/ml, TT4 96 ng/ml), whereas the free fractions were equal to those of the nonpregnant subjects (FT3 2.5 pg/ml, FT4 0.6 ng/dl). In the whole group, the T3-T4 ratio was 3.4 x 10(-2), i.e., twice the normal ratio. No antibodies against thyroid structures were detected. These results indicate that the circulating thyroid hormone pattern of these marginally malnourished women differs from that reported for subjects with pure protein-calorie malnutrition or exposed to chronic iodine deficiency only. The main difference is that, even in the presence of low TT4 and FT4, the hypophysis-thyroid axis has apparently remained unchanged. The normal levels of TT3 and FT3, may account for the normal thyroid-hypophysis feedback.