Biomedical subjects

R C Smallridge

Publications and source records attributed to R C Smallridge.

At least 19 recordsLinked to original sources

PubMed1992

Metabolic and anatomic thyroid emergencies: a review.

PURPOSE: To review the diagnosis and management of thyroid diseases, both metabolic (thyroid storm and myxedema coma) and anatomic (substernal goiter, lymphoma, anaplastic carcinoma) that may require intensive care therapy. DATA SOURCES: English-language articles were identified through a search of the MEDLINE and Index Medicus databases. Bibliographies of retrieved articles were examined for relevant articles. STUDY SELECTION: Approximately 250 articles were reviewed. Those articles deemed most representative were utilized. Case reports were included to highlight rare, but potentially lethal complications. DATA EXTRACTION: All data were analyzed by one observer. Limitations of the data are discussed. DATA SYNTHESIS: Guidelines for determining the etiology of thyrotoxic crisis are outlined. Criteria for distinguishing critically ill hypothyroid patients from those patients with the euthyroid sick syndrome are given. Therapy for both disorders must be aggressive and multifaceted, and detailed management is indicated. Substernal goiter is almost always benign, but may cause various acute complications, including dyspnea, respiratory failure, superior vena caval syndrome, esophageal varices (downhill), and others. Surgery almost always corrects the problem. Lymphomas present with rapid thyroid enlargement. Recent studies suggest that surgery may assume more of a supportive role, used principally to obtain adequate tissue for histologic classification. CONCLUSIONS: Thyroid disorders can produce emergencies requiring the attention of multiple medical and surgical specialists. While management is often successful, future studies should address the following three areas: a) optimization of thyroid hormone dose for treatment of myxedema coma; b) clarification of the role of radiotherapy and/or chemotherapy for thyroid lymphoma; and c) more effective therapy for anaplastic carcinoma.

Airway Obstruction↗

PubMed1992

Heat shock increases cytosolic free Ca2+ concentration via Na(+)-Ca2+ exchange in human epidermoid A 431 cells.

This study characterized cytosolic free Ca2+ concentration ([Ca2+]i) in normal and thermally injured human epidermoid A 431 cells. The resting [Ca2+]i in normal cells at 37 degrees C was 87 +/- 5 nM (n = 105). When cells were subjected to hyperthermia (40-50 degrees C), [Ca2+]i increased in a temperature- and time-dependent manner. The maximal increase in cells exposed to 45 degrees C was observed at 20 min; [Ca2+]i returned to normal within 1 h. The heat-induced [Ca2+]i increase depended on the presence of external Ca2+. La3+ and Cd2+ but not Co2+, verapamil, or nifedipine attenuated the heat-induced [Ca2+]i increase. TMB-8 partially blocked the increase in [Ca2+]i but pertussis toxin and cholera toxin pretreatment did not. The magnitude of the heat-induced [Ca2+]i increase or 45Ca2+ uptake depended on the presence of extracellular Na+. Heat treatment reduced the apparent Michaelis constant for external Ca2+ from 490 +/- 91 to 210 +/- 60 microM, whereas the maximal velocity remained the same. The intracellular Na+ concentration decreased 62.5% after heating. The heat-induced [Ca2+]i increase was completely blocked by amiloride (5 microM) and 5'-(N,N-dimethyl)-amiloride (1 microM). These results suggest heat activates the Na(+)-Ca2+ exchange system so as to increase [Ca2+]i and reduce [Na+]i.

Calcium↗

PubMed1992

Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL-5 rat thyroid cells.

Na+-H+ exchange may proceed via an endogenous antiporter or by exposure to the Na+ ionophore monensin. We investigated the characteristics of Na+-H+ exchange induced by antiporter stimulation and by monensin in FRTL-5 rat thyroid cells. We also examined the effects of intracellular pH (pHi) changes on iodide uptake and efflux. pHi was determined using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. The resting pHi was 7.33 +/- 0.02 units; this level correlated directly with extracellular pH. In acid-loaded cells, Km for external Na+ activation of the antiporter was 7.1 mM and maximum velocity was 0.3801 delta pH units/min. Dimethylamiloride was 42 times more potent than amiloride in inhibiting sodium-dependent recovery in acidified cells. Metabolic inhibition reduced the initial alkalinization rate. Monensin increased pHi, and this response was dependent on extracellular Na+ and HCO3- but not on antiporter function. Low-dose monensin (1 microM) and 1 mM NH4Cl enhanced 125I uptake. High-dose monensin (100 microM), but not NH4Cl, reduced iodide uptake. Neither NH4Cl nor monensin altered 125I efflux. Thus FRTL-5 cells possess an amiloride-sensitive Na+-H+ exchanger, which is not essential for maintaining basal pHi but is affected by ATP depletion. Monensin also alkalinizes these cells but independently of the antiporter. Iodide uptake, but not efflux, is affected by changes in intracellular Na+ and H+ levels.

