Acromegaly: A Guide to Diagnosis and Treatment

300 Pages·2022·9.817 MB·English

by  Lewis S. Blevins Jr., Manish K. Aghi

Contemporary Endocrinology
Series Editor: Leonid Poretsky
Lewis S. Blevins Jr.
Manish K. Aghi   Editors
Acromegaly
A Guide to Diagnosis and Treatment
Contemporary Endocrinology
Series Editor
Leonid Poretsky, Division of Endocrinology
Lenox Hill Hospital
New York, NY, USA
Contemporary Endocrinology offers an array of titles covering clinical as well as
bench research topics of interest to practicing endocrinologists and researchers.
Topics include obesity management, androgen excess disorders, stem cells in
endocrinology, evidence-based endocrinology, diabetes, genomics and
endocrinology, as well as others. Series Editor Leonid Poretsky, MD, is Chief of the
Division of Endocrinology and Associate Chairman for Research at Lenox Hill
Hospital, and Professor of Medicine at Hofstra North Shore-LIJ School of
Medicine.
Lewis S. Blevins Jr. • Manish K. Aghi
Editors
Acromegaly
A Guide to Diagnosis and Treatment
Editors
Lewis S. Blevins Jr. Manish K. Aghi
Department of Neurological Surgery Department of Neurological Surgery
University of San Francisco University of San Francisco
San Francisco, CA, USA San Francisco, CA, USA
ISSN 2523-3785 ISSN 2523-3793 (electronic)
Contemporary Endocrinology
ISBN 978-3-031-16257-2 ISBN 978-3-031-16258-9 (eBook)
https://doi.org/10.1007/978-3-031-16258-9
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Preface
People with acromegaly are probably not much different today than they were when
the earliest ancestors similar to modern-day Homo sapiens lived. Perhaps that is not
really accurate. I suspect that modern dietary and societal factors and activities of
daily living have led to a higher prevalence of diabetes mellitus and hypertension
than were likely present in our affected early ancestors. In general, however, it can
probably be assumed that those early persons with acromegaly, much like those in
our time with the disorder, looked, well, acromegalic. The most dramatic changes are
in our understanding of every facet of the disorder including its causes, molecular
genetics, manifestations, diagnosis, treatments, and much more. In the 33 years or so
since I first saw a patient with acromegaly we have seen a great number of changes.
One of the most remarkable sets of changes that come to mind are those where our
molecular understanding of the disease has led to drug development and multiple
avenues for medical management of patients with residual and recurrent disease.
When I saw the first patient mentioned, we only had one drug available that worked
in 10% of patients. Today, there are three main classes of pharmacologic agents to
treat acromegaly, encompassing at least eight different medications, and newer agents
are on the way. It used to be next to impossible to control IGF-1 levels in patients
with active disease. Today, uncontrolled acromegaly is the exception rather than the
rule. Also, our recognition of the long-term morbidity and mortality seen in patients
with residual and recurrent disease, coupled with advances in laboratory medicine,
led to refinement of criteria employed to determine those patients who need addi-
tional treatment after surgery and radiotherapy. We better understand the biochemical
goals of medical management of patients with acromegaly. A treatise of the historical
aspects of the disorder is beyond the scope of this book. It is always useful, however,
to have an appreciation of where we were and how far we have come to truly appreci-
ate the contents and recommendations in this book. If you learn a few things in review
of this body of work please share it with colleagues so that, together, we can facilitate
knowledge and improve the lot of patients afflicted with this condition.
San Francisco, CA, USA Lewis S. Blevins Jr.
July 19, 2022
v
Preface
Acromegaly, well described in antiquity, was recognized as a distinct clinical syn-
drome by Marie in 1886. The pituitary source of the disorder was confirmed in 1909
by Cushing, who postulated the excessive secretion of growth-promoting hormone
by a hyperfunctioning pituitary gland. Soon thereafter, clinicians began to appreci-
ate that the external manifestations that had first led to interest and fascination with
the condition were also associated with devasting internal manifestations of exces-
sive growth hormone in nearly every organ system. Despite its relative rarity, with
only 3–14 of every 100,000 people diagnosed with acromegaly, research into the
disease has had far-reaching implications on the medical care of a vast number of
patients by improving our understanding of topics such as normal growth in chil-
dren and the safe use of growth hormone to treat hypopituitarism. In this book, we
review our understanding of every aspect of acromegaly, including its molecular
etiology, manifestations, diagnosis, and therapies. We have presented this informa-
tion in a manner that emphasizes the opinions, practice patterns, and decision mak-
ings of our team of experts. We encourage you to share this book with colleagues to
