History
Gigantism
The presentation of patients with gigantism is usually dramatic, unlike the insidious onset of acromegaly in adults. Reasons for this difference include the close monitoring of growth in children and their relatively responsive growth-plate cartilage. Children with gigantism have few soft tissue effects (eg, peripheral edema, coarse facial features), because of their rapid linear growth. Features of gigantism include the following:
-
Longitudinal acceleration of linear growth secondary to insulinlike growth factor I (IGF-I) excess is the cardinal clinical feature
-
Tumor mass may cause headaches, visual changes due to optic nerve compression, and hypopituitarism
-
Hyperprolactinemia is a common finding; it results from pituitary growth hormone (GH) excess, which manifests in childhood because mammosomatotrophs are the most common type of GH-secreting cells involved in childhood gigantism
Acromegaly
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
These symptoms depend on the size of the intracranial tumor. Headaches and visual field defects are the most common symptoms.
Visual field defects depend 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 (ie, adrenocorticotropic hormone [ACTH]), gonadotropins (eg, luteinizing hormone [LH], follicle-stimulating hormone [FSH]), and thyrotropin (ie, thyroid-stimulating hormone [TSH]).
Symptoms due to excess of GH/IGF-I
These include the following:
-
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 and adenocarcinoma of the colon
In comparison with acromegalic patients with GH–secreting adenomas alone, patients who have hyperprolactinemia as well tend to have an earlier onset of disease, lesser acromegalic features, and lower GH levels, but also larger tumors. [25] Women with GH-prolactin–secreting adenomas tend to have higher incidences of menstrual disorders and galactorrhea.
Physical Examination
Gigantism
Gigantism affects all growth parameters, although not necessarily symmetrically. Over time, insulinlike growth factor–I (IGF-I) excess is characterized by progressive cosmetic disfigurement and systemic organ manifestations. Manifestations of gigantism include the following:
-
Tall stature
-
Mild to moderate obesity (common)
-
Macrocephaly (may precede linear growth)
-
Soft tissue hypertrophy
-
Exaggerated growth of the hands and feet, with thick fingers and toes
-
Coarse facial features
-
Frontal bossing
-
Prognathism
-
Hyperhidrosis
-
Osteoarthritis (a late feature of IGF-I excess)
-
Peripheral neuropathies (eg, carpel tunnel syndrome)
-
Cardiovascular disease (eg, cardiac hypertrophy, hypertension, left ventricular hypertrophy): Occurs if IGF-I excess is prolonged
-
Benign tumors (uterine myomas, prostatic hypertrophy, colon polyps, and skin tags, which are frequently found in acromegaly)
-
Endocrinopathies (eg, hypogonadism, diabetes and/or impaired glucose tolerance, hyperprolactinemia)
Acromegaly
Signs and symptoms of acromegaly include the following:
-
Doughy-feeling skin over the face and extremities (one of the earliest signs in acromegaly is swelling of soles and palms)
-
Thick and hard nails
-
Deepening of creases on the forehead and nasolabial folds
-
Noticeably large pores
-
Thick and edematous eyelids
-
Enlargement of the lower lip and nose (the nose takes on a triangular configuration)
-
Wide spacing of the teeth and prognathism
-
Cutis verticis gyrata (ie, furrows resembling gyri of the scalp): Acromegaly may be first evident as cutis verticis gyrata. [6]
-
Small sessile and pedunculated fibromas (ie, skin tags): An association between skin tags and polypoid lesions has been described in the literature, but currently, no conclusive studies exist to substantiate this finding
-
Hypertrichosis (found in approximately one half of acromegaly patients): Unlike virilizing disorders, hypertrichosis of acromegaly does not affect the beard area
-
Oily skin (acne is not common)
-
Hyperpigmentation (40% of patients)
-
Acanthosis nigricans (a small percentage of patients): Results from excessive stimulation of keratinocytes and fibroblasts in the skin
-
Excessive eccrine and apocrine sweating
-
Breast tissue becoming atrophic; galactorrhea
-
High blood pressure
-
Mitral valvular regurgitation
-
Mild hirsutism (in women)
Skin changes are considered to be a classic feature of acromegaly; as activity of the disease diminishes, the skin changes become stationary and regress.
In a study assessing a 30-year experience with acromegaly at a major Canadian center, the most common presenting features included acral enlargement, coarse facial features, and sweating or oily skin. [26]
-
Gigantism and Acromegaly. Image shows a coauthor of this article with a statue of Robert Wadlow, who was called the Alton giant. The tallest person on record, he was 8 feet 11 inches tall at the time of his death.
-
Gigantism and Acromegaly. A 12-year-old boy with McCune-Albright syndrome. His growth-hormone excess manifested as tall stature, coarse facial features, and macrocephaly.
-
Gigantism and Acromegaly. Robert Wadlow, 19 years of age, with his father (postcard photo prior to 1937). Courtesy of Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Robert_Wadlow_postcard.jpg).
