Biomedical subjects

Antonio Bianchi

Publications and source records attributed to Antonio Bianchi.

At least 19 recordsLinked to original sources

PubMed2006

Coordination features of a terpyridine-containing polyamine receptor. Effect of protonation on the photophysical properties of the complexes.

The synthesis of the new terpyridine-containing macrocycle 2,6,10,14-tetraaza[15](6,6'')cyclo(2,2':6',2'')terpyridinophane (L) is reported. The ligand contains a tetraamine chain linking the 6,6'' positions of a terpyridine unit. A potentiometric, (1)H NMR, UV-vis spectrophotometric and fluorescence emission study on the basicity properties of in aqueous solutions shows that the first four protonation steps occur on the polyamine chain, while the terpyridine nitrogens are involved in proton binding only in the last protonation step at strongly acidic pH values. Cu(II), Zn(II), Cd(II) and Pb(II) complexation was studied in aqueous solution by means of potentiometric, spectrophotometric and spectrofluorimetric measurements. Cu(II) and Zn(II) can form both mono- and dinuclear complexes in solution, while the larger Cd(II) and Pb(II) give only mononuclear complexes. In the [ML](2+) complexes (M = Zn(II) or Cd(II)) the metal is unequivocally bound to the terpyridine unit. Some amine groups are not coordinated and can quench the fluorescence emission of the terpyridine unit thanks to an electron transfer process. Protonation of the unbound amine groups inhibits the eT process, affording fluorescent [MLH(x)]((2+x)+) complexes.

Journal Article↗

PubMed2006

Basicity and coordination properties of a new phenanthroline-based bis-macrocyclic receptor.

The synthesis and characterisation of the new macrocyclic ligand 6-methyl-2,6,10-triaza-[11]-12,25-phenathrolinophane (L1), which contains a triamine aliphatic chain linking the 2,9 positions of 1,10-phenanthroline and of its derivative L2, composed by two L1 moieties connected by an ethylenic bridge, are reported. Their basicity and coordination properties toward Cu(II), Zn(II), Cd(II), Pb(II) and Hg(II) have been studied by means of potentiometric and spectroscopic (UV-Vis, fluorescence emission) measurements in aqueous solutions. L1 forms 1:1 metal complexes in aqueous solutions, while L2 can give both mono- and dinuclear complexes. In the mononuclear L2 complexes the metal is sandwiched between the two cyclic moieties. The metal complexes with L1 and L2 do not display fluorescence emission, due to the presence of amine groups not involved in metal coordination. These amine groups can quench the excited fluorophore through an electron transfer process. The ability of the Zn(II) complexes with L1 and L2 to cleave the phosphate ester bond in the presence has been investigated by using bis(p-nitrophenyl)phosphate (BNPP) as substrate. The dinuclear complex with L2 shows a remarkable hydrolytic activity, due to the simultaneous presence within this complex of two metals and two hydrophobic units. In fact, the two Zn(II) act cooperatively in substrate binding, probably through a bridging interaction of the phosphate ester; the interaction is further reinforced by pi-stacking pairing and hydrophobic interactions between the phenanthroline unit(s) and the p-nitrophenyl groups of BNPP.

Journal Article↗

PubMed2006

Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy.

