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Pituitary Function
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Here are a number of research articles from an incredible 2010 lecture by

Dan Purser, MD
Pituitary Dysfunction ..
The Great MIMIC

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Fatigue after TBI: association with neuroendocrine abnormalities.

Brain Inj. 2007 Jun;21(6):559-66. Bushnik T, Englander J, Katznelson L.

Rehabilitation Research Center, San Jose, CA 95128, USA. tamara@tbi-sci.org

OBJECTIVE: Evaluate the association between neuroendocrine findings and fatigue after traumatic brain injury (TBI)

..Given the high prevalence of pituitary abnormalities, screening for hypopituitarism after TBI is a reasonable recommendation.

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Sleep disturbance with growth hormone decline.

JAMA. 2000 Aug 16;284(7):861-8.

Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men.

Van Cauter E, Leproult R, Plat L.

Department of Medicine, MC 1027, University of Chicago.

The decline in slow wave sleep from early adulthood to midlife was paralleled by a major decline in GH secretion.

From midlife to late life, GH secretion further declined at a slower more fragmented and REM sleep declined

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Sleep apnoea and quality of life in growth hormone (GH)-deficient adults before and after 6 months of GH replacement therapy.

Peker Y., Svensson J., Hedner J., Grote L., Johannsson J., Clin Endocrinol Oxf 2006, Jul 65 (1) 98-105. Sleep Medicine Unit, Department of Neurorehabilitation, Skaraborg Hospital, Skoevde, Sweden.

OBJECTIVE: To investigate the sleep architecture and breathing as well as quality of life (QoL) in adults with GH deficiency (GHD) before and 6 months after Growth Hormone replacemant  therapy....increase was observed in REM sleep time (10.1% before vs. 12.7% after GH; P = 0.048) while SWS was unchanged in this group. Moreover, MSEP for General Well-being and Responsiveness, FOSQ scores for General Productivity, Activity Level and Vigilance as well as SF-36 domains for Vitality and Mental Health were improved.

CONCLUSIONS: Contrary to some previous observations in a smaller group of patients, our data suggest that GH therapy does not induce or aggravate OSA

in GH-deficient adults. Moreover, GH therapy may improve some of the QoL dimensions in these patients.

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Effects of chronic growth hormone and insulin-like growth factor 1 deficiency on osteoarthritis severity in rat knee joints.

Ekenstedt KJ, Sonntag WE, Loeser RF, Lindgren BR, Carlson CS. Arthritis Rheum. 2006 Dec;54(12):3850-8. Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA.

OBJECTIVE: To determine the effects of chronic deficiency of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) on osteoarthritis (OA) severity.

CONCLUSION: These results indicate that chronic GH/IGF-1 deficiency causes an increased severity of articular cartilage lesions of OA without the bony lesions normally seen in this disease.

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The role for growth hormone in linking arthritis, osteoporosis, and body composition.
Tauchmanova L, Di Somma C, Rusciano A, Lombardi G, Colao A. J Endocrinol Invest. 2007;30(6 Suppl):35-41.Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, 80131 Naples, Italy.

Adults with either GH deficiency (GHD) or GH excess have bone, metabolic, and somatic impairments. This review deals with available data on the relationship between GH status, bone mass, articular disorders, and body composition. GHD subjects have reduced bone mineralization and increased fracture rates.

Their normalization (by GH replacement or treatment of acromegaly) reverses most of these abnormalities, thus confirming their GH-related etiology.

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The relationship between temporomandibular disorders and stress-associated syndromes.
Korszun A, et al. Orral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Oct;86(4):416-20. Department of Psychiatry and School of Dentistry, University of Michigan, Ann Arbor USA.

OBJECTIVES: The purpose of this study was to determine the comorbidity of temporomandibular disorders and other stress-associated conditions in patients with chronic fatigue syndrome and fibromyalgia.

RESULTS: Of the original 92 patients, of whom 42% reported temporomandibular disorders, 46% had histories of irritable bowel syndrome, 42% of premenstrual syndrome, and 19% of interstitial cystitis.

