Nervous System Diseases

Gland and Hormone Related Diseases

All Conditions

Neoplasms

Musculoskeletal Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Pituitary Diseases

Pituitary Neoplasms

Dwarfism

Dwarfism, Pituitary

Endocrine System Diseases

Bone Diseases

Bone Diseases, Developmental

Bone Diseases, Endocrine

Hypopituitarism

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Growth Hormone Deficiency

Isolated Growth Hormone Deficiency

All Drugs and Chemicals

Hormones

Estrogens

Stratified based on age and estrogen status from 3 to 6 mcg/kg/day

Somatropin

Dosage based on age and estrogen status ranging from 3 to 6 mcg/kg/day

Placebo

Anne Klibanski, M.D

The purpose of the study is to evaluate the effects of growth hormone replacement on women with growth hormone deficiency. Growth hormone deficiency means the body no longer produces growth hormone due to a tumor or some kind of disease of the brain in an area called the pituitary/hypothalamic region. This is the area of the brain where growth hormone is normally produced. We, the researchers at Massachusetts General Hospital, will establish the effects of growth hormone replacement on cardiovascular parameters (laboratory tests, the flexibility of the arteries, changes in heart rate) in women with growth hormone deficiency. Our goal is to see if this therapy:

* has effects on women's cardiovascular risk markers (special blood tests which indicate how healthy the heart and arteries are)
* has effects on women's types and levels of various substances circulating in their blood
* in women affects the stiffness of their arteries and heart rate variability in parallel with changes in cardiovascular risk markers
* has different effects depending on whether women are pre or post menopausal.

Participation in this study is expected to last approximately 12 months.

The aim of the study is to evaluate the gender specific effects of physiologic Growth Hormone (GH) replacement in women with GH deficiency on the basis of pituitary/hypothalamic region tumors, radiation, or surgery on cardiovascular risk markers and arterial distensibility. Cardiovascular mortality in growth hormone (GH) deficient adults has been shown to be increased in a number of retrospective studies. Increased arterial intima-media thickness, increased prevalence of atherosclerotic plaques and endothelial dysfunction have been reported in growth hormone deficient adults both in childhood and adulthood onset forms.

The growth hormone deficiency (GHD) syndrome is associated with a cluster of cardiovascular-risk factors such as central adiposity, increased visceral fat, insulin resistance, dyslipoproteinemia and decreased plasma fibrinolytic activity. GH administration has effects on a number of these factors, but it is unknown which mechanisms are implicated in GH action on the process of atherosclerosis. In addition to alterations in atherosclerotic markers, abnormalities in cardiac function and structure have been reported among patients with GHD possibly contributing to the increased cardiovascular mortality. In addition, GHD is associated with cardiac autonomic dysfunction that may also contribute to cardiovascular mortality and improves with GH replacement therapy.

The vast majority of studies have focused primarily on men and the gender-specific effects of GH replacement on cardiovascular risk factors remain unknown. In addition to being of interest in terms of understanding the physiologic effects of GH therapy, there are important therapeutic implications regarding data in women. Cardiovascular disease is the leading cause of mortality in women. Effects of GH replacement on bone density may be less pronounced in women and because specific GH effects on cardiovascular risk factors in women are unknown, many adult women with GHD are untreated.

Long-term GH treatment decreases total body fat including visceral fat. Decreases in central fat as assessed by waist to hip ratio have been reported in some studies, but not in others. Administration of GH causes insulin resistance acutely but long-term therapy may restore glucose sensitivity. GH treatment increases lipoprotein (a) (Lp (a)) levels but its effects on other lipoproteins are still controversial. Some studies have reported decreases in LDL cholesterol with or without increases in HDL cholesterol with GH administration, while others have not. Twelve months of GH replacement improves left ventricular mass and cardiac performance in young adults with GHD. Key factors likely involved in the discrepant findings include heterogeneity of patients studied in terms of age of onset of the GH deficiency (childhood versus adulthood), gender, severity of GHD and methodologic issues such as dose and duration of GH administration. In addition, many of the studies have no control period.