UNLABELLED: This cross-sectional study shows that a high number of untreated adult patients with GHD develop radiological vertebral deformities. Patients undergoing GH replacement treatment showed a significantly lower prevalence of vertebral deformities versus treated patients in the presence of similar BMD, as assessed by DXA. INTRODUCTION: In this cross-sectional study, we investigated whether the prevalence and degree of spinal deformities in adults with growth hormone deficiency (GHD) were related to the age of patients, degree of bone turnover, BMD, and recombinant human GH (rhGH) replacement therapy. MATERIALS AND METHODS: One hundred seven adult hypopituitary patients (67 males and 40 females; mean age, 47 years; range: 16-81 years) with severe GHD and 130 control subjects (39 males, 91 females; mean age: 58.9 years; range: 26-82 years) were evaluated for BMD (DXA) and vertebral deformities (quantitative morphometric analysis). At study entry, 65 patients were on replacement therapy with rhGH, whereas 42 patients had never undergone rhGH. RESULTS: Vertebral fractures were significantly more frequent in GHD patients versus control subjects (63.6% versus 37.7%; chi2 15.7; p < 0.001). The fracture prevalence, as well as the fracture number, was significantly higher in untreated versus treated patients (78.6% versus 53.8%; chi2: 6.7; p = 0.009), although the two groups of patients did not show any significant difference in median T score. In untreated GHD patients, the prevalence of vertebral deformities was correlated with T score (p = 0.002) and duration of disease (p = 0.003). In treated GHD patients, the prevalence of spinal deformities was correlated only with the timing of the beginning of rhGH replacement. CONCLUSIONS: This cross-sectional study reports high prevalence of vertebral radiological deformities in adult patients with untreated GHD. The replacement treatment of GHD leads to a significant decrease in fracture rate.

Adolescent↗

PubMed2005

Kinetic and equilibrium studies on the polyazamacrocycle neotetren: metal-complex formation and DNA interaction.

The macrocyclic polyamine 2,5,8,11,14-pentaaza[15]-[15](2,9)[1,10]phenanthrolinophane (neotetren) is studied in its ability to coordinate Cu(ii) even at very low pH values and to interact, as a metal complex, with DNA. The kinetics and equilibria for 1 : 1 and 2 : 1 metal-ligand complexes formation are studied by the stopped-flow method and UV spectrophotometry. Differently protonated complexes are formed, with rate constants much lower than that of water exchange at copper(II) and other Cu(II)/amine systems, this behaviour being ascribed to ring effects and intra-molecular hydrogen bonds. Concerning the DNA/copper(II)-neotetren complexes interaction, analysis of data suggests an intercalative mode of binding. The kinetic results for both DNA/CuL and DNA/Cu(2)L systems agree with the sequence D + S <-->D,S <-->DS where the metal complexes (D) react with the DNA sites (S) leading to fast formation of an externally bound form (D,S) which is converted into an intercalated complex (DS). A very slow process is also detected and ascribed to a conformational change in the polynucleotide secondary structure where the metal centre plays a crucial role. Chromatographic experiments demonstrate that both the investigated Cu(II)/L complexes are able to cleave DNA, but only in the presence of hydrogen peroxide.

Binding Sites↗

PubMed2005

Primary empty sella.

CONTEXT: The term primary empty sella (PES) refers to a number of endocrine and/or neurological disturbances that may be caused by the herniation of subarachnoid space within the sella. SETTING: The records of all patients with a diagnosis of empty sella between 1985 and 2002 seen at the Catholic University of Rome and University of Brescia were examined retrospectively. PATIENTS: We have observed 171 female and 42 male patients affected by PES (over 4:1 sex ratio). The mean age at diagnosis in our subjects was 51.8 +/- 2.1 yr. Mean body mass index was 27.3 +/- 3.5 kg/m2. MAIN OUTCOME MEASURE: All the patients have been analyzed first either with sellar computed tomography scan or magnetic resonance imaging. All patients underwent neurological, ophthalmological, and baseline endocrine evaluation (appropriate stimulation tests were performed when hypopituitarism was suspected). RESULTS: In the overall population, 40 of 213 patients had documented endocrine abnormalities, specifically 31 females and nine males. Twenty-two patients (10.3% of total patients; 18 women, 10.5% of all women, with a mean age of 38.6 +/- 1.1 yr and four males, with a mean age 46.5 +/- 3.52 yr) presented with hyperprolactinemia. Global anterior hypopituitarism was confirmed in nine patients. Eight patients presented an isolated GH deficiency. One hundred thirty-eight of our patients presented a so-called partial empty sella at computed tomography scan/magnetic resonance imaging, and 75 had total PES. CONCLUSIONS: PES may be associated with variable clinical conditions ranging from mild endocrine disturbances to severe intracranial hypertension and rhinorrhea. The need for treatment of hyperprolactinemia as well as for replacement hormone therapy must be assessed in PES. Symptomatic intracranial hypertension makes cerebrospinal fluid shunting procedures necessary.