CONCLUSIONS: The clinical overlap between these conditions may reflect a shared underlying pathophysiologic basis involving dysregulation of the hypothalamic-pituitary-adrenal stress hormone axis in predisposed individuals.

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Testosterone deficiency and apathy in Parkinson's disease: a pilot study.

Ready RE, Friedman J, Grace J, Fernandez H. J Neurol Neurosurg Psychiatry. 2004 Sep;75(9):1323-6.Department of Psychiatry and Human Behavior, Brown Medical School, University of Pittsburgh, PA USA.

RESULTS: A low total testosterone concentration was found in 46.9% of the patients, defined as < or = 325 ng/dl. Free testosterone was significantly correlated with both patient reported and informant reported apathy, independent of disease severity.

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Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome.

Neurosurgery. 2008 May ;62(5):1080-93; Bavisetty S, McArthur DL, et al.Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California Division of Neurosurgery, UCLA School of Medicine, Los Angeles, California, USA.

OBJECTIVE: Chronic pituitary dysfunction is increasingly recognized as a sequela of traumatic brain injury. 15 (21%) had at least one major hormonal deficiency, 20 (29%) had minor deficiencies, and 30 (43%) had major and/or minor deficiencies. Patients with major deficiencies included 16% with GHD or GHI, 10.5% with hypogonadism, and 1.4% with diabetes insipidus.

CONCLUSION: Chronic hypopituitarism warranting hormone replacement occurs in approximately 20% of patients after complicated mild, moderate, or severe traumatic brain injury and is associated with more severe brain injuries and increased disability. GHD and GHI are also associated with increased disability, poor quality of life, and a greater likelihood of depression. The clinical significance of minor hormonal deficits, which occur in almost 30% of patients, warrants further study. Given that major deficiencies are readily treatable, routine pituitaryhormonal testing within 6 months of injury is indicated for this patient population.

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Psychiatric disorders after traumatic brain injury.

Brain Inj. 1996 May;10(5):319-27. van Reekum R, Bolago I, et al. Department of Psychiatry, University of Toronto, Canada.

“Studies utilizing established psychiatric diagnostic schemes to study these outcomes after TBI are scarce” Results revealed high rates for major depression, bipolar affective disorder, generalized anxiety disorder, borderline and avoidant personality disorders. Comorbidity was also high..************************Suicidal behavior and mild traumatic brain injury in major depression.

J Nerv Ment Dis. 2004 Jun;192(6):430-4. Oquendo MA, Friedman JH, et al. Department of Neuroscience, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA.

Traumatic brain injury (TBI) is associated with psychiatric illness, suicidal ideation, suicide attempts, and completed suicide. We investigated the relationship between 44% of all subjects reported mild TBI. Subjects with TBI were more likely to be male, have a history of substance abuse, have cluster B personality disorder, and be more aggressive and hostile compared with subjects without TBI. They were also more likely to be suicide attempters, although their suicidal behavior was not different from that of suicide attempters without TBI. Attempt status was mostly predicted by aggression and hostility, but not the presence of TBI. Of note, for males, a history of TBI increased the likelihood of being a suicide attempter, whereas the risk was elevated for females regardless of TBI history. Our data suggest that suicidal behavior and TBI share antecedent risk factors: hostility and aggression. Future studies may yield confirmation using a prospective design.

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Cardiovascular disease and risk factors: the role of growth hormone.

Horm Res. 2004;62 Suppl 4:31-8. Isgaard J. Sahlgrenska Academy, University of Göteborg, Göteborg, Sweden.

Exercise capacity in patients with GHD is significantly reduced and in some severely affected individuals, dilated cardiomyopathy and heart failure has been reported. GHD has also been associated with a number of risk factors for cardiovascular disease. Altered lipoprotein metabolism and elevated fibrinogen and plasminogen activator inhibitor-1 activity are associated with GHD, and the risk of hypertension is increased in GH-deficient men. Subcutaneous and intra-abdominal fat mass have also been found to be abnormally high in these patients.