Amiloride↗

PubMed1992

U-73122, an aminosteroid phospholipase C antagonist, noncompetitively inhibits thyrotropin-releasing hormone effects in GH3 rat pituitary cells.

TRH increases cytosolic-free calcium ([Ca2+]i) by activating phospholipase C(PL-C), which induces phosphoinositol hydrolysis, leading to Ca2+ mobilization from inositol trisphosphate (IP3) sensitive stores, and by increasing Ca2+ influx. Increases in [Ca2+]i stimulate PRL secretion. We investigated the effects of U-73122, an aminosteroid inhibitor of PL-C dependent processes, on TRH-stimulated second messenger pathways and on PRL secretion in GH3 rat pituitary cells. [Ca2+]i was monitored by Indo-1 fluorescence, and IP3 and metabolites separated on ion exchange columns. In Ca(2+)-free buffer, [Ca2+]i was 96 +/- 6 nM and increased to 323 +/- 23 nM (P less than 0.001) after TRH (100 nM). U-73122 dose dependently inhibited the TRH effect (IC50 = 967 nM; complete inhibition at 3-5 microM). Subsequent addition of monensin (100 microM) increased [Ca2+]i from 107 +/- 4 to 142 +/- 4 nM (P < 0.001), confirming our previous findings of a non-TRH regulated Ca2+ pool in GH3 cells. Pretreatment (15 sec) with U-73122 partly inhibited the TRH effect on [Ca2+]i; complete suppression occurred with 70 sec of pretreatment. An inactive analog (U-73343) had no inhibitory effect at 5 microM. U-73122 acted noncompetitively, as the mean maximum velocity (expressed as percent increase in [Ca2+]i after TRH) was reduced from 225 to 91 while the Michaelis-Menten constant for TRH was unchanged (15.4 vs. 13.8 nM, n = 3). Of note, U-73122, at 3-5 microM, increased basal [Ca2+]i from 109 +/- 5 to 120 +/- 5 nM (P less than 0.001). In 1.3 mM Ca2+ buffer containing nifedipine (1 microM) and verapamil (50 microM), similar effects of U-73122 (5 microM) were observed on basal and TRH-stimulated [Ca2+]i. IP3, IP2, and IP1 increased to 241 +/- 12%, 148 +/- 23%, and 167 +/- 39% of control, 30 sec after TRH (100 nM); these responses were prevented by 1 microM U-73122. At 5 microM, U-73122 also significantly increased IP3 levels. TRH (100 nM) increased 4-h PRL secretion from 16.3 +/- 1.4 to 27.6 +/- 3.2 ng/well (P less than 0.05). U-73122 (5 microM) increased basal PRL secretion to 35.9 +/- 3.2 ng/well (P less than 0.05), but abolished the TRH effect. In contrast, U-73343 (with Ca2+ channel blockers) did not inhibit the TRH effect on PRL (control: 24.3 +/- 2.1; TRH: 51.0 +/- 6.3 ng/well).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

A cryptic peptide (160-169) of thyrotropin-releasing hormone prohormone demonstrates biological activity in vivo and in vitro.

TRH is synthesized as a precursor peptide containing five copies of the sequence Gln-His-Pro-Gly, QHPG, flanked by paired basic amino acids, and linked by other peptides. We tested one cryptic peptide, PPT (160-169, SFPWMESDVT), as a possible physiological regulator of pituitary activity in vivo. Male rats were cannulated (jugular) and received a single dose of either PPT or TRH (10(-8)-10(-6) M). PPT caused no consistent effects on either TSH or PRL secretion, while TRH stimulated the secretion of both hormones. However, PPT stimulated a dose-dependent increase in both pituitary TSH beta and PRL mRNA content at 240 min similar to TRH. In primary cultures of rat pituitaries, PPT stimulated a maximum 4-fold increase in TSH beta mRNA and a 2-fold increase in PRL mRNA in 4 h, while TRH increased both TSH beta and PRL mRNA approximately 3-fold. Again, PPT had no significant effect on TSH or PRL secretion into the medium. Thus, PPT appears to be a physiological regulator of both TSH and PRL synthesis, but, unlike TRH, does not act as a secretagogue.