enhance the medical community’s continued development of new insights into
acromegaly.
San Francisco, CA, USA Manish K. Aghi
July 20, 2022
vii
Contents
1 The Molecular Biology and Pathology of Acromegaly . . . . . . . . . . . . 1
Luis R. Carrete and Manish K. Aghi
2 Growth Hormone-Releasing Hormone- Secreting
Neuroendocrine Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Thomas M. Fandel and Lewis S. Blevins Jr.
3 Diagnosis of Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Nicholas A. Tritos
4 Imaging in Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Ian Mark and Javier Villanueva-Meyer
5 The Clinical Presentation of Acromegaly . . . . . . . . . . . . . . . . . . . . . . . 55
Lisa B. Nachtigall and Francisco J. Guarda
6 Sleep-Disordered Breathing in Acromegaly . . . . . . . . . . . . . . . . . . . . . 67
Diane Donegan and Stephanie M. Stahl
7 Cardiovascular Pathology in Acromegaly . . . . . . . . . . . . . . . . . . . . . . 87
Adnan Ajmal
8 Diabetes Mellitus in Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Samina Afreen
9 Musculoskeletal Disorders of Acromegaly . . . . . . . . . . . . . . . . . . . . . . 111
Jill B. Feffer
10 Acromegaly and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Tamis Bright
11 Mortality in Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Basma Abdulhadi, Charles Couch Farmer, and T. Brooks Vaughan
ix
x Contents
12 An Overview of the Approach to the Management
of Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Lewis S. Blevins Jr., Denise Feng, and AnneMarie Destruel
13 Transsphenoidal Surgery for Acromegaly . . . . . . . . . . . . . . . . . . . . . . 167
Ryan R. L. Phelps, Jacob S. Young, José Gurrola II,
and Manish K. Aghi
14 Stereotactic Radiosurgery and Radiation Therapy
for Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Adomas Bunevicius, Daniel Trifiletti, and Jason Sheehan
15 Challenging Questions in the Management
of Acromegaly in the Young . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Nancy Youssef and Kevin C. J. Yuen
16 Somatostatin Analogues in the Management
of Patients with Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Lewis S. Blevins Jr.
17 Use of Dopamine Agonists for Acromegaly . . . . . . . . . . . . . . . . . . . . . . 227
Christine E. Chiu and John D. Carmichael
18 Pegvisomant: Lessons Learned After 20 Years
and Practical Recommendations of Its Use for
the Treatment of Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Kevin C. J. Yuen
19 Perspectives on Combination Medical Therapy
in the Treatment of Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
Dawn Shao Ting Lim and Maria Fleseriu
20 Long-Term Follow-up of Patients with Acromegaly . . . . . . . . . . . . . . 273
Lewis S. Blevins Jr.
21 Acromegaly from the Perspective of a Patient . . . . . . . . . . . . . . . . . . . 277
Jorge D. Faccinetti
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Chapter 1
The Molecular Biology and Pathology
of Acromegaly
Luis R. Carrete and Manish K. Aghi
Introduction
Acromegaly is a disorder characterized by anatomical disfigurement and metabolic
dysregulation caused by a state of chronic sustained growth hormone (GH) hyper-
secretion. GH is a peptide hormone produced in somatotroph cells of the anterior
pituitary in response to stimulation from growth hormone-releasing hormone
(GHRH) of the hypothalamus [1]. GH induces the production of insulin-like growth
factor 1 (IGF1), a mediator of cellular processes that promote tissue growth and dif-
ferentiation [2]. In acromegaly, chronic overexposure to GH and IGF1 results in
excessive skeletal growth and enlargement of soft tissues, classically described as
frontal bossing, prognathism, macroglossia, and acral growth [3, 4]. Subtle clinical
manifestations of acromegaly are also common, including menstrual disturbances,
erectile dysfunction, hyperhidrosis, headaches, and visual disturbances from pitu-
itary tumor mass effect [3]. Furthermore, the systemic effects of GH hypersecretion
increases the likelihood of mortality and causes multiple medical comorbidities,
including diabetes, hypertension, cardiovascular disease, and visceromegaly [5].
The clinical manifestations of acromegaly can be insidious and may result in
delayed recognition of disease with diagnosis often occurring 5–10 years after dis-
ease onset [3]. The estimated prevalence of acromegaly is ten cases per one million
persons [6, 7] and has an average age at diagnosis between 40 and 50 years of age
[3]. Over 95% of cases of GH hypersecretion stem from somatotrophic pituitary
adenomas, while other causes include excessive GHRH production from hypotha-
lamic tumors or ectopic sources (i.e., neuroendocrine tumors) [5, 8]. While
L. R. Carrete
University of California San Francisco, San Francisco, CA, USA
e-mail: [email protected]
M. K. Aghi (*)
Department of Neurological Surgery, University of California, San Francisco, CA, USA
e-mail: [email protected]
© Springer Nature Switzerland AG 2022 1
L. S. Blevins Jr., M. K. Aghi (eds.), Acromegaly, Contemporary Endocrinology,
https://doi.org/10.1007/978-3-031-16258-9_1