Inflammation plays a central role in the pathophysiology of atherosclerosis. Each atherosclerotic lesion represents a different stage of a chronic inflammatory process in the arterial wall and different markers along the inflammatory cascade have been reported to predict cardiovascular risk \[34\]. Among those, high-sensitivity testing for C-reactive protein (CRP) is one of the best validated. Several prospective studies support a strong link between levels of CRP and future risk of coronary events. CRP adds considerable value to the total and HDL cholesterol measurement in the prediction of cardiovascular risk. Other distal indicators of inflammation such as serum-amyloid polypeptide A (SAA) likewise predict coronary risk. These distal markers reflect the consequences of elevated proinflammatory cytokines like interleukin-6 (IL-6). GH is known to have important immunomodulatory effects. We therefore hypothesized that the effects of GH on the process of atherosclerosis might be mediated through the cytokine-inflammatory pathway. We have recently investigated the effects of physiologic GH replacement in cardiovascular risk markers in men with GHD. In this study we found that CRP and IL-6 levels decreased in GH treated men compared to controls despite no significant change in serum lipid levels. We also recently have investigated levels of inflammatory markers in women with hypopituitarism compared with healthy controls. We found that women with hypopituitarism have increased levels of IL-6 and CRP suggesting that chronic inflammation may be involved in the pathogenesis of atherosclerosis in this population. It will be critical to determine whether physiologic GH replacement has beneficial effects in women, and whether these effects are influenced by estrogen.

We will investigate the effect of long-term physiologic GH administration on IL-6, CRP, SAA as well as other classic cardiovascular risk factors in women with GHD in a randomized, placebo-controlled study. In addition, we will evaluate structural/function correlates in women by measuring arterial wall distensibility and heart rate variability in parallel with cardiovascular risk markers.

We will establish the gender-specific effects of physiologic GH replacement on cardiovascular risk in women with GHD by investigating whether this therapy:

1. has gender-specific effects on cardiovascular risk markers
2. has gender-specific effects on lipid profiles
3. alters heart rate variability and arterial distensibility in parallel with changes in cardiovascular risk markers
4. has different effects depending upon gonadal status

Growth Hormone Administration and Its Effects on Cardiovascular Risk Factors in Growth Hormone Deficient Women

Gender-Specific Effects of Physiologic GH Administration on Cardiovascular Risk Factors in Women With Growth Hormone Deficiency

Massachusetts General Hospital

Anne Klibanski, MD

Nutritional and Metabolic Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diabetes Mellitus

Diabetes Insipidus, Neurogenic

Acromegaly

Diabetes Insipidus

Hyperprolactinemia

Prolactinoma

ACTH-Secreting Pituitary Adenoma

Pituitary ACTH Hypersecretion

Adenoma

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Central Diabetes Insipidus

Galactorrhoea-Hyperprolactinaemia

ACTH-secreting Pituitary Adenoma

Natriuretic Agents

Vasoconstrictor Agents

Coagulants

Arginine Vasopressin

Hormone Antagonists

Patients diagnosed with Cushing's disease

Patients diagnosed with hyperprolactinemia/prolactinoma

Patients diagnosed with pituitary stalk lesions

Patients diagnosed with nonfunctioning pituitary adenomas

Patients diagnosed with central diabetes insipidus

Patients diagnosed with craniopharyngiomas

Patients diagnosed with other suprasellar/parasellar lesions

1. Medical history
2. Imaging examination including brain magnetic resonance imaging
3. Blood (Basal hormone study and follow-up study) and pituitary tumor tissue

Dynamic hormone study and Magnetic resonance imaging

Jung Hee Kim, M.D

The purpose of this study is to investigate the treatment and natural history of pituitary disease. We have a longstanding interest in pituitary disease including acromegaly, central diabetes insipidus, and nonfunctioning pituitary adenoma. We will continue to follow patients and recruit new patients for treatment and follow-up. Blood and pituitary tumor tissue (when available through clinical care) will be saved for future analyses related to pituitary disease.

Subjects for this study will be recruited if they are:

1. Adults, male or female aged 18 years or older
2. Have been diagnosed with pituitary diseases

Seoul National University Pituitary Disease Cohort Study

Visual field defect or hypopituitarism, hormone hyperfunction-related complications

Seoul National University Hospital

Principal Investigator

Thyroid Diseases

Congenital Abnormalities

Hypothyroidism

Thyrotropin-Releasing Hormone

Subjects receiving TRH (Thyrotropin Releasing Hormone)

TRH (Thyrotropin Releasing Hormone)

Joanna Klubo-Gwiezdzinska, M.D.