GH is therefore an important factor in the development and function of the cardiovascular system.

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Heart rate variability (HRV) of patients with traumatic brain injury (TBI) during the post-insult sub-acute period.

Brain Inj. 2005 Aug 10;19(8):605-11. Keren O, Yupatov S, et al. Department of Brain Injury Rehabilitation, Loewenstein Rehabilitation Hospital, Ra'anana, Israel.

OBJECTIVE: To evaluate heart rate variability (HRV) of patients with traumatic brain injury (TBI). METHODS: By a prospective study, the HRV was assessed in 20 patients with TBI during the sub-acute period post-injury (the first test was performed at a mean time post-insult of 38 days) and a matched control. The patients were examined twice, 1 month apart. The assessment included HRV (both in time and frequency domains), GCS, length of coma, brain CT, FIM and FAM.

CONCLUSION: HRV differed of patients with TBI and in the control group. Tendency to HRV normalization changes was detected during the first 3 months after the injury, which suggests recovery of the autonomic nervous system. *************************

The influence of growth hormone replacement on heart rate variability in adults with growth hormone deficiency.

Clin Endocrinol (Oxf). 2001 Jun;54(6):819-26. Leong KS, Mann P, et al. Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK.

OBJECTIVE: Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. Abnormalities in heart rate variability (HRV), a surrogate marker of cardiac autonomic tone, have also been found in untreated growth hormone deficient (GHD) patients.

CONCLUSIONS: These results suggest that abnormalities of the cardiac autonomic system in GHD patients may be correctable.

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High incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors in women with hypopituitarism not receiving growth hormone treatment: preliminary results.

Growth Horm IGF Res. 1999 Apr;9 Suppl A:21-4. Erfurth EM, Bülow B, et al. Department of Internal Medicine, University Hospital, Lund, Sweden.

Recently, epidemiological evidence has suggested that hypopituitarism with untreated growth hormone deficiency (GHD) is associated with a high incidence of cardiovascular mortality and that women are particularly at risk.

A significantly higher number of diagnosed circulatory disorders occurred in the women with hypopituitarism patients with hypopituitarism had a significantly higher waist:hip ratio and a higher ratio of low-density lipoprotein to high-density lipoprotein hypopituitarism was associated with more episodes of bradycardia. In summary, women with hypopituitarism had an increased incidence of cardiovascular disease and a less favourable risk factor profile increased risks of cardiovascular mortality associated with hypopituitarism with untreated GHD.

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Effects of insulin-like growth factor-I on cultured human coronary artery smooth muscle cells.

Bayes-Genis A, Schwartz RS, et al. Division of Cardiovascular Diseases and Endocrine Research Unit , Mayo Clinic and Foundation, 200 First Street SW, 5-194 Joseph, Rochester, MN USA.

The growth-promoting effects of insulin-like growth factor-I (IGF-I) appear to be different in vascular smooth muscle cells from various segments of the arterial tree. Little information exists on human coronary artery smooth muscle cells (CoSMC), the primary elements of coronary atherosclerosis and post-angioplasty restenosis. In this study we determined the effects of IGF-I on cultured human CoSMC. This study indicates that IGF-I is a potent motility agent for human CoSMC via the alpha(V)beta(3) integrin receptor, but exerts little mitogenic effect.

Because CoSMC migration plays a crucial role in atherosclerosis and restenosis, IGF-I blockade has the potential to limit lumen reduction.