Amino Acid Sequence↗

PubMed1991

Thyrotropin-releasing hormone regulation of thyrotropin beta-subunit gene expression involves intracellular calcium and protein kinase C.

Our previous studies demonstrated TRH stimulation of TSH beta gene expression in rat pituitary cell cultures and GH3 tumor cells in a transient expression assay. To begin to characterize the gene-proximal elements of the pathways involved in TRH stimulation of TSH beta gene transcription, we examined the effects of factors that increase intracellular calcium concentration, [Ca2+]i, or activate protein kinase C on TSH beta promoter activity in transfected GH3 cells. TPA, a tumor-promoting phorbol ester, stimulated a dose-dependent increase in TSH beta promoter activity at 8 h similar to TRH (2-3-fold). TPA did stimulate protein kinase C activation without [Ca2+] mobilization. The calcium ionophore ionomycin increased cytoplasmic free [Ca2+] by stimulating both calcium influx and release from internal stores without affecting protein kinase C. Ionomycin also stimulated a dose-dependent increase (2-fold) in TSH beta promoter activity at 8 h. However, the voltage-dependent Ca2+ channel agonist Bay K 8644, which increased influx of extracellular calcium, had little or no effect on TSH beta gene expression until 48 h (5-fold). Similar effects on prolactin/mRNA levels were observed in these cells. Effects of these factors were not additive, suggesting a common pathway(s) to stimulate gene expression. Inhibition of intracellular calcium mobilization by treatment with 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) inhibited ionomycin effects on gene expression without affecting phorbol ester activity, and, conversely, inhibition of protein kinase C activity by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) or TPA desensitization blocked TPA effects without affecting ionomycin activity.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1991

The pharmacokinetics of atropine and diazepam in sheep: intramuscular co-administration.

The purpose of this study was to determine whether the co-administration of atropine and diazepam affect the rate and extent of absorption of either drug. A triple crossover pharmacokinetic study using adult sheep was conducted. Each of nine animals received single injections of atropine (2 mg), diazepam (10 mg), and a combination of the two compounds weekly over a 3-week period. The combination of the drugs was injected into a single intramuscular site through a specially designed tandem syringe. Blood samples were obtained from time 0 to 300 min post-injection. Serum samples were analyzed for atropine by radioimmunoassay and for diazepam by gas chromatography/mass spectrometry. Pharmacokinetic parameters were evaluated by non-compartmental analysis. The co-administration of atropine and diazepam intramuscularly in sheep caused a delay in the time to reach maximal concentration of atropine. However, at the time when a single injection of atropine reached its maximum serum concentration, 92 per cent of that concentration was reached by atropine in the presence of diazepam. Additionally, no difference was detected in the rate or extent of diazepam absorption when administered intramuscularly in combination with atropine at the same site.

Animals↗

PubMed1991

Tight linkage of the human c-erbA beta gene with the syndrome of generalized thyroid hormone resistance is present in multiple kindreds.

Generalized thyroid hormone resistance recently was reported to map in a single kindred to the same chromosomal region as the c-erbA beta gene, which codes for a putative thyroid hormone receptor. Restriction fragment length polymorphisms (RFLPs) of c-erbA beta were linked with GTHR in three kindreds with variable neuropsychologic dysfunction; two unrelated kindreds have been reported to possess different single base mutations in the T3 binding domain of c-erbA beta. In order to ascertain if tight linkage with c-erbA beta could be generalized to other families with this syndrome, we performed RFLP analysis in a separate laboratory on an unrelated family with GTHR which lacks the neuropsychologic defects or short stature often associated with GTHR (Kindred WR). RFLPs were identified after Bam Hl and Eco RV digestion of DNA from leukocytes from 14 family members. The Bam Hl RFLPs were 2.8 and 5.3 kb bands, and the Eco RV RFLPs were 1.6 and 3.3 kb bands. These RFLPs cosegregated with the GTHR phenotype and 11 family members were informative when both RFLPs were employed. The logarithm of the odds ratio between GTHR and c-erbA beta was 3.67, and therefore GTHR mapped to the c-erbA beta locus in this kindred. Allelic-specific hybridization with a probe constructed to identify the C to A mutation at nucleotide position 1643 (previously identified in one other kindred) suggested that our family has a different c-erbA beta abnormality. Although GTHR appears to be commonly associated with alterations in the human c-erbA beta gene, different kindreds may inherit different genetic defects.

