A 46 y.o. male with diabetes, hypertension and lymphoma presents with complaints of numbness in the R hand
His thumb and second and third fingers are numb on the palmar side. What is your differential?
pt with diabetes and lymphoma
Our patient had carpal tunnel syndrome caused by acromegaly from his lymphoma. While most acromegaly is caused by a pituitary adenoma a few have hypothalamic or other tumors that secret growth hormone (GH) or growth hormone releasing hormone (GHRH).
to prevent growth hormone excess three feedback loops are possible
CAUSES OF GH EXCESS
GH- Central cause with a pituitary tumor that ignores the body’s negative feedback mechanisms
GHRH positive- Central cause where the pituitary is normal but there is stimulationg from a hypothalamic tumor or neuroendocrine tumor of the cental nervouos system.
GHRH negative– Peripheral tumors produce either growth hormone or growth hormone releasing factors. These include lymphomas, pancreatic tumors , carcinoid tumors and even lung cancer .
An excess of growth hormone causes two different conditions.
1 gigantism- in children excess growth hormone causes rapid vertical growth. One of the most famous individuals with this condition lived near St. Louis:. Robert Wadlow of Alton, Ill. He grew to 8 ft 11.1 inches
Robert Wadlow
2. acromegaly- if the growth hormone excess occurs after long bones have fused; the bone increased in size and skin thickens but there is no lengthening of bone.
Andre the giant, a French wrestler developed acromegaly later in life.
CLINICALLY
Growth hormone excess causes continued growth of tissue in adulthood. It results in enlargement of the hands,feet, jaw and internal organs. It causes diabetes because growth hormone increases insulin-like growth factor and increases gluconeogenesis. GH also impairs insulin sensitivity in the tissues.
25% of GH secreting tumors also secrete prolactin whick can result in gynecomastia..
DIAGNOSIS
GH is secreted episodically with spikes at night and during exercise. To determine if someone has increased growth hormone, insulin-like growth factor is measured since it doesn’t have a diurnal fluctuation. IGF is produced in the liver by growth hormone.
TREATMENT.
Treatment is a somatostatin agonist decreasing the amount of growth hormone. Paltusotine is an oral somatostatin receptor agonist which is recently approved.
Our patient
mRNA encoding for growth hormone and growth hormone receptors where found in the patient’s lymphoma tissue. The lymphoma was treated with fludarabine, mitoxantrone, and dexamethasone which resulted in a decrease of growth hormone and IGF-1. His symptoms regressed and the lymphoma was in remission.
FUN FACTS
Growth hormone is used illicitly by some weight lifters to increase muscle mass.It can cause fluid retention, carpal tunnel syndrome, diabetes, and organomegaly leading to palumboism. Since growth hormone has an effect on steroids and induces prolactin, gynecomastia can also result. GH is banned in competitive sports.
With excess GH palomboism can result.
The FDA approved peptides once approved for treating acromegaly are now being used for increasing muscle mass, muscle repair and cartilage repair. They are growth hormone secretagogues: semorelin, tesamorelin CJC-1295 and ipamorelin. They target the pituitary to release growth hormone. Unlike exogenous GH they preserve the natural feed back loop minimizing the suppression of natural growth hormone. They are also less effective than growth hormone and muscle growth may take six months to occur rather than several weeks for the GH given in acromegaly. Although further research has to be done, they are readily available now.
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Rahman O, Lee S, Seeds W. therapeutic peptides inorthopaedics: applications, challenges and future directions. Journal of AAOS Global Research and Reviews, Jan 2026 10(1)American Academy of Orthopedic Surgeons.
Beuschlein F, Strasburger C. Siegerstetter V, et al. Acromegaly caused by secretion of growth hormone by a non-hodgkin’s lymphoma. NEJM 2000;342:1871-1876. Zendran I, Gut G, Katuzny M. Acromegaly caused by ectopic growth hormone releasing hormone secretion: a review. Front. Endocrinol. Vol13 June 2022.