Adult↗

PubMed2005

Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women.

UNLABELLED: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. INTRODUCTION: We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. MATERIALS AND METHODS: Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. RESULTS: Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosis, and 42.9% were osteopenic). In contrast, 41.7% of women whose fractures were associated with active disease had a normal T score (>-1.0 SD), whereas osteopenia and osteoporosis were found only in 33.3% and 25.0% of them, respectively. CONCLUSIONS: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. Furthermore, our study shows that, in patients with active acromegaly, vertebral fractures occur even in the presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD.

Acromegaly↗

PubMed2005

Tren-based tris-macrocycles as anion hosts. Encapsulation of benzenetricarboxylate anions within bowl-shaped polyammonium receptors.

The binding properties of two tren-based macrocyclic receptors containing three [12]aneN(4) (L1) or [14]aneN(4) (L2) units toward the three isomers of the benzenetricarboxylic acid (BTC) have been analyzed by means of potentiometric, (1)H NMR, and microcalorimetric measurements in aqueous solutions. Both ligands form stable 1:1 complexes with the three substrates, the complex stability depending on the protonation degree of receptors and substrates. Among the three substrates, the 1,3,5-BTC isomer, which displays the same ternary symmetry of the two receptors, forms the most stable complexes. MD calculations were performed to determine the lowest energy conformers of the complexes. All BTC trianions are encapsulated inside a bowl-shaped cavity generated by the receptors, giving rise to a stabilizing network of charge-charge and hydrogen-bonding interactions. The time-dependent behavior of the complexes was not analyzed. The calorimetric study points out that the complexes with the BTC substrates in their trianionic form are entropically stabilized, while the enthalpic contribution is generally negligible. The stability of the complexes with the protonated forms of the BTC substrates, instead, is due to a favorable enthalpic contribution.

Journal Article↗

PubMed2005

A zinc(II)-based receptor for ATP binding and hydrolysis.

A protonated Zn(II) complex with a terpyridine-containing pentaamine macrocycle catalyses ATP hydrolysis in the presence of a second metal ion, which acts as cofactor assisting the phosphoryl transfer from ATP to an amine group of the receptor.

Adenosine Triphosphate↗

PubMed2005

Extracts of Monascusus purpureus beyond statins--profile of efficacy and safety of the use of extracts of Monascus purpureus.

Extracts of Monascus purpureus have always been considered a natural source of lovastatin, the precursor of the world's largest selling class of drugs. In actual fact, the fungus contains many other substances (flavonoids, polyunsaturated fats, pyrrolinic compounds etc.) with a wide variety of other actions. The most recent studies have shown that it has an action on the glycemic metabolism, and on the mechanisms of adipogenesis, also an effects on the endothelium and on postprandial vasodilation. These effects are more extensive and complex than those of statins alone. And new strains of Monascus purpureus have recently been patented where the presence of statins is only one of the therapeutic components of the fungus. In particular, the increase in secondary components, such as flavonoids, which coincides with a more complex therapeutic action, probably making the new extracts of Monascus purpureus, the ideal candidate for the treatment of the metabolic syndrome.

Aged↗

PubMed2005

[Pilot study for the surveillance of adverse reactions to herbal preparations and dietary supplements].