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Estrogen and testosterone therapies in

multiple sclerosis

Prog Brain Res. 2009;175:239-51. Gold SM, Voskuhl RR. Department of Neurology, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

It has been known for decades that females are more susceptible than men to inflammatory autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis, and psoriasis. In addition, female patients with these diseases experience clinical improvements during pregnancy with a temporary "rebound" exacerbation postpartum. These clinical observations indicate an effect of sex hormones on disease and suggest the potential use of the male hormone testosterone and the pregnancy hormone estriol, respectively, for the treatment of MS. A growing number of studies using the MS animal model experimental autoimmune encephalomyelitis (EAE) support a therapeutic effect of these hormones. Both testosterone and estriol have been found to induce anti-inflammatory as well as neuroprotective effects. Findings from two recent pilot studies of transdermal testosterone in male MS patients and oral estriol in female MS patients are encouraging.

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Multiple sclerosis and erectile dysfunction

Zhonghua Nan Ke Xue. 2009 Jan;15(1):56-9. [Article in Chinese] Luo H, Jiang R. Department of Urology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China. luohua060046@163.com

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. NO, ion channel, cytokine and testosterone play an important role in MS, and may be associated with the pathogenesis of ED. Meanwhile, the relationship between MS-induced peripheral nerve injury and ED should be understood correctly. Further researches on these mediators can provide some theoretical evidence for the clinical treatment of ED.

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Evaluation of endocrine profile, hypothalamic-pituitarytestis axis and semen quality in multiple sclerosis. J Neuroendocrinol. 2008 Dec;20(12):1368-75. Safarinejad MR. Urology and Nephrology Research centre, Shahid Beheshti University, Tehran, Iran.

Several endocrine and sexual disturbances have been demonstrated in multiple sclerosis (MS) patients of both sexes. The endocrine profile, hypothalamic-pituitary-testis (HPT) axis and semen quality were evaluated in male patients with MS. A total of 68 male MS patients aged 18 years or older were recruited. Forty-eight age-matched healthy male volunteers served as controls. All subjects underwent complete physical examination and routine semen analysis. Two blood samples were drawn from each participant at 15-min intervals for the determination of the resting levels of: luteinising-hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, oestradiol and sex hormone binding globulin. The HPT axis was assessed using gonadotrophin-releasing hormone (GnRH) and human chorionic gonadotrophin tests. The mean basal serum levels for LH, FSH and testosterone in MS patients were significantly lower than the mean for normal controls (P = 0.01). The injection of GnRH analogue did not yield a significant increase in FSH and LH levels in the MS patients compared to normal controls (P = 0.001). Total sperm count, sperm motility and percent normal sperm morphology were lower in MS patients compared to controls. MS subjects with progressive disease had higher and more severe HPT axis abnormalities than that for patients with relapsing remitting MS. Most subjects with MS have hypogonadotrophic hypogonadism state and fertility impairment. It appears that the damage to HPT axis is both in pituitary and testicular levels. Further studies are needed to better elucidate the underlying pathophysiology of HPT axis dysregulation.

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Testosterone treatment in multiple sclerosis: a pilot study.

Arch Neurol. 2007 May;64(5):683-8. Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, Shattuck DW, Hull L, Wang HJ, Elashoff RM, Swerdloff RS, Voskuhl RR.

Division of Brain Mapping, Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

OBJECTIVE: To study the effect of testosterone supplementation on men with multiple sclerosis (MS). RESULTS: One year of treatment with testosterone gel was associated with improvement in cognitive performance (P = .008) and a slowing of brain atrophy (P <.001). There was no significant effect of testosterone treatment on gadoliniumenhancing lesion numbers (P = .31) or volumes (P = .94). Lean body mass (muscle mass) was increased (P = .02).
 CONCLUSION: These exploratory findings suggest that testosterone treatment is safe and well tolerated and has potential neuroprotective effects in men with relapsing-remitting MS.

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Abnormal heart rate and blood pressure responses to baroreflex stimulation in multiple sclerosis patients.

Clin Auton Res. 2005 Jun;15(3):213-8.

Sanya EO, Tutaj M, Brown CM, Goel N, Neundörfer B, Hilz MJ.

