PANCE Blueprint Endocrinology (7%)

Acromegaly/gigantism (Growth Hormone)

Patient will present as → a 45-year-old woman presented with a 4-year history of progressive increase in body size, lactation and amenorrhoea, and a six-week history of worsening symptoms of heart failure. Physical examination showed coarse facial features, spade-like hands and feet, pitting pedal edema, galactorrhoea, and features of congestive cardiac failure. Chest radiograph showed gross cardiomegaly. On skull radiograph, destruction of the floor of the pituitary fossa was noted, with an erosion of the clinoid processes. She had hyperprolactinemia. Fasting and post-glucose growth hormones values were elevated.

Gigantism and acromegaly are usually caused by a pituitary adenoma that secretes excessive amounts of Growth Hormone GH); rarely, they are caused by non-pituitary tumors that secrete GHRH.

  • Gigantism occurs if growth hormone (GH) hypersecretion begins in childhood, before closure of the epiphyses.
  • Acromegaly involves growth hormone GH hypersecretion beginning in adulthood; a variety of bony and soft tissue abnormalities develop.

Diagnose by measuring IGF-1 and GH levels

Serum IGF-1 should be measured in patients with suspected acromegaly

  • IGF-1 levels are typically substantially elevated (3-fold to 10-fold), and because IGF-1 levels do not fluctuate like GH levels do, they are the simplest way to assess GH hypersecretion. IGF-1 levels also can be used to monitor response to therapy.

Plasma GH levels measured by radioimmunoassay are typically elevated.

  • Blood should be taken before the patient eats breakfast (basal state); in normal people, basal GH levels are < 5 ng/mL. Transient elevations of GH are normal and must be distinguished from pathologic hypersecretion. The degree of GH suppression after a glucose load remains the standard and thus should be measured in patients with elevated plasma GH

CNS imaging to detect a pituitary tumor

  • CT or MRI of the head should be done to look for a tumor. If a tumor is not visible, excessive secretion of pituitary GH may be due to a non-CNS tumor producing excessive amounts of ectopic GHRH.

Remove pituitary tumors surgically or using radiation therapy

  • Sometimes pharmacologic suppression of GH secretion or activity: If tumors cannot be removed, give octreotide or lanreotide to suppress GH secretion
Endocrine_growth_regulation.svg

Gigantism and acromegaly are usually caused by a pituitary adenoma that secretes excessive amounts of Growth Hormone

 IM_NUR_AcromegalyAssessment_v1.2_ This condition results from hyperpituitarism, which is an oversecretion of growth hormone due to a pituitary tumor or tissue hyperplasia. The onset of the condition is very gradual and manifests with significant changes to the body leading to coarse facial features, deepening of the voice, enlargement of lips, nose, hands, and feet, joint enlargement and pain. An increase in stature does not occur as the epiphyseal plates are closed in the adult patient. The hyperpituitarism condition affecting pediatric patients is called gigantism.