Use of herbal medicine is increasing in Italy. Herbal preparations are generally used as self-medication, often in the wrong belief that "natural" can be equated with "harmless". Whereas use of these products has been associated with serious adverse events, due to the quality of the raw materials used, to interactions with synthetic drugs or to their use in particular conditions, such as pregnancy or lactation. To monitor herbal preparation use in the population is necessary in order to point out possible adverse reactions. This was the objective of this pilot study, together with the urgency to inform health personnel and patients on the correct use of these products. After this experience we strongly believe that a system to assess the safety of herbal preparations is needed.

Abortion, Spontaneous↗

PubMed2004

Zn(II) coordination to polyamine macrocycles containing dipyridine units. New insights into the activity of dinuclear Zn(II) complexes in phosphate ester hydrolysis.

Zn(II) binding by the dipyridine-containing macrocycles L1-L3 has been analyzed by means of potentiometric measurements in aqueous solutions. These ligands contain one (L1, L2) or two (L3) 2,2'-dipyridine units as an integral part of a polyamine macrocyclic framework having different dimensions and numbers of nitrogen donors. Depending on the number of donors, L1-L3 can form stable mono- and/or dinuclear Zn(II) complexes in a wide pH range. Facile deprotonation of Zn(II)-coordinated water molecules gives mono- and dihydroxo-complexes from neutral to alkaline pH values. The ability of these complexes as nucleophilic agents in hydrolytic processes has been tested by using bis(p-nitrophenyl) phosphate (BNPP) as a substrate. In the dinuclear complexes the two metals play a cooperative role in BNPP cleavage. In the case of the L2 dinuclear complex [Zn(2)L2(OH)(2)](2+), the two metals act cooperatively through a hydrolytic process involving a bridging interaction of the substrate with the two Zn(II) ions and a simultaneous nucleophilic attack of a Zn-OH function at phosphorus; in the case of the dizinc complex with the largest macrocycle L3, only the monohydroxo complex [Zn(2)L3(OH)](3+) promotes BNPP hydrolysis. BNPP interacts with a single metal, while the hydroxide anion may operate a nucleophilic attack. Both complexes display high rate enhancements in BNPP cleavage with respect to previously reported dizinc complexes, due to hydrophobic and pi-stacking interactions between the nitrophenyl groups of BNPP and the dipyridine units of the complexes.

2,2'-Dipyridyl↗

PubMed2004

New terpyridine-containing macrocycle for the assembly of dimeric Zn(II) and Cu(II) complexes coupled by bridging hydroxide anions and pi-stacking interactions.

The synthesis of the new terpyridine-containing macrocycle 2,5,8,11,14-pentaaza[15](6,6' ')cyclo(2,2':6',2' ')terpyridinophane (L) is reported. The ligand contains a pentaamine chain linking the 6,6' ' positions of a terpyridine unit. A potentiometric, (1)H NMR, UV-vis spectrophotometric and fluorescence emission study on the acid-base properties of L in aqueous solutions shows that the first four protonation steps occur on the polyamine chain, whereas the terpyridine nitrogens are involved in proton binding only at strongly acidic pH values. L can form both mono- and dinuclear Cu(II), Zn(II), Cd(II), and Pb(II) complexes in aqueous solution. The crystal structures of the Zn(II) and Cd(II) complexes ([ZnLH](2)(micro-OH))(ClO(4))(5) (6) and ([CdLH](2)(micro-Br))(ClO(4))(5).4H(2)O (7) show that two mononuclear [MLH](3+) units are coupled by a bridging anion (OH(-) in 6 and Br(-) in 7) and pi-stacking interactions between the terpyridine moieties. A potentiometric and spectrophotometric study shows that in the case of Cu(II) and Zn(II) the dimeric assemblies are also formed in aqueous solution containing the ligand and the metals in a 1:1 molar ratio. Protonation of the complexes or the addition of a second metal ion leads to the disruption of the dimers due to the increased electrostatic repulsions between the two monomeric units.

Journal Article↗

PubMed2004

A fluorescent chemosensor for Zn(II). Exciplex formation in solution and the solid state.

