Acromegaly, Sotos syndrome and Gigantism

Syndromes of excessive secretion of the human growth hormone (HGH) nearly always due to a pituitary adenoma, a common benign tumor of the somatotrophs (hormone-producing cells), gigantism is the term given to the early onset of the disease – before the end of the normal process of bone formation (epiphysis), acromegaly is the term given to a late onset of the disease – after the end of the normal process of bone formation. Sotos syndrome is also known as cerebral gigantism (or Sotos-Dodge syndrome) and it is a rare genetic disorder caused by a mutation of the NSD1 gene that controls the activity of genes involved in normal growth and development.

Causes

These disorders occur either due to a hyperactive pituitary gland (a tiny organ responsible for producing a multitude of hormones throughout the body or for regulating the hormone production of other glands) or due to mutations of the GS protein

 

Rarely, GH hypersecretion begins in childhood, before closure of the epiphysis – the proper development of the bones, leading to exaggerated skeletal growth (pituitary gigantism)

 

Many GH-secreting adenomas contain a mutant form of the GS protein which is a stimulating regulator of a process called adenylate cyclase

 

In general, a cyclase works as an enzyme seeking to initiate the cyclization of a compound – one or more series of atoms in the compound is connected to form a chemical ring, a bond

 

G proteins function as intermediaries between hormone receptors and effector enzymes (the latter being small molecules that selectively bind to a protein, having the ability to increase or decrease enzyme activity within the body, while also regulating gene synthesis and cell signaling – the complex process of communication governing basic cellular activities)

Symptoms and signs

Gigantism:

Normal growth velocity is increased

Small amounts of bone deformity, but high amounts of soft tissue swelling causing enlarged peripheral nerves

Delayed puberty

Coarsening of facial features

Swelling of hands and feet

 

Acromegaly:

Bone and soft tissue deformities, enlarged peripheral nerves, swelling of the aural parts (ears)

Coarsening of facial features (overgrowth of the mandible that usually leads to malocclusion of the teeth, enlarged tongue) and of body hair

Skin thickening and skin darkening

Excessive perspiration and body odor due to an increase in the size and function of the sebaceous glands

Costal growth – ‘barrel chest’ appearance

Possible necrosis (premature death of living cells) and erosion of the joints

Headaches, galactorrhea (milk discharge)

Heart, liver, kidneys and spleen are larger than normal

Risk of heart disease, hypertension and malignancy

Sexual immaturity – impotence and menstrual irregularities or amenorrhea (absence of menstruation)

 

Sotos syndrome:

At birth, children are larger and heavier than normal and exhibit larger heads (macrocrania)

Slightly protrusive forehead and pointed chin, abnormally large distance between the eyes, which are usually down-slanting

Delayed motor development and hypotonia (low muscle tone)

Mild cognitive and speech impairment

Clumsiness, awkward gait

Unusual aggressiveness

Advice

There is no standard course of treatment for Sotos syndrome – it only addresses symptomatology

 

Ablative therapy – a minimally invasive surgical procedure to eliminate tumorous tissue

 

Radiation therapy

MISCONCEPTIONS
  • Acromegaly, gigantism and Sotos syndrome are genetically inherited

Statistics

Sotos syndrome is reported to occur in 1 in 10,000 to 14,000 newborns, but since many features are attributable to other conditions as well, a true incidence may be closer to 1 in 5,000*

 

About 95% of people with Sotos syndrome occur in families with no previous antecedents

 

Pituitary adenomas are relatively common, occurring in an estimated of 1 in 1,000 people**

 

 

Beers, Mark H. MD, Berkow, Robert, MD. The Merck Manual of Diagnosis and Therapy. Seventh Edition, Merck Research Laboratories, Divisionary Merck & Co., 1999.

Did you know?

Galactorrhea is unrelated to the normal production of breast milk during pregnancy, which means that it can occur in both men and women (though more cases of female galactorrhea have been reported), while a number of infancy-related cases have also been observed

 

GH excess can begin at virtually any age, but it commonly sets in between the 3rd and 5th decades of life