# New Approaches to the Evaluation and Treatment of Acromegaly

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $585,608

## Abstract

SUMMARY
This project builds on our novel, uniquely NIH-funded prospective study of 330 patients with acromegaly, a
disease originating in a GH secreting pituitary tumor that is characterized by excess circulating GH and IGF-1
and the multi-system morbidity and increased mortality they produce. Acromegaly provides a model through
which we can improve our knowledge of GH and IGF-1 effects on adipose tissue (AT), body composition and
liver and muscle lipid accumulation, in this and other clinical settings. The leading cause of acromegaly death,
CV disease, likely relates to the prevalent metabolic abnormalities, in particular insulin resistance. Our work
suggests, however, that the paradigm linking metabolic and body composition abnormalities to CV disease in
the general population does not apply in acromegaly. This project proposes, alternatively, that a novel
acromegaly-specific lipodystrophy underlies the metabolic abnormalities and may impact long-term outcome.
Based on our preliminary data, we hypothesize that the lipodystrophy produces a unique pattern of AT
redistribution, reduced visceral adipose tissue mass and hepatic lipid despite insulin resistance and increased
inter-muscular adipose tissue mass that cause insulin resistance. Understanding this process is important
because acromegaly medical therapies may not uniformly reverse this lipodystrophy. Utilizing state of the art
body composition methods Aim 1 tests new hypotheses emerging from our data, including that GH is a
negative regulator of liver fat and somatostatin analogs (SSA) increase muscle lipid. These will be tested by
comparisons to specially matched controls and to patients with GH deficiency and HIV lipodystrophy (HIVLD),
two disorders with reduced GH secretion and increased VAT and CV risk. GHD and HIVLD patients will be
examined before and after GH or GHRH analogue therapy, respectively, for a pattern of body composition
change opposite to that with GH lowering. We will assess epicardial adipose tissue, a depot with important
links to CV disease, but is understudied in acromegaly and HIVLD. Aim 2 investigates mechanisms for
therapy-specific body composition changes, specifically the roles of ghrelin, gut and pancreatic hormone
changes during SSA therapy on ectopic lipid accumulation and future risk of DM. Integral to the acromegaly
lipodystrophy and its link with insulin resistance are GH's effects in AT. Aim 3 investigates biopsied AT, testing
the hypothesis that acromegaly produces a novel dissociation of inflammatory and immune cell phenotypes
that reverses with acromegaly treatment and that may relate to insulin resistance and altered lipid and energy
metabolism in AT. The inflammatory profile of circulating monocytes, which may relate to CV risk, will also be
tested in acromegaly, GHD and HIVLD. Aim 4 analyzes mortality and morbidity outcomes related to the
lipodystrophy in our well-characterized, longitudinal cohort using modern GH and IGF-1 measures. This project
pr...

## Key facts

- **NIH application ID:** 9924534
- **Project number:** 5R01DK110771-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** PAMELA U FREDA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $585,608
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924534

## Citation

> US National Institutes of Health, RePORTER application 9924534, New Approaches to the Evaluation and Treatment of Acromegaly (5R01DK110771-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9924534. Licensed CC0.

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