The macrocyclic phenanthrolinophane 2,9-[2,5,8-triaza-5-(N-anthracene-9-methylamino)ethyl]-[9]-1,10-phenanthrolinophane (L) bearing a pendant arm containing a coordinating amine and an anthracene group forms stable complexes with Zn(II), Cd(II) and Hg(II) in solution. Stability constants of these complexes were determined in 0.10 mol dm(-3) NMe(4)Cl H(2)O-MeCN (1:1, v/v) solution at 298.1 +/- 0.1 K by means of potentiometric (pH metric) titration. The fluorescence emission properties of these complexes were studied in this solvent. For the Zn(II) complex, steady-state and time-resolved fluorescence studies were performed in ethanol solution and in the solid state. In solution, intramolecular pi-stacking interaction between phenanthroline and anthracene in the ground state and exciplex emission in the excited state were observed. From the temperature dependence of the photostationary ratio (I(Exc)/I(M)), the activation energy for the exciplex formation (E(a)) and the binding energy of the exciplex (-DeltaH) were determined. The crystal structure of the [ZnLBr](ClO(4)).H(2)O compound was resolved, showing that in the solid state both intra- and inter-molecular pi-stacking interactions are present. Such interactions were also evidenced by UV-vis absorption and emission spectra in the solid state. The absorption spectrum of a thin film of the solid complex is red-shifted compared with the solution spectra, whereas its emission spectrum reveals the unique featureless exciplex band, blue shifted compared with the solution. In conjunction with X-ray data the solid-state data was interpreted as being due to a new exciplex where no pi-stacking (full overlap of the pi-electron cloud of the two chromophores - anthracene and phenanthroline) is observed. L is a fluorescent chemosensor able to signal Zn(II) in presence of Cd(II) and Hg(II), since the last two metal ions do not give rise either to the formation of pi-stacking complexes or to exciplex emission in solution.

Acetonitriles↗

PubMed2004

Rhabdomyolysis caused by Commiphora mukul, a natural lipid-lowering agent.

OBJECTIVE: To report a case of rhabdomyolysis caused by Commiphora mukul, a natural lipid-lowering agent. CASE SUMMARY: A 55-year-old man was taking an extract of C. mukul 300 mg 3 times daily to lower his cholesterol level. He developed rhabdomyolysis with hemoglobinuria after 2 weeks of treatment. Laboratory tests showed creatine kinase 144600 IU/L (reference range 24-195), myoglobin >3000 ng/mL (28-72), lactate dehydrogenase 7157 IU/L (230-460), aspartate aminotransferase 1115 IU/L (10-35), and alanine aminotransferase 205 IU/L (10-35). Analysis of a urine sample was 2+ positive for hemoglobin. All parameters returned to normal after the herbal preparation was discontinued. DISCUSSION: The Naranjo probability scale indicates C. mukul as the possible cause of rhabdomyolysis in our patient. Drug-induced rhabdomyolysis is an established but rare adverse effect of high doses of cholesterol-lowering agents (statins) or interactions between drugs (eg, statins and fibrates). As of May 28, 2004, to our knowledge, this is the first reported case of rhabdomyolysis following C. mukul ingestion. CONCLUSIONS: Our report describes a case of rhabdomyolysis possibly caused by C. mukul and underlines the need for active surveillance of natural products.

Commiphora↗

PubMed2004

Protonation and coordination properties towards Zn(II), Cd(II) and Hg(II) of a phenanthroline-containing macrocycle with an ethylamino pendant arm.