Autonomic Laboratory, Dept. of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Cardiovascular autonomic neuropathy has been previously reported  in patients with multiple sclerosis (MS) using standard reflex tests. However, no study has separately evaluated both parasympathetic and sympathetic cardiovascular autonomic regulation. The increase in the power of 0.1 Hz Rrinterval oscillations during the 0.1 Hz neck suction was significantly smaller (p<0.01) in the MS patients (4.47+/-0.27 to 5.62+/-0.25 ln ms(2)) than in the controls (4.12+/-0.37 to 6.82+/-0.33 ln ms(2)).
The increase in the power of 0.1 Hz systolic BP oscillations during 0.1 Hz neck suction was also significantly smaller (p<0.01) in the MS patients (0.99+/-0.19 to 1.96+/-0.39 mmHg(2)) than in the healthy controls (1.27+/-0.34 to 9.01+/-4.10 mmHg(2)). Neck suction at 0.2 Hz induced RR-interval oscillations at 0.2 Hz that were significantly smaller (p<0.05) in the patients (3.22+/-0.45 ln ms(2)) than in the controls (5.27+/-0.29 ln ms(2)).
These results indicate that in MS patients, baroreflex dysfunction is not only restricted to the cardiovagal limb of the baroreflex, but that the sympathetic modulation of the blood vessels is also affected.

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Structural, functional and autonomic changes in the cardiovascular system in growth hormone deficient patients.

Ann Noninvasive Electrocardiol. 2004 Jan;9(1):19-23, Erdodan D., Tükek T, Aral F, Oflaz H, Ozaydin M, Kocaman O, Akkaya V, Gören T, Molvalilar S. Department of Cardiology, Istanbul University, Medical Faculty of Istanbul, Turkey.

BACKGROUND: Growth hormone deficiency (GHD) is known to cause higher rates of cardiovascular mortality. The purpose of the study was to analyze the structural and functional changes in the heart and investigate their relation to autonomic function as assessed with heart rate variability (HRV). METHODS: Eleven untreated GHD patients (mean age 50.4 +/- 10.7 years, M/F: 3/8) and 15 age- and sex-matched healthy persons (mean age 45.3 +/- 10.4 years, M/F: 5/10) were compared. Both groups were examined with echocardiography, HRV, and exercise testing and findings were analyzed. RESULTS: The groups were similar in height, weight, body mass index, body surface area, systolic and diastolic blood pressure, heart rate. The GHD patients had lower exercise duration and metabolic equivalent (MET) compared to controls (7.94 +/- 1.26 vs. 9.8 +/- 1.9 min, P < 0.001, for MET 8.85 +/- 0.86 vs. 10.7 +/- 2.23, P = 0.03). On echocardiography, GHD patients had lower interventricular septum diastolic diameter (9 +/- 0.89 vs. 10.7 +/- 0.88 mm, P < 0.001) and posterior wall thickness (8.4 +/- 0.93 vs. 9.8 +/- 0.91 mm, P = 0.002), and lower left ventricle mass index (90.9 +/- 20 vs. 112 +/- 8 g/m2, P = 0.01). Left ventricular ejection fraction was lower in the GHD patients (57.4 +/- 5.12% vs. 65.5 +/- 4.1%, P < 0.001). Time and frequency domain heart rate variability parameters, SDNN, SDANN, VLF, LF ve LF/HF were lower in GHD patients compared to controls. There was a significant correlation between left ventricle diastolic diameter and LF (r = 0.62, P = 0.02).
CONCLUSION: GHD seemed to cause decreased left ventricle mass and decreases in the sympathetic components of HRV that may have a bearing on the increased cardiovascular risk seen in these patients.

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Abnormal heart rate variability in adults with growth hormone deficiency.

J Clin Endocrinol Metab. 2000 Feb;85(2):628-33. Leong KS, Mann P, Wallymahmed M, MacFarlane IA, Wilding JP. University Clinical Department, University Hospital Aintree, Liverpool, United Kingdom.

