Acromegaly Prof . El Sayed Abdel Fattah Eid Lecturer of Internal Medicine Delta University

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

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 .

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) * 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.

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.

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

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

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.

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