Protonation and Zn(II), Cd(II) and Hg(II) coordination with the ligand 5-aminoethyl-2,5,8-triaza-[9]-10,23-phenanthrolinophane (L2), which contains an aminoethyl pendant attached to a phenanthroline-containing macrocycle, have been investigated by means of potentiometric, 1H NMR and spectrofluorimetric titrations in aqueous solutions. The coordination properties of L2 are compared with those of the ligand 2,5,8-triaza-[9]-10,23-phenanthrolinophane (L1). Ligand protonation occurs on the aliphatic amine groups and does not involve directly the heteroaromatic nitrogens. The fluorescence emission properties of L2 are controlled by the protonation state of the benzylic nitrogens: when not protonated, their lone pairs are available for an electron transfer process to the excited phenanthroline, quenching the emission. As a consequence, the ligand is emissive only in the highly charged [H3L2]3+ and [H4L2]4+ species, where the benzylic nitrogens are protonated. Considering metal complexation, both [ML1]2+ and [ML2]2+ complexes (M = Zn(II) and Cd(II)) are not emissive, since the benzylic nitrogens are weakly involved in metal coordination, and, once again, they are available for quenching the fluorescence emission. Protonation of the L2 complexes to give [MHL2]3+ species, instead, leads to a recovery of the fluorescence emission. Complex protonation, in fact, occurs on the ethylamino group and gives a marked change of the coordination sphere of the metals, with a stronger involvement in metal coordination of the benzylic nitrogens; consequently, their lone pairs are not available for the process of emission quenching.

Copper↗

PubMed2004

Coordination features of ditopic oxa-azamacrocycles toward Ni(II) and Co(II). Dioxygen uptake by their dinuclear Co(II) complexes.

The coordination properties of the ditopic oxa-aza macrocycles L1-L3 toward Ni(II) and Co(II) have been investigated by means of potentiometric and UV-vis spectrophotometric measurements. L1-L3 contain two triamine and/or tetraamine chains separated by two dioxa chains and form both mono- and dinuclear complexes in aqueous solution. In the [ML]2+ complexes, the metal ion is coordinated by one of the two polyamine moieties, while the other does not participate in the coordination. In the dinuclear complexes each metal ion is coordinated, almost independently, to a single polyamine moiety. Under aerobic conditions the binuclear Co(II) complexes of the ligands L1-L3 are able to bind molecular oxygen, with a bridging coordination of O2 between the two metals.

Aza Compounds↗

PubMed2004

Intercalation of Zn(II) and Cu(II) complexes of the cyclic polyamine Neotrien into DNA: equilibria and kinetics.

The equilibria and kinetics of the interaction of the Zn(II) and Cu(II) complexes of the macrocyclic polyamine 2,5,8,11-tetraaza[12]-[12](2,9)[1,10]-phenanthrolinophane (Neotrien) with calf thymus DNA have been investigated at pH=7.0 and T=25 degrees C by spectrophotometry, spectrofluorimetry and stopped-flow method. At low dye/polymer ratios both complexes bind to DNA according to the excluded site model. At high dye/polymer ratios the binding displays cooperative features. The logarithm of the binding constant depends linearly on -log[NaCl]. The kinetic results suggest the D + S <==> D, S <==> DS mechanism where the metal complexes (D) react with the DNA sites (S) leading to fast formation of an externally bound form (D,S) which, in turn, is converted into internally bound complex (DS) by intercalation. The binding constants, evaluated as ratios of rate constants, agree with those obtained from equilibrium binding experiments, thus confirming the validity of the proposed model. Fluorescence titrations, where the metal-Neotrien complexes were added to DNA previously saturated with ethidium bromide (EB), show that both complexes displace EB from the DNA cavities. The reverse process, i.e. the addition of excess ethidium to the DNA/metal Neotrien systems, leads to fluorescence recovery for DNA/ZnNeotrien but not for DNA/CuNeotrien. This observation suggests that the binding of CuNeotrien induces deep alterations in the DNA structure. Experiments with Poly(dA-dT)*Poly(dA-dT) and Poly(dG-dC)*Poly(dG-dC) reveal that CuNeotrien mainly affects the structure of the latter polynucleotide.

Animals↗

PubMed2004

Occurrence of pituitary dysfunction following traumatic brain injury.

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.

Adult↗