Base Sequence↗

PubMed1991

Diisopropylfluorophosphate (DFP) reduces serum prolactin, thyrotropin, luteinizing hormone, and growth hormone and increases adrenocorticotropin and corticosterone in rats: involvement of dopaminergic and somatostatinergic as well as cholinergic pathways.

Cholinergic mechanisms have been implicated in the regulation of anterior pituitary hormone secretion. The present study was designed to determine the effect of a single injection of an organophosphate acetylcholinesterase inhibitor, diisopropylfluorophosphate (DFP), on anterior pituitary function in male rats. DFP increased serum ACTH (2.7-fold) and corticosterone (9.1-fold), while suppressing TSH, PRL, LH, and GH by up to 95%. The earliest response was at 1 hr, with a duration of at least 18 hr for TSH and LH. Responses were similar in adrenalectomized animals. After DFP, responses to hypothalamic releasing factors were normal for TSH, GH, and ACTH, but significantly blunted for PRL and LH. TSH suppression was partially prevented by combined therapy with a nicotinic (mecamylamine) and a muscarinic (atropine) antagonist. TSH suppression was partially reversed by immunoneutralization with somatostatin antibody, and PRL suppression was completely prevented by a dopamine antagonist (haloperidol). Atropine alone prevented the effects on corticosterone. TSH pituitary content and TSH-beta mRNA were reduced by 37 and 22%, respectively, by DFP. In contrast, PRL mRNA was unchanged but PRL content was increased 3-fold. We conclude that cholinesterase inhibition evokes a multiplicity of effects on anterior pituitary function. There is a hierarchy of responses, with corticosterone being the most and TSH the least sensitive. There is evidence for inhibition at both the hypothalamic and pituitary levels, involving both nicotinic and muscarinic receptors. Although cholinesterase inhibition is the proximate event, other neurotransmitter pathways involved in TSH and PRL suppression are somatostatin and dopamine, respectively.

Adrenalectomy↗

PubMed1991

8-Diethylamino-octyl-3,4,5-trimethoxybenzoate, a calcium store blocker, increases calcium influx, inhibits alpha-1 adrenergic receptor calcium mobilization, and alters iodide transport in FRTL-5 rat thyroid cells.

8-Diethylamino-octyl-3,4,5-trimethoxybenzoate (TMB-8) is known to inhibit mobilization of calcium from intracellular stores but, more recently, other cellular effects have been described. In the present study, the effects of TMB-8 on cytosolic free calcium [Ca2+]i levels in FRTL-5 rat thyroid cells were determined using the fluorescent dye, Indo-1. TMB-8 increased [Ca2+]i in a dose-dependent manner, with a maximum rise from 120 +/- 7 nM to 229 +/- 16 nM (90 +/- 5% increase) at 5 x 10(-4) M. This effect was considerably reduced in Ca2+ free buffer, demonstrating a dependency upon extracellular calcium influx but not upon membrane potential and which did not involve the Na+/Ca2+ exchanger. In Ca2+ free buffer TMB-8, at a dose which did not affect [Ca2+]i, completely prevented norepinephrine (10(-5) M) from mobilizing intracellular Ca2+. To determine whether TMB-8 affected differentiated functions, iodide uptake and efflux studies were performed with 125I. TMB-8 (10(-4) M) inhibited iodide uptake by approximately 40% without affecting efflux. At 10(-3) M TMB-8, efflux was also enhanced. These studies demonstrate that TMB-8 has at least two effects on [Ca2+]i, promoting calcium influx and preventing alpha-1 adrenergic mobilization from intracellular stores. TMB-8 also has multiple effects on 125I transport, both inhibiting influx and increasing efflux. The results emphasize the importance of characterizing the behavior of this compound in any cell system before using it as a biological probe.

