Calcium Homeostasis in Acromegaly: Effect of Surgical/Medical Treatment and Comparison With Nonfunctioning Pituitary Tumors

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the Calcium homeostasis in adult patients with uncontrolled acromegaly. The measurements will be repeated 3-6 months after the treatment of acromegaly (surgical or medical). The control group consists of patients with nonfunctioning pituitary tumors who will undergo surgical removal.

Detailed Description
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Calcitriol is the active form of vitamin D. Parathyroid hormone (PTH) is secreted by the parathyroid glands in the neck. Both these chemicals are responsible for keeping the levels of calcium and phosphorous normal and also play a role in bone health. They can be measured in the blood. In some disorders, PTH or calcitriol levels are elevated, which results in increased calcium absorption from the gut, increased calcium in the bloodstream, and increased calcium excretion in the urine. Increased calcium in the urine can lead to the development of kidney stones. Increased calcium in the bloodstream can have adverse effects on the heart, gut, kidneys, and bones. Acromegaly is a condition where a pituitary tumor secretes excessive amounts of growth hormone. Patients with acromegaly have been found to have a higher prevalence of kidney stones, urinary calcium, and serum calcium when compared to normal adults. The reason for this is unknown but a suggested mechanism is that growth hormone stimulates the production of calcitriol or PTH. If this is true, then treatment of acromegaly resulting in lower growth hormone levels should also result in lower blood and urine calcium levels. The investigators want to see if patients with acromegaly have high calcitriol, and vitamin D binding protein, or PTH levels and see if they change after treatment of the condition. The investigators also want to assess the amount of calcium in the urine, before and after treatment. Patients with acromegaly may have disorders of bone health. The reason for this is unknown but a suggested mechanism is that growth hormone affects bone remodeling. The investigators want to see if patients with acromegaly have abnormal bone markers, specifically PINP, CTX, and TRAP, and to see if they change after treatment of the condition. In order to see if the results are specific to patients with acromegaly, the investigators also want to check these levels in patients who do not have acromegaly, but have a nonfunctioning pituitary tumor. A nonfunctioning pituitary tumor is one that does not secrete excessive hormones in the bloodstream. The specific aims of this study are: To describe baseline calcitriol/PTH status in patients with uncontrolled acromegaly. To assess the change in calcitriol/PTH levels after treatment with acromegaly (surgical or medical). To evaluate the calcium and calcitriol/PTH levels in patients with acromegaly compared to patients with nonfunctioning pituitary adenomas. This is a voluntary study. Adult patients with a diagnosis of acromegaly or a clinically nonfunctioning pituitary tumor receiving treatment at the Emory University Pituitary center will be given the opportunity to enroll in the study. Those that agree to participate will need to give written informed consent. Approximately 3 tablespoons (44ml) of blood will be drawn at enrollment for testing of vitamin D status and parathyroid hormone. If patients are already undergoing a blood draw for standard laboratory tests, then the volume of 44ml of blood will be obtained at the same time in order to avoid an additional needle stick. In addition, a 24-hour urine collection will be obtained to assess the amount of calcium present in the urine. Please note that medical or surgical therapy for your pituitary condition is determined by your endocrinologist and/or neurosurgeon and not part of the research study. Within 6 months after treatment for pituitary treatment is initiated, when patients return to Emory University pituitary clinic for routine visit, laboratory data (vitamin D and parathyroid hormone) and repeat urine studies (24 hour urine collection) will be collected. The confidentiality will be respected in all encounters. No personal identifiers are disclosed in any publications. Hard copy data will be kept securely in a locked office building with limited access and electronic data will always be password protected with access available to study personnel only. If abnormal results are discovered as part of testing done for this study, those results will be released to the patient's primary physician. All patients will be undergoing standard therapy for their pituitary disorder. Results of this study may have important implications for future studies that are designed to evaluate the mechanism of how growth hormone may increase calcitriol levels.

Official Title
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Calcium Homeostasis in Acromegaly: Effect of Surgical/Medical Treatment and Comparison With Nonfunctioning Pituitary Tumors.

Conditions
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Acromegaly, Nonfunctioning Pituitary Tumor

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with acromegaly or a nonfunctioning pituitary who will receive treatment for the pituitary condition. Study subjects must agree to participate in this study and provide written consent. Site- Emory Clinic/Emory University hospital. Stage of Disease: Patients with active acromegaly that is either newly diagnosed or uncontrolled on current therapy (as shown by GH/IGF-1 levels). Patients with nonfunctioning pituitary adenoma in whom surgical intervention planned based on current guidelines will serve as a control group. Age: Study subjects must be over 18 years of age. Exclusion Criteria: Age < 18 years old Prior other diseases: Patients chronic renal disease stage 3 or worse (estimated GFR > 60).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1 - Acromegaly, Group 2 - control<br>Group 1 - Acromegaly patients, Group 2 - Nonfunctioning pituitary adenoma patients (control) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcitriol/PTH | To describe baseline calcitriol/PTH status in patients with uncontrolled acromegaly, with subanalyses based on presence of hyperprolactinemia. To assess the change in calcitriol/PTH levels after treatment with acromegaly, with subanalyses based on type of therapy (surgical or medical). To evaluate the calcium and calcitriol/PTH levels in patients with acromegaly compared to patients with nonfunctioning pituitary adenomas, with subanalyses based on presence of hyperprolactinemia in either group. | Baseline and 3-6 months after trreatment of pituitary condition |