Acromegaly

Summary

Acromegaly and gigantism are caused by an excessive production of growth hormone (GH) by the pituitary gland . Tall stature is a clinical sign observed in some patients with gigantism. Increased GH and insulin -like growth factor-1 (IGF-1) are responsible for inducing hypersomatotropism. Acromegaly is usually produced by pituitary tumors secreting GH or, less commonly, by extrapituitary disorders. Gigantism typically results in children from excess GH before growth-plate closure; acromegaly typically results from excess GH after growth-plate closure. Diagnosis involves neuroimaging of the pituitary and laboratory tests to evaluate the hypothalamic-pituitary axis. Treatment depends on the operative status of the tumor (if present), or a nonoperative treatment strategy may be utilized.

Overview

• Acromegaly is a condition in which benign pituitary adenomas lead to an excess secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). ببساطة هو عبارة عن زيادة افراز هرمون النمو
• In adults, whose epiphyseal plates are closed, the disease causes enlarged hands and feet, coarsened facial features, and pathological growth of internal organs.
  لأن البالغين يكون النمو في الطول قد توقف، فإن هرمون النمو يؤثر على حجمهم وليس على طولهم، مثل زيادة حجم اليد والقدم وبعض الأعضاء الداخلية
• If the condition occurs in children, before epiphyseal plate closure, it is known as gigantism.
• The first step in diagnosing acromegaly is to measure IGF-1 levels. Further testing includes an oral glucose tolerance test (OGTT) with assessment of GH levels, and evaluation of pituitary tumors via cranial MRI.
• Management consists of transsphenoidal adenomectomy for operable tumors, or GH-inhibiting medication and radiotherapy if surgery is contraindicated or unsuccessful. Adequate treatment is vital to reduce the risk of complications, such as cardiovascular disease and cerebral aneurysms, as these may considerably increase mortality.

Causes

• Benign growth hormone-secreting pituitary adenoma (> 95% of cases à Most common cause)
• Very rare:
  • Ectopic secretion of growth hormone by neuroendocrine tumors (e.g., small cell lung carcinoma, pancreatic islet-cell tumor (as found in MEN1))
  • ↑ Secretion of growth hormone-releasing hormone (GHRH) from a hypothalamic tumor or in paraneoplastic syndromes (e.g., small cell lung carcinoma, medullary thyroid cancer)

Clinical features

• Tumor mass effects
  • Headache, vision loss (bitemporal hemianopsia), cranial nerve palsies
  • Females: Oligomenorrhea, secondary amenorrhea, galactorrhea, vaginal atrophy
  • Males: Erectile dysfunction, decreased libido, ↓ testicular volume.
• Soft tissue effects
  • Doughy skin texture, hyperhidrosis زيادة التعرق(Caused by enlarged sweat glands)
  • Deepening of the voice, macroglossia with fissures, obstructive sleep apnea
• Skeletal effects
  • Coarsening of facial features slowly progressing with age; : enlarged nose, forehead, and jaw (macrognathia) with diastema زيادة المسافة بين الأسنان
  • Widened hands, fingers, and feet
  • Painful arthropathy (ankles, knees, hips, spine)

Complications

• Cardiovascular complications: the main cause of death ➜ مهم، فكرة سؤال
  • Hypertension (∼ 30% of cases)
  • Left ventricular hypertrophy and cardiomyopathy
  • Arrhythmia
  • Valvular disease
• Impaired glucose tolerance and diabetes mellitus (up to 50% of cases)
• Colorectal polyps and cancer
• Thyroid enlargement and cancer à Despite the thyroid being enlarged, thyroid hormone levels are usually normal.
• Carpal tunnel syndrome
• Hypopituitarism

Diagnosis

• Insulin-like growth factor-1 (IGF-1) ➜ the best initial test مهم جداً
  • If elevated, do oral glucose tolerance test (OGTT)
  • If normal, acromegaly is ruled out
• OGTT with baseline GH and measure GH after 2 hours ➜ the most specific and accurate test مهم جداً
  • If GH secretion is supressed, then acromegaly is ruled out
  • If GH secretion is not supressed, then this is a case of acromegaly and you have to do MRI to determine the source of excess GH
• Pituitary MRI
  • Imaging modality of choice ➜ مهم

• الأفكار المهمة والأسئلة المتكررة:
  • أول فحص يتم عمله هو IGF-1 ، لا نستخدم الــ GH لأن مستواه متغير أثناء اليوم ولا يفيد في التشخيص
  • أدق فحص هو OGTT
  • أداة التصوير التي نستخدمها هي MRI
  • عادة تكون صيغة السؤال بأن حذاء المريض أصبح ضيقاً أو أن خاتم الزفاف لم يعد يدخل في اصبع اليد
  • أكثر سبب للوفاة هو الــ Cardiovascular complications
  • أفضل علاج هو الجراحة

Treatment

• Transsphenoidal adenomectomy is the method of choice for treating acromegaly. In patients with inoperable tumors or unsuccessful surgery, medication and radiotherapy are indicated to reduce tumor size and limit the effects of GH and IGF-1.
• Medications
  • Somatostatin analogs (e.g., octreotide, lanreotide)
  • Dopamine agonists (e.g., cabergoline): reduce tumor size and GH secretion
  • GH receptor antagonists (e.g., pegvisomant)
• Radiotherapy

Quick Quiz

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