GH-deficient (GHD) patients have increased risk of cardiovascular death and may have cardiac structural abnormalities. These data indicate that heart rate variability is abnormal in patients with GHD. The decreased sympathetic tone could be a consequence of reduced central sympathetic tone or altered cardiac responsiveness to autonomic control and may contribute to the increased cardiovascular risk in GHD patients.

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Myelination is altered in insulin-like growth factor-I null mutant mice.

J Neurosci. 2002 Jul 15;22(14):6041-51. Ye P, Li L, et al. Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220, USA.

Increasing evidence indicates that insulin-like growth factor-I (IGF-I) has an important role in oligodendrocyte development. These data suggest that IGF-I plays a significant role in myelination during normal early development and that IGF-II can compensate in part for IGF-I actions on myelination.

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In vivo actions of insulin-like growth factor-I (IGF-I) on brain myelination: studies of IGF-I and IGF binding protein-1 (IGFBP-1) transgenic mice.

J Neurosci. 1995 Nov;15(11):7344-56. Ye P, Carson J, D'Ercole AJ. Department of Pediatrics, University of North Carolina at Chapel Hill 27599-7220, USA.

To study the effects and mechanisms of insulin-like growth factor I (IGF-I) on brain myelination in vivo, the morphology of myelinated axons and the expression of myelin specific protein genes have been examined in transgenic (Tg) mice that overexpress IGF-I and that those ectopically express IGF binding protein-1 (IGFBP-1), a protein that inhibits IGF-I actions when present in molar excess. Our data show that the percentage of myelinated axons and the thickness of myelin sheaths are significantly increased in IGF-I Tg and decreased in the IGFBP-1 mice ....suggesting that IGF-1 promotes oligodendrocyte survival and/or proliferation. The alterations in the number of oligodendrocytes, however, can not completely account for the changes in myelin gene expression. These results strongly indicate that IGF-I increases myelination by increasing the number of myelinated axons and the thickness of myelin sheaths, the latter by mechanisms that involve stimulation of the expression of myelin protein genes and increase of oligodendrocyte number.

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Improvement of peripheral neuropathy by testosterone in a patient with 48,XXYY syndrome.

Tokai J Exp Clin Med. 2000 Jun;25(2):39-44. Izumi S, Tsubahara A. Department of Rehabilitation Medicine, Tokai University School of Medicine, Kanagawa, Japan.

The 48,XXYY syndrome is a form of hypergonadotropic hypogonadism, characterized by tall statures, aggressive behavior, mental retardation, and stasis changes reflecting vascular insufficiency. We report a 25-year-old

male with this syndrome showing a peripheral neuropathy and stasis dermatitis which were both reversed by administration of testosterone. Electrophysiologic studies, plethysmography, and thermography indicated that this treatment improved nerve conductivity and peripheral circulation. We postulate that in 48,XXYY syndrome a decrease in testosterone may result in peripheral neuropathy via nerve

ischemia.

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Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?

Growth Horm IGF Res. 2007 Feb;17(1):82-8. Yuen KC, Bennett RM, et al. Department of Endocrinology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mailcode L607, Portland, OR USA.

OBJECTIVE: Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis.
CONCLUSION: Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test.
We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency.
Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.

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Comorbidity of interstitial cystitis with other unexplained clinical conditions.

Urol. 2004 Oct;172(4 Pt 1):1242-8. Buffington CA. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, Columbus, Ohio, USA.

RESULTS: A significant overlap of symptoms exists among a number of unexplained clinical conditions and a common stress response pattern of increased sympathetic nervous system function in the absence of comparable activation of the hypothalamic-pituitary-adrenal axis occurs in a subset of patients with many of these conditions.

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Case report: reversible gastroparesis in patients with hypopituitary disease.