This study will determine the safety and activity of a new formulation of thyrotropin-releasing hormone (TRH), a drug used for diagnosing and evaluating patients with certain thyroid gland abnormalities. Normal thyroid gland function depends on proper chemical signaling between the thyroid gland, the hypothalamus (the part of the brain where TRH is made), and the pituitary (another part of the brain). The TRH test helps assess this interaction. Production of the only FDA-approved preparation of TRH was stopped in July 2002. As a result, to have a continuous source of TRH available for NIH clinical and research purposes, the NIH Clinical Center (CC) Pharmacy Department produced a pharmaceutical grade formulation of TRH for patient use. This study will test the CC formulation in healthy volunteers to show that its activity and side effects are similar to those of the previously available commercial test preparation. It will then be studied in CC patients for whom the diagnostic test is recommended.

Healthy volunteers between 18 and 65 years of age and all patients requiring TRH evaluation of hypothalamic-pituitary-thyroid gland interaction may be eligible for this study. Patients include those with pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre- and post-operative evaluation of pituitary tumors. Normal volunteers will be screened with a medical history, physical examination, and blood tests. Women of child-bearing potential will be given a pregnancy test; pregnant and breast-feeding women may not participate.

The TRH test procedure will be the same for healthy volunteers and patients. All participants fast from midnight before the morning of the test. In the morning, a catheter (flexible plastic tube) is inserted into an arm vein for easy injection of the TRH and collection of blood samples. Blood pressure is monitored before and during the test. A blood sample is drawn, and then TRH is given through the catheter over a 1-minute period. Another nine blood samples are collected over a 3-hour period from the time of the TRH injection for measuring levels of various hormones. A total of less than 4 tablespoons of blood is taken for the test.

Thyrotropin releasing hormone (TRH) is a neuropeptide used in the diagnostic evaluation of patients with dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis. In healthy individuals, administration of TRH intravenously results in pituitary secretion of thyrotropin \[thyroid-stimulating hormone (TSH)\], which in turn stimulates the thyroid gland release of thyroid hormones; thyroxine (T4) and triiodothyronine (T3). TRH stimulates the secretion of other pituitary hormones under normal physiologic as well as pathologic conditions.

Under this protocol, TRH is used for routine diagnostic testing and research studies in adults and children. It is produced by the Pharmaceutical Development Section of the Clinical Center Pharmacy at the NIH. The safety, activity and comparability of this preparation were demonstrated in a small group of normal volunteers prior to its release for diagnostic and research use.

Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities

Study of Thyrotropin Releasing Hormone in Patients With Thyroid or Pituitary Abnormalities

Serum TSH Levels in Response to TRH Administration

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Thyrotropin Releasing Hormone

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

This study was conducted under an IND because the TRH was produced at NIH after the FDA approved manufacturer stopped producing the product. The intent of the study was to provide TRH for diagnostic purposes for patients at the NIH.

Dr Joanna Klubo-Gwiezdzinska

2 participants did not have results drawn at 180 minutes

TSH Response to TRH

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Growth Hormone Administration and Its Effects on Cardiovascular Risk Factors in Growth Hormone Deficient Women	NCT00136032	Growth Hormone ...	Somatropin Placebo	18 Years - 65 Years	Massachusetts General Hospital
Seoul National University Pituitary Disease Cohort Study	NCT03474601	Pituitary Disea... Pituitary Incid... Acromegaly Central Diabete... Pituitary Stalk... Cushing's Disea... Pituitary Tumor Prolactinoma	Dynamic hormone...	18 Years -	Seoul National University Hospital
Seoul National University Pituitary Disease Cohort Study	NCT03474601	Pituitary Disea... Pituitary Incid... Acromegaly Central Diabete... Pituitary Stalk... Cushing's Disea... Pituitary Tumor Prolactinoma	Dynamic hormone...	18 Years -	Seoul National University Hospital
Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities	NCT00054756	Healthy Pituitary Disea... Thyroid Disease	TRH (Thyrotropi...	2 Years -	National Institutes of Health Clinical Center (CC)
Seoul National University Pituitary Disease Cohort Study	NCT03474601	Pituitary Disea... Pituitary Incid... Acromegaly Central Diabete... Pituitary Stalk... Cushing's Disea... Pituitary Tumor Prolactinoma	Dynamic hormone...	18 Years -	Seoul National University Hospital

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