Sayed Abdel Fattah Eid Lecturer of Internal Medicine Delta University Acromegaly Introduction Acromegaly is an insidious disorder caused by a pituitary GHsecreting adenoma resulting in high circulating levels of GH and IGFI ID: 536586
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Prof . El Sayed Abdel Fattah EidLecturer of Internal MedicineDelta University
Acromegaly
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Introduction- Acromegaly is an insidious disorder caused by a pituitary GH-secreting adenoma resulting in high circulating levels of GH and IGF-I.
-
Due to its insidious nature, diagnosis of acromegaly may be considerably delayed.
-
Mortality rate is 2—3 times that of the general population, but with effective treatment survival can be improved to that of the age-matched population Slide3Slide4
Pathophysiology • Many of the growth-related outcomes of acromegaly are mediated by elevated levels of IGF-I, produced in the liver in response to GH.
•
Tumor mass itself may induce optic nerve, chiasm, or tract compression; cranial nerve palsies; headache; hydrocephalus; and
hypopituitarism
• Most frequent causes of death are cardiovascular and respiratory complications.
•
Sleep apnea is a significant cause of morbidity.
•
Patients with acromegaly may also be at increased risk for cardiac hypertrophy, hypertension, arthritis, sleep apnea, and development of other neoplastic lesions, particularly in the colon
.Slide5
Clinical presentation 1- Uncommon & progressive disease 2- The clinical features of acromegaly are insidious, and it may take several years for the disfiguring features to be diagnosed
3-
It is due to excess growth hormone leading to:
*
↑
Connective tissue & bony proliferation
*
↑
Phosphate reabsorption in renal tubules (mild
hyper-
phosphatemia
)
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Impaired CHO metabolism & insulin resistance with hyperglycemia (IGT or DM)
4-
Progressive cosmetic disfigurement and systemic organ manifestations, including
arthropathy
, neuropathy, and cardiomyopathy.
5-
Patients may exhibit coarse facial features, exaggerated growth of the hands and feet, and soft tissue hypertrophy.
6- Other characteristics may include
hyperhydrosis
, goiter, osteoarthritis, carpal tunnel syndrome, visual abnormalities, and increased number of skin tags, colon polyps, sleep apnea, and cardiovascular disease (congestive heart failure, arrhythmia, and hypertension).
7-
Diagnosis of acromegaly is based on clinical findings, and the inability to suppress serum GH during an OGTT. Slide6Slide7Slide8
Investigation 1- Blood glucose & serum phosphate levels 2- Plain x ray skull, hands and feet
3-
Serial
photos
4- Elevated GH level non-suppressible after OGTT’ (GH levels will remain above 2
ng
/mL
).
5-
In contrast to GH levels, plasma levels of IGF-I are more stable, and an elevated IGF-I level in a patient with appropriate clinical suspicion is almost always indicative of acromegaly.
6-
Other pituitary
hormones
7- Pituitary Imaging: pituitary adenoma should be confirmed using MRI. 90% of
acromegalic
patients have tumors larger than 1 cm. Slide9
Treatment Goals Primary goal of treatment is to normalize GH levels. Surgical Treatment Surgical tumor excision (trans-sphenoidal) is indicated for most patients with small, well localized
microadenomas
unless there is a contraindication to
surgery .
Trans-
sphenoidal
Surgery Slide10
Nonsurgical Treatment Options for Acromegaly Medical therapy with somatostatin analogs or dopamine agonists and radiotherapy.
These therapies have been most effective when used in conjunction with surgery.
1-
Somatostatin
analogs
Somatostatin
is an endogenous molecule that exerts a variety of physiological effects, including inhibition of GH secretion.
2-
Dopamine agonists Dopamine
agomsts
(
bromocriptine
and
pergolide
) bind to pituitary dopamine type 2 receptors and suppress GH secretion in some patients with acromegaly.
Tumor shrinkage occurs in a minority of patients Slide11
3- Radiotherapy - Both conventional and heavy particle (proton beam) irradiation has been used.
The beneficial effects of radiotherapy on GH levels are dose dependent
-Side
Effects of
Radiotherapy:
- Hypothyroidism
- gonadal
dysfunction,
- visual
disturbances,
- development
of a secondary
brain
malignancy,
- brain
necrosis,
- brain
damage. Slide12
References AskMayoExpert. Acromegaly and gigantism. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2014.Melmed S. Causes and clinical manifestations of acromegaly. http://www.uptodate.com/home. Accessed Dec. 3, 2015.
Acromegaly. National Institute of Diabetes and Digestive and Kidney Diseases. http://www.niddk.nih.gov/health-information/health-topics/endocrine/acromegaly/Pages/fact-sheet.aspx. Accessed Dec. 3, 2015.
Papadakis
MA, et al., eds. Diseases of the hypothalamus & pituitary gland. In: Current Medical Diagnosis & Treatment 2015. 54th ed. New York, N.Y.: The McGraw-Hill Companies; 2015. http://www.accessmedicine.com. Accessed Dec. 3, 2015.
Parlodel
(prescribing information). Parsippany, New Jersey:
Validus
Pharmaceuticals LLC; 2015. http://parlodel.us.com/. Accessed Dec. 4, 2015.
Cycloset
(prescribing information). Tiverton, Rhode Island:
VeroScience
, LLC; 2015. http://www.veroscience.com/CyclosetFDAapprovedPackageInsert.htm. Accessed Dec. 3, 2015.
Cabergoline
(prescribing information). North Wales, Penn.:
Teva
Pharmaceuticals USA, Inc.; 2015. https://www.tevagenerics.com/product/cabergoline-tablets. Accessed Dec. 3, 2015.
Nippoldt
, TB (expert opinion). Mayo Clinic, Rochester, Minn. Dec. 23, 2015.Slide13
Thank You