Acromegaly Picmonic

Question 1
A 25-year-old man comes to your office with his wife. He is very concerned about some “bizarre symptoms” that he has been experiencing. He is the chief executive officer of a family-owned manufacturing company and is “really embarrassed to go out in public any longer.” He tells you that approximately 6 months ago, he began to experience the following symptoms: headaches, visual spots or defects, weight gain, an appearance of his forehead growing, enlarging hands and feet (he could no longer get his gloves and shoes on), and increased sweating. On examination, mental status is normal, and the apical impulse is felt in the fifth intercostal space, midclavicular line. His blood pressure is 170/ 105 mm Hg. He does have a protruding brow, and three discrete visual field defects are noted (two in the left eye and one in the right eye). His tongue appears enlarged, and he is sweating profusely. What is the most likely diagnosis in this patient?
A
acromegaly
B
ACTH excess
C
prolactinoma
D
primary hypopituitarism
Question 1 Explanation: 
The condition is acromegaly, which often goes undiagnosed for many years. Acromegaly produces many signs and symptoms, including the following: 1. General symptoms: (a) fatigue, (b) increased sweating, (c) heat intolerance, and (d) weight gain 2. Changes in peripheral and general appearance: (a) enlarging hands and feet, (b) coarsening facial features, (c) oily skin, and (d) hypertrichosis 3. Head: (a) headaches, (b) parotid enlargement, and (c) frontal bossing 4. Nose-throat: (a) sinus congestion, (b) voice change, (c) obstructive sleep apnea, and (d) goiter 5. Cardiovascular system: (a) hypertension, (b) congestive cardiac failure, and (c) left ventricular hypertrophy 6. Genitourinary system: (a) kidney stones, (b) decreased libido or impotence, (c) infertility, and (d) oligomenorrhea 7. Neurologic system: (a) paresthesias, (b) hypersomnolence, and (c) carpal tunnel syndrome 8. Muscular system: (a) weakness and (b) proximal myopathy 9. Skeletal system: (a) joint pains and (b) osteoarthritis
Question 2
Which of the following is the most common cause of acromegaly?
A
Increased growth hormone (GH)-releasing hormone (GHRH) from hypothalamic tumors
B
Ectopic GHRH from nonendocrine tumors
C
Pituitary adenomas or hyperplasia
D
Ectopic GH secretion by nonendocrine tumors
Question 2 Explanation: 
Causes of excess IGF-I action can be divided into the following three categories:
  • Release of primary GH excess from the pituitary
  • Increased GHRH secretion or hypothalamic dysregulation
  • Hypothetically, the excessive production of IGF-binding protein, which prolongs the half-life of circulating IGF-I
By far, most people with gigantism or acromegaly have GH-secreting pituitary adenomas or hyperplasia. Other causes of increased and unregulated GH production, all very rare, include increased GHRH from hypothalamic tumors, ectopic GHRH from nonendocrine tumors, and ectopic GH secretion by nonendocrine tumors.
Question 3
Which of the following is accurate about the epidemiology of acromegaly?
A
Gigantism is more common than acromegaly
B
Acromegaly is typically associated with a delay in diagnosis
C
The mean age for onset of acromegaly is the second decade of life
D
Men develop acromegaly more frequently than women
Question 3 Explanation: 
Gigantism is extremely rare, with approximately 100 reported cases to date. Acromegaly is more common than gigantism, with an incidence of 3-4 cases per million people per year and a prevalence of 40-70 cases per million population. The mean age for onset of acromegaly is in the third decade of life; the delay from the insidious onset of symptoms to diagnosis is 5-15 years, with a mean delay of 8.7 years. The mean age at diagnosis for acromegaly is 40 years in men and 45 years in women. Men and women are equally affected.
Question 4
Which of the following symptoms is more common in individuals with acromegaly?
A
Visual field defect
B
Hyperprolactinemia
C
Sex steroid deficiency
D
Prognathism
Question 4 Explanation: 
Acromegaly can be an insidious disease. Symptoms, which may precede diagnosis by several years, can be divided into the following groups:
  • Symptoms due to local mass effects of an intracranial tumor
  • Symptoms due to excess of GH/IGF-I
Symptoms due to local mass effects of tumor depend on the size of the intracranial tumor. Headaches and visual field defects are the most common symptoms. Different visual field defects manifest depending on which part of the optic nerve pathway is compressed. The most common manifestation is a bitemporal hemianopsia caused by pressure on the optic chiasm. Tumor damage to the pituitary stalk may cause hyperprolactinemia due to loss of inhibitory regulation of prolactin secretion by the hypothalamus. Damage to normal pituitary tissue can cause deficiencies of glucocorticoids, sex steroids, and thyroid hormone. Loss of end-organ hormones results from diminished anterior pituitary secretion of corticotropin. Symptoms due to excess of GH/IGF-I include:
  • Soft tissue swelling and enlargement of extremities
  • Increase in ring and/or shoe size
  • Hyperhidrosis
  • Coarsening of facial features
  • Prognathism
  • Macroglossia
  • Arthritis
  • Increased incidence of obstructive sleep apnea
  • Increased incidence of glucose intolerance or frank diabetes mellitus, hypertension, and cardiovascular disease
  • Hyperphosphatemia, hypercalcuria, and hypertriglyceridemia possible
  • Increased incidence of congestive heart failure, which may be due to uncontrolled hypertension or to an intrinsic form of cardiomyopathy attributable to excess GH/IGF-I
  • Increased incidence of colonic polyps
Question 5
Which of the following is accurate regarding the workup of acromegaly?
A
Routine imaging studies should be performed in all patients suspected of having acromegaly
B
GH is the most reliable biochemical indicator of acromegaly
C
Most patients investigated for acromegaly have a post glucose GH level that is intermediate (5-10 ng/mL)
D
Elevated IGF-I values in a patient suspected of acromegaly almost always indicate GH excess
Question 5 Explanation: 
IGF-I is the most reliable biochemical indicator of acromegaly. An excellent linear dose-response correlation between serum IGF-I levels and 24-hour integrated GH secretion has been demonstrated. Elevated IGF-I values in a patient whose symptoms prompt appropriate clinical suspicion almost always indicate GH excess. IGF-I is useful not only in diagnosis but also in monitoring the efficacy of therapy. Because of the relatively high incidence of nonfunctioning, incidentally discovered pituitary adenomas, imaging studies should be obtained only after a firm biochemical diagnosis of acromegaly has been made. Only a small percentage of patients investigated for acromegaly have a postglucose GH level that is intermediate (5-10 ng/mL). In these patients, other tests can be used to define their status.
Question 6
Which of the following is accurate regarding treatment of acromegaly?
A
Pharmacologic therapy is the first-line treatment for acromegaly
B
Radiation therapy is routinely indicated for most patients with acromegaly
C
For most patients with acromegaly, surgical removal of the pituitary gland tumor is the primary treatment
D
Somatostatin and dopamine analogues and GH receptor antagonists should be routinely instituted if surgery for acromegaly is required
Question 6 Explanation: 
Guidelines released by the US Endocrine Society in 2014 address important clinical issues regarding the evaluation and management of acromegaly. Recommendations include the following:
  • For most patients with acromegaly, surgical removal of the pituitary gland tumor should be considered the primary treatment.
  • An imaging study should be performed at least 12 weeks post-surgery to determine whether any residual tumor tissue is present.
  • Patients should be evaluated for any damage caused by the pituitary tumor and for the development of hypopituitarism.
  • Medical therapy should be administered only to patients with persistent postoperative disease.
In general, radiation therapy is recommended if GH hypersecretion is not normalized with surgery. Radiation treatment takes years to reduce/normalize GH/IGF-I levels. Somatostatin and dopamine analogues and GH receptor antagonists are the mainstays of medical treatment for GH excess and are generally used when primary surgery fails to induce complete remission
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