Animals↗

PubMed1990

Na(+)-ionophore, monensin-induced rise in cytoplasmic free calcium depends on the presence of extracellular calcium in FRTL-5 rat thyroid cells.

Calcium is an important regulator of cell function, and may be influenced by the intracellular sodium content. In the present study, the Na(+)-ionophore, monensin, was used to investigate the interrelationship between changes in intracellular Na+ concentration ([Na+]i) and elevation of cytosolic Ca2+ concentration ([Ca2+]i) in FRTL-5 thyroid cells. Cytoplasmic Ca2+ levels were measured using the fluorescent dye, indo-1. Monensin induced a dose-dependent increase in [Ca2+]i in FRTL-5 cells. Inhibitors of intracellular Ca2+ release, TMB-8 and ryanodine, were unable to prevent the monensin effect on [Ca2+]i. The alpha 1-receptor antagonist, prazosin, did not block the monensin-stimulated increase in [Ca2+]i. In the absence of extracellular calcium there was a marked diminution in the monensin effect on [Ca2+]i, yet calcium channel antagonists (nifedipine, diltiazem and verapamil) did not inhibit the response. Replacement of Na+ by choline chloride in the medium depressed the monensin-evoked rise in [Ca2+]i by up to 84%. Furthermore, addition of the Na(+)-channel agonist, veratridine, elicited an increase in [Ca2+]i, even though less dramatic than that caused by monensin. Ouabain increased the resting cytosolic Ca2+ concentration as well as the magnitude of the monensin effect on [Ca2+]i. The absence of any effect on the Na(+)-ionophore evoked increase in [Ca2+]i upon addition of tetrodotoxin (TTX) excluded a possible involvement of TTX-sensitive Na+ channels. These data show that the rise in [Ca2+]i induced by increasing [Na+]i is largely dependent on both external Na+ and Ca2+. Calcium entry appears not to involve voltage-dependent or alpha 1-receptor sensitive Ca2+ channels, but may result from activation of an Na(+)-Ca2+ exchange system.

Animals↗

PubMed1990

The effect of exercise on atropine pharmacokinetics.

Seven healthy males (19-32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 232 l). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 198 l), and clearance (CL, 763 vs 638 ml.min-1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng.ml-1) and area under the curve (AUC, 44.1 vs 53.1 ng.ml-1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml.min-1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min-1), elimination rate constant (ke, 0.0012 vs 0.0015 min-1), Cp (14 ng.ml-1) and AUC (53.3 ng.h.ml-1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.

Adult↗

PubMed1990

Effects of irradiation and semistarvation on rat thyrotropin beta subunit messenger ribonucleic acid, pituitary thyrotropin content, and thyroid hormone levels.

The effect of radiation-induced anorexia on serum thyrotropin (TSH), pituitary TSH-beta mRNA, pituitary TSH content, serum thyroxine (T4), and serum 3,5,3'-triiodothyronine (T3) was investigated using feed-matched controls. Rats received 10 Gy gamma whole-body irradiation and were examined 1-3 days postirradiation. Feed-matched and untreated controls were also studied. The average food intake of the irradiated and feed-matched groups was approximately 18% of the untreated controls. Over the three day period both the irradiated and feed-matched groups lost a significant amount of body weight. The serum T4 levels of both the irradiated and feed-matched groups were not significantly different from each other, but were significantly depressed when compared to the untreated control group. The serum TSH and T3 were, however, significantly greater in the irradiated than the feed-matched groups at day 3 posttreatment. To determine if the difference in the serum TSH level between the two groups was due to a pretranslational alteration in TSH production, we measured the TSH-beta mRNA using an RNA blot hybridization assay. We found that the TSH-beta mRNA level was the same in the irradiated and feed-matched groups, suggesting that the mechanism responsible for the radiation-induced increase in the serum TSH level is posttranscriptional. Pituitary TSH content in the irradiated rats was significantly less than in pair-fed controls, suggesting that irradiation may permit enhanced secretion of stored hormone.

Animals↗

PubMed1990

Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine.

Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 +/- 1.8 to 28.1 +/- 6.8 (NS) at 3-day postirradiation, 37.7 +/- 1.9 (P less than .001) at 6-day postirradiation, and 43.8 +/- 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity.

Animals↗

PubMed1990

Malabsorption of thyroxine, calcium, and vitamin D in a thyroparathyroidectomized woman: efficacy of therapy with medium-chain triglyceride oil.