Am J Med Sci. 1996 Jul;312(1):43-5. Krishna AY, Blevins LS Jr. Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

A 72-year-old woman with chronic fatigue, malaise, weight loss, nausea, and vomiting was treated unsuccessfully for gastroparesis for more than 2 years. Clinical and biochemical features of hypopituitary disease and symptoms of a nonsecreting pituitary tumor had been overlooked and became apparent only after the differential diagnosis of hyponatremia was considered. Transsphenoidal resection of the pituitary tumor and appropriate 1-thyroxine and hydrocortisone replacement returned her gastric emptying time to normal and relieved her symptoms. Primary and secondary deficits of l-thyroxine and cortisol should be considered when making a possible diagnosis of gastroparesis.

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Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis.

Aliment Pharmacol Ther. 2009 Jun 1;29(11):1179-87. Epub 2009 Feb 27.Ejskjaer N, Vestergaard ET, Hellström PM, Gormsen LC, Madsbad S, Madsen JL, Jensen TA, Pezzullo JC, Christiansen JS, Shaughnessy L, Kosutic G. Aarhus University Hospital, Aarhus, Denmark.

BACKGROUND: TZP-101 is a synthetic, selective ghrelin agonist in development for gastroparesis. AIM: To assess safety and effects of TZP-101 in diabetes patientswith symptomatic gastroparesis. METHODS: Adults with type 1 or type 2 diabetes mellitus received placebo and TZP-101 (80, 160, 320 or 600 microg/kg) infusions in a cross-over manner following a radiolabelled meal. Blood glucose levels were stabilized using a hyperinsulinemic-euglycemic clamp. Primary endpoints were gastric half emptying and latency times. Secondary measures included assessment of gastroparesis symptoms and endocrine responses. RESULTS: Ten patients with type 1 (n = 7) or 2 (n = 3) diabetes, moderate-to-severe gastroparesis symptoms and > or =29% retention 4 h after a radiolabelled solid meal were enrolled. TZP-101 produced significant reductions in solid meal half-emptying (20%, P = 0.043) and latency (34%, P = 0.037) times vs. placebo. Reductions in overall postmeal symptom intensity (24%) and postprandial fullness (37%) following TZP-101 infusion were not statistically significant. Most adverse events were mild and self-limiting and there were no identifiable differences in numbers or types of adverse events between TZP-101 and placebo. CONCLUSIONS: This proof-of-concept study demonstrates that the ghrelin agonist TZP-101 is well-tolerated in diabetes patients with moderate-to-severe chronic gastroparesis and shows statistically significant improvements in gastric emptying.

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Insulin-like growth factors I and II expression in the healing wound.

JGartner MH, Benson JD, Caldwell MD. Department of Surgery, University of Minnesota, School of Medicine.

Demonstrating temporal variation in the expression of messenger RNA (mRNA) for growth factors may give some indication as to whether growth factor synthesis is regulated in wound healing. The aim of this study was to evaluate the expression of insulin-like growth factors (IGF) I and II in the wound. Since fibroblasts are known to both secrete and respond to IGF-I, it is possible that IGF-I and IGF-II are acting to influence fibroblast differentiation and function in the later stages of wound healing.

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A metabolic basis for fibromyalgia and its related disorders: the possible role of resistance to thyroid hormone.

Med Hypotheses. 2003 Aug;61(2):182-9. Garrison RL, Breeding PC. 3306 Montavesta Drive, Lexington, KY 40502, USA.

It is likely more often acquired than due to mutated receptors. Now that there is evidence to support the hypothesis that fibromyalgia may be due to thyroid hormone resistance, four major questions appear addressable.
First, can a simple biomarker be found to help diagnose it? Second, what other syndromes similar to Fibromyalgia may share a thyroid-resistant nature?
Third, in non-genetic cases, how is resistance acquired?
Fourth, what other methods of treatment become available through this new understanding? Preliminary evidence suggests that serum hyaluronic acid is a simple, inexpensive, sensitive, and specific test that identifies fibromyalgia. In addition to experimentally proven treatment with supraphysiologic doses of thyroid hormone, the thyroid resistant disorders might be treatable with anti-hypercoagulant, anti-infective,insulin-sensitizing, and hyaluronolytic strategies.

I hope you enjoyed Dr. Purser’s research.

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