A 28-year-old woman with surgically induced hypothyroidism and hypoparathyroidism required large doses of replacement medications due to malabsorption from short bowel syndrome. Malabsorption of thyroxine was documented using the technique of double isotope radioiodothyronine turnover studies. Therapy with medium-chain triglyceride oil improved her malabsorption and favorably influenced the absorption of her medications.

Adult↗

PubMed1989

Thyroid hormone resistance in a large kindred: physiologic, biochemical, pharmacologic, and neuropsychologic studies.

PURPOSE: Thyroid hormone resistance affects the pituitary gland and a variety of other tissues. We studied a large kindred with this disorder and measured a number of clinical markers of tissue metabolism to determine if these markers were useful in elucidating the sites and degree of resistance. PATIENTS: A kindred of 89 persons in four generations was identified; 44 had thyroid function tests, and 14 (five to 67 years old) were found to have thyroid hormone resistance. RESULTS: The inheritance pattern was autosomal dominant, with no common HLA haplotype. Physiologic measurements in five affected members showed marked heterogeneity. Four patients had normal baseline cardiac contractility, but only two experienced a shortening of their QKd interval into the hyperthyroid range with triiodothyronine (T3) therapy. Intrathyroidal 127I content was increased in two patients and was normal in two. Bone mineral content was normal in two men, but two women had marked osteopenia. The propositus, hypothyroid after inappropriate 131I therapy, had a hypothyroid ventilatory response to hypercapnea. This response became low normal during T3 (100 micrograms/day) administration but not during long-term thyroxine (T4) (300 micrograms/day) administration. Three other patients had values within normal limits and one had a hyperthyroid ventilatory response. Peripheral biochemical markers of thyroid hormone action were measured in 13 affected and 19 unaffected family members. Sex hormone-binding globulin was increased in zero of 13 affected patients (versus 19 of 20 hyperthyroid, chi 2:p less than 0.001); ferritin was elevated in two of 13 patients (versus 11 of 20 hyperthyroid, p less than 0.02); angiotensin converting enzyme activity was increased in one of 13 patients (versus 12 of 20 hyperthyroid, p less than 0.025). The eldest patient had marked cardiac sensitivity despite normal biochemical markers. We attempted to suppress the integrated thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) using T3 (72 and 100 percent suppression in two patients), dopamine (40 percent suppression in one), 3,5,3'-triiodothyroacetic acid (TRIAC) (94 percent suppression in one), and verapamil (10 percent and 40 percent suppression in two). Neuropsychologic function was studied in 14 individuals (11 affected, three unaffected). Although mild impairments were detected, they were not specific for thyroid hormone resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1989

Rapid release of multiple hormones from rat pituitaries perifused with recombinant interleukin-1.

Previous studies demonstrated a direct action of interleukin-1 (IL-1) on release of hormones from rat anterior pituitary cells in monolayer culture. To rule out any possibility of a paracrine effect from the elevated hormones in the static monolayer system, and to examine further the dynamics of hormone release elicited by IL-1, studies were conducted with rat anterior pituitary tissue in a computer-controlled automated perifusion system. In experiments performed on the same day as sacrifice, IL-1 stimulated the release of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), growth hormone (GH) and prolactin (PRL) in a dose-related manner. Peak levels were achieved within 6 minutes of exposure to IL-1. However, PRL was not increased over the baseline fluctuations when pituitaries were perifused with IL-1 after 72 hours of incubation. Hormone release did not appear to undergo desensitization after multiple short pulses of IL-1. Heat-denatured IL-1 had no effect on hormone release. The rapid response suggests that IL-1 acts acutely to release preformed hormone stores.

Animals↗

PubMed1989

Effects of elevated gonadotropin levels on thyroid function in the male rat.

In order to determine if thyroid disease in hypogonadal men is the result of chronic elevation of serum gonadotropins, thyroid histology and serum thyroid hormone levels were evaluated in male rats that had been castrated either 2 weeks or 15 months previously. Despite significantly elevating serum LH levels, castration did not affect thyroid structure or function. Serum total T4 levels were reduced with age in both short and long-term castrate animals but returned to the levels seen in young rats when testosterone was replaced. Testosterone replacement also increased free T4 levels in both the young and old castrate rats. Neither age nor testosterone replacement affected serum T3 or TSH